Yakut Medical Journal» Is Included in the Approved by Chuvashova I.I., the Higher Attestation Commission of the Russian Kononova S.L

ISSN 1813-1905 (print) ISSN 2312-1017 (online) 3(67) `2019 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

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

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, Professor (Yakutsk) Registered by the Office of the Federal Service on Mikhailova E.I., Doctor of Pedagogics, supervision in the field of communications, information 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) Puzyrev V.P., MD, Professor, Registration number PI No.ТU 14-00475 Acad. RAMS (Tomsk) Reutio Arya, MD, PhD, Professor (Finland) Subscription index: 78781 Fedorova S.A., Doctor of Biology (Yakutsk) Free price Husebek Anne, MD, Professor (Norway) Khusnutdinova E.K., Doctor of Biology, Professor (Ufa)

Editors: «Yakut Medical Journal» is included in the approved by Chuvashova I.I., the Higher Attestation Commission of the Russian Kononova S.l. Federation List of leading peer-reviewed scientific Semenova T.F. (English) journals and publications, in which the main scientific results of dissertations for the acquisition of scientific Computer design degrees of Doctor and Candidate of science on Sannikova M.I. (English) biological sciences and medicine should be published.

Address: The journal is included in the international directory Sergelyakhskoe Highway, 4, Yakutsk Republic system under periodic and proceeding editions “Ulrich’s Sakha (Yakutia) Russian Federation 677019 International Periodicals Directory” 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

Editor-in-Chief column

Editorial

6 Romanova A.N., Klimova T.M., Egorova A.G., Kuzmina A.A., Malogulova I.S., Arkhipova N.S. Prevalence and treatment of arterial hypertension in the native rural population of Yakutia

Original researches

9 Ammosova E.P., Klimova T.M., Sivtseva T.M., Fedorov A.I., Baltakhinova M.E., Zakharova R.N. Lipoprotein lipase gene polymorphism rs320 and metabolic syndrome in native people of Yakutia 13 Dyakonova A.T., Kurtanov Kh.A., Pavlova N.I., Solovyova N.A., Filippova N.P., Aleksandrova T.N. Determination of HLA alleles using single nucleotide polymorphism of rs3104413 HLA-DQA1 gene among patients with type 1 diabetes of the RS (Ya) 16 Sofronova S.I., Romanova A.N., Kirillina M.P. Correlation of the M235T polymorphism of the AGT gene with arterial hypertension and its risk factors in the indigenous people of the arctic territory of Yakutia 20 Kit O.I., Bazaev A.L., Zlatnik E.Yu., Novikova I.A., Ulianova E.P., Shulgina O.G., Sagakyants A.B., Kolesnikov E.N., Trifanov V.S., Mezentsev S.S., Snezhko A.V., Katsieva T.B. Expression of some molecular and biological markers in different periods of progression after radical surgical treatment of esophageal cancer 23 Popovich A.A., Trifonova E.A., Bocharova A.V., Vagaitseva K.V., Maksimova N.R., Stepanov V.A. Genetic diversity in Yakut population by loci associated with body mass index and obesity 26 Kim L.B., Osipova L.P., Rozumenko A.A., Putyatina A.N., Russkikh G.S., Kozaruk T.V., Voronina N.P. Lipid spectrum features and relationship between specific classes of lipids and sex hormone levels in Asian North men 30 Nelunova T.I., Burtseva T.E., Postoev V.A., Chasnyk V.G., Slobodchikova M.P. Patent ductus arteriosus association with the congenital heart disease in the newborns of the RS (Ya)

Diagnostic and treatment methods

32 Anikin S.V., Yanovoy V.V., Khodus S.V. The risk stratification of the venous thromboembolic complications in oncocoloproctology 34 Aleksandrova T.N., Mulina I.I., Yadrikhinskaya V.N., Solovieva I.E., Terekhova L.D., Pavlova N.I., Kurtanov Kh.A. Clinical and epidemiological aspects of chronic myeloproliferative diseases in the RS (Ya) 37 Kirillina M.P., Kononova I.V., Sofronova S.I., Ivanova A.K., Lushnikova E.L. The incidence of dysplastic changes in cervix uteri among women of different age groups 40 Semyonova E.I., Olesova L.D., Yefremova A.V., Okhlopkova E.D., Konstantinova L.I., Yakovleva A.I., Romanova A.N., Sofronova S.I., Egorova A.G. 3’ 2019 3

The structured spot of blood pressure from the perspective of the golden ratio proportion 45 Okhlopkova E.D., Konstantinova L.I., Olesova L.D., Semenova E.I., Yakovleva A.I., Mironova G.E. Study of the lactate level in the blood serum of athletes training in the conditions of the Far North 47 Kononova S.K., Barashkov N.A., Pshennikova V.G., Sidorova O.G., Davydova T.K., Sofronova S.I., Romanova A.N., Khusnutdinova E.K., Fedorova S.A. DNA diagnostics in clinical practice applied to translational medicine

Healthy lifestyle. Prevention 51 Starostina L.D. Comparative analysis of health-saving behaviour of students of comprehensive schools and university in Yakutsk 54 Latyshevskaya N.I., Mikhalchenko V.F., Yatsyshena T.L., Davydenko L.A., Shestopalova E.L. Regional characteristics of permanent teeth eruption in Volgograd schoolchildren 57 Ivanova O.N. Recurrent stomatitis in children

Hygiene, sanitation, epidemiology and medical ecology 59 Pavlov N.G., Alekseeva G.I., Vinokurova M.K. Ermolaeva E.I., Chernykh M.V. Comprehensive indicative analysis of the performance and quality of acid-fast bacteria detection by primary care facilities in the RS (Ya)

Actual topic 62 Klimova T.M., Egorova A.G., Zakharova R.N., Ammosova E.P., Baltakhinova M.E., Fedorov A.I., Romanova A.N. Metabolic syndrome among Yakutia’s indigenous female population 65 Nikitina M.A., Zhukova N.G., Bragina E.Yu., Alifirova V.M., Zhukova I.A., Gomboeva D.E., Brazovskaya N.G., Izhboldina O.P., Zhalsanova I.Zh. The heterogeneity of non-motor symptoms in patients with Parkinson’s disease in Tomsk region 70 Epanov V.V., Borisova A.P., Epanova A.A., Palshin G.A. Age-related dynamics of bone mineral density in the adult population of Yakutsk 73 Garmaeva D.K., Alexeev A.A., Zakharova I.S., Popova T.I., Arsakova V.A. Analysis of gallstone disease risk factors using samples from patients after cholecystectomy at Republic hospital №1 -NCM surgical ward (Yakutsk) 76 Alekseeva Z.N., Arkhipova N.S., Tatarinova O.V., Sleptsov S.S., Efremova S.D. The gender features of manifestations of frailty, emotional condition and life quality of long-livers in Yakutsk 4 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

Arctic medicine 80 Vorontsova E.V., Vorontsov A.L. Environmental state and human health in the Arctic zone: medical and socio-legal aspect 85 Novitskaya V.P., Prakhin E.I. Influence of additional vitaminization of schoolchildren rations in the Arctic on variability of morphofunctional parameters of the immune system 88 Kolomeichuk S.N., Morozov A.V., Petrashova D.A., Pozharskaya V.V., Stafeeva E.B., Vinogradova I.A., Bochkarev M.V., Tarasov B.A. Daytime sleepiness and sleep parameters in children living in the European North of Russia

Scientific reviews and lectures 90 Boyko E.R., Kaneva A.M. Indices of lipid metabolism for the early diagnosis of cardiovascular disease in residents of the North 94 Moskalenko O.L., Smirnova O.V., Kasparov E.V. Obesity in various ethnic populations 97 Chamsutdinov N.U., Huseynov A.A., Abdulmanapova D.N. Endocrine mechanisms of bronchial control in patients with bronchial asthma

Point of view 102 Shcheglov B.O., Galkina I.V., Shcheglova S.N., Shchelkanov M.Yu. Effectiveness of 3d-modelling laboratory implementation into therapeutic and diagnostic medical institutions 104 Kudrina P.I., Sofronova S.I., Tatarinova O.V. Ethnic and age-related characteristics of neurological symptoms and functional state of the kidneys in elderly and senile age people of Yakutia 107 Gouriev I.P. Distribution of carriers of “Indo-European” haplotypes of HLA system on the territory of Eurasia

Clinical case 111 Shevchenko A.A., Kashkarov E.A., Zhila N.G., Koshevoy A.V. Clinical case of successful application of reosteosynthesis sternum in chronic postoperative sternomediastinitis

Experience exchange 113 Ivanov V.A., Bolshev K.N., Alekseev R.Z., Andreev A.S. Determination of the thermal characteristics of the material of the insulating sheath for the treatmentof cold injuries 115 Saleev R.A., Abdrashitova A.B. Comparative analysis of maxillofacial area diseases, which led to temporary disability in dental medical organizations 118 Savvina M.S., Evseeva S.A., Nelunova T.I., Burtseva T. Е., Slobodchikova M.P. Risk factors influencing the persistence of patent ductus arteriosus in neonates with CHD in the RS (Ya) 3’ 2019 5 КОЛОНКА ГЛАВНОГО РЕДАКТОРА

the established mechanism, the result The “Yakut Medical Journal” was es- of which is the next issue. Here comes tablished to more fully cover a wide range the third issue of the “Yakut Medical of health problems, prevention, revealing Journal”. and treatment of widespread diseases of In 2018-2019 the portfolio of materials the Republic Sakha (Yakutia) population. submitted for publication in the “Yakut Besides, its tasks surely include promot- Medical Journal” is quite complete. The ing the achievements of medical science geography of the authors is wide. The and medical education not only in the subjects are diverse. Among the authors republic, but also in the Russian Feder- there are graduate students, applicants ation and the entire world community. for academic degrees, the materials of Therefore, the "Yakut Medical Journal" which are accepted for publication in the is not limited to the publication of materi- first instance. als only in its scientific profile. Until now, “Yakut Medical Journal” is a multidis- the journal has had enough space for the Dear Colleagues! ciplinary publication. The editorial board publication of a wide range of scientific adheres to the editorial policy developed problems; it exists today, and will contin- September has come. Autumn time. in accordance with the Charter of the ue to be so. The work of the editorial board of the publication. One of the main principles of I wish you, our authors, good health, “Yakut Medical Journal” is a continuous the journal’s editorial policy is the princi- success in research activities, inter- cycle. The journal should be published ple of strict observance in each issue of esting publications! And we thank our quarterly on an approved schedule re- its scientific profile. These are molecular users for being with us, we are glad gardless of vacation period, long holi- genetics and biochemistry, cardiology, that papers of our journal are interest- days and vacation days. No doubt, the pediatrics, oncology, neurology. Materials ing for you! editorial staff rests, goes on vacation, on these topics are given priority in the See you in the next issues of our “Ya- but this does not violate the work of publication. kut Medical Journal”!

Editor-in-chief Anna Romanova 6 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

ПЕРЕДОВАЯ СТАТЬЯ

A.N. Romanova, T.M. Klimova, A.G. Egorova, A.A. Kuzmina, I.S. Malogulova, N.S. Arkhipova PREVALENCE AND TREATMENT OF ARTERIAL HYPERTENSION IN THE DOI 10.25789/YMJ.2019.67.01 NATIVE RURAL POPULATION OF YAKUTIA

The objective of the research was to study the prevalence and characteristics of treatment of arterial hypertension (AH) in the indigenous rural population of the Sakha (Yakutia) Republic. Epidemiological research was conducted among the population (20 years and older) of 3 districts of the Sakha (Yakutia) Republic, and representatives of indigenous ethnic groups (Yakuts, Evens, and Evenks). The prevalence of AH among the surveyed population was 45.9% (95% CI: 42.5-49.3). There were no statistically significant differences in the frequency of hypertension in men and women (45.3 and 46.2%, respectively, p = 0.805). According to the survey, antihypertensive drugs (AHD) were taken by 51.2% of individuals with hypertension according to research criteria. Among women, the proportion of individuals using AHD was statistically significantly higher than among men (57.6 and 39.2%, respectively, p < 0.001). In 75.4% of cases, patients took one antihypertensive drug. In 52.8% of cases, drug therapy included angiotensin-converting enzyme inhibitors, in 42% of cases – calcium channel blockers, in 13.6% – β-blockers, 8.4% – angiotensin II receptor blockers, and in 3.1% – diuretics. The level of blood pressure corresponded to the “target” in 30.9% of those taking AHD. Along with improving the diagnosis of hypertension and finding and eliminating risk factors, it is necessary to take measures to increase patient adherence to treatment and control blood pressure levels, as well as to conduct pharmacogenetic studies of the effectiveness of antihypertensive drugs. Keywords: arterial hypertension, arterial hypertension, prevalence, antihypertensive drugs, treatment efficacy, Yakutia.

Introduction. Arterial hypertension The aim of the research was to study is a major risk factor for coronary heart the prevalence and characteristics of disease, chronic renal failure, cerebral treatment of hypertension in the indige- ROMANOVA Anna Nikolaevna, Doctor of stroke and other cardiovascular diseas- nous rural population of the Sakha (Ya- Medical Sciences, Director of Yakut Science es. According to WHO, in 2015, 22% of kutia) Republic. Centre of Complex Medical Problems, Yakutsk, the world’s population aged 18 years and Materials and Methods. A screen- Russia, +7-968-151-88-87, e-mail: ranik@ older had elevated blood pressure [8]. ing survey was conducted in 2017-2018, mail.ru, ORCID: 0000-0002-4817-5315, While in high-income countries there is among the population of 3 districts of the KLIMOVA Tatiana Mikhailovna, Candidate currently a decrease in the prevalence of Sakha (Yakutia) Republic aged 20 years of Medical Sciences, Associate Professor of AH, in low- and middle-income countries and older (Oymyakonsky, Gorny and Tat- Department of Pharmacology and Pharmacy, Medical Institute of the M.K. Ammosov the number of AH patients continues to tinsky), who were representatives of in- North-Eastern Federal University, Senior increase. This is caused not only by the digenous ethnic groups (Yakuts, Evens, Researcher, Department of Epidemiology aging of the population but also by the and Evenki) The study was conducted of Chronic Noncommunicable Diseases, presence of such risk factors as over- subject to the voluntary informed consent Yakut Science Centre of Complex Medical weight or obesity, decreased physical ac- of the participants. The survey program Problems, Yakutsk, Russia, +7-914-233- tivity, stress, environmental degradation, included: a survey using a special ques- 67-24, e-mail: [email protected], ORCID: etc. tionnaire, an anthropometric examination 0000-0003-2746-0608, EGOROVA Aitalina In the Russian Federation, according using a standardized method, a threefold , Candidate of Medical Sciences, Grigorevna to the multicenter study called Epide- measurement of blood pressure (BP), Head of the Department of Epidemiology of Chronic Non-Communicable Diseases of the miology of Cardiovascular Diseases in and venous blood sampling after fasting. Yakut Science Centre of Complex Medical Various Regions of Russia (ECCD), the The content of glucose, total cholesterol Problems, Yakutsk, Russia, +7-914-234-64-11, prevalence of hypertension among the (cholesterol), triglycerides, high-density e-mail: [email protected]. ORCID: 0000-0002- population of 25–64 years old was 44%. lipoprotein cholesterol (HDL cholester- 8526-9644, KUZMINA Ariana Afanasevna, The study showed variability in the preva- ol) was determined using the express Candidate of Pharmaceutical Sciences, Head lence rate depending on the region of the analyzer CardioChek PA, USA. The of Department of Pharmacology and Pharmacy participant (from 37.8 to 56.1%) [1]. concentration of low-density lipoprotein at Medical Institute of the M.K. Ammosov Sakha (Yakutia) Republic is the larg- cholesterol (LDL cholesterol) was calcu- North-Eastern Federal University, Yakutsk, Russia, [email protected], ORCID: est subject of the Russian Federation, lated using the Friedewald formula with 0000-0001-5220-0766, MALOGULOVA characterized by unfavorable climatic a blood triglyceride level of less than 4.5 Irina Shamilevna, Candidate of Biological conditions for living and working people. mmol/L. Arterial hypertension (AH) was Sciences, Associate Professor of Department For the period from 2004 to 2018, the established by the criteria of ESH/ESC, of Pharmacology and Pharmacy at Medical prevalence of diseases associated with 2013 [9]. The group with hypertension Institute of the M.K. Ammosov North- high blood pressure increased among also included individuals who took an- Eastern Federal University, Yakutsk, Russia, the adult population of the Republic from tihypertensive drugs (AHD) during the [email protected], ORCID: 0000-0003-0687- 65.0 to 108.4 per 1000 population [2, 5]. survey or stopped taking them less than 7949, ARKHIPOVA Natalia Spartakovna, At the same time, official statistics proba- 2 weeks before the survey, regardless Candidate of Medical Sciences, Head of the Laboratory of Clinical Population and Medical bly do not fully reflect the entire situation. of the measured blood pressure level. Social Research, Yakut Science Centre of Additional research may help to make Effective treatment of hypertension was Complex Medical Problems, Yakutsk, Russia, adjustments to ongoing prevention pro- considered the achievement of target +7-962-739-80-77, e-mail: [email protected]. grams in the region. values of blood pressure on the back- 3’ 2019 7

Table 1

Main Characteristics of the Surveyed Indigenous Population of the Sakha (Yakutia) Republic, 20 Years and Older

20-43 years 44-59 years 60-74 years 75 year and old Indicator n=237 n=310 n=177 n=53 р Мужчины n=287 SBP, mm Hg 120.0 (111.8-133.3) 130.0 (116.3-143.0) 141.0 (130.0-160.0) 130.0 (120.0-152.5) <0.001 DBP, mm Hg 80.0 (70.3-84.3) 80.0 (73.3-90.0) 90.0 (80.0-100.0) 90.0 (80.0-92.5) <0.001 Height, cm 168.0 (164.1-172.0) 167.0 (163.0-172.0) 162.0 (158.0-165.8) 160.0 (157.0-166.8) <0.001 Body mass, kg 69.0 (62.0-79.8) 74.0 (64.0-81.0) 66.0 (62.0-76.0) 64.5 (55.8-73.8) <0.001 Body mass index, kg/m2 24.1 (21.9-27.3) 26.8 (23.7-29.3) 25.3 (23.1-29.2) 25.1 (22.1-26.7) 0.007 Waist circumference, cm 81.5 (76.3-94.0) 92.0 (84.0-99.8) 92.0 (84.0-97.5) 92.0 (88.0-97.0) <0.001 Triglycerides, mmol/L 0.9 (0.6-1.2) 1.1 (0.8-1.8) 0.9 (0.6-1.3) 0.8 (0.6-1.4) 0.048 Total cholesterol, mmol/L 4.8 (4.1-5.8) 5.4 (4.3-6.2) 5.0 (4.2-5.7) 4.7 (3.7-5.6) 0.103 HDL cholesterol, mmol/L 1.4 (1.2-1.7) 1.4 (1.2-1.6) 1.5 (1.2-1.6) 1.1 (0.9-1.5) 0.032 LDL cholesterol, mmol/L 2.5 (1.9-3.1) 2.9 (2.2-3.4) 2.8 (2.2-3.7) 2.8 (2.2-3.7) 0.038 Atherogenic index, c.u. 2.4 (1.8-3.3) 2.8 (2.1-3.5) 2.4 (1.9-3.1) 2.7 (2.1-3.9) 0.106 Glucose, mmol/L 4.8 (4.5-5.3) 5.1 (4.6-5.6) 4.9 (4.3-5.5) 4.7 (3.9-5.0) 0.006 Women n=526 SBP, mm Hg 120.0 (110.0-130.0) 134.0 (120.0-150.0) 140.0 (120.0-165.4) 150.0 (138.5-176.7) <0.001 DBP, mm Hg 78.5 (70.0-84.2) 85.0 (80.0-94.0) 89.5 (80.0-100.0) 90.0 (80.0-100.0) <0.001 Height, cm 158.0 (152.9-162.0) 154.0 (150.0-158.0) 150.0 (147.5-154.0) 146.0 (141.5-150.0) <0.001 Body mass index, kg 61.9 (54.0-72.0) 67.0 (58.2-76.0) 63.0 (55.0-74.0) 58.0 (49.0-69.5) <0.001 BMI, kg/m2 24.9 (22.4-28.4) 27.9 (24.9-31.6) 27.9 (24.3-32.3) 27.6 (23.4-32.0) <0.001 Waist circumference, cm 82.0 (74.0-93.8) 91.0 (83.0-100.0) 94.0 (83.5-103.0) 93.0 (84.3-101.0) <0.001 Triglycerides, mmol/L 0.8 (0.6-1.1) 1.1 (0.8-1.5) 1.0 (0.7-1.4) 0.9 (0.7-1.1) <0.001 Total cholesterol, mmol/L 4.6 (3.9-5.3) 5.7 (4.9-6.4) 5.4 (4.7-6.2) 5.4 (4.6-5.9) <0.001 HDL cholesterol, mmol/L 1.6 (1.3-1.8) 1.5 (1.4-1.7) 1.4 (1.3-1.7) 1.5 (1.2-1.7) 0.253 LDL cholesterol, mmol/L 2.2 (1.8-2.8) 3.1 (2.5-3.8) 3.1 (2.6-3.8) 3.3 (2.5-4.0) <0.001 Atherogenic index, c.u 2.2 (1.5-2.7) 2.8 (2.2-3.5) 2.7 (2.0-3.5) 2.6 (2.1-3.1) <0.001 Glucose, mmol/L 4.6 (4.3-5.1) 4.9 (4.5-5.6) 4.6 (4.2-5.4) 4.5 (4.1-4.9) <0.001 Note: p is the achieved level of statistical significance of differences when comparing age groups by gender (Kruskal–Wallis test). ground of antihypertensive therapy [9]. Table 2 Statistical data analysis was carried out in the IBM SPSS STATISTICS Prevalence of hypertension among the indigenous population of Yakutia, n (%) 22 package. When comparing groups Men Women depending on the type of data, Krus- Age, years n=287 n=526 Both genders n=813 р kal-Wallis criteria were used, as well as 20-43 29 (26.6) 35 (21.3) 64 (23.4) 0.315 Pearson’s chi-squared test (χ2). The crit- 44-59 38 (41.80) 115 (52.5) 153 (49.4) 0.085 ical value of the level of statistical signifi- 60-74 51 (71.80) 63 (59.4) 114 (64.4) 0.091 cance of differences (p) was taken to be 75 and older 12 (75.0) 30 (81.1) 42 (79.2) 0.616 All 130 (45.3) 243 (46.2) 373 (45.9) 0.805 5%. Descriptive statistics of quantitative data are presented as median (Me) and Note: p is the achieved level of statistical significance of differences when comparing groups interquartile range (Q1-Q2). AH preva- by gender (Pearson's test χ2). lence rates are presented with a 95% confidence interval (95% CI). The prevalence of AH among the sur- there are also no significant differences Results and Discussion. During the veyed population was 45.9% (95% CI: between women and men in the frequen- epidemiological study in 3 districts of Ya- 42.5-49.3). Among the male population, cy of hypertension [1]. kutia, 813 men and women aged 20 years the figures were 45.3% (95% CI: 39.5- Evaluation of antihypertensive ther- and older were examined. Men and women 51.2), and among women 46.2% (95% apy was carried out according to the were comparable in age, the average age CI: 41.9-51.5), respectively. With an inpatients’ self-reports, which makes pos- of the men surveyed was 49.3 (15.9) years, crease in the age of the examined, the sible the presence of a systematic error women – 50.9 (15.3) years (p = 0.138). frequency of hypertension increased sig- associated with a “memory error”. Some Analysis of the main anthropometric nificantly (Table 2). There are no statis- patients could not specify all drugs that and metabolic indicators of the sample tically significant differences in the prev- were taken in connection with high blood showed that, in general, the indigenous alence of hypertension among men and pressure. At the same time, it is closer to rural population is characterized by in- women, both in general and in each age the actual practice of taking the drugs by creased body weight, waist circumfer- group separately. These data are close the patients themselves. Conducting a ence, and a fairly favorable lipid profile to the results of the ECCD study in 9 re- future study with simultaneous evaluation (Table 1). At the same time, from the age gions involving 15,300 people, where the of the doctor’s prescriptions and patient of 44, the upper quartile of the distribution prevalence of AH was on average 44%. self-report could help eliminate these of systolic and diastolic blood pressures The prevalence rates of hypertension in shortcomings and objectively assess the is in the range corresponding to the crite- 8 regions were higher for men than for patients’ adherence to treatment, as well rion of AH. These features were noted by women. In the Tyumen Region, which as the treatment tactics used by the med- us in previous studies [4, 6, 7]. also belongs to the northern territories, ical staff. 8 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

ers (CCB) were respondents noted the use of 3 drugs, of used, in 13.6% – which in 4 cases it was a combination of β-blockers (β-АБ), an ACE inhibitor + CCB + ARBs. 8.4% – angiotensin When measured in 59 out of 191 II receptor block- (30.9%) respondents taking AHD, the ers (ARBs), 3.1% level of blood pressure corresponded to – diuretics (Fig. 1). the “target”. In women, the proportion of According to the people with a normal level of blood pres- research of ECCD, sure on the background of drug intake ACE inhibitors were was slightly higher, but the differences also the most fre- did not reach a statistically significant quently used drugs level (32.1 and 27.5%, respectively, p Fig. 1. Frequency of use of different groups of antihypertensive drugs: ACE inhibitors – inhibitors of the angiotensin-converting in other territories = 0.535). According to the results of the enzyme; CCB – calcium channel blockers; β-AB – beta of the Russian Fed- ECCD study, the treatment efficiency was blockers; ARBs – angiotensin II receptor blockers. eration [1]. But in 53.5% among women and 41.4% among Yakutia, in contrast men, which is much higher than our data According to the survey, 191 people to the regions stud- [1]. from among 373 persons diagnosed with ied, the second in use are CCBs. The Thus, the results of the study showed AH by screening (51.2%) were taking proportion of people receiving CCB was a high incidence of hypertension among AHD. Among women, the proportion of 18.8% in the Russian study, against 42% the indigenous population of Yakutia drug users was statistically significantly in Yakutia. The proportion of β-AB, di- (45.9%). AHD was taken by 57.6% of higher than among men (57.6 and 39.2%, uretics and ARBs was significantly lower. women and 39.2% of men with hyperten- respectively, p <0.001). According to the The revealed features require additional sion according to the research criteria. At results of the ECCD study, on average studies, since the high frequency of pre- the same time, target blood pressure was in Russia 60.9% of women and 39.5% scribing CCBs may be due to their high achieved only in 30.9% of patients. Along of men with hypertension took AHD [1]. efficiency in this ethnic group. with improving the diagnosis of hyperten- Thus, the attitude of patients to the treat- 144 (75.4%) respondents taking AHD sion, finding and eliminating risk factors, ment of hypertension in Russia has com- indicated using 1 drug. In 52.8% of cas- measures are needed to increase patient mon features, regardless of the region. es, these were ACE inhibitors, in 31.9% adherence to treatment and controlling The most commonly used drugs were – calcium antagonists, in 9% – β-AB. Of blood pressure levels, as well as phar- angiotensin-converting enzyme inhibitors the 47 patients taking 2 or more drugs, 22 macogenetic studies of the effectiveness (ACE inhibitors), which were used as (46.8%) indicated that an ACE inhibitor of antihypertensive drugs in this ethnic monotherapy or were part of combina- was taken in combination with CCB. The group. tion therapy in 59% of treatment cases. second in frequency (14.9%) was a com- The work was carried out as part of In 42% of cases, calcium channel block- bination of an ACE inhibitor with β-AB. 6 the research project “The Contribution of Metabolic Syndrome to the Development Table 3 of Coronary Artery Atherosclerosis in Ya- kutia’s Residents” (Reg. No. 01-20-128- Range of used groups of antihypertensive drugs 08-00).

References Drug intake Monotherapy Combined n=191 (100%) n=144 therapy Group of drugs (75.4%) n=47 (24.6%) 1. Бойцов С.А., Баланова Ю.А., Шальнова С.А. [и др.]. Артериальная гипертония n % n % n % среди лиц 25-64 лет: распространенность, ACE inhibitors 76 39.8 76 52.8 осведомленность, лечение и контроль, По CCB 46 24.1 46 31.9 материалам исследования ЭССЕ. Кардиовас- кулярная терапия и профилактика. 2014; 4 β-АБ 13 6.8 13 9.0 (13): 4–14. [Boytsov SA, Balanova YA, Shalnova ARBs 5 2.6 5 3.5 SA. [et al.]. Arterial Hypertension Among Individ- Alpha adrenomimetics 2 1.0 2 1.4 uals of 25–64 Years Old: Prevalence, Awareness, Treatment, and Control. By the data from CD- Diuretics 2 1.0 2 1.4 VRR. Kardiovaskulyarnaya terapiya i profilaktika. ACE inhibitors + CCB 22 11.5 22 46.8 2014; 4 (13): 4–14. (In Russ.)] ACE inhibitors + β-AB 7 3.7 7 14.9 2. Заболеваемость взрослого населения CCB + β-AB 4 2.1 4 8.5 Республики Саха (Якутия): Стат.материалы. ГУ ЯРМИАЦ МЗ РС (Я). Якутск. 2003-2017 гг. ACE inhibitors + AV + ARBs 4 2.1 4 8.5 [Morbidity of the Adult Population of the Sakha CCB + ARBs 3 1.6 3 6.4 (Yakutia) Republic: statistical materials. Yakutsk. ACE inhibitors + ARBs 2 1.0 2 4.3 2003-2017. (In Russ.)] 3. Соболева М.С., Жмеренецкий К.В., CCB + Diuretics 1 0.5 1 2.1 Воронина Н.В., Лоскутова Е.Е., Добрых В.А. ARBs + Diuretics 1 0.5 1 2.1 Использование фиксированных комбинаций β-AB + ARBs 1 0.5 1 2.1 при проведении медикаментозной терапии артериальной гипертензии в северных ACE inhibitors + CCB + Diuretics 1 0.5 1 2.1 субъектах Дальневосточного федерального ACE inhibitors + β-AB + Diuretics 1 0.5 1 2.1 округа Якутский медицинский журнал. 2018; 4: 92–96. [Soboleva MS, Zhmerenetsky KV, Vo- Note: ACE inhibitors – inhibitors of the angiotensin-converting enzyme; CCB – calcium ronina NV, Loskutova EE, Dobryh VA. Usage of channel blockers; β-AB – beta blockers; ARBs – angiotensin II receptor blockers. the fixed-doses combinations for drug therapy of 3’ 2019 9

arterial hypertension in northern regions of the Adult Population of Russia in 2017. Statistical тония и метаболический синдром у коренных Far Eastern Federal district. Yakutskij medicinskij materials. Part IV. Moscow, 2018. Accessed малочисленных народов Севера в Якутии. zhurnal. 2018; 4: 92–96. (In Russ.)] 15.05.2019. (In Russian)] https://www.ros- Якутский медицинский журнал. 2018; 1: 14–16. 4. Климова Т.М., Федорова В.И., minzdrav.ru/ministry/61/22/stranitsa-979/statis- [Sofronova SI. Arterial hypertension and meta- Балтахтинова М.Е. Критерии ожирения для ticheskie-i-informatsionnye-materialy/statistich- bolic syndrome in small indigenous people of the идентификации метаболических факторов eskiy-sbornik-2017-god North of Yakutia. Yakutskij medicinskij zhurnal. риска у коренного сельского населения 6. Климова Т.М., Федорова В. И., 2018; 1: 14–16. (In Russ.)] Якутии. Сибирский медицинский журнал. 2012; Балтахинова М. Е. [и др.]. Содержание холес- 8. WHO.Noncommunicable Diseases Coun- 8:110–113. [Klimova TM, Fedorova VI, Baltakhi- терина и риск атеросклероза у сельского try Profiles. 2018: 223. Accessed 25.05.2019. nova ME. Obesity Criteria for Identifying Metabol- корен-ного населения Республики Саха https://www.who.int/nmh/publications/ncd-pro- ic Risk Factors Among Indigenous Rural Popula- (Якутия). Экология человека. 2014; 4: 22–27. files-2018/en/ tion of Yakutia. Sibirskij medicinskij zhurnal. 2012; [Klimova TM, Fedorova VI, Baltakhinova ME [et 2013 ESH/ESC Guidelines for the manage- 8:110–113. (In Russ.)] al.]. Cholesterol and Risk of Atherosclerosis in ment of arterial hypertension: the Task Force for 5. Общая заболеваемость взрослого на- Rural Indigenous Population of the Sakha (Ya- the management of arterial hypertension of the селения России в 2017 году. Статистические kutia) Republic. Ekologiya cheloveka. 2014; 4: European Society of Hypertension (ESH) and of материалы. Часть IV. Москва, 2018. Ссыл- 22–27. (In Russ.)] the European Society of Cardiology (ESC). J. Hy- ка активна на 15.05.2019. [Prevalence of the 7. Софронова С.И. Артериальная гипер- pertens. 2013; 7 (31): 1281–1357.

ORIGINAL RESEARCHES

E.P. Ammosova, T.M. Klimova, T.M. Sivtseva, A.I. Fedorov, M.E. Baltakhinova, R.N. Zakharova LIPOPROTEIN LIPASE GENE POLYMOR- DOI 10.25789/YMJ.2019.67.02 PHISM rs320 AND METABOLIC SYNDROME IN NATIVE PEOPLE OF YAKUTIA

The aim of the study was investigation the relationship of allelic variants and genotypes of the rs 320 polymorphism of the LPL gene with the metabolic syndrome and its components in adult population of the Yakut ethnic group. In the studied group, it was not possible to establish a direct connection between the allelic variants, the genotypes of the LPL rs320 gene with the metabolic syndrome and its components. However, it is important to note individuals with the TT genotype had somewhat higher level of triglycerides in the blood. It may be associated with a small sample size. We assume that the T allele is associated with low enzyme activity in this population, and plays a key role in the development of diseases associated with metabolic disorders. Keywords: obesity, metabolic syndrome, multiple metabolic risk factors, population, genetics, rs320 polymorphism of the LPL gene, dyslipidemia, indigenous population, Yakutia, North.

One of the variants of the LPL gene, betes in the Yakut population has shown 39 dated June 26, 2014). Participation in which encodes the enzyme lipoprotein [1, 2, 3]. However, the mechanism of the the study was completely voluntary. Ob- lipase, is the replacement of thymine (T) influence of polymorphism on the devel- tained clinically useful information was by guanine (G) at position 495 in intron opment of metabolic disorders has not available to study participants. The ini- 8. The Hind III (rs320) polymorphism been studied enough. It is known that tial participant’s selection was based on changes the recognition site of the Hind the inhabitants of the North from time im- household lists. The study included per- III restriction enzyme and affects the ac- memorial adapted to a diet rich in fats. sons of the Yakut nationality (by self-de- tivity of the enzyme. In recent studies, it Currently, there is an intensive increase termination) at the age of 18 and older, was shown that the polymorphism rs320 in the incidence of metabolic disorders in regardless of whether they have any so- of the LPL gene has a significant effect the Yakut population. In this regard, the matic disease (n = 363). on the structure of the precursor RNA study of the mechanisms of the influence Analyze of rs320 polymorphism was [9]. The frequency of minor G allele in of the LPL gene on the metabolism of in- performed in 189 representatives (142 different world populations varies from digenous peoples is a very interesting. women and 47 men aged 18 years and 24 to 38%, the highest frequency is ob- The purpose of this study was to esti- older) who gave voluntary informational served among the population of Saudi mate of the allele and genotype frequen- consent to conduct genetic studies. The Arabia (37,6%) [3, 5]. The literature pres- cy of LPL gene rs 320 polymorphism and average age was 52.7 (13.7) years. All ents conflicting data on the role of Hind its association with metabolic parameters participants were examined by a single III (rs320) polymorphism in the develop- and components of the metabolic syn- program, including anthropometric exam- ment of diseases associated with lipid drome in the adult population of Yakut ination by the standard method, analysis metabolism disorders. In some studies, nationality living in Central Yakutia. of body composition for bio-impedance the presence of a minor allele was asso- Materials and methods: The gen- analysis “Tanita” (Japan) SSC 330, two- ciated with a lower risk of diseases asso- otype frequency of the LPL gene rs320 fold blood pressure measurement (BP), ciated with impaired lipid metabolism [4, was estimated among the unorganized fasting venous blood sampling. The con- 10, 12, 16], in other studies the presence population of the Central region (Gorny tent of glucose, total cholesterol (choles- of this polymorphism was a risk factor for ulus, village Berdigestyakh) of the Sakha terol), triglycerides, high density lipopro- the development of metabolic disorders Republic (Yakutia). The research project teins (HDL cholesterol) was determined and related diseases [7, 13]. was approved by the local bioethics com- on the express analyzer Cardiochek PA, In early studies the significant associ- mittee of the Yakut Scientific Center for USA. The concentration of low-density ation between LPL rs320 with type 2 dia- Complex Medical Problems (Protocol No. lipoprotein cholesterol (LDL cholesterol) 10 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

was calculated using the Friedwald for- common; GG (12%) was a rare geno- pared with carriers of G [7, 8, 15, 17]. mula with a blood triglyceride level of less type. The frequency of the heterozygous Early studies in the Yakut population than 4.5 mmol/l. variant was 29%. Thus, homozygous showed association of T alleles with an Hypertriglyceridemia was established genotypes were more common than het- increased risk of type 2 diabetes [1, 2, with triglycerides ≥1.7 mmol/l, hypoal- erozygous (table 1). These distributions 3]. Our data show that the TT genotype phalesterolemia - at HDL cholesterol are consistent with data from other Euro- may be associated with low enzyme ac- concentrations <1.0 mmol/l in men and pean and Asian populations [3]. Table 2 tivity and an increase in triglyceride levels <1.3 mmol/l in women; elevated blood presents the quartile distribution of some in the blood. Contradictory results of the pressure — with CAD ≥130 mmHg and/ biochemical and anthropometric data different authors may be related to the or DBP ≥85 mmHg; fasting hyperglyce- depending on the genotype and allelic fact that, the functioning of a gene is sig- mia - with blood plasma glucose ≥5.6 variants of the rs320 polymorphism. The nificantly affected by the lifestyle, phys- mmol/l. Persons received specific med- triglycerides level in the blood of individ- ical activity of a person and the type of ical treatment for these conditions were uals with the TT genotype was slightly food, because the gene product associ- also referred to patients with metabolic higher than that of GG homozygotes. The ated with energy metabolism [1, 2]. The disorders. Multiple metabolic disorders GT genotype was associated with lower lower prevalence of diabetes and cardio- were established with 2 or more of the 4 diastolic pressure values compared to vascular diseases among the indigenous above-mentioned risk factors. The follow- homozygotes. There were no statistically people of the North in historical past is ing criteria were used to diagnose obesity: significant differences in the levels of oth- probably associated with a change in the body mass index ≥30 kg/m2; the ratio of er indicators. energy balance of modern man. waist circumference to height ≥0.5; waist Metabolic syndrome was observed in Conclusion. In the studied indige- circumference by IDF criteria (IDF1) for 27 studied patients (14.3%). The most nous population of Yakutia, we did not European populations (more than 80 cm common variant of the metabolic syn- reveal an association of the rs320 poly- in women and 94 cm in men); IDF (IDF2) drome was a combination of central morphism of the LPL gene and meta- for Asian populations (more than 80 cm in type of obesity, high blood pressure and bolic parameters, which may be due to women and 90 cm in men) [13]. dyslipidemia. The frequency of the met- limitations in the formation of the group. LPL rs320 SNP was genotyped by the abolic syndrome and its components did The allele and genotype frequency were PCR-RFLP method. Amplification was not depend on the genotypes and allel- close to those described for rs320 in oth- performed with specially selected prim- ic variants of the studied polymorphism er groups of the world’s population. The ers and ready-made commercial reaction (table 3). This result may be due to the obtained data and the analysis of litera- mixtures on the T-100 amplifier (Bio- limited number of observations with met- ture suggest that the T allele carrier, as- Rad). Next, the PCR products were sub- abolic syndrome and lipid disorders. To sociated with a low activity of the enzyme jected to Hind III restriction enzyme (New date, the effect of rs320 polymorphism that hydrolyzes triglycerides in chylomi- England Biolabs) according to the man- on the enzyme lipoprotein lipase activity crons and LDL, may increase the risk of ufacturer's protocol. Restriction products and metabolic processes in the human metabolic disorders under conditions of were visualized using electrophoresis in body is not completely clear. Most stud- changes of energy balance. a 3% agarose gel on the gel documen- ies have shown that allele G is associ- Considering that this population is tation system BDA digital system 20 ated with a low risk of developing met- evolutionarily adapted to food rich in (Biometra). Each reaction was carried abolic syndrome, acute cardiovascular fats, study of the rate of utilization of out in triplicate. conditions (strokes, heart attacks), and dietary fats in individuals with different The verification of the distribution of a lower risk of developing hypertension LPL rs320 genotypes could be of scien- genotypes to the equilibrium state of Har- [4, 10, 15]. But at the same time, there tific interest. dy-Weinberg was carried out using an are works indicating that carriers of the The study was supported by the Min- online calculator at https://wpcalc.com/ GG genotype have a high risk of diabet- istry of Education and Science of the en/equilibrium-hardy-weinberg / [6]. Sta- ic dyslipidemia and type 2 diabetes [11, Russian Federation (project “Clinical and tistical data analysis was carried out in 13]. There are studies that suggest the genetic aspects of diseases character- the IBM SPSS STATISTICS 22 package. association of the genotype and nutri- istic of the indigenous people of Yakutia The comparison of groups was performed tion in the form of greater sensitivity to in modern conditions” (0794-2017-0016, using Mann-Whitney and Pearson χ2 cri- the diet of carriers of the T allele, com- FSRG-2017-0016)). teria depending on the type of data. The critical value of the level of statistical sig- Table 1 nificance of differences (p) was 5%. Results and discussion. The distribution of genotypes, both in general Frequency distribution of alleles and genotypes of the rs 320 polymorphism of the LPL gene among the population among all examined, and in groups by age and sex, did not correspond to the rs 320 n (%) Hardy-Weinberg equilibrium (Table 1). This is probably due to due to insufficient Alleles size of the studied group. However, an at- G 78 (32) tempt to assess the relationship between T 166 (68) lipid, anthropometric parameters and LPL Genotypes GG 23 (12.2) rs320 was made as the part of explorato- χ2= 12.47 ry research. GT 55 (29.1) р<0.001 In the studied group, the T allele fre- TT 111 (58.7) quency was 68%, and the G allele - 32%. Note: χ2 - Pearson Chi-square test; p - the achieved level of significance when checking The TT genotype (58.7%) was the most compliance with the Hardy-Weinberg equilibrium distribution. 3’ 2019 11

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Effects of lipoprotein lipase gene varia- 0.59 (0.54; 0.64) 0.58 (0.53; 0.65) 0.58 (0.53; 0.65) 0.59 (0.53; tions, a high-carbohydrate / Huang Xin [et al.] // 0.64) BioScience Trends. -2011. -№5 (5). - P. 198-204. Note: p - the achieved level of statistical significance of differences when comparing groups using the Mann-Whitney test; Me (Q1; Q3) - median (25-75%); BMI - body mass index, OT- waist circumference; AMMOSOVA Elena Petrovna, candidate of Medical Sciences, leading researcher, Re- search Center of the Medical Institute of the дицинский журнал. – 2011. – №3. – С. 29-30. North-Eastern Federal University named after References Osakovskij V L Lipoprotein lipase is an import- M.K. Ammosova, 677000, Moscow Yakutsk, ant genetic factor in the development of T2DM in str. Oiunskogo, 27, Russia. tel. 8-964-424- 1. Метаболический синдром у аборигенно- the aboriginal population of Yakutia / V.L. Osa- 39-08 Mail: [email protected]. ORCID: го населения Якутии / В.Л. Осаковский [и др.] kovskij, M.N. Yakovleva //Ibid. – 2011. - №3 (35). 0000-0002-7973-6103, KLIMOVA Tatyana // Якутский медицинский журнал. - 2010.-№ 2. – P. 29-30. Mikhailovna, candidate of Medical Sciences, -С. 98-102. 3. Сравнительная характеристика вариан- assistant professor of Department of Phar- Metabolic syndrome in the aboriginal popula- та LPL rs320 липопротеинлипазы в различных tion of Yakutia / V L Osakovskij [et al.] // Yakut популяциях /Сивцева Т.М. [и др.] // Там же. – macology and Pharmacy, Medical Institute of medical journal -. 2010. - №2 (30). – P. 98-102. 2014. -№2. - С. 67-69. the North-Eastern Federal University named 2. Осаковский В.Л. Липопротеин липа- Comparative characteristics of lipoprotein after M.K. Ammosova, senior researcher of за – важный генетический фактор развития lipase gene variant LPL rs320 in different popu- the Department of Epidemiology of Chronic СД2 у аборигенного населения Якутии / В.Л. lations / T M Sivceva [et al.] //Ibid. – 2014. -№ 2 Non-Communicable Diseases, Yakutsk Sci- Осаковский, М.Н. Яковлева // Якутский ме- (46). – P.67-69. entific Center for Complex Medical Problems, 12 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

Moscow. Yakutsk, Russia, +79142336724, Table 3 e-mail: [email protected]. ORCID: 0000- 0003-2746-0608, SIVTSEVA Tatyana The frequency of the metabolic syndrome and its components depending on the allelic Mikhailovna, cand. biol. sc., senior scien- variant and the genotypes of the rs 320 polymorphism of the LPL gene tist, Research Center of the Medical Institute North-Eastern Federal University named af- Genotypes n (%) Alleles n (%) ter M.K. Ammosov, 677000, Yakutsk, str. Oi- 2 2 Factor χ , p χ , p unskogo, 27, Russia. tel. +7 914 223-74-32, GG n=23 GT n=55 TT n=111 G n=78 T n=166 e-mail: [email protected]. ORCID 0000-0002- Raised blood pressure 1501-7433, FEDOROV Afanasy Ivanovich, Yes 13 (10.9) 36 (30.3) 70 (58.8) χ2=0.776 49 (31.6) 106 (68.4) χ2=0.003 cand. biol. science, senior researcher, Re- No 9 (14.1) 16 (25) 39 (60.9) р=0.67 25 (31.3) 55 (68.8) р=0.955 search Center of the Medical Institute of the North-Eastern Federal University named Reduced HDL cholesterol after M.K. Ammosova, 677000, Yakutsk, str. Yes 4 (28.6) 3 (21.4) 7 (50) χ2=3.845 7 (41.2) 10 (58.8) χ2=0.713 Oiunskogo, 27, Russia. tel. 8-914-2332966, No 19 (10.9) 52 (29.7) 104 (59.4) p=0.146 71 (31.3) 156 (68.7) p=0.425 e-mail: [email protected]. ORCID: 0000- 0002-7973-6103, BALTAKHINOVA Marina Raised triglycerides Egorovna, junior researcher, Research Cen- Yes 4 (16) 4 (16) 17 (68) χ2=2.468 8 (27.6) 21 (72.4) χ2=0.290 ter of the Medical Institute of the North-East- No 19 (11.6) 51 (31.1) 94 (57.3) p=0.291 70 (32.6) 145 (72.4) p=0.590 ern Federal University named after M.K. Am- Raised fasting plasma glucose mosova, 677000, Yakutsk, str. Oiunskogo, 27, Russia. Tel. 89142710634, e-mail: bmeg@ Yes 4 (16) 4 (16) 17 (68) χ2=2.315 8 (27.6) 21 (72.4) χ2=0.287 rambler.ru. ORCID: 0000-0003-0986-7754, No 19 (11.9) 49 (30.6) 92 (57.5) p=0.314 68 (32.5) 141 (67.5) p=0.675 ZAKHAROVA Raisa Nikolaevna, cand. med. Obesity science, scientific director, Research Center of the Medical Institute of the North-Eastern Fed- 2 2 Yes 11 (12.4) 25 (28.1) 53 (59.6) χ =0.087 36 (31.6) 78 (68.4) χ =0.002 eral University. M.K. Ammosov, 677000, Ya- No 6 (11.3) 16 (30.2) 31 (58. 6) p=0.957 22 (31.9) 47 (68.1) p=1.0 kutsk, str. Oiunskogo, 27, Russia. tel. 8-914- 2223002, e-mail: [email protected]. ORCID: Abdominal obesity IDF1 0000-0002-1395-8256. Yes 14 (10.9) 37 (28.7) 78 (60.5) χ2=0.23 51 (30.7) 115 (69.3) χ2=0.124 No 5 (12.8) 12 (30.8) 22 (56.4) p=0.891 17 (33.3) 34 (66.6) p=0.732

Abdominal obesity IDF2 Yes 14 (11.6) 36 (29.8) 71 (58.7) χ2=0.129 50 (31.8) 107 (68.2) χ2=0.069 No 5 (10.6 %) 13 (27.7) 29 (61.7) 0.938 18 (30) 42 (70) p=0.871 Multiple metabolic risk factors Yes 7 (18.4) 9 (23.7) 89 (58.9) χ2=2.013 16 (34) 31 (66) χ2=0.45 No 16 (10.6) 46 (30.5) 89 (58.9) p=0.366 62 (31.5) 135 (68.5) p=0.734 Metabolic syndrome 23 (69.7 Yes 4 (14.8) 6 (22.2) 17 (63) 2 2 χ =0.945 10 (30.3) %) χ =0.019 p=0.623 p=1.0 No 15 (10.6) 43 (31.5) 83 (58.9) 58 (31.5) 126 (68.5) Note: χ2 * - Pearson Chi-square test, p – significance level 3’ 2019 13

A.T. Dyakonova, Kh.A. Kurtanov, N.I. Pavlova, N.A. Solovyova, N.P. Filippova, T.N. Aleksandrova DETERMINATION OF HLA ALLELES USING SINGLE NUCLEOTIDE POLYMORPHISM OF RS3104413 HLA-DQA1 GENE AMONG DOI 10.25789/YMJ.2019.67.03 PATIENTS WITH TYPE 1 DIABETES OF THE REPUBLIC SAKHA (YAKUTIA)

In this paper, we analyzed the polymorphism rs3104413 of the HLA-DQA1 gene among patients with type 1 diabetes and a control sample of the population of the Republic of Sakha (Yakutia). Type 1 diabetes (diabetes mellitus type 1) among all forms of diabetes is no more than 10-15%, and type 1 diabetes is related to the most important medical and social problems associated with the often occurring childhood and adolescence, severe course, early disability and mortality. In the study of rs3104413 polymorphism, a significantly lower frequency of the C allele (47.1) was observed in the group of healthy individuals compared with the group of people with type 1 diabetes (78.3%). The calculation of the odds ratio showed that the frequency of the C allele in the group of people with type 1 diabetes was significantly higher (OR - 4.036; 95% CI: 2.71-6.02; p <0.001). The study revealed 6 haplotypes and genes. The haplotype DRB1 * 03: 01-DQA1 * 05: 01-DQB1 * 02: 01, DR3 / X, DRX / X was associated with the allele C of the rs3104413 polymorphism. The allele G of rs3104413 polymorphism was associated with the haplotype carrier DRB1 * 04: 01 – DQA1 * 03: 01-DQB1 * 03: 02 (DR4-DQ8) and DRB1 * 04: 01-DQA1 * 03: 01-DQB1 * 03: 01 (DR4-DQ7). Thus, the data obtained can be used as biological predictors of the development of type 1 diabetes in order to carry out timely personalized preventive measures. Keywords: type 1 diabetes mellitus, HLA typing, HLA-DQA1 gene, polymorphism.

Type 1 diabetes is a disease in which hood and adolescence, characterized by - a unique scientific installation “The Ge- the body is not able to properly metabo- severity, early disability and mortality [3]. nome of Yakutia” (reg. No. US_507512). lize carbohydrates and to a lesser extent According to modern data, a large The sample of patients consisted of 92 other components of food. This disease number of genes are involved in the de- patients of the Yakut Scientific Center for is caused by a lack of insulin, a hormone velopment of type 1 diabetes [3], more Complex Medical Problems, state auton- that is produced by the pancreas and than half of the genetic risks are due to omous institution of the Republic Sakha that is required by the body to convert the participation of polymorphic variants (Yakutia) "Republic Hospital №1 National glucose from other food components into of HLA genes located on the short arm of Center of Medicine » and Endocrinology energy. The most severe form of diabe- chromosome 6 (6p21). The main genetic Department of Yakutsk Clinical Hospital, tes is type 1 diabetes (type 1 diabetes contribution to the susceptibility to type Yakutsk. The sample of patients included mellitus). Despite the fact that its share 1 diabetes is made by genes of the HLA 92 patients with a diagnosis of type 1 dia- among all forms of diabetes is no more system encoding class II molecules of betes, aged 4 to 56 years, living in the RS than 10-15%, it is type 1 diabetes that the main human histocompatibility com- (Ya), Yakuts by ethnicity. By gender there is considered to be the most important plex, especially the DR and DQ genes were 44 (47.8%) male and 48 (52.2%) fe- medico-social problem of health care, of the HLA class, whose association with male. The average age of patients was since this disease often occurs in child- the development of type 1 diabetes has 23.04 ± 0.27 years (from 4 to 56 years), been shown in numerous publications for the average age of male patients was various population groups [1, 4]. 20.5 ± 2.3 years (from 5 to 40 years), and YSC CMP, Yakutsk, Republic Sakha (Yakutia), In Russia, studies on the definition of female - 25.11 ± 2 , 59 years old (from 4 Russia: D'YAKONOVA Aleksandra Timo- HLA alleles using single nucleotide poly- to 56 years old). The control sample con- feevna – Junior researcher of the laboratory morphisms are not carried out. In this re- sisted of 210 Yakuts who did not suffer of heritable pathology Tel.: 8 (914) 238 68 gard, today there is a need for research from type 1 diabetes. Ethnicity counted to 93. E-mail: [email protected]; KURTANOV aimed at developing a regionally-adapted the third generation. Ethnicity counted to Khariton Alekseevich – Candidate of Scienc- method for the HLA-typing of type 1 di- third generation. es., Chief Scientific Officer - Head of the De- abetes using single nucleotide polymor- Amplification of the HLA-DQA1 gene partment of Molecular Genetics. Tel.: +7 (914) phisms (SNP). region containing the single nucleotide 106 00 30. E-mail: [email protected]. PAVLOVA Nadezhda Ivanovna – Candidate Objective: to determine HLA alleles polymorphism rs3104413 was performed of Sciences, chief scientific officer - head of using single nucleotide polymorphism of during real-time PCR using primer pairs the laboratory of heritable pathology. Tel.: +7 rs3104413 HLA-DQA1 gene and its as- and allele-specific probes for DNA ampli- (914) 289 39 36. E-mail: solnishko_84@inbox. sociation with type 1 diabetes. fication described in Serr I. et al. [6] Prim- ru; SOLOV'EVA Natal'ya Alekseevna – Can- Material and research methods: An ers and probes were synthesized by the didate of Sciences, - researcher of the Lab- experimental part of the work on the ge- company Biotech-Industry (Lumiprobe) oratory of Population Genetics. Tel.: 8 (924) notyping of the rs3104413 polymorphism, LLC (Moscow, Russia). The sequence 171 34 89. E-mail: [email protected]; the HLA-DQA1 gene, was carried out in of primers: Forward primer 5'-CAGCT- FILIPPOVA Natal'ya Pavlovna – Candidate the laboratory of hereditary pathology of GAGCACTGAGTAG-3 ', reverse prim- of Sciences, associate professor, researcher of the Laboratory of Population Genetics. Tel.: the Department of Molecular Genetics of er 5'-GCAGTTGAGAAGTGAGAG-3'. 8 (914) 303 43 95. E-mail: [email protected]; the Yakutsk Scientific Center for Com- Probes structure: FAM - Probe rs3104413 АLEKSANDROVA Tujara Nikonovna - Junior plex Medical Problems (YSC CMP). DNA LPC [6FAM] CAGCCT [+ G] CT [+ C] TC researcher of the laboratory of heritable pa- samples from the collection of the YSC [+ C] TA [+ T] TGG [BHQ1], HEX - Probe thology E-mail: [email protected]. CMP biomaterial are used for the study rs3104413 LPG [HEX] CAGCCT [+ G] CT 14 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

Table 1

Temperature polymorphism amplification program rs3104413

Stages Temperature, °С Time Cycles First denaturation 95 10 s 1 Denaturation 95 30 s 50 Annealing 55 1 min

[+ G] TC [+ C] TA [+ T] TGG [BHQ1]. ing the program: "Office Microsoft Excel Amplification was carried out accord- 2010", "Statistics 8.0". The frequencies ing to the temperature program below of alleles and rs3104413 genotypes were (Table 1): determined by direct counting. Results The fluorescence signal was mea- were considered significant when the “p” sured at the second stage of the reaction value was less than 0.05 (p <0.05). Figure 2. Electrophoregram of the HLA DRB1 (55 ° C - 1 min). The detection of fluores- Genotyping of HLA DRB1 and DQB1 and DQB1 amplification product on 2% agarose cence was carried out "at the end point" alleles was carried out with the commer- gel (HLA DRB1 and DQB1 genotyping using according to the protocol of the device cial HISTOTYPE kits, the HLA alleles commercial HISTOTYPE kits). Note: b.p.. - base "Real-time CFX 96 Touch" ("Biorad", of DRB1 * 03: 01 (DR3), DRB1 * 04: 01 pair. 1 - DRB1 * 03 (220 bp); 2, - DRB1 * 04 (200 USA). An example of the distribution of (DR4), DQB1 * 02: 01 (DQ2), DQA1 * 05: bp); 3 - DQB1 * 02: 01 (800 bp); 4 - DQB1 * 02: 02 (150 bp); 5 - DQA1 * 05: 01 (235 bp). Internal clouds of genotypes of PCR and detec- 01 were progenotyped. control: 1070 b.p. (1, 2, 4, 5) and 429 bp (3). 6 - tion of fluorescence "at the end point" is The amplification parameters were DNA marker "Step100". presented in Figure 1. optimized for a total reaction volume of Statistical analysis of the results of the 10 μl. PCR was performed according to (Biolabmix LLC, Novosibirsk, Russia). medical genetic study was conducted us- the manufacturer’s instructions in an MJ Results and discussion. The results Mini Gradient Thermal Cycler (BioRad) of the analysis of the frequency distri- thermal cycler (Table 2). bution of alleles and genotypes of the The results of the amplification were rs3104413 polymorphism among pa- fractionated in 2% agarose gel, with tients with type 1 diabetes and control ethidium bromide, at a voltage of 120- sample are presented in table 3. 300 V, for 45-120 minutes. Documen- In the study of rs3104413 polymor- tation and visualization of PCR ampli- phism, a significantly lower frequency of fication was performed by photograph- the C allele (47.1) was observed in the ing in UV light using a Vil-ber Lourmat group of healthy individuals compared gel-documenting instrument (Fig. 2). with the group of people with type 1 di- The interpretation of the results of abetes (78.3%). The calculation of the genotyping according to the HISTO- odds ratio showed that the frequency of TYPE kits (updated 01 / 2015_3.19.0 the C allele in the group of people with (6.2)) was carried out on the basis Figure 1. Distribution of genotype clouds of type 1 diabetes was significantly high- rs3104413 polymorphism of the HLA-DQA1 gene. of the assessment chart: for HISTO- er (OR - 4.036; 95% CI: 2.71-6.02; p Note: “K–” - negative control, C / C - homozygous TYPE, specific bands have sizes of <0.001). for ancestral allele C. C / G - heterozygote, G / G - 220, 200, 800, 150 and 235 bp. In all Analysis of the distribution of geno- homozygote for mutant allele G. Compliance with lanes without an allele-specific am- fluorescent dyes: allele C - FAM channel, allele G types showed that the most common gen- plification, an internal control of 429 - channel HEX. otype of the studied polymorphism in the or 1070 bp should be clearly visible. group of people with type 1 diabetes is C Evaluation of the bands was carried / C (69.6%), and in the group of people out using a DNA marker “Step 100” not suffering from type 1 diabetes is the homozygous genotype G / G (41.9% ). Table 2 The calculated conjugacy coefficient Temperature polymorphism amplification program HISTOTYPE of Pearson (C) allele C (0.278) shows the average strength of the connection between the carriage of the allele C and Steps Temperature, °С Time Кол-во циклов type 1 diabetes. The normalized value of First denaturation 96 5 min 1 the Pearson coefficient (C ') indicates the Denaturation 96 20 s average relationship between the car- Annealing and 5 Elongation 68 1 min riage of the allele C (0.393) and type 1 Denaturation 96 20 s diabetes. Annealing 64 50 s 10 The analysis revealed 6 haplotypes and genes. The haplotype DRB1 * 03: Elongation 72 45 s 01-DQA1 * 05: 01-DQB1 * 02: 01, DR3 Denaturation 96 20 s / X, DRX / X was associated with the al- Annealing 61 50 s 15 lele C of the rs3104413 polymorphism. Elongation 72 45 s The allele G of rs3104413 polymorphism Final elongation 72 5 min 1 was associated with the haplotype carrier 3’ 2019 15

associated with the haplotype carrier Table 3 DRB1 * 04: 01 – DQA1 * 03: 01-DQB1 The frequency of occurrence of genotypes and alleles of the rs3104413 polymorphism in * 03: 02 (DR4-DQ8) and DRB1 * 04: 01- the group of patients with type 1 diabetes and control sample DQA1 * 03: 01-DQB1 * 03: 01 ( DR4- DQ7). There is a significantly low frequency Patient with control OR Haplotypes, 2 of allele C (47.1) in the control sample alleles T1D (n = sample (n = Х (95% CI) Significance, p 92),аbs. (%) 210), аbs.(%) For alleles compared with patients with type 1 diabetes (78.3%) in the rs3104413 polymor- С/С 64 (69.6) 76 (36.2) phism. The calculation of the odds ratio С/G 16 (17.4) 46 (21.9) 32.099 4.036 <0.001* G/G 12 (13.0) 88 (41.9) (2.708- showed that the frequency of the C allele С 144 (0.783) 198 (0.471) 6.017) in the group of people with type 1 diabe- 49.184 <0.001** G 40 (0.217) 222 (0.529) tes was significantly higher (OR - 4.036; 95% CI: 2.71-6.02; p <0.001). Note. The achieved level of significance when comparing the distribution of genotypes (*) and Thus, the data obtained can be used allele frequencies (**) in comparison groups 1 and 2 is the number of samples, X2 with the Yeats amendment. as biological predictors of the development of type 1 diabetes in order to carry Table 4 out timely personalized preventive measures. Identification of HLA haplotypes and genotypes using single nucleotide polymorphism The study was conducted in the frame- rs3104413 work of research on the study of the genetic structure and burden of hereditary The number Genotype, % pathology of populations of the Republic of people Allele Allele Haplotype by genes HLA of Sakha (Yakutia). with this С/С С/G G/G С G haplotype DRB1*03:01- References 16 87.5 12.5 0 0.938 0.063 DQA1*05:01-DQB1*02:01 1. Волыкина А.П., Горшков И.П., Прилуцкая DRB1*04:01– О.А. Генетические маркеры сахарного диабе- DQA1*03:01-DQB1*03:02 20 0 40 60 0.200 0.800 та (часть 1). Успехи современной медицины. (DR4-DQ8) 2017; 2(5):123-126. [Volykina AP, Gorshkov IP, DR3/4-DQ8 8 0 100 0 0.500 0.500 Priluckaya OA. The role of genetic factors in the DR3/X 50 100 0 0 1.000 0.000 formation of different levels of type 1 diabetes mellitus in Europe and the Russian Federation. DRB1*04:01- Modern science success. 2017; 2(5):123-126. (In DQA1*03:01-DQB1*03:01 132 0 33.3 66.7 0.167 0.833 Russ.)] (DR4-DQ7) 2. Кураева Т.Л., Ширяева Т.Ю., Прокофьев DRX/X 76 100 0 0 1.000 0.000 С.А. Роль генетических факторов в формиро- вании разного уровня заболеваемости сахар- Note: DRX / X - the absence of both DR3 and DR4; DR3 / X - carrier variant 1 of type DR3 ным диабетом 1-го типа в Европе и Российской and type DR3, not related to DR4 Федерации. Проблемы эндокринологии. 2011; 1:19-25. [Kuraeva TL, Shiryaeva TYU, Prokofiev DRB1 * 04: 01 – DQA1 * 03: 01-DQB1 * is the haplotype DRB1 * 04: 01-DQA1 * SA. The role of genetic factors in the formation 03: 01-DQB1 * 03: 01 (DR4-DQ7) [5]. of different levels of type 1 diabetes mellitus in 03: 02 (DR4-DQ8) and DRB1 * 04: 01- Europe and the Russian Federation. Problems of DQA1 * 03: 01-DQB1 * 03: 01 ( DR4- Thus, the study of this rs3104413 poly- Endocrinology. 2011; 1:19-25. (In Russ.)] DQ7). Table 4. morphism in determining the haplotype is 3. Atkinson M. A. The pathogenesis and natu- According to the literature, more than insufficient and requires further research ral history of type 1 diabetes. Cold Spring Harbor 90 percent of patients with type 1 diabe- in combination with other SNPs. perspectives in medicine. 2012; 2(11) a007641. doi:10.1101/cshperspect.a007641 tes are carriers of either HLA-DR3, DQB1 Conclusion 4. Redondo MJ, Steck AK, Pugliese A. Genet- * 0201 (DR3-DQ2), or DR4, DQB1 * 0302 The study revealed 6 haplotypes and ics of type 1 diabetes Pediatric Diabetes. 2017; (DR4-DQ8). About 30% of patients have genes. The haplotype DRB1 * 03: 01- 19(3):346-353. doi: 10.1111/pedi.12597 the combined genotype DR3 / 4, which is DQA1 * 05: 01-DQB1 * 02: 01, DR3 / X, 5. Nguyen C. Varney MD, Harrison LC, Mora- DRX / X was associated with the allele han G. Definition of high-risk type 1 diabetes associated with the greatest susceptibility HLA-DR and HLA-DQ types using only three sin- to the disease [2]. Associated previously C of the rs3104413 polymorphism. The gle nucleotide polymorphisms. Diabetes. 2013; with a low risk of developing the disease allele G of rs3104413 polymorphism was DB_121398. doi: 10.2337/db12-1398 16 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

S.I. Sofronova, A.N. Romanova, M.P. Kirillina CORRELATION OF THE M235T POLYMORPHISM OF THE AGT GENE WITH ARTERIAL HYPERTENSION AND ITS RISK DOI 10.25789/YMJ.2019.67.04 FACTORS IN THE INDIGENOUS PEOPLE OF УДК 616-008.9. 1-81(571.56) THE ARCTIC TERRITORY OF YAKUTIA

A case-control study was conducted for the indigenous population living in the Arctic territory of Yakutia to determine the association of the M235T polymorphism of the AGT gene with hypertension and its risk factors. A higher average blood pressure, elevated cholesterol and its fractions, a higher incidence of abdominal obesity in carriers of the mutant GG genotype were found both in the general population and separately for people with hypertension. The study shows the contribution of the G allele of the AGT gene to the development of hypertension, lipid disorders and abdominal obesity. Keywords: AGT gene, polymorphism, arterial hypertension, risk factors, indigenous people, Yakutia.

Arterial hypertension is the leading risk Materials and research methods. ly selected samples were subjected to factor for disability and premature mortal- The collection of material for the study repeated genotyping. ity in the global population. As of 2010, was carried out in expeditionary con- Biochemical methods of the research 31.1% of the adult population of the world ditions in the Arctic territory of Yakutia, included blood lipid profile: total choles- (1.39 billion people) was suffering from including the places of compact resi- terol (TC), LDL Cholesterol, HDL Choles- hypertension (30.7% of men and 28.8% dence of the indigenous peoples (Nizh- terol, TG, glucose test. of women) [10]. In Russia, according to an nekolymsky, Verkhnekolymsky and Tom- When judging the incidence of disor- ESSE-RF epidemiological study, which ponsky districts). 348 people of the indig- ders of the blood lipid profile in a popula- was conducted in 12 regions, the prev- enous nationality were surveyed with the tion, we used the Russian recommenda- alence of AH was 50.2% (51.1% in men, continuous method. The sample consist- tions of the V revision of Society of car- 49.7% in women) [2]. It is recognized that ed of an adult population aged 20 to 70 diology of Russian Federation (VNOK), hypertension is a polygenic multifactorial years (225 women and 123 men). The 2012, into account the European recom- disease, the genetic role of which has al- response was 75%. The average age mendations, 2011. Hypercholesterolemia ready been proven. Currently, more than of respondents was 48.16 ± 0.52 years, (HCE) is the level of total cholesterol (TC) 1.500 genetic polymorphisms associated 49.71 ± 0.63 in women and 44.98 ± 0.91 ≥ 5.0 mmol/l, the high LDL Cholesterol with blood pressure have been identified, in men. level≥3.0 mmol/l, the low HDL Cholester- which contribute through various patho- Inclusion criteria: representatives of ol level ≤1.0 mmol/l in men; 1.2 mmol/l genetic mechanisms [7]. A particularly indigenous people (Evens, Chukchi, Yu- in women. Hypertriglyceridemia (HTG) is important role belongs to the genes of the kaghirs, Yakuts). the TG level ≥1.7 mmol/l; a hyperglyce- renin-angiotensin system (RAS) respon- Exclusion criteria: representatives of mia on an empty stomach (a glucose in a sible for vascular tone. The most relevant non-indigenous nationalities. blood plasma on an empty stomach ≥ 6.1 polymorphisms of the RAS genes for The research program included the mmol/l) or glucose intolerance (a glucose hypertension are angiotensinogen gene following sections: a survey on the ques- in a blood plasma in 2 hours after glucose polymorphisms (AGT). The results of var- tionnaire to assess the objective state; loading within ≥7.8 and ≤11.1 mmol/l). ious researches are ambiguous. Despite informed consent of the respondent to Blood pressure (BP) was measured numerous studies, the degree and reli- conduct research; anthropometric exam- twice with an OMRON automatic tonom- ability of associations vary, for some loci ination with hip and waist measurement; eter (Japan) on the right hand in a sitting the data are contradictory. blood sampling for biochemical studies position with the calculation of the aver- The aim of the study was to research from the cubital vein in the morning on age BP. Hypertension is present at the the relationship of angiotensinogen (AGT) an empty stomach with a 12-hour absti- 140/90 mmHg (2017 ACC/AHA Guide- gene polymorphism with arterial hyperten- nence from food. Blood sampling from line). sion and its risk factors in the indigenous the cubital vein for molecular genetic The abdominal obesity (AO) is ex- people of the Arctic territory of Yakutia. studies was carried out in a tube with posed to the value of the waist measure- EDTA. Genomic DNA was isolated from ment (WM) ≥ 80 cm on women, ≥94 cm peripheral blood leukocytes by the meth- on men. Yakut science centre of complex medical od of phenol-chloroform extraction. Allel- The study was conducted according to problems, 677000, Sergelyakhskoe shosse, ic variants of the AGT gene were tested the Local Ethics Committee protocol YSC 4, Yakutsk, The Republic of Sakha (Yakutia), using a polymerase chain reaction with CMP on the respondent's informed con- Russia: SOFRONOVA Sargylana Ivanovna – real-time results (real-time PCR). Geno- sent to the processing of personal data PhD, Head of Scientific-organizational and in- typing of the polymorphic AGT gene was and the study. formation publishing Department; sara2208@ performed with the usage of kits (Lytech Statistical data processing was per- mail.ru; ROMANOVA Anna Nikolaevna – R&D LLC, Moscow) on the «Real-time formed using standard methods of math- MD, Director, ORCID: 0000-0002-4817-5315; KIRILLINA Maria Petrovna – PhD (Biology), CFX96» amplifier (BioRad, USA) in ac- ematical statistics using the SPSS soft- leading researcher, head of lab., kirillinamp@ cordance with the manufacturer’s instruc- ware package (version 19.0). To define mail.ru. tions. For quality control, 10% of random- the characteristics, the arithmetic mean 3’ 2019 17

(M) and the characteristic’s standard At analyzing the frequencies of lipid genotypes of the AGT gene among error of the mean (m) were calculated. and carbohydrate disorders in respon- groups was compared. None of the data Intergroup differences were evaluated dents, it was found that all carriers of sets (Table 1) showed significant devia- using analysis of variance or non-para- genotypes showed high numbers of tion from Hardy-Weinberg equilibrium (χ2 metric criteria. When comparing the fre- hypercholesterolemia (HCE), especial- = 0.32, p = 0.24 for “case” and χ2 = 4.84, quencies of genotypes, the standard χ2 ly atherogenic HCE, and GG genotype p = 0.02 for “control”) and there was no criterion with the Yates correction was carriers showed the highest frequency significant difference in the frequencies of used. The relative risk (OR – odds ratio) of hypo-alpha-cholesterolemia (Hypo-α- genotypes or alleles between hyperten- of disease development at a certain gen- CE). The frequencies of HCE, LDL HCE, sive and normotonic patients, with the ex- otype was calculated using the standard Hypo-α-CE in the general population did ception of the homozygous AA genotype formula OR=a/b x d/c, where a and b is not have significant differences between (χ2 = 5.21, p = 0.001, OR = 0.39, 95% CI the number of patients with and without genotypes. Thus, in individuals with the = 0.27-0.89) (Table 2). the mutant genotype, respectively, and d, AA genotype, the frequency of HCE was We used 2 types of genetic models c is the number of people in the control 46.3%, АG - 41.4%, GG - 49.6%. More in order to verify the connection of the group with and without the mutant gen- than half of the respondents had the M235T polymorphism of the AGT gene otype. OR is indicated with a 95% confi- highest frequency of LDL HCE in individ- with AH (Table 3). Analyzing the models, dence interval. Differences were consid- uals with AA genotype, 64.8% and GG we found a link between AH and the mu- ered statistically significant at p <0.05. genotype - 59.8%. The frequency of Hy- tant homozygous genotype GG and G al- Results and discussion. In the to- po-α-CE was 33.3% in the AA genotype lele in the recessive model. What is also tal population of the indigenous people individuals, AG - 29.9%, GG - 43.1%. The confirmed by a number of foreign studies, of the Arctic territory of Yakutia, the fre- frequency of HTG in the carriers of ho- in particular, the effect of the G allele and quency distribution of the AA, AG and GG mozygous AA and GG genotypes signifi- the GG genotype on the risk of developing M235T genotypes of the AGT gene was cantly differed (5.5% and 17.5%, respec- essential hypertension [4,6,8,9,15,16]. In 15.5% (n = 54), 45.1% (n = 157), 39.4% tively, p = 0.033). Also significantly higher the Russian study, which included 514 (n = 137), respectively, which corre- was the frequency of HG in heterozygous patients, the association of the G allele sponds to the Hardy-Weinberg equilibri- AG carriers compared with individuals with the risk of developing hypertension um (χ2 = 0.18, p = 0.66), A alleles - 38.1% with the mutant GG genotype (8.3% and in men with an odds ratio of 1.95 (p = (n = 265), G - 61.9% (n = 431). 2.9%, respectively, p = 0.048). 0.003) was shown [1]. In contrast, in Co- When comparing the mean values of We also conducted a study of the con- lombia, Mongolia, the Caucasus, Leb- lipids and glucose depending on a par- jugation of AGT polymorphism with the anon, and India, no reliable association ticular AGT gene genotype, we obtained presence of abdominal obesity. Carriers of AG and GG genotypes with AH was statistically significant differences in all of the AG and GG genotypes (59.2% and found [3,5,11,14,18]. It was assumed that indicators in carriers of heterozygous AG 60.6%) had the largest statistically insig- the population is heterogeneous in these and mutant homozygous GG genotypes. nificant frequency of AO versus 46.3% of countries, polymorphism is associated In GG carriers all values were higher: to- individuals with the AA genotype, thereby with differences in populations. tal cholesterol AG 4.93 ± 0. 06 and GG indicating a certain conjugacy of the G al- Depending on the genotype, we ana- 5.12 ± 0.06, respectively, p = 0.037; HDL lele with the presence of AO. lyzed the average level of systolic blood 1.32 ± 0.02 and 1.22 ± 0.02 (p = 0.003); Considering the high frequency of oc- pressure (SBP) in hypertensive patients. LDL 3.12 ± 0.05 and 3.33 ± 0.05, (p = currence of AH in the population (53.3%), In individuals with arterial hypertension, 0.005); TG 1.06 ± 0.02 and 1.21 ± 0.04 for further study, the general population of the average level of SBP in carriers of (p = 0.005). Our study confirms the con- the indigenous people of the Arctic terri- AA, AG and GG genotypes was 173.53 tribution of the G allele to impaired lipid tory of Yakutia was divided into 2 groups. ± 3.62, 161.72 ± 1.40 and 159.72 ± 1.92 metabolism. On the contrary, their aver- For the study, 2 groups were formed - mmHg, respectively, there were signif-

Table 1

Frequencies of genotypes and alleles of the M235T polymorphism of the AGT gene and correspondence to Hardy-Weinberg equilibrium (HWE) Frequencies of alleles Genotype Case HWE χ2 p Control HWE χ2 p Allele Case Control AA 0.097 0.12 0.214 0.17 A 0.347 0.416 AC 0.497 0.45 0.32 0.24 0.405 0.49 4.84 0.02 C 0.653 0.584 CC 0.406 0.43 0.381 0.34 age glucose values are significantly low- “case” and “control”: “case” - persons icant differences in individuals with the er compared with AG genotype carriers suffering from hypertension (175 people), AA genotype compared with others (p (4.83 ± 0.11 and 4.35 ± 0.08, respec- “control” - people without hypertension = 0.001). We did not detect any special tively, p = 0.001). Significant differences (173 people). The average age of hyper- differences in the mean values of SBP in were also obtained when comparing the tensive patients was 53.07 ± 0.49 years, normotonics. mean values in individuals with homozy- those without AH - 38.88 ± 0.60 years. Comparison of mean concentrations gous AA and GG genotypes, namely, in This case-control study was includ- of blood lipids and glucose in individuals TG values (1.03 ± 0.05 and 1.21 ± 0.04, ed to determine the association of AGT with and without hypertension was car- p = 0.029), glucose (4.88 ± 0.14 and 4.35 gene variants with AH and its risk factors. ried out, depending on whether the AGT ± 0.08, p = 0.001). The frequency of occurrence of M235T gene is a member of a particular M235T 18 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

in the development of atherogenesis. In Table 2 normotonics, significant differences were Frequency distribution of M235T genotypes of the AGT gene among persons with and noted in the frequency of Hypo-α-choles- without AH terol, where the highest frequency was observed in GG carriers. In many studies Frequencies of genotypes examining the association of the M235T Genotype χ2 p OR 95%CI Case Control AGT gene polymorphism with lipid dis- AA 0.097 0.214 5.21 0.001 0.39 0.27-0.89 orders, no significant reliable links have AG 0.497 0.405 1.71 нд 1.45 0.83-2.54 been identified. Only a few studies con- GG 0.406 0.381 0.13 нд 1.11 0.63-1.96 firm the fact that the G allele has a significant effect on increasing the concentra- genotype (Table 4). For all respondents We determined the frequency of lipid tion of total cholesterol and atherogenic in the “case” values of lipid metabolism, and carbohydrate disorders for persons cholesterol [12]. except for HDL cholesterol, and glucose with and without AH, depending on gen- The study of conjugation of AGT poly- were higher compared to “control”. Signif- otype carriership (Fig. 1). In hypertensive morphism in the case and control with the icant differences were found in the aver- patients, all values exceeded those of presence of abdominal obesity revealed age concentrations of TG in all represen- normotonics. When comparing certain the highest incidence of AO in individuals tatives, total cholesterol in the homozy- types of lipid disorders and carbohydrate with AH - carriers of AG and GG geno- gous carriers of AA and GG genotypes, metabolism with respect to one or anoth- types from 76.1% to 83.9%. In the control, LDL cholesterol in carriers of the mutant er genotype, individuals in the “case” and the frequency of AO varied from 28.6% in GG genotype, glucose in individuals with “control” identified significant differences carriers of the heterozygous genotype to the AA and AG genotype. The average in the frequency of LDL HCE in hyper- 43.9% in homozygous GG carriers. Both concentrations of total cholesterol, ath- tensive patients of heterozygous and in the group with AH and in the “control”, erogenic cholesterol and TG in hyper- mutant homozygous genotypes, thereby the highest frequency of AO is associated tensive patients were higher with the GG proving the contribution of the G allele with the G allele, thereby proving its con- genotype. tribution to the development of the metabolic syndrome. This was also confirmed Table 3 by a number of foreign studies [13, 17]. Conclusion. Based on our findings, Frequency distribution of genotypes M235T of AGT gene among persons with and there is, indeed, a single genetic compo- without AH according to the dominant and recessive model nent in the implementation of hypertension and its risk factors for development, Frequencies of genotypes Genotype χ2 p OR 95%CI such as lipid disorders and abdominal Case Control obesity. Proof of this are higher average AA+ AG 0.581 0.618 blood pressure, elevated cholesterol and 0.28 0.51 0.86 0.56-1.31 GG 0.418 0.382 its fractions, a higher incidence of ab- AA 0.095 0.214 9.58 0.001 0.39 0.21-0.72 dominal obesity in carriers of the mutant AG+ GG 0.905 0.786 GG genotype both in the general population of the indigenous people of the Arc- а b tic territory of Yakutia, and separately for people with arterial hypertension. Thus, the genetic mechanisms of hypertension in the group of patients with arterial hypertension are realized through the G allele, which programs obesity, increased pressure, and lipid metabolism disorders. The research was conducted within research projects of YSC CMP "A contribution of a metabolic syndrome to devel- 1а. The frequency of disorders of lipid and carbohydrate metabolism in individuals with hyperten- opment of atherosclerosis of coronary ar- sion, depending on the genotypes M235T AGT, 1b. The frequency of disorders of lipid and car- teries in residents of Yakutia", R&D "De- bohydrate metabolism in individuals without hypertension, depending on the genotypes M235T AGT. Note: *- p<0,05 Table 4 Mean levels of lipid spectrum and blood glucose in hypertensive patients and those without hypertension depending on the M235T genotypes of the AGT gene (M±m)

Blood AA genotype AG genotype GG genotype parameters case p control case p control case p control TC 5.16±0.11 <0.05 4.74±0.16 4.98±0.08 >0.05 4.78±0.10 5.29±0.07 <0.01 4.74±0.09 LDL 3.30±0.08 >0.05 3.06±0.12 3.17±0.06 >0.05 2.98±0.08 3.47±0.06 <0.01 3.04±0.08 HDL 1.32±0.06 >0.05 1.26±0.05 1.29±0.02 <0.05 1.40±0.04 1.22±0.02 >0.05 1.23±0.03 TG 1.17±0.08 <0.02 0.90±0.06 1.14±0.03 <0.01 0.87±0.04 1.29±0.05 <0.05 1.05±0.06 glucose 5.37±0.24 <0.01 4.43±0.14 5.10±0.15 <0.01 4.15±0.10 4.40±0.10 >0.05 4.24±0.10 3’ 2019 19

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O.I. Kit, A.L. Bazaev, E.Yu. Zlatnik, I.A. Novikova, E.P. Ulianova, O.G. Shulgina, A.B. Sagakyants, E.N. Kolesnikov, V.S. Trifanov, S.S. Mezentsev, A.V. Snezhko, T.B. Katsieva EXPRESSION OF SOME MOLECULAR AND BIOLOGICAL MARKERS IN DIFFERENT PE- RIODS OF PROGRESSION AFTER RADICAL SURGICAL TREATMENT OF ESOPHAGEAL DOI 10.25789/YMJ.2019.67.05 CANCER

30 patients with stage II and III of squamous cell carcinoma of the esophagus after surgical treatment were analyzed retrospectively. Prognostic significance of the expression of immunohistochemical markers p53, bcl-2, ki-67 and E-cadherin and tumor proliferative activity were studied. A significant decrease in the frequency of tumors expressing p53, as well as an increase in the number of tumors expressing bcl-2, was detected in the group of patients with an increase in the event-free period for up to 365-540 days. The mean numbers of bcl-2 positive cells in groups Rostov, Russia: Oleg I. KIT, D.Med.Sc., Pro- with progression from 181 to 364 days and from 365 to 540 days were 2.3 and 2.8 times higher fessor, Corresponding Member of RAS, Gen- than in patients with progression in 180 days and earlier. The ki-67 index in the latter was signifi- eral Director of Rostov Research Institute of cantly higher than in groups with progression within 181-364 and 365-540 days. Oncology, [email protected], Adlan L. An increased proliferative activity was registered only in patients with progression in 180 BAZAEV, post-graduate student, Rostov Re- days and earlier. The E-cadherin expression in the group with progression in 365-540 days was search Institute of Oncology, tel. 89286146603, significantly higher than in patients with progression in < 180 and 181-364 days. [email protected], Elena Yu. ZLATNIK, Keywords: esophageal cancer, immunohistochemical markers, proliferative activity, p53, D.Med.Sc., Professor, Chief Researcher at bcl-2, ki-67, E-cadherin, progression. Laboratory of Immunophenotyping of Tumors, Rostov Research Institute of Oncology, tel. 89612726968, [email protected], Inna Esophageal cancer is one of the most tic factor due to the fact that it contributes A. NOVIKOVA, Cand.Med.Sc., Deputy Gen- aggressive malignant diseases of the to the survival of tumor cells [6, 8]. Oth- eral Director for Science, Rostov Research gastrointestinal tract significantly affect- er researchers showed high expression Institute of Oncology, tel. 89064162909, no- ing the quality of life of the patient with of bcl-2 to be a prognostically favorable [email protected], Elena P. ULIANO- VA, Researcher at Laboratory of Immunophe- high rates of poor outcome [3, 10]. Tu- factor [5, 9]. notyping of Tumors, Rostov Research Institute mors of epithelial origin, mainly squa- Analysis of proliferative activity (PA) of of Oncology, tel. 89064248556, uljanova_ele- mous cell carcinoma and adenocarcino- a tumor is the most important character- [email protected], Oksana G. SHULGINA, Junior ma, are the most common. According to istic of cancer, which allows characteriz- Researcher at Laboratory of Immunopheno- the International Agency for Research on ing its biological behavior. It is estimated typing of Tumors, Rostov Research Institute of Cancer (IARC), EC incidence and mor- by the ki-67 index, as only dividing cells Oncology, tel. 89185570986, ggaalliinnaa1@ tality in 2008 were 49.2 and 34.3, respec- detect antibodies to ki-67 [7]. mail.ru, . , Cand. Aleksandr B SAGAKYANTS tively, per 100 000 per year [12]. Disorders of intercellular adhesion as- Biol.Sc., Associate Professor, Head of Lab- oratory of Immunophenotyping of Tumors, High expression of p53 mutant protein sociated with pathological changes in the Rostov Research Institute of Oncology, tel. is known to predict poor survival in can- membrane protein E-cadherin are one of 89604458653, [email protected], Evgeniy cer of the stomach, lung, and other can- the factors contributing to the metastasis N. KOLESNIKOV, Cand.Med.Sc., Head of cers [4]. However, the predictor role of and progression of malignant tumors [1]. Department of Abdominal Onkology No. 1, p53 for EC remains a debatable [14]. In Studies of E-cadherin expression in lung, Rostov Research Institute of Oncology, tel. 2015, British journal of cancer published bladder and gastric cancers showed the 89185538854, [email protected], Vladimir a meta-analysis review of 11 large-scale significance of its determination. Stud- S. TRIFANOV, Cand.Med.Sc., Senior Re- studies on the role of p53 in EC over the ies have shown that E-cadherin has the searcher at Department of Abdominal Onkolo- past 20 years, in order to identify potential properties of a tumor growth suppressor gy No. 1, surgeon oncologist, Rostov Research Institute of Oncology, tel. 89185544312, Tri- biomarkers that are sensitive and predic- and its invasion [2]. An imbalance in the [email protected], Stanislav S. MEZENT- tive in EC. As a result, only three studies cadherin system, in particular inhibition of SEV, Cand.Med.Sc., oncologist at Department including 268 patients showed a connec- E-cadherin expression and overexpres- of Abdominal Onkology No. 1, surgeon oncol- tion between the poor prognosis and high sion of N-cadherin, is considered an im- ogist, Rostov Research Institute of Oncolo- expression of p53. The results of other portant component of the epithelial-mes- gy, tel. 89185028118, [email protected], studies contained conflicting data, most enchymal transition process. Aleksandr V. SNEZHKO, D.Med.Sc., Assis- of which showed that the prognostic role Thus, these IHC markers allow char- tant at Department of Oncology, Rostov State of this marker was not obvious [13]. acterization of the processes of adhe- Medical University, tel 89185131837, snezh- Among other markers considered to sion, apoptosis and proliferation of tumor [email protected], Tanzila B. KATSIEVA, Cand.Med.Sc., oncologist at Department of be oncogenes, the bcl-2 gene involved in cells, which seems significant for assess- Abdominal Onkology No. 1, surgeon oncolo- the negative apoptosis regulation can be ing the potential of tumor progression. gist, Rostov Research Institute of Oncology, marked. Some authors regard high ex- That is why we selected these markers tel. 89895113131, [email protected]. pression of bcl-2 as a negative prognos- and studied their expression in EC cells 3’ 2019 21

in different periods of the disease pro- ysis of the frequency of expression and decrease in the proportion of p53 positive gression after radical surgical treatment. average values of indicators depending tumor cells was detected as the time to The purpose of the study was a com- on the time to EC progression. An in- progression increased. With an increase parative assessment of the expression of creased time interval to disease progres- in the time to progression to 540 days, p53, bcl-2, ki-67, E-cadherin IHC mark- sion was accompanied by an increase in the number of p53 positive cells was 2.2 ers in the tumor tissue of EC patients at the frequency of expression of bcl-2+ and times lower than in patients with progres- different progression periods after surgi- a decrease in p53+ (table 1). No correla- sion within 180 days from the surgery, cal treatment. tion was observed between the disease and 1.5 times lower than in cancer pro- Material and methods. The study in- stage and event-free period. gression from 181 to 364 days. The dif- cluded 30 patients diagnosed with stage Table 1 demonstrates that longer references were statistically significant in II (n=15) and III (n=15) middle and lower lapse-free survival was accompanied by all cases (p<0.05). thoracic esophageal squamous cell car- decreased rates of tumors expressing While expression of p53+ positive cinoma undergoing treatment in Rostov p53, with their minimal number (1.5 times cells decreased significantly with longer Research Institute of Oncology. All pa- lower compared with patients who did not time to progression, expression of bcl-2 tients received Lewis surgery with stan- survive six months without progression) showed the opposite tendency. The av- dard bizonal lymph node dissection. No in patients with the longest event-free pe- erage number of bcl-2 positive cells in tu- special antitumor therapy was performed riod (365-540 days). mors was 2.3 times higher in progression until progression was detected. Median age of patients was 57.83 years. All pa- Table 1 tients developed progression within 1.5 years (up to 540 days). Depending on the Frequency of expression of IHC markers (p53 and bcl-2) depending on the time time to progression, the patients were di- to progression, absolute count (%) vided into 3 groups: up to 180 days; from 181 to 364; from 365 to 540 days. In 11 of Markers (IHC) Time to progression, 30 cases (36.7%), progression occurred days p53+ p53- bcl-2+ bcl-2- within 180 days; in 9 (30%) - from 181 to 364; in 10 (33.3%) - from 365 to 540 < 180 9 (81.8) 2 (18.2) 7 (63.6) 4 (36.4) days. The median event-free survival from 181 to 364 6 (75) 2 (25) 6 (75) 2 (25) was 9 months. from 365 to 540 6 (54.5) 5 (45.5) 10 (90.9) 1 (9.1) The IHC study was performed on 3-4 µm sections from paraffin blocks pre- In these patients, the maximum rate of from 181 to 364 days, compared to pa- pared using the Thermo Scientific Mi- positive bcl-2 expression was found – 1.4 tients with progression within 180 days. crom HM 325 rotary microtome (Great (p<0.05) and 1.2 (p<0.05) times higher When progression-free period lasted for Britain). Automated immunohistochemi- than in groups with progression-free pe- up to 540 days, the value increased by up cal staining was carried out in the Ther- riods of ˂180 and 181-364 days, respec- to 2.8 times (differences were statistically mo Scientific 480S IHC stainer. The tively (Table 1, Figure 1). significant, p<0.05). following monoclonal antibodies were The maximal index of proliferation of used for the study: to p53 (clone DO-7, tumor cells determined by ki-67+ was de- DAKO, 1:100 dilution), bcl-2 (clone Sp tected in tumors with the shortest time to 66, DAKO, 1:100 dilution), ki-67 (clone progression. It was 3.1 and 2.5 times high- H3060, Spring Biosience, 1:200 dilu- er, compared to the values in groups with tion), E-cadherin (clone EP700Y, Ther- progression in 181-364 and 365-540 days. mo scientific, 1:100 dilution). Dewaxing No statistically significant differenc- and dehydration stages were performed es in proliferation indices determined by according to the standard scheme. The Fig. 1. Squamous cell carcinoma of the esoph- ki-67+ cell proportion were observed in PT-LinkThermo was used for antigen agus: A - 360 days to progression. Low ex- patients with progression within 181-364 unmasking. The Reveal Polyvalent HRP- pression of bcl-2; Б - 540 days to progression. and 365-540 days. Therefore, this indi- High expression of bcl-2. 400x magnification DAB Detection System (Spring Biosci- cator can be considered as a marker of ence) was used for imaging. The cut-off early (up to six months after surgery) pro- point for positive tumor assessment was Table 2 presents the results of a com- gression of esophageal cancer. 25% for both nuclear staining for p53 and parative analysis of average expression Assessment of the proliferative poten- cytoplasm staining for bcl-2. Proliferative of IHC markers. A statistically significant tial of tumors in the same patients also reactivity (PA) was calculated by counting the proportion of positively stained cells Table 2 to the ki-67 marker per 100 tumor cells. The ki-67 index was determined by the Expression of studied markers in patients with different periods to progression, % formula: proliferative activity = the number of positively stained cells to the tumor Time to progression, Expression of IHC markers marker ki-67 x 100/total number of cells. days p53 bcl-2 ki-67 E-cadherin Statistical analysis of the results was pro- < 180 60.9±7.4 21.4±3.9 49.7±8.6 65.5±4.6 cessed using the Statistica 8.0 program from 181 to 364 41.9±6.6°↓ 48.9±4.6°↑ 15.9±4.8°↓ 66.3±8.8 [9], and the Student’s t-test was calculat- from 365 to 540 28.2±4.2°↓ 59.5±4.8°↑ 19.7±4.9°↓ 89.1±4.9°↑°°↑ ed. Results and discussion. The results Note. ° – differences from values < 180 days; °°– differences from values 181–364 days. were expressed in a comparative anal- Differences were statistically significant in both cases (p<0.05). 22 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

яичников. Иммуноонкология. 2015;1:84-89. [Novichkova ON, Yakovleva LM, Novichkov EV. Immunohistochemical study of prognostic tumor markers in recurrent mucinous carcinoma of the ovaries. Immunoonkologiya. 2015;1:84-89. (In Russ.)] 6. Кит О.И., Ващенко Л.Н., Тодоров С.С., Ибрагимова Е.Л., Аушева Т.В. Способ прогно- зирования рецидивирования сарком мягких тканей. Патент №2532332 Российская Феде- рация, МПК A61B. Опубл. 10.11.2014, Бюл- летень № 31. [Kit OI, Vashchenko LN, Todorov Figure 2. Proliferative activity of tumors (per- SS, Ibragimova EL, Ausheva TV. Method to centage) in dependence on time to progression predict recurrence of soft tissue sarcoma. Pat- in patients with stage II-III EC. The Y axis - %. ent №2532332 of the Russian Federation, МПК Fig. 3. Squamous cell carcinoma of the A61B. Published 10.11.2014, Bulletin № 31. (In vealed a number of differences (Figure 2). esophagus. Days to progression: A – 180, Б - Russ.)] Tumors with high PA were found only 364 days, В – 540. Expression of E-cadherin. 7. Смолякова Р.М., Машевский А.А., Кохнюк 400x magnification. В.Т. и др. Прогностическая значимость экс- in patients with an early period before прессии маркеров опухолевой пролиферации progression (up to 180 days), while such ki-67, p53 и bcl-2 у больных колоректальным activity was not detected in tumors of pa- high expression of bcl-2 and E-cadherin раком и полипозом. Онкологический журнал. tients with progression from 181–364 and with low proliferative activity of the tumor 2008;2(1):29-39. [Smolyakova RM, Meshevsky 365–540 days. AA, Kokhnyuk VT et al. Prognostic significance and low expression of p53, suggesting of ki-67, p53 and bcl-2 expression in colon can- Tumors with low PA were most often the potential use of these markers as cer and adenomas. Onkologicheskiy zhurnal. observed in the group with progression in prognostic ones along with well-known 2008;2(1):29-39. (In Russ.)] 181-364 days, and tumors with moderate clinical prognosis factors. 8. 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A.A. Popovich, E.A. Trifonova, A.V. Bocharova, K.V. Vagaitseva, N.R. Maksimova V.A. Stepanov GENETIC DIVERSITY IN YAKUT POPULATION BY LOCI ASSOCIATED DOI 10.25789/YMJ.2019.67.06 WITH BODY MASS INDEX AND OBESITY

Obesity is one of the main risk factor for the development of socially important diseases, determining the life quality and human longevity. Ac- cording to the World Health Organization (WHO) overweight and obesity are dramatically increased all over the world. This problem is particularly acute in industrialized countries, where it is becoming a non-infectious pandemic. Thus, it is critically important to focus our research efforts on studying of the genetic basis of the obesity spread in modern human populations. Genetic markers that are related to obesity and quantitative characters as body mass index (BMI), blood lipid levels and others have been identified as a result of number of studies. In the present study the variability of the GWAS-identified SNP allele frequencies associated with BMI and obesity was studied. The results of our study were compared with data on 20 populations from the international project “1000 Genomes”. Genetic markers that make the greatest contribution to the genetic differentiation of populations were identified. Keywords: human populations, polymorphism, obesity, body mass index.

Obesity is a complex, largely prevent- of many socially significant diseases. In on the association of candidate genes able disease that, together with over- particular, overweightness and obesity with obesity have been published, but the weightness, affects more than a third of can contribute to the development of type results of these studies are largely con- the world's population today. This pheno- 2 diabetes even in the absence of other tradictory [19]. This is probably due to the type is known to increase the morbidity metabolic disorders (hypertension, dys- influence of adaptive, ethnic, economic lipidemia, insulin resistance) [29]. Over- and sociocultural factors. In particular, weightness is a recognized risk factor for the indigenous populations of the Siberia POPOVICH Anastasia Andreevna, Ph.D. Ju- cardiovascular diseases and ischemic and the Far East in the period of adap- nior Researcher, Research Institute of Medical stroke that are responsible for the majori- tation to low atmospheric temperatures Genetics, Federal State Budgetary Scientific ty of deaths in the modern world. Obesity acquired special anatomical features Institution «Tomsk National Research Medical is also associated with oncological dis- contributing to a decrease in heat trans- Center of the Russian Academy of Sciences», eases. About 6% of cancer diseases (4% fer (constitution with a developed muscu- anastasia.cherednichenko@medgenetics. in men, 7% in women) have been shown loskeletal mass, high body density, etc.) ru; TRIFONOVA Ekaterina Aleksandrov- to be associated with obesity [27]. More [1]. The Republic of Sakha (Yakutia) is , Ph.D. Scientific Researcher, Research na recently, evidence has been obtained that one of the arctic and subarctic regions Institute of Medical Genetics, Federal State Budgetary Scientific Institution «Tomsk Na- overweightness and obesity increase the of the Russian Federation. According to tional Research Medical Center of the Rus- risk of developing cancer of the gallblad- the 2017 data of the Ministry of Health of sian Academy of Sciences», ekaterina-trifon- der, prostate, ovarian epithelium, liver, as the Russian Federation, the frequency of [email protected], BOCHAROVA Anna well as leukemia. [11, 21-23, 26]. obesity in the Yakut population is 593.0 Vladimirovna Junior Researcher, Research Obesity is associated with anatomi- per 100 thousand people [5]. It should be Institute of Medical Genetics, Federal State cal as well as functional changes in the noted that the relatively high prevalence Budgetary Scientific Institution «Tomsk Na- human brain. Studies of elderly people of obesity among individuals living in the tional Research Medical Center of the Russian have shown that the body mass index Republic of Sakha (Yakutia) can be asso- Academy of Sciences», anna.bocharova@ (BMI) is negatively correlated with the ciated not only with their adaptive prop- medgenetics.ru, VAGAITSEVA Ksenia Valer- ievna, Ph.D. Scientific Researcher, Research brain volume and is associated with at- erties, but also with changes in the tradi- Institute of Medical Genetics, Federal State rophy of the frontal lobes, hippocampus tional lifestyle and characteristic features Budgetary Scientific Institution «Tomsk Na- and thalamus. [10]. Moreover, obesity in of modern nutrition. tional Research Medical Center of the Russian children and adolescents is associated The aim of this work is to investigate Academy of Sciences», kseniya.simonova@ with a smaller amount of gray matter in the genetic markers associated with obe- medgenetics.ru, MAXIMOVA Nadezhda Ro- the orbitofrontal cortex [28]. Overweight- sity and BMI as part of the genome-wide manovna, Dr.Sc. Chief Researcher of the ness in middle-aged patients increases association study (GWAS), to study the Clinic of the Medical Institute of Federal state the risk of developing Alzheimer's dis- variability of these markers in the pop- Autonomous educational institution of higher professional education «North-Eastern Fed- ease and vascular dementia by 35% and ulation sample of Yakuts in comparison eral University named after M. K. Ammosov», 33%, respectively; an even higher risk of with world populations using the methods [email protected], STEPANOV Vadim Ana- these diseases is observed in obesity [9]. of the statistical analysis of the data ob- tolevich, Dr.Sc., correspondent member RAS Thus, the influence of overweightness tained. Head of the Laboratory of Evolutionary Genet- and obesity on human health is signifi- Materials and methods. The study ics, Research Institute of Medical Genetics, cant, especially in combination with other was conducted on a population sample of Federal State Budgetary Scientific Institution concomitant diseases. Yakuts. The sample included 95 non-ad- «Tomsk National Research Medical Center As is known, this phenotype has a mixed and unrelated individuals: 30 men of the Russian Academy of Sciences» Acting genetic nature. According to studies of (mean age of 27.56±18.61 years) and Director of Federal State Budgetary Scientific Institution «Tomsk National Research Medical twins, the coefficient of obesity heritabili- 65 women (mean age of 31.02±16.49 Center of the Russian Academy of Sciences», ty has been found about 40% [12]. Over years). This sample was collected the [email protected]. the past decade, many scientific papers Byadi village, the Republic of Sakha (Ya- 24 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

kutia). Additionally, the study included the tional significance of SNPs. In general, the polymorphic variants of the ADCY3 results of genotyping of 20 populations the population sample of Yakuts is char- gene are associated with obesity [6, 25]. from the “1000 Genomes” project (Esan, acterized by a significant genetic variabil- Epigenetic studies have shown the sig- Gambian, Luhya, Mende, Yoruba, Peru- ity: the frequencies of ancestral alleles nificance of the methylation of the CpG vian, Bengali, Chinese Dai in Xishuang- range from 0.00 for the rs13021737 lo- sites of the ADCY3 gene in the molec- banna, Han Chinese in Bejing, Southern cus to 1.00 for the rs11847697 locus ular mechanisms of obesity develop- Han Chinese, Japanese, Kinh, Finnish, located in the intergenic region and the ment. The smallest genetic differences British, Iberian, Toscani, Gujarati In- rs13107325 locus of the SLC39A8 gene. between populations have been found dian, Indian Telugu, Punjabi, Sri Lankan The frequency of the ancestral allele of for the rs13021737 and rs1800437 loci, Tamil). the rs13021737 locus in the populations where Fst comprises 1.9%. Genetic markers were selected from from the “1000 Genomes” project varies Fig. 1 presents an analysis of the ge- the GWAS catalog, where they have in the range from 0.05 in Luhya to 0.21 in netic relationships of world populations shown statistically significant associa- Toscani; rs11847697 – from 0.56 in Yoru- according to frequencies of the ances- tions with BMI and/or obesity in two or ba to 1.00 in Han Chinese from Bejing, tral alleles of genetic markers associ- more studies. Thus, 58 single nucleo- Southern Han Chinese, Kinh, and Japa- ated with obesity and BMI. The first 2 tide polymorphisms (SNPs) were stud- nese; rs13107325 – from 0.89 in Toscani main components account for 68.4% of ied, genotyping of which was conduct- to 1.00 in 15 out of 20 population sam- the total variability of allele frequencies ed using the MALDI-TOF mass spec- ples from the “1000 Genomes” project. in the analyzed population samples. The trometry method [3]. 7 out of 58 SNPs Thus, the indices of the variability of the position of the studied populations in (rs10968576, rs13130484, rs11671664, ancestral allele frequencies of the SNP the space of the principal components rs12566985, rs17381664, rs2287019 data in Yakuts correspond to those in the reflects their geographical localization, and rs657452) demonstrated a low ge- world populations. i.e. geographically close populations get notyping efficiency (less than 70%) and The average level of genetic diver- into one cluster (African, East Asian, were excluded from the analysis. sity in the population sample of Yakuts West European clusters and Hindustan To verify the Hardy-Weinberg equi- for 51 SNPs was 0.340, this index cor- cluster), which corresponds to the re- librium in the obtained distribution of responds to the average level of genetic sults obtained in previous works [4]. The genotypes and allele frequencies, the c diversity in 21 population samples for all population sample of Yakuts is located criterion was used. The expected hetero- studied SNPs – 0.328. The highest ge- in the space of the principal components zygosity reflecting the percentage of het- netic diversity were shown for the loci together with the East Asian populations, erozygotes in the population sample was rs2112347 of the gene LOC441087 and which characterizes its genetic proximity estimated. To study genetic diversity, we rs7141420 of the gene NRXN3, the low- to this cluster. Yakuts, as well as popula- calculated the values of expected hetero- est – for the loci rs6804842 of the gene tion samples of Chinese, Japanese and zygosity, but not observed one, because RARB and rs9540493 located in the in- Kinh, belong to the Mongoloid race. in small samples the frequencies of gen- tergenic region. These genetic markers The first main component is likely to otypes and the observed heterozygosity, are characterized by an average level correspond to the contribution of sever- for random reasons, can significantly de- of between-population genetic diversity al climatic and geographical factors: a viate from the general values [2]. Genetic (from 2% to 6,2%), which corresponds correlation of the values of this compo- differentiation of the populations under to the level of genetic differences be- nent with absolute latitude (R=-0.596, study was calculated using analysis of tween populations for different genetic p=0.004) and longitude (R=-0.636, molecular variance (AMOVA). To study markers, according to the results of other p=0.002) and temperature indices (aver- genetic relationships, we used the prin- studies [8]. The greatest contribution to age annual temperature (R = 0.556, p = cipal components method. Statistical the genetic differentiation of populations 0.009), temperature of the coldest (R = processing of the results was carried out is made by the rs1167827 loci of the 0.642, p = 0.002) and warm (R = 0.438, using the software packages «Arlequin HIP1 gene, where the Fst index is equal p = 0.047) months and temperature vari- 3.5» and «Statistica 7.0». 45.9%, which significantly exceeds the ation (R = -0.607, p = 0.004)) was found Results and discussion. In this average Fst in the studied populations for 51 SNPs. The second main compo- work, an analysis of the genetic diversity (9.8%). This locus is associated with nent reflects a change in the absolute of the Yakut population was conducted. BMI in several studies; the HIP1 gene longitude index (R=0.599, p=0.004). The frequencies of the ancestral alleles product is involved in clathrin-mediated Conclusion. Currently, obesity has of the Yakut population sample, the av- endocytosis in cells and is associated become one of the most important med- erage values of expected heterozygosity with the development of prostate can- ical and social problems, due to its pro- (He) and genetic differentiation (Fst) for cer and Huntington's disease [15, 17, gressive spread and severity of compli- the studied polymorphic variants in the 18]. The rs10182181 and rs11847697 cations. Genetic predisposition is one of 21 populations are presented in Table markers located in the intergenic region the important factors in the pathogene- 1. The deviation of the conformity of the are also characterized by high values of sis of obesity. In this work, we identified distribution of genotype frequencies with Fst. According to the GWAS catalog, the high genetic diversity and differentiation the Hardy-Weinberg equilibrium in Ya- 10182181 marker was shown to be asso- in the 21 world populations according to kuts was shown for 2 out of 51 studied ciated with obesity and BMI, rs11847697 the studied genetic markers associated SNPs: rs2207139 located in the intergen- – with BMI [7, 13, 14, 16]. According to with obesity and body mass index. The ic region and rs7903146 of the TCF7L2 the HaploReg v4.1 online resource, the Yakut population is characterized by a gene. Statistically significant deviations rs10182181 marker is closely linked to an significant intrapopulation genetic vari- (p<0.05) from the Hardy-Weinberg equi- rs11676272 allelic variant of the ADCY3 ability (0.340). We found a correlation librium probably reflect specific features gene (r2=0,97; D'=0,99) [20]. The prod- between allele frequencies for 51 SNPs of population-genetic processes, among uct of this gene is known to be widely and changes in climatic and geographi- which may be such a factor as the func- expressed in various tissues, whereas cal conditions. The analysis of the main 3’ 2019 25

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L.B. Kim, L.P. Osipova, A.A. Rozumenko, A.N. Putyatina, G.S. Russkikh, T.V. Kozaruk, N.P. Voronina LIPID SPECTRUM FEATURES AND RELA- TIONSHIP BETWEEN SPECIFIC CLASSES OF LIPIDS AND SEX HORMONE LEVELS IN DOI 10.25789/YMJ.2019.67.07 ASIAN NORTH MEN

We studied lipid spectrum features in indigenous and non-indigenous residents of Asian North in Russia against the levels of dehydroepiandrosterone sulfate (DHEA-S) and testosterone. Ma- terials and methods: We compared the main parameters of lipid and sex hormone metabolism in indigenous and non-indigenous men inhabitants of Asian North with those of relatively healthy KIM Lena Borisovna – Doctor of Medical men in Western Siberia (comparison group). Results: lipid profile of indigenous men featured Sciences, chief researcher, Head of Group lipoprotein spectrum shifted towards high-density lipoprotein cholesterol compared with lipid proof Connective Tissue Biochemistry, Fed- file of non-indigenous population and comparison group. Atherogenicity coefficient in indigenous eral Research Center of Fundamental and people lied within permissible values. We revealed that low-density lipoprotein cholesterol level Translational Medicine (FRC FTM), contacts: and atherogenic coefficient positively correlated with chronological age, and high-density lipo- [email protected], +7(383)334-82-11, 2 protein cholesterol level positively correlated with DHEA-S both in native and non-indigenous ul. Timakova, 630117, Novosibirsk, Russia. residents of Asian North. DHEA-S level in non-indigenous population was found to negatively OSIPOVA Lyudmila Pavlovna – Candidate correlate with triglycerides and atherogenic coefficient. This group of men was characterized by of Biological Sciences, 1Head of Laboratory high levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol and high athero- of Population Ethnogenetics, Institute of Cy- genic coefficient. tology and Genetics SB RAS, 10 pr. akad. Keywords: lipid profile, sex hormones, indigenous and non-indigenous residents, Asian Lavrent'eva, Novosibirsk, Russia; 2Novosibirsk North, Arctic zone of the Russian Federation. State University, 2 ul. Pirogova, Novosibirsk, Akademgorodok, Russia. ROZUMENKO Aleksandr Anatol'evich – Candidate of Bi- Introduction. For the last decade, regions. In particular, it is known that total ological Sciences, senior researcher of Lab- economic development of the Arctic zone primary incidence by ICD-10 (A00–T98) oratory of Medical Biotechnology, FRC FTM, of the Russian Federation (AZRF) has per 100.000 population in Yamal-Nenets 2 ul. Timakova, 630117, Novosibirsk, Russia. been considered a priority of state policy Autonomous District (Asian North of Rus- – Candidate PUTYATINA Anna Nikolaevna as exploration and development of huge sia) in 2007-2016 was higher than in Mur- of Medical Sciences, researcher in Group of Connective Tissue Biochemistry, FRC FTM, reserves of natural gas and oil in the Arc- mansk Region (European North of Rus- 2 ul. Timakova, 630117, Novosibirsk, Russia. tic will help to achieve sustainable eco- sia) [3]. The same ratio was for arterial RUSSKIKH Galina Sergeevna – Candidate nomic growth and improve life quality not hypertension incidence. of Biological Sciences, senior researcher of only of AZRF residents but nationwide. The prevalence of major circulatory Laboratory of Medical Biotechnology, FRC Some researchers often distinguish diseases in non-indigenous population of FTM, 2 ul. Timakova, 630117, Novosibirsk, between European and Asian North of AZRF and a high risk of cardiovascular Russia. KOZARUK Tat'yana Vladimirovna Russia based on climatic factors and pathology are caused by the negative – specialist in clinical laboratory diagnostics, geographical location [4, 7, 8]. It is not impact of extreme climatogeographic RI ECM, FRC FTM, 2 ul. Timakova, 630117, unlikely that these factors as well as factors, such as cold, wind, dry air, con- Novosibirsk, Russia. VORONINA Natal'ya Petrovna – Doctor of Biological Sciences, se- food patterns, nationality, age, degree trasting photoperiodism, intense cosmic nior researcher, specialist in clinical laboratory of physical fitness and activity, ecologi- radiation, geomagnetic fluctuations and diagnostics, RI ECM, FRC FTM, 2 ul. Timako- cal situation and heredity determine the increasing anthropogenic pollution of va, 630117, Novosibirsk, Russia. current demographic situation in these some areas. 3’ 2019 27

Many authors also attribute the growth ulation (group 2, men (n=19) with the ELISA. The results were read using a of cardiovascular diseases (CVD) inci- mean age of 43.79±2.68, polar expe- microplate reader Stat Fax-2100 (Aware- dence in extreme AZRF conditions to rience of 23.75±5.22). The indigenous ness Technology Inc., USA). unfavorable lipid profile [5, 9, 11, 21]. population included forest and tundra Data were statistically processed us- Individual characteristics of lipid metabo- Nenets who preserved a traditional food ing Statistica v. 10 package (Stat Soft lism are influenced by numerous factors: pattern, engaged in reindeer husband- Inc., USA). Mann-Whitney U–test was nutrition, degree of physical fitness and ry, fishing and hunting. Representatives used to compare two independent groups activity, ecological situation, heredity, of non-indigenous population were en- by the same parameter. Nonparametric age, nationality, place of residence. For gaged in physical labor, preferred Eu- Spearman’s rank correlation coefficient instance, the residents of the eastern part ropean food patterns. Both groups had (r) was used to assess the correlation of the southern Arkhangelsk region (61- comparable physical activity (1.4–1.6). between individual characteristics. The 62° N) had higher levels of low-density The comparison group consisted of ap- data are presented as M±m, where “M” is lipoprotein cholesterol (LDL-C) and phos- parently healthy men of the same age the arithmetic mean and “m” is the mean pholipids compared with those in western (group 3, men (n=14) with the mean age error. Differences were considered statis- part of the region [17]. Studying the rep- of 42.86±3.45) living in Novosibirsk (55° tically significant at p<0.05. resentatives of indigenous and non-indig- N, 82° E, Western Siberia). 1. Results and discussion. Table enous residents living in the same area This study approved by the Ethics 1 shows the levels of lipids, sex hor- can be expected to reveal group-specific committees of FRC ICG SB RAS and mones and AC in study groups. Except features of lipid metabolism that are not FRC FTM was performed in accordance for HDL-C, group 1 men had significantly associated with the influence of AZRF cli- with the requirements of "Ethical prin- lower lipid levels compared to group 2. matic factors. ciples for medical research involving Group 1 had 2.3-, 2.8- and 1.2-times It is common knowledge that LDL-C human subjects" and "Rules for clinical higher levels of TG, LDL-C and TC, re- plays a leading role in atherogenesis. Un- practice in the Russian Federation". spectively, compared to group 2. This af- der oxidative stress, LDL-C modifies and Blood was sampled from ulnar vein fected AC value that was 2.1-times lower increases its atherogenic properties. The on an empty stomach after night fasting. than in group 2. HDL-C levels in group levels of oxidized LDL-C significantly in- The levels of the following components 1 was 1.4-times higher than in group 2. crease with age [22]. Sex hormone levels were determined: total cholesterol (TC), TG levels in group 1 was 1.3-times lower also change with age. Men aged 60-69 very low-density lipoprotein cholesterol than in group 3. Characteristics of lipid residing in European North had 1/3 of de- (VLDL-C), LDL-C, high-density lipoprotein metabolism were identified in the study hydroepiandrosterone sulfate (DHEA-S) cholesterol (HDL-C), triglycerides (TGs), of first- and second-generation young levels in young group (up to 29) [25]. DHEA-S, and testosterone. Atherogen- Caucasians born in the North and indig- There was no positive correlation be- ic coefficient (AC) was also calculated. enous students of Magadan Region (the tween DHEA-S and lipid levels. Some Levels of TC and TG, as well as HDL-C Evens, the Koryaks, the Chukchis) [1]. epidemiological studies of men, however, and LDL-C were determined using Ther- The characteristics reflect ethnic differ- found a link between low levels of DHEA mo Fisher Scientific (USA) and DiaSyS ences in metabolic processes shaped by and DHEA-S with increased CVD risk (Germany) kits, respectively. Measure- long-term adaptation to North conditions. [19, 20], while another study shows no ments were carried out using automatic In the indigenous group, TC, TG, LDL-C correlation [23]. SCORE-based cardio- biochemical analyzer AU 480 Beckman levels were lower and the concentration vascular risk in European North miners Coulter (USA). Levels of DHEA-S and of HDL-C was higher than in the group of was significantly higher than in group of testosterone were measured using "Ste- Caucasians born in the North. men living in Western Siberia [25]. Car- roid ELISA-DHEA-sulfate" and "Steroid Levels of TG, TC, LDL-C and AC value diovascular risk of northerners increased ELISA-testosterone" tests (Russia) for in group 2 study exceeded the permissi- from low to very high values with chronological age. Table 1 The relevance of this study is also related to emerging reports that differences Lipid and sex hormone levels in serum of male representatives of indigenous in lipid profile of indigenous and non-in- and non-indigenous population of AZRF (M±m) digenous northerners tend to erase, which may be due to changes in the life- Group p style of the former [2]. Parameter indigenous non-indigenous comparison Objective: to identify the features of 1 2 3 lipid spectrum in indigenous and non-in- Age, years 38.06±2.92 43.79±2.68 42.86±3.45 – digenous Asian North residents living at 1-2=0.034 TC, mM/l 4.76±0.24 5.70±0.35 4.41±0.26 the same latitude and to assess the rela- 2-3=0.006 tionship between specific indicators of lip- 1-2=0.002 ТG, mM/l 0.82±0.06 1.86±0.32 1.40±0.22 id metabolism and the levels of DHEA-S 1-3=0.010 and testosterone. VLDL-C, mM/l 0.24±0.04 0.66±0.15 – 1-2=0.011 Materials and methods. The study 1-3=0.050 LDL-C, mM/l 3.06±0.23 3.67±0.31 2.49±0.17 was conducted among men of Samburg 2-3=0.002 village (67° N, 78° E), Yamal-Nenets 1-2=0.001 HDL-C, mM/l 1.32±0.07 0.97±0.07 0.92±0.07 Autonomous District, in spring (March– 1-3=0.001 1-2=0.001 April). The study involved informed con- AC 2.30±0.23 4.91±0.57 4.28±0.59 sent enrollment of indigenous population 1-3=0.002 (group 1, men (n=18) with the mean age DHEA-S, μg/ml 2.33±0.19 2.14±0.17 1.84±0.15 1-3=0.050 of 38.06±2.92) and non-indigenous pop- Testosterone, nM/l 23.04±1.74 18.88±1.99 18.43±2.10 1-3=0.034 28 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

ble values, which indicated lipid metab- LDL-C and AC, which suggests lipid me- level of LDL-C and age, AC index and olism disorder, hypertriglyceridemia and tabolism disorder and enable us to clas- calendar age of men were common for hypercholesterolemia. Notably, group 2 sify these men to those at risk of cardio- men in groups 1 and 2. Only group 1 had lipid profile did not differ from that iden- vascular pathology. This is confirmed by correlations between LDL-C and TG lev- tified by Z.N. Krivoshapkina and col- more pronounced deviations of lipid pro- els and between LDL-C and AC. leagues [14] when studying non-indige- file in non-indigenous people suffering Group 2 demonstrated a positive nous residents of Yakutia with more than from coronary heart disease compared correlation between TC level and age, 20 years of polar experience. TC and with the indigenous population with the VLDL-C and TG levels, LDL-C and LDL-C levels of group 2 exceeded those same pathology [15]. The differences HDL-C levels, VLDL-C level and AC, of group 3 with normal lipid parameters, between group 1 and 2 appear to be re- negative correlation between HDL-C with the exception of AC (Table 1). lated to lifestyle and diet, which reflect and TG levels, DHEA-S and TG levels, Lipoprotein lipase is known to bind ethnicity. VLDL-C and HDL-C levels, DHEA-S level endothelium capillary and hydrolyzes TG Correlations between studied parame- and AC. This group featured correlations in chylomicrons (CM) and VLDL-C with ters were investigated to understand the between more atherogenic lipid fraction latter transforming into HDL-C. There features of hormonal and metabolic rela- – LDL-C and AC, TG – compared with could be the following reasons of hyper- tionships (Table 2). The analysis showed group 1 (LDL-C). triglyceridemia: increased formation of a number of correlations between lipid Negative correlations between VLDL in liver; disorders of TG hydrolysis metabolism indicators inherent in all three DHEA-S and AC, as well as DHEA-SC in CM and VLDL-C and their transforma- groups: a) strong positive correlation be- and TG, observed in group 2 only, sug- tion into remnants; and blockade of re- tween TC and LDL-C levels; b) positive gest the active DHEA-S participation ceptor absorption by the cells of CM and correlation between TG and AC levels in lipid metabolism regulation among VLDL-C remnants [16]. with average and strong correlation in non-indigenous population of the Asian Lipoprotein spectrum shift towards groups 1, and 2 and 3, respectively; c) North. It can be assumed that increased HDL-C in group 1 can be considered as negative correlation between HDL-C DHEA-S will reduce AC and TG levels. a manifestation of reasonable and eco- and AC levels. Group 1 had an average There is evidence of DHEA presence in nomical metabolic background described correlation, while groups 2 and 3 had a HDL-C and LDL-C particles of healthy earlier as a "northern" or "polar" type of strong correlation. The identified relation- young and middle-aged volunteers [18]. metabolism [6, 12, 13]. Normolipidemia ships reflect strong positive correlations Levels of DHEA and DHEA-S in LDL-C in group 1 can be explained by liver ca- between proatherogenic lipid fractions particles progressively decreased with pability of active esterification of TC, in- and negative correlations between the age and were almost undetectable in tensive biosynthesis of bile acids and anti-atherogenic fraction and AC. persons over 65. The same in vitro model transportation of sterols to bile [10]. Of great interest were significant cor- study demonstrated that DHEA increased It is generally accepted that increased relations identified in groups of men LDL-C resistance to oxidation. LDL-C ox- LDL-C level is a key factor of cardiovas- living in the same geographical area of idation inhibition potential of DHEA were cular pathology. In one of the studies [24], the Asian North. Positive correlations higher than that of vitamin E [18]. Our LDL-C level was predictive of cardiovas- between DHEA-S and HDL-C levels, the study revealed significant correlations cular risk in patients with type 2 diabetes. In persons with diabetes and insulin Table 2 resistance, as well as in elderly patients, the prognostic value of this parameter is Relationship between lipid profile indicators and sex hormone levels / age in indigenous and non-indigenous population of Asian North (r; p) higher. The average level of LDL-C may slightly differ in different populations due Group to both genetic characteristics and envi- Parameter ronmental factors. indigenous non-indigenous comparison The content of sex hormones in TC – Age – 0.54; 0.021 – groups 1 and 2 did not differ Table ( 1). TC – TG – – 0.71; 0.005 However, DHEA-S and testosterone lev- TC – LDL-C 0.83; 0.0005 0.81; 0.0005 0.99; 0.0005 els in group 1 were higher than in group TC – AC – – 0.73; 0.003 3. Sex hormone levels in all groups were TC – Testosterone – – -0.58; 0.031 within reference values. TG – VLDL-C – 0.85; 0.0005 – Thus, significant differences of lipid TG – LDL-C 0.51; 0.031 – 0.73; 0.003 metabolism were found when compar- TG – HDL-C – -0.75; 0.0003 -0.63; 0.015 ing two groups of men of similar age and TG – AC 0.66; 0.004 0.92; 0.0005 0.79; 0.001 the same class of physical activity living TG – DHEA-S – -0.47; 0.044 – in the same geographical area of Asian HDL-C – VLDL-C – -0.74; 0.001 – North located at the same northern lat- HDL-C – AC -0.61; 0.015 -0.81; 0.0005 -0.82; 0.0005 itude. Group 1 had more favorable lip- HDL-C – DHEA-S 0.68; 0.005 0.48; 0.046 – id profile as evidenced by lower levels LDL-C – Age 0.52; 0.028 0.81; 0.0005 – of TC, TG, LDL-C and higher levels of HDL-C compared to those of group 2. LDL-C – HDL-C – 0.52; 0.026 – AC, which is considered as a prognos- LDL-C – AC 0.72; 0.001 – 0.80; 0.001 tic indicator of atherogenesis and pre- LDL-C – Testosterone – – -0.59; 0.026 disposition to cardiovascular pathology, AC – Age 0.55; 0.022 0.47; 0.045 – did not exceed 2.30 in group 1. Group 2 AC – VLDL-C – 0.81; 0.0005 – had increased levels of TC, TG, LDL-C, AC – DHEA-S – -0.62; 0.005 – 3’ 2019 29

between DHEA-S and lipid metabolism and classifies these men into a high car- ova IE. Current trends in the nature of nutrition indicators (HDL-C and TG) in groups 1 diovascular disease risk group. and blood lipid spectrum in the indigenous peoples of Far North. Prof. zabol. i ukrep. zdorov'ya. and 2 only, which indicates characteristic Lipid profile correlations were identi- 2005;(3):16–19 (In Russ.).] relationships between lipid metabolism fied that are "united" by living conditions 3. Атлас санитарно-эпидемиологической indicators and DHEA-S level in men liv- of the same geographical area and are обстановки на территории Арктической зоны ing in the Asian North. characteristic for Asian North residents. Российской Федерации (2017) / Под ред. д.м.н. С.А. Горбанева. СПб., 2017: 52. [Atlas of Group 3 demonstrated positive cor- Calendar age was found to correlate the sanitary and epidemiological situation in the relations between TC and TG levels, with LDL-C, AC (for indigenous and Arctic zone of the Russian Federation (2017)] / TC level and AC, TG and LDL-C levels, non-indigenous residents), and TC (for Ed. by PhD SA. Gorbanev. St. Peterburg, 2017: 52. (In Russ.).] LDL-C level and AC and negative cor- non-indigenous residents). Northerners 4. Гудков А.Б., Попова О.Н. Внешнее ды- relations between cholesterol and tes- (indigenous and non-indigenous) also хание человека на Европейском Севере. Ар- tosterone levels, TG and HDL-C levels, featured a positive correlation between хангельск: Изд-во Северного государствен- LDL-C and testosterone levels. These DHEA-S with HDL-C with only non-indig- ного медицинского университета, 2012: 252. [Gudkov AB, Popova ON. External breathing of correlations indicate unfavorable lipid enous men having negative correlations a person in the European North. Arkhangel'sk: profile and moderate cardiovascular risk. between DHEA-S, AC, and TG. These Izd-vo Severnogo Gos. Med. Univ., 2012: 252. (In Group 3 featured important role of testos- correlations indicate significant positive Russ.).] terone in lipid metabolism. The identified contribution of DHEA-S to lipid metabo- 5. Даренская М.А. Особенности метаболи- ческих реакций у коренного и пришлого насе- correlations between TC, LDL-C and TG lism regulation in indigenous northern- ления Севера и Сибири. Бюл. ВСНЦ СО РАМН. levels may predetermine increased AC. ers, and a possible negative impact of 2014;(2):97–103. [Darenskaya MA. Peculiarities Lipid profiles and sex hormone levels DHEA-S in non-indigenous northerners, of metabolic reactions in indigenous and migrant in men differentiate them by risk of dis- taking into account the known age dy- populations of the North and Siberia. Byul. VSNTs SO RAMN. 2014;(2):97–103. (In Russ.).] eases accompanied by lipid metabolism namics of this hormone. 6. Казначеев В.В. Механизмы адаптации disorder. The first group of men can be Average positive correlations between человека в условиях высоких широт. Л.: considered favorable as lipid metabolism TG and TC levels, TG and LDL-C levels, Медицина, 1980: 200. [Kaznacheev VV. Mech- indicators are within normative values. as well as between TC level and AC was anisms of human adaptation in high latitudes. Leningrad: Meditsina, 1980: 200. (In Russ.).] This is possibly due to high sex hormone a distinctive feature of the comparison 7. Ким Л.Б. Транспорт кислорода при адап- level and features of traditional food pat- group. Testosterone levels negatively тации человека к условиям Арктики и карди- terns. It should not be however forgotten correlated with TC and LDL-C levels in ореспираторной патологии. Новосибирск: Наука, 2015: 216. [Kim LB. Oxygen transport in that this group had correlations between this group. The analysis of lipid profile human adaptation to Arctic conditions and cardio- LDL-C, TG and AC. Due to hypertri- and relationships between its indicators respiratory pathology. Novosibirsk: Nauka, 2015: glyceridemia, hypercholesterolemia and in men from Western Siberia allows us 216. (In Russ.).] increased AC, group 2 can be classified to classify them into a group of moderate 8. Ким Л.Б., Кожин П.М., Путятина А.Н. Ис- следование молекулярного маркера старения into a high risk group. Correlation analy- atherogenic disease risk. у мужчин Европейского Севера России. Журн. sis demonstrated the role of age, LDL-C The study was carried out with the мед.-биол. исследований. 2017;5(3):70–78. and DHEA-S in atherogenic disease risk. partial support of the Presidium of the [Kim LB, Kozhin PM, Putyatina AN. Study of Such lipid spectrum changes can be con- Russian Academy of Sciences under the molecular marker of ageing in male residents of the European North of Russia. Zhurn. med.- sidered as a "fee" for living in extreme basic research Program «Exploratory biol. issledovanij. Zhurn. med.-biol. issledovanij. climatic conditions. Group 3 can be char- Fundamental studies for the development 2017;5(3):70–78. (In Russ.).] DOI: 10.17238/ acterized to have moderate risk of ath- of Arctic region of the Russian Federa- issn2542-1298.2017.5.3.70 erogenic diseases. Complex interactions tion» (FRC FTM) and the project budget 9. Уварова Т.Е., Бурцева Т.Е., Софронова С.И. [и др.]. Липидный профиль крови и осо- between pro- and anti-atherogenic lipid № 0324-2019-0041 (FRC ICG SB RAS). бенности нарушений липидного обмена у ко- fractions and testosterone involvement in We used the equipment of Core Fa- ренных малочисленных народов севера Яку- regulation of TC and LDL-C levels only cility “Modern Optical Systems”, Federal тии. Дальневост. мед. журн. 2012;(3):85–88. increased AC. Research Center of Fundamental and [Uvarova TE, Burtseva TE, Sofronova SI [et al.]. The bloode lipid profile and the lipid metabolizm Conclusion. Comparative study re- Translational Medicine (Novosibirsk, disorders to indegenious people of the Yaku- vealed some features of lipid profile and Russia). tia. Dal'nevost. med. zhurn. 2012;(3):85–88 (In sex hormones in indigenous and non-in- Conflict of interests. The authors de- Russ.). 10. Цуканов В.В., Ноздрачев К.Г., Тонких digenous men of the same age who live clare that they have no conflict of interest. Ю.Л. [и др.]. Механизм обратного транспорта in the same climatogeographic area of холестерина и холелитиаз у северных народ- the Asian North, but have different food References ностей. Клин. медицина. 2007;85(2):33–35. patterns. Indigenous men had optimal [Tsukanov VV, Nozdrachev KG, Tonkikh YuL [et al.]. The mechanism of reverse transport of content of TC, TG, and VLDL-C but 1. Аверьянова И.В., Максимов А.Л., cholesterol and cholelithiasis among in northern their lipid spectrum was shifted towards Борисенко Н.С. Особенности липидного и peoples. Klin. medicina. 2007;85(2):33–35 (In HDL-C compared with lipid profile of углеводного обмена у юношей-аборигенов Russ.).] и укорененных европеоидов Магаданской non-indigenous men. AC also indicates 11. Воевода М.И., Романова А.Н., Рагино области. Вест. Сев. (Арктич.) федер. ун-та. Ю.И. [и др.]. Некоторые особенности факто- more favourable lipid profile of indige- Сер.: Мед.-биол. науки. 2016;(2):5–15. [Av- ров риска коронарного атеросклероза у жите- nous people. It can be assumed that the eryanova IV, Maksimov AL, Borisenko NS. Lipid лей Якутии. Бюллетень СО РАМН. 2010;30(3): favorable lipid profile of the indigenous and carbohydrate metabolism in indigenous and 52–58. [Voevoda MI, Romanova AN, Ragino YuI Caucasian young males living in the Magadan people induced by traditional way of [et al.]. Some features of coronary atherosclero- Region. Vest. Sev. (Arktich.) feder. un-ta. Ser.: sis risk factors in the inhabitants of Yakutia. Byul- life and food patterns will preserve their Med.-biol. nauki. 2016;(2):5–15. (In Russ.).] DOI: leten' SO RAMN. 2010;30(3): 52–58. (In Russ.).] health and prevent diseases of civiliza- 10.17238/issn2308-3174.2016.2.5 12. Панин Л.Е. Фундаментальные проблемы tion, including CVD. 2. Агбалян Е.В., Ионова И.Е. Современные приполярной и арктической медицины. тенденции характера питания и липидного Non-indigenous men had increased Бюллетень СО РАМН. 2013;33(6):5–10. [Panin спектра крови жителей коренной националь- LE. Fundamental problems of the circumpolar TC, TG, LDL-C levels and AC (4.91), ности Крайнего Севера. Проф. забол. и укреп. and the Arctic medicine. Byulleten' SO RAMN. which suggests unfavorable lipid profile здоровья. 2005;(3):16–19. [Agbalyan EV, Ion- 2013;33(6):5–10. (In Russ.).] 30 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

13. Авцын А.П., Жаворонков А.А., Марычев и низкой плотности: функция, транспорт The epidemiology of DHEAS and cardiovascular А.Г. [и др.]. Патология человека на Севере. М.: жирных кислот и диагностическое значение. disease. Ann. NY Acad. Sci. 1995;774(1):259– Медицина, 1985: 415. [Avtsyn AP, Zhavoronkov Клин. лаб. диагностика. 2000;(11):25–32. [Ti- 270. DOI: 10.1111/j.1749-6632.1995.tb17386.x-i1 AA, Marytchev AG [et al.]. Human pathology in tov VN. Very low and low density lipoproteins: 21. Chateau-Degat M-L, Dewailly E, Louchini the North. Moscow: Meditsina, 1985: 415. (In function, fatty acid transport and diagnostic val- R [et al.]. Cardiovascular burden and related risk Russ.).] ue. Klin. lab. diagnostika. 2000;(11):25–32 (In factors among Nunavik (Quebec) Inuit: Insights 14. Кривошапкина З.Н., Миронова Г.Е., Се- Russ.).] from baseline findings in the circumpolar Inuit мёнова Е.И. [и др.]. Показатели липидного об- 17. Бичкаева Ф.А., Жилина Л.П., Бойко Health in Transition cohort study. Can. J. Cardi- мена у пришлых жителей Якутии в зависимо- Е.Р. [и др.]. Физиологические особенности ol. 2010;26(6):190–196. DOI: 10.1016/s0828- сти от сроков проживания на Севере. Якутский липидного, углеводного и белкового обменов 282x(10)70398-6 медицинский журнал. 2018;2(62):28–30. [Krivo- у жителей южных районов Архангельской 22. Alique M, Luna C, Carracedo J [et al.]. LDL shapkina ZN, Mironova GE, Semenova EI [et al.]. области. Экология человека. 2006;3:7–11. biochemical modifications: a link between athero- Lipid metabolism in the nonindigenous population [Bichkayeva FA, Zhilina LP, Boyko ER [et al.]. sclerosis and aging. Food Nutr. Res. 2015;59. of Yakutia depending on length of stay in the Nor- Physiological features of metabolic activity of DOI: 10.3402/fnr.v59.29240 th. Yakut medical journal. 2018;2(62):28–30 (In lipids, carbohydrates and proteins in inhabitants 23. Kiechl S, Willeit J, Bonora E [et al.]. No as- Russ.).] DOI: 10.25789/YMJ.2018.62.09 of southern districts of Archangelsk Region. sociation between dehydroepiandrosterone sul- 15. Яковлева А.И., Охлопкова Е.Д., Ekologiya cheloveka. 2006;3:7–11 (In Russ.).] phate and development of atherosclerosis in pro- Кривошапкина З.Н. [и др.]. Состояние анти- 18. Khalil A, Fortin J-P, LeHoux J-G [et al.]. spective population study (Bruneck Study). Arterio- оксидантной защиты организма у больных Age-related decrease of dehydroepiandroste- scler. Thromb. Vasc. Biol. 2000;20(4):1094–1100. ишемической болезнью сердца в условиях rone concentrations in low density lipoproteins 24. Turner RC, Millns H, Neil HA [et al.]. Risk Севера в зависимости от этнической при- and its role in the susceptibility of low density factors for coronary artery disease in non-insu- надлежности. Якутский медицинский журнал. lipoproteins to lipid peroxidation. J. Lipid Res. lin dependent diabetes mellitus: United King- 2018;2(62):38–40. [Yakovleva AI, Okhlopko- 2000;41(10):1552–1561. dom prospective diabetes study (UKPDS: 23). va ED, Krivoshapkina ZN [et al.]. The state of 19. Thijs L, Fagard R, Forette F [et al.]. Are BMJ. 1998;316(7134):823–828. DOI: 10.1136/ antioxidant protection of the body in patients low dehydroepiandrosterone sulphate levels bmj.316.7134.823 with coronary heart disease in the North de- predictive for cardiovascular diseases? A review 25. Kim LB, Russkikh GS, Gevorgian MM pending on ethnicity. Yakut medical journal. of prospective and retrospective studies. Acta [et al.]. Sex hormones and cardiovascular risk 2018;2(62):38–40 (In Russ.).] DOI: 10.25789/ Cardiol. 2003;58(5):403–410. DOI: 10.2143/ in male mining workers living in the European YMJ.2018.62.12 AC.58.5.2005304 North. Human Physiology. 2016;42(2):195–202. 16. Титов В.Н. Липопротеиды очень низкой 20. Barrett-Connor ED, Goodman-Gruen D. DOI: 10.1134/S0362119716020080

T.I. Nelunova, T.Ye. Burtseva, V.A. Postoev, V.G. Chasnyk, M.P. Slobodchikova PATENT DUCTUS ARTERIOSUS ASSOCIATION WITH THE CONGENITAL HEART DISEASE IN THE NEWBORNS DOI 10.25789/YMJ.2019.67.08 OF THE REPUBLIC OF SAKHA (YAKUTIA)

Long-term persistence of the ductus arteriosus is considered as a variant of pathology. Therefore, the identification of the most significant factors in the persistence of the ductus arteriosus is the basis for prevention. The aim of the study was to determine the factors associated with the persistence of the ductus arteriosus in newborns with congenital heart defects. This kind of study is performed for the first time in the Republic of Sakha (Yakutia). The article represents retrospective clinical study. The database included 1.824 cases of children with congenital heart defects. The most common association of the patent ductus arteriosus with congenital heart defects was found among the newborns with a gestation period of less than 32 weeks. It was determined that the prevalence of association of congenital heart disease with a patent arterial duct considerably increased depending on the severity of the heart failure. Keywords: birth defects, heart, patent ductus arteriosus, children, Yakutia.

– postgrad- NELUNOVA Tuyara Ivanovna Introduction. Congenital heart defects defect of development [1,3]. There are uate, St. Petersburg state pediatric medical (CHDs) represent heterogenic groups of single publications of such kind concern- university, [email protected], CHASNYK Vyacheslav Grigorievich – MD, a head of diseases, including comorbities, isolated ing Caucasian population. It is hypothet- the department of hospital pediatrics, St. Pe- and combined anomaly of multifactorial ically believed, that it should be closed tersburg state pediatric medical university, etiology. The problem of blood circulation during the first two weeks of life. Under [email protected], BURTSEVA Tatiana defects is significant as it causes high such criteria, the prevalence of the iso- Egorovna – MD, professor of the department mortality rate, especially during the first lated anomaly is 0.14-0.3 per 1000 live- of pediatrics and pediatric surgery, Medical in- year of life, and disability afterwards. It born children, 7% among all CHDs and stitute of the North-Eastern federal university, is determined that CHDs are related to 3% among all the critical defects [6]. Per- a head of the laboratory of the Yakut science Centre of complex medical problems, bourt- the disturbances of embryogenesis in the sistence of the ductus arteriosus signifi- [email protected], POSTOEV Vitaliy Alexan- 2nd-8th week of gestation as result of ge- cantly depends on the term of pregnancy, drovich – assistant lecturer of the department netic factors, environment and mother’s besides that there are factors caused by of public healthcare and social work, a head physical condition [3,5,7]. mother, as intrauterine hypoxia, nonste- of Arkhangelsk international school of public Long-term persistence of the ductus roidal anti-inflammatory drugs use and healthcare Federal state budget educational arteriosus is considered as a variant of others [2,4]. The list of some other fac- institution of higher education “Northern state pathology. However, the prevalence of tors, which can be associated with the medical university”, [email protected], patent (open) ductus arteriosus among long-term persistence of the patent duc- SLOBODCHIKOVA Maya Pavlovna – a senior lecturer of the department of foreign lan- the indigenous population of the North is tus arteriosus among the children with guages with the course of Russian language, still undetermined as there are no distinct CHDs is not enough studied in the Re- St. Petersburg state pediatric medical univer- criteria from what period of gestation the public of Sakha (Yakutia). sity, [email protected]. ductus arteriosus is considered to be a Objective The objective is to deter- 3’ 2019 31

mine the association of the patent ductus Table 1 arteriosus with CHDs in newborns of the Republic of Sakha (Yakutia) by the method The distribution of patent ductus arteriosus cases in children with CHD according to of logit and regression analysis. This kind the weeks of gestation of investigation is performed for the first Gestation period Absolute number of cases Prevalence, % time in the Republic of Sakha (Yakutia). Less than 32 weeks 78 30.3 Materials and methods: A retrospective clinical research work was performed 32-37 weeks 119 16.4 on the base of the Perinatal centre of the 38 weeks and more 189 22.6 Republican hospital No1, National centre of medicine. A research work is based Table 2 on 1,824 clinical results of medical tests, taken from the medical records of the patients with a diagnosed “Congenital heart The prevalence of patent ductus arteriosus association with other CHDs disease” (CHD). The time distance of the medical records is registered two times, CHD case Absolute number of cases Prevalence thus from 2001 to 2003 and from 2013 CHD without heart failure (HF): isolated interatri- to 2015. The CHD is recorded according al septum defect, mild or in association with patent 73 7.2 ductus arteriosus less than 0.2 cm. to Q20-Q28 (ICD-10, chapter XVII: Con- st genital malformations, deformations and CHD with HF of 1 class, NYHA classification 1: moderate interatrial septum defect or in associa- 24 13.0 chromosomal abnormalities). The deliv- tion with patent ductus arteriosus less than 0.2 cm. ery case reports (#010u) and patient’s CHD with HF of 1st and 2nd class and more, NYHA discharge statistic card (#066/u-02) were classification of thest 1 and 2nd class and more, the initial documentations for analysis. NYHA classification 2 and more: non-complicated 289 46.0 All the newborns had experienced (simple) CHD + complicated (complex) CHD ultrasound examination (Doppler echocardiography) of the heart to evaluate the anatomical structure and cardiovas- Table 3 cular function. The selection is based Association of patent ductus arteriosus with CHDs according to nosologies on the cases with bypass through interatrial septum according to the results of CHD group Absolute number of cases Prevalence, % ultrasound investigation. The functioning Non-complicated (simple) CHDs 347 19.8 activity of the arterial duct was evaluated by colour Doppler test to define additional Complicated (complex) CHDs, including: 33 51.3 flow in the vessel projection, i.e. pulmo- atrioventricular canal, complete 2 33.3 Anomalous pulmonary veins drainage, total 2 40.0 nary trunk. The research was performed Pulmonary artery atresia Ebstein’s anomaly, 5 71.4 from 2001 to 2003 on the base of ATL- tricuspid valve anomaly 3 50.0 HDI-3000 Philips, from 2013 to 2015 on Tricuspid valve atresia 0 0 the base of EPIQ-7 Philips. Double-outlet right ventricle 2 50.0 Logit and regression analysis is per- Obstructive heart defects, coarctation of the 1 100.0 formed to define the association of patent aorta, interrupted aortic arch ductus arteriosus with CHD. Pulmonary artery stenosis 2 33.3 When p<0.05 the intergroup accura- Transposition of great vessels 3 60.0 Fallot’s tetrad 10 58.9 cy was considered significant. The initial Abdominal aortic aneurysm 0 0 data were accumulated in the database Complex CHD 3 60.0 by means of Microsoft Excel software, all the statistic operations were conducted by means of SPSS Statistics soft- Table 4 ware (IBM, USA). Results. The association of patent Factors associated with patent ductus arteriosus in newborns with CHD ductus arteriosus with CHD was revealed in 386 cases, 21.2%. No significant dif- Indicator Corrected OS 95% DI for corrected OS ferences between gender association of patent ductus arteriosus was revealed, Body weight 1.00 1.00 1.00 prevalence of patent ductus arteriosus Sex: was 21.8% in boys, and 20.4% (p=0.436) male 1.00 0.66 1.10 in girls. female 0.85 Most commonly the association of Gestation, weeks 0.89 0.84 0.95 patent ductus arteriosus with CHD was noticed in newborns with the period of CHD groups: group 1 1.00 1.11 3.01 gestation less than 32 weeks, rarely in group 2 1.83 9.12 16.76 groups of newborns with 32-37 weeks of group 3 12.36 gestation (p<0.001) (Table 1). Complex CHD: The association of patent ductus ar- no 1.00 teriosus with CHD differed not only by yes 1.44 0.89 2.36 32 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

groups of defects depending on the pres- CHDs is most common for newborns 3. Жученко Л. А. Распространенность и ence / absence of impaired heart failure, with the gestation period of less than структура врожденных пороков сердечно- сосудистой системы у детей до 1 года. but also nosological groups of defects. It 32 weeks. The association of CHD with Медицинская генетика. 2006. 1:20-22. is estimated that the prevalence of CHD the patent ductus arteriosus differed not [Zhuchenko L. A. Prevalence and structure of association with patent ductus arterio- only groups of defects depending on the congenital defects of cardiovascular system in sus considerably increased depending prevalence of the heart failure, but also children under 1 year. Meditsinskaia genetika. the nosologic groups of defects. The 2006. 1:20-22. (In Russ.).] on the expression of the heart failure 4. Прийма Н.Ф. Эхокардиография в (p<0.0001), see tabe2. prevalence of CHD association with pat- дифференциальной диагностике арте- Complicated (complex) CHDs more ent ductus arteriosus depending on the риального протока у детей. Педиатрия. Журнал often were associated with patent duc- heart failure expression is revealed. The имени Г.Н. Сперанского.2016;7(4):119-127. [Pri- tus arteriosus (51.3% as against 19.8%, patent ductus arteriosus was also associ- ma N. F. Echocardiography in differential diagnosis of arterial duct in children. Pediatria. Journal p<0.0001), see table 3. ated with complex heart defects. imeni G. N. Speranskogo. 2016;7(4):119-127. (In According to the logit and regression Russ.).] analysis with the correction of the ges- References 5. Черкасов Н.С. Заболевания сердца у новорожденных и детей раннего возраста. tation, it was determined (see table 4) 1. Бабак O.A. Гемодинамически значимый Астраханская государственная медицинская функционирующий артериальный проток that CHD with heart failure of 1st degree академия. 2009;268. [Cherkasov N. S. Heart dis- у недоношенных новорожденных факторы (NYHA classification 1) moderate intera- ease in newborns and young children. Astrakhas- риска, клиническая картина, последствия. kaia gosudarsvennaia meditsinskaia academia. trial septum defect or in association with Вопросы практической педиатрии. 2006;1 2009;268. (In Russ.).] patent ductus arteriosus less than 0.2 cm (4):38. [Babak O. A. Hemodynamically significant 6. Шарыкин А.С. Врожденные пороки and CHD with HF of 1st and 2nd class and functioning arterial duct in premature newborns risk factors, clinical picture, consequences. Voprosi сердца. Руководство для педиатров, more (NYHA classification of the 1st and prakticheskoi pediatrii. 2006; 1(4): 38. (In Russ.).] кардиологов, неонатологов. Теремок. 2nd class and more), NYHA classification 2. Бурмистров В.В. Определение пре- 2005;384. [Sharykin A. S. Congenital heart de- 2 and more were significantly associated дикторов и групп риска по развитию функцио- fects. Guidelines for pediatricians, cardiologists, neonatologists. Teremok, 2005; 384. (In Russ.).] with patent ductus arteriosus. Moreover, нальных сердечно-сосудистых заболеваний в разные возрастные периоды у детей, 7. Яковлева Т.В. Региональные there is no significant association of pat- родившихся недоношенными: автореф. … особенности и пути снижения смертности ent ductus arteriosus with complex con- дис. канд. мед. наук. 2000; 25. [Burmistrov V. детского населения РФ: автореф. дис.… канд. genital malformation. V. Determination of predictors and risk groups мед. наук. РАМН. 2001;20. [Yakovleva T. V. Re- gional peculiarities and the ways to reduce mor- Conclusion: According to the logit and for the development of functional cardiovascular diseases in different age periods in children born tality of children population of the Russian Fed- regression analysis, the association of prematurely: autoref. … dis. cand. med. scienc- eration.: avtoref. diss. cand.med. nauk. RAMN. the patent ductus arteriosus with other es.2000;25. (In Russ.).] 2001; 20. (In Russ.).]

DIAGNOSTIC AND TREATMENT METHODS

S.V. Anikin, V.V. Yanovoy, S.V. Khodus THE RISK STRATIFICATION OF THE VENOUS THROMBOEMBOLIC COMPLICATIONS IN DOI 10.25789/YMJ.2019.67.09 ONCOCOLOPROCTOLOGY

The article is devoted to the problem of the venous thromboembolic complications stratification in cases of the colorectal cancer. We performed prospective, randomized, blind study in colorectal surgery department. We analyzed the TEC risk factors due to up-to-date recommendations of the 100 consecutive patients with operable colorectal cancer. The doctors didn’t know about the study (blind) to decrease the ability for study aggravation. After all, 100 cases were get numbers and randomized by the method of random number for 2 groups: Main group (n50) – the TEC stratification performed by our method; control group (n50) – the TEC level got from history of the patients. The underestimation of the risk level of these complications was revealed. The reason of ANIKIN Sergey Vladimirovich, PhD (Med- this risk underestimation was the absence of some risk factors evaluation connected with the icine), MD, Assistant professor of the hospi- patients’ comorbidity and surgery. The authors of the article described method of the thrombo- tal surgery department, Amur state medical embolism risk stratification by new soft for PC with ability to evaluate the risk objectively, unified academy, Russia. 675000, Blagoveshchensk. and with mathematical accuracy with minimal effort. Gorkogo street, 95. [email protected]. https:// It was found out the patients suffering from colorectal surgery has extremely high risk of the orcid.org/0000-0002- 2613-0781, YANOVOY thromboembolic complications. Valeriy Vladimirovich, Professor, Doctor of Keywords: colorectal cancer, thromboembolic complications, thromboembolism of the pul- medical sciences, MD, The head of the hospi- monary artery, stratification. tal surgery department, Amur state medical academy, Russia. 675000, Blagoveshchensk. Gorkogo Introduction. The problem of the ve- The VTEC is situated on the second street, 95. [email protected]. ttps://orcid.org/0000- nous thromboembolic complications place in the structure of mortality and 0002-4481-8520, KHODUS Sergey Vasilievich, PhD (Medicine), MD, The of the anesthesiology (VTEC) of the oncological surgical pa- take place approximately in 20% [2]. and resuscitation department, Amur state medical tients is still urgent. The risk of VTEC at The recent investigations has shown academy, Russia. 675000, Blagoveshchensk. Gork- this case is 10 till 40% without prophy- high risk of VTEC in cases of colorectal ogo street, 95. [email protected]. laxis and fatal in about 10% cases [11]. cancer [1, 3, 7]. 3’ 2019 33

The multifactorial analysis has shown calculate the prophylactic and cure dose trol group had prophylaxis of TEC due to that the risk of lethal outcome, shock of the most actual anticoagulants in ap- recommendations for the moderate risk or thromboembolism of the pulmonary pliance with the patients’ weight. After all, level with no more than 2 points of TEC artery (TEPA) increased in 3 times dur- the doctor has ability to print the protocol risk factors, we found statistically true dif- ing 30 days in case of cancer [14]. Ob- of stratification and put it into the history ference (р=0,023) between the patients viously, the best method of TEC care is case. This protocol reflects all risk factors of the main and control group because primary prophylaxis. The primary TEC and overall risk level for every patient to of the underestimation of the TEC risk by prophylaxis is based on risk stratification protect doctor in a case of judicial trial. doctors without software. Some authors and prophylaxis with accordance to risk Results and discussion. Both groups shown us in their investigation that this level – physical, pharmacological (drug) weren’t statistically differing by the age. underestimation of the TEC risk is world- or surgical methods. Nowadays, the most The age of patients has a great impact wide tendency [8, 13] popular stratification scheme is method to TEPA stratification: 41-60 years – 1 In spite of this, we didn’t get manifest- of Ch. Samama proposed in 1999 [15]. points, 61-74 years – 2 points, 75 and ed TEC in both groups. Though, some But, this scheme is based on only one more – 3 points. First group average age researchers shown [5, 10] that even fatal factor evaluation that has most serious was 63,32±7,58 years (31 - 81 years), TEPA can occur in remote period after the impact to thromboembolism. However, the second group - 64,21±5,62 (34 – 80 surgery and discharge form the hospital. the TEPA risk is defined by summation of years). It's necessary to stress that both Our software is very simple in usage the risk factors connected with comorbid groups has more than 70% patients with – to fill the forms surgeon need no more status and type of surgical intervention. the age more than 61 years and more than 1 min. The possibility to print the Currently, we have a waste majority of than 20% among them was in a group protocol of stratification let us to get ob- the individual TEC evaluation with the of the maximal risk by the age – more jective calculation of the TEC risk score point grading system of every risk factor than 75 years and only 2 (4%) patients of and protect the doctor from some juridical [4, 9, 12]. the first group and 1 patient (2%) of the problems. But unfortunately these methods are second group wasn’t in a high TEC risk Conclusions. “The program for auto- quite complicated and that’s why can’t be because of the age less than 40 years. matic evaluation of the thromboembolic useful in real clinical practice. All patients had colorectal cancer. But complications and its prophylaxis” gives Objective – to improve the TEC the localization of the tumor doesn’t mat- us opportunity to evaluate objectively the prophylaxis for the patients with colorec- ter due to our program and correspond risk of thromboembolical complications; tal cancer. to 2 points. Patients suffering from colorectal can- The design of research. We per- All patients were passed through the cer and passed through the radical sur- formed prospective, randomized, blind radical surgery with the duration more gery have extremely high risk of TEC. study in colorectal surgery department. than 45 minutes that is also risk factor The accuracy of the TEC stratification We analyzed the TEC risk factors due to with 2 points. by our method corresponds to modern up-to-date recommendations of the 100 Moreover, the patients of the both recommendations and surgeon could be consecutive patients with operable colo- group had risk factors: varicose of the protected from some legal problems; rectal cancer. The doctors didn’t know leg veins – n=8 (16%) of the main group Our method allows optimizing and uni- about the study (blind) to decrease the and n=11 (22%) of the second group, the fies the prophylactic of the TEC program. ability for study aggravation. After all, leg puffiness – n=10 (20%) and 12 (24%) 100 cases were get numbers and rand- accordingly, obesity – n=11 (22%) and References omized by the method of random number 8 (16%) accordingly, chronic obstructive for 2 groups: Main group (n50) – the TEC disease n=7 (14%) and n=5 (10%). Fur- 1. Аникин С.В., Яновой В.В. Тромбоэмбо- stratification performed by our method; thermore, the coexistence of 4 and more лические осложнения у больных колорек- Control group (n50) – the TEC level got factors was in 92% for the 1 group and тальным раком. Вестник РГМУ. 2006;2:102. [Anikin SV, Yanovoy VV. Thromboembolic compli- from history of the patients. 86% for the second. Thus, all patients of cations in the colorectal cancer patients. Bulletin Materials and methods. We invented both groups had extremely high risk of of Russian state medical University. 2006; 2:102. software “The program for automatic eval- TEC (more than 5 points). (In Russ).] uation of the thromboembolic complica- Nonetheless, all patients of both 2. Воробьева Л.И. Тромбоэмболические tions and its prophylaxis” (Russian state groups got TEC prophylaxis only in a осложнения у больных онкологического профиля. Онкология. 2002; 1(4): 70–73. [Voro- registration certificate for software for IBM level of compression therapy and early biyeva LI. Thromboembolic complications in the PC №2015619184, from 26.08.2015). activation of the patients after the surgery oncological patients. Oncology. 2002; 1(4):70–73. This software has interface of dialogue (no more than 72 hours). This prophylax- (In Russ)] window with ability for a doctor to point is program corresponds to the moderate 3. Касюк А.А., Прудывус И.С. Оценка риска развития летальной послеоперационной the risk factors of TEC: the age (41-60, level of TEC risk. And only one case of тромбоэмболии легочной артерии у онко- 61-74, 75 and more), risk factors con- the main group and 2 cases of the con- логических пациентов. Военная медицина. nected with the patient (29 factors) and trol group correspond to the level of the 2014;1(30):48-51. [Kasyuk AA, Prudyvus IS. with the surgery (9 factors). The software high TEC risk because of the decompen- Risk assesment of lethal postoperative pulmo- automatically calculates the level of TEC sated varicose disease of the leg veins nary thromboembolism development in cancer patients. Military medicine. 2014;1(30):48-51(In risk (low, moderate, high and extremely- that’s why patients were consulted by Russ).] high) with the accordance to the quality angiosurgeon, ultrasound investigation 4. Баринов В.Е., Лобастов К.В., Бояринцев and quantity risk factors individually to performed and after all anticoagulants in В.В., Счастливцев И.В. Клиническая оценка every patient due to up-to-date stratifica- prophylactic dosage were used in periop- шкалы «Caprini» для индивидуального прогнозирования риска развития после- tion models [4, 12]. Besides, our software erative period. операционных венозных тромбоэмболий у offers the prophylaxis program individu- Thus, the main group patients had av- хирургических больных. Фундаментальные ally with the accordance to the TEC risk erage risk level 6,69±1,2 points (from 5 till исследования. 2013; 12-1:11-16. [Barinov VE, level [6]. The software also has ability to 10 points). If we took as a basis that con- Lobastov KV, Boyarintzev VV., Schastlivtzev IV. 34 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

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T.N. Aleksandrova, I.I. Mulina, V.N. Yadrikhinskaya, I.E. Solovieva, L.D. Terekhova, N.I. Pavlova, Kh.A. Kurtanov CLINICAL AND EPIDEMIOLOGICAL ASPECTS OF CHRONIC MYELOPROLIFERATIVE DISEASES DOI 10.25789/YMJ.2019.67.10 IN THE REPUBLIC SAKHA (YAKUTIA)

Chronic myeloproliferative diseases are characterized by excessive proliferation of myeloid cell lines and a high risk of thrombotic complications. The purpose of the research was to analyze the clinical features and epidemiology of chronic myeloproliferative diseases in the Re- public Sakha (Yakutia). We carried out a retrospective analysis of medical records of patients followed-up by hematologists of Yakutsk from 1995 to 2018. The study included 104 patients, 39 of them were diagnosed with ET (27 women and 12 men), 40 had PV (21 women and 19 men), and 25 had PMF (11 women and 14 men). The diagnosis was established based on the current diagnostic criteria of the World Health Society (WHO). Republican Hospital No. 1 - National Centre of The results of study demonstrated an increase of disease incidence in 2015-2016, preva- Medicine (Yakutsk, Russia): ALEKSANDRO- lence of thrombotic complications among people younger than 60 years and the prevalence of VA Tuiara Nikonovna – hematologist, junior the latent onset of the disease. The average time from thrombosis onset to disease diagnosis researcher of the laboratory of heritable pa- was 1 year. Arterial thrombosis such as acute disorders of cerebral circulation and myocardial thology [email protected]; MULI- infarction occurred more often. NA Inna Ivanovna – Head of the Department It is necessary to carry out a molecular genetic study to identify driver mutations. During fol- of hematology; SOLOVIEVA Irina Eremeevna low up 19.4% of patients have developed re-thrombosis. – hematologist; TEREKHOVA Lena Dmitriev- Keywords: chronic myeloproliferative diseases, thrombosis, cardiovascular risk. na – hematologist; YADRIKHINSKAYA Vera Nikolaevna – candidate of medical sciences, associate professor of department «Hospital therapy, professional diseases, clinical phar- Introductio.Chronic myeloprolifera- CMPD [11, 13]. Polycythemia vera (PV) macology» Medical Institute of North-Eastern tive diseases (CMPD) result from malig- is characterized by proliferation of three Federal University; Yakut science Centre of nant transformation of pluripotent stem myeloid cell lines, while in essential the complex medical problems: PAVLOVA cell followed by clonal proliferation of one thrombocythemia (ET) hyperplasia of the Nadezhda Ivanovna – PhD, temporary acting or more myeloid cell lines (erythroid, my- megakaryocytic line with thrombocytosis chief scientific officer - head of the laboratory eloid, megakaryocytic) that differentiate are mainly observed. In case of primary of heritable pathology E-mail: solnishko_84@ inbox.ru; KURTANOV Khariton Alekseevich into mature forms. Mutations of genes myelofibrosis (PMF) abnormal mega- – PhD, Chief Scientific Officer - Head of the De- JAK2, MPL and CALR, leading to hy- karyocytes produce cytokines leading to partment of Molecular Genetics. Tel.: +7 (914) peractivation of the JAK-STAT signaling the development of bone marrow fibrosis 106 00 30. E-mail: [email protected]. pathway, play a key role in developing and extramedullary hematopoiesis [7]. 3’ 2019 35

The main clinical problem of patients Table 1 with CMPD, leading to disablement and death, is thrombotic complications [5]. In Four-field contingency table large international studies, it was shown that thrombosis is observed in 23.4% of Patients with Patients without patients with PV and 12% of patients with thrombosis thrombosis Total ET [12]. Arterial thrombosis, especially in Presence of risk factor A B A + B cerebrovascular system, is more common Absence of risk factor C D C + D than venous one. Mortality of patients with CMPD because of cerebrovascular Total A + C B + D A + B + C + D diseases is 1.5 times higher than in general population [4]. Venous thrombosis is to literature review CMPD are mainly Thrombotic complications were re- less common, but affects patient survival found in the elderly. The median age of corded in 42,5% of patients with PV and development of microcirculatory dis- patients at the moment of disease mani- (17/40), 30,8% of patients with ET orders causing decrease in quality of life. festation in our study was 50 years in ET (12/39) and 28,0% (7/25) with PMF (ta- Thrombotic complications are less com- (from 38 to 77 years), PV – 56 years (from ble 3). According to the literature, throm- mon in patients with PMF, which can be 21 to 80 years) and PFM – 60 years (from explained by transformation into second- 28 to 80 years). The median time of fol- ary acute myeloid leukemia and lower low-up was 48 months (from 2 months to survival rates [7]. 23 years). In Republic of Sakha (Yakutia), Disease manifestation can have a the primary incidence of ET in different long-term latent course without obvious years ranged from 0 to 0,83, PV – from signs of myeloproliferation, which com- 0 to 0,73, and PMF – from 0 to 0,52 per plicates early disease diagnosis and in- 100 thousand population per year (fig. 1). creases the risk of complications. The primary incidence of CMPD reached Objective: to analyze the clinical and its maximum in 2015-2016 years, which epidemiological features of CMPD in the is most likely due improvement of diag- Morbidity of CMPD in Republic of Sakha Republic Sakha (Yakutia). nosis with molecular genetic testing. Ac- (Yakutia) 2008-2018 years Materials and methods. We carried cording to foreign researchers’ data, the out a retrospective analysis of medi- primary incidence of ET is 0,38-1,7, PV – bosis is more common among patients cal records of patients followed-up by 0,68-2,6, and PMF – 0,1-1 per 100 thou- with PV [6, 15], which is associated with hematologists of Yakutsk from 1995 to sand population per year [8], in Russian an extreme increase in the number of 2018. The study included 104 patients, Federation there are no large epidemio- blood cells, hematocrit, and increased 39 of them were diagnosed with ET (27 logical studies. blood viscosity. In 58,3% (21/36) cases women and 12 men), 40 had PV (21 At the moment of diagnosis in patients thrombosis was the first clinical symptom women and 19 men), and 25 had PMF with ET isolated thrombocytosis was the of disease. On average, the time from (11 women and 14 men). The diagnosis most common sign. Patients with PV thrombosis to diagnosis of disease was 1 was established based on the current demonstrated the signs of three-lineage year. CMPD often has a latent manifesta- diagnostic criteria of the World Health hyperplasia and in PMF patients – leuko- tion. Polycythemia or thrombocytosis can Society (WHO) [14]. The epidemiolog- cytosis with thrombocytosis. Splenomeg- be masked by increased plasma volume ical, clinical, laboratory, therapy data aly was more common in patients with and/or hypersplenism, which causes diffi- obtained during outpatient consultation. PMF (table 2). culties in interpreting laboratory data, and Primary incidence was calculated as ratio of newly diagnosed patients` number Table 2 to average region population number per 100 thousand populations. Complete Clinical characteristics of patients at diagnosis blood cells (hemoglobin, platelet, leukocyte counts and number of blast cells) ET PV PMF and spleen size were recorded at the Men, % (abs.) 30.8 (12) 47.5 (19) 56 (14) time of diagnosis. Analysis of correlation Women, % (abs.) 69.2 (27) 52.5 (21) 44 (11) of risk factors with incidence of thrombo- Median age 50 лет 56 лет 60 лет sis was performed using a four-field con- (from min to max) (от 38 до 77 лет) (от 21 до 80 лет) (от 28 до 80 лет) tingency table (table 1) and a χ-square Average erythrocytes test with Yeats correction (p ). Results * 4.7±0.9 6.6±1.4 5.1±1.4 χ2 count, М±mм were considered significant at p <0.05. Average hemoglobin 135±19.6 171±25.2 127±30.5 χ-square test with Yeats correction count, М±mм Average hematocrit, 46.5±4.6 51.3±7.7 41.7±42.6 М±mм Average leukocytes 9.4±2.7 14.1±13.3 31.4±9.0 count, М±mм calculated by formula: Average thrombocytes 1113±442.2 711.8±445.3 881.5±615.2 count, М±m where Oij is the actual number of ob- м Splenomegaly, servations ij, Eij is the expected number % (абс.) 38.5 (15) 47.5 (19) 60 (15) of observations.

Results and discussion. According *М±mм – mean value ± standard deviation 36 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

JAK2V617F mutation, thrombotic compli- Table 3 cations were observed in 62,5% of cases. First-line therapy with interferon was Prevalence of thrombotic complications in patients with CMPD, % (abs.) prescribed to 42,5% of patients (17/40) with PV, 51,3% (20/39) with ET and ET PV PMF Localization (n=39) (n=40) (n=25) 24% (6/25) with PMF. Hydroxyurea was administered to 30% (12/40) of patients Arterial, total 25.6 (10) 30.0 (12) 16.0 (4) with PV, 23,1% (9/39) with ET, and 44% Cerebral blood flow acute disturbances 12.8 (5) 22.5 (9) 12.0 (3) (11/25) with PMV. In other cases, patients Myocardial infarction 12.8 (5) 7.5 (3) 4.0 (1) receive antiplatelet and vascular therapy. Venous, total 6.0 (2) 12.5 (5) 12.0 (3) 6 patients are currently receiving target- Deep vein thrombosis 6.0 (2) 10.0 (4) 4.0 (1) ed therapy with Ruxolitinib with positive Splanchnic vein thrombosis - 2.5 (1) 8 (2) effect. During therapy with Ruxolitinib, thrombotic complications were not ob- the clinical picture is represented only by and leukocytosis more than 11*109/l) served in patients. thrombosis [6]. [3]. The contribution of different factors Conclusion. In the Republic Sakha Arterial thrombosis (30,0 and 25,6%) to pathogenesis of thrombosis is widely (Yakutia) for the research period (1995- prevailed among thrombotic complica- discussed in literature, and a number of 2018) the primary incidence of ET per tions in patients with PV and ET — acute scales have been proposed for risk strat- 100 thousand population per year was 0 disorders of cerebral circulation and ification. Most authors agree that statisti- – 0.83, PV – 0 - 0.73, and PMF – 0 – 0.52, myocardial infarction, less frequently cally significant risk factors for thrombotic reaching maximum values in 2015-2016. seen venous thrombosis (12,5 and 6%). complications are age over 60 years and Thrombotic complications, which are a In patients with PMF, arterial thrombosis history of thrombosis [2]. Among ad- serious clinical problem, are observed in was observed in 16% of cases, and ve- ditional risk factors, some authors pay patients with CMPD in 28-42.5% of cas- nous in 12%. The median time between special attention to leukocytosis. It was es. In a half of the cases, thrombosis was the diagnosis of the disease and the de- demonstrated that activated leukocytes a first clinical symptom of myeloprolifera- velopment of thrombosis was 3 years synthesize prothrombotic substances tive disease. A statistically significant risk (from 0 to 30 years). Recurrent throm- that cause functional changes in the en- factor for thrombosis is the presence of botic complications were observed in dothelium, stimulate platelet activity, and cardiovascular risks, which determines 19,4% (7/36). The predominance of arte- they contribute to generation of thrombin the need for a comprehensive approach rial thrombosis over venous thrombosis and development of thrombosis [15]. to the treatment of this group of patients. is explained by the direct participation in Statistically significant differences in the pathogenesis of clot formation of the the group of patients with thrombosis and References vascular endothelium. Damage to the without thrombosis were revealed only vascular wall caused by hyperviscosity by the presence of cardiovascular risk 1. Шихбабаева Д.И., Полушкина Л.Б., Шу- syndrome and the production of proteo- factors (p <0.05) (table 4). There were no ваев В.А., Мартынкевич И.С., Капустин С.И., Замотина Т.Б., Фоминых М.С., Удальева В.Ю., lytic enzymes by activated neutrophils, statistically significant differences in inci- Зотова И.И., Шмелева В.М., Смирнова О.А., morphological and functional changes dence of thrombosis in groups of people Волошин С.В., Бессмельцев С.С., Чечеткин of blood cells and procoagulant state older than 60 years and younger. Throm- А.В., Абдулкадыров К.М. Генетические марке- of plasma represent a multicomponent botic complications in people of working ры наследственной тромбофилии и риск тром- ботических осложнений у больных с истинной mechanism of clot formation. A number age have a high social significance, since полицитемией. Клиническая онкогематология. of publications report a higher thrombo- they can lead to disability and a decrease 2017;10(1):85-92. [Genetic markers of hereditary genic potential of platelets in patients in quality of life. thrombophilia and risk of thrombotic complica- with JAK2V617F mutation [9]. During follow-up molecular genetic tions in patients with polycythemia vera. Shikh- The analysis of risk factors for throm- testing was performed in 20,2% of pa- babaeva DI, Polushkina LB, Shuvaev VA, Martyn- kevich IS, Kapustin SI, Zamotina TB, Fominykh botic complications included both ma- tients (21/104), of which in 15,4% of pa- MS, Udal’eva VU, Zotova II, Shmeleva VM, jor factors (age over 60 years, history tients (16/104) mutation of JAK2 gene Smirnova OA, Voloshin SV, Bessmel’tsev SS, of cardiovascular risks) and additional was fond and in 3,8% (4/104) mutation Chechetkin AV, Abdulkadyrov KM. Klinicheskaja (thrombocytosis more than 1000*109/l of CALR gene. Among patients with onkogematologija. 2017;10(1):85-92. (In Russ.).] DOI: 10.21320/2500-2139-2017-10-1-85-92 2. Меликян А.Л, Суборцева И.Н. Биоло- Table 4 гия миелопролиферативных заболеваний. Клиническая онкогематология. 2016;4(3):314- Prevalence of thrombosis risk factors in patients with and without thrombosis, % (n) 325. [Melikyan AL, Subortseva IN. Biology of myeloid malignancies. Klinicheskaja onkogematologija. 2016;4(3):314-325. (In Russ.).] DOI: Patients with chronic myeloproliferative 10.21320/2500-2139-2016-9-3-314-325 diseases Risk factor 3. Танашян М.М., Кузнецова П.И., Лагода without thrombosis with thrombosis О.В., Шабалина А.А., Суборцева И.Н., Мели- (n=68) (n=36) кян А.Л. Миелопролиферативные заболева- Age 60 and older 51.5 (35) 47.2 (17) ния и ишемические инсульты. Анналы кли- нической и экспериментальной неврологии. Cardiovascular risk factors 19.1 (13) 38.6 (15) 2014;8(2):41-45. [Tanashyan ММ, Kuznetsova 9 PI, Lagoda OV, Shabalina AA, Subortseva IN, Thrombocytosis>1000*10 /l 30.9 (21) 19.4 (7) Melikyan AL. Myeloproliferative diseases and Leukocytosis >11*109/l 27.9 (19) 33.3 (12) ischemic stroke. Annaly klinicheskoj i eksperimental'noj nevrologii. 2014;8(2):41-45.(In Russ.)] 4. Танашян М.М., Кузнецова П.И., Раскура- * pχ2 – χ-square test with Yeats correction 3’ 2019 37

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M. P. Kirillina, V. I. Kononova, S. I. Sofronova, A. K. Ivanova, E. L. Lushnikova THE INCIDENCE OF DYSPLASTIC CHANGES DOI 10.25789/YMJ.2019.67.11 IN CERVIX UTERI AMONG WOMEN OF DIFFERENT AGE GROUPS

Yakutsk, Republic Sakha (Yakutia), Russia: KIRILLINA Maria Petrovna – Candidate of The article presents an analysis of the incidence of dysplasia degrees and cervical cancer Biological Sciences, Senior Research Scien- (CC) in women of different age groups based on cytological studies from 2016 to 2018 inclusive. tist, Head of Yakut Science Centre of Complex The frequency of incidence of CIN 1, CIN 2, CIN 3 and CC was determined, which is inversely Medical Problems Laboratory, Head of NEFU dependent on the dysplasia degree in all age groups of women. While the incidence of CIN 2, Medical Institute Clinic Laboratory,kirillinamp@ CIN 3 and CC was decreasing, CIN 1 increased between 2016 and 2018. Women 26-35 years mail.ru,89142716881, KONONOVA Irina had the highest incidence of CIN 1, CIN 2 and CIN 3; also CIN 2 was detected in women 36-45 Vasilievna – Candidate of Medical Science, years, as in the first group; women of 46-55 years had a sharp rise in CC - it is 2.5 times higher Research Worker of Yakut Science Centre of than in previous two groups. The peak incidence of CC was in patients aged 56 years and older. Complex Medical Problems Laboratory, irina- Keywords: screening, oncocytology, diagnosis, dysplasia, cervical cancer. [email protected] 89243683673, SOFRONOVA Sargylana Ivanovna – Candidate of Medi- cine, Senior Research Associate, Head of Sci- Relevance. According to various au- (HPV) [8,9].The state of local immunity, entific and Organizational Department of Yakut thors, cervical pathology makes up from as a regeneration process control agent Science Centre of Complex Medical Problems 10 to 15% of all gynecological diseases [1], has great importance in the devel- Laboratory, [email protected] 89841094825, [3]. Occurrence and development of the opment of dysplastic processes in the IVANOVA Anna Konstantinovna - Clinical causes and mechanisms of cervix uteri cervix uteri, as well as a hormonal state, Pathologist of NEFU Medical Institute Clin- pathological processes are rather com- since cell developing and differentiation ic, [email protected], 89248647588, plex and understudied process [2]. As is in the stratified squamous epithelium LUSHNIKOVA Elena Leonidovna- Doctor known, dysplastic changes in the cervix of the cervix uteri is hormone-depen- of Biological Science, professor, the head of uteri epithelium are considered as pre- dent. Because of the hormonal status in FSBIS Institute of Molecular Pathology and Pathomorphology “Federal Research Center cancerous states [6], there is evidence women depends on age, it determines of Fundamental and Translational Medicine” that one of the main conditions for the the usefulness of studying the features 630117,Novosibirsk,Timakova st.,2, pathol@ development of dysplasia and CC is the of dysplastic changes in cervix uteri in inbox.ru8(383)334-80-03. persistence of the human papillomavirus different age groups, irrespective of the 38 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

HPV detection in patients. In addition, the Materials and methods of research: years – 192 women (20.6%), 56 years frequency of epithelial dysplasia increas- The analysis of cytologic material of a and older – 161 women (17.3%).The es with age [6]. However, the greatest cervix of 7600 women aged from 18 up CIN incidence of varying degrees is pathogenic effect of HPV manifests in to 88 years with the preventive and di- analyzed, as well as CC in the cytologi- young women, and it realizes in the de- agnostic purpose, during 2017 – 2018 is cal smears of all women who underwent velopment of cervical intraepithelial neo- carried out to laboratory of a pathomor- examination from 2016 to 2018 inclusive. plasia (CIN) of severe degree [9], which phology, histology and cytology of Clinic It is clear that the highest rate is in CIN requires careful study of age-related fea- of Medical institute of NEFU. 1, which was registered in 578 women tures of pathomorphological dysplasia The material of the study was smears and amounted to 62.1% of all women presentation. Dysplasia is a morpholog- from the mucosa of the cervix uteri and studied, CIN 2 was found in 241 women ical concept, so diagnosis is made only the cervical canal. Cytological diagnosis (25.9%), and CIN3 was diagnosed in 97 on the basis of cytological and histolog- was carried out by staining, the method women, which amounted to 10.4% of all ical data [6].Cells with dyskaryosis are of Romanovskiy - Giemsa. Cytological cytologically detected in dysplasia of cer- diagnosis – degree CIN (cervical cancer) vical smear. Depending on the severity of is made in accordance with the clinico- changes in the nucleo-cytoplasmic ratio pathologic classification of Y. V.Bokhman and other structural features (shape, nu- (1976). The incidence of CIN 1, CIN 2, clei, content, and distribution of chroma- CIN 3 (CC) in smears was expressed in tin, inclusions in the cytoplasm) there are percentage of the total number of women 3 degrees of CIN: CIN 1 (mild dysplasia), with dysplasia. CIN 2 (moderate dysplasia) and CIN 3 Results and discussion. The total (severe dysplasia) [7]. Cytological pic- number of patients with dysplastic chang- ture of CIN 1 is represented by relatively es in the cervix uteri of different degrees Fig. 3. Dynamics of incidence of dysplasia of mature cells with relatively large nuclei. was 931 people. Of them, 128 women different degrees for the period 2016-2018 These cells are located separately or (13.7% of the total) went through cyto- in the two-dimensional assembly of un- logical examination in 2016, 322 women cervical dysplasia in the examined group changed squamous epithelial cells. Cells (34.6 %) in 2017, and 481 women (51.6%) (pic.1,2).Cervical cancer was cytologi- retain signs of cytoplasmic differentiation in 2018. Cytological material was studied cally detected in 15 cases and amounted characteristic of the surface and interme- in women according to the age groups, to 1.6% of the total number of examined diate layers of the flat epithelium. Nuclei the distribution was as follows: women women (pic.5).It should be noted that the – slightly hyperchromic, with the same under 25 years - 144 people (15.5%), high frequency of CIN 1 incidence is de- type of uniform granular structure of 26-35 years – 222 people (23.8%), 36- tected in the inflammation of the cervix chromatin, nucleoli are absent. Signs of 45 years – 212 women (22.7%), 46 – 55 when a cytological study reveals repara- infection with the human papillomavirus tive atypical cells – equivalents of dyspla- (HPV) are often occurred . In CIN 2 the sia. These phenomena often disappear shape and size of cells resemble cells of after anti-inflammatory treatment, elimi- immature squamous metaplasia, but with nation of the viral agent [4]. larger nuclei. The cytoplasm has a sharp As Fig.3 shows analysis of the fre- contour (a distinction of squamous cell quency of CIN 1, CIN 2, CIN 3 incidence differentiation). Nuclear-cytoplasmic ratio and CC over a three-year period (from is increased. There is hyperchromia of 2016 to 2018 inclusive), depending on the nuclei, the granular structure of chro- the year of the examination, CIN 1 is in- matin, and nucleoli are not visible. Some- creasing from year to year while CIN 2 times signs of HPV infection are found. In Fig. 1. The distribution of the incidence rate of and CIN 3 are reducing. The frequency cytological preparations with CIN 3 signs the dysplasia of different degree for the period of CIN 1 incidence in 2018 increased 2016-2018 of atypia are more intensive. Sharp con- by 52.6% compared to 2016, while the tours of the cytoplasm are visible in cells, CIN 2 incidence decreased by 24.3%, making them relate to the squamous and the CIN 3 incidence decreased 3.3 epithelium cells. Nuclear-cytoplasmic ra- times. The incidence of СС decreased tio strongly increased. Severe atypia is 2.2 times in the studied smears during particularly visible in the nucleus: lumpy a three-year period. It indicates a pos- chromatin, nuclear membrane are irregu- itive dynamics in the development of lar, nucleoli are absent. There are remote dysplasia. The growth of CIN1 can be signs of HPV infection [5]. Purpose of research. To determine the features of the occurrence of dysplastic changes in cervix uteri in women of different age groups, we decided to analyze the frequency of incidence of CIN 1, CIN 2, CIN 3 and CC in cytological smears of women of different age groups who were examined from 2016 to 2018 inclusive; to Fig. 2 А – Cells with signs of mild dysplasia identify the frequency and dynamics of CIN (CIN 1), B – cells with signs of moderate dys- 1, CIN 2, CIN 3 and CC depending on the plasia (CIN 2), C, D– severe dysplasia (CIN Fig. 4. Incidence of cervical dysplasia in differ- year of examination and age of women. 3), X200 ent age groups 3’ 2019 39

explained by reactive epithelial changes groups than in women 26-45 years age grees, including severe degree, women in various inflammatory diseases. Re- group (in women under 25 years, CC was of 1960 (age group 46-55 years and duction of CIN2 and CIN3, CC can be not detected).The study confirms that the older), who had a sharp increase of CC. associated with constant monitoring of progression of the severity of dysplasia The paper was written as part of R&D patients and the development of dyspla- is going many decades [10]. Also, when “The epidemiological aspects of can- sia in the dynamics and effectiveness of the severity of dysplasia increases -the cer on the Far North living environment, the treatment. risk of its progression increases and the development of modern early detection In studying the incidence of cervical chance of regression decreases. methods, and prevention methods with dysplasia depending on age, our analy- Conclusion. The frequency of CIN high-informative fundamental research. sis showed that the most frequently di- 1, CIN 2, CIN 3 and CC incidence in (М06; 01; 01)" (№ 0556-2014-0006). agnosed cervical pathology in all age smears of cervix uteri and the cervical groups was CIN 1(pic.4).The maximum canal was inversely dependent on the References frequency of CIN 1(14.2%) incidence degree of dysplasia in all age groups of was observed in women of 26-35 age women who were examined from 2016 1. Бабаева А.Г. Регенерация: факты и group, the minimum value of this indica- to 2018.The incidence rate of CIN 1 in- перспектива. М., 2009:336. [Babayeva AG. Re- tor (10%) was in the group of 56 years creased from 2016 to 2018, while CIN 2 generation: facts and perspective. M., 2009: 336. (In Russ.).] and older. The maximum frequency of and CIN 3 and CC have been decreas- 2. Краснопольский О.Ф., Серова В.А., CIN 2 (6.4%) incidence was observed in ing the rates. Analysis of the nature of Туманова и др. Влияние инфекций на the same population in two groups (26-35 CIN 1, CIN 2, CIN 3 and CC incidence, репродуктивную систему женщин. Российский years and 36-45 years). Both groups rep- depending on age revealed that women вестник акушера- гинеколога. 2004;4(5):26-29. resent women of childbearing age. The of 26-35 years had the highest incidence [Krasnopolsky ОF, Serova VA, Tumanova et al. The effect of infections on the reproductive sys- minimum frequency of CIN 2 (3.7%) inci- of CIN 1, CIN 2 and CIN 3, women of tem of women. Russian vestnik akushera-gine- 36-45 years had CIN 2 with the same kologa. 2004; 4(5): 26-29. (In Russ.).] frequency as in the previous group, and 3. Новик В.И. Факторы эффективности women of 46-55 years had a sharp in- цитологического скрининга рака шейки матки. Практическая онкология. 2010; 11 (2):66-71. crease in CC by 2.5 times, compared [Novik VI. Factors of the effectiveness of cytolog- with the previous two groups, but pa- ical screening for cervical cancer. Prakticheskaya tients of 56 years and older had the peak onkologiya. 2010; 11(2):66-71. (In Russ.).] incidence of CC. 4. Полякова В.А. Онкогинекология. Regular cytological examination of cer- Медицинская книга.2001:192. [Polyakova VA. Medicinskaya kniga. 2001:192. (In Russ.).] vix uteri leads not only to decrease in the Fig. 5. A - adenocarcinoma of the cervix uteri, 5. Полонская Н.Ю., Некрасов П.И., Роговская B - squamous cell carcinoma of the cervix number of newly diagnosed patients from С.И. Повышение эффективности диагностики uteri, X200 year to year but also to absence or slow- заболеваний шейки матки: в помощь цитологу down of negative dynamics and possible и специалисту по кольпоскопии. Доктор.ру. 2015;2(12):6-9. [Polonskaya NYu, Nekrasov dence was in the group of women 46-55 regression of existing pathological chang- PI, Rogovskaya SI. Improving the efficiency years. The highest incidence of CIN3 was es in cervix uteri. Prevention, early detec- of diagnosis of diseases of the cervix uterus: observed in women aged 26-35 years and tion and effective treatment of malignant to help the cytologist and specialist in colpos- was 3%. The minimum incidence of CIN3 tumors is one of the most important part copy. Doktor.ru. 2015; 2(12):6-9. (In Russ.).] (0.8%) was in women under 25 years. of modern medicine. The need of regu- 6. Прилепская В.Н. Заболевания шейки матки, влагалища и вульвы МЕД пре-информ, The obtained data is indicating the maxi- lar preventive examinations of women 2005:432. [Prilepskaya VN. Diseases of the cer- mum number of women who became ill with the necessary cytological examina- vix, vagina and vulva. MED pre-inform. 2005:432. at fertile age, and it is an alarming fact tion, clinical examination, and treatment (In Russ.).] since this group of patients is not only a of patients with background CC diseases 7. Сидельникова В.М. Первичная потеря беременности. Триада-Х. 2000:304. [Sidelniko- reproductive considerable part of the fe- is appears based on the data analysis of va VM. Primary pregnancy. Triada-X. 2000:304. male population but also an active social the incidence of dysplasia and CC. Such (In Russ.).] group. Cervical cancer was detected cy- an arrangement should be optimized ac- 8. Munoz N, Bosch FX, de Sanjose S, Herrero tologically in 15 cases and amounted to cording to the age of women. Our results R, Castellsague X, Shah KV, Snijders PJ, Meijer 1.6% of the total number of women ex- require special studies on developing the CJ. Epidemiological classification of human papillomavirus types associated with cervical cancer. amined. The maximum incidence of CC lines of approach on the main problems N. Engl. J. Med. 2003; 348 (6):518-527. was observed in of 56 years and older associated with the detection, preven- 9. Ed. Fattaneh A. Tavassoli, Peter Devilee. age group-6 cases (0.6%). It should be tion, and treatment of early forms of CC. Pathology and Genetics of Tumours of the Breast noted that the incidence of CC increases However, at present, we recommend and Female Genital Organs (WHO Classification of Tumours). Lyon.: IARC Press. 2003:266-268. depending on the age of patients. The paying more attention to women born 10. Richart R. M., Barron B. A. A follow-up rate is 2.5 and 3 times higher in women in 1980-1990 (age group 26-35 years), study of patients with cervical dysplasia. Amer.J. of 46-55 years and 56 and older age who most often had dysplasia of all de- Obstet. Gynecol.1969;105:386-393. 40 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

E.I. Semyonova, L.D. Olesova, A.V. Yefremova, E.D. Okhlopkova, L.I. Konstantinova, A.I. Yakovleva, A.N. Romanova, S.I. Sofronova, A. G. Egorova THE STRUCTURED SPOT OF BLOOD PRESSURE FROM THE PERSPECTIVE DOI 10.25789/YMJ.2019.67.12 OF THE "GOLDEN RATIO" PROPORTION

The analysis of blood pressure indicators for residents of the Republic (Yakutia) from the position of the golden ratio using the structural spot of blood pressure (SSBP) - the ratio of DBP / SBP with a value close to the value of the golden ratio (ZP) - 0.618 (harmonious ratio) was performed. Existing blood pressure standards (120/80 mmHg) are not always acceptable for all categories of the population, especially for older people. Therefore, each person needs an individual approach. It has been established that SSBP opens up new possibilities in terms of the proportion of the golden ratio in predicting the stability of the course of blood pressure during functional studies in patients with arterial hypertension. Keywords: Yakutia, blood pressure, arterial hypertension, golden ratio.

Introduction. In recent decades, es- morbidity rate of the adult population in way as the length of the whole interval sential arterial hypertension (EH) and 2017, the index of hypertensive heart and to the length of AB (AB: BC = AC: AB ). coronary heart disease (CHD) have firm- kidney disease was 264.3 per 100,000 of The golden ratio is made if the whole is to ly taken the leading place in the structure the total population [10]. the one part as 1:0.618, and most to the of cardiovascular and overall population In recent years, the prevalence sta- lesser as 0.618:0.382 [17, 18]. Also, the morbidity. Arterial hypertension (AH) is tistics of AH in the territory of the Sakha concept of the “golden ratio” is described significant because it is the most import- (Yakutia) Republic continues to grow. by the proportions found by using the val- ant risk factor for cardiovascular diseas- Therefore, in 2016-2017, the prevalence ue that is the universal quotient of divid- es, mainly affecting the statistics of com- of AH was 43.7 and 44.82%, respective- ing a larger number by the next smaller plications, disability and high mortality ly. According to the latest statistics, the number in the gold series of Fibonacci in the world community. More than half number of deaths from circulatory sys- numbers (1, 1, 2, 3, 5, 8, 13, 21, 34, 55, of the deaths in the Russian Federation tem diseases from January to December 89 etc.; that is 89:55 = 1.618 ...) [17,18]. are due to circulatory system diseases. 2018 in Yakutia was 355.0 per 100,000, In recent years, scientists have active- According to the statistics of the general and 325.6 from January to February ly studied the relationship of the golden 2019 [5, 19]. ratio with the heart function and hemody- Yakutsk, Russia, Yakut Science Centre of According to the synergetics theory, namic indices. V.D. Tsvetkov was the first Complex Medical Problems: SEMYONOVA the human body is a multi-level hierar- to show the role of the golden ratio and Evgenia Ivanovna – Candidate of Biological chically organized complex system. Dif- Fibonacci numbers in the organization of Sciences, Senior Scientist, E-mail: kunsun- ferent levels interact with each other in the cardiac systems, he found that the [email protected], OLESOVA Lyubov Dygynova different ways and thereby determine the golden numbers are the guarantors of the – Candidate of Biological Sciences, Leading state of dynamic equilibrium [6,15]. optimal heart activity, the most economi- Research Scientist, Head of the Laboratory The state of dynamic equilibrium sup- cal in terms of energy and living matter of biochemical studies at the “Yakut Science ports the functioning of the organism, [7, 18]. Moreover, it was researched that Centre of Complex Medical Problems”. EFRE- and a change of this state as a result of the ratio of heart rate variability to the di- MOVA Agrafena Vladimirovna – Candidate of Biological Sciences, Senior Scientist of the external influences or diseases leads to astolic interval was 1.618, which is the Laboratory of biochemical studies at the “Ya- disturbances in hierarchical interactions. golden ratio [8, 21]. Similar studies were kut Science Centre of Complex Medical Prob- These disorders are either quickly com- conducted to find out whether diastolic lems”. KONSTANTINOVA Lena Ivanovna pensated or lead to the development of and systolic blood pressure is consistent – Research Scientist of the Laboratory of bio- the pathological process [3]. with this ratio [22]. chemical studies at the “Yakut Science Centre Thus, the circulatory system can also Deviations from ideal indices (1.618 or of Complex Medical Problems”. YAKOVLEVA be viewed as a multi-level hierarchically 0.618) among healthy people are consid- Alexandra Ivanovna – Research Scientist of complex system and at the level of its ered to be no more than 5–8%, even with the Laboratory of biochemical studies, Adap- constituent subsystems that determine tation Mechanism Research Division, “Yakut the changes of hemodynamic indices by Science Centre of Complex Medical Prob- the balance of the body. One of the dis- 1.5–2 times [1]. lems”. OKHLOPKOVA Elena Dmitrievna plays of such structural and functional In 1998 V.V. Shkarin and E.V. Gur- – Candidate of Biological Sciences, Leading balance is a correspondence with the vich studied the clinical value of diastolic Research Scientist, Head of the Laboratory of “Golden ratio” rule [17,18]. (DBP) and systolic (SBP) blood pressure immunology, “Yakut Science Centre of Com- The rule of the golden ratio has been (BP) ratio. This ratio has the term "struc- plex Medical Problems”. ROMANOVA Anna known to mankind for a long time and has tured spot of blood pressure" (SSBP). Nikolaevna – Doctor of Medicine, Director of found application both in science and art. Currently, it is known that SSBP is ap- the “Yakut Science Centre of Complex Med- Pythagoras introduced the concept of the proaching the value of the “golden ratio” ical Problems”. SOFRONOVA Sargylana gold division into science. The “golden ra- proportion - 0.618. Regardless of BP in- Ivanovna – Candidate of Medical Sciences, Chief Research Scientist, Chief of the “Yakut tio” is known as proportions: the division dicators, SSBP aims for a constant value Science Centre of Complex Medical Prob- of the AC interval into two parts, so that [3, 4]. lems”. EGOROVA Aytalina Grigorievna – the length of the bigger part AB is to the V.G. Bochkov developed a universal Candidate of Medical Sciences. length of the smaller part BC in the same table of the quality zones of the systems 3’ 2019 41

functioning, depending on the value of in- Smirnov nonparametric test. Differences Oymyakonsky District, Ust–Nera village dices similar to SSBP for any biological were considered statistically significant at (32.89 + 3.00) (Table 1). system, applicable for BP, too [4]. p <0.05. The results of the obtained blood The purpose of this study was to as- Research results. According to the pressure (BP) data and SSBP in the sur- sess and analyze the structured spot of blood pressure data of the studied pop- veyed residents by district are presented blood pressure in residents of Yakutia ulation, the structured spot of blood pres- in Table 2. The average indices of blood from the perspective of the "golden ratio". sure was calculated as the clinical value. pressure and SSBP in the districts were Materials and methods. The study At the moment, it has been shown that SBP 129.94 + 0.544 mm Hg, DBP 81.10 used the existing database of biomed- SSBP is approaching the value of the +, 297 mm Hg. at a harmonious SSBP of ical expeditions of the Yakut Science proportion of the golden ratio = 0.618 [4]. 0.629 + 0.00. A SSBP close to the golden Centre of Complex Medical Problems The results of anthropometric indices proportion (0.618) was found in the res- from 2008-2018, including data on 1959 close to the golden proportion (GP) in idents of Anabarsky (0.615 + 0.00) and people. Blood pressure data of 12 re- terms of blood pressure and SSBP are Ust-Aldansky (0.619 + 0.00) districts, gions of the Republic of Sakha (Yaku- presented in Table 1. With the indices of where blood pressure corresponded to tia) was analyzed. Districts were divid- SSBP equal to (0.615-0.618), the resi- SBP 135.45 ± 2.29 mm Hg. and 134.05 + ed by socio-economic zones: Northern dents of Tomtor village, Oymyakonsky 1.59, DBP 82.13 ± 0.82 and 81.92 + 0.76 (Arctic) - Anabarsky, Verkhnekolymsky, District had the shortest height (1,547 ± mm Hg respectively (Table 2). Srednekolymsky; Eastern - Ust-Maysky, 0,03), and the residents of Yakutsk are With age, there is a tendency of in- Oymyakonsky (Tomtor, 2018), Oymya- the tallest 1,731 ± 0.06 m ( p <0.05). creased blood pressure and decreased konsky (Ust-Nera, 2008); Western – Vi- The body weight of the residents of the SSBP, while significant differences in lyuysky; Southern - Lensky, Aldansky; Srednekolymsky District corresponded pressure and SSBP have been observed Central - Megino-Kangalasky, Ust-Aldan- to 81.10 + 7.24 kg and was the highest since the age of 30. High pressure, ex- sky, Yakutsk. indicator in the compared groups, and ceeding normal values, begins at the age The body mass index (BMI) was calcu- the residents of the Megino-Kangalasky of 50 and reaches the highest value in the lated by the formula: BMI = body weight district had the smallest weight - 61.42 age group of 80-89 years old (Table 3). It in (kg) / height (m)2 [16]. For overweight + 7.36 kg (p <0.05). Body mass index should be noted that from the surveyed took the values were > 25 and < 30 kg / (BMI) showed as overweight almost population, only 1.61-3.23% of the pop- m2. Obesity was recorded with a BMI > in all groups. Obesity was observed in ulation had a harmonious (0.615) SSBP 30 kg / m2 (according to European rec- residents of the Verkhne- and Sred- indices, close to the GP (0.618) (Table 3). ommendations of the III revision, 2003). nekolymsky districts (30.83 + 3.06, 31.59 The surveyed population was divided During the classification of blood pressure + 4.32 respectively), as well as in the into 2 groups: the 1st group included res- levels of mm Hg. data from VNOK (2009) [2] was used, so the optimal was <120 Table 1 and <80 mm Hg, normal 120–129 and / or 80–84 mm Hg, high normal 130-1139 Anthropometric measurements and BMI among the examined residents with the SSBP / or 85–89 mm Hg; Grade 1 hypertension indices close to the Golden proportion (0,615-0,618) corresponded to 140–159 and / or 90–99 mm Hg, grade 2 hypertension - 160–179 Height, Weight BMI SBP, DBP, DISTRICT SSBP and / or 100–109 mm Hg, 3rd degree hy- m kg mm Hg mm Hg pertension - ≥ 180 and / or ≥110 mm Hg. For the assessment of blood pressure in- Anabarsky 1.62 74.41 29.35 130.0 80.0 0.615 dices, the “structured spot of blood pres- n=16 (13.11%) ±0.05 ±8.30 ±3.59 0±.00 0±.00 0±.00 sure” (SSBP) and the ratio of DBP/SBP Lensky 1.61 68.25 26.25 128.1 78.84 0.616 was used. It is now known that SSBP is n=13 (9.15%) ±.04 6±.30 ±2.49 3±.65 2±.19 ±0.00 Megino-Kangalasky 1.53 26.31± 130.00 80.00 0.615 approaching the value of the golden pro- 61.42±7.36 portion of the RFP - 0.618 (harmonious n=12 (6.15%) ±0.04 2.69 ±5.73 ±3.44 ±0.00 Oymyakonsky 2018 ratio). The values of blood pressure with 1.55 62.33 26.14 121.67 75.00 0.617 (Tomtor village) SSBP in the range from 0.564 to 0.673 ±0.03 ±11.43 5±.14 ±10.97 ±6.58 ±0.00 n=3 (1.62%) among healthy people were considered Srednekolymsky 1.67 81.10 31.59 130.75 80.50 0.616 stable. In patients with arterial hyper- n=4 (8.51%) ±0.02 ±7.24 ±4.32 ±12.43 ±7.52 ±0.00 tension (AH), “disharmony” ranged from Ust-Aldansky 1.61 68.68 26.49 132.50 81.56 0.616 0.549 to 0.687 (the deviation of GP from n=16 (4.97%) ±0.05 ±4.65 ±1.61 ±8.90 ±5.46 ±0.00 up to 8% - 11%).The greatest differenc- Ust-Maysky 1.59 73.87 29.25 129.12 79.38 0.615 es from the GR proportion, “imbalance or n=8 (5.63%) ±0.04 ±9.23 ±4.11 ±14.47 ±8.77 ±0.00 disbalance” (12% and above), which are Vilyuysky 1.59 63.25 25.026 125.75 77.50 0.617 characteristic of unstable states: border- n=4 (5%) ±0.05 ±13.73 ±4.84 ±15.64 ±9.35 ±0.00 line arterial hypertension, severe forms of Verkhnekolymsky 1.65 83.57 30.83 119.14 73.57 0.618 AH, possibly crisis forms of AH [3]. n=7 (8.05%) ±0.05 ±9.53 ±3.06 ±6.48 ±3.85 ±0.00 Statistical processing of the results Yakutsk 1.73 83.23 27.79 130.00 80.00 0.615 was performed using the SPSS applica- n=13 (3.54%) ±0.06 ±7.45 ±2.10 ±0.00 ±0.00 ±0.00 tion package (version 17) and Microsoft Aldansky 1.67 77.13 27.60 133.33 82.00 0.615 Office Excel 2003.The accuracy of dif- n=15 (8.93%) ±0.05 ±8.40 ±2.53 ±6.56 ±3.94 ±0.00 ferences between average indices was Oymyakonsky 2008 1.59 83.80 32.89 121.57 75.00 0.617 (Ust-Nera village) assessed using Student’s t-test, Wilcox- ±0.48 ±5.19 ±3.00 ±6.67 ±3.97 ±0.00 on–Mann–Whitney (Ζ) and Kolmogorov– n=7 (6.94%) 42 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

(or quite close to this value within 6/11 Table 2 - 8/11), as it is approaching the golden The indices of BP and SSBP by districts ratio (0.618). Meanwhile, in group 2, harmonious SSBP (0.615) was indicated in SBP, DBP, only 1.84% of people. Harmonious SSBP Districts n SSBP mm Hg mm Hg in group 1 was significantly different from Anabarsky 122 135.45±2.29 82.13±0.82 0.615+0.00 all other indices of SSBP and blood pres- Lensky 142 137.64+2.19 81.77+0.86 0.604+0.00 sure of group 2 (χ 2 = 0.000, p = 0.001) Megino-Kangalasky 195 117.79+1.44 73.59+0.81 0.627+0.00 (Table 5). In the study of SSBP, depending on Oymyakonsky 2018 (Tomtor Village) 185 144.52+2.02 90.19+1.02 0.632+0.01 the classifications of blood pressure, the Srednekolymsky 47 126.32+2.54 78.50+1.62 0.625+0.01 following results were obtained. Out of Ust-Aldansky 322 134.05+1.59 81.92+0.76 0.619+0.00 the total number of people studied, hypo- Ust-Maysky 142 132.26+1.97 85.34+1.25 0.648+0.00 tonia was detected in 75 people (3.84%) Vilyuysky 80 130.76+2.34 82.71+1.57 0.634+0.00 with an average BP of 94.06 / 61.75 mm Verkhnekolymsky 87 129.57+2.77 77.53+1.26 0.605+0.06 Hg, SSBP was disharmonious. 578 peo- Yakutsk 367 123.30+0.96 77.99+0.70 0.632+0.00 ple (29.57%) had optimal pressure, BP Aldansky 168 125.80+1.10 82.05+0.71 0.653+0.00 was 108.65 / 70.4 mm Hg, SSBP was Oymyakonsky 2008 (Ust-Nera village) 101 125.13+2.00 80.96+1.17 0.649+0.00 disharmonious. Normal blood pressure Overall 1959 129.94+0.54 81.10+0.29 0.629+0.00 was observed in 401 people (20.51%), blood pressure was 123.56 / 81.35 mm idents who did not have high blood pres- Maysky and Oymyakonsky (Ust-Nera, Hg, and SSBP was disharmonious. High sure, the 2 group included people diag- 2008) districts - p <0.05. Southern zone normal blood pressure was present in nosed with arterial hypertension. When - a significant difference was observed 262 people (13.40%), blood pressure comparing the average indices of SSBP between Lensky and Aldansky, p <0.001, was 131.97 / 90.59 mm Hg, SSBP was by districts in the 1st group with harmo- the Central zone - Magino-Kangalass- disbalanced. Moderate hypertension nious SSBP, residents of the Verkhne- ky district and Yakutsk, p <0.001. Also, was detected in 378 people (19.34%), kolymsky district amounted to mean the difference in SSBP indices between blood pressure was 145.61 / 90.47 mm 0.609 ± 0.05, and disharmonious SSBP the zones was significant: between the Hg, SSBP was disharmonious. Hyper- was found among residents of Yakutsk Northern and Eastern, Northern and tension of moderate severity occurred 0.631 ± 0.06. In group 2, harmonious Western (p <0.02), Western and South- in 169 people (8.44%), blood pressure SSBP (0.614 ± 0.07) was observed in ern, (p <0.001), Southern and Central ranged 165.70 / 94.87 mm Hg, SSBP the residents of Tomtor village, Oymya- zones (p <0.02) (Table 4). was disbalanced. 92 people (4.71%) ap- konsky District and Megino-Kangalasky Results of the comparative analysis peared to have severe hypertension, BP (0.609 ± 0.05) District. Residents of Len- of the groups 1 and 2 are presented in 192.33 / 103.04 mm Hg, SSBP was dis- sky District turned out to have a dishar- table 5. Indices of blood pressure of the balanced (Table 6). Unbalanced SSBP monious SSBP (0.566 ± 0.07). 1st group were within the limits of the (0.542) occurred in all classifications of When analyzing data by districts, har- permissible rate, harmonious SSBP was blood pressure, however, the highest monious SSBP was observed among the detected in 70 people, which amounted incidence was observed in people with population of Ust-Aldansky, Anabarsky to 3.57% (Table 5). In group 2, blood moderate (16.57%) and severe hyper- and Lensky districts, and when compar- pressure was higher than normal - tension (64.13%). Harmonious SSBP ing across SSBP zones, harmonious SBP144.36 ± 0.88 and DBP 89.15 ± 0.51, (0.615) is observed only in residents indices were found among residents however, it should be noted that dishar- with high normal pressure. SSBP was of the Arctic (Table 4). Within the zone monic SSBP was 0.619 ± 0.00, which disharmonious in all classifications of by districts, a significant difference was is very close to the golden proportion blood pressure and the largest numbers found in the Northern (Arctic) zone - be- (0.618). Thus it is possible to confirm the had residents with hypotension (50.67%) tween Anabarsky and Verkhnekolymsky statement of K. Nishi that the main indi- (Table 6). With an increased blood pres- districts - p <0.04 (according to Kolmog- cator of health is the ratio of upper (SBP) sure and BMI, a decrease in SSBP and orov). The eastern zone - between Ust– and lower (DBP) pressure, which is 7/11 remoteness from the golden proportion (0.618) was observed, and a strong in- Table 3 verse correlation was noted between them (r = -0.854, p <0.05) (Table 6). The indices of BP and SSBP in relation to age When the heart is working in the vessels, hydrodynamic pressure is created, with SSBP SBP, DBP, which is caused by the resistance of the Age N SSBP (0,615) P<0,05 mm Hg mm Hg vessel walls. For an adult, a convention- in % ally normal blood pressure is: the max- 20-29 247 112.07+3.83 73.29+2.35 0.635+0.00 3.23 - imum (systolic) -100 - 140 mm Hg. and 30-39 360 118.32+0.84 76.13+0.57 0.644+0.00 2.5 + the minimum (diastolic) - 70 - 90 mm Hg. 40-49 417 125.79+0.95 80.73+0.63 0.643+0.00 2.63 + Thus, the range of possible BP in hu- 50+59 574 135.88+0.98 84.83+0.54 0.629+0.00 2.09 + mans is 0–100–140 mm Hg. We divide 60-69 249 147.32+1.69 87.43+0.87 0.599+0.00 1.61 + this range in relation of 1.61:1, we get 70-79 75 153.28+3.03 86.40+1.31 0.572+0.00 2.66 + 100 / 1.618 = 61.8 mm Hg. 140 / 1.618 = 80-89 19 154.42+6.04 84.742.99 0.555+0.02 - + 86.5 mm Hg., which is very close to the 90 + y. o. 1 160 80 0.500 - - parameters of diastolic pressure. With 3’ 2019 43

hypertensive disease or with increased Table 4 physical exertion, blood pressure rises. The indices of SSBP by districts, divided by the socio-economic zones The maximum possible systolic pressure in humans can reach 230 mm Hg. The limiting value of blood pressure differs Socio-economic division of Group 1 Group 2 from normal systolic by 1.618 times: 140 Total amount districts by zones (without AH) (with AH) * 1.618 = 226.5 mm Hg. From this we can conclude that the ratio of blood pressure Northern (Arctic) with the golden proportion is obvious. Anabarsky 0.654±0.03 n=64 0.573±0.05 n=58 0.615±0.04 n=122 It is believed that the fluctuations of Verkhnekolymsky 0.609±0.05 n=60 0.598±0.08 n=27 0.606±0.06 n=87 the upper pressure are harmful to the Srednekolymsky 0.625±0.05 n=47 body. However, as it was written above, TOTAL 0.615±0.05 Professor Katsuzo Nishi (2006), lived in Eastern the early 20th century, the ratio between Ust-Maysky 0.655±0.04 n=72 0.641±0.07 n=71 0.648±0.06 n=143 upper and lower pressure and vice versa 0.614±0.07n Oymyakonsky 2018 0.674±0.05 n=55 0.632±0.07 n=186 considered to be especially dangerous =130 Oymyakonsky 2008 0.662±0.03 n=55 0.641±0.04 n=56 0.650±0.04 n=101 disruptions. He considered the "golden TOTAL 0.643±0.04 ratio" of blood pressure, which is 7/11 Western (or rather close to this value within (6/11 - 8/11)), as an indicator of health, which Vilyuysky 0.642±0.05 n=52 0.621±0.06 n=28 0.635±0.06 n=80 should be aligned with. With this ratio, TOTAL 0.635±0.06 practically any figures of upper and low- Southern er pressure are absolutely not danger- Lensky 0.642±0.04 n=71 0.566±0.07 n=71 0.604±0.07 n=142 ous for a person, even 274/174 mm Hg 0.657±0.03 Aldansky 0.644±0.05 n=48 0.653±0.04 n=165 (0.635). But if this "golden ratio" is vio- n=117 lated, for example, at the level of BP of TOTAL 0.628±0.05 Central 127/95 mm Hg (0.748), there is a signif- Megino-Kangalasky 0.637±0.03 n=30 0.609±0.05 n=65 0.628±0.04 n=195 icant health hazard. And, of course, the 0.646±0.03 0.588±0.06 greater the difference between the ratio Ust-Aldansky 0.619±0.06 n=322 n=170 n=152 of upper/lower pressure and the "golden 0.631±0.06 0.633±0.06 ratio" is, the higher the risk of develop- Yakutsk 0.632±0.06 n=367 n=251 n=116 ing cardiovascular diseases. It should be TOTAL 0.626±0.05n=1959 noted that this formula is applicable only to people over 20 years of age [9]. O.V. Tatarinova (2014) in a result of Table 5 a 7-year prospective observation of residents of Yakutia over 60 years old with The indices of BP and SSBP among the examined residents without AH and with AH a minimal risk of death, revealed that in both sexes, the SBP was 148.3 ± 24.2 SBR, DBR, and the DBP was 87.4 + 11.7, BMI - 26.7 Indices SSBR % mm HG mm HG. ± 5.1. Let's make the calculation from Stable disharmony the point of view of the Nishi’s golden (0.564-0.673) 116.24±0.53 74.14±0.03 0.638±0.00 37.37 proportion: 87.4 x11 = 961.4 / 148.3 = n=732 6.48, which is an indicator of health in the Lower disbalance (from “golden ratio”, SSBP turned out to be dis- 0.564 and lower) 118.57±1.85 63.45±0.81 0.537±0.00 4.9 harmonious - 0.589. Our obtained results n=96 upon the age gradient above 60 years old Higher disbalance correspond with the data of O.V. Tatarino- Group 2 (from 0.673 and higher) 116.81±1.05 82.79±0.35 0.709±0.00 11.84 va (Table 3) [14]. (without AH) (without n=232 M.A. Karpenko et al. (2010) re- Harmonious. close to GP searched the clinical value of quantita- 126.13±1.27 77.60±0.62 0.619±0.00 3.57 (0.618) n=70 tive analysis of ECG and BP using the “golden ratio” method and found that if Stable disharmony (0.549-0.687) 144.36±0.88 89.15±0.51 0.619±0.00 27.31 the ECG and blood pressure values devi- n=535 ate from the optimal values by more than 15%, the probability of having CHD in the Lower disbalance examined patients is 85% [6]. (from 0.549 and lower) 170.70±1.56 86.01±0.95 0.505±0.00 7.76 n=152 It is interesting how according to a large-scale HOT study (Hypertension Higher disbalance Group 2 (with AH) (with (from 0.687 and higher) 134.46±1.37 96.24±0.98 0.716±0.00 5.41 Optimal Treatment), which included the n=106 study of 18,790 patients with hypertension, the optimal blood pressure in terms Harmonious. close to GP 131.11±1.95 80.69±1.19 0.615±0.00 1.84 of the lowest risk of death due to cardio- n=36 vascular causes, is considered to be BP Total n=1959 100% = 138.8 / 86.5 mm Hg. The calculation of 44 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

точки артериального давления с позиции Table 6 пропорции «золотого сечения»: автореферат дис. ... кандидата медицинских наук. Нижегор. The indices of SSBP in relation to the qualification of BP гос. мед. акад. Нижний Новгород, 2003: 27. [Gurvich EV. The clinical value of the structured SBP, DBP, spot of the cardiac cycle and structured spot Classification SSBP SSBP (0,615) SSBP mm mm SSBP of blood pressure from the perspective of the of BP (0,542) harmonious (0,667) "Golden ratio» proportion: abstract of a Candi- Hg Hg date of Medical Science thesis. Nizhegor. gos. Hypotonia lower 94.06 61.75 0.657 (1.33%) (50.67%) med. academ. Nizhny Novgorod, 2003: 27. (In than 100/60 - ±2.30 ±1.70 ±0.01 n=1 n=38 Russ.).] n=75 5. Ефремова А.И. Уровни артериального Optimal BP давления и распространенность артериальной 108.65 70.40 0.649 (14.19%) (5.53%) гипертонии у пожилого населения г. Якут-ска 100-119/60-79 - ±1.37 ±1.91 ±0.02 n=82 n=32 с цереброваскулярными. Якутский медицин- n=578 ский журнал. 2010; 2(30): 26-28. [Efremova AI. The norm Blood pressure levels and prevalence of arterial 123.56 81.35 0.659 (1.74%) (53.87%) 120-129/80-84 - hypertension in the elderly population of Yakutsk 2±.39 ±2.43 ±0.02 n=7 n=216 n=401 with cerebrovascular. Yakutskiy medicinskiy zhurnal. 2010; 2(30: 26-28 (In Russ.).] High normal BP 131.97 90.59 0.688 (262%) (35.87%) (8.6%) 6. Карпенко М. А. Значение анализа электро- 130-139/85-89 кардиограммы с позиций синергетики в оценке ±1.21 ±16.73 ±0.13 n=5 n=94 n=22 n=262 степени поражения коронарных артерий у больных ИБС. Бюллетень Федерального Moderate Центра сердца, крови и эндокринологии им. hypertension (1st 145.61 90.47 0.622 (2.91%) (6.08%) В. А. Алмазова. 2010; 5: 39-43. [Karpenko MA. degree AH) - 1±.30 ±1.88 ±0.01 n=11 n=23 The value of electrocardiogram analysis from the 140-159/90-99 standpoint of synergetics in assessing the degree n=378 of coronary artery disease in patients with CHD. V. A. Almazov Bulletin of the Federal Center for Hypertension heart, blood and endocrinology. 2010; 5: 39-43. of intermediate (In Russ.).] severity (2nd 165.70 94.87 0.573 (1.18%) (16.57%) - 7. Кузнецова Т. Г., Иванов В. В. «Золотые» degree AH) ±1.59 ±3.07 ±0.02 n=2 n=28 пропорции в динамике сердечного ритма. 160-179/100-109 СПб.: Изд-во Политехн. ун-та, 2016:146 . n=169 [Kuznetsova TG, Ivanov VV. "Golden" proportions in the dynamics of the heart rate. SPb.: Publish- Severe ing house of Polytechnical Institute. 2016: 146. (In hypertension Russ.).] (3rd degree 192.33 103.04 0.537 (64.13%) (1.08%) (3.26%) 8. Марочков А. В., Точило С. А. Оценка hypertension) ±5.07 ±4.53 0±.02 n=54 n=1 N=3 артериального давления с использованием Higher than 180/ правила «золотого сечения». Новости хирур- Higher than 110 гии. 2008; 3 (16): 126-131. [Marochkov AV, Tochi- n=92 lo SA. 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(In Russ.).] lowest risk of developing cardiovascular 2015: 56-59. [Alexandrov SG. The use of the phe- 11. Корнильева И. В., Иванов К. И., nomenon of the "golden ratio" in the assessment complications was found at BP = 138.5 / Алексеева Е. Ю., Распространенность арте- of hemodynamic indices. Problemy sovremennoj риальной гипертонии в РС (Я). Артериальная 82.6 mm Hg. SSBP in this case is equal mediciny: aktual'nye voprosy. Irkutsk, 2015: 56- гипер-тензия. 2003; 5 (9):182-184. [Kornilyeva I. to 0.5942, which is also included in the 59 (In Russ.).] V., Ivanov K. I., Alekseeva E. U. The prevalence range of SSBP ± 1s [3]. 2. Всероссийское научное общество of arterial hypertension in the Republic of Sakha Thus, the existing norms of blood pres- кардио-логов (ВНОГ). Национальные рекомен- (Yakutia). Arterial hypertension. 2003; 5 (9):182- дации по профилактике, диагностике и лече- sure (according to WHO: 120/80 mm Hg) 184. (In Russ.).] нию артериальной гипертонии. Москва: 12. Рослый И. 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E.D. Okhlopkova, L.I. Konstantinova, L.D. Olesova, E.I. Semenova, A.I. Yakovleva, G.E. Mironova STUDY OF THE LACTATE LEVEL IN THE BLOOD SERUM OF ATHLETES TRAINING DOI 10.25789/YMJ.2019.67.13 IN THE CONDITIONS OF THE FAR NORTH

The article presents the results of studies of the lactate level, physical performance and lipid peroxidation in highly skilled athletes in the Far North. We examined 85 men of Yakut nationality, including 60 highly qualified athletes (candidates for masters of sports (kmc) and masters of sports (ms)), aged 17 to 21 years old, the first group consisted of free-style wrestlers -30 people, the second - boxers 30 people. The control group consisted of young students engaged in physical exercises at least twice a week. It was shown that the level of lactate de- pended on the level of physical performance of athletes and the accumulation of lipid peroxidation products. The highest values of lactic acid were noted at the recovery stage. Keywords: lactate, lipid peroxidation, physical performance, athletes, Far North.

Introduction. The level of lactate cant increase in lipid peroxidation (LPO), students, of the same age, engaged in (lactic acid) in the blood serum, and the which has a negative effect on muscle physical education at least twice a week. intensity of free-radical processes in the activity [5]. In conditions of high energy All examined according to the results of body are one of the criteria characterizing production in anaerobic mode, lactate is an in-depth medical examination were the fitness of athletes and show their tol- a carrier of energy from those places in practically healthy. erance to physical exertion [3, 4, 6]. With which it is impossible to transform en- The research material was heparin- intense physical exertion, active forms of ergy, due to increased acidity, to those ized blood and serum. Blood was taken - oxygen are formed leading to a signifi- places in which it can be transformed in the morning on an empty stomach from into energy (heart, respiratory muscles, the cubital vein. The study was approved slowly contracting muscle fibers, others by the decision of the local Ethics Com- Yakutsk, Republic Sakha (Yakutia), Russia: OKHLOPKOVA Elena Dmitrievna - Candi- muscle groups). Lactate plays a special mittee at the Yakutsk Research Center date of Biological Sciences, Leading Special- role in maintaining the body's ability to for Complex Medical Problems. ist, Yakut Science Centre of Complex Medical perform strenuous physical work. The intensity of lipid peroxidation was Problems, [email protected]. KON- It has been established, that with in- determined by spectrophotometric meth- STANTINOVA Lena Ivanovna – Researcher, tense physical exertion in the muscles od [8]. The level of lactate in the blood Yakut Science Centre of Complex Medical a large amount of lactic acid is formed, serum was determined during ongoing Problems, [email protected]. OLESOVA which inhibits their contractility and caus- examinations in a state of relative rest, Lyubov Dygynovna - Candidate of Biolog- es muscle fatigue [3, 5]. The importance on a semi-automatic analyzer "Screen ical Sciences, Leading Researcher, Yakut of individual metabolites of anaerobic gly- Master" (Italy). Science Centre of Complex Medical Prob- lems, [email protected]. SEMENOVA Evgenia colysis, lactate (lactic acid), is currently The overall physical performance of Ivanovna - Candidate of Biological Sciences, being widely studied. the PWC170 was determined using a Senior Researcher, Yakut Science Centre of Material and research methods. A Neurosoft bicycle ergometer (Ivanovo). Complex Medical Problems, kunsuntar@mail. survey of 85 men of Yakut nationality was The subjects performed two loads of ru. YAKOVLEVA Alexandra Ivanovna – Re- conducted, of which 60 athletes of high moderate intensity with a pedaling fre- searcher, Yakut Science Centre of Complex qualification (candidates for masters of quency of 60 rpm on a bicycle ergometer, Medical Problems, e-mail: [email protected]. sports (сms) and masters of sports (ms)), separated by a 3-minute rest interval. MIRONOVA Galina Egorovna - Doctor of Bio- aged 17 to 21 years old. The first group Each load lasted 5 minutes [2]. logical sciences, Professor, Biological department of the Institute of Natural Sciences, M.K. consisted of free-style wrestlers -30 peo- Statistical processing of the obtained Ammosov North eastern Federal University, ple, the second – boxers (30 people). data was carried out using the package [email protected]. The control group consisted of 25 young of applied statistical programs STATIS- 46 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

TICA 6.0. We used standard methods of are significantly accel- variation statistics: calculation of average erated. A comparative values, standard errors, 95% confidence analysis of the data we interval. Statistical data processing was cited among athletes of carried out by the non-parametric Kol- the martial arts group mogorov-Smirnov method. The probabil- showed that these ity of validity of the null hypothesis was processes are more taken at p <0.05. intense in wrestlers. Results and discussion. According Possibilities of anaero- to our data, the lactate content in both bic oxidation in athletes groups of martial arts athletes in the with medium and good blood serum is at the upper limit of the performance are higher norm and has no significant differences than in athletes with low (p> 0.05). The highest values of lactic performance and lower acid were noted at the recovery stage, in Fig. 1. Note: * p <0.01 compared with the control group than average groups, the first group of athletes higher in 1.47 as evidenced by higher and the second -1.40 times (p <0.01), the PWC170 value and the lactate level rates of lactate. Despite respectively, compared with the control (p <0.01). It is known that the concen- the higher level of lactic acid in the blood group (Fig. 1). tration of lactic acid (lactate) in venous serum, the body of these athletes is char- The increase in the level of lactate blood is an indicator of anaerobic perfor- acterized by greater resistance to work in both groups of athletes in the blood mance. in conditions of oxygen deficiency, which serum is due to the high rate of oxygen A low level of lactate was observed indicates the fitness of their body. utilization and developing hypoxia in the in martial arts athletes, with low working working muscles. Since the high muscle capacity, with an increase in the level of References demand for energy substrates in condi- training and working capacity of athletes, tions of oxygen deficiency is satisfied due the lactate content increased 1.1, 1.3 1. Артахинова С.Р., Захарова Я.Ю., Захаров to anaerobic oxidation of glucose. The and 1.4 times (Fig. 2). In wrestlers with А.А. Изменения концентрации лактата в крови accumulation of lactate stimulates pro- excellent physical performance after the в результате соревновательных схваток по мас-рестлингу. Ученые записки университета teolysis and supplies glycogenic amino maximum load was fulfill, the lactate con- им. П.Ф. Лесгафта. 2014;10 (116):19-21. [Ar- acids for the increasing energy needs of tent was 1.1 times higher than in in the takhinova SR., Zakharova YYu, Zakharov AA. athletes. Fights of fighters, and fights of athletes with average and good physical Changes in the blood lactate concentration as boxers are characterized by work of sub- performance, which is consistent with the a result of mas-wrestling competitive fights. maximal power. With submaximal power literature data [7]. A comparative analysis Uchenyye zapiski universiteta im. P.F. Lesgafta. 2014; 10 (116):19-21.(In Russ.)] in the body, although to a lesser extent, of the level of lipid peroxidation products 2. Белоцерковский З.Б. Эргометрические anaerobic processes in the release of en- at rest, before the test load showed that и кардиологические критерии физической ergy prevail over aerobic ones. As a re- athletes with low working capacity and работоспособности у спортсменов. М.: sult of intense glycolysis in the muscles, with working capacity lower than the av- Советский спорт, 2005:312 [Belotserkovsky ZB. Ergometric and cardiological criteria for phys- a large amount of lactic acid accumulates erage concentration of thiobarbiturate- ical performance in athletes. M.: Soviet Sport, in the blood. According to published data, active products (TBA - AP) (was 1.87 and 2005:312. (In Russ.)] the level of lactate in the skin extract after 1.96 times higher (p < 0.01), compared 3. Михайлов С.С. Биохимия двигательной exercise in untrained people rises 2 to 3 with athletes with good performance. деятельности. М.: Спорт, 2016:296. [Mikhailov times compared with the results before High aerobic performance among ath- SS. Biochemistry of motor activity. 6th edition. M.: Sport, 2016:296. (In Russ.)] exercise. For novice athletes, this indica- letes with good working capacity is ex- 4. Голец В.А., Евдокимов Е.И. Оценка tor increased by 1.5-2 times. The quanti- plained by the fact that aerobic perfor- информативности биохимических показателей tative content of lactate in the skin extract mance is most manifested under those в тренировочном процессе. Педагогика, психо- in professional athletes before and after loads where it is possible to fully satisfy логия и медико-биологические проблемы фи- зического воспитания и спорта. 2007; 6:74-76. physical activity remained unchanged the oxygen demand and where a steady [Golets VA, Evdokimov EI. Assessment of infor- [6]. It was also shown, that it saliva the level of oxygen consumption is main- mativeness of biochemical parameters in the lactate content increases by 2–3 times tained for a long time. training process. Pedagogika, psikhologiya i me- after prolonged training [6]. The results Anaerobic performance, in which it is diko-biologicheskiye problemy fizicheskogo vos- of the study revealed significant increas- not possible to provide the working mus- pitaniya i sporta. 2007; 6:74-76. (In Russ.)] 5. Корнякова В.В., Конвай В.Д., Муратов es in the concentration of lactate in the cles with an adequate amount of oxygen, В.А. Процессы свободнорадикального blood of athletes in response to competi- plays a decisive role in short-term high- окисления при утомлении, развившемся tive loads (at p≤0.01). In this case, the intensity exercises. вследствие интенсивных физических наг- maximum concentration of lactate after Conclusion. Thus, competitive fights for mas-wrestling was a higher concentra- recorded in the region of 10-12 mmol / l, tion of lactate in ath- which corresponds to the level of anaero- letes, compared with bic (An1) physical activity [1]. a group of people en- In the athletes physical performance gaged in physical ed- considered low at PWC170 870 ± 41 kgm, ucation at least twice lower than average –1160 ± 31, average a week, indicates - 1305 ± 22 and good - 1614 ± 82 kgm. that during physical Correlation analysis showed that exertion, anaerobic Fig. 2. Serum lactate level (mmol / L) in athletes with different there is a positive relationship between glycolytic processes physical performance PWC 3’ 2019 47

рузок. Успехи современного естествознан как показатель физической тренированности Современные проблемы физической куль- ия.2015;9(2):308-311.[Kornyakova VV. Konvay спортсменов. Теория практика физической туры, спорта и молодежи: материалы III рег- VD, Muratov VA. The processes of free radical культуры.2000;1:1-3. [Savvin GA, Ushakova EV, иональной научной конференции молодых oxidation during fatigue, developed as a result Perfiliev O.N. The lactate level in the skin extract ученых. Чурапча: ЧГИФКиС, 2017:363. [Sivtse- of intense physical exertion. Uspekhi sovremen- as an indicator of the physical fitness of athletes. va AA, Filippova YuV. Changes in blood lactate nogo yestestvoznaniya. 2015; 9(2):308-311. (In Teoriya i praktika fizicheskoy kul'tury. 2000; 1:1-3. levels in athletes involved in freestyle wrestling. Russ.)] URL:http://www.natural-sciences.ru/ru/ (In Russ.)] Modern problems of physical education, sports article/view?id=35583 7. Сивцева А.А., Филиппова Ю.В. and youth: proceedings of the III regional science 6. Саввин Г.А. Ушакова Е.В., Перфильев Изменение уровня лактата в крови у спорт- conference of young scientists. Churapcha: Ch- О.Н. Уровень лактата в кожном экстракте сменов, занимающихся вольной борьбой. GIFKiS, 2017:363. (In Russ.)]

S.K. Kononova, N.A. Barashkov, V.G. Pshennikova, O.G. Sidorova, T.K. Davydov, S.I. Sofronova, A.N Romanova., E.K Khusnutdinova., S.A. Fedorova DNA DIAGNOSTICS IN CLINICAL PRACTICE DOI 10.25789/YMJ.2019.67.14 APPLIED TO TRANSLATIONAL MEDICINE

The review presents examples of the translation of genomic studies into practical medicine of two common European hereditary diseases - autosomal recessive cystic fibrosis and autosomal dominant Huntington’s chorea. With the development of genetic technologies in the Republic Sakha (Yakutia), translational medicine is becoming a reality, and it is necessary to outline the approaches and problems in this field of research using the examples of type 1 spinocerebellar ataxia and type 1A autosomal recessive deafness which are frequent in the republic. Keywords: translational medicine, hereditary diseases, DNA diagnostics, patient.

Introduction. So-called translational oratories at research centers or universi- KONONOVA Sardana Kononova - senior studies are becoming increasingly more ties. The second phase is the translation researcher of the laboratory of molecular developed as of lately. Translational of the discoveries and achievements of genetics, Yakut Science Centre of Complex medicine is a modern multidisciplinary genomic research and the development Medical Problems, Yakutsk, Russian Feder- science that will have a leading role in of approaches to the application of the ation; [email protected]; BARASHKOV the development of genomic medicine. results of genetic research in practical Nikolay Alekseevich -head of the laboratory Translational medicine can be consid- medicine, the assessment of their effec- of molecular genetics, Yakut Science Cen- ered as a process involving the transfer tiveness and safety, as a rule, is done tre of Complex Medical Problems, Yakutsk, of discoveries made as a result of funda- with the help of clinical trials conducted Russian Federation; barashkov2004@mail. ru, PSHENNIKOVA Vera Gennadevna - re- mental research in biomedicine into med- in specialized medical centers associ- searcher of the laboratory of molecular genet- ical practice in order to improve diagnosis ated with research institutions [36]. The ics, Yakut Science Centre of Complex Medi- and treatment [11, 38]. third phase is the conclusive step for the cal Problems, Yakutsk, Russian Federation; The National Institutes of Health implementation of translational genom- [email protected], SIDOROVA Oksa- (USA) proposed the following definition ic research into the healthcare system, na Gavril’evna - researcher of the laboratory of translational medicine: “translational and, very importantly, this process also of hereditary pathology Yakut Science Centre research includes two areas of transla- includes the revision and development of Complex Medical Problems, Yakutsk, Rus- tion, the first of which is to bring the re- of legal and bioethical norms, taking the sian Federation; [email protected], DAVYDO- sults of discoveries made in laboratories application of genomic technologies in VA Tatyana Kimovna - PhDs in Medicine, head of the laboratory of neurodegenerative and preclinical studies to the stage of practice into account. The final stage es- diseases Yakut Science Centre of Complex clinical research and human studies; the tablishes adequate recommendations for Medical Problems, Yakutsk, Russian Federa- second area of translation is associated the optimal, safe and efficient use of new tion [email protected], SOFRON- with research aimed at increasing the medical technologies in order to improve OVA Sargylana Ivanovna, PhD, Chief Re- efficiency of introducing advanced tech- public health [12]. searcher of Yakut Science Centre of Complex nologies into wide medical practice”[22]. In this review, we aim to display ex- Medical Problems, Yakutsk, Russian Federa- In accordance with this definition, trans- amples of the translation of genomic tion, [email protected], ROMANOVA Anna lational studies are part of a unidirection- studies into practical medicine of two Nikolaevna, MD, the director of Yakut Sci- ence Centre of Complex Medical Problems, al continuum in which research results common European hereditary diseas- Yakutsk, Russian Federation, [email protected], move from the experimenter's laboratory es - autosomal recessive cystic fibrosis KHUSNUTDINOVA Elsa Kamilevna - doctor table to the patient’s bed and to society (CF) and autosomal dominant Hunting- of biological sciences, professor, academician as a whole [17]. ton’s chorea (HC). With the develop- of the Academy of Sciences of the Republic In turn, translational genomic research ment of genetic technologies in the Re- of Bashkortostan, Director of the Institute of can be included in translational medi- public of Sakha (Yakutia), translational biochemistry and genetics, Ufa Federal Re- cine. Translational genomic research is medicine is becoming a reality, and it search Center, Ufa, Russian Federation; elz- centered around the development of ev- is necessary to outline the approaches [email protected], FEDOROVA Sardana Ark- idence-based guidelines [32]. The whole and problems in this field of research adyevna - doctor of biological sciences, head of the laboratory of molecular biology, M.K. process includes at least three phases. using the examples of type 1 spinoc- Ammosov North-Eastern Federal University, The first phase is fundamental genomic erebellar ataxia (SCA1) and type 1A Yakutsk, Russian Federation; sardaanafedor- research carried out by qualified special- autosomal recessive deafness (DFN- [email protected]. ists in specialized molecular genetic lab- B1A) which are frequent in the republic. 48 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

Cystic fibrosis (CF). In European sTCA17, 557171TCA17, 55717TCA17, lies allows direct molecular diagnostics of populations, cystic fibrosis occurs with a 55717TCA17, 55717TCA17, 55717 -1G> the disease at any stage of ontogenesis, frequency of 1: 2500, while in Asian pop- A, 2184delA. Thus, using a specially de- including the pre-symptomatic period [7]. ulations it is equal to 1: 90,000. If a fre- signed panel that includes 28 mutations, At the same time, it is important to note quent monogenic disease acquires social it is possible to detect only about 82.5% that genetic counseling in families with significance, a need for a number of mea- of the mutant alleles in the total sample HC (as in the case of other diseases with sures to prevent the hereditary disease of examined CF patients. Almost 20% of late manifestation) is fraught with ethical from spreading appears. A spectrum of patients with CF need an additional ex- difficulties. Given the dominant type of in- more than 1900 different mutations of the amination to detect rarer mutations or heritance, the risk of obtaining a mutant CFTR gene has been described in 25394 polymorphisms, including the ones which gene for children and siblings of a patient patients from 23 European countries [40]. require the usage of the sequencing with HC is 50%. Naturally, the exclusion A permanent European Cystic Fibrosis method, which is not yet routinely used in of carriage, of course, should have a pos- Society Patient Register (ECFSPR) has the Russian Federation [14]. itive impact on the mental state of people been created that collects, quantifies and Huntington’s chorea (HC) is a pro- at risk. On the other hand, given the lack compares data on CF patients living in gressive autosomal dominant neuro- of effective methods of treatment for HC, Europe and neighboring countries who muscular disease characterized by the the identification of an allele in a patient agree to be included in the registry. This development of choreic hyperkinesis and with expansion is almost the same as is done in order to better understand CF, dementia. Symptoms of the disease are a death sentence. At present, it is cus- develop new European standards for caused by atrophy of the putamen and tomary to conduct a pre-symptomatic care and treatment, conduct research the caudate nucleus in the brain of pa- examination exclusively of adults from and treatment (https://www.ecfs.eu/proj- tients, associated with premature selec- the risk group when they directly seek ects) [45]. The CF gene is mapped on tive death of neurons. In most Russian advice. A serious argument in favor of a the long arm of chromosome 7 (7q31.1) populations, the prevalence of HC is 1 in pre-symptomatic examination of relatives in 1985. At the end of 1989, the CF gene 10,000. Significant differences are noted of patients is the possibility of preventing itself was identified. The protein product in relation to the age of onset and sever- the disease in high-risk families by con- of this gene was characterized, which ity of the disease. Moreover, even within ducting prenatal diagnosis. But if we are was called the “Cystic Fibrosis Trans- individual families, pronounced clinical talking about prenatal DNA testing as a membrane conductance Regulator” heterogeneity is observed. When HC is method of preventing hereditary diseas- (CFTR) and the most frequent mutation inherited on the paternal side, the effect es with late onset, which include HC, we was revealed — a deletion of phenylal- of anticipation is sometimes manifested cannot ignore the complex moral and eth- anine at the 508 position of the amino — an increase in the severity and a de- ical aspects that inevitably arise during acid sequence of the protein (delF508), crease in the age of onset of the disease prenatal medical and genetic counseling leading to the disease [28,29]. In addition in a number of generations [6]. [18, 43]. to deletions, many other mutations have The IT15 gene, in which dynamic mu- Therefore, as shown by the practice been detected in the CFTR gene. Unlike tations lead to the development of HC, of DNA diagnosis of HC in different coun- delF508, the vast majority of them are is expressed in many types of cells and tries, a very small number of burdened represented by sporadic cases, that is, encodes a protein with a molecular mass families agree to prenatal diagnosis. For they are quite rare. By the end of 2006, of 348 kDa, called huntingtin. In the IT15 example, in Portugal, over 5 years of re- more than 1,500 point mutations, several coding region, at a distance of 18 codons search, 158 families burdened with HC deletions and duplications were identified downstream from the start of the trans- conducted 338 genetic tests, of which in the CFTR gene. lation, a polymorphic trinucleotide repeat 234 were for diagnosis, 96 for pre-symp- The neonatal screening protocol for (CAG)n is localized. The number of CAG tomatic and only 4 for prenatal DNA test- CF in the Russian Federation includes repeats in the IT15 gene normally varies ing [34]. In Canada, 1061 pre-symptom- 4 stages: determination of immunore- from 9 to 37, while the mutant alleles of atic DNA tests of HC and 636 diagnostic active trypsin (IRT1), re-determination patients with HC carry 36 to 121 triplets. tests were performed over 14 years, of of immunoreactive trypsin (IRT), sweat An inverse correlation was found be- which 15 burdened families agreed to test and DNA diagnostics, and only the tween the length of the CAG repeat and prenatal testing [37]. In Greece, DNA first three stages are mandatory in the the age of onset of the disease and a di- testing of HC was performed in 461 peo- national protocol and are provided by rect correlation with the rate of progres- ple with clinical symptoms and 256 peo- the state. Therefore, DNA diagnostics in sion of clinical symptoms. The change in ple for pre-symptomatic diagnosis. Muta- many cases are limited. The availability the length of the repeat during transmis- tion (allele extension) was confirmed in of DNA diagnostics is limited by the high sion to the offspring explains the majority 278 individuals. Prenatal diagnosis was cost and the small number of laborato- of cases of anticipation [25]. carried out in 6 cases [27]. The authors ries capable of conducting this analysis Mutant alleles in the range of 36–40 note that the main reasons for rejecting [9,14]. DNA testing of CF is carried out triplets are characterized by incomplete prenatal diagnosis are the hope of de- using diagnostic panels, for example, penetrance. A significant number of pa- veloping treatment for HC and the re- in the “RCMG” a panel is used that in- tients with HC with a similar number of luctance to terminate the pregnancy for cludes the most frequent mutations in repetitions on the mutant allele have been psychological reasons [24]. the world: F508del, CFTRdele2.3 (21kb), described, and at the same time, clinical- Spinocerebellar ataxia of the 1st 3849 + 10kbC> T, W1282X, 2143delT, ly healthy individuals older than 70 can type belongs to the group of neurodegen- 2184insA, 1677delTA , N1303K, G542X, be found in the same pedigrees. Alleles erative diseases with late manifestation. R334W, E92K, L138ins, 394delTT, with a number of CAG repeats ≥ 40 are Inheritance is characterized by a high 3821delT, S1196X, 2789 + 5G> A, always associated with the development degree of penetrance, the phenomenon G85E, 2183AA> G, 604insA, 621 + of the disease. The study of the state of of anticipation. The mutation of the SCA1 1G> T, R117H, R347P, R553X, 3667in- CAG repeats by PCR in high-risk fami- gene located on the short arm of the 6th 3’ 2019 49

chromosome consists in an uncontrolled time, DNA testing and prenatal DNA di- According to V.G. Pshennikova (2017), increase in the number of trinucleotide agnostics work algorithms and bioethical the proportion of pathogenic variants of CAG repeats in the coding region of the rules for medical and genetic counseling the GJB2 gene was 51.10% of the num- gene. The clinical manifestations of the for patients from burdened families were ber of chromosomes studied in 393 un- disease are very diverse, the main ones developed [2,4]. related patients. Among them, the three are: a slow progressive loss of coordina- Hereditary deafness. Studies have most common (allelic frequency >1%) tion of movements and speech, the pres- shown that about 50-60% of congenital pathogenic variants were identified: c.- ence of the cerebellar-pyramidal syn- hearing loss are hereditary. The most 23+1G>A (42.3%), c.35delG (5.9%) and drome, various degrees of damage to the common of the hereditary forms is sen- c.109G>A (1,9%). When distributing un- cerebellum and its pathways [8]. sorineural hearing loss, which is caused related patients by ethnicity: among the In the 1970s Pierre-Marie cerebellar by mutations in the GJB2 gene encoding Yakut patients, the most frequent patho- ataxia was first differentiated from the the connexin 26 protein, currently there genic variant is c.-23+1G>A (51.8%), clinical forms of Vilyui encephalomyeli- are more than 150 of them [21]. This form the second most frequent is c.109G>A tis (VE), previously this disease was at- of hereditary hearing loss is detected in (2.4%), and the third is c.35delG (1.6%). tributed to one of the forms of chronic VE 1 out of 2,000 newborns, which is twice Among Russian patients, c.35delG [3]. A comprehensive study of hereditary as often as cystic fibrosis and five times (22.3%) and c.-23+1G>A (5.3%) were cerebellar ataxia (HCA) in Yakutia was as often as phenylketonuria. Usually the most frequently encountered [13]. Giv- launched in 1992 during the implemen- parents of a deaf child have normal hear- en the identified spectrum and frequen- tation of the scientific program “Biology of ing, because they are heterozygous car- cy features of pathogenic variants in the Vilyuisky Encephalomyelitis”. Molecular riers of the mutation [5]. GJB2 gene in patients with hereditary genetic studies of HCA were carried out Around the world, the spectrum of the hearing impairment in Yakutia, a rou- as part of the scientific project “Identifi- main pathological mutations that cause tine DNA diagnostic algorithm for auto- cation of genes and genetic mechanisms hearing impairment is wide and diverse. somal recessive deafness type 1A was that cause hereditary neurological dis- So, in various ethnic groups: Europe- developed. The algorithm is based on a eases”, developed by the Department of ans, Indians, Jews, Arabs, Bedouins, sequential search for the most common Neurogenetics of the National Institute Pakistanis, etc., the mutation c.35delG variants of the GJB2 gene (c.-23+1G>A, of Neurological Disorders and Stroke was found, among Ashkenazi Jews, the c.35delG and c.109G>A), followed by (NINDS / NIH) in the USA. In 1993, the mutation c.167delT is the most com- resequencing of the protein-non-cod- research work of Dr. H. Orr et al. for the mon, in Asian populations - the mutation ing (exon1) and protein-coding regions isolation of the Spinocerebellar ataxia c.235delC [26,35]. Among Yakuts, the (exon 2) of the GJB2 gene, as well as type 1 (SCA1) gene was accomplished population frequency of c35delG is ex- the search for an extended deletion of [23]. In 1994, the first work on the mo- tremely low (0.2%), which may indicate c.del (GJB6-D13S1830), which allows to lecular genetic study of HCA in the Yakut the non-specificity of this deletion for the detect up to 99% of pathogenic variants population was published. A. Lunkes et Yakut population or be single cases of responsible for ARD1A in Yakutia [15]. al. (1994) revealed an allelic association crossbreeding [1]. In the Yakut popula- DNA testing of hearing impaired/deaf of highly informative markers D6S274 tion, the main cause of congenital hear- people involves many organizational and and D6S89 flanking the SCA1 locus on ing loss is a mutation in the donor site ethical issues. When communicating with chromosome 6 with HCA disease. The of splicing of c.-23+1G>A gene GJB2 deaf people, it must be borne in mind that association was absolute in the case of (Cx26) and, according to the international they are members of a socially isolated D6S274 microsatellite, while for D6S89 OMIM catalog (Online Mendelian Inher- community of the “world of the deaf” with allelic substitution was recorded only in itance in Men), is classified as an allelic their own language, culture and habits two families, which gave rise to the as- variant of autosomal recessive deafness [39]. The number of assorted marriages sumption of historical recombination and type 1A (ARD1A) [44]. among the deaf is growing, sometimes date of the spread of the disease in the According to N.A. Barashkov (2011), spouses may express a desire to have a Yakut population [19]. In 1996, the results the prevalence of ARD1A is 16.2 per deaf child, despite the unfairness of such of a joint project by Yakut and American 100,000 of the Yakut population, and the a decision in relation to the child. researchers were published, in which frequency of heterozygous carriage of In any case, comparing themselves to hereditary cerebellar ataxia, common in the mutation c.-23+1G>A varies from 3.8 hearing people, most deaf people consid- Yakutia, was identified as Spinocerebel- to 11.7% among the indigenous popula- er themselves to be flawed and socially lar ataxia type 1 (SCA1). In these studies, tion of Yakutia (Evens, Evenks, Dolgans, deprived [42]. The use of DNA testing to the Siberian site of disease accumulation Yakuts). The results of the study of the detect mutations responsible for the de- is defined as the largest known in the GJB2 (Cx26) mutation gene splicing site velopment of deafness can pose a risk world, prone to further increase [41]. indicate the existence of the world's larg- of psychological stress and exacerbate The molecular genetic methods of est “endemic focus” of c.-23+1G>A accu- the sense of inferiority in the individual. DNA testing of SCA1 were introduced mulation in Eastern Siberia [20]. Therefore, it is necessary to create spe- in 1999 in the medical practice of the The high frequency of deafness mu- cial conditions for genetic counseling and medical and genetic consultation of the tations c.35delG (22.3%) in patients obtaining informed consent among the Republican Hospital No. 1 - the Nation- of Caucasian origin in the Republic of deaf [10]. al Center of Medicine of the Ministry of Sakha (Yakutia) suggests the possibility Conclusion. It is impossible to over- Health of the Republic of Sakha (Yaku- of direct DNA diagnostics, differential and estimate the importance of translational tia) and acquired the status of routine prenatal diagnosis, as well as screening medicine for solving practical problems clinical analyzes, despite the absence of of hereditary forms of deafness among of healthcare, because such an approach relevant instructions and orders for DNA wide groups of people, because approx- has already led to the transfer of the role diagnostics of hereditary diseases in clin- imately 50% of the inhabitants of Yakutia and place of a practical doctor to a differ- ical diagnostic laboratories. For the first are Caucasians [31]. ent plane, where they operate with fun- 50 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

damentally new technologies. Moreover, the prevalence of 35delG mutation of the GJB2 rologii i psihiatrii. 1996; 1:29-33 (In Russ.)]. the ever-increasing distance between gene in patients with sensorineural hearing loss 9. Кусова З. А., Каширская Н. Ю., Капра- in Yakutia. Nauka i obrazovanie. 2006; 42: 129- нов Н. И. Особенности массового скрининга practical health care and the accumulat- 33 (in Russ.).] новорожденных на муковисцидоз. Русский ing information in the field of fundamental 2. Кононова C. К., Сидорова О.Г., Сухо- медицинский журнал (Человек и лекарство. biomedicine dictates the need for direct мясова А.Л. и др. Биоэтические проблемы Часть 1). 2010;18(5): 265–270. [Kusova ZA, professional contact between clinicians пресимптоматической ДНК-диагностики спи- Kashirskaya NYu, Kapranov NI. Features of mass and research scientists. Moreover, this ноцеребеллярной атаксии 1-го типа в прак- screening of newborns for cystic fibrosis. 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HEALTHY LIFESTYLE. PREVENTION

L.D. Starostina COMPARATIVE ANALYSIS OF HEALTH-SAVING BEHAVIOUR OF STUDENTS OF COMPREHENSIVE DOI 10.25789/YMJ.2019.67.15 SCHOOLS AND UNIVERSITY IN YAKUTSK

This research compares the behaviour components defining the attitude of the person to his health at comprehensive schools and university in Yakutsk. So, distinctions in value-required, cognitive, emotional and behavioural components have been found. Individual peculiarities, consciousness and attitude to health-saving behaviour have been revealed. Health-saving set and readiness for actions in this area are insufficiently generated in both groups. We should rely on youth high aspirations to self-assertion and self-development when we work with them in the field of health-saving consciousness and behavior. Keywords: healthy lifestyle, health-saving behavior, teenage age, student's age, attitude to health, consciousness.

Introduction. Formation of health- of the person. Many scientists have been of students and factors, promoting its saving behaviour is an important part of studying the attitude to health, forma- realisation [1]. Youth health as object of education. The researchers mark close tion factors of health-saving behaviour social policy was considered by I.V.Zhu- interrelation between health, health-sav- at the teenager age. For instance, R.A. ravleva, N.V.Lakomova [3]. G.Y. Коzina ing behaviour and potential development Berezovskaya's researched the problem studied the youth attitude to healthy of the attitude to health and developed lifestyle factors [4, 6]. L.G.Rozenfild has the questionnaire for assessment of described major risk factors of health STAROSTINA Lyubov Dmitrievna, candidate health-saving behaviour [2]. Ya.V.Ush- disorders of students and Y.G.Mironova of psychological sciences, associate professor of psychology and social sciences department, akova devoted her works to self-saving – self-saving behaviour of student's youth Institute of psychology, North-Eastern federal behaviour, health control of the youth [7, 9]. Researches on the yielded subjects university named after M.K.Ammosov, Ya- and its formation factors [8, 12, 13]. were made also among teenagers [5, 11]. kutsk, Russia, +79241661252, e-mail:. lyudmi- N.N.Avdeeva, I.I.Ashmarina, G.B.Ste- Formation of health-saving behaviour [email protected] ORCID: 0000-0002-9609-9900 panova researched the human potential and responsibility for your health should 52 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

be an integral part of educational process Predominant values and attitude to health at schools and universities [14]. In modern life this period is frequently interfaced to Schoolchildren Students untimely food intake, non-regular sleep, Predominant requirements for system of values insufficient stay in the open air, low motor activity, absence of harden procedures, 1) health 1) Friends smoking, etc. Successful strategy reali- 2) independence 2) health 3) career 3) happy family sation of youth healthy lifestyle values at the university is frequently circumscribed Block «What I do for health preservation» by insufficient material base, absence of health-saving technologies adapted for Preventive procedures and diet Baths and saunas the region, methods of diagnostics, medical-rehabilitation actions, and also the irre- Block «What prevents me from healthy lifestyle» sponsible attitude of the majority of youth Financial possibilities, absence of to the health [10]. The objective situation Other causes (are not specified) assessment and search of key parts of conditions, shortage of time the impact, considering different stag- Actions at deterioration of health state es of formation of health-saving sets is I go to polyclinic I consult to my friends, relatives necessary to overcome these obstacles. I do not pay attention Considering all this, the aim of our research is a comparative analysis of value «Family well-being» among girls- nal of reception of the information about health-saving behaviour of students at students (in comparison with school- health for students are: doctors, further comprehensive schools and university girls), also confirms the assumption of on decreasing: television and the Inter- in Yakutsk, to define all possible ways of their sets for the future home life. Aver- net, friends and people, special literature, formation of healthy lifestyle sets. age values of "Career" among students periodic printed editions. Thus, if girls- Material and methods. Re- and schoolgirls are identical, however at students prefer opinion of real doctors, search was made among students of females-students, "Career" is only on the schoolgirls prefer Internet resources. North-Eastern federal university named fifth position, unlike schoolgirls where this Schoolboys besides doctors trust the lit- after M.K.Ammosov and pupils of com- value occupies one of leading places. Ac- erature, and students trust their friends’ prehensive schools of Yakutsk. The tualisation of the yielded value at school- advices. following methods were used to get girls can be probably explained by school According to students, the factors neg- psychological information: «Personal exams period, and with the plans to con- atively influencing on health are: wrong differential» (adapted version of scien- tinue education. lifestyle and nutrition, insufficient health tific research institute by V.I.Bekhterev); Value "Health" among schoolboys care, bad ecology and medicine. Thus R.L.Berezovskoy's questionnaire «Atti- is on the first place while at students it the most significant factor is "lifestyle", tude to health [2]. 124 respondents have concedes values "Friends". It is possible "food", “lack of health care”, “quality of taken part in our research, 64 students to assume that in student's years, young health services” and "ecology". School- at the age from 18 to 21 years old and men are more adhered to friends (fellow- boys showed the following - "lifestyle", 60 schoolchildren at the age of 14-15 students), they like to spend their free "ecology", “quality of medical services”, years old. Both groups were compara- time together. "food". Thus schoolgirls equally evolve ble by girls and boys share (р=0,687). Thus, predominant requirements in the importance for health of "lifestyle" The statistical analysis of the data has the system of values are: at schoolboys and "food", and schoolboys mark "ecol- been executed in package IBM SPSS – health, independence, career; at stu- ogy" and " lifestyle". STATISTICS 22. Mann-Whitney U-test dents – friends, health, happy family. Refusal of bad habits, overweight and Pearson’s test χ2 were used for Thus value «Recognition of people» at control, sleep regime, physical exercises groups comparison. Critical value of lev- students takes higher places in hierarchy were considered to be significant ways el of the statistical importance of distinc- of values, than at schoolboys (p <0,001) of health maintenance among girls-stu- tions (p) was taken equal to 5 %. that speaks about the importance of a so- dents. The rating differed a little at stu- Results and discussion. Let's con- cial recognition at student's age. dents-boys, and has been presented in sider the list of predominant require- Both schoolboys and students bind the following sequence: physical exercis- ments for values system among school- success in life first of all to diligence, abili- es, avoiding bad habits, sports, sleep re- children and students by scales “Attitude ties, necessary communications, thus the gime. According to schoolgirls, the most to health” R.A.Berezovskaya (Table). important factor defining working capac- important ways of health preservation are In the list of leading values, "Health" ity and persistence – "Health", does not bad habits refusal, physical exercises, takes the first position among girls that undertake them in attention. At females diet and healthy nutrition. Among boys — can be explained by future motherhood (students and schoolchildren) the interre- bad habits avoiding, regular physical ex- sets whereas among boys "Health" is lation of the personal qualities promoting ercises, sleep and wakefulness regime, on the fourth position after social values vital successes, has similar allocation, ex- various sports sections. The analysis (p <0,001). Comparing predominant re- cept for scales "Health" and "Prosperity". of the actions made by youth for health quirements for values system of it is pos- Here as well as in the previous compari- preservation has shown that students sible to notice that at school age girls do son, value "Health" at schoolgirls takes visit baths and saunas much more often, not reflect yet about health (but among lower places, than at students (p <0,001). than schoolboys (p <0,001), and school- females -students the yielded value is on The analysis of the role of various in- boys have preventive procedures more the first place that can be caused by their formation resources in the field of health often and keep to a diet (p <0,001) (table). reproductive behaviour). Prevalence of has shown that the most important ca- Students have specified the causes 3’ 2019 53

of insufficient healthcare: time lack, ab- of development, self-assessment level. 2018-62-4-8. [Zhuravleva IV. Youth Health as sence of necessity, unprofitable, ab- However it is possible to assert that for an object of social policy. Social aspects of public health. 2018; 4. URL: http://www.vestnik. sence of conditions, employment. Thus school and student's youth health is- mednet.ru/content/view/999/30/lang.ru. DOI: females-students, first of all, mark a lack sues are more "abstraction" rather than 10.21045/2071-5021-2018-62-4-8 (In Russ.).] of time and cost-based, then absence a necessary reality. Even if health is 4. Козина Г.Ю. Отношение студенческой of will power, absence of necessity and proclaimed as a part of students’ value молодежи к факторам здорового образа conditions. Accordingly, male-students: (especially among girls), nevertheless, is жизни. Вестник международной академии наук. 2011;2:141-142. [Kozina GYu. Attitude of absence of necessity and shortage of poorly presented in individual conscious- students to the factors of a healthy lifestyle. Bul- time, unprofitable, not to stint themselves ness. That is the concept "health" is not letin of the international Academy of Sciences. in everything. The causes of insufficient included into sphere of personal senses 2011; 2:141-142. (In Russ.).] health care s also are “absence of neces- of the individual at this age. The com- 5. Журавлева И.В. Здоровье студентов: sity” as they consider themselves healthy parative analysis has allowed revealing социологический анализ. Москва. 2014. [Jurav- leva IV. Health of students: a sociological analy- and do not wish to apply any efforts on existence of distinctions concerning stu- sis. Moscow. 2014. (In Russ.).] health conservation, referring to employ- dents and schoolchildren to health on the 6. Козина Г.Ю. Здоровье нации как ment and “absence of time”. following points: dominant requirements; основополагающий фактор экономического At deterioration of physical state of actions for health preservation; causes благополучия общества. Общество и здоровье: preventing healthy lifestyle; actions at современное состояние и тенденции развития. health students consult to their friends Москва. 2013;620–631. [Kozina GYu. Health of and relatives more often, self-medicate, health deterioration. the nation as a basic factor of economic well-be- try not to pay attention to illness, and only Students and schoolchildren can’t ad- ing of society. Society and health: current state in severe case they visit medical institu- here to the taken over line of behaviour and development trends. Moscow. 2013; 620- tion. Schoolboys more often, than stu- with healthy lifestyle, owing to insufficient 631. (In Russ.).] 7. Миронова Ю.Г. Особенности самосох- dents go to doctors, or also do not pay development of self-control and depen- ранительного поведения современной сту- attention to the state. dence on circumstances and assess- денческой молодежи. Теория и практика The information concerning features ments. However students understand a общественного развития. 2016;6. URL: http:// of individual peculiarities, conscious- role of strong-willed regulation for healthy teoria-practica.ru/vipusk-6-2016/. [Mironova YuG. ness and attitudes has been received lifestyle more. The student's period is Features of self-preservation behavior of modern students. Theory and practice of social develop- by method “Personal differential” (scien- marked by bigger social activity than at ment. 2016; 6. (In Russ.).] tific research institute by V.I. Bekhterev). school which is expressed in change of 8. Ушакова Я.В. Практика самосох- Results of diagnostics have shown that a social situation of development, social ранительного поведения студенческой моло- 68% of students have high values by self- status and environment. Level of aspi- дежи: социологический анализ. Нижний Нов- ration by self-esteem scale also raises город. 2010. [Ushakov YaV. The practice of esteem scale to themselves as a person- self-preservation behavior of students: sociolog- ality, average values at 28%, that is, stu- at student's age that speaks well for that ical analysis. Nizhny Novgorod. 2010. (In Russ.).] dents take over themselves as positive, the youth would like to be more awake 9. Розенфельд Л.Г. Здоровье студентов socially-desirable characters. 71% of and sociable «in ideal». All features set по данным субъективной оценки и факторы students and 60% of schoolboys showed forth above specify in the big readiness риска, влияющие на него. Здравоохранение Российской Федерации. – 2008;4:38-39. [Ros- mean level of strong-willed ability. Thus of students to acceptance of values and enfeld LG. Health of Students according to sub- 21% of schoolboys have low indexes observance of norms of healthy lifestyle, jective assessment and risk factors affecting it. on will power. Low values speak about in comparison with schoolchildren, but Health Care Of The Russian Federation. – 2008; insufficient self-control, inability to keep health-saving and readiness for actions 4:38-39. (In Russ.).] in this area are insufficiently generated in 10. Страхова И.Б. Здоровый образ жизни to the taken over line of behaviour, de- как способ интеграции в социум (на примере pendence on choronomic circumstances both groups. At work with youth in the field студентов с ослабленным здоровьем). and assessments. Students have realis- of formation consciousness and behaviour Новосибирск, 2005. [Strakhova IB. Healthy life- tic enough representations about a role it is necessary to lean against high claims style as a way of integration into society (on the of strong-willed regulation in healthy life- of youth to self-affirmation and require- example of students with poor health). Novosi- ment for self-development. We should birsk. 2005. (In Russ.).] style, than schoolboys. 11. Сурмач М.Ю. Качество жизни подростков We may assume that student's life rely on youth high aspirations to self-as- Республики Беларусь: связь со здоровьем. period has more social activity than at sertion and self-development when we Гродно. 2013. [Surmach MYu. Quality of the life school which is expressed in change of work with them in the field of health-sav- of teenagers of the Republic of Belarus: con- a social situation of development, social ing consciousness and behavior. nection with health. Grodno. 2013. (In Russ.).] 12. Ушакова Я.В. Человеческий капитал и status and environment. 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[Ushakova YV. Health of students and factors of its formation. Bulletin of Nizhny Novgorod can specify in occurrence of problems in 2. Березовская Р.А. Отношение к здоровью. Здоровая личность. 2013;214–244. University. 2007; 4:197-202. (In Russ.).] interaction with a social environment. [Berezovskaya RA. Attitude to Health. Healthy 14. Шувалова И.Н. Здоровьесохраняющее Conclusion. Thus, the analysis of personality. 2013; 214-244. (In Russ.).] образование как система организационных health-saving behaviour of schoolchil- 3. Журавлева И.В. Здоровье молодежи и психолого-педагогических установок. Гума- нитарные науки. 2018;1(41):46-51. [Shuvalova dren and students has shown the pres- как объект социальной политики. Социальные аспекты здоровья населения. 2018;4. IN. 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N.I. Latyshevskaya, V.F. Mikhalchenko, T.L. Yatsyshena, L.A. Davydenko, E.L. Shestopalova REGIONAL CHARACTERISTICS OF PERMANENT TEETH ERUPTION IN VOLGOGRAD SCHOOLCHILDREN

The physical development assessing, reflecting the formation of morphological and functional properties of the organism is the most important part of the children health studying. One of the criteria for a child’s biological development is tooth maturity. Dental maturity as a criterion of biological age is determined by the timing of the milk and permanent teeth eruption. At the same time, the overwhelming majority of hygienic work on the assessment of regional characteristics of children's physical development contains information on morphofunctional indicators: length and body weight, chest circumference, muscular strength of the hand, lung capacity, but very rarely provide information about "dental age". Analysis of the results of assessing the morphofunctional state of schoolchildren using the local standard is preferable for preventive medicine, including for developing priority health measures for this category of the population. The objective of the investigation was to identify the characteristics of the permanent teeth eruption in the Volgograd schoolchildren, to compare the obtained data with the dynamics of anthropometric indicators (height, body weight), taking into account gender differences; to analyze the differences in the indicator “permanent teeth eruption” in different regions of the country (according to literary sources). The number and timing of the permanent teeth eruption in Volgograd schoolchildren from 7 to 17 years old were estimated. The differences in number and timing of the permanent teeth eruption in comparison with similar indicators in regions with other climate, socio-economic, ethnic and ecological peculiarities were identified. The relationship between the timing of the permanent teeth eruption and dynamics of somatometric parameters was established. The necessity of the permanent teeth eruption standards development and the usage of this indicator in assessing the physical development of schoolchildren are justified. Conclusions: it is necessary to include standards for the permanent teeth eruption in regional standards for the physical development of children and adolescents. During preventive medical examinations of minors, it is necessary to indicate not only the sexual development formula of the child, but also the terms of the permanent teeth eruption. According to the teething indicators in different regions of the country, differing in climatic-geographical, socio-economic, ethnic and ecological characteristics, it is necessary to develop standards and further studying the characteristics of the eruption process for each region in Russia. Keywords: physical development, dental maturity, permanent teeth eruption, somatometric indicators, morphofunctional status.

Introduction. The physical develop- There are various methods and scientific signs of puberty and the connection of ment assessing, reflecting the formation approaches in assessing the physical the average degree - with the number of of morphological and functional proper- development of children and adoles- permanent teeth erupted, which charac- ties of the organism is the most import- cents [12]. terizes them as leading informational cri- ant part of the children health studying. The main method of studying the teria in school-age children [3, 9]. At the physical development of children and same time, the overwhelming majority of adolescents is a comprehensive as- hygienic work on the assessment of re- LATYSHEVSKAYA Natalya Ivanovna - Doc- sessment in hygienic practice, firstly gional characteristics of children's physi- tor of Medicine, full Professor, the Head of the approved by the Civil Code of the RF cal development contains information on department for Hygiene and Ecology FGBOU SEC in 1996. Modern techniques, rules morphofunctional indicators: length and "Volgograd State Medical University", Volgo- for examining and assessing the phys- body weight, chest circumference, mus- grad, 400131,Glazkova Avenue 1-16, Latysh- ical development of a child, as well as cular strength of the hand, lung capacity, nata@ mail.ru 89377023030, MIKHALCHEN- KO Valery Fedorovich - Doctor of Medicine, organized groups of children and ad- but very rarely provide information about full Professor, Professor of the Department for olescents of school age, is described "dental age" [1]. Generally, in assessing Therapeutic Dentistry FGBOU VO "Volgograd in the manual for medical workers "As- the indicators of a child’s biological de- State Medical University", Volgograd, 400048, sessment of the physical development of velopment (development of secondary Zhukova Avenue 127-42, vefmed@rambler. children and adolescents in educational sexual characteristics, number of perma- ru, 89023810014, YATSYSHENA Tatyana organizations" ed. by V.R.Kuchma [8]. nent teeth), the authors, as a rule, use Leonidovna - candidate of medical scienc- Comprehensive assessment supposes all-Russian data. es, associate professor of the department for assessing the morphofunctional status The main question is to develop and Hygiene and Ecology FGBOU VO "Volgograd State Medical University", Volgograd,400107, of the child (the balance development) use of regional standards for assessing Сhorosheva Avenue 48-1, tatyat@mail. and the level of biological development. the physical development of children and ru, 89178338541, DAVYDENKO Lyudmi- One of the criteria for a child’s biologi- adolescents. According to many authors, la Aleksandrovna – Doctor of Medicine, full cal development is tooth maturity. Dental the objective assessment of physical de- professor, Professor of the department for maturity as a criterion of biological age is velopment is possible in the presence of Hygiene and Ecology FGBOU VO "Volgo- determined by the timing of the milk and "standards" in a particular region, charac- grad State Medical University", Volgograd, permanent teeth eruption; biological age terized by a certain ethnic composition, 400131, Avenue of Heroes 5-6, Ladav52@ for school children can be determined by climate, geographical and socio-eco- mail.ru 89047704714, SHESTOPALOVA Ele- dental maturity before the age of 14 [1, nomic conditions [4, 5, 12]. The use of na Livovna - candidate of medical sciences, associate professor of the department for Hy- 10]. During assessing the studied indica- other regions standards is undesirable giene and Ecology FGBOU VO "Volgograd tors from the point of their informational due to differences in these indicators. State Medical University", Volgograd, 400131, significance as criteria of biological age, Standards of physical development of Avenue of Heroes 4- 54, shestopalova.77@ a statistically strong direct connection of children and adolescents require regular yandex.ru, 89377353535 the level of biological development with (at least 1 in 10-15 years) updates [4, 5]. 3’ 2019 55

Analysis of the results of assessing the teeth eruption is 9 years and includes 11 years in Volgograd boys and girls, i.e. morphofunctional state of schoolchildren two phases of active eruption (from 7 to a year later in comparison with growth using the local standard is preferable for 8 years and from 10 to 13 years) and two jumps (Fig. 1) and falls on the age period preventive medicine, including for devel- periods of relative rest: the first is after between two growth jumps. The inverse oping priority health measures for this the first molars and incisors eruption (8 relationship was determined in compari- category of the population [2]. years old in girls and 8–9 years old in son the “dental age” with the weight gain Objective of the study: to identify the boys), the second is after the all perma- indicators in Volgograd schoolchildren characteristics of the permanent teeth nent teeth eruption (except the third mo- (Fig. 2). Thus, the greatest increase in eruption in the Volgograd schoolchildren, lars). In girls, it began at age 13, in boys the “body mass” indicator is 12 years for to compare the obtained data with the at age 14 [3]. boys and 13 years for girls, which is 1-2 dynamics of anthropometric indicators It was determined that the first phase years later than the “jump” for the perma- (height, body weight), taking into account of the examined schoolchildren of both nent teeth eruption (Fig. 2). gender differences; to analyze the differ- sex groups was at the age of 7 years, According to the results of the Lin- ences in the indicator “permanent teeth and the most significant increase in the ear pairwise correlation analysis (the eruption” in different regions of the coun- number of permanent teeth (intensive pe- Pearson correlation coefficient was try (according to literary sources). riod of teething or the second phase) was determined using MS Excel), a close Material and methods. The dentists of at the age of 11 years in Volgograd boys positive relationship was indicated be- the children's dental treatment-and-pro- and girls. And it is 2 years ahead of the tween the timing and intensity of the phylactic institutions of Volgograd carried average terms in Russia [10, 11]. permanent teeth eruption and changes out the study and the "dental age" as- To our minds, the important thing is the in height and body weight. Correlation sessing, including the number and timing question of the relationship between the coefficients, respectively, were 0,95 and of the permanent teeth eruption in Vol- results of the “teething” indicator and the 0,92 for boys, and 0,97 and 0,95 for gograd schoolchildren during 2015-2017 dynamics of the somatometric parame- girls. This confirms the fact of a close (еру patient examination was carried out ters of the physical development of chil- biological connection in children of this in such health care facilities as: APH- dren and adolescents in the Volgograd age group (7–17 years old) between CI “Children's dental clinic №2”, APHCI oblast. We conducted a comparative mass and growth changes and chang- “Dental clinic №11”, APHCI “Dental clinic analysis of the intensity and timing of the es in the dental system. At the same №12”, APHCI “Volzhski city dental clin- permanent teeth eruption in Volgograd time, children with low and below aver- ic”). In total about 2,000 schoolchildren schoolchildren with dynamic characteris- age somatometric parameters are more were examined, including 965 girls and tics of height and body weight. likely to have late teething, which coin- 999 boys aged from 7 to 17 years. During It was indicated that the first growth cides with the data of Zolotareva L.А. [6]. the same period, about 3,000 schoolchil- jump in boys took place at 10 years The comparative analysis of the peri- dren from 7 to 17 years old were exam- (+7.0 cm). The age of pubertal growth od of "rest" among adolescents living in ined (1,388 boys and 1,602 girls) in order jump was at 13-14 years (+7.0). The different regions of the country is worth to study the morphofunctional state of assessment of the corresponding indi- studying. The data of V.A. Petrov [7] (Pri- children and adolescents living in Volgo- cator in girls showed that grad. Somatometric indicators were stud- the first growth jump was ied: height and body weight. The mea- also at 10 years (+7.9 surements were carried out according to cm), the second - at 12 generally accepted methods in the first years (+8.5 cm). Analy- Boy’s height … half of the day. Standing body height was sis of the indicator “body Girl’s height - - measured by using an wooden height weight” revealed the fact Boy’s teeth - . - Girl’s teeth — meter with an accuracy of 0.5 cm. Body of a sharp increase in the weight was measured with the help of indicator “body weight” in lever medical scales such as Fairbanks boys from the age of 12 with an accuracy of 50 g. The calculation and older: the difference of the main statistics - the mean value, between 11-year-old and the standard deviation, as well as the 12-year-old boys is almost construction of regression dependencies 8 kg. Girls have a sharp Fig. 1. Dynamic characteristics of indicators of body height and of height and weight; analysis of the num- increase in body weight "dental age" in children of Volgograd ber and timing of the permanent teeth from the age of 13. eruption in boys and girls within the age A comparative anal- group from 7 to 17 years was carried out ysis of the dynamics of using the statistical package Statistica V changes in mass-growth 6. Linear pairwise correlation analysis of parameters and their com- somatometric signs and the number and parison with the perma- Boy’s weight … timing of the permanent teeth eruption in nent teeth eruption data Girl’s weight - - boys and girls conducted using MS Excel in schoolchildren showed Boy’s teeth - . - Girl’s teeth — 2007. that these processes are Results and discussion. Analysis of multidirectional. It WAS the permanent teeth eruption in Volgo- revealed that the second grad children and adolescents of school stage of the most signifi- age showed that this stage covers the cant increase in the num- period from 6-7 to 15 years. According to ber of permanent teeth Fig. 2 Dynamic characteristics of indicators of body mass and some authors, the period of permanent corresponds to the age of "dental age" in children of Volgograd. 56 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

morsky Krai) and S.Yu. Kasyugi et al. [7] of the eruption process for each region 5. Година Е.З. Секулярный тренд и регио- (Nizhny Novgorod ) indicate the onset of in Russia. нальные особенности его протекания: зачем нужны локальные стандарты. Актуальные the second period of “rest” in girls from проблемы здоровья детей и подростков и пути the age of 13, in boys - from the age of 14. References их решения: материалы 3-го Всероссийского According to our data, the second “rest конгресса с межд. участием по школьной и университетской медицине. М. 2012; 42. [Go- period” in Volgograd boys and girls be- 1. Харитонов В.М., Ожигова А.П., Година dina E.Z. Secular trend and regional features of gins at the age of 12 (the least statistical- Е.З. Антропология: учеб. для студ. высш. учеб. its course: why do we need local standards. Ac- заведений / М.: Гуманит. изд. центр ВЛАДОС. ly significant increase). It was also found tual problems of the health of children and ado- 2004; 272. [Haritonov VM, Ozhigova AP, Godina that in the Volgograd oblast, the period of lescents and ways to solve them: materials of the EZ. Anthropology: textbook for higher institutions 3rd All-Russian Congress with int. participation in the most intense dentition occurs in boys stud. M.: Gumanit. izd. centr VLADOS. 2004; 272. school and university medicine. M., 2012: 42. ( and girls at 11 years old (in Primorsky ( In Russ.).] In Russ.).] 2. Богомолова Е.С. Гигиеническое обосно- Krai, it begins at 10 years in both boys 6. Золотарева Л.А. Влияние регионально- вание мониторинга роста и развития школь- and girls, in the Nizhny Novgorod oblast: этнических факторов на сроки прорезывания ников в системе «здоровье-среда обитания »: in boys at 11 12 years old, in girls 10-11 постоянных зубов у детей Удмуртии: дис. … автореф. дис. … докт.мед.наук, Нижний Новго- канд.мед.наук. Москва. 2004; 126. [Zolotare- years old). It is possible that the revealed род.2010; 23. [Bogomolova ES. Hygienic justifi- va LA. The influence of regional and ethnic fac- differences are due to climate, nutritional, cation for monitoring the growth and development tors on the timing of teething of permanent teeth of schoolchildren in the "health-environment": ethnic, and ecological peculiarities of liv- in children of Udmurtia: dis. … kand.med.nauk. avtoref. dis. … dokt.med.nauk. Nizhnij Novgorod. ing, which requires further scientific study Moskva, 2004; 126. ( In Russ.). ] 2010; 23. ( In Russ.).] 7. Косюга С.Ю., Богомолова Е.С., Киселе- and confirmation [6]. 3. Волкова С.И., Гретченко Я.В. Особенно- ва О.С. и др. Стоматологические критерии оценки биологического возраста детей и под- Comparative data on the number of permanent teeth in different regions (M±δ) ростков. Стоматология. 2013; 92(6): 56-58. [Kosyuga SYu, Bogomolova ES, Kiseleva OS. Nizhny Novgorod Primorsky Krai Volgograd oblast Dental criteria for assessing the biological age of Age children and adolescents. Stomatologiya. 2013; boys girls boys girls boys girls 92(6): 56-58. ( In Russ.).] 6 - - - - 2.62±2.19 3.06±2.29 8. Кучма В.Р., Скоблина Н.А., Бокарева и др. Оценка физического развития детей и 7 7.7±2.6 8.5±2.6 7±3 9±3 7.53±2.94 8.21±3.22 подростков в образовательных организаци- ях. М. Научный центр здоровья детей РАМН, 8 10.6±1.8 11.4±2.4 12±2 12±3 11.12±2.09 11.48±1.98 2014; 38. [Kuchma VR, Skoblina NA, Bokareva 9 12.9±2.6 13.8±3.1 14±2 15±3 13.24±2.54 13.07±2.22 NA i dr. Assessment of the physical development of children and adolescents in educational institu- 10 14.6±3.9 16.8±4.4 18±3 19±3 15.49±3.19 16.47±4.39 tions. V.R. Kuchma, - M.: Izd-vo. Nauchnyj centr 11 18.8±5.2 20.0±4.7 20±4 21±3 22.15±4.29 22.48±4.08 zdorov'ya detej RAMN. 2014; 38. ( In Russ.).] 9. Петров В.А. Методы определения и 12 23.5±4.1 24.5±3.8 24±3 25±2 25.29±3.11 25.97±2.36 оценки состояния здоровья и физического 13 25.6±3.2 26.7±2.0 27±1 28 26.90±1.65 26.78±1.64 развития детей и подростков: учебное посо- бие. Владивосток. Медицина ДВ. 2014; 168. 14 27.3±1.4 27.5±1.2 28 28 27.29±1.69 27.35±1.25 [Petrov VA. Methods for determining and assess- 15 27.6±0.8 27.7±0.9 28 28 27.62±1.15 27.83±0.63 ing the state of health and physical development of children and adolescents: a training manual. 16 - ± 28 28 27.84±0.72 28±0.00 Vladivostok. Medicina DV. 2014; 168. ( In Russ.).] 10. Пивоваров Ю.П., Королик В.В. Руковод- 17 - ± 28 28 27.82±1.16 27.97±0.30 ство к лабораторным занятиям по гигиене и ос- новам экологии человека. М. Академия. 2006; 512. [Pivovarov YuP, Korolik VV. Guide to labora- сти формирования зубной системы у детей и tory classes on hygiene and the basics of human Conclusions: подростков г. Сергача Нижегородской области ecology. M. Akademiya. 2006; 512. ( In Russ.).] 1. It is necessary to include standards как один из показателей их биологического со- 11. Полосухина Е.И. Индивидуально-типо- for the permanent teeth eruption in re- зревания. Молодой ученый. 2016; 3: 359-361. логическая изменчивость прорезывания по- gional standards for the physical devel- [Volkova SI. Gretchenko YaV. Features of the for- стоянных зубов в связи с цефало и соматоти- mation of the dental system in children and ado- opment of children and adolescents. пами: клинико-анатомическое исследование: lescents of the city of Sergach, Nizhny Novgorod автореф. дис. … канд.мед.наук. Волгоград. During preventive medical examinations region as one of the indicators of their biological 2007; 22. [Polosuhina EI. Individual-typological of minors, it is necessary to indicate not maturation. Molodoj uchenyj. 2016; 3: 359-361( variability of teething of permanent teeth in con- only the sexual development formula of In Russ.).] nection with cephalo and somatotypes: clinical the child, but also the terms of the perma- 4. Гаврюшин М.Ю., Березин И.И., Сазоно- anatomical study: author. dis. ... Candidate of ва О.В. Антропометрические особенности фи- nent teeth eruption. Medical Science. Volgograd. 2007; 22 .] зического развития школьников современного 12. Баранов А.А., Кучма В.Р., Скоблина Н.А. 2. According to the teething indicators мегаполиса. Казанский медицинский журнал. Физическое развитие детей и подростков на in different regions of the country, differ- 2016; 4: 629-633. DOI 10.17750/ КMol 2015- рубеже тысячелетий. М. Научный центр здо- ing in climatic-geographical, socio-eco- 629. [Gavryushin MYu, Berezin II, Sazonova OV. ровья детей РАМН. 2008; 216. [Baranov AA, Anthropometric features of the physical develop- nomic, ethnic and ecological characteris- Kuchma VR, Skoblina NA. The physical devel- ment of schoolchildren in a modern metropolis. opment of children and adolescents at the turn tics, it is necessary to develop standards Kazanskij medicinskij zhurnal. 2016; 4: 629-633. of the millennium. M. Nauchnyj centr zdorov'ya and further studying the characteristics ( In Russ.). ] detej RAMN. 2008; 216. (In Russ.).] 3’ 2019 57

O.N. IVANOVA DOI 10.25789/YMJ.2019.67.17 RECURRENT STOMATITIS IN CHILDREN

This article is devoted to the actual problem of recurrent aphthous stomatitis in children. The authors studied the features of the course of recurrent aphthous stomatitis in children and the effectiveness of the use of Imudon in the treatment of this disease. We surveyed 100 children with recurrent aphthous stomatitis, within a year at the age of 7 to 12 years on the basis of the Consultative Clinic RH №1- National center of medicine (Yakutsk). All children were examined by a pediatrician and profile specialists: an endocrinologist, a hematologist, an otolaryngologist, and a dentist. General blood and urine tests, biochemical studies (CRP, ASLO), blood sugar levels, a study of the level of immunocompetent cells in peripheral blood and the level of immunoglobulins A, M, G were examined in all children. Then a group of 50 children with recurrent stomatitis was identified, all of them except of local therapy (cauterization of ulcers by the stomatofit) received treatment with Imudon (the group under study). A group of children (50 people) received only local treatment (the control group). All children showed a decrease in immunity, changes in the general blood test. In the treatment of recurrent stomatitis, in addition to local treatment, treatment with Imudon is recommended, which leads to a reduction in clinical symptoms, normalization of immune status indicators and a general blood test. Keywords: stomatitis, aphthae, children, immunity, ulcers, therapy, Imudon. Stomatitis is a disease of the oral mucosa. Pathogens are more often streptococci. Stomatitis is most often caused by a failure of the immune system or a number of diseases of various organs (diabetes mellitus, kidney disease, blood deficiency disease, vitamin deficiency).

In children, aphthous form of stomati- of immunocompetent cells in peripheral that 15 (15%) people had iron deficiency tis is more common. Aphthae appear as blood and the level of immunoglobulins A, anemia, 70 (70%) children had chronic small white or yellowish plaques of var- M, G were examined in all children. Then tonsillitis, 50 (50%) children had caries. ious sizes, surrounded by a red rim, on a group of 50 children with recurrent sto- Then we decided to study the main the mucous membrane of the cheeks, matitis was identified, all of them except symptoms in children with recurrent sto- gums, lips or tongue. Characterize by a of local therapy (cauterization of ulcers matitis: 90 children (90%) had a burning sharp pain when eating and symptoms by the stomatofit) received treatment with sensation and soreness of the oral muco- of intoxication. Their outcome is often Imudon (the group under study). A group sa when eating, 65 children (65%) had a favorable, after 6-8 days the process of children (50 people) received only lo- weight loss of 1 to 3 kg during the year, 30 subsides, aphthae heal, erosion epithe- cal treatment (the control group). % growth retardation, 60 (60%) decrease lialized. Sometimes stomatitis becomes All the data obtained were subjected in appetite, 90% weakness, fatigue. chronic and tends to recur. to thorough statistical processing: the All patients with recurrent stomatitis As a result of treatment with antiseptic numerical data were calculated as the had a general blood count. agents of the oral cavity, aphthae heal, arithmetic mean and standard error of According to the results of a general but new ones appear. The process can the mean M ± m; differences were con- blood test in patients with stomatitis, the last for years, affecting the patient's qual- sidered significant at p <0.05. Compari- level of erythrocytes, platelets, hemoglo- ity of life; children try to eat liquid food in sons of mean values were performed by bin and erythrocytes is reduced (Figure 1). order not to injure the oral mucosa. In single-factor analysis of variance using All patients with recurrent stomatitis the process of the disease, children lose Student's t-test to assess the equality were examined for their immune status. weight, are stunted in growth and psy- of the averages of the Fisher's F-test to The following results were obtained: a chomotor development [1,2]. assess the equality of the variance. The decrease in the content of CD4 + lym- Objective: To study the peculiarities of relationship between the parameters was phocytes, that is, activated T-cells, a the course of recurrent aphthous stomatitis estimated using linear and rank correla- decrease in the number of natural killer in children and the effectiveness of the use tion coefficients. cells (CD16 +), T-helper cells (CD4 +), of Imudon in the treatment of this disease. Results. A survey of 100 children with cytotoxic T-lymphocytes (CD8 +), and an Materials and methods. We sur- recurrent stomatitis by specialists revealed increase in IgM (Table 1). veyed 100 children with recurrent aphthous stomatitis for a year, aged from 7 to Table 1 12 years based on the Consultative Clinic RH №1- National center of medicine. All Indicators of the immune status in children of RS (Ya) in children with recurrent stomatitis and healthy children, M±m children were examined by a pediatrician and profile specialists: an endocrinolo- Children with recurrent gist, a hematologist, an otolaryngologist, Indicator stomatitis (n = 100) Health children(n = 2000) and a dentist. General blood and urine СD3+ 18.1 ± 1.03* 27.2±1.04 tests, biochemical studies (CRP, ASLO), СD4+ 16.2 ± 0.5* 28.3±0.6 blood sugar levels, a study of the level СD8+ 15.9 ± 0.8* 24.1±2.5 СD16+ 10.1 ± 1.2* 22.0±1.01 IVANOVA Olga Nikolaevna, MD, Professor, IRI 0.7 ± 0.6 1.08±0.02 Department of Pediatrics and Pediatric IgA 1.1 ± 0.1* 2.9±0.6 Surgery, Medical Institute of the Federal State IgG 18.2 ± 0.7 17.1±0.09 Autonomous Educational Institution of Higher IgM 1.0 ± 0.08* 2.2±0.09 Educational Institution "Northeast Federal University named after MK Ammosov". Mailing СD25+ 13.9 ± 1.2* 24.6±0.7 address: 677018, Yakutsk, ul. Krupskaya 37, CIK 186.2 ± 1.5<0.05* 70±0.07 apt. 107; to / tel. 8 (4112) 39-56-09; e-mail: [email protected]. Note. In the Tables 1-2 *p < 0.05 between standards and indicators in each group 58 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

tus in children of the control group who Table 2 received only topical antiseptic treatment Indicators of the immune status in children with recurrent stomatitis of the examined of stomatitis. and control groups after therapy, M±m Thus, there is a positive dynamics of indicators of immune status, clinical man- Children of the examined group Children of the control group ifestations of recurrent stomatitis of chil- Indicator after therapy (n = 50) (n = 50) dren of the examined group as a result of СD3+ 27.1 ± 1.1 22.1 ± 1.03 the treatment. СD4+ 21.6 ± 0.9 18.9 ± 0.5 Conclusion. In the treatment of recur- СD8+ 18.2 ± 0.2 16.9 ± 0.8 rent stomatitis, in addition to local anti- СD16+ 20.3 ± 1.0 13.1 ± 1.2* septic treatment, treatment with Imudon IRI 1.9 ± 0.1 0.7 ± 0.6 is recommended, which leads to a reduc- IgA 2.6 ± 0.1 1.8 ± 0.1* tion in clinical symptoms, normalization IgG 18.9 ± 0.2 18.2 ± 0.7 of immune status indicators and a gen- IgM 2.4 ± 0.2 1.2 ± 0.08* eral blood test. СD25+ 20.1 ± 1.2 13.9 ± 1.2 CIK 172.1 ± 1.0 186.2 ± 1.5<0.05

examined group in children during the month, the symptoms of the children in the control group remained the same. Thus, as a result of the treatment carried out in the examined group of children (local antiseptic treatment Fig. 2. Dynamics of changes in the general blood count Fig. 1. General blood count in patients with recurrent and imudon), there was in children with recurrent stomatitis of the examined and stomatitis compared with normal values a positive dynamics of control groups after the treatment clinical manifestations Standards of immune status indica- in comparison with children of the References tors were developed by the team of the control group who received only local an- 1. Крючко Т.О., Бабанина С.М., Карпенко Immunology Laboratory of the Medical tiseptic treatment. О.О. и [и др]. Пути оптимизации эффектив- Institute in 2018 based on a survey of In the examined group of children, ности лечения пациентов с рецидивирующим герпетическим стоматитом. Современная пе- 2,000 healthy children aged 5 to 10 years there was a positive trend in the indica- диатрия. 2012; 1 (41):150-154. [Kryuchko TO, (Table 1). tors of the general blood test (Figure 2). Babanina SM, Karpenko OO, Babanina MY, Pili- Treatment of recurrent stomatitis was All children were examined for im- penko OA. Ways to optimize the effectiveness carried out jointly with the dentist. With- mune status in the control and survey of treatment of patients with recurrent herpetic in 1 month, 50 children of the examined groups. It was revealed that the immune stomatitis. Sovremennaya pediatriya. 2012; 1 (41):150-154. (In Rus.)] group with recurrent stomatitis received indices improved in the group of children 2. Спиридонова С.А., Толмачева С.М., Лу- the drug Imudon 1 tablet 3 times a day. with recurrent stomatitis after therapy (lo- киных Л.М. Комплексная терапия хроническо- Patients from the control group of 50 chil- cal treatment and imudon): an increase in го рецидивирующего стоматита. Современные dren received only antiseptic treatment cellular and humoral immunity: the level технологии в медицине. 2013; 1 (5): 118-121. [Spiridonova SA, Tolmacheva SM, Lukinykh LM. with stomatofit, cauterization of aphthae. of normal killer CD16 + and the level of Combined therapy of chronic recurrent stomatitis. During the therapy and after the treat- IgA, IgM (Table 2). These changes are Sovremennye tekhnologii v medicine. 2013; 1 (5): ment, the aphthasis did not appear in the significantly higher than the immune sta- 118-121. 3’ 2019 59

HYGIENE, SANITATION, EPIDEMIOLOGY AND MEDICAL ECOLOGY

N.G. Pavlov, G.I. Alekseeva, M.K. Vinokurova, E.I. Ermolaeva, M.V. Chernykh COMPREHENSIVE INDICATIVE ANALYSIS OF THE PERFORMANCE AND QUALITY OF ACID-FAST BACTERIA DETECTION BY PRIMARY CARE FACILITIES IN THE SAKHA DOI 10.25789/YMJ.2019.67.18 REPUBLIC (YAKUTIA)

The study takes a look at the work of clinical laboratory service performing microscopic diagnosis of tuberculosis in the Sakha Republic (Yaku- tia). We analyzed results of Ziehl-Neelsen microscopic detection of tuberculosis (TB) in clinical diagnostic laboratories of primary care facilities in 2005, and over the period from 2012 to 2016. Analysis was based on national-level and industry sectoral reports, and annual reports of laboratories performing microscopic diagnosis of TB. Data from the following statistical forms were studied: Form 30, Form 33, Form ‘7-ТБ’, Register ‘03-ТБ/у’, Register ‘4-ТБ/у’ for the years 2005, and 2012-2016. Keywords: Mycobacterium tuberculosis, clinical diagnostic laboratory, acid-fast bacilli, Ziehl-Neelsen microscopy, primary care.

Introduction. Today’s epidemiological and preventive healthcare facilities, irre- all levels were functioning in the Sakha situation with tuberculosis (TB) in Rus- spective of their departmental affiliation Republic (Yakutia). sia, and in the world, is demanding fast or forms of ownership [9]. Of 209 laboratories, Ziehl-Neelsen mi- and effective detection and control of the One of the viable focus areas in rais- croscopic tests for AFB were performed causative agent, to prevent its spread. ing the effectiveness of anti-TB measures by 144 (68.9%) labs. Due to substandard Microscopic method based on acid-fast is the application of indicative approach resources, 60 (28.7%) labs were not li- biological properties of Mycobacterium to state monitoring and management censed to work with RG3 and RG4 bio- tuberculosis is one of the detection meth- system. Monitoring trends in indicators logical agents, and were not performing ods that are both fast and inexpensive [9]. can be useful in terms of more effective tests for AFB. Detection of acid-fast bacilli (AFB) in management of prevention and treatment Based on WHO recommendations diagnostic specimens is significant in practices, and to assess the performance for primary care facilities, the key per- terms of identifying infectious TB cases, of anti-TB measures. Based on indica- formance quality indicators for Zie- which present the biggest epidemiologi- tive approach, improved epidemiological hl-Neelsen (ZN) microscopy are AFB cal risk. As is recognized, these patients monitoring and quality assessment sys- detection rate in diagnostic specimens, can infect 20-30 or even more persons a tems in TB care system have been de- multiplicity of tests performed, population year, on average [1, 5, 9]. veloped and implemented at a regional coverage (%) with tests, and proportion In this view, intensifying the detection level [7]. of new TB cases with positive ZN sputum of cases by microscopic methods is con- Aim. Analyze performance and qual- microscopy detected in primary care lab- sidered more and more as an urgent task ity of AFB detection by means of Zie- oratories. Based on these criteria, we as- for laboratory services within all medical hl-Neelsen staining-based microscopic sessed performance for ZN microscopic examination performed in laboratories of tests conducted in clinical diagnostic lab- primary care facilities in the Sakha Re- oratories of primary care facilities over PAVLOV Nikolai Gerasimovich, Cand.Sci. public (Yakutia). the period from 2012 to 2016. (Veterinary Medicine), senior researcher, Material and methods. We analyzed As is seen in Table 1, over the spec- Bacteriological laboratory, Phthisiatry Re- the work of laboratory service performing ified period, number of tests performed search-Practice Center, Yakutsk, Russia; microscopic diagnosis of TB in Yakutia. and number of individuals tested for Mobile: 79644240417 E-mail: png_74@mail. Analysis was based on national-level AFB in primary care laboratories had re- ru, ALEKSEEVA Galina Ivanovna, Dr.Sci. and industry sectoral reports, and mained practically at the same level, with (Medicine), Head of Bacteriological labo- annual reports of laboratories performing minor variations ranging from 79 258 ratory, Phthisiatry Research-Practice Cen- ter, Yakutsk, Russia; Mobile: 79644260609 microscopic diagnosis of TB. (2012) to 79 544 (2016) tests/year, and E-mail: [email protected], VINOKUROVA Data from the following statistical forms from 30 760 (2012) to 30 174 (2016) pa- Maria Konstantinovna, Dr.Sci. (Medicine), were analyzed: Form 30, Form 33, Form tients/year. Proportion of AFB-positive Deputy Director for Science, Phthisiatry Re- ‘7-ТБ’, Register ‘03-ТБ/у’, Register ‘4- patients had been declining each year search-Practice Center, Yakutsk, Russia; Mo- ТБ/у’ for the years 2005, and 2012-2016. (WHO reference level: 1%), with 0.3% in bile: 79644239494 E-mail: [email protected], Statistical data processing was per- 2016, compared to 0.5% in 2012. Multi- ERMOLAEVA Elena Innokentievna, Head formed using commonly available software plicity of tests (WHO reference value: of Clinical diagnostic laboratory, Phthisiatry (Microsoft Excel), and StatSoft Statistica 3.0) remained stably at 2.6. Population Research-Practice Center, Yakutsk, Russia; 6, and was based on mean values (M±m), coverage (WHO reference level: 5%) Mobile: 79142378470 E-mail: ermolaeva.50@ mail.ru, CHERNYKH Marina Valerievna, bac- and statistical significance measure ranged from 3.4% to 3.1%. teriologist, Bacteriological laboratory, Phthisiat- for observed statistical differences (P). It can be said, that AFB detection rate, ry Research-Practice Center, Yakutsk, Russia; Results and discussion. As of Jan- multiplicity of ZN tests, and population Mobile: 79142221306 E-mail: [email protected]. uary 1, 2017, 209 clinical laboratories of coverage with ZN testing in primary care 60 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

laboratories had been below the reference is allowed, if AFB are detected in the first cline trend in number of new cases of pul- WHO levels over the period from 2012 sputum sample. Optimal multiplicity for monary TB, with a decrease by 15.3%, to 2016, and showed a trend to decline. sputum tests per 1 patient, performed on average (from 577 in 2005 to 489 in Therefore, with the aim to comprehen- with diagnostic purpose, could be 2.7. 2016). Among new pulmonary TB cases, sively assess performance of microsco- The third indicator describing the diagnosis of infectious TB (i.e. case iden- pies for AFB, we analyzed some aspects performance of primary-level facilities is tification and notification) by means of mi- in generating the values for indicative population coverage with microscopy, croscopy (ZN, fluorescence) decreased statistics. calculated using the formula: by 5% (from 34.0% in 2005 to 32.3% in The first indicator, AFB detection 2016) (Table 2). rate, is used to describe the percent of Number of patients with There was a noticeable increase in smear-positive TB patients among pa- suspicion tested for TB AFB detection rate by microscopies per- tients suspected for TB and tested in pri- x 100 formed in primary-level facilities. In 2005, mary care laboratories. Indicative value is proportion of AFB+ results in primary-lev- calculated based on ratio of smear-posi- Total population of an area el facilities was 18.4%, but during the pe- tive patient number to total number of riod from 2012 to 2016, there was a sta- Reference level for this indicator is persons tested for TB (% of infectious TB tistically reliable increase by a factor of 5%. This level is achievable with ade- patients identified by microscopy). Calcu- 2.4 (p<0.05), and in 2016, the proportion quate patient classification to social and lation is made using the formula: was 44.3%. medical risk groups for TB. In the Far-East Federal District, the The forth indicator, a significant one, is Number of smear-positive proportions of new infectious (smear-pos- the proportion of smear-positive patients patients itive) TB cases detected by microscopy with TB detected in primary-level labora- were lower, compared to Sakha Republic x 100 tories among all notified new smear-pos- (Table 3): 32.2 (2012); 30.2 (2013); 31.5 itive TB cases. Number of patients with (2014); 32.8 (2015); 30.2% (2016). In With well-organized workflow, the ma- suspicion tested for TB Russian Federation, the proportions were jority of infectious TB cases identified by almost the same as in Sakha Republic: This indicator is used to assess perfor- sputum microscopy should be detected 33.8 (2012); 34.2 (2013); 34.0 (2014); mance of primary level laboratories in de- by primary-level facilities. Recommend- 34.1 (2015); 33.8% (2016) [2,3,4,8]. tecting TB cases. It is in correlation with TB ed detection level is estimated as no less For the last 5 years, the proportion of prevalence level in a region. Reference than 50-70%. This indicator is calculated AFB-positive cases detected by prima- value for AFB detection rate should be 1%. using the formula: ry-level facilities, among all notified AFB+ Data in Table 1 show that in the Sakha cases, was stably above 40% (except Republic, the reference value for AFB Number of smear-positive TB 39.8% in 2015), which was meaningful- detection rate is achieved only in spe- patients detected by primary-level ly higher, compared to Far-East Federal cialized TB service facilities. Considering facilities District and Russian Federation (2.3 and the existing estimated TB incidence in x 100 2.4 times (p<0.05), respectively). Russia, primary level laboratories could Hence, taking into consideration the be able to detect, respectively, 1-2% and Number of all notified new smear- increase in microscopic detections by 2-3% of TB cases in cities and in rural ar- positive TB cases primary-level facilities in Sakha Republic, eas, per every 100 individuals tested [6]. To analyze this indicator, results of mi- observed over the study period, an ap- Reaching these proportions will de- crobiological examinations were studied in propriate reference level for this indicator mand rigorous adherence to require- newly identified patients within annual co- would be no less than 60%. ments: appropriate patient referral for horts of pulmonary TB cases in Sakha Re- Conclusion. All reference indicators AFB-test; adequate multiplicity of tests public for the years 2005, and 2012-2016. discussed are suitable for estimation of the performed; adequate quality of diagnos- Over the study period, there was a de- performance, quality of work, and work- tic specimens. The second indicator, multiplicity of tests, is calculated using the formula: Table 1

Number of samples tested Number and quality of ZN microscopies for AFB in clinical diagnostic laboratories x 100 of primary care facilities in 2012-2016

Number of patients with suspicion Years Indicators tested for TB 2012 2013 2014 2015 2016 Number of tests, total 79258 83501 79305 80034 79544 WHO recommends collecting three Of them, AFB+ 322 228 226 187 162 samples from each patient suspected for Detection % 0.4 0.3 0.3 0.2 0.2 TB to perform sputum microscopy. Ideal- (WHO reference: 1%) ly, an average number of slides (samples) Patients tested 30760 32584 30797 29920 30174 observed to diagnose 1 patient should Of them, AFB+ 149 126 110 101 87 be 3 or close to 3. Too many (>3) or too Detection % 0.5 0.4 0.4 0.3 0.3 few (<2) samples would be considered (WHO reference: 1%) as noncompliance to sputum collection Test multiplicity 2.6 2.6 2.6 2.7 2.6 procedure [6]. But taking into consider- (WHO reference: 3.0) ation the new recommendations, cancel Population coverage % 3.2 3.4 3.2 2.8 3.1 of further diagnostic tests of specimens (WHO reference: 5%) 3’ 2019 61

flow management of primary-level laboratories performing ZN microscopy for AFB. Table 2 The indicators are easy to calculate, and are currently included in official sta- AFB detection among new cases of pulmonary TB, Sakha Republic, 2005, 2012-2016 tistical recording and reporting forms. In conclusion, present-day reality is Of them AFB+ Of them, AFB+ Total demanding further dedicated manage- Year (microscopy) (microscopy in primary care) number rial efforts to continue actively using mi- n % n % croscopic method in case detection, in 2005 577 196 34,0 36 18,4 particular, pulmonary TB cases, and es- 2012 576 215 37,3 88 40,9 pecially, among social and medical risk 2013 591 199 33,7 81 40,7 groups. In view of this, more emphasis 2014 558 212 38,1 94 44,3 is put on comprehensive indicative ap- 2015 517 171 33,1 68 39,8 2016 489 158 32,3 70 44,3 proach to estimation and continuous Trend over monitoring of workflow organization and - 15,3% - 19,4% - 5% +1.9 times +2.4 times 2005-2016 quality of microscopic tests performed, for the purposes of TB detection. Table 3 References Proportion of new cases of pulmonary TB with positive microscopy, Sakha Republic, Far-East Federal District, Russian Federation, 2012-2016 1. Выявление туберкулеза методом микро- скопии: учебное пособие для проведения ба- Years Indicator зового курса обучения. Москва, Тверь: Триада; 2012 2013 2014 2015 2016 2008. [Detection of tuberculosis using microscopy method: study guide for basic studies courses. Notified Moscow, Tver: Triada Publ.; 2008. (In Russ.)]. with AFB+ microscopy: 37.3 33.7 38.1 33.1 32.4 2. Ревякина О.В. и др. Основные показа- Yakutia: (М±m) = 34.9±1.2 32.2 30.2 31.5 32.8 30.2 тели противотуберкулезной деятельности в Far-East: (М±m) = 31.4±0.5 33.8 34.2 34.0 34.1 33.8 Сибирском и Дальневосточном федеральных Russia: (М±m)=34.0±0.1 округах. Новосибирск; 2013. [Revyakina OV et al. Key indicators for anti-tuberculosis measures Of them. proportion of AFB+ in Siberian and Far-East Federal Districts. Novo- detected in primary care facilities: 40.9 40.7 44.3 39.8 44.3 sibirsk; 2013 (In Russ.)]. Yakutia: (М±m) = 42.0±0.9 19.2 18.7 16.1 17.2 18.1 3. Габбасова Л.А. и др. Отраслевые и эко- Far-East: (М±m) =17.9±0.5 18.3 17.9 16.8 17.5 16.8 номические показатели противотуберкулезной Russia: (М±m) =17.5±0.3 работы в 2009-2014 гг. Методика расчета по- Increase in Yakutia, compared to Far-East Federal District and Russia: by a factor of 2.3 and 2.4. казателей и статистические материалы по ре- зультатам пятилетнего наблюдения. Москва: ЦНИИОИЗ; 2015. [Gabbasova LA et al. Industry berkuleza. 2014; 11:18-22 (In Russ.).] https://doi. fight against tuberculosis in the current socioeco- sectoral and economic indicators for measures org/10.21292/2075-1230-2014-0-11-18-22 nomic and epidemiological settings [dissertation]. against tuberculosis in 2009-2014. Indicator cal- 6. Севастьянова Э.В. и др. Разработка Moscow; 2008 (In Russ.)]. culation methodology and statistical materials, критериев оценки качества и эффективности 8. Туберкулез в Российской Федерации based on the results of 5-year observation. Mos- микробиологических исследований в учрежде- 2011 г.: аналитический обзор статистических cow: TSNIIOIZ Publ.; 2015 (In Russ.)]. ниях противотуберкулезной службы и общей показателей, используемых в Российской Фе- 4. Стерликов С.А. и др. Отраслевые и эко- лечебной сети. Проблемы туберкулеза и бо- дерации и в мире. Москва; 2013. [Tuberculosis номические показатели противотуберкулезной лезней легких. 2009; 3:55-60. [Sevast’yanova in Russian Federation 2011: analytical review of работы в 2015-2016 гг.: статистические мате- EV et al. Development of criteria for assessing the indicators used in Russian Federation and in the риалы. Москва: ЦНИИОИЗ; 2017. [Sterlikov SA quality and performance of microbiological testing world. Moscow; 2013 (In Russ.)]. et al. Industry sectoral and economic indicators in TB facilities and in primary care network. Prob- 9. Ерохин В.В. и др. Унифицированный for measures against tuberculosis in 2015-2016: lemy tuberkuleza i bolezney legkikh. 2009;3:55- метод микроскопического выявления кисло- statistical materials. Moscow: TSNIIOIZ; 2017 (In 60 (In Russ.)]. тоустойчивых микобактерий: руководство для Russ.)]. 7. Скачкова Е.И. Научное обоснование и клинико-диагностических лабораторий лечеб- 5. Павлунин А.В. и др. Проблемы органи- разработка региональной модели организации но-профилактических учреждений. Москва, зации выявления и диагностики туберкулеза борьбы с туберкулезом в современных соци- Тверь: Триада; 2008. [Erokhin VV et al. Unified в общей лечебной сети. Проблемы туберкуле- ально-экономических и эпидемиологических method of microscopic detection of acid-fast my- за. 2014;11:18-22. [Pavlunin AV et al. Problems условиях [диссертация]. Москва; 2008. [Skac- cobacteria: manual for clinical diagnostic labora- in organizing the detection and diagnosis of tu- hkova E.I. Scientific substantiation and develop- tories of healthcare facilities. Moscow, Tver: Tria- berculosis in primary care network. Problemy tu- ment of the regional model for organization of the da Publ.; 2008 (In Russ.)]. 62 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

ACTUAL TOPIC T.M. Klimova, A.G. Egorova, R.N. Zakharova, E.P. Ammosova, M.E. Baltakhinova, A.I. Fedorov, A.N. Romanova METABOLIC SYNDROME AMONG YAKUTIA’S DOI 10.25789/YMJ.2019.67.19 INDIGENOUS FEMALE POPULATION

ABSTRACT The aim of the study was to assess the prevalence and structure of metabolic syndrome among the indigenous female population (n=628) of the Republic of Sakha (Yakutia). The screening survey was conducted among the female population of 2 districts of the Republic of Sakha (Yakutia) at the age of 20 and older (Oimyakonsky, Gorny, Tattinsky). IDF metabolic syndrome was established in 142 women, thus prevalence was at 22.6%. The most common variant of the clinical manifestations of metabolic syndrome was a combination of abdominal obesity with high blood pressure and dyslipidemia (in 62.7% of cases). The dynamics of the frequency of metabolic disorders in different age groups suggests that abdominal obesity is the main pathogenetic factor contributing to the development of a chain of metabolic disorders in a given population. Keywords: metabolic syndrome, Yakutia, abdominal obesity, diabetes mellitus, fasting hyperglycemia.

Introduction. Metabolic syndrome The study was conducted subject to is a complex of pathological conditions the voluntary informed consent of the KLIMOVA Tatyana Mikhailovna, Candidate of characterized by abdominal obesity, in- participants. The examination program Medical Sciences, Associate Professor, Depart- sulin resistance, hypertension, and hy- included: anthropometric examination ment of Pharmacology and Pharmacy, Medical perlipidemia. The syndrome contributes by the standard method, triple measure- Institute of the M.K. Ammosov North-Eastern to the development of diseases such as ment of blood pressure (BP), fasting Federal University, Senior Researcher, Depart- diabetes mellitus type 2, coronary heart venous blood sampling. The content of ment of Epidemiology of Chronic Non-Commu- nicable Diseases, Yakutsk Scientific Center for disease, stroke, and other disorders. The glucose, total cholesterol (cholesterol), Complex Medical Problems, Yakutsk, Russia, prevalence of metabolic syndrome has triglycerides, high-density lipoproteins +79142336724, e-mail: [email protected]. increased markedly over the past de- (HDL cholesterol) was determined on the ORCID: 0000-0003-2746-0608. EGOROVA cades worldwide [5]. The main reasons express analyzer Cardiochek PA, USA. Aitalina Grigorevna, Candidate of Medical for this are the changes in nutrition and a The concentration of low-density lipo- Sciences, Head of the Department of Epi- decrease in physical activity [6]. protein cholesterol (LDL cholesterol) was demiology of Chronic Non-Communicable In the Sakha (Yakutia) Republic, calculated using the Friedwald formula Diseases of the Yakutsk Scientific Center for changes in the socio-economic struc- with a blood triglyceride level of less than Complex Medical Problems, Yakutsk, Russia, ture of the population in the 20th century 4.5 mmol/L. Hypertriglyceridemia was +79142346411, e-mail: [email protected]. OR- CID: 0000-0002-8526-9644. ZAKHAROVA changed the structure of diseases and established with a triglyceride content of Raisa Nikolaevna, Cand. Candidate of Med- their prevalence. Epidemiological transi- ≥ 1.7 mmol/L, hypercholesterolemia – at ical Sciences, Senior Researcher, Research tion is accompanied by an increase in the a concentration of HDL cholesterol < 1.0 Center of the Medical Institute of the M.K. number of non-communicable diseases, mmol/L in men and < 1.3 mmol/L in wom- Ammosov North-Eastern Federal University, including cardiovascular and type 2 di- en; elevated blood pressure – with sys- 677000, Yakutsk, 27 Ulitsa Oiunskogo, Russia. abetes. According to the state statistics tolic blood pressure (SBP) ≥ 130 mmHg tel. +79142223002, e-mail: [email protected], bodies, the incidence of type 2 diabetes and/or diastolic blood pressure (DBP) ≥ ORCID: 0000-0002-1395-8256. AMMOSOVA among the adult population of the repub- 85 mm Hg; fasting hyperglycemia (FHG) Elena Petrovna, Candidate of Medical Sci- ences, Senior Researcher, Research Center lic increased from 2004 to 2017. from 14 – when the plasma glucose level is ≥ 5.6 of the Medical Institute of the M.K. Ammosov to 40.3 per 1000 population, diseases mmol/L, or when an established diagno- North-Eastern Federal University, 677000, of the circulatory system from 164.8 to sis of diabetes mellitus (DM). Persons Yakutsk, 27 Ulitsa Oiunskogo, Russia. tel. 236.2 per 1000 population. Undoubtedly, receiving specific medical treatment for +79644243908, e-mail: ammosovael@mail. this also entails an increase in longevity, these conditions were also referred to ru, ORCID: 0000-0002-7973-6103. FEDOR- but on the whole, indicates a significant as persons with these disorders. As cri- OV Afanasy Ivanovich, Candidate of Biolog- burden on society. Effective control of teria for metabolic syndrome, IDF 2006 ical Sciences, Senior Researcher, Research risk factors for these diseases is possible criteria were used, according to which Center of the Medical Institute of the M.K. with an objective assessment of the epi- MS was established in the presence of Ammosov North-Eastern Federal University, 677000, Yakutsk, 27 Ulitsa Oiunskogo, Russia. demiological situation. abdominal obesity (waist circumference tel. +79142332966, e-mail: fedorow@yandex. In this regard, the purpose of the study more than 80 cm) and 2 or more of the 4 ru, ORCID: 0000-0002-7973-6103. BALTAKH- was to assess the prevalence and struc- above-mentioned risk factors [6]. INOVA Marina Egorovna, Research Asso- ture of the metabolic syndrome among Statistical data analysis was per- ciate, Medical Institute of the M.K. Ammosov the indigenous female population of the formed in the IBM SPSS STATISTICS North-Eastern Federal University’s Scientific Sakha (Yakutia) Republic. 22 package. When comparing groups Research Center, 677000, Yakutsk, 27 Ulit- Materials and Methods. A screening depending on the type of data, Krus- sa Ojunskogo, tel. +79142710634, e-mail: survey was conducted in 2017 among kal-Wallis and Pearson χ2 criteria were [email protected]. ORCID: 0000-0003-0986- the female population of 2 districts of used. The critical value of the level of 7754. ROMANOVA Anna Nikolaevna, Doctor of Medical Sciences, Director of the Yakutsk the Republic of Sakha (Yakutia) aged statistical significance of differences (p) Scientific Center for Complex Medical Prob- 20 and over (Oymyakonsky, Gorny, Tat- was taken to be 5%. Descriptive statis- lems, Yakutsk, Russia, +79681518887, e-mail: tinsky), representatives of indigenous tics of quantitative data are presented [email protected]. ORCID: 0000-0002-4817-5315. ethnic groups (Yakuts, Evens, Evenks). as median (Me) and interquartile range 3’ 2019 63

(Q1-Q2). Frequencies are presented with cesses. The median value of body mass abdominal obesity was detected in 444 a 95% confidence interval (95% CI). In index from 40-49 years was in the range women and its prevalence was 70.7% calculating the age-standardized preva- of "increased" body weight. The median (95% CI: 66.9 -74.2). In 283 women, the lence rate, MS used the age structure of waist circumference, ranging from 30-39 blood pressure level was rated as “ele- the world population (WHO World Stan- years, met the criteria for abdominal obe- vated”, prevalence rates were 45.1% dard) [4]. sity. From 40-49 years for dap and 50-59 (95% CI: 41.2-49.0). Reduced HDL cho- The work was carried out as part of the years for CAD, the values of blood pres- lesterol levels were found in 162 patients, research “The Contribution of Metabolic sure corresponding to the upper quartile which was 25.8% (95% CI: 22.5-29.4). Syndrome to the Development of Ath- of the distribution were in the range of Hypertriglyceridemia occurred in 63 erosclerosis of the Coronary Arteries in “arterial hypertension” according to the women, respectively, the prevalence was Yakutia Residents Reg. No. 01-20-128- criteria of Moscow Society of Obstetri- 10.0% (95% CI: 7.9-12.7). Fasting hyper- 08-00 Modern Conditions” (Registration cian Gynecologists (www.moag.pro). The glycemia or an earlier diagnosis of diabe- Number АААА-А17-117021310139-5, cholesterol content was elevated from tes was found in 72 women, 11.5% (95% 17.6344.2017/8.9.). 40-49 years old, while the proportion of CI: 9.2-14.3). The frequency of all these Results and Discussion. During the HDL cholesterol was maintained at a disorders increased significantly from the epidemiological study, 628 women 20 fairly high level in all age groups. Low age of 40-49 years. years and older were examined. The av- triglyceride levels are noteworthy. Thus, IDF metabolic syndrome was estab- erage age of participants was 47.4 (stan- in general, the metabolic profile of wom- lished in 142 women, the prevalence dard deviation 15.1) years. The propor- en of Yakutia of indigenous nationality is was respectively 22.6% (95% CI: 19.5- tion of women 50–59 years old was 28%, characterized by the following features: 26.1). The highest frequency of MS was 20-39 years old – 32.7%, 40-49 years old increased body mass index, abdominal observed at the age of 50-69 years. The – 19.4%, 60 and older – 19.6%. obesity, a fairly favorable lipid profile, and age-standardized MS prevalence rate by Table 1 presents the main anthropo- normal blood glucose. These results are IDF criteria among the female indigenous metric and metabolic characteristics of consistent with data previously obtained population of Yakutia was 21.2% (95% the women examined. The dynamics of in epidemiological studies among the Ya- CI: 17.7-24.7). The study of the preva- indicators in the age groups correspond- kut population [1]. lence of MS among various groups of the ed to the natural changes associated with The frequency of metabolic syndrome population of Yakutia was also carried out the age of the subjects. The growth of and its components, depending on the by other authors. Thus, the prevalence of women of young age groups was statisti- age of the examined, is presented in MS according to IDF criteria, among in- cally significantly higher than that of older table 2. If we consider the frequency of digenous women in Yakutsk 60 years and women, which reflects acceleration pro- metabolic disorders in the whole group, older was 34.8%, which is comparable

Table 1

The main anthropometric and metabolic characteristics of the female indigenous population of Yakutia, Me (Q1-Q3)

20 years 70 years and 20-29 years 30-39 years 40-49 years 50-59 years 60-69 years Indicator and older older р n=91 n=114 n=122 n=178 n=72 N=628 n=51 120.0 108.2 110.0 140.0 119.0 130.0 140.0 SBP, mm Hg (110.0- (100.0- (100.0- (125.0- <0.001 (107.5-135.3) (113.8-150.0) (120.0-160.0) 140.0) 115.0) 120.3) 170.0) 80.0 72.3 79.5 80.0 82.7 81.5 90.0 DBP, mm Hg <0.001 (70.0-90.0) (65.0-80.0) (70.0-84.0) (70.0-90.0) (75.3-99.3) (71.8-95.3) (80.0-100.0) 155.5 158.8 158.0 148.0 157.0 154.3 151.0 Height, cm (151.0- (155.0- (155.0- (143.0- <0.001 (154.0-161.0) (151.0-158.5) (147.6-154.2) 160.0) 163.2) 163.0) 151.0) 61.8 54.2 58.5 64.0 65.0 64.0 61.0 Body mass, kg <0.001 (53.3-72.0) (49.2-61.3) (53.3-68.0) (55.4-75.0) (56.9-75.8) (54.8-74.8) (48.5-68.0) Body mass 25.3 21.7 23.5 26.2 27.3 27.3 27.1 <0.001 index, kg/m2 (22.2-29.7) (19.4-24.2) (21.2-26.6) (23.2-30.1) (24.1-31.2) (24.2-32.9) (22.5-31.4) Waist 87.0 75.0 80.0 85.0 93.9 95.4 92.0 circumference, <0.001 (78.0-97.2) (70.0-84.0) (71.8-85.5) (79.0-97.1) (85.0-102.0) (86.3-106.5) (84.0-102.0) cm Cholesterol 5.2 4.2 4.8 5.2 5.7 5.4 5.3 <0.001 mmol/L (4.4-5.9) (3.6-4.9) (4.1-5.5) (4.6-5.7) (5.1-6.3) (4.7-6.2) (4.6-6.1) 1.6 1.7 1.6 1.6 1.6 1.5 1.4 HDL mmol/L <0.001 (1.3-1.9) (1.3-2.1) (1.3-1.9) (1.3-2.0) (1.3-1.9) (1.2-1.7) (1.1-1.7) 2.9 1.9 2.5 3.0 3.2 3.3 3.4 LDL mmol/L 0.003 (2.2-3.6) (1.5-2.4) (2.0-3.2) (2.4-3.4) (2.7-3.9) (2.5-4.0) (2.8-4.1) 0.4 0.3 0.4 0.5 0.5 0.4 0.4 VLDL mmol/L <0.001 (0.3-0.6) (0.3-0.5) (0.3-0.5) (0.3-0.7) (0.4-0.7) (0.3-0.6) (0.3-0.6) Triglycerides 0.9 0.8 0.8 0.9 1.0 1.0 0.9 <0.001 mmol/L (0.7-1.2) (0.6-1.0) (0.6-1.0) (0.7-1.3) (0.8-1.4) (0.8-1.4) (0.7-1.2) Glucose 4.4 4.3 4.1 4.4 4.5 4.4 4.3 <0.001 mmol/L (4.0-5.0) (3.9-4.9) (3.9-4.6) (4.0-5.2) (4.1-5.1) (4.0-5.2) (4.1-4.7)

Note: p-value is an achieved level of significance of differences when comparing groups by age (Kruskal–Wallis test). 64 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

Table 2

Prevalence of metabolic syndrome and its components among the female indigenous population of Yakutia

Возраст Age 20-29 years 30-39 years 40-49 years 50-59 years 60-69 years 70-79 years Total n=91 n=114 n=122 n=178 n=72 n=51 n=628 Triglycerides ≥ 1.7 mmol/L n 4 6 14 28 8 3 63 % 4.4 5.3 11.5 15.7 11.1 5.9 10.0 (95%ДИ) (0.6-11.9) (1.6-11.8) (6.4-18.9) (10.8-22.1) (4.6-21.6) (0-18.1) (7.9-12.7) HDL < 1.29 mmol/L n 17 31 30 42 24 18 162 % 18.7 27.2 24.6 23.6 33.3 35.3 25.8 (95%ДИ) (11.3-28.6) (19.4-36.5) (17.4-33.4) (17.7-30.6) (22.7-45.6) (22.3-50.3) (22.5-29.4) Fasting blood glucose ≥ 5.6 mmol/L or Type 2 Diabetes n 6 3 17 31 12 3 72 % 6.6 2.6 13.9 17.4 16.7 5.9 11.5 (95%ДИ) (2.1-14.7) (0-8.5) (8.4-21.7) (12.3-23.9) (8.8-27.9) (0-18) (9.2-14.3) SBP ≥ 130 mm Hg and/or DBP ≥ 85 mm Hg n 12 31 52 101 49 38 283 % 13.2 27.2 42.6 56.7 68.1 74.5 45.1 (95%ДИ) (6.9-22.4) (19.4-36.5) (33.8-51.9) (49.2-64.0) (55.8-78.5) (59.7-85.9) (41.2-49.0) Waist circumference more than 80 cm n 34 61 89 150 64 46 444 % 37.4 53.5 73.0 84.3 88.9 90.2 70.7 (95%ДИ) (27.5-48.2) (44.0-62.8) (64.0-80.5) (77.9-89.2) (78.4-95.4) (77.2-97.6) (66.9-74.2) Metabolic syndrome by IDF criteria n 3 13 30 54 27 15 142 % 3.3 11.4 24.6 30.3 37.5 29.4 22.6 (95%ДИ) (0-10.5) (6.2-19.2) (17.4-33.4) (23.8-37.7) (26.4-49.9) (17.4-44.4) (19.5-26.1) with our data in the corresponding age cases of primary dyslipidemia. In general, dominal obesity is the main pathogenetic group (33.5%) [2]. In a study conducted options with the inclusion of disorders of factor contributing to the development of among small indigenous peoples of the carbohydrate metabolism in the form of a chain of metabolic disorders. North, the prevalence of MS according to fasting hyperglycemia or diabetes were Conclusion. Thus, according to the the criteria of GNOK ranged from 25 to recorded from the age of 40-49 years. results of a screening survey, the prev- 61% [3]. This suggests that in this population ab- alence of metabolic syndrome accord- Elevated blood pressure was one of the components of MS in 90.1% of cases Table 3 of MS, hypercholesterolemia in 71.1%, Fasting Hyperglycemia/Diabetes Mellitus Variants of clinical manifestations of metabolic syndrome depending on the age of the examined, % in 35.9%, and GGT in 34.5%. The most common variant of the clinical manifes- AO+EBP+ DLP tations of MS was the combination of ab- AO+EBP+ AO+EBP+ AO+FHG/ FHG/ (GGT, CS dominal obesity with high blood pressure DLP FHG/DM DM+DLP Age DM+DLP HDL ↓) and dyslipidemia (Table 3). This combination of risk factors was observed in n % n % n % n % n % 20-29 years 89 of 142 women with MS. A combina- 2 66.6 0 0 0 0 0 0 1 33.3 tion of 4 risk factors (abdominal obesity, n=3 30-39 years elevated blood pressure, dyslipidemia, 12 92.3 0 0 0 0 1 7.7 0 0.0 fasting hyperglycemia (DM)) was detect- n=13 40-49 years ed in 21 cases of MS. In 18 women, MS 17 56.6 5 16.6 3 10.0 5 16.7 0 0.0 was a combination of abdominal obesi- n=30 50-59 years ty, elevated blood pressure and fasting 29 53.7 9 16.7 11 20.4 3 5.6 2 3.7 hyperglycemia (or DM). A rare variant of n=54 60-69 years MS without elevated blood pressure was 17 63.0 6 22.2 3 11.1 1 3.7 0 0.0 n=27 found in 10 women aged 30-69 years. 70-79 years Four cases of isolated lipid spectrum 12 80.0 1 6.7 1 6.7 0 0.0 1 6.7 n=15 disorders in the form of a combination of Total hypertriglyceridemia and a reduced level 89 62.7 21 14.8 18 12.7 10 7.0 4 2.8 n=142 of HDL cholesterol on the background of abdominal obesity were recorded in dif- Note. AO – abdominal obesity; EBP – elevated blood pressure; DLP – dyslipoproteinemia; ferent age groups, and possibly reflect FHG/DM – fasting hyperglycemia and/or proven case of DM. 3’ 2019 65

ing to IDF criteria among the indigenous statement of this fact contains the poten- metabolic syndrome in the elderly population of female population was 22.6% (95% CI: tial for correction by informing the public Yakutia. Yаkutskij medicinskij zhurnal. 2013; 44 ( 4): 19-22. (in Russ.)] 19.5-26.1). With standardization on the about the risks, creating conditions for an 3. Софронова С.И. Артериальная гипер- age structure of the world’s population, active lifestyle, improving the eating hab- тония и метаболический синдром у коренных the prevalence of MS was 21.2% (95% its of the population, restricting advertis- малочисленных народов Севера в Якутии. CI: 17.7-24.7). The most common variant ing of unhealthy foods in the media, etc. Якутский медицинский журнал. 2018; 61 (1): of the clinical manifestations of MS was 14–17. [Sofronova SI. Arterial hypertension and References metabolic syndrome in the indigenous peoples of a combination of abdominal obesity with the north in Yakutia. Yakutskij medicinskij zhurnal. high blood pressure and dyslipidemia 1. Климова Т.М., Федорова В.И., Балтахи- 2018; 61 (1):14-17. (in Russ.)] (in 62.7% of cases). A combination of 4 нова М.Е. Метаболические факторы риска 4. Borch-Johnsen K. The metabolic syn- risk factors (abdominal obesity, elevat- хронических неинфекционных заболеваний drome in a global perspective. The public health impact--secondary publication. Dan. Med. Bull. ed blood pressure, dyslipidemia, fasting у коренного сельского населения Якутии. Экология человека. 2013; 2: 3–7. [Klimova 2007; 54 (2): 157–159. hyperglycemia/diabetes) was detected TM, Fedorova VI, Baltakhinova ME. Metabolic 5. Elabbassi W.N., Haddad H.A. The epidemic in 14.8% of cases of MS. Variants with risk factors for chronic non-communicable dis- of the metabolic syndrome.Saudi Med. J. Current the inclusion of disorders of carbohydrate eases among the indigenous rural population of Hypertension Reports. 2005; 26 (3):373–375. metabolism in the form of FHG/DM were Yakutia. Ekologiya cheloveka. 2013; 2: 3-7. (in 6. IDF. The IDF consensus worldwide defini- Russ.)] tion of the metabolic syndrome. 2006. 24 p. URL: recorded from the age of 40-49 years. 2. Симонова Г.И., Созонова К.К., Тата- http://www.idf.org/webdata/docs/ IDF_Meta_def_ The dynamics of the frequency of met- ринова О.В., Мустафина С.В., Неустроева final.pdf (accessed 11 May 2019) abolic disorders in different age groups В.Н., Щербакова Л.В. Распространенность 7. Ahmad O.B., Boschi-Pinto C., Lopez suggests that abdominal obesity is the метаболического синдрома у пожилого A.D., Murray Ch. JL., Lozano R., Inoue M. Age насе-ления в Якутии. Якутский медицинский standardization of rates: a new WHO standard. main pathogenetic factor contributing to журнал. 2013; 44 (4): 19–22. [Simonova GI, EIP/GPE/EBD, World Health Organization. 2001; the development of a chain of metabol- Sozonova KK, Tatarinova OV, Mustafina SV, 31. https://www.who.int/healthinfo/paper31.pdf ic disorders in a given population. The Neustroeva VN, Shcherbakova LV. Prevalence of (accessed 11 May 2019)

DOI 10.25789/YMJ.2019.67.20 M.A. Nikitina, N.G. Zhukova, E.Yu. Bragina, V.M. Alifirova , I.A. Zhukova, D.E. Gomboeva, N.G. Brazovskaya, NIKITINA Maria A. – MD, PhD, Associate O.P. Izhboldina , I.Zh. Zhalsanova Professor, Department of Neurology and Neu- rosurgery, Siberian State Medical University, THE HETEROGENEITY OF NON- Tomsk, Russian Federation, 8-913-865-4918, e-mail: [email protected], ORCID 0000- MOTOR SYMPTOMS IN PATIENTS WITH 0002-2614-207X, ZHUKOVA Natalya G. –MD, PhD, Professor, Department of Neurology and Neurosurgery, Siberian State Medical Uni- PARKINSON'S DISEASE IN TOMSK REGION versity, Tomsk, Russian Federation, znatali@ yandex.ru, 8-913-824-6202, BRAGINA Ele- This study was designed to survey the prevalence and distribution of non-motor symptoms na Yu. - PhD, Senior Researcher, Laboratory (NMS) in Parkinson's disease (PD) patients in Siberian region, Russia, and to investigate the of Population Genetics, Research Institute of association between NMS and health-related quality of life. Medical Genetics, Tomsk NRMC, Tomsk, Rus- Materials and methods. Two hundred six PD patients were evaluated using a battery of vali- sian Federation, [email protected], dated scales recommended by leading PD research Societies (Movement Disorders Society and 8-913-823-4122, ALIFIROVA Valentina M., the European Academy of Neurology). Clinical assessments were conducted using Uniform Par- MD, PhD, Professor, Head of the Department kinson's Disease Rating Scale (UPDRS), Hospital Anxiety and Depression Scale, Beck depres- of Neurology and Neurosurgery, Siberian State sion inventory II, Apathy Scale, Montreal Cognitive Assessment (MoCAtest), Epworth Sleepiness Medical University, Tomsk, Russian Federation, Scale, Sleep Assessment Questionnaire, Columbia-Suicide Severity Rating Scale, Parkinson's [email protected], 8-913-850-0240, ZHUKO- Disease Questionnaire-39 – PDQ-39. Results. Each PD patient had eight different individual VA Irina A. – MD, PhD, Associate Professor, NMS on average. The constipation (87%), depression (67%), insomnia (66%), anxiety (52%), Department of Neurology and Neurosurgery, apathy (35%), and impulsive behavior disorders (27%) were the most frequent complaints. NMS Siberian State Medical University, Tomsk, Russian Federation, irina.a.zhukova1@gmail. prevalence in PD patients in Tomsk region was consistent with that in the international study, com, 8-913-800-6296, GOMBOEVA Densema although the composition proportions were different. There was a significant association of PDQ- E. – PhD student of the Laboratory of Popu- 39 score with anxiety (r = 0,474, p = 0,000), depression (r = 0,471, p = 0,000), apathy (r = 0,322, lation Genetics, Research Institute of Medical p = 0,000), UPDRS III score (r = 0,316, p = 0,000), Hoehn and Yahr stage (r = 0,267, p = 0,000), Genetics, Tomsk National Research Medical disease duration (r = 0,220, р = 0,005), and levodopa equivalent dosage (r = 0,213, р = 0,001). Center, Tomsk NRMC, Tomsk, Russian Fed- Conclusion. This study confirmed that NMS are common in PD, occurring across all disease eration, [email protected], 8-923-409-6698, stages and have a great impact on quality of life. NMS progression contributes significantly to BRAZOVSKAYA Natalia G. – PhD, Associate health-related quality of life decline, and should be well recognized and treated. Professor, Department of Medical and Biolog- Keywords: Parkinson's disease, apathy, anxiety, depression, impulsive behavioral disorders, ical Cybernetics, Siberian State Medical Uni- insomnia, constipation. versity, Tomsk, Russian Federation, brang@ mail.ru, 8-913-884-7333, IZHBOLDINA Olga P. - MD, PhD, Neurologist, Siberian State Med- Introduction. Parkinson’s Disease some European countries the prevalence ical University, Tomsk, Russian Federation, (PD) is one of the most common neu- of this neurodegenerative disease rang- [email protected], 8-913-853-6047, rological disease reaching 1% among es in wide limits from 18 to 328 cases per ZHALSANOVA Irina Zh. – PhD student of population with age more than 60. PD’s 100 000 of population, but on the aver- the Laboratory of Population Genetics, Re- morbidity is up to 40 cases per 100 000 age it is about 120 cases per 100 000 of search Institute of Medical Genetics, Tomsk National Research Medical Center, Tomsk of population per year. According to the population [9]. In the Russian Federation NRMC, Tomsk, Russian Federation, irina. results of different epidemiological re- the prevalence of PD is at worldwide lev- [email protected], 8-923-409-6698 searches conducted in the USA and el and according to the epidemiological 66 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

researches conducted in different regions scales and questionnaries. Diagnose of worth Sleepiness Scale (ESS) and Sleep it is in the limit from 40 to 140 cases per PD was established according to UK Par- Attack Questionnaire (SAQ). Quality 100 000 of population. The amount of pa- kinson’s Disease Society Brain Bank Di- of life was studied by using specialized tients with Parkinson’s disease (PwPD) is agnostic Criteria. While establishing the self-questionnaire for life quality assess- suggested to increase in 1,5-2 times to diagnosis clinical form, Hoehn and Yahr ment in PwPD, PDQ-39. 2030 year [4]. stage of disease (according to «Modified Statistical result processing was per- Non-motor symptoms of PD are com- Hoehn and Yahr Scale», 1967), rate of formed by using application package mon but might stay unrecognized in clini- progression, presence of postural un- SPSS 11.5 for Windows. cal practice due to the insufficient target- steadiness, impaired walking, sidedness Results and discussion. During re- ed detection by physicians and absence with a predominance of motor symptoms sults analysis it was revealed that among of active complaints from patients and in the limbs, severity of different non-mo- the examined 206 PwPD 27% (56 pa- their relatives [1]. While dominating in tor manifestations (depression, anxiety, tients) had subclinical anxiety accord- clinical case and being main factors that apathy, cognitive and vegetative disor- ing to HADS and 25% (51 patients) had influence life quality and length of PwPD, ders) were considered. clinically manifested anxiety (table 1). such non-motor symptoms like emotion- Average age of examined patients The average was 66 (61; 73) years al-affective, behavioral and psychotic symptoms accelerate progressing of in- Table 1 validization and cause patients’ accom- modation in nursing home [13]. Characteristics of patients with Parkinson's disease, depending on the presence For the first time non-motor symptoms and severity of anxiety according to the HADS scale of PD were systematically described in 2006 by K. Ray Chaudhuri and all [9] Выраженность тревоги по шкале HADS, баллы and nowadays non-motor symptoms are Indicator abs. Norm subclinical Clinical paid great attention [7, 23]. Wide range % of non-motor symptoms includes vegeta- 0—7 8—10 ≥11 tive, neuropsychic, sensor disorders, fa- n=206 99 56 51 tigue, sleep and wakefulness disturbanc- 100 % 48.06 27.18 24.76 es. Some PD’s non-motor symptoms are registered in almost all patients regard- was about 65,9±9,8 years (66 (60;74) in the group without anxiety, 64 (60; 74) less of the age of onset and Hoehn and years), varying from 40 to 85 years. Peo- years in the group with subclinical anxiety Yahr stage of disease and become more ple with secondary professional educa- and 64 (57; 75) years in the group with expressed with the course of the disease tion (39,3%) and with higher education clinically manifested anxiety (χ²=0,162, [2]. Some of non-motor symptoms (anxi- (46,6%) prevailed. p=0,922). During intergroup comparison ety, fatigue and vegetative disorders) are The study involved patients matching it was revealed that younger patients registered at the early stage of disease certain criteria: men and women from 50 (aged 50-59 years, 31,4%) prevailed in before the beginning of treatment [12]; to 86 years; presence of PD’s diagnosis the group with clinically manifested anxi- the others according to literature data with I-IV stage by Hoehn and Yahr scale; ety as opposed to groups without anxiety and own clinical observations precede patients who signed and dated voluntary and with subclinical anxiety which con- PD’s motor symptoms for a few years informed agreement for taking part in the sisted of more older patients. (olfactory dysfunction, disturbed eye research. In the result of our research it was re- movement in the sleep phase with fast Severity of motor manifestations of vealed that patients with clinically man- eye movement – REM sleep phase, con- PD such as resting tremor, hypokine- ifested anxiety had the longest duration stipation, pain and depression) [1]. At late sia, rigidity and postural unsteadiness of PD – about 8 (4; 10) years, patients stages of disease non-motor symptoms was determined according to III part of with subclinical anxiety had the shortest – are observed in almost all patients with the Unified Parkinson's Disease Rating 4 (3; 9) years and without anxiety – 6 (3; motor fluctuations [10]. A lot of research- Scale (UPDRS) [11]. 10) years. The received data correspond es have established that at the time of Validated neuropsychological tests to the literary described as “parkinsonian PD diagnose verification its prevalence is provided in the study were focused on de- personality” according to which anxiety 21%, but in only 7 years after the disease tection of such non-motor manifestations preceding to first motor manifestations onset it is 88% [12]. of PD as impulsive behavioral disorders, of PD is characteristic. On advanced The aim of this study is to analyze het- cognitive and emotional-affective disor- stages of the disease PwPD with motor erogeneity of non-motor manifestation of ders, psychotic manifestation and sleep fluctuations have anxiety level depending PD in Tomsk region. disorders. Impulsive-compulsive disor- on levodopa action phase. Thus, anxiety Materials and methods. This study ders were evaluated by questionnaire for symptoms are increased by relative over- was performed on the base of Depart- Questionnaire for Impulsive-Compulsive dose of dopaminergic drugs [11, 16]. ment of Neurology and Neurosurgery, Disorders in PD Rating Scale (QUIO- Analisys of motor disorders by III part Siberian State Medical University. We RS). Anxiety-depressive disorders were of UPDRS depending on severity of anxi- examined 206 PwPD, 57 % (118 people) evaluated according to Hospital Anxiety ety revealed that patients with anxiety had out of them were women. The examina- and Depression Scale (HADS), Beck’s more expressed motor manifestations of tion of all patients was held according to Depression Inventory – II (BDI-II), Apa- PD: in the group of patients without anxi- our own designed individual registration thy Scale and Columbia Suicide Severity ety, with subclinical expressed and mani- card including information about social Rating Scale (C-SSRS). Cognitive sta- fested anxiety average mean by UPDRS status, history of previous diseases, tus was analyzed according to Montreal was 32 (25; 43), 33 (27; 46) и 35 (28; 44) passport details, neurological status and Cognitive Assessment (MoCA). Sleep points respectively. This fact can be ex- results of neuropsychological testing with disorders were studied according to Ep- plained on the one side by progressive 3’ 2019 67

neurodegenerative process, from the sive disorders are different from obses- is 3–6 years [10]. According to the results other side by not always correct usage of sive-compulsive, there is phenomeno- of a study conducted at the Mayo Clin- antiparkinsonian drugs treatment in pa- logical duplication indicating community ic, the risk of developing PD is 1.9 times tients with emotional-affective disorders. of certain neurobiologocal mechanisms. higher in patients with depressive disor- While analyzing clinical form of PD debut Both disorders have common diagnos- ders, with anxious disorders - 2.2, and we revealed that anxiety prevailed in pa- tic criteria such as “excessive behavior” with both - 2.4 [9, 12]. tients with acinetic-rigidity form. leading to “significant deterioration” in the Depression can be manifested by dys- Statistically significant positive mean main areas of life [13]. thymia (the frequency of which is about force correlation between anxiety and Analysis of impulsive behavior disor- 13% in PwPD), major (17%) and minor depression was revealed both by HADS ders rate indicates that it occurs in 27% (22%) depressive disorders. About 35% (r=0,446; p<0,0001) and BDI-II (r=0,436; of cases (in 56 patients) with the majority of PwPD have clinically expressed de- p<0,0001) questionnaires. Statistically prevailing in men: gambling was regis- pressive symptoms [12, 16], however, significant difference in severity of apa- tered in 6,7 %, among women – 2,7 %, according to various literary, the propor- thy in patients with clinically manifested p>0,05, hypersexuality – in 6,7 %, among tion of patients with severe depression anxiety 14 (7; 19), with subclinical anxiety women – 0,0 %, p>0,05, punding – in is 3-8%, reaching a psychotic level, and – 12 (7; 15) and without anxiety – 8 (5; 20,0 %, among women – 8,1 %, p>0,05, it does not end with suicide attempts. In 14), p=0,001 (table 2) was also detected. hobbysm – in 20,0 %, among women – patients with motor fluctuations, transient The obtained results indicate that anxi- 5,4 %, p>0,05, dofamin dysregulation depression (“off-period”) occurs that is ety in PD more often is not a separate syndrome – in 20,0 %, among women – changes in depression and maniacal neuropsychological disorder but a part of 13,5 %, p>0,05. Whereas among wom- state, marked against the background of depression structure. en such disorders as shopping mania motor fluctuations [15]. That means PwPD and more ex- prevailed in women and occurs in 8,1 One of the main problems that impede pressed anxiety usually have other emo- %; among men such impulsive behav- the diagnosis of depression in PD is sim- tional-affective disorders. ior disorder was not registered in men ilarity, common features inherent in de- It was revealed that among our 206 p>0,05 and compulsive overeating was pressive syndrome and PD: hypomimia, researched patients with clinically signif- registered in women – 10,8 % was not hypophony, decreased psychomotor icant diagnosis of PD there were only 4 registered in men – 0,0 %, p>0,05. It activity, attention disorders, increased patients with identified suicidal intent in should be noted that there are no statis- fatigue, decreased appetite, decreased history according to Columbia suicide tically significant differences between the libido and sleep disorder [3, 4, 13]. severity rating scale C-SSRS and sub- groups of both men and women in terms There is a point of view that depres- sequent interviewed physicians. Here- of the prevalence of any behavioral dis- sion in PwPD does not depend on the with no active suicidal attempts were turbance. age, duration of PD and severity of dis- observed in anamnesis of these patients. According to literary data prevalence ease [10]. However, some researchers Our results prove the literary data that of depression is 3-10% among popula- claim that the most prevalence of this “suicidal thoughts are rarity for PwPD” [7]. tion [10]. On the early stages of PD de- emotional and affective disorder occurs Analysis of drug-induced dyskinesia pression occurs in 27,6% patients [15], in patients with the initial stage of PD prevalence in PwPD with anxiety demon- on later stages in 40-50% of patients [5, (first stage by Hoehn and Yahr scale). strated statistically more significant prev- 8]. The last one is characteristic for all Such dependence can be explained by alence (39,2%) in comparison with pa- stages of PD. At the same time, it was the importance of psychological factors tients without anxiety (17,2%), z=2,77; established that in 30% of cases the di- in the development of depressive disor- p=0,006. agnosis of depression preceded the first ders in the early stages of PD associat- Significant influence of anxiety on qual- motor symptoms of PD. Emotional affec- ed with the onset of the disease and the ity of life in PwPD was revealed. Com- tive disorders can manifest themselves establishment of a diagnosis. Then it mon health status index by self-question- in some cases 20 years before the motor decreases slightly to stage II (due to the naire quality of life PDQ-39 in patients manifestation, but on average this period patient's internal adaptation to a chronic without anxiety was significantly lower in comparison with patients with subclin- Table 2 ical and clinically manifested anxiety and Severe apathy and characteristic of quality of life in people with Parkinson's disease, means 28 (20; 44), 37 (26; 46) и 48 (39; depending on the severity of anxiety, in points; - Me (Q1; Q3) 57) points, p<0,001 respectively. The more the total overall health status index Subclinical Clinical is, the worse the quality of life of the sub- Norm Kruskal-Wallis anxiety anxiety ject is (table 2). n=99 Criteria n=56 n=51 Mann-Whitney Among studied PwPD with anxiety Criteria there are statistically more occurring im- Мe (Q1; Мe (Q1; Q3) Мe (Q1; Q3) χ² p pulsive behavior disorders such as gam- Q3) bling (p=0,004), hobbysm (p=0,042) and р =0.093 Apathy, 1—2 compulsive obsessive taking of dopami- 8 (5;14) 12 (7;15) 14 (7;19) 13.193 0.001* р =0.002* points 1—3 nergic drugs within dofamin dysregula- р =0.170 tion syndrome (p=0,010) that correlates 2—3 р =0.090 PDQ-39, 1—2 with literary data according to which anx- 28 (20;44) 37 (26;46) 48 (39;57) 32.704 <0.001* р <0.001* points 1—3 iety disorders can be manifested both р <0.001* by common anxiety and panic attacks, 2—3 social phobia and obsessive-compulsive Note. In the Tables 2, 3 * - statistically significant differences at p <0.005. Quantitative attri- disorders. Although impulsive compul- butes are presented in the form of a median and interquartile interval - Me (Q1; Q3). 68 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

disease and the start of antiparkinsonian out chronically lowered mood - 6 (3; 8), p=0.352), anxiety (z=2.63; p=0.009), de- dopaminergic therapy, which has an an- (χ2=8.424; p=0.038). pression (z=2.13; p=0.034) and impulsive tidepressant effect [2, 4]. Stages III — IV In recent years a new approach to de- behavioral disorders (z=2.70; p=0.008), again are characterized by high preva- fining apathy has been taken as a “loss drug-induced dyskinesias (z=2.77; lence of depression due to a continuously of initiative” [12], that is, a lack of desire p=0.006), and cognitive impairment in progressive neurodegenerative process. for any activity and indifference to what the field of visual and constructive skills Among patients with stage V of PD the is happening around. Particular attention (χ2=3542,000; p=0,002). proportion of people with severe depres- should be paid to the differential diagnosis Analyzing antiparkinsonian dopaminer- sion is reduced. Other researchers think of depression and apathy in PD, because gic therapy, it was found that patients with that the frequency of depression is high- they have such common symptoms as apathy had a daily dose of various levodo- er at the oneset of PD with akinetic-rigid hypomimia, fatigue, social isolation, a pa preparations in terms of equivalent form, at a younger age, in women, as well decrease in pleasure from previously fa- dose of levodopa, LED (L-Dopa), higher as at a faster rate of disease progression vorite activities and a decrease in interest - 300 (156; 375) mg, compared to patients and burdened family anamneses of neu- in them. Often, these two emotional and without apathy - 150 (0; 350) mg, p<0.001. rodegenerative pathology [9]. affective states are combined in PD [16]. After assessing the quality of life ac- Among researched PwPD 10% had se- However, anxiety and melancholy affects cording to the specialized questionnaire vere depression and 27% had depression are not characteristic of apathy as an infor PwPD PDQ-39, it was found that the with middle severity according to Beck’s dependent syndrome [15]. overall health index in patients without depression inventory scale (BDI-II). Apathy is one of the most frequent apathy was statistically significantly low- The results of our researches prove affective disorders in PD, characterized er - 33.3 (21.8; 47.4) than in patients with that prevalence of depression in PD is by a loss of interest in the environment, apathy - 43.6 (32.7; 55.8) 43,6 (32,7; more at the initial stage of the disease a decrease in motivation, initiative and 55,8) (χ2=3346,5; p<0,001). (up to 54%); it decreases at stage II of emotional dullness [4, 10, 19]. According Sleep disorders have significant im- the disease to 45% and increases again to some researchers, the apathy rate in pact on the quality of life registered up to 58% in patients with stages III and PD varies from 7 to 70% [4], while oth- in 66% of cases of PD (136 patients). IV of PD. ers researches suggest the much lower Comparable results were obtained in a Using a correlation analysis of the spread - from 30% to 40% [19]. It can study conducted in Honolulu (The Ho- obtained data, a middle strength of the occur both in the structure of depression, nolulu-Asia Aging Study, HAAS), the risk positive relationship between depres- and independently of it (approximately in of developing PD in patients with exces- sion and poor quality of life was revealed 14% of patients) [4]. sive daytime sleepiness was significantly in PwPD (r = 0.471; p<0.001 under the According to our research 35% (71 higher compared with people not suffer- PDQ-39 questionnaire “cognitive func- PwPD) had apathy according to Apathy ing from it (3.3 times). In contrast, the tions” (r=0.451; p<0.001) and “emotional Scale. presence of other sleep-related disorders well-being”(r=0,450; p<0.001). It has been established that the on- - insomnia, naps, morning shakiness (in- A special place in our work was devot- set of apathy is not affected by the age toxication), and frequent nighttime awak- ed to analysis of motor disorders severity of PwPD and the age of neurodegener- enings - is not significant when consider- and drug-induced movement disorders in ative disease onset. Patients with ap- ing the risk of developing PD. It should be PwPD depending on the severity of emo- athy have a longer duration of the dis- noted that sleep disorders in the REM – tional-affective disorders. In individuals ease (U=3791.5; p=0.020), as a result, a phase precede the onset of other disease without depression the lowest frequency more developed stage of PD according symptoms [9]. of occurrence of drug-induced movement to Hoehn and Yahr scale (III and IV) and Constipation is perhaps the most com- disorders was found (9.0%), while in pa- accordingly more severe motor disorders mon symptom in PD, due to the formation tients with depression this index reached (U=3548.5; p=0.003). of α-synuclein in the dorsal motor nucleus 31.7% (z=2.39; p=0.019). In the group of patients with apathy, of the vagus nerve (nucleus dorsalis ner- Analyzing the frequency of occurrence there are statistically significantly more vi vagi), pre-vertebral ganglia and intesti- of motor disorders in PwPD according to patients with daytime sleepiness (z=0.93; nal submucosal plexuses [6]. It has been III part of the UPDRS scale depending on the severity of depression, it was found Table 3 that in patients with severe depression they were more pronounced (p=0.007). Characteristics of the severity of motor disorders in patients with Parkinson's disease It can be assumed that this fact is not (according to the sum of the third part of the UPDRS) depending on the severity always explained by the incorrect treat- of depression, in points - Me (Q1; Q3) ment of antiparkinsonian dopaminergic drugs by patients with emotional-affective Mild Moderate Severe Kruskal- Norm depression depression depression Wallis disorders. So in patients without depres- n=67 n=62 n=56 criterion Mann-Whitney sion overall average score for UPDRS n=21 criterion Мe (Q1; was 31 (24; 37), with slight depression - Мe (Q1; Q3) Мe (Q1; Q3) Мe (Q1; Q3) χ² p 32 (27; 43), with moderate - 35 (27; 47) Q3) and severe - 39 (33; 47), (table 3). р =0.139 When assessing drowsiness it was 1—2 р =0.264 found that the average score according 1—3 р1—4=0.003* to the Epworth sleepness scale (ESS) UPDRS 31 (24;37) 32 (27;43) 35 (27;47) 39 (33; 47) 12.0 0.007* р2—3=0.614 was statistically significantly higher in the р2—4=0.185 group of patients with depression - (5; р3—4=0.103 11) points, compared with those with- Movement impairments 3’ 2019 69

recently established that the pathology of and their behavior. 45-51. [Levin O.S. Parkinson's disease: modern α-synuclein can be detected by biopsy of Disclosure: The study was performed approaches to diagnosis and treatment / O.S. Levin, D.V. Artemyev, E.V. Bril, T.K. Kulua. PM. the colon submucosa in patients with PD with the support of Council on grants of 2017; 1 (102): 45-51. (In Russ.).] [9]. Studies have shown that constipation the President of the Russian Federation 6. Эпидемиология болезни Паркинсона в usually precedes the development of PD (Grant № МК-813.2019.7, "Clinical and Республике Саха (Якутия) / Попова Т.Е., Тап- for more than 10–18 years [1, 2]. Ac- epidemiological features of neurodegen- пахов А.А., Николаева Т.Я., Оконешникова Л.Т. cording to the results of our study, it was [и др.] // Якутский медицинский журнал. 2017; erative diseases of the Tomsk region") 3(59): 98-101. [Epidemiology of Parkinson’s dis- found that 87% of patients with PD had ease in the RS(Ya) / Popova T.E., Tappakhov these gastroenterological disorders (con- References A.A., Nikolaeva T.Ya., Okoneshnikova L.T. [et al.] stipation was regarded as reduction of // Yakut medical journal. – 2017; 3(59): 98-101. the bowel movements frequency to once (In Russ.)] 1. Анализ методов оценки обоняния у па- 7. Fenelon, G. Epidemiology of psychosis in or less a week). This is one of problems циентов с болезнью Паркинсона / И.А. Жукова, Parkinson's diseas. Fenelon, G., Alves, G. Jour- of current interest for patients with PD Н.Г. Жукова, О.П. Ижболдина [и др.]. Журнал nal of the Neurological Sciences. 2010; 289(1-2): and their physicians, as problems with неврологии и психиатрии имени С.С. Корса- 12-17 DOI: 10.1016/j.jns.2009.08.014 кова. Выпуск 2. Неврология и психиатрия по- the evacuation function of the intestine 8. Hauser, R. Determination of minimal clin- жилого возраста. 2015; 115(2): 47-52. 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V.V. Epanov, A.P. Borisova, A.A. Epanova, G.A. Palshin AGE-RELATED DYNAMICS OF BONE MINERAL DENSITY IN THE ADULT DOI 10.25789/YMJ.2019.67.21 POPULATION OF YAKUTSK

ABSTRACT. There has been conducted a study of the age dynamics and characteristics of the of the bone mineral density (BMD) in the adult population of the Yakutsk city. There have been revealed the BMD maximum age rates in both women (aged between 40 and 49 years old) and men (aged between 60 and 69 years old). The first 10 years after menopause onset in women, BMD decreases by 18%. The correlation of body mass index and BMD depending on gender and ethnicity was revealed. Keywords: bone mineral density, osteoporosis, body mass index, menopause.

Relevance. Yakutsk is acknowledged risk of developing osteoporosis. This is nationality is as follows: in most cases, to be the largest city of central Yakutia. supposed to be due to the peculiarities of there were investigated Yakuts (76%) The climatic and geographical features of the hormonal status; during the onset of and Russians (20%), whereas there were the location are known to be accompa- menopause, the process of bone resorp- also examined 4% of patients of other nied by a low level of insolation and a long tion is acknowledged to be accelerated, nationalities. The survey was conducted winter period of 6-9 months per year [3, 4]. the volume of bone mass is stated to de- on an X-ray axial densitometer Lunar GE A low level of insolation is stated to crease, whereas the risk of fractures is iDXA (USA) with the study of the BMD in lead to a deficiency in the synthesis of accepted to increase [11]. the lumbar spine L1-L4 (g/cm2) [13]. BMD vitamin D, which in turn appears to be a The severity of osteoporosis is known was evaluated according to the WHO cri- trigger in the development of osteoporo- to be caused by the presence of low-en- teria (1970): in postmenopausal women sis [7]. ergy fractures one of which appears to be and in men over 50 years old, the norm Osteoporosis is accepted to be one a fracture of the proximal femur including is T-test + 2.5-0.9 of standard deviations; of the most common diseases which the femoral neck fracture. Some epide- osteopenia is -1.0 – -2.4 of standard de- have been given a leading position in the miological studies which have been con- viations: osteoporosis is T-criterion -2.5 structure of morbidity and mortality in the ducted in a number of Russian cities have and below. In women before menopause world [1, 6]. revealed significant differences in the and in men younger than 50 years, the According to the International Os- prevalence of proximal femur fractures Z-test was evaluated [14]. teoporosis Foundation, more than 200 in a population over 50 years of age. On In addition, there was calculated the million people worldwide have been suf- average, the incidence of proximal femur body mass index, BMI according to WHO, fering from osteoporosis. In Russia, the fractures among residents in the Russian 2004 (18.50-24.99 is a normal weight, number of patients with osteoporosis is Federation has been accessed to be 25.00-29.99 is overweight, ≥30.00 is obe- estimated to be about 14 million. The ten- 174.7 for men and 267.5 for women for sity, 30.00-34.99 is the 1st degree, 35.00- dency to increase the life expectancy of 100 thousand people [18]. 39.99 – the 2nd degree, ≥40.00 – the 3rd the population is admitted to result in an According to the undertaken multi-site degree) [15]. increase in the incidence of osteoporosis epidemiological study, the incidence of Apart from that, there was indicated in postmenopausal women, as well as in fractures of the proximal femur in Yakutsk the hormonal status of women and the men, in the older age group [12, 17]. has been estimated to be 216.64 per 100 presence of menopause (absence of the Women are known to have a higher thousand people [8]. menstrual cycle after 12 months), distin- Considering that Yakutia has its cli- guishing between an early menopause matic and geographical features (which up to 40–45 years old and a timely meno- EPANOV Viktor Vladimirovich, Candidate are low insolation, type of nutrition, long pause at 46–54 years old [10]. of Medical Sciences, Head of Scientific Lab- winter period, remoteness of settlements, In the course of collecting the histo- oratory of osteoporosis of the Clinic of the their inaccessibility), the need to study ry, there was revealed the presence of Medical Institute of North-Eastern Federal the problem of osteoporosis and its com- low-energy fractures (falling from the own University, Associate Professor of the Depart- plications is supposed to be viewed as height) as a risk factor for osteoporosis ment of Public Health and Health Care, Gen- relevant both for the Republic of Sakha [11]. eral Hygiene and Bioethics; 36 Kulakovskogo str., Yakutsk, Russia; +7 (4112) 49-66-55, (Yakutia) and for Russia in general. Checking the normality of the distri- +79141770273, e-mail: orthos.med@rambler. Objective: to identify the age and bution of quantitative variables was im- ru; BORISOVA Afrafena Pavlovna, master gender features of the dynamics of bone plemented using Kolmogorov-Smirnov, student of North-Eastern Federal University mineral density in the adult population of Shapiro-Wilk with the amendment of Lil- named after M.K. Ammosov, Medical Institute, the city of Yakutsk. io-Fords. The descriptive statistics were Yakutsk, Russia +79644236965; EPANOVA Materials and methods: During the presented in the form of Median (Me) and Anastasia Aleksandrovna, Candidate of period of 2016-2017, in the Clinic of the interval distribution (Q1; Q3). In the course Medical Sciences, Associate Professor of the Medical Institute of North-Eastern Feder- of comparing independent groups, the Department of Organic Chemistry and Radia- al University named after M.K. Ammosov Kruskal-Wallis test was used. To as- tion Diagnostics; 27 Oiunskogo str., Yakutsk, Russia ; +7 (4112) 49-66-55, +79141770273. Yakutsk, X-ray densitometry was per- sess the strength of the direction of the PALSHIN Gennady Anatolyevich, MD, Pro- formed in 868 patients. The analysis in- relationship between the variables, the fessor, Head of the Department of TO and cluded data on 776 people aged 20 years Spearman rank analysis was used. The DM MI NEFU named after M.K. Ammosov. and older, of which 22.7% were men and level of the statistical significance of dif- Yakutsk, st. Oyunskogo, 27.8 (4112) 49-67-65. 79.3% were women. The distribution by ferences was compared to p = 0.05. 3’ 2019 71

Table 1

Distribution of the patients on gender and age, n (%)

Age, years Total Men Women 20-29 17 (2.19) 4 (0.5) 13 (1.7) 30-39 25 (3.23) 9 (1.2) 11 (1.6) 40-49 77 (9.92) 22 (2.8) 55 (7.1) 50-59 222 (28.62) 56 (7.3) 166 (21.4) Fig.1. The mineral density of the bone tissue in men 60-69 319 (41.11) 64 (8.3) 255 (32.9) and women (g/sm2) of various age groups 70-79 100 (12.87) 18 (2.3) 82 (10.6) 80-87 16 (2.06) 4 (0.5) 14 (1.8)

Results and discussion of the re- after menopause (40-49) during the search first 10 years has been estimated We have investigated 776 people: 176 to decrease by 18% (0.113 g/sm2). men (22.7%) and 601 women (79.3%) of BMD in men aged 60-69 years old the medium age of 59.0±1.0 (Table 1). has been witnessed to reach its The maximum frequency of the exam- maximum indexes and to decrease ined patients has been witnessed in the to 4% in the next decade (Fig. 1). age group of 50-79 years old, which com- In accordance with the results prises 82%. A decrease in bone mineral of the undertaken research [5], Fig.2. Comparison of BMI, BMD, and low-energy density is more often detected in women the high body mass index is ac- fractures based on the gender and nationality after menopause and in the age group cepted to be associated with the over 70 years, regardless of gender [9, 10]. mineral density of the bone tissue. One of the risk factors for osteoporosis There have been revealed a di- in women is considered to be early meno- rect tight correlation between BMI pause [20]. Early menopause occurred in and BMD in men (р = 0.714) and a 10% of the surveyed women. reverse correlation in women (р = The formation of peak bone mass, as -0.277) (Table 2). well as the general processes of bone tis- Despite the great experience sue remodeling in men and women are which has been gained, the results acknowledged to differ [2]. of the research by many authors are The bone mineral density in women likely to be viewed as contradictory [16, 19]. Fig.3. The rate of low-energy fractures based in Table 2 The mineralization of the bone the age ranks and gender (n, %) tissue in Russians has been as- 2 The rates of the BMD g/sm and the body sessed to be 13% higher than that in 2 The mineralization of the bone tissue mass index (BMI) kg/m in men and Yakuts. Low-energy fractures are seen to women of various age groups in Yakuts has been estimated to be 13% have occurred in Yakuts 4 times as often. lower than that in the Russians, and, The ratio of fractures in men and wom- hence, the number of low-energy frac- Age, years BMD, g/sm2 BMI, kg/m2 en has not appeared to depend on the tures in them is assessed to be 4 times nationality and has been 1:3 respectively. Men as high. The ratio of fractures in men and The frequency of fractures is proved to 20-29 1.1 (0.9; 1.2) 25.32 women has not been revealed to depend depend on the age, in the age group of 30-39 1.0 (0.9;1.6) 25.39 on the nationality. 50 years and older (low-energy) fractures 40-49 1.1 (1.0;1.2) 25.93 The studies were conducted as part of are likely to occur more common than in the implementation of the topic of state 50-59 1.1 (1.1;1.2) 28.31 younger age groups (95% CI from 1.07 to assignment No. 19.9242.2017 / ITR. 60-69 1.2 (1.1;1.3) 29.18 1.13). Most fractures – up to 83% –have 70-79 1.1 (1.0;1.3) 26.91 been witnessed in women. 80-87 1.1 (0.9;1.2) 27.7 The history of low-energy fractures is References р <0.001 <0.001 known to be more common in the older Women 1. Гависова А.А., Твердикова М.А., Якушев- age group [2]. ская О.В. Остеопороз: современный взгляд 20-29 1.0 (0.9;1.2) 19.72 Conclusion. Therefore, the mineral- на проблему. Российский медицинский жур- 30-39 1.1 (1.0;1.2) 24.78 ization of the bone tissue in women is ad- нал. Мать и дитя. 2012;21:1110. [Gavisova AA, 40-49 1.1 (1.1;1.2) 26.94 mitted to reach its peak values in women Tverdikova MA, Yakushevskaya OV. Osteopo- aged 40-49 years old and in men aged rosis: a modern insight on the issue. Rossijskij 50-59 1.0 (0.9;1.1) 29.33 medicinskij zhurnal. Mat' i ditya. 2012;21:1110.. 60-69 0.9 (0.9;1.0) 29.65 60-69 years old. The first 10 years after 2012;21:1110. (In Russ.)]. 70-79 0.8 (0.8;0.9) 28.67 the onset of the menopause, the bone 2. Горбунов Н.С., Тутынин К.В., Тутынина 80-86 0.8 (0.7;1.1) 26.16 mineral density in women is accepted to О.В., Дятлова М.А. Анатомические особенно- reduce by 18%. BMI is proved to have a сти женщин пожилого возраста с перелома- p >0.001 >0.001 ми проксимального отдела бедренной кости: reverse correlation with the bone mineral обзор литературы. В мире научных открытий. Note: the data is presented in the format of density in women (p = -0.277) and a di- 2015:7. [Gorbunov NS. Tutynin KV, Tutynina

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D.K. Garmaeva, A.A. Alexeev, I.S. Zakharova, T.I., Popova, V.A. Arsakova ANALYSIS OF GALLSTONE DISEASE RISK FACTORS USING SAMPLES FROM PATIENTS AFTER CHOLECYSTECTOMY AT REPUBLIC HOSPITAL №1- NCM SURGICAL DOI 10.25789/YMJ.2019.67.22 WARD (YAKUTSK)

The article analyzes the risk factors for the development of gallstone disease on the example of patients of the surgical ward the Republican hospital No.1 – NCM (Yakutsk, Russia) after cholecystectomy. It presents data on the analysis of the organic composition of gallstones using infrared spectrometry. It was revealed that gallstone disease is most common in hypersthenic women of the second adult stage, every third patient has a burdened familial history. Most of the examined stones were cholesterol ones. Analysis, synthesis, and accumulation of analytical material will bring to an understanding of the pathogenetic mechanisms of gallstones in the indigenous population, the role of endogenous and environmental factors, timely prevention and effective treatment of gallstone disease. Keywords: gallstone disease, sludge, lithogenic bile, risk factors, chemical composition of gallstones, IR spectroscopy.

Introduction. In modern conditions, lem among the indigenous people of the m is the body weight in kilograms and the there is an increase in the incidence of Sakha (Yakutia) Republic. In the Russian height in meters. The study examined 11 gallstone disease in the Sakha (Yakutia) Federation, the frequency of chronic cal- samples of stones obtained after chole- Republic, which can be attributed to the culous cholecystitis is about 12–20% [2]. cystectomy of the patients surveyed. The urbanization of the population and chang- As a rule, in the initial stages of gallstone organic status of the samples was deter- es in the diet of the indigenous population disease, it is asymptomatic and is detect- mined by the method of IR spectrosco- of the Republic. Historically, the indige- ed by chance with an ultrasound exam- py using a Spotlight 200i IR microscope nous peoples of the North have devel- ination of the abdominal cavity organs. with an MCT-detector based on the FTIR oped a protein-lipid type of exchange The generally accepted risk factors for SPECTRUM Two spectrometer in the according to the nature of their diet, due gallstones are female gender, age over Training Laboratory of Biophysics of NE- to the consumption of venison, fish prod- 50, obesity, multiple pregnancies, liver FU’S Physics-Technical Institute. ucts that are hypoallergenic and easi- diseases (cirrhosis, hepatitis), and infec- Results and Discussion. The results ly digestible products containing large tions (giardiasis, amebiasis, opisthorchi- of the data obtained revealed that fe- amounts of polyunsaturated fatty acids. asis, ascariasis, echinococcosis) [9, 10, males are more susceptible to gallstone The separation of the inhabitants of the 11, 14]. However, further research of the disease than men. Thus, during the indigenous nationality from the natural etiological and environmental factors of study period, 66 (85.7%) turned out to habitat, traditional way of life and food gallstone disease, chemical composition be in the female department; 11 (14.3%) ration cause their growth of the digestive of gallstones, elucidation of the mecha- were males. When analyzing the data system diseases [3, 9]. Currently, gall- nisms of education, detection of gallstone obtained, the relationship between the stone disease has become a social prob- disease at at an early stage, before the frequency of occurrence of gallstones formation of stones, when it is possible to and female reproductive activity was re- successfully use organ preservation, and vealed. So, out of 66 women surveyed, GARMAEVA Darima Kyshektovna, Doc- conservative treatment methods remains 40.9% had births up to 3 times, 48.5% tor of Medical Sciences, Professor at Medi- relevant and needs to be clarified. from three or more times, whereas only cal Institute of M.K. Ammosov North-Eastern Research Objective: identify risk 10.6% did not give birth. Perhaps this is Federal University, [email protected], +7-914- factors for gallstone disease and estab- due to both the increased lithogenicity 234-96-80; ALEKSEEV Aleksandr Alek- lish their priority importance, identify the of bile and dyskinesia of the biliary tract seevich, Candidate of Biological Sciences, features of the elemental composition of against the background of changing hor- Docent at Physical-Technical Institute of M.K. stones using IR spectrometry on the ex- monal levels. The lithogenicity of bile in- Ammosov North-Eastern Federal University, [email protected], +7-914-275-71-18; ample of patients after cholecystectomy creases during pregnancy by increasing ZAKHAROVA Irina Sergeevna, Medical In- of the surgical ward of the FRH (NHC). the level of estrogen, which increases stitute of M.K. Ammosov North-Eastern Fed- Study Materials: Using the surgical cholesterol transition through the sinu- eral University, an undergraduate student of ward of FRH (NHC), we conducted a sur- soidal membrane of hepatocytes, which General Medicine-16-03-1, namelessdarkill@ vey of 77 patients with gallstone disease leads to its saturation in bile, reducing yahoo.com, +7-964-417-77-04; POPOVA Ta- in the period from February 4 to April 15, the synthesis of fatty acids, changing the tiana Igorevna, Medical Institute of M.K. Am- 2019. The majority of the studied were biochemical composition of bile and the mosov North-Eastern Federal University, an representatives of the indigenous na- formation of stones from cholesterol crys- undergraduate student of General Medicine: tionality – 64 (83.1%). The respondents tals [6, 8]. Hypokinesia of the gallblad- 16-03-1, [email protected], +7-996-316-72- 39; ARSAKOVA Viktoriia Anatolevna, Med- were asked to answer questions from a der and biliary tract during pregnancy ical Institute of M.K. Ammosov North-Eastern test questionnaire adapted to identify risk also contribute to the formation of biliary Federal University, an undergraduate student factors for gallstone disease. The calcu- sludge, and subsequently the formation of General Medicine: 16-03-1, victoriaarsako- lation of body mass index (I) was deter- of gallstones [5]. [email protected], +7-964-424-80-45 mined using the formula I = m/h², where According to our data gallstone dis- 74 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

ease among the interviewed patients strong tea (51.7%), meat (48.1%), fried sion, which develops, as a rule, in obe- mainly occurs in the age period from 36 foods (40.3 %). There was little plant food sity and overweight, as a result of which to 74 years. This is due to an increased in their diet. It is known that the formation an elevated level of cholesterol and a level of bile acid formation, that is, an of gallstones is associated with a low con- change in the lipid profile are observed increase in the lithogenic bile mainly in tent of fiber in food and a longer passage in the blood. The overwhelming majority the elderly. According to the literature, of food through the gastrointestinal tract, of respondents (64.9%) have impaired the metabolism slows down and disrupts which contributes to increased absorp- stool, manifested mainly by constipation over the years, the activity of enzyme tion of secondary bile acids (deoxycho- (76%), which is a manifestation of de- systems is significantly reduced, in par- lic) and makes bile more lithogenic. Fatty creased contractility of the gallbladder ticular, the main enzyme for the synthesis foods increase the level of lipids in the and lack of bile in the intestine. Accord- of bile acids, which in turn keep choles- blood, respectively, increases the content ing to our data, cholecystitis (42.5%) and terol in bile in a dissolved state [1]. In ad- of cholesterol in bile, which changes its pancreatitis (38.9%) were the most com- dition, the incidence of gallstone disease normal ratio to cholates, increasing the mon background diseases in patients with increasing age is due to the evolu- lithogenicity of bile. Analysis of the multi- with gallstones, due to the characteristics tionary processes of the gallbladder, re- plicity of nutrition of patients showed that of the anatomy and topography of the ducing the body’s need for cholesterol, as more than half of patients eat 4-5 times a gallbladder and pancreas ducts. This is in building material, which increases its day. As is known, the number of evacua- followed by gastritis (32.5%), which is ex- concentration in bile [2, 5]. tions of bile per day is multiple to meals, plained not only by the dysfunction of the According to the survey, we can talk therefore, with rare consumption of food, sphincter of Oddi in gallstone disease but about the hereditary factor. It turned out bile becomes concentrated. also by impaired duodenal motor activi- that 36 (46.8%) patients have close rel- Analysis of bad habits showed that ty, which leads to duodenogastric reflux. atives with gallstones in history. From lit- about half of patients have addictive ad- The above diseases are a consequence erary sources, it is known that there is a dictions, such as drinking alcohol (26%), of gallstone disease [7]. gene for the lithogenic bile. Disruption of smoking (18%), and both of them (11%). IR absorption spectra of three stones cholesterol metabolism is associated with Alcohol and smoking lead to a decrease of different chemical composition are pre- the polymorphism of apolipoprotein E in high-density lipoproteins, narrowing of sented in Figures 1-3. respectively. The (Apo-E), which is genetically determined blood vessels and, as a result, to their peak of the cholesterol, bilirubin, mixed and determines the nature of changes in obliteration. When vascular inflammation wavelengths corresponds to the values cholesterol metabolism. It has been prov- occurs, lipoprotein receptors are acti- indicated in the literature [14]. Based en that differences in cholesterol metabo- vated for low-density lipoproteins (LDL), on these data, we identified the type of lism in different Apo-E phenotypes affect very low-density lipoproteins (VLDL). stones. The results of IR spectrometry bile cholesterol secretion and its stability Next, cholesterol is separated from them, showed that 9 (81.8%) of 11 stones are in bile [4, 10]. and settles in the inner lining of the ves- cholesterol, 1 (9.1%) concrement was bil- According to our data, among the sels and contributes to the development irubin and 1 (9.1%) was mixed [12]. examined patients who indicated their of atherosclerosis. Due to this process, Fig. 1 shows the IR spectrum of sam- height and weight, 77.3% turned out to the level of LDL and VLDL in the blood- ple gall_1. The IR spectrum of the exam- be individuals with hypersthenic type, stream increases, which leads to hyper- ined gallstone sample contains absorp- 18.7% with normosthenic type, 4% with cholesterolemia, which is one of the main tion bands in the 3401, 2933, and 2902, asthenic type. Thus, gallstone disease factors for the formation of cholesterol 2867, 2849 cm-1 oscillations, which cor- occurs mainly in individuals with a BMI > stones [12, 13, 14]. respond to asymmetric and symmetric

24.9. It is known that obesity is most of- Considering that the quantity and qual- C–H bonds in the CH2 and CH3 groups of ten associated with increased synthesis ity of water consumed can to some extent cholesterol. Intensive absorption bands and excretion of cholesterol. Its excess influence the formation of gallstones, we at 1466 cm-1 and the absorption band at is transferred in phospholipid vesicles, have analyzed the drinking regime of the 1377 cm-1 are related to ring deformation which are unstable, easily aggregated. At interviewed patients. It was revealed that of cholesterol and deformation vibrations the same time, large multi-layered bub- more than 51.9% of patients consume of C–H bonds in the CH2 group of choles- bles are formed, from which cholesterol less than 1200 ml per day. At the same terol, respectively. The intense absorp- monohydrate crystals precipitate, creat- time, mainly the examined patients use tion band at 1057 cm-1 is characteristic of ing the basis for the biliary sludge. While river water (28.6%), bottled (36.4%), fil- the C–C vibrations of the ring bonds in maintaining the conditions supporting tered (28.6%), lake water (28.6%), which the cholesterol molecule. the processes of lithogenesis, gallstones contain a small number of mineral sub- The intense absorption bands at 3302 form over time [5]. stances (including sulfate, sulfate-chlo- and 2931 cm-1 observed in the IR spec- Of the patients we surveyed, 63.6% ride compounds) (Fig.4). These com- trum of the gall-3 sample (Fig. 2) corre- lead an inactive lifestyle, 10.4% have pounds enhance bile formation and bile spond to the stretching vibrations of the high physical activity, and 26% have av- secretion, reduce the level of total cho- pyrrole NH group in bilirubin. Oscillations erage physical activity. Thus, a sedentary lesterol in the blood. Moreover, perhaps, in the region of 1662 cm-1 and 1628 cm-1 lifestyle leads to the formation of gall- the use of insufficient amounts of water are characteristic of vibrations of the O– stones. This explains the opinion that as leads to a thickening of bile and conse- C=O bonds in the bilirubin molecule and a result of physical inactivity, the rate of quently the formation of stones. the absorption band at 1571 cm-1 corre- bile evacuation from the gallbladder de- Analysis of comorbidities showed that sponds to the stretching vibrations of the creases and, as a result, the concentra- 20.7% of the interviewed patients suffer C=C bonds in the calcium bilirubinate tion of bile increases. from hypertension. The results obtained molecule. The absorption band in the As a result of our study, it was found are consistent with the opinion that the oscillation region of 1250...1235 cm-1 is that the patients examined mainly con- predisposing factor for the development characteristic of asymmetric stretching sumed flour (59.7%) dairy (59.7%), of gallstones is the presence of hyperten- vibrations of the COOH group in the bil- 3’ 2019 75

at 3395 cm-1 and 2932 cm-1 stipation (76%), which may complicate are due to the asymmetric the course of the disease being studied.

stretching of CH2 and the In addition, many of the interviewed pa- asymmetric stretching of tients suffer from hypertension (20.7%), CH3. and the absorption which may contribute to stone formation. band at 2867 cm-1 aris- We have begun studies on the ele- es due to the symmetric mental composition of gallstones. The

stretching of CH2. Calci- results of IR spectroscopy showed that um bilirubinate has char- most of the stones studied are cholester- acteristic bands at 1250 ol (81.8%). cm-1 (amide III), which is Thus, identifying the features of litho- associated with stretching genesis will bring us closer to under- (C–O) or stretching C–N in standing the pathogenetic mechanisms combination with the defor- of gallstone disease, the role of endog- mation of N–H (C – N) [M. enous, environmental and technological A. Subhan 1,2 *, P. Sarker, factors in the formation of micro-elemen- and T. Ahmed]. The ab- tal imbalances, as well as the correct sorption band at 1378 cm-1 choice of treatment tactics for patients Fig. 1. IR spectrum of cholesterol stone (gall_1) is explained by the bending with gallstone disease.

(CH3) vibration of cholesterol in a mixed gallstone. References Conclusion. Our analysis showed that gallstone 1. Вахрушев Я.М., Хохлачева Н.А. Желчно- disease is a polietiologic каменная болезнь: эпидемиология, факторы disease. According to our риска, особенности клинического течения, профилактика. Архив внутренней медицины. data, the leading factors re- 2016; 3(29):30-35. [Vakhrushev YM, Khokhlache- flecting the risk of calculus va NA. Gallstone Disease: Epidemiology, Risk are age, gender, lifestyle, Factors, Clinical Features, Prevention. Arhiv vnu- and hereditary predisposi- trennej mediciny. 2016; 3(29):30-35. (In Russ.).] tion. So, gallstone disease DOI: 10.20514/2226-6704-2016-6-3-30-35 2. Гребенев А.Л. Пропедевтика внутрен- is most common in hyper- них болезней: Учебник. М.: Медицина.2001. sthenic women of the sec- [Grebenev AL. Propedeutics of Internal Diseases: ond mature age (50%) and Textbook. M.: Medicine.2001. (In Russ.).] identified the relationship 3. Мараховский Ю.Х. Желчнокаменная болезнь: современное состояние проблемы. of the frequency of occur- Российский Журнал гастроэнтерологии, гепа- Fig. 2. IR spectrum of bilirubin stone (gall_3) rence of gallstones with тологии, колопроктологии. 2003; 13(1):81–92. the reproductive activity of [Marakhovsky YH. Gallstone Disease: Current women. State of the Problem. Rossijskij ZHurnal gastro- In addition, important jenterologii, gepatologii, koloproktologii. 2003; 13(1):81–92] (In Russ.).] risk factors for the occur- 4. Селезнева Э. Я., Ильченко А. А. Желчно- rence of gallstones are каменная болезнь, сочетающаяся с язвенной lifestyle hypodynamia (in болезнью двенадцатиперстной кишки (обзор 63.6% of respondents), литературы). Экспериментальная и клиниче- ская гастроэнтерология. 2008; 5:48-55. [Selez- which undoubtedly affect neva EY, Ilchenko AA. Gallstone Disease Com- the reduction of bile evac- bined with Duodenal Ulcer (Literature Review). uation. Also, the consump- Eksperimental'naya i klinicheskaya gastroenter- tion of foods rich in animal ologiya. 2008; 5:48-55. (In Russ.).] fats is observed in almost 5. Семенов Д. Ю., Смолина Е. Н., Айлама- зян А. Н. Факторы риска развития желчнока- all the examined patients. менной болезни у женщин репродуктивного This diet leads to a vio- возраста. Ученые записки СПБГМу им. акад. lation of fat metabolism, И.П. Павлова.- Том XX. 2013; 3:41- 44. [Se- which is the main cause of menov D Y, Smolina EN, Aylamazyan AN. Risk Factors for the Development of Cholelithiasis in increasing cholesterol lev- Women of Reproductive Age. Uchenye zapiski els in body fluids, including SPBGMu im. akad. I.P. Pavlova. Vol. XX. 2013; bile, whose lithogenicity 3:41-44. (In Russ.).] increases. Low fluid intake 6. Парфенов И.П., Зорбасов М.А., Ярош Fig. 3. IR spectrum of mixed stone (gall_8) (in 52% of the examined) М.А., Карапчев А.А., Солошенко А.В. Совре- менные представления об этиопатогенезе leads to the loss of its body желчнокаменной болезни. Научные ведомости irubin molecule, as well as for vibrations and, as a result, the con- Белогородского государственного университе- of the ν(C–O), ν(C–H), δ(N–H) bonds in densation of all body fluids, including bile. та. 2011; 16(111):27-31. [Parfenov IP, Zorbasov the molecule calcium bilirubinate. It was revealed that gallstone disease MA, Yarosh AL. [et al.] Modern view on etiopatho- genesis of cholelithiasis. Nauchnye vedomosti The infrared spectrum of the gallstone is closely associated with such patholo- Belogorodskogo gosudarstvennogo universiteta. of sample gall_8 (Fig. 3) shows the char- gies of the digestive system, such as cho- 2011; 16 (111):27-31. (In Russ.).] acteristic infrared absorption spectrum of lecystitis (41.5%), pancreatitis (38.9%), 7. Трухан Д.И., Викторова И.А. Гастроэнте- mixed gallstones. The absorption bands gastritis (32.5%), hepatitis (13%), con- рология: учебное пособие для студентов ме- 76 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

дицинских вузов. Санкт-Петербург: СпецЛит. (Якутия)). Якутский медицинский журнал. [Yakubchik TN. Clinical Gastroenterology: Text- 2013. [Trukhan DI, Viktorova IA. Gastroenterolo- 2015; 3(51):58-61. [Krivoshapkin VG, Sivtseva book for Medical Students, Interns, Clinical Resi- gy: textbook for medical students. St. Petersburg: AI, Sivtseva EN, Krivoshapkin MV. Factual Nutri- dents, Gastroenterologists, and Physicians. Man- SpecLit. 2013. (In Russ.).] tion of the Indigenous Peoples of the North (on ual. Grodno. 2014. (In Russ.).] 8. Тяптиргянова Т. М., Тобохов А.В., За- the example of the Evenks of the Olenek region of 12. Kleiner OI., Ramesh J, Huleihel M, Cohen харов А.Д., Яковлева З.А. Желчнокаменная the Sakha Republic). Yаkutskij medicinskij zhur- B. [et al.]. A Comparative Study of Gallstones from болезнь как причина острого билиарного nal. 2015; 3 (51):58-61. (In Russ.).] Children and Adults using FTIR spectroscopy and панкреатита. Якутский медицинский журнал. 10. Циммерман Я. С. Клиническая гас- Fluorescence Microscopy. BMC Gastroenterol. 2018; 2(62):82-84. [Tyaptirgyanova TM, Tobok- троэнтерология: избранные разделы. М.: 2002; 2: 1-14. DOI: 10.1186/1471-230X-2-3 hov AV, Zakharov AD, Yakovleva ZA. Gallstone ГЭОТАР-Медиа. 2009. [Zimmerman YC. Clinical 13. Sherlock’s Diseases of the Liver and Bil- Disease as a Cause of Acute Biliary Pancreatitis. Gastroenterology: selected sections. M.: GEO- iary System. Edited by James S. Dooley, Anna Yаkutskij medicinskij zhurnal. 2018; 2(62):82-84. TAR-Media. 2009. (In Russ.).] S.F. Lok, Guadalupe Garcia-Tsao, Massimo (In Russ.).] DOI 10.25789/YMJ.2018.62.24 11. Якубчик Т.Н. Клиническая гастроэнте- Pinzani. Wiley-Blackwell. 2018; 260-264. 9. Кривошапкин В.Г., Сивцева А.И., Сивце- рология: пособие для студентов лечебного, 14. Sleisenger and Fordtran’s Gastrointestinal ва Е.Н., Максимова С.С., Саввин Р.Г., Криво- педиатрического, медико-психологического and Liver Disease: Pathophysiology, Diagnosis, шапкина М.В. Фактическое питание коренных факультетов, врачей-интернов, клинических Management [Edited by] Mark Feldman, Law- малочисленных народов Севера (на примере ординаторов, врачей гастроэнтерологов и rence S. Friedman, Lawrence J. Brandt. 2 Volume эвенков Оленекского района Республики Саха терапевтов. Учебное пособие. Гродно. 2014. Set - 10th edition. 2015; 1100-1104.

Z.N. Alekseeva, N.S. Arkhipova, O.V. Tatarinova, S.S. Sleptsov, S.D. Efremova THE GENDER FEATURES OF MANIFESTATIONS OF FRAILTY, EMOTIONAL CONDITION AND LIFE DOI 10.25789/YMJ.2019.67.23 QUALITY OF LONG-LIVERS IN YAKUTSK

The article analyzes the severity of frailty, anxiety and depression, parameters of quality of life depending on gender, and evaluates the effect of asthenia and anxiety-depressive states on the quality of life of long-livers in Yakutsk. The data of 70 long-livers are analyzed, whose average age was 92 ± 2.21 years. By gender distribution, the number of people was the same, with 35 respondents in each group. According to the ethnic composition of the sample was represented mainly by indigenous people. The study used the methods “Age is not a hindrance” (national validated questionnaire), the hospital scale of anxiety and depression (HADS) and the questionnaire for assessing the quality of life (SF-36). According to the results of the study, frailty was diagnosed in 64.3%, prevalence in 35.7% of the examined, no significant differences were found by gender. Indicators of frailty correlated with the level of anxiety, depression, and low rates across all scales of quality of life. Clinically significant anxiety was diagnosed in 5.8%, and depression in 2.9% of subjects. Subclinical anxiety and depression were noted in 42.8% and 35.7% of subjects, respectively. Anxiety and depression rates were significantly higher among females. The positive ALEKSEEVA Zinaida Nikolaevna – clini- correlation of anxiety and depression was also noted. The results of assessing the quality of life cal psychologist, junior research Laboratory of long-livers were within the age norm, except for indicators of role physical, role emotional and of clinical-populational, and medico-social social functioning, which were higher among our respondents. Depending on the gender, values researches, Yakut Science Centre of Com- on the scales “bodily pain, “social functioning”, “role emotional” and on the general indicator of plex Medical Problems, 677010, Yakutsk, physical health were obtained significantly lower among women. The assessment of the quality Sergelyakhskoye Shosse, 4 km. gzinaida@ of life, depending on the degree of asthenia, showed significant differences in all scales of quality mail.ru; ARKHIPOVA Natal’ya Spartakovna of life, except for role physical condition. And the presence of anxiety and depression was asso- - Candidate of Medical Sciences, cardiolo- ciated with pain and a decrease in general health. gist, Republican Hospital #1 – National Medic Keywords: frailty, anxiety, depression, quality of life, long-livers, gender. Centre, Yakutsk, Sergelyakhskoye Shosse, 4 km. [email protected]; TATARINOVA Ol’ga Viktorovna – MD, Ph.D., Head, Republican Introduction. WHO experts noted the durance, and physiological functioning, Hospital #3, Leading Researcher - Labora- tory of clinical-population and medico-social problem of population “aging”. This prob- which increases the risk of dependence researches, Yakut Science Centre of Com- lem includes not only the increase in el- and death. According to some research- plex Medical Problems, 677010, Yakutsk, derly population but also the population ers, the prevalence of SAS among peo- Sergelyakhskoye Shosse, 4 km. tov3568@ of people living 90 years and more. This ple aged 80 to 84 years old reaches 16% mail.ru; SLEPTSOV Spiridon Spiridonovich category of people is the most vulnerable and at among the people elder than 85 - Candidate of Biological Sciences, Leading and their share is growing faster than the years - 26% [4, 12]. Researcher - Laboratory of clinical-popula- share of people 60 years and older. Thus, Some authors note that the main fac- tion and medico-social researches, Yakut Sci- over the past 25 years, the longevity in- tors determining the quality of life in later ence Centre of Complex Medical Problems, dex in Russia has increased by 1.7 times ages are somatic vulnerabilities, affective 677010, Yakutsk, Sergelyakhskoye Shosse, 4 km. [email protected]. EFREMOVA Svet- (from 9.0 to 15.4%) [8]. disorders and personal traits [17]. lana Dmitrievna - junior researcher, Labora- It is also well known that the incidence Therefore, it is obvious that issues re- tory of Immunology, Yakut Science Centre of of senile asthenia syndrome (SAS) in- lated to the preservation of the life qual- Complex Medical Problems, 677010, Yakutsk, creases with age. Clinical manifestations ity of long-livers in the future will be even Sergelyakhskoye Shosse, 4 km. of SAS include reduced strength, en- more relevant. 3’ 2019 77

Research objective: study gender primary sarcopenia (a syndrome char- differences in indicators of frailty, emo- acterized by progressive and general- tional state and life quality of long livers ized loss of muscle mass and strength) in Yakutsk. among people over 80 years of age Materials and Methods: In the period reaches 50% [4]. Our results are much from February to March 2019 in the Re- lower than indicated. However, it should publican Hospital No. 3 and with home be noted that the body mass index visits, we conducted a socio-psychologi- among all the respondents in the normal cal and medical examination of 82 people range, but they did not have objective at the age of 89 to 100 years. 70 people Fig.1. “Age is not a hindrance” questionnaire data about their weight and indicated that (92 ± 2.21) were able to undergo the psy- results. they do not monitor their weight. In earlier chodiagnostic examination. The criteria studies, it was stated that the incidence for exclusion from the study are severe es 32-45% among persons older than 90 of symptoms of urinary incontinence in dementia, complete deafness, and blind- [16]. The data we obtained are higher Russian women over 65 reaches 41.4%, ness. Gender distribution is equal: 35 than the presented and close to the re- and among men from 15 to 50% de- women (92 ± 2.48) and men (92 ± 1.92). sults of a study conducted by Soselia pending on living conditions [13], but in The ethnic composition of the sample N.N. among seniors and long-livers with S.Maggi studies among people over 80 was represented mainly by indigenous acute coronary syndrome: there is the years, urinary incontinence was detected people - Yakuts (75.7%), small peoples of prevalence of SAS equal to 66.1% [1]. It in 22.9% of men and 29.3% of women the North (2.8%) and Russians (21.5%). should be noted that the screening ques- [15], which is consistent with our results. A screening questionnaire “Age is not tionnaire “Age is not a hindrance” was Also, literature data often indicates that a hindrance,” which includes 7 questions also used in this study. Also, cardiovas- symptoms associated with dysfunction of with two answers (yes or no) [2] had been cular disease in a patient is accompanied the urinary tract, and especially urinary used to identify the SAS. If there are 3 by a threefold increase in the frequency incontinence, are not always easy to ex- or more affirmative answers we diagnose of senile asthenia [10]. Thus, it is possible press patients' complaints due to patient SAS, at 1-2 points - preasthenia. The that the results we obtained may be relat- embarrassment [14], which can also af- Hospital Anxiety and Depression Scale ed to the greater sensitivity of the ques- fect the accuracy. (HADS) and the Quality of Life Evaluation tionnaire we used, or with the severity of According to the results of the Hospi- Questionnaire (SF-36) were also used. chronic diseases and their comorbidity. tal anxiety and depression rating scale Statistical processing of the research Analysis of the items on the ques- (HADS), the results of more than half of results was carried out using the IBM tionnaire showed that the overwhelming the subjects were within the normal range SPSS Statistics 23 software package majority, regardless of gender, noted a in terms of anxiety and depression (Fig. with the calculation of the Spearman cor- decrease in hearing and vision (85.7% 2). Clinically significant anxiety was diag- relation coefficient and the significance of of men and 82.8% of women) (Table 1). nosed in 5.8%, and depression in 2.9% of differences for independent samples — Women more often complained of emo- subjects. Subclinical anxiety and depres- the Mann-Whitney test. The significance tional depression, anxiety, falls and trau- sion were noted in 42.8% and 35.7% of of the statistical significance of differenc- matization, and difficulties in moving subjects, respectively. es was taken at a value of p <0.05. around the house and on the street. Men Indicators of anxiety and depression more often answered affirmatively to the Results and Discussion: According depending on sex are presented in Table to the results of the “Age is not a hin- question of a decrease in memory and 2. It was noted that indicators of either drance” questionnaire, senile asthenia orientation in the locality. Both groups anxiety and depression are significantly was diagnosed in 64.3%, preasthenia in rarely complained about weight loss and higher among females. A positive correla- 35.7% of the patients. The absence of as- urinary incontinence. tion between anxiety and depression was thenia had been not detected. The maxi- The last two points with the lowest also noted (p = 0.000). mum number of affirmative answers was rates - weight loss and incontinence According to the literature, the symp- 6 and was noted in 4.3% of the subjects. should be discussed. The prevalence of The average rate for the SAS index Table 1 for the group was 2.96 ± 1.12 (M ± m), which corresponds to the index between Distribution of the affirmative answers in the “Age is not a hindrance” questionnaire, the preasthenia and asthenia. The SAS (%) index correlated with the level of anxiety (p = 0.000), depression (p = 0.000) and Question Men Women with a low index of life quality (p≤0.01). Have you lost 5 kg or more in the last 6 months? 5.7 8.6 In terms of gender distribution, the Do you experience any restrictions in everyday life due to SAS index was slightly higher among 85.7 82.8 women (3.09 ± 1.01) but has not reached decreased vision or hearing? the level of statistical significance (Fig. During the past year, have you got a fall injury? 25.7 37.1 1). In other studies, it is also noted that the prevalence of SAS among women Do you feel depressed, sad, or anxious in recent weeks? 34.3 51.4 is higher than among men, which is also Do you have problems with memory, understanding, 62.8 54.3 seen in our study [16]. orientation, or the ability to planning? This is known that depending on the method of determining the prevalence of Do you have urinary incontinence? 22.8 22.8 senile asthenia among persons over 65 Do you have difficulties in moving around the house or 48.6 68.6 ranges from 4.0% to 59.1% [7]. It reach- outdoor? 78 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

in our study and requires further consid- Table 2 eration. Considering the severity of cog- Anxiety and depression assessment results (HADS) (М±m) nitive deficit overestimated rates of activity may be noted, although this should have affected other indicators. In general, Total Men Women p-value during the survey, there was satisfactory Anxiety 6.91 ± 2.23 5.74 ± 1.75 8.09 ± 2.04 р=0.000 independence of respondents in daily life Depression 6.54 ± 2.47 5.83 ± 2.14 7.26 ± 2.60 р=0.020 - the majority served themselves independently and showed sufficient physical toms of anxiety and depression are ob- Deterioration of physical functioning activity. Many were engaged in everyday served in 25-30% of people over 65 and is considered one of the key character- exercise, Nordic walking. For example, with concomitant somatic diseases, this istics of the deterioration in the quality of one respondent noted that she was do- reaches 50% [5]. 10-14% of inpatients life, and even minor negative changes ing a set of exercises every day, con- and residents of nursing homes have in functional status are associated with sisting of one hundred different options. major depression, even more, have com- an increase in mortality, an increase in We also evaluated the effect of anxiety ponents of depressive disorders [3]. Ac- the need for additional care and health- and depression on quality of life: subjects cording to the results of our study, the related expenses. Nevertheless, the low were divided into 2 groups, where the rate of clinically expressed depression data we obtained are normal for this age first group is individuals without detected was lower which could be explained by group, as in the study conducted in Be- anxiety and depression, the second is re- the fact that almost all our subjects lived larus, the average value of the physical spondents with subclinical and clinically with their relatives, which is an alleviat- functioning scale among the long-livers significant anxiety and depression. The ing factor to depression. It should also be was 32.1, and the physical component results of statistical processing showed noted the prevalence of depression was of health was 33.1, which corresponds significant differences in the group of indi- significantly lower among people over 90 to our results. Focusing on the data of a viduals with anxiety and depressive states years [9]. Regarding the gender distribu- multicenter MIRAGE study of the quality for all scales of psychological health and tion of depression, it was found that in of life [11] among persons over 75 years some scales of physical health. The rela- old age (75–90 years), the difference in old, it can be noted that the indicators on tionship of these indicators with the psy- the frequency of depression in men and the scales are mostly within the average chological components of health is clear, women decreases, and at an over-elderly values of the population, except for role so we are focusing on physical indicators. age (after 90 years) it almost disappears. functioning based on physical and emo- Thus, the presence of anxiety was asso- In our study, these data were not con- tional state. In another study conducted ciated with pain syndrome (p = 0.038) firmed: we had obtained significant differ- in Yakutsk among the elder, high values and with a decrease in general health ences between men and women in terms on the scales of emotional and social (p = 0.024). The presence of depres- of anxiety and depression. functioning were found [6]. Regarding sion was also associated with a worse We also analyzed the severity of anxi- gender differences, many authors noted general health assessment (p = 0.002). ety and depression depending on the that the parameters of quality of life are Conclusion: presence of preasthenia and SAS and higher among men of longevity than 1. Manifestations of senile asthenia obtained a significant difference in anxi- women [18]. In general, the obtained syndrome were diagnosed in 64.3% of ety and depression between preasthenia data are consistent with data from com- subjects. The SAS indicators correlated and SAS (indicators prevail in the group parative studies of the quality of life in with the level of anxiety, depression, and with SAS) (p = 0.001 for these indicators) men and women. low rates across all scales of quality of life. According to the results of assessing The assessment of the life quality 2. Anxiety and depression rates were life quality, the average values ranged depending on the degree of asthenia, significantly higher among females. Val- from 33.50 to 80.47. The lowest values showed significant differences in all ues were positively correlated with each were noted for the general indicator scales of quality of life, except for role other and reflect comorbidity. High rates of physical health and “physical func- functioning based on physical condition. It of anxiety and depression were associ- tioning” (Table 3). The values of these is logical to expect a decrease in daily ac- ated with low rates of quality of life. scales correlate with age (p = 0.001), tivity due to SAS, which was not reflected 3. In general, indicators of the quality which indicates that the age of each age negatively affects physical well-being. The following scales are "intensity of pain" and "general health". The highest rates (role functioning based on physical and emotional condition) indicates that the daily activities of long-livers are not limited to a physical or emotional state. At the same time, the indicators of the mental component of health are reduced less than the physical component. Depending on the sex, reliable low values were obtained on the scale “pain intensity” (p = 0.002), “social functioning” (p = 0.015), “role functioning based on the emotional state” (p = 0.037) and on overall indication of physical health (p = 0.015). Fig. 2. Anxiety and depression distribution among respondents (%, n=70) 3’ 2019 79

бенности и предпосылки долголетия в России. Table 3 Социальное пространство. 2016; 4(06): 1-18. [Korolenko A.V. Regional features and precondi- Life quality assessment results (SF-36) (М±m) tions of longevity in Russia. Social'noe prostrans- tvo. 2016; 4(06): 1-18. (In Russ.).] 9. Краснов В.Н. Психиатрически расс- Total Men Women p-value тройства в общей медицинской практике. Русский медицинский журнал. 2001; Physical component 9(25):1187–1191. [Krasnov. V.N. Psychiatric dis- 33.57 ± 6.87 35.57 ± 7.36 31.56 ± 5.77 р= 0.015 of health orders in medical practice. Russkij medicinskij zhurnal. 2001; 9(25):1187–1191. (In Russ.).] Physical functioning 33.50 ± 17.96 37 ± 17.49 30 ± 17.98 р= 0.163 10. Ткачева О. Н., Рунихина Н. К., Котовская Ю. В., Шарашкина Н. В., Остапенко РRole-Physical В. С. Лечение артериальной гипертонии у 78.57 ± 24.55 84.29 ± 21.07 72.86 ± 26.68 р= 0.064 Functioning пациентов 80 лет и старше и пациентов со старческой астенией. Кардиоваскулярная терапия и профилактика. 2017;16(1): 8-21. Bodily pain 45.89 ± 17.14 52.14 ± 19.82 39.63 ± 11.07 р= 0.002 [Tkacheva O. N., Runikhina N. K., Kotovskaya Yu. V., Sharashkina N.V., Ostapenko V.S. Arte- General Health 46.84 ± 12.79 49.17 ± 13.22 44.51 ± 12.09 р= 0.20 rial hypertension management in patients aged older than 80 years and patients with the senile Рsychological component asthenia. Kardiovaskulyarnaya terapiya i profilak- 52.51 ± 6.91 53.47 ± 6.60 51.54 ± 7.16 р= 0.30 of health tika. 2017;16(1): 8-21. (In Russ.).] http://dx.doi. org/10.15829/1728-8800-2017-1-8-21 Vitality 50 ± 11.97 51.43 ± 12.40 48.57 ± 11.54 р= 0.28 11. Амирджанова В.Н., Горячев Д.В., Коршунов Н.И., Ребров А.П., Сороцкая В.Н. Популяционные показатели качества жизни по Social Functioning 69.28 ± 21.14 76.07 ± 22.14 62.50 ± 17.93 р= 0.015 опроснику SF-36 (результаты многоцентрового исследования качества жизни «Мираж»). Role-Emotional 80.47 ± 23.74 85.71 ± 21.82 75.23 ± 24.72 р= 0.037 Научно-практическая ревматология. 2008; 1: 36-48. [Amirdjanova V.N., Goryachev D.V., Kor- shunov N. I., Rebrov A.P., Sorotskaya V.N. SF- Mental Health 70.91 ± 12.10 71.43 ± 10.93 70.40 ± 13.30 р= 0.57 36 questionnaire population quality of life indices. Nauchno-prakticheskaya revmatologiya. 2008; 1: 36-48. (In Russ.).] of life among long-livers corresponded gerontologii. 2017; 30(2):236-242. (In Russ.).] 12. Турушева А.В., Фролова Е.В., Дегриз 3. Воробьев П.А., Власова А.В. Депрессия в Ж.М. Эволюция теории старческой астении. to average values, except for the scales Вестник Северо-Западного государственного on “role functioning associated with the пожилом возрасте. Клиническая геронтология. 2007; 3:22-28. [Vorobiev P.A., Vlasova A.V. De- медицинского университета им. И.И. physical and emotional state” and “social pression in old age. Klinicheskaya gerontologiya. Мечникова. 2017;9(1):117-124. [Turusheva А.V., functioning”, which indicates sufficient in- 2007; 3:22-28. (In Russ.).] Frolova E.V., Degryse J.M. Evolution of the frailty dependence in daily life and intact daily 4. Кононова Л.И., Миронова А.С. concept. Vestnik Severo-Zapadnogo gosudarstvennogo medicinskogo universiteta im. I.I. Mech- activity of long-livers. Выявление и особенности введения пациен- тов с синдромом старческой астении: мето- nikova. 2017;9(1):117-124. (In Russ.).] 4. Quality of life scales such as the дическое пособие для врачей первичного 13. Чукаева И.И., Ларина В.Н. Возраст- physical component, pain intensity, so- звена здравоохранения. Красноярск: 2017. 50 ассоциированные состояния (гериатрические cial functioning, and role functioning due с. [Kononova L.I., Mironova A.S. Identification and синдромы) в практике врача-терапевта features of the introduction of patients with se- поликлиники. Лечебное дело. 2017;1:6-15. to the emotional state was significantly [Chukaeva I.I., Larina V.N. Geriatric syndrome in lower among women. nile asthenia syndrome: metodicheskoe posobie dlya vrachej pervichnogo zvena zdravoohraneni- a primary care setting. Lechebnoe delo. 2017;1:6- ya. Krasnoyarsk: 2017. 50 p. (In Russ.).] 15. (In Russ.).] 14. Initial Manifestations of Frailty Criteria References 5. Захарченко Д.В. Клинико-динамическая характеристика реккурентного депрессивного and the Development of Frailty Phenotype in расстройства в позднем возрасте: автореф. the Women's Health and Aging Study / K. Ban- 1. Соселия Н.Н., Багманова Н.Х., дисс…. канд. мед. наук. СПб., 2015. [Zakharch- deen-Roche, R. Varadhan, J. Zhou [et al.] // Виллевальде С.В., Кобалава Ж.Д. Ассоциации enko D.V. Clinical and dynamic characteristics of The Journals of Gerontology: Series A. – 2008. синдрома старческой астении с маркерами recurrent depressive disorder in late age: abstract - 63(9). – Р. 984–990 повреждения почек и миокарда у пациентов dis. ... Phd. Saint-Petersburg., 2015. (In Russ.).] 15. Maggi S. Prevalence rate of urinary incon- с острым коронарным синдромом. Трудный 6. Ефремова А.И., Никитин Ю.П., Симонова tinence in community-dwelling elderly individuals: пациент. 2018; 3(16):53-55. [Soseliya N.N., Bag- Г.И., Щербакова Л.В. Качество жизни жителей the Veneto study./ S. Maggi, N. Minicuci, J. Lan- manova N. Kh., Villevalde S.V., Kobalava Z.D. г. Якутска в возрасте 60 лет и старше. Вестник glois, M. Pavan, G. Enzi, G. Crepaldi // J Gerontol Association of the senile asthenia syndrome with СВФУ. 2011;8 (3):32-35. [Efremova A.I., Nikitin A Biol Sci Med Sci. – 2001. - 56(1). – P. 14-18. markers of kidney and myocardium damage in Yu. P., Simonova G. I., Sherbakova L.V. Quality of 16. Prevalence of frailty in community-dwell- patients with acute coronary syndrome. Trudnyj life of Yakutsk citizens at the age of 60 and older. ing older persons: a systematic review / R.M. pacient. 2018; 3(16):53-55. (In Russ.).] Vestnik SVFU. 2011;8 (3):32-35. (In Russ.).] Collard, H. Boter, R.A. Schoevers [et al.] // J Am 2. Ткачева О.Н., Рунихина Н.К., Остапенко 7. Киселева Г.В., Рафальская К.А. Geriatr Soc. - 2012. - 60(8). – Р.1487-92. В.С., Шарашкина Н.В., Мхитарян Э.А., Онучина Распространенность гериатрических синдро- 17. Quality of life in old age International and Ю.С., Лысенков С.Н. Валидация опросника мов у пациентов врача общей практики. Multi-Disciplinary Perspectives / Ed. H. Mollen- для скрининга синдрома старческой астении в Российский семейный врач. 2017;21(4):21- kopf, A. Walker //Dordrecht: Springer. 2007. 259 р. амбулаторной практике. Успехи геронтологии. 28. [Kiseleva G.V., Rafalskaya К.A. The preva- 18. Shaw C. Functional abilities and conti- 2017; 30(2):236-242. [Tkacheva O.N., Runikhina lence of geriatric syndromes in general practice. nence: the use of proxy respondents in research N.K., Ostapenko V.S., Sharashkina N.V., Mkhitary- Rossijskij semejnyj vrach. 2017;21(4):21-28. (In involving older people. / C. Shaw, E. McColl, S. an E.A., Onuchina U.S., Lysenkov S.N. Validation Russ.).] DOI: 10.17816/RFD2017421-28 Bond // Qual Life Res. — 2000. - 9(10). — P. of the questionnaire for screening frailty. Uspekhi 8. Короленко А.В. Региональные осо- 1117-1126. 80 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

ARCTIC MEDICINE

E.V.Vorontsova, A.L.Vorontsov ENVIRONMENTAL STATE AND HUMAN HEALTH IN THE ARCTIC ZONE: MEDICAL DOI 10.25789/YMJ.2019.67.24 AND SOCIO-LEGAL ASPECT

The authors investigate the environmental impact of the Arctic zone of the Russian Federation on human health. Noting the importance of the Arctic region for our country, the authors draw attention to the huge role of human capital in the processes of its further development. In their opinion, it is the “human factor” that is the main factor determining the possibility of implementing projects for the development of the Arctic zone. In turn, the quality of human capital in the extreme conditions of the North determined primarily by the state of health. This actualizes the need to study the adverse factors affecting the human body in the Arctic. The aim of the work was to analyze environmental problems in the Arctic zone of the Russian Federation and their impact on the health of the population living in this region. The analysis of these problems carried out by the authors not only from biomedical positions, but also from the positions of legal support of environmental protection as a condition for reducing risks to human health. The main research methods were the methods of statistical and logical analysis, the system-functional method, the comparative method, the generalization method. Results. In the course of the study, the authors identified the main factors of the negative impact of the environment of the Arctic zone on human health, having a natural and anthropogenic character. According to the authors, the main natural factorsare cold, increased electromagnetic activity and radiation, low absolute humidity of the air, frequent fluctuations in atmospheric pressure, unusual photoperiodism. The authors attributed the anthropogenic factors to pollution of surface and groundwater, as well as the soil cover with oil products; air pollution by emissions of mining, mining and metallurgical and metallurgical enterprises; radionuclides of technogenic origin. The paper describes the consequences of the impact of these environmental factors in the Arctic zone on human health. According to the results of the study, conclusions was drawn about the immanent nature of environmental risks, and, accordingly, risks to public health during intensive industrial development of the Arctic zone. The natural and climatic conditions of the Polar region objectively increase the harmful effects on human health of the effects of anthropogenic pressure on the environment. In order to prevent and minimize the risks of human health violations in the Arctic zone and environmental protection, it is necessary to amend a number of legislative acts of the Russian Federation, as well as to adopt a comprehensive Federal law "On the Arctic zone of the Russian Federation", which should be based on a unified concept of legal regulation, taking into account the climatic, environmental, medical and biological specifics of theArctic. Keywords: the Arctic, the Arctic zone of the Russian Federation, the Arctic region, natural factors of negative impact on health, negative environmental factors of anthropogenic origin, risks of impairment of health, environment, legislation, “Arctic synergy”, diseases, health protection.

In international law, the Arctic is usu- ka Autonomous Districts, as well as the tal. In turn, the quality of human capital ally understood as a part of the Earth's lands and islands adjacent to these ter- is largely (and in the first place in the spheroid, whose center is the North Pole ritories, internal sea waters, the territorial extreme conditions of the North) de- and the marginal boundary is the Arctic sea, the exclusive economic zone and termined by the state of health. Hence, Circle (parallel 66 ° 33ʹ north latitude)[13]. the continental lf the Russian Federation, when planning and implementing plans The Arctic region connects together two within which Russia has sovereign rights for the development of the Arctic, it is continents - Eurasia and North America, and jurisdiction in accordance with inter- extremely important to take into account within its borders there are five states - national law. This territory is the largest a wide range of adverse factors affect- Russia, Norway, Denmark, the USA and source and strategic reserve of mineral ing the human body. This actualizes the Canada, each of which has an exclusive and energy resources of Russia. It pro- study of biomedical problems of the de- economic zone and a continental shelf duces 100% of domestic diamonds, 98% velopment of the Arctic zone in a wide in the Arctic Ocean [3]. According to the of platinum, 97.5% of gas, 75% of oil, range of scientific fields, including in the Fundamentals of the State Policy of the 95% of nickel and cobalt [22, p.50-51]. aspect of environmental protection and Russian Federation in the Arctic for the The Arctic zone can rightly be called the its legal support as directly related to hu- period up to 2020 and beyond, the Arctic source of raw materials for the develop- man health. zone of the Russian Federation is under- ment of the domestic economy. In addi- The purpose of this work was to ana- stood as part of the Arctic which includes tion, the Russian Arctic zone has a pow- lyze environmental problems in the Arctic all or part of the territory of the Sakha Re- erful logistical potential - in conditions zone of the Russian Federation and their public (Yakutia), Murmansk and Arkhan- of climatic warming, the Northern Sea impact on the health of the population liv- gelsk Regions, Krasnoyarsk Territory, Route we are reviving is able to reverse ing in this region. Nenets, Yamalo-Nenets and the Chukot- the existing global logistics schemes. Based on the results of the analysis, Thus, the importance of the Arctic for our the authors will propose legal measures country cannot be overestimated. to reduce risks to human health in the Arc- VORONTSOVA Elena Vladimirovna, PhD, Realization of the Arctic potential re- tic region (in the regions of the Far North). associate Professor of Department of finan- quires the involvement of human resourc- Materials and methods of the re- cial law, constitutional, civil and administrative es. This is also required by defense proj- search. The research process was based proceedings, South-West state University, ects, since our competitors in the Arctic on the principles of scientific knowledge 305040, Kursk, street 50 let Oktyabrya, 94, region are increasing their military pres- and objectivity of the knowledge gained. e-mail: [email protected]; VORONTSOV ence and are seeking to question the sov- The material for the analysis undertaken Andrey Leonidovich, PhD, associate Pro- fessor, associate Professor of Department of ereign rights of the Russian Federation was the results of previously conducted administrative and labor law South-West state to the natural resources belonging to it. research in the field of human physiology University, 305040, Kursk, street 50 let Okty- The circumstances noted above in- and hygiene in the Far North, identifying abrya, 94, e-mail: [email protected]. crease the importance of human capi- the main risk factors for health problems 3’ 2019 81

in these areas, as well as materials from on the body of chemicals. It should be membranes, which leads to a decrease other biomedical research. In addition, added that the super cooled organism in their protective functions. It should be data obtained from environmental mon- more sensitive to industrial poisons. noted that low air humidity is a constant itoring in specific regions of the Arctic In addition to the respiratory system, environmental factor for residents of the zone, as well as data from integrated the primary objects of cold exposure in Arctic and is typical not only for open ar- geo-environmental studies were used. the Arctic zone are open areas of the face eas of the territory, but also for residen- In addition, the content of the program and head (most often the nose and ears), tial and industrial premises, which in turn strategic documents of the Russian state as well as the hands and feet. Blood sup- requires the moistening of air in these in the field of development and devel- ply in these parts of the body is peripheral premises during the winter period and the opment of the Arctic zone, as well as and therefore and they are more prone to development of individual means protec- the content of environmental legislation frostbite. In addition, the narrowing of pe- tion of the respiratory system to work in were analyzed. A specific methodology ripheral blood vessels under the influence the cold 11 [8, p.213-217]. comprised a complex of general scientif- of cold strengthens the central circulation The Arctic zone is also characterized ic and private scientific methods, among and provokes an increase in blood pres- by frequent daily fluctuations in atmo- which the main ones were the method of sure.Even cooling the forehead and head spheric pressure, and very significant statistical and logical analysis, the sys- can increase blood pressure and heart ones. This fact also leads to serious risks tem-functional method, the comparative rate. Joints also suffer in this situation: of health disorders of the population. method, the generalization method. under the influence of cold, they lose mo- A feature of the Arctic region is an un- Results and discussion. bility due to an increase in the viscosity usual photoperiodism: polar night and 1. The impact of environmental fac- of synovial fluid [12]. It should be added polar day. Both natural phenomena affect tors on the human body in the Arctic. that the effect of the cold factor in the Arc- the state of the human body, in particular, The natural and climatic environment of tic is enhanced by the high speed of air the development of aging, age-related the Arctic zone is characterized by an movement (i.e. strong wind). pathology and neoplasm[9]. abundance of factors that have a nega- Another natural factor in the Arctic In general, it should be concluded tive impact on the health of the popula- zone of the Russian Federation, which that the human in the Arctic zone is a re- tion living here. First of all, such factors has a negative impact on human health, structuring of all types of metabolism and should include cold, by which many re- is increased electromagnetic activity and hormonal regulation. The body of the in- searchers tend to understand the entire radiation. The first adverse phenome- habitants of the Arctic is functioning more set of cooling meteorological conditions non is due to the strong variability of the intensively, in connection with which the — low air temperatures, a long period of natural physical environment and is as- physiological reserves are gradually de- standing snow, strong winds, lack of solar sociated with the structural features of pleted. In the Far North, morbidity and insolation [18, p.5]. the Earth's magnetosphere in the Polar mortality rates of the population are in- Cold affects the heat transfer and hu- Regions. In these areas, the fluctuations creasedcompared with central Russia man performance. Labor load in cold con- of the variable geomagnetic field and the [17]. More often, there are diseases of ditions requires large physiological costs. intensity of cosmic solar rays at the sur- the cardiovascular system and respirato- Coefficient of performance (COP) of phys- face of the planet are most pronounced. ry organs, musculoskeletal and nervous ical work in the open air in the conditions This leads to the so-called geomagnetic systems, digestive organs, damage to of the Extreme North is approximately 15– storms, which affect the functional state teeth and bone tissue. There is a reduc- 25% lower than in middle latitudes [12]. of the human body [6, p. 44-52]. During tion in the reproductive period and the ac- At the same time, there is an increased this period, the number of hypertensive celeration of age-related changes in oth- risk of chronic exposure to the cold fac- crises, strokes, myocardial infarction in- er physiological functions. In our opinion, tor in the Arctic zone for many workers. creases, the course of some mental dis- this is due to negative natural-climatic The respiratory system, which is most eases worsens, etc. Causing geomag- and anthropogenic factors that give rise vulnerable, as it cannot be completely netic storms, solar activity also affects to the effect of "Arctic synergy"in their protected from external conditions, is ex- the radon content in the atmospheric air combined effect on the human body. This posed to cold most often.The cold factor of the Arctic zone, thereby increasing the effect increases the harmful effects of also contributes to the fact that the respi- dose of ionizing radiation. For example, a each adverse environmental factor in the ratory tract and respiratory membranes study conducted in the Murmansk region Arctic zone. All this leads to significant have the largest environmental contact (Apatity) showed that the average dose labor losses, early disability and reduced surface among all tissues of the body, the from natural sources of ionizing radia- life expectancy [16, p. 33-40]. area of which is approximately 50 times tion due to atmospheric air is 12.5 times Unfortunately, it is impossible to elim- the surface of the body [20]. According to higher than the average in Russia [7, p. inate the adverse effects of natural and medical research, the local exposure to 93-111]. climatic factors of the Arctic. At the same cold air on the mucous membrane of the A characteristic natural factor of the time, the interests of public health require upper respiratory tract, trachea and bron- Arctic that has a negative impact on hu- the adoption of state measures aimed at chial tree causes a significant loss of heat man health is low humidity (especially on reducing the harmful effects of such ex- and moisture, which are used to warm frosty days). This reduces the oxygen uti- posure. It seems to us that in this case and moisten the inhaled air. Negative lization factor in the lungs [8, p. 213-217]. it is necessary to focus on preventive temperature values of inhaled air require In dry air the lungs hard to lose moisture. measures and the development of new significant functional stress from the re- This leads to disruption of gas exchange personal protective equipment. Note that spiratory system and, in general, create in the alveoli and the formation of hy- this, among other things, is prompted an extremely aggressive environment for poxemia in the northerners (low oxygen by Russian legislation [2; 1], as well as the respiratory system. In addition, the content in the blood). In addition, the dry documents adopted by the World Health increase in pulmonary ventilation caused air of the Arctic region contributes to the Organization (WHO) [24] and the Arctic by cold exacerbates the harmful effects loss of moisture in the skin and mucous Council. 82 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

2. Human health and human impact Protected Natural Territories”, nor other ucts per year [19, p.118]. As a result, the on the environment. In addition to nat- federal laws and other regulatory legal concentration of pollutants in the Rus- ural factors, technogenic pollution has a acts in this area take into account the sian part of the Arctic Ocean is several significant impact on human health in the natural and climatic specifics of the Arctic times higher than normal. As a result - Arctic zone of the Russian Federation (as zone. After all, it causes need of estab- accumulation in the Arctic food chains well as in the entire Arctic). lishment of special (issued author) envi- - fish, terrestrial and especially marine The intensity and scale of the current ronmental protection requirements when mammals - persistent toxic substances anthropogenic impact on the environment carrying out economic and other activities (PTS). Many representatives of the Arc- is already incommensurable with the in a given region. However, the Russian tic fauna are traditional food sources for ability of the Arctic ecosystem to natural legislator in these matters is limited to the indigenous peoples of the North, and self-purification.The assimilation poten- existing legal approaches, i.e. legal tools this pathway for PTS in the human body tial of the ecosystem has been exhausted used in the Arctic are almost the same as remains one of the main risks to human at the present stage and the situation is those used in mid-latitudes. For example, health in the Arctic zone. close to critical. The Arctic ecosystem is despite the fact that the Strategy for the The main way of getting oil and oil under stress[4, p.85]. In this regard, the Development of the Arctic Zone provides products into the environment of the Arc- environmental problems of the Arctic at- for the need to increase the responsibility tic region of the Russian Federation is oil tract the attention of both the Arctic states of nature utilization enterprises operating spills. However, relatively small accidents and the states located outside its territory in the Arctic, neither the Criminal Code of on oil pipelines occur with enviable reg- [10, p.133]. the Russian Federation nor the Russian ularity in Russia. At the same time, the Wherein the possibility of eliminating Federation Code on Administrative Of- cumulative amount of spilled oil is simply the consequences of emergency situ- fenses still does not contain special rules shocking - more than 5 million tons of ations in Arctic is complicated by the governing liability for environmental pol- oil annually (this figure was cited by an conditions of the polar night, numer- lution in the Arctic zone. employee of the Department of American ous storms with high waves, thick fog, The special vulnerability of the Arctic Studies at St. Petersburg State Univer- multi-meter ice and the possibility of colli- ecosystem urgently requires the man- sity - N. A. Chenskikh, after comparing sion with icebergs [14, p.159]. datory state environmental review when the published data on the volumes of oil Our country, as a state with a third part planning all types of economic activities produced and mining and transportation of its territory in the Far North, is aware without exception (issued by the author.). in Russia). For comparison, this is more of its responsibility for the preservation However, the current Federal Law "On than the volume of oil spilled as a result of the environment of the Arctic region Ecological Expertise" allows not to do of the disaster in the Gulf of Mexico in and notes this in the fundamental stra- this, allowing the possibility of carrying 2010, which led to environmental con- tegic documents.The key document in out certain types of economic activity sequences of a global scale. According this sense is the “Fundamentals of the without an expert examination. Of course, to experts, hundreds of drilling sites and state policy of the Russian Federation in this lack of regulation creates the risk of pipelines cross the migration routes of the Arctic for the period up to 2020 and irreversible environmental damage to the wild animals and the routes of domestic further perspective”. One of Russia's environment of the Arctic region, as well deer migrations, having had a negative main national interestsin this document as harm to the health of the population impact to date on more than 40% of the is saving unique ecological systems of living there. areas of reindeer pastures and hunting the Arctic. The next most important docu- In addition to the federal laws men- grounds [15, p.48]. In addition to damage ment regarding the Arctic is the “Strategy tioned by us, adjustments require other to the environment, this circumstance for the Development of the Arctic Zone regulations that play a huge role in the creates real risks to human health, taking of the Russian Federation and Ensuring industrial development of the Arctic: the into account the food chain of indigenous National Security until 2020”, which spec- law of Russian Federation "On Subsoil", peoples of the North that we noted earlier. ified the planned results of environmental the Federal Law "On the Continental Oil pollution of water and soil cover are protection in stages: the first stage of the Shelf of the RF" and a number of others. not the only negative environmental fac- implementation of the Strategy should en- A more radical and more acceptable op- tors in the Arctic, which are of an anthro- sure the development of a unified nation- tion would be the adoption of a compre- pogenic character. In addition, the enor- al monitoring system the state and pollu- hensive Federal Law “On the Arctic zone mous risks of disruption to public health tion of the environment of the Arctic zone, of the Russian Federation”, which would are created by the activities of mining synchronized with similar international be based on a single concept of legal enterprises, as well as enterprises of fer- systems; at the second stage - the reduc- regulation, taking into account the spe- rous and non-ferrous metallurgy. In areas tion and prevention of the negative impact cific climatic, ethnic, cultural and medical with developed industry concentrations on the environment of the Arctic zone. biological features of the Arctic region of heavy metals, fluorides, sulfates, nitro- Note that other Arctic states - the Unit- and providing special approach to the gen compounds in surface and ground- ed States, Canada, Norway, Denmark use and protection of the environment as water are often at the level of high and also pay serious attention to environmen- an environment that forms human health. extremely high pollution. Serious anthro- tal protection and environmental safety A powerful factor in the pollution of pogenic impact on the atmosphere. If the in the Arctic, but at the level of strategic the Arctic is oil pollution in the basin of total world industrial emissions of SO2 planning, our country regulates these is- the Arctic Ocean. Most of the rivers of (sulfur dioxide, sulfur dioxide) is about sues in more detail. the Urals and Siberia flow into the Arc- 100 million tons per year, in Russia this The above cannot be attributed to the tic seas, carrying oil emissions into them figure is 9.2 million tons [23, pp.370-373]. current Russian legislation in the field that have fallen into the rivers thousands At the same time, mining industry enter- of environmental protection. Neither the of kilometers from the ocean coast. The prises emit more than 3 million tons into Federal Law “On Environmental Protec- scale of such pollution is several hun- the atmosphere annually [11, p.73-75]. tion”, nor the Federal Law “On Specially dred thousand tons of petroleum prod- The emissions of solid compounds, espe- 3’ 2019 83

cially insoluble nickel, copper and cobalt the same time, harsh climatic conditions References compounds, carried out by enterprises in create significant problems in the process the north of the Krasnoyarsk Territory and of industrial and infrastructural develop- 1. Об основах охраны здоровья граждан the Kola Peninsula, are of great negative ment of the Arctic region, having a neg- в Российской Федерации: федер. закон от importance for human health in the Arctic ative impact on human health. The con- 21.11.2011 № 323-ФЗ [ред. от 06.03.2019]. Со- zone. Emissions from ore-dressing en- sequences of anthropogenic pressure on брание законодательства РФ. 2011; 48: 6724. terprises largely determine the chemical the environment that have accumulated [On the basis of the protection of public health in the Russian Federation: Feder. Law of 21.11.2011 composition of dust in the Arctic region. over many years have a huge negative No. 323-FZ [ed. from 06.03.2019]. Sobranie za- Thus, in the Western and Central Arctic, impact on the health of the population of konodatel'stva RF.2011; 48: 6724. (In Russ.).] dust contains up to 25% Cu, 15% Ni, 11% the Arctic; 2. Об утверждении Концепции демографи- S and 4% Co [5; 21, p. 369-374]. - the main natural factors of negative ческой политики Российской Федерации на период до 2025 года: указ Президента РФ от The impact of air pollution is most pro- impact on human health in the Arctic are 09.10.2007 № 1351 [ред. от 01.07.2014]. Со- nounced in the large industrial centers the cold factor, increased electromagnet- брание законодательства РФ. 2007; 42: 5009. of the Arctic zone, especially in Norilsk, ic activity, increased ionizing radiation, [On approval of the Concept of the demographic the coal-mining cities of the Komi Repub- low absolute air humidity, frequent and policy of the Russian Federation for the period lic, and the industrial centers of the Kola abrupt changes in atmospheric pressure, until 2025: Presidential Decree of 09.10.2007 No. 1351 [ed. from 01.07.2014]. Sobranie zakonoda- Peninsula. This leads to pronounced and specific photoperiodism. These nat- tel'stva RF. 2007; 42: 5009. (In Russ.).] changes in the immune, hormonal, car- ural factors are immanent characteristics 3. Основы государственной политики Рос- diorespiratory, hematopoietic and other of the environment of the Arctic region сийской Федерации в Арктике на период до vital human systems (especially in chil- and have a constant negative impact on 2020 года и дальнейшую перспективу: утв. dren). In addition, the atmospheric air of human health; Президентом РФ от 18.09.2008 № Пр-1969. Российская газета. 2009; 53п. (разделы I-IV). a number of settlements, for example, the - negative environmental factors of [The fundamentals of the state policy of the Rus- city of Monchegorsk (Murmansk region) the Arctic zone, which are of anthropo- sian Federation in the Arctic for the period up to and the city of Norilsk (Krasnoyarsk Terri- genic origin, are pollution of surface and 2020 and further perspective: app. by the Presi- tory), has an increased carcinogenic risk. groundwater, as well as soil cover with oil dent of the Russian Federation of 18.09.2008 No. Pr-1969. Rossiyskaya gazeta. 2009; 53p. 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Грамберг И. С., Додин Д. А., Лаверов Н. nuclear tests at arctic test sites. Falling clides accumulated in the environment of П. и др. /Отв. ред. д. г. -м. н. Додин Д. А. Ар- ктика на пороге третьего тысячелетия (ресурс- out with precipitation, these radionuclides the Arctic zone as a result of past nuclear ный потенциал и проблемы экологии). Санкт- affected a huge area, causing significant tests, as well as the potential danger from Петербург: Наука. 2000; 247. [Gramberg IS, Do- harm to human health. The termination existing man-made sources of radiation. din DA, Laverov NP. The Arctic on the threshold of nuclear tests reduced the value of ra- It should be noted that the negative im- of the third millennium (resource potential and en- diation exposure as a risk of impairment pact of many of these factors on human vironmental problems). Sankt-Peterburg: Nauka. 2000; 247 (In Russ.).] of health in the Arctic region, but didn’t health is increasing (the effect of “Arctic 6. Белишева Н.К. Значение вариаций гео- completely eliminate it. Even now, resi- synergy”) due to the influence of the nat- магнитного поля для функционального состо- dents of certain Arctic areas, especially ural climatic conditions of the North. In яния организма человека в высоких широтах. the Murmansk region, are exposed to the addition, environmental risks (due to the Геофизические процессы и биосфера. 2005; potential danger of radiation contamina- vulnerability of Arctic ecosystems) and, Т.4.(1/2): 44-52. [Belisheva NK. The value of geomagnetic field variations for the functional state of tion. This is facilitated by the presence accordingly, risks to human health as a the human body in high latitudes. Geofizicheskie of a large number of radiation sources of result of anthropogenic environmental processy i biosfera. 2005; T.4. (1/2): 44-52. 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V.P. Novitskaya, E.I Prakhin INFLUENCE OF ADDITIONAL VITAMINIZATION OF SCHOOLCHILDREN RATIONS IN THE ARCTIC ON VARIABILITY OF MORPHOFUNCTIONAL PARAMETERS DOI 10.25789/YMJ.2019.67.25 OF THE IMMUNE SYSTEM

The paper reports a representative study of the effect of vitaminization of children of the North on one of the most important indicators of health - immunity. Objective of the study: to identify the features of the variability of morphofunctional indicators of the immune system of schoolchildren after prolonged vitaminization in the Arctic. Materials and methods. Practically healthy schoolchildren aged 10-11 years (60 people) living in the city of Norilsk was examined. Children from the same school, who regularly took a domestic multivitamin complex of 1 tablet once a day from September to March, made up the main group (n = 30). Children from another school who did not take multivitamins formed a comparison group (n = 30). The luminescent-histochemical method of H. Yokoo et al. (1982) modified by V.P. Novitskaya (2000), the content of catecholamines (CA) and serotonin (Ser.) in lymphocytes and the ratio of catecholamines: serotonin (CA / Ser.) were determined; hematological method was used to determine the blood composition indicators in percent: basophils, %, eosinophils, %, band neutrophils,%, neutrophils,%, lymphocytes,%, monocytes, %, and the Garkavi index : lymphocytes / neutrophils. Results and discussion. It was established that after the inclusion of multivitamins in the diet of children, a decrease in the level of CA and an increase in the serotonin content in blood lymphocytes was observed. It was revealed that in boys of the main group the level of CA decreased by 2.6 times (p <0.001), whereas in girls it was only 1.5 times (p <0.01) relative to the children of the comparison group. Along with a change in the balance of neurotransmitters after taking multivitamins in girls and boys in the main group, an increase of 1.5-1.6 times (p<0.05) was observed in the percentage of band neutrophils relative to children in the comparison group. Conclusion. The results of the study showed the multivariate functioning of the immune system of schoolchildren in the conditions of the Far North after the inclusion of multivitamins in the diets. A change in the balance of regulatory indicators in schoolchildren's lymphocytes, which can change the functional activity of these cells, has been established. Carried out vitaminization, among schoolchildren of the Polar region significantly changes the balance of the cellular elements of peripheral blood in children in this region. Keywords: North, schoolchildren, vitaminization, variability of blood parameters.

Introduction. The demand for scien- sized that one of the methods of choice ducing the level of the immune response tific studies detailing the results of addi- that favorably differ from others is the [2, 3, 10]. In the literature there is infor- tional vitaminization of schoolchildren is vitaminization of children's food rations mation that the complexes of vitamins related to the fact that the actual nutrition using multivitamin preparations [5]. This and minerals exhibit immunomodulatory of children aged 7-14 years in the Arctic has been justified earlier in Russia [1, 5, and antioxidant activity have an adapto- is characterized by significant shortcom- 7] and abroad [9, 11, 12]. genic effect on the organism [1, 3, 7. ings in the form of a deficiency of micro For reliable evidence of the effect of There are no studies on the variabil- and macro nutrients, which increases the the use of vitamin complexes for prophy- ity of the immune system parameters in risk of developing many diseases [1, 5, lactic purpose the object of study should children of primary school age after pro- 7, 12]. Especially important is the optimal include the characteristics of homeostatic longed vitaminization in the conditions of supply of vitamins of children of primary systems of indicators of the adaptive ca- the Far North, which determines the rele- school age, when intensive growth and pabilities of the organism. These require- vance and scientific novelty of this work. formation of the organism. ments are met by blood cells as com- Aim of the study: to identify the fea- The national program for the optimi- ponents of the immune system involved tures of the variability of morphofunction- zation of the provision of vitamins and in adaptive responses to preserve the al indicators of the immune system of minerals of children in Russia empha- changed homeostasis [3, 10]. schoolchildren after prolonged vitamini- It is well known the participation of zation in the Arctic. blood cells in the mechanisms of the Material and methods of research. FRC КSC SB RAS Research Institute of Med- adaptation syndrome, including the con- Schoolchildren - representatives of the ical Problems of the North, Krasnoyarsk, Rus- ditions of the Far North [2, 4]. Monoami- alien population of the North aged 10–11 sia: NOVITSKAYA Valentina Petrovna – Doc- tor of Biological Sciences, Senior Researcher nergic systems exert their influence on years living in the city of Norilsk (60 peo- Clinical Pathophysiology Laboratories FRC immune responses through the hypothal- ple) were under observation. The children KSC SB RAS Research Institute MPN, ad- amus-pituitary-adrenal system. The reali- of the same school, who regularly took a dress: 660022, Krasnoyarsk, st. Partizana zation of these processes occurs through domestic multivitamin complex, 1 tablet Zheleznyaka d.3 "g", tel.: 8 (391) 228 - 06 the action of mediators and hormones on once a day, during the school year from – 83, Е-mail: [email protected], ORCID 0000- the corresponding receptor structures of September to March, made up the main 0002-7556-7699; PRAКHIN Efim Isaakovich the cells of the immune system [3, 10]. observation group (n = 30, 15 girls and – Doctor of Medical Sciences, Professor, Chief It is known that hormones and neu- 15 boys). Children from another school Researcher, Laboratory of Clinical Pathophys- iology, FRC KSC SB RAS Research Institute rotransmitters can affect the functional who did not take multivitamins constitut- MPS, address: 660022, Krasnoyarsk, st. Par- activity of these cells, causing either stim- ed the comparison group (n = 30, 15 girls tizana Zheleznyaka d. 3 "g", tel.: 8 (391) 228 ulation of the immune response with an and 15 boys). - 06 - 83, Е-mail:[email protected], ORCID increase in the proliferative abilities of the Both schools were located in areas 0000-0003-1583-9928 cells, or activate suppressor activity, re- with the same environmental situation. 86 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

The criterion for inclusion in the study of all, it was revealed that the level of cat- lower by 41.7% (p <0.001) than in girls. was that the children were somatically echolamines in lymphocytes of children When comparing the degree of in- healthy, did not take other medications living in conditions of the North (compari- crease in the serotonin content in the and vitamin complexes, did not under- son group) is significantly higher, and the lymphocytes of children, it was found go vaccination during this period. The level of serotonin is significantly lower that in girls of the main group the level examination of children was carried out than in children living in middle latitudes of serotonin increased 2 times (p <0.01) in consultation with the school adminis- [6]. This ratio is probably related to the whereas in boys only 1.5 times (p <0.05) tration, when parents signed an informed initially large voltage of adrenergic sys- compared to children of the comparison consent to conduct this observation and tems, in extreme polar conditions, when group. Accordingly, the ratio of СA / study. the child’s organism is to some extent Ser. in boys of the main group, it was The exclusion criterion from the study protected from the effect of their excess, lower by 3.8 times (p <0.01), and in girls was deviations in the condition of the by accumulating catecholamines mainly it was only 2.5 times lower (p <0.01) rel- children and the disagreement of the chil- in the blood cells. ative to the children of the comparison dren and the parents. The inclusion of a multivitamin com- group. Thus, the ratio of СA / Ser. in boys As a means for prophylactic vitamini- plex in the diets of children of the Po- 2 times lower (p<0.01) than in girls of the zation, a multivitamin complex containing lar region, made it possible to identify main group (Table 1). basic vitamins was used, whose compo- the dependence of the variability of the By themselves, these facts indicate a sition is close to the physiological daily morphofunctional parameters of the impossible decrease in the rate of capture of needs of school-age children [4]. The mune system on the sex of the child. СA by lymphocytes or a decrease in their composition of one multivitamin bean After vitaminization in children of the synthesis by cells. On the other hand, the contains the following components: vi- main group of Norilsk, revealed a de- level of monoamines characterizes sexu- tamins − A − 3300 IU (200% of daily crease in the content of СА and an inal dimorphism of the reactivity of immune − − need); B1 0.002 g (133%); B2 0.002 crease in the level of serotonin in blood cells in schoolchildren of the Far North. − − g (153%); B6 0.003 g (143%); B12 lymphocytes were found relative to the The decrease in this ratio in children of 0.000002 g (6.7%); PP − 0.02 g (100%); indicators of children in the comparison the North after vitaminization indicates a P − 0.01g (6.7%); E − 0.01 g (56%); C − group (Table 1). So, when comparing change in the balance of neurotransmit- 0.075 g (107%); folic acid − 0.00007 g the degree of decrease in the content ters, which play a huge role in the pro- (17.5%) and calcium pantothenate 0.03 in the lymphocytes of СA, it was found cess of human adaptation to the condi- g (60%). that in boys of the main group, the level tions of the North. The study showed that After vitaminization, the children took of СA decreased by 2.6 times (p <0.001), the use of multivitamins selectively mod- blood from a finger. On blood smears us- whereas in girls only 1.5 times (p <0.01) ulates the activity of peripheral monoami- ing the fluorescent-histochemical meth- relative to children comparison groups. nergic structures, od of H. Yokoo et al. (1982) modified Thus, after taking multivitamins in boys Analysis of hematological parameters by V.P. Novitskaya (2000), the content of the main group, the level of CA was obtained by us (Table 2) in children of of monoamines, catecholamines (CA) and serotonin (Ser.) [6] was determined Table 1 in lymphocytes. The level of catecholamines and serotonin was expressed in he content of monoamines in the blood lymphocytes of children of two schools in conventional units (cu) and the ratio of Norilsk after vitaminization (X ± x) catecholamines: serotonin (CA / Ser.) was calculated. Main group Comparison group The hematological method deter- Indicator Girls Boys Girls Boys mined the composition of blood leuko- n=15 n=15 n=15 n=15 ± cytes in percent (leukocyte formula): Catecholamines (cu) 42.0 3.57** 24.5± 1.9*** 62.2± 3.99 63.93± 3.23 Serotonin (cu) 130.8± 21.34** 127.7± 12* 65.86± 6.14 85.2± 5.11 eosinophils,%, basophils,%, band СA / Ser. 0.42± 0.09*** 0.21± 0.02** 1.05± 0.11 0.8± 0.07 neutrophils,%, neutrophils,%, lymphocytes,%, monocytes,%. As an in- Note. In the Tables 1 and 2 statistically significant differences between the groups of children tegration test, the adaptation index taking vitamins (main group) and the comparison group: * р<0,05; ** р<0,01; ***р<0,001. Garkavi was used, calculated the ratio of lymphocytes:neutrophils. Statistical Table 2 processing was performed using the software package “Statistica v. 6.1”. The data are presented as X ± x, where X – is the Leukocyte blood counts in children from two schools in the city of Norilsk after arithmetic average, x – is the average er- vitaminization (X ± x) ror. The Mann – Whitney U-test was used to estimate the difference between the Группа основная Группа сравнения average in pairwise unrelated samples, Показатель девочки мальчики девочки мальчики the difference of values was considered n=15 n=15 n=15 n=15 significant at p <0.05. Eosinophils, % 5.3± 1.31 4.47± 0.82 4.2± 0.93 5.53± 0.65 Basophils, % 0.3± 0.16* 0.31± 0.11 1.13± 0.28** 0.26± 0.12 Results and discussion. Studies Band neutrophils, % 4.7± 0.12* 4.15± 0.11* 3.13± 0.15 2.53± 0.12 have shown that changes in the morpho- Neutrophils, % 40.9± 1.74 39.73± 2.02 41.93± 1.79 43.4± 1.68 logical and functional parameters of the Lymphocytes, % 46.5± 1.69 50± 1.92 48.13± 1.49 47.06± 1.87 cells of the immune system in the exam- Monocytes, % 2.3± 0.38** 1.26± 0.2 1.46± 0.28 1.2± 0.2 ined groups of children are characterized Lymphocytes : 1.16± 0.08 1.34± 0.1 1.19± 0.01 1.12± 0.08 by significant differences (Table 1). First Neutrophils 3’ 2019 87

the alien population of the Polar region usually occurs during acute or moder- Monoaminergic regulation of blood formation un- (comparison group) showed that the ate chronic stress. The development of der extreme conditions. Byulleten' eksperimental'noj biologii i mediciny. 2011; 151(2): 132−139. characteristic of the cellular composition neutrophilic leukocytosis is mainly asso- (In Russ)]. of peripheral blood is mainly subject to ciated with an increased intake of bone 3. Практические аспекты диагностики и patterns, studied in detail and well known marrow or vascular neutrophils from лечения иммунных нарушений: руководство in the literature. In these groups, high val- the cellular reserve into the circulation, для врачей. Козлов В.А., Борисов А.Г., Смир- ues of the Garkavi adaptation index are which are recruited by glucocorticoid and нова С.В. [и др.]. Новосибирск: Наука, 2009: 274. [Practical aspects of the diagnosis and recorded, which correspond to the reac- monoamines. According to modern con- treatment of immune disorders: a guide for phy- tion of increased activation of the organ- cepts, central adrenergic, dopaminergic sicians. Kozlov VA., Borisov AG., Smirnova SV. ism. and serotonergic structures play a co- [et al.].Novosibirsk: Nauka 2009: 274. (In Russ)]. The shift in the level of neurotransmit- ordinating role in the implementation of 4. Методические рекомендации. Нормы the response of the blood system to the физиологических потребностей в энергии и ters we noted after prophylactic vitamini- пищевых веществах для различных групп zation is also reflected in the composition effects of extreme irritants of various eti- населения РФ. МР 2.3.1. 24-32-08 от 18 декабря of the leukocyte formula. (Table 2). The ologies [2]. 2008. Вопросы детской диетологии. 2011; initial structure of the blood composition In addition, in the main group of girls, 9(6):62 −76. [Guidelines. Norms of physiological indicators (the comparison group) by an increase of 45.2% (p<0.01) in the per- needs for energy and nutrients for various groups centage of monocytes relative to the main of the population of the Russian Federation. MR gender did not significantly differ among 2.3.1. 24-32-08 dated December 18, 2008. Vo- schoolchildren in the Polar region. We group of boys was established (Table 2) prosy detskoj dietologii 2011; 9(6): 62−76. (In can only note that in the comparison After vitaminization in the main groups Russ)]. group girls, the level of basophils is 80% of schoolchildren, high values of the 5. Национальная программа по оптими- (p<0.01) higher than in boys. Such a Garkavi adaptation index were also ob- зации обеспеченности витаминами и мине- ральными веществами детей России: (и structure of blood parameters, apparent- served, which correspond to the reaction использованию витаминных и витаминно- ly, can be regarded as one of the variants of increased activation of the organism. минеральных комплексов и обогащенных of regional specificity. Conclusion. The research results продуктов в педиатрической практике) / Союз We found that after vitaminization showed the complexity and multivariabili- педиатров России [и др.]. М.: ПедиатрЪ. 2017: ty of the functioning of the immune system 152. [National Program on Optimization of the there are differences in the leukocyte Provision of Vitamins and Minerals of Russian formula between girls and boys. Thus, in of schoolchildren in the conditions of the Children: (and the use of vitamin and vitamin-min- the girls of the main group, a decrease Far North after the inclusion of multivita- eral complexes and fortified products in pediatric in the basophil content by 3.76 times (p mins in the diets. A change in the balance practice) Union of Pediatricians of Russia [et al]. <0.05) relative to the girls of the compar- of regulatory indicators in schoolchil- M.: Pediatr. 2017: 152. (In Russ)]. dren's lymphocytes, which can change 6. Новицкая В.П. Модификация метода ison group was revealed. It is known that определения моноаминов в лейкоцитах на there is a close functional relationship the functional activity of these cells, has мазках периферической крови. Клиническая between peripheral blood basophils and been established. The decrease in the лабораторная диагностика. 2000; 1: 24,33. [No- tissue basophils. It is noticed that with a level of СА and the increase in the se- vitskaya VP. Modification of the method for the rotonin content are associated not only determination of monoamines in leukocytes on decrease in cells of one type, the number peripheral blood smears. Klinicheskaya labora- of cells of another type increases [3]. Ac- with the effect of the vitamin complex on tornaya diagnostika. 2000; 1: 24.33. (In Russ)]. tivation of tissue basophils is usually ac- biochemical mechanisms, the synthesis 7. Шевченко И. Ю. Научное обоснование companied by the release of biologically and decomposition of monoamines, but коррекции питания и пищевого статуса детей active components, such as serotonin also with the state of the metabolic and школьного возраста Красноярского края: regulatory systems of the inhabitants of автореф. дисс…. д-ра мед. наук Кемерово, [3]. Confirmation of this, we see that after 2009: 33. [Shevchenko IYu. Scientific rationale vitaminization in the lymphocytes of chil- the North. for the correction of nutrition and nutritional status dren in the main group of Norilsk, the lev- Vitaminization among schoolchildren of school-age children in the Krasnoyarsk Territo- el of serotonin was higher than in children of the Polar region significantly changes ry: author. diss ... Dr. med Sciences. Kemerovo. of the comparison group. the balance of the cellular elements of 2009: 33. peripheral blood in children in this region. 8. Chavan SS, Tracey KJ. Essential Neurosci- Along with a change in the balance ence in Immunology. J. Immunol. 2017; 198 (9): of neurotransmitters after taking multivi- 3389 – 3397. DOI: 10.4049/jimmunol.1601613 tamins in children of the main group, a References 9. Suboptimal micronutrient intake among change in the percentage of band neutro- children in Europe. Kaganov В, Caroli М, Mazur А, Singhal А, Vania А. Nutrients. 2015; 7(5): 1. Васильев А.В. Каспаров Э.В., Прахин phils was revealed. In both girls and boys 3524 − 3535. DOI: 10. 3390/nu7053524 Е.И. Перспективные задачи оптимизации of the main group, an increase of 1.5- 10. Nicholson LB. The immune system. питания на основе современных методов Essays Biochem. 2016; 60 (3): 275 − 301. 1.6 times (p<0,05) was observed in the оценки пищевого статуса и энерготрат. percentage of band neutrophils relative Вопросы детской диетологии. 2010; 8(3): 44- DOI:10.1042/EBC20160017 to the children in the comparison group. 46. [Vasilyev AV, Kasparov EV, Prakhin EI. Per- 11. Sichet-Hellert W, Kersting M. Vitamin and mineral supplements use in German children and The increased level of band neutrophils spective tasks of optimizing nutrition based on modern methods of assessing food status and adolescents between 1986-2003: results of the in the blood indicates the activation of energy expenditure. Voprosy detskoj dietologii. DONALD study. Ann.Nut.Metab. 2004; 48 (6): bone marrow cells to enhance prolifera- 2010; 8(3): 44-46 (In Russ).]. 414− 419. DOI: 10. 1159/000083574 tion and mitotic activity, probably due to 2. Дыгай А.М., Скурихин Е.Г. Моноами- 12. Use of multiple micronutrient powders for point-of-use fortification of foods consumed by multivitamins. нэргическая регуляция кроветворения при экстремальных воздействиях Бюллетень infants and young children aged 6–23 months The results described clarify the idea экспериментальной биологии и медицины. and children aged 2–12 years. WHO. 2016: 60. that an increase in band neutrophils 2011;151(2):132-139. [Dygai AM, Skurikhin EG. Licence: CC BY-NC-SA 3.0 IGO. 88 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

S.N. Kolomeichuk, A.V. Morozov, D.A. Petrashova, V.V. Pozharskaya, E.B. Stafeeva1, I.A. Vinogradova, M.V. Bochkarev, B.A. Tarasov DAYTIME SLEEPINESS AND SLEEP PARAMETERS IN CHILDREN LIVING DOI 10.25789/YMJ.2019.67.26 IN THE EUROPEAN NORTH OF RUSSIA

Parameters of sleep and excessive daytime sleepiness were studied in 601 children aged 7-12 years living in the Arctic zone of Russia. No gender differences in daytime sleepiness were found. Our work also found the delay in bedtime onset for most children 7-12 years old. Self-questionnaires revealed awakenings in the middle of the night in almost half of the children, and insomnia was mild or moderate in 43.3% of the examined children in the European North of Russia. We have shown that children’s age affects the level of daytime sleepiness. Consequently, older children must sleep more than younger ones to achieve the same level of alertness and cognitive ability. Thus, children compensate for lack of sleep during the next day via daytime nap. Keywords: daytime sleepiness, chronotype, children, Arctic, children, age, sex, sleep duration.

Introduction. Sleep parameters are showed that the phase of the sleep-wake of the Institute of Biology of the Karelian determined by a number of biological, rhythm (chronotype) of a person is de- Scientific Center of the Russian Acad- environmental and social factors [3]. In termined by the time of sunrise [18]. emy of Sciences and by the Joint Ethics modern society people spend a signifi- With the growth of industrialization of Committee on Medical Ethics under the cant part of their time in a closed space, society, the difference between social Ministry of Health of the Republic of Ka- so it is logical to assume that the signals and biological clocks is growing. Among relia (Protocol No. 41 from 08.01.2018). of social time play a major role in syn- the population of megacities, the fre- All respondents or their legal representa- chronizing the rhythm of sleep-wakeful- quency of detecting individuals with a tives were informed with the purpose of ness. On the other hand, a recent study late chronotype, which is characterized the upcoming study and signed an in- by desynchronization of the circadian formed consent to participate in it. Ques- system, called the “social jet lag” [2], tionnaires were distributed to students by KOLOMEICHUK Sergey Nikolaevich Cand. is increased. For this reason, individu- teachers or school psychologists. Incom- Sci. (Biol.), Senior Researcher Laboratory of als with a late chronotype exhibit lower plete questionnaires and questionnaires Genetics, Institute of Biology of the Karelian school performance [14] and are prone with several answers instead of one were Scientific Center of the Russian Academy to consume stimulants 2]. At school age, excluded from the analysis. of Sciences, Petrozavodsk, Russian most children retain a sleep duration of At the preliminary stage, we conducted Federatrion: sergey_kolomeychuk@rambler. 10–11 hours, however, increased edu- a study to assess the reliability and valid- ru; MOROZOV Artem Vladimirovich leading biologist Institute of Biology of the Karelian cational and physical activity can neg- ity of the Russian version of the children's Scientific Center of the Russian Academy of atively affect a child’s sleep. These dis- daily sleepiness scale (PDSS-RUS) [17]. Sciences, Petrozavodsk, Russian Federation orders often come in conjunction with Further, in the framework of the project, [email protected]; STAFEEVA attention deficit hyperactivity disorder in a sample of schoolchildren it was pro- Elena Borisovna Leading biologist Institute (emotional reactions and cognitive im- posed to evaluate the occurrence of vari- of Biology of the Karelian Scientific Center pairment) [1]. Studies of daytime sleep- ous sleep disorders and to identify the of the Russian Academy of Sciences, iness of schoolchildren in different coun- relationship of sleep characteristics with Petrozavodsk, Russian Federation bio@ tries revealed a rather high frequency of various lifestyle factors. Assessed: de- krc.karelia.ru; PETRASHOVA Dina Aleksandrovna Cand. Sci. (Biol.), Senior spread, especially during puberty, from mographic data, lifestyle, school perfor- Researcher, Head of the Laboratory of 51% in Turkey [15] to 63% in Japan [12] mance and the self-adminstered scale of the medical and biological technologies, and 68% in Canada [20]. In Russia, this daytime sleepiness in children (Pediatric Kola Science Centre, Russian Academy of problem has hardly been studied among Daytime Sleepiness Scale). Each re- Sciences, Apatity dinapetrashova@mail. schoolchildren of primary school age. spondent was asked to answer questions ru; POZHARSKAYA Viktoria Viktorovna The aim of our work was to study the regarding personal data, as well as fill out Cand. Sci. (Biol.), researcher Research influence of various factors on excessive a questionnaire: Munich Chronotype As- Center for Biomedical Problems of Human daytime sleepiness of children and ado- sessment Test (MCTQ). Questionnaires Adaptation in the Arctic, Kola Science Centre, lescents living in the north of the Europe- were processed according to the work Russian Academy of Sciences,, Apatity vvp@ medknc.ru; VINOGRADOVA Irina A. Doctor an part of Russia. of MCTQ [18]. The chronotype was ex- (Biol), Professor, Head of Dept Human & Materials and methods. The study pressed as the middle of the sleep phase Animal Physiology, Pathology, Histology, was conducted in 2018 among students on the day off in hours, adjusted for the Medical Institute, Petrozavodsk State of grades 1-6 of secondary schools locat- "duty" of sleep accumulated over the University, Petrozavodsk, Russian Federation ed in 8 settlements of the European North school days. The higher the value of the [email protected]; BOCHKAREV of the Russian Federation: in the Repub- indicator, the more a person belongs to Mikhail V. junior research associate Almazov lic of Karelia - Petrozavodsk, Kem, Ko- a later chronotype. The average weekly National Medical Research Centre, St. stomuksha, Vidlitsa, Rabocheostrovsk; sleep duration was calculated. Petersburg, Russian Federation; TARASOV in the Murmansk region - Apatity, Olene- Statistical processing was performed Boris A. Cand. Sci. (Biol.), Head of Expert Board Project Office for Arctic Development gorsk, Umba. The research program was in the PAST package (PALEONTOLOGI- PORA Moscow, [email protected] approved by the Committee on Bioethics CAL STATISTICS SOFTWARE PACK- 3’ 2019 89

AGE FOR EDUCATION AND DATA 0.02). This suggests that children com- а ANALYSIS, Norway). pensate for the lack of drinking during Results and discussion. The aver- the next day due to daytime sleep. Our age age of the children was 10.62 ± 2.87 work also shows a delay in bedtime for years. Table 1 presents information on most children 7-12 years old. According the sex and age composition of the re- to self-questionnaires, awakenings were spondents. In the questionnaires, the an- revealed in the middle of the night in al- swers to the questions corresponded to most half of the children, and in 43.3% the normal distribution, and the average of the examined children in the European total score was 11.95 ± 6.2. We did not North of Russia insomnia is expressed find gender differences on the daytime in mild or moderate degree (Table 2). sleepiness scale. The reliability and reli- In all the settlements of the European ability of the PDSS-RUS questionnaire North of the Russian Federation, where is validated and confirms its one-factor we conducted studies, it was found that б structure. The Russian version of PDSS daytime sleepiness increased with age can be used in our study to assess sleep (Fig. 1A). This fact is consistent with ear- hygiene among Russian children and lier studies for various ethnic groups [12, adolescents [17]. 4]. Thus, older children must sleep more Most of the surveyed children showed than younger children in order to achieve excess daytime sleepiness within nor- the same level of alertness and cognitive mal limits (less than 16 points on the ability [16, 20, 6]. Feinberg and Camp- PDSS scale). Significant differences in bell suggested an alternative hypothesis the level of drowsiness were found in - increased drowsiness in adolescents in children of primary school age, both in the daytime is a consequence of the re- northern Karelia and in the Murmansk reorganization of their brain, which reduces gion (PDSS (May) M ± m (11.95 ± 6.24) the intensity of activity of the waking brain versus PDSS (February) M ± m (12.75 [11]. Surprisingly, these brain changes Fig. 1. Dynamics of infant drowsiness in chil- ± 6.06, p <0.05) .For the group of indig- are not associated with puberty, but are dren of the European North of the Russian enous people of the same age category, reliably associated with age. Also, as a Federation: a- age dependence, b – season dependence there is a tendency to increase this indi- result of our research, it was found that cator (PDSS (May) M ± m (12.01 ± 5.72) gender is not associated with daytime as well as for monitoring the monitoring of versus PDSS (October) M ± m (12.79 ± sleepiness. side effects of sleepiness treatment [13, 5.79, p> 0.05), respectively ) (Fig. 1B). In In most studies, PDSS was used as a 7]. In several works, the authors used a addition, there was an inverse correlation tool for assessing drowsiness associated questionnaire to assess healthy children for the duration of sleep with estimates with sleep pathologies (respiratory, neu- and adolescents [21, 19, 22]. In a number of the drowsiness scale (r = -0.122, p = rological and developmental disorders), of works, scores ranged from 6.7 to 25.7, showing a tendency to excessive drowsi- Table 1 ness in the daytime. In addition, higher PDSS scores were associated with de- Sample parameters creased overall sleep time, poor school performance, and frequent illnesses in Variable Result different countries [18, 19]. The values Sex, 321 / 280 (51.3 % / 48.7 %) obtained by us for the PDSS scale cor- male/female, n (%) respond to published data for healthy Age, n (%) 42 (6.9%) 7 years 135 (22.6%) 8 years Table 2 111 (18.5%) 9 years 118 (19.6%) 10 years 124 (20.6%) 11years Sleep disorders in children living in the European North of 71 (11.8%) 12 years the Russian Federation, identified in the study (n = 601) Physical activity 421 (70 %) 1-2 per week Low subjective sleep assessment, n (%) 341 (56.7) 90 (15%) Every day 90 (15%) Night awakenings, n (%) 360 (58.3) Rarely Duration of falling asleep, n (%) Caffeine consumption, n (%) 120 (19.9 %) 0-15 min 180 (30) Daily 331 (55 %) 15-30 min 350 (58.3) Rarely 150 (25.1 %) 30-60 min 51 (8.4) Never >60 min 20 (3.3) Alcohol consumption, n (%) 40(6.7%) Daytime sleepiness, n (%) 92 (15) Often (every week) 561(93.3%) Never Insomnia severity scale, n (%) Smoking, n (%) None 341 (56.7) 110 (18.3%) Yes Light 220 (36.6) 491(81.7%) No Moderate 40 (6.7) 90 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

children from the USA [9], Argentina [19], 2. Roenneberg T, Kuehnle T, Juda M et al. A Japanese version of the Pediatric Daytime Sleep- China [5] and Italy [9]. It should be not- marker for the end of adolescence. Epidemiology iness Scale (PDSS-J). Chronobiology Int. 2016; of Human Circadian ClockSleep Med Rev. 2007; 33: 1311-1319. ed that the average age in this sample 11 (6): 429-38. 13. Pereira EF, Teixeira CS, Louzada FM. was 10.62 years. This fact explains why 3. Roenneberg T, Kuehnle T, Pramstaller PP Sonolência diurna excessiva em adolescentes: in our study, scores on the PDSS scale et al. A marker for the end of adolescence. Cur- Prevalência e fatores associados. Rev. Paul Pe- are slightly lower than in studies on the rent Biology. 2004; 14:1038-1039. diatr. 2010; 28 (1): 98–103. drowsiness of Brazilian [10] or Argentine- 4. Perez-Lloret S, Videla AJ, Richaudeau A et 14. Randler C, Kolomeichuk SN, Morozov AV al. A multi-step pathway connecting short sleep et al. Psychometric characterization of the Rus- an children [4]. duration to daytime somnolence, reduced atten- sian version of the Pediatric Daytime Sleepiness Conclusion. We have shown that tion, and poor academic performance: an explor- Scale (PDSS). Heliyon. 2019; 5 (7): е02134. doi: the age of the child affects the level of atory cross-sectional study in teenagers. J Clin 10.1016/j.heliyon.2019.e02134 daytime sleepiness, which, in turn, cor- Sleep Med. 2012; 9: 469-473. 15. Bektas M, Bektas I, Ayar D et al. Psycho- responds to the level of sexual develop- 5. Gau SS-F, Shang C-Y, Merikangas KR et al. metric properties of Turkish version of Pediatric Association between morningness-eveningness Daytime Sleepiness Scale (PDSS-T). Asian Nurs ment. Consequently, older children must and behavioral / emotional problems among ado- Res. (Korean SocNurs Sci.). 2016; 10 (1): 62-67. sleep more than younger children in or- lescents. Journal of Biological Rhythms. 2007; 16. Randler C, Frech D. Correlation between der to achieve the same level of alertness 22: 268-274. morningness–eveningness and final school leav- and cognitive ability. Thus, children com- 6. Carskadon MA, Acebo C, Jenni OG. Regu- ing exams. Biol. Rhythm Res. 2006; 37: 233–239. pensate for lack of sleep during the next lation of adolescent sleep: implications for behav- 17. Rhie S, Lee S, Chae KY. Sleep patterns ior. Ann N Y Acad Sci.. 2004; 1021: 276–91. and school performance of Korean adolescents day due to daytime sleep. 7. Randazzo AC, Muehlbach MJ, Schweitzer assessed using a Korean version of the pediatric Acknowledgements. This work was PK, Walsh JK. Cognitive function following acute daytime sleepiness scale. Korean J Pediatr. 2011; supported by budget topics (No. 0218- sleep restriction in children ages 10–14. Sleep. 54 (1): 29-35. 2019-0077), (No. 0218-2019-0073), 1998; 6 (21): 861– 865. 18. Roenneberg T, Merrow M. Entrainment (No. 0226-2019-0064), (No. 0186-2019- 8. Maganti R, Hausman N, Koehn M et al. Ex- of the human circadian clock. Cold Spring Harb. cessive daytime sleepiness and sleep complaints Symp. Quant. Biol. 2007; 72: 293–299. 0009). Also, the work was supported by a among children with epilepsy. Epilepsy Behav. 19. Perez-Chada D, Perez-Lloret S, Videla grant from the Expert Council of the Au- 2006; 8 (1): 272-277. AJ et al. Sleep disordered breathing and daytime tonomous Non-Commercial Organization 9. Esposito M, Antinolfi L, Gallai B et al. Ex- sleepiness are associated with poor academic (Arctic Project Development Office). ecutive dysfunction in children affected by ob- performance in teenagers. A study using the Pe- The research was carried out using structive sleep apnea syndrome: an observational diatric Daytime Sleepiness Scale (PDSS). Sleep. study. Neuropsychiatr Dis Treat. 2013; 9: 1087- 2007; 30: Р. 1698-1703. the equipment of the Core Facility of the 1094. doi: 10.2147 / NDT.S47287. 20. Gibson ES, Powles AC, Thabane L et al. Karelian Research Center of the Russian 10. Ferrari Junior GJ, Drake CL, Barbosa DG “Sleepiness” is serious in adolescence: two sur- Academy of Sciences. et al. Factor structure of the Brazilian version of veys of 3235 Canadian students. BMC Public Pediatric Daytime Sleepiness Scale. Chronobiol- Health. 2006; 6: 116. ogy Int. 2018; 35 (8): 1088-1094. 21. Drake C, Nickel C, Burduvali E et al. The References 11. Feinberg I, Campbell IG Sleep EEG pediatric daytime sleepiness scale (PDSS): sleep changes during adolescence: an index of funda- habits and school outcomes in middle-school chil- 1. Полуэктов M.Г., Пчелина П.В. Сон у детей mental brain reorganization. Brain Cogn. 2010; 72 dren. Sleep. 2003; 26 (455): 8. от физиологии к патологии. Медицинский совет. (1): 56-65. doi: 10.1016 / j.bandc.2009.09.09.008. 22. Felden EP, Carniel JD, Andrade RD et 2017; №9: 97-102. [Poluektov MG, Pchelina PV 12. Komada Y, Bregelmans K. Social jetlag al. Tradução e validação da Pediatric Daytime Sleep in children from physiology to pathology. affects subjective daytime sleepiness in school- Sleepiness Scale (PDSS) para o português do Medical Council. 2017; V. 9: 97-102. (In Russ.)] aged children and adolescents: A study using the Brasil. J Pediatr (Rio J). 2016; 92: 168–173.

SCIENTIFIC REVIEWS AND LECTURES

E.R. Boyko, A.M. Kaneva INDICES OF LIPID METABOLISM FOR THE EARLY DIAGNOSIS OF CARDIOVASCULAR DOI 10.25789/YMJ.2019.67.27 DISEASE IN RESIDENTS OF THE NORTH

Cardiovascular disease is one of the leading causes of morbidity and mortality among the adult population. In Russia, over a million people (around 700 people out of each 100 thousand population) die each year from cardiovascular diseases. The high prevalence of cardiovascular disease is observed in people living in the North, whose severe climatic conditions produce increased demands for a human body. Northern climatic factors lead to significant changes in human’s physiological functions based on modified functional condition of the endocrine sys- BOJKO Evgeny Rafailovich – Doctor of tem, metabolic processes, and lipid metabolism in particular. According to L.E. Panin’s concept Medical Sciences, Professor; Head of IPh (1978), in high-latitude regions we can observe “the changeover from carbohydrate-type metab- Komi SC UB RAS, FRC Komi SC UB RAS; olism to the lipid one”. This concept states transformation of the lipid profile in residents of the e-mail: [email protected]; tel. +7-8212-24- North caused by a number of external factors frequently leading to changes in metabolic path- 14-74; ORCID ID: 0000-0002-8027-898X. ways and abnormalities in lipid metabolism. Adequate assessment and correct interpretation of KANEVA Anastasiya Mikhailovna – Doctor lipid metabolism variables are of major importance for early detection and timely prevention of in Biological Sciences; Senior Researcher of cardiovascular pathology. The review considers key lipid metabolism indices. We also present environmental and medical physiology depart- our own data about the role of compound indices in lipid metabolism assessment in healthy ment of IPh Komi SC UB RAS, FRC Komi SC inhabitants of the North. UB RAS; tel. +7-8212-24-14-74; ORCID ID: Keywords: lipid metabolism, adaptation, North, cardiovascular disease, apolipoproteins. 0000-0002-7789-4300. 3’ 2019 91

The issues related to preservation of Northern environment one can observe a digenous inhabitants, which has resulted health in the North are of great medical phase of regulatory and homeostatic pro- in disturbed adaptive processes followed and social significance. The process of cesses destabilization (from 6 months to by increased morbidity. In addition, the in- human adaptation to adverse northern over 1 year long), a phase of regulatory digenous populations of the North suffer factors is aimed at maintenance of stable and homeostatic processes stabilization adverse metabolic changes with inten- functioning of various systems separately and synchronization (10–15 years long) sified carbohydrate metabolism and in- and of a human body as a whole to en- and a phase of lowered resistance of creased atherogenic lipid levels in blood sure normal vital activities under inade- one’s body. It is considered that the stage more frequently now [3, 9, 18-20, 33]. quate environmental conditions. Trans- of resistance in residents of the North is Atherogenic disorders of lipid metab- formation of energy metabolism through explained by efficient changeover from olism play a major role in the pathogenic changeover of all types of metabolism (of carbohydrate metabolism to the lipid one. mechanism of atherosclerosis [17, 47]. lipids, proteins, carbohydrates, vitamins, Such lipid metabolism transformations At present time, atherosclerosis is one macro and microelements) plays an im- occurring throughout the “polar metabolic of the most relevant and important health portant role in the complex sequence of type” development are to be accompa- problems. Atherosclerosis mostly affects adaptive changes [6, 28, 32]. According nied by lipoprotein spectrum shifting to- aorta, arteries of heart, brain, lower limbs to the member of the Academy of Scienc- wards an increase in the number of high and kidneys. Therefore, coronary dis- es L.E. Panin [27, 28], the northerners density lipoproteins (HDL). However, ease, myocardial infarction, aortic aneu- develop a peculiar type of metabolism multiple studies showed that migrants of rism rupture, ishemic and haemorrhagic – the so-called “polar metabolic type” the North do not develop an optimal meta- stroke are among top causes of death. characterized by decreased role of car- bolic background as a rule. Contrariwise, In this connection, diagnostics and pre- bohydrates and increased role of the they develop “northern dyslipidemia” vention of lipid metabolism disorders are proteins and lipids in energy metabolism. which is reflected as increased athero- some of the most significant tasks of to- The increased significance of lipids in genic lipid fractions in blood [8, 12, 30]. day’s medicine. the energy metabolism of a human body Metabolism with predominantly pro- Currently, much attention is paid to finds its reflection in the changed lipid tein-lipid metabolism (“arctic adaptive studying the role of apolipoproteins in a profile of blood [2, 4, 6, 13, 28]. Within type”) is observed in the indigenous pop- human’s lipid metabolism. It is believed L.E. Panin’s concept, we suggest the ulations of the North. Descendants of that the analysis of the level of apolipo- term “adaptive polar metabolic type” as several generations of migrants who had proteins in health and lipid metabolism a special type of metabolism typical for been adapting to the northern environ- disorders doubtlessly bring certain ben- the adapted population of the North, in- ment for centuries possess similar ability efits, as it allows to identify accurately cluding the indigenous residents of the to switch to the northern type of metab- features and defects of lipoprotein me- Far North. Development of this “adaptive olism. For the indigenous populations of tabolism. Apolipoproteins were discov- polar metabolic type” includes forming of the North, the change of energy metab- ered more than 40 years ago. Over 10 a peculiar hormone profile and metabo- olism from the carbohydrate type to the apoproteins have been identified and de- lism ensuring comfortable living in the lipid one comes on account of exoge- scribed so far. Apolipoproteins are clas- Far North conditions in particular. For in- nous fats, i.e. food lipids [26]. In general, sified into major and minor proteins. The habitants of the North, if compared to res- the basal metabolic rate in the northern former ones include apoA, apoВ, apoC, idents of middle latitudes, such adaptive aborigines is higher than the one in the apoD, apoЕ. Minor apolipoproteins in- changes are related to the transformed residents of the middle latitudes [32]. clude apoF, apoJ, prolin-rich protein, metabolism, which is preconditioned by The protein-fatty diet in the northerners etc. [34, 39]. Depending on the key role more active basal metabolic rate in par- implies primarily the use of lipids as the performed, apolipoproteins are condition- ticular seasons of year and more short- most energy intensive utilizable materi- ally divided into two classes. One is apo- term reactions connected with some en- al and is accompanied by the increased proteins forming the micellar structure vironmental factors of the North [6]. activity of lipolytic enzymes and activated of lipoprotein complexes and serving as At present time, ideas of the regulari- lipid mobilizing processes [26, 35]. lipoprotein “nucleus”. This group of apoli- ties of adaptive processes in residents of The indigenous inhabitants of the poproteins includes apoВ (apoВ-100 and the North are based both on the studies of North following the traditional lifestyle apoВ-48) and apoА (А-I and А-II) which transformation mechanisms of physiolog- and diet with their “polar” metabolic type are responsible for afferent and efferent ical functions and biochemical processes demonstrate more favourable lipid me- transport of lipids. The other class con- in migrants, and on detection of mor- tabolism profiles with regard to the risk of tains apolipoproteins focusing on lipopro- phofunctional features in the indigenous development of a cardiovascular disease tein and lipid metabolism regulation in the populations for which the subextreme than the non-native populations of the bloodstream and their internalization by and extreme conditions of the northern North. The indigenous residents of the cells. These apolipoproteins are present regions can be considered adequate. North (Evenki Autonomous Area, Yakutia, in lipoproteins in low concentrations and The analysis of the literature on metabo- Amur River Region, Khanty-Mansi Auton- transfer between lipoprotein classes as lism in non-native residents of the North omous Area, Yamal-Nenets Autonomous protein-lipid complexes in the process of demonstrated that data on their lipid me- Area) have lower total cholesterol (TC) lipoprotein particles’ interconversion in tabolism transformation are quite various levels and its atherogenic fractions and the bloodstream. Key representatives of and often contradictory, which is proba- higher levels of HDL cholesterol (HDL-C) metabolically active apolipoproteins are bly related to the fact that most studies in blood serum than migrants of the North apoЕ with three isoforms (Е2, Е3, Е4) were carried out on migrants of the North [10, 11, 21-23, 25, 31]. and apoC (С-I, С-II, С-III) [34, 63]. Mean- found at different stages of the adapta- However, social and economic chang- while, the functional role of apolipopro- tion [1, 6, 21, 28, 31, 35]. According V.P. es of the recent decades, the inflow of teins in lipid metabolism in residents of the Kaznacheyev’s classification [13], in the migrants and urbanization have affected North has not been studied thoroughly. process of a person’s adaptation to the the traditional lifestyle and diet in the in- For the first time ever we have ana- 92 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

lyzed plasma apoЕ levels in residents of tween lipoprotein particles [71]. Unlike li- tween them have not been found out yet. the European North of Russia. It has been poprotein cholesterol, the lipid-transport- The results of our studies made it pos- established that apoE levels in residents ing apoproteins – apoВ and apoА-I do sible to enlarge today’s view about the of the North shifted towards lower values not leave the lipoprotein molecules they lipid metabolism in residents of the North [7, 16, 62]. This observation is consistent build [69]. Therefore, apoB and apoA-I and to define main indices for early de- with the results of a large international re- are assumed to be superior markers tection and monitoring of dyslipidemia search comparing apoE levels in people for lipid abnormalities. ApoB (we mean risk. The comprehensive study of the lip- residing in six European countries. Ac- apoВ-100) is an essential structural com- id profile in apparently healthy residents cording to results of this study, there is a ponent of very low-density lipoproteins of the North (157 men aged 20-59) with north-south increasing gradient of apoE (VLDL), intermediate-density lipoproteins normolipidemia (TC<5.2 mmol/l, TG<1.7 concentrations. The lowest apoE levels (IDL) and low-density lipoproteins (LDL). mmol/l, HDL cholesterol>1.0 mmol/l) were observed in residents of Finland [38, Because each particle of these lipopro- showed nonmanifest disturbances of 75]. Low apoE levels in the northerners teins contains one molecule of apoB, the lipid metabolism. Increased atheroge- can be considered as adaptive changes total atherogenic particles number can nicity of the lipid profile in subjects with providing metabolic transformation, on be accurately estimated by measuring normolipidemia occurred as a distorted the other hand, it can serve as a cause the plasma level of this apoprotein. By balance between atherogenic and an- for adverse changes in the lipid pro- contrast, apoА-I is the structural com- tiatherogenic lipoproteins and changed file. One of the key mechanisms for the ponent of antiatherogenic HDL. So, the qualitative composition of lipoproteins. “northern” dyslipidemia was determined apoВ/apoА-I ratio displays the balance The analysis of individual data revealed during the research. It has been shown between atherogenic and antiatherogen- that values above the reference limits for that a low apoE level is risk factor for ic lipoproteins in blood and serves as an the atherogenicity coefficient, Castelli 2 the development of hypertriglyceridemia early potential marker for the cardiovas- index, atherogenic index of plasma (AIP) [7]. ApoE distribution among the major cular risk [64, 70, 76, 78, 79]. and atherogenic index (ATH index) were lipoprotein classes was also studied. It Other indices (LDL-C/apoВ, TC/TG observed in 7.0-10.2% of the men with has been found that the preservation of and atherogenic index of plasma (AIP)) normolipidemia. The study subjects most constant concentration of apoE in HDL are surrogate markers of LDL particle size frequently demonstrated lower values of fraction due to its redistribution among [44, 54, 59, 77, 78]. These indices are LDL-C/apoВ (26.0%) and higher apoB/ lipoprotein classes is priority at decrease thought to indicate the presence of small apoA-I ratio (19.1%). Deviation of these of the total plasma apoE level [15]. dense LDL particles which are known indices from the reference range was ob- The levels of TC, HDL-C, low densi- to be the most atherogenic lipoproteins. served on the background of low levels ty lipoprotein cholesterol (LDL-C) and These particles are characterized by of apoE which is a regulatory protein of triglycerides (TG) are used as classic in- prolonged plasma half-life, lower resis- lipid transport system [14, 24, 52, 74]. It dicators of lipid metabolism. However, it tance to oxidative stress, affinity to pro- is known that insufficient amount of apoE has been recently established that these teoglycans, and higher penetration into leads to slower receptor-mediated elimi- conventional lipid parameters do not al- the arterial wall [66, 68]. Of note, since nation and accumulation of TG-rich lipo- ways reflect correctly the pro-atherogenic the determination of LDL-C levels in sub- proteins in blood [5, 39, 58]. In our case, potential of blood [48, 51, 73]. Cases of jects with a predominance of small dense higher levels of TG in the subjects with atherosclerosis occurrence among sub- LDL leads to significant underestimation the unfavorable LDL-C/apoВ and apoB/ jects with normal TC levels have been de- of the total amount of these lipoproteins apoA-I ratios indicated the delayed clear- scribed [60, 61, 65]. According to the liter- [69-71], it explains the need to take the ance of TG-rich lipoproteins. Thus, the ature, determination of TC and TG levels qualitative composition of this lipoprotein atherogenic changes of lipid profile ob- contributes to detection of 50% of all lipid fraction into account as well. There are served in the healthy subjects with nor- metabolism disorders only [29]. Several different views on the rationale for using molipidemia may be due to disturbances computed indices have been defined in the LDL-C/apoB ratio as a marker of LDL in catabolism and metabolic turnover of an attempt to raise the clinical benefit particle size. Some authors found high lipoproteins. Decrease of regulatory ef- of lipid metabolism indicators [56, 80]. correlation between LDL-C/apoB values fect of apoE on lipoprotein metabolism in There are several types of lipid indi- and the measured LDL particles’ size healthy subjects at early stages is latent ces. Some indices reflect the balance be- [43, 54, 57, 77], while the others do not and it does not appear as hyperlipidemia. tween atherogenic and anti-atherogenic recommend using this ratio as marker of The LDL-C/apoВ and apoB/apoA-I ratios lipids, these include atherogenicity coeffi- small dense LDL particles [40, 53]. are more sensitive indices compared to cient, Castelli 1 (TC/HDL-C) and Castelli Clinical studies globally widely use conventional indicators and are capable 2 (LDL-C/HDL-C) indices, apoB/apoA-I lipid metabolism indices to characterize to detect atherogenic changes of the lipid ratio, and atherogenic index (ATH index). lipid profile changes in case of various profile even in case of normolipidemia. Their predictive capacity has been proved pathologies or to monitor the results of In general, it should be noted that the by many clinical examinations [36, 37, 47- hypolipidemic or hormone replacement results of our own studies indicate the 49, 50, 55, 56]. Meanwhile, of these, the therapy, as well as in prospective epide- necessity to conduct determination of apoB/apoA-I ratio is the best marker of miology research aimed at detection of the apolipoprotein levels and calculation cardiovascular risk. The common method predictive factors of atherosclerosis and of compound lipid indices in addition to for assessing lipoprotein levels in blood related cardiovascular diseases [41, 42, the conventional indicators of lipid me- by measuring cholesterol content in them 45-47, 54, 67, 72, 80]. At the same time, tabolism, which makes it possible to de- does not always reflect the exact number usefulness of composite indices in the tect metabolic disorders at early stages. of lipoproteins adequately. It is related to overall evaluation of lipid metabolism in Deviation of lipid metabolism indices the fact that the amount of cholesterol healthy subjects has hardly been stud- from the reference range in case of nor- within lipoproteins may vary widely due to ied. The variation range for lipid metab- molipidemia can be considered as early active exchange of lipid components be- olism indices and functional relations be- predictor of metabolic transformations 3’ 2019 93

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O.L. Moskalenko, O.V. Smirnova, E.V. Kasparov DOI 10.25789/YMJ.2019.67.28 OBESITY IN VARIOUS ETHNIC POPULATIONS

This article presents a review of the literature. The authors conducted a scientific search on the epidemiology of obesity and overweight in different ethnic groups, using the relevant keywords, on the search engines PubMed and Google Scholar, on the Scopus, Web of Science, MedLine, The Global Health databases, CyberLeninka, eLIBRARY.RU and others. Obesity is widespread among children, adolescents and adults. Most of the epidemiological studies conducted to identify obesity and overweight used the most accessible method - the determination MOSKALENKO Olga Leonidovna, senior of body mass index (BMI). Data on ethnic origin can provide additional information for a person- researcher, candidate of biological sciences, alized prognosis; to date, there is no single classification for obesity and overweight forAsians. Federal State Budgetary Scientific Institution Keywords: obesity, overweight, body mass index, ethnos, population, prevalence, compli- «Scientific Research Institute of medical prob- cations. lems of the North», Krasnoyarsk, Krasnoyarsk territory (krai), Russia, 660022, 3g, Partizan Zheleznyaka str., Krasnoyarsk, Russia, E-mail: Obesity is an increase in body fat, ations (psychogenic overeating), hormo- [email protected], тел. 8-923-289-96-25; leading to the appearance of overweight, nal drugs, a sedentary image life (motor SMIRNOVA Olga Valentinovna, MD, Head of the Laboratory of Clinical Pathophysiology, is a common chronic metabolic disease mode must be combined with proper nu- Research Institute of Medical Problems of the in Russia and the world that occurs at trition and the rejection of bad habits). North, Federal State Budgetary Scientific Insti- any age. Currently, there is an increase Overweight is not only a socio-eco- tution «Scientific Research Institute of medical in overall morbidity and mortality from nomic and cosmetic problem, but primar- problems of the North», Krasnoyarsk, Kras- complications (metabolic syndrome, type ily a medical one. It is proved that the noyarsk territory (krai), Russia, 660022, 3g, 2 diabetes, liver steatosis, arterial hyper- greater the body weight, the lower the Partizan Zheleznyaka str., Krasnoyarsk, Rus- tension, IHD, etc.) in this condition. life expectancy due to the development sia, е-mail: [email protected]; KASPAR- It is well known that the causes of of serious diseases. In this regard, sig- , MD, professor, OV Eduard Vilyamovich obesity are: hereditary predisposition nificant efforts of modern endocrinology Director Federal State Budgetary Scientific Institution «Scientific Research Institute of (increased activity of lipogenesis en- are aimed at studying the causes and medical problems of the North» Krasnoyarsk, zymes and reduced activity of lipolysis mechanisms of the development of over- Krasnoyarsk territory (krai), Russia, 660022, enzymes), failure to follow the mode and weight and obesity [3; 12; 13] and their 3g, Partizan Zheleznyaka str., Krasnoyarsk, nature of nutrition (frequent, excessive correction. Russia, e-mail: [email protected]. food), endocrine disorders, stressful situ- The epidemiology of obesity depends 3’ 2019 95

on the characteristics of ethnic groups, Currently, the complex effect of genet- Abdominal obesity and body mass in- many complications directly correlate ic, geographical, socio-economic factors dex of the elderly (Yakuts) of elderly and with ethnicity. behind ethnic groups has been proven. senile age were recorded less than those In this regard, the study of the preva- Over the past few years, there has been of non-indigenous (Caucasians), and lence of obesity in various ethnic popu- a deterioration in the quality of life of patients who were not overweight, ab- lations is one of the urgent problems of small peoples living in conditions of the dominal obesity and metabolic syndrome modern medicine. Russia, being a mul- North and Siberia. Compared to the Rus- were observed equally in indigenous and tinational state, is characterized by a sians, the Buryat population is character- non-indigenous [nineteen]. large ethnocultural diversity. The struc- ized by a favorable course of diabetes, Obesity in the Chuvash Republic is ture of the Russian Federation includes cardiovascular diseases, arterial hyper- (5.5-39.1%) depending on the area of 85 subjects: 46 - regions, 22 - republics tension [5]. residence. The prevalence of obesity in 9 - edges, 3 - cities of federal value, 4 When examining the population of the Chuvash Republic is lower than in the - autonomous regions, 1 - autonomous Kyrgyz nationality, it was established that Russian Federation, the author explains region. There are about 157 thousand in this ethnic group the ATP III (2005) this by an ethnic factor: for the most part, settlements in the country. classification is the optimal classification the incidence among Chuvash ethnic In Russia, more than 2 million people for diagnosing MS. [20]. groups, who live in this region is about are obese, and patients with overweight For comparison, in the population of 70% of the population, for the Russian are even more, each year the problem Novosibirsk 45-69 years old, the preva- population is comparable to the preva- only increases. lence of abdominal obesity according to lence of obesity in other regions of Russia. This review analyzes scientific studies the NCEP ATP III criteria (2001) is only Factors affecting the formation of obesity: on the epidemiology of obesity in various 43%, according to the criteria of VNOK Russian ethnic group, female gender, ethnic populations and, depending on the (2009) 65% and according to the crite- city residence, age over 50 years [7]. place of residence, urban or rural popula- ria of IDF (2005), IDF and AHA / NHLBI According to the results of several tion. (2009 ) 67% [17, 8]. studies, it was established that all pa- The prevalence of obesity in the world The prevalence of metabolic syn- tients with arterial hypertension of the according to WHO (2016) is 11% in men drome increases significantly with age Russian and Mordovian nationalities, and 15% in women older than 18 years and has gender, ethnic and regional dif- regardless of gender, had a predisposi- and 39% of men and 40% of women ferences, with a significant role played by tion to overweight according to the defini- were determined to be overweight. age and ethnicity. The IDF criteria (2005) tion of BMI. This indicator was increased According to the results of studies emphasize the relevance of research in in 29.1% of Russian women and 33.0% conducted in the Republic of Buryatia in various ethnic groups in order to further in the Mokshan ethnic group, 22.9% adolescents of ethnic groups in rural ar- refine the criteria [9]. Erzyan, which made it possible to iden- eas, it was revealed that, regardless of Ethnic differences are revealed not tify overweight. Obesity was observed their ethnicity, the risk factors for obesity only in MS, but also in normal body in 64.1% of Russian women, 57.8% of and overweight are the presence of overweight [22]. moksha and 66.7% of Erzi. In men with weight in the mother and the irregular To this day, there is no classification hypertension, BMI was increased in nutrition of adolescents. Risk factors for of obesity and overweight for Asians. 25.6% of Russians, 38.9% of mokshan adolescents of indigenous Asian ethnic For example, for residents of Thailand and 35.5% of Erzyans, and with obesity, groups (Buryats and Soyots) and Slavic they apply their own criteria, for the Ko- respectively, in 56.4%, 41.7% and 45.2% ethnic groups can be social factors, such rean subpopulation - their own. Repre- [4]. Thus, in the population of the Kyrgyz as children living in single-parent fami- sentatives of various Asian ethnic groups Republic, abdominal obesity is 52.3%, for lies, and in families where mothers do not (Buryats, Yakuts, etc.) live on the territory women, abdominal obesity and arterial work [16]. of our country, so there are difficulties hypertension are typical, for men, hyper- The prevalence of obesity and diabe- with the use of the classification [2]. triglyceridemia is observed [15]. tes in various ethno-social populations The Asian population is characterized In European countries, the prevalence of the urban and rural populations of the by a large amount of fat with a low BMI of metabolic syndrome in the general European Far North and the territories and waist circumference [23, 27]. population is 3-4 ‰ at the age of 18 to equated to the Far North from 1996 to It has been established that in women 40 years, in Russia this figure rises to 2006 was reported in studies [1]. It has of the Far North, the prevalence of obe- 5.5 with a tendency to increase after 40 been established that among the rural sity is 34.7%, the metabolic syndrome years [24-26]. inhabitants of the European North, obe- is 14.6% and is more often recorded in The indigenous population of the Bai- sity is more pronounced among the lo- non-indigenous women. The abdominal kal region has a high degree of adaptation cal Russians of the Far North compared type of distribution of adipose tissue with to the region in which they live relative to to the Komi who live in the territories of low lipid metabolism was observed in the alien population. The representatives the Far North. The Komi people living in the population of indigenous women. In of the Buryat ethnogroup have a higher the Far North and leading a traditional non-indigenous women, the abdominal incidence of arterial hypertension, car- lifestyle have a lower incidence of obe- distribution of adipose tissue was formed diovascular diseases, and diabetes mel- sity compared with other populations of mainly during obesity. The author deter- litus type I than among Russians. Con- northerners [1]. mined the high diagnostic value of MC sequently, information on ethnic origin Metabolic syndrome and type I diabe- markers, which are recommended by IDF may provide additional information for a tes are common in the Asian part of Rus- (2005), for non-indigenous women of the personalized forecast [6]. sia, and in the indigenous people of the Far North. In the population of indigenous It should be noted that in the adult North and the Far East both types of dia- women, the low diagnostic value of HDL population of Cheboksary, in a random betes are less common than among Cau- cholesterol indicator was found, the eth- sample, a high incidence of traditional casians who live in the same regions [10]. nic marker of MS was identified [11; 21]. risk factors was recorded, such as eating 96 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

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N.U. Chamsutdinov, A.A. Huseynov, D.N. Abdulmanapova ENDOCRINE MECHANISMS OF BRONCHIAL CONTROL IN PATIENTS WITH BRONCHIAL DOI 10.25789/YMJ.2019.67.29 ASTHMA

The analysis of works published according to the results of studies by foreign and domestic authors on the role of the pulmonary neuroendocrine system in the functioning of the bronchi is carried out. Modern ideas about the endocrine mechanisms of bronchial control in patients with bronchial asthma are presented. A brief description of pro-inflammatory and anti-inflammatory peptide substances produced in the bronchopulmonary system is given. The possibilities of using some peptide substances as drugs in the treatment of patients with bronchial asthma are indicated. Keywords: pro-inflammatory peptides, anti-inflammatory peptides, bronchopulmonary system, bronchial asthma.

Introduction. According to GINA The active study of the role of the endo- mune competent cells (mast cells, mac- (2018), bronchial asthma (BA) is a het- crine system in the development of lung rophages, neutrophils, eosinophils and erogeneous disease characterized by diseases, including bronchial obstruction, lymphocytes), as well as neurons, also chronic inflammation of the airways and began at the end of the 20th century. The have the ability to secrete peptides [22]. the presence of respiratory symptoms impetus for their active study in pulmonol- The presence of receptors for neuro- (wheezing, shortness of breath, conges- ogy was the confirmation by a number of peptides on the surface of the cell mem- tion in the chest, cough), which vary in scientists of the influence of gastrointes- branes of immune-competent cells, as time and intensity and occur along with tinal peptides previously detected in the well as neurons, was found [12]. It has variable airway obstruction [16]. At the gastrointestinal tract (GIT) on the bron- been found that neuropeptides, acting same time, the neurogenic and immune chopulmonary system (BPS) [1]. Later, through different types of receptors, can mechanisms of the development of BA endocrine cells secreting similar peptides lead to different pharmacological effects, are described in detail in the literature; at were also detected in the BLS. One of i.e. possess multidirectional pharmaco- the same time, the role of the endocrine the first to be identified was the Klara and logical activity. The latter was the theoret- system in the development of this dis- Kulchitsky cells. By the beginning of the ical justification for a more in-depth study ease has not been studied enough. twenty-first century, a large number of of the pro- and anti-inflammatory effects endocrine-active cells were synthesized of various peptide substances on BPS in in the BPS, synthesizing peptides similar animal experiments and in patients with CHAMSUTDINOV Nabi U., MD, Professor, to gastrointestinal peptides: the tachyki- BA. It was found that the pro-inflamma- Head of the Faculty Therapy Department, nin family, bradykinin, a peptide related to tory effect on the bronchi has: a family of Dagestan State Medical University, Makhach- the calcitonin gene (PRCG), bombesin, a tachykinins (substance P, neurokinins, kala, Republic of Dagestan, Russian Feder- vasoactive intestinal peptide (VIP), pep- chemokinin-1), bradykinin, PRCG, endo- ation, E-mail: [email protected]; mobile phone: 89604094661 (contact with editorial tide-histidine-methionine (PHM), adreno- thelin-1, bombesin, granin. The anti-in- staff); ORCID iD: https://orcid.org/0000-0002- medullin, neuropeptide "Y" and others. It flammatory peptides included: VIP, neu- 3124-0272; GUSEYNOV Ali A., MD, assoc., was found that the effect of peptide sub- ropeptide “Y”, neuropeptide pituitary ade- Professor, Department of Faculty Therapy, stances on the functioning of the lungs is nylate cyclase-activating polypeptide-38 Dagestan State Medical University, Makhach- carried out by means of receptors locat- (PACAP-38), PHM, adrenomedullin, atri- kala, Republic of Dagestan, Russian Federa- ed throughout the BPS [12, 22, 23]. Their al natriuretic peptide (ANP). tion, E-mail: [email protected]; ORCID iD: https:// functional activity was manifested in the Pro-inflammatory peptides and their orcid.org/0000-0002-1829-9077. ABDUL- blockade of the parasympathetic and role in the development of inflammatory MANAPOVA Jariyat N., PhD, assistant De- sympathetic nervous systems, in con- diseases of the lower respiratory tract partment of Faculty Therapy, Dagestan State Medical University, Makhachkala, Republic nection with which non-adrenergic and Tachykinins play an active part in the of Dagestan, Russian Federation, E-mail: non-cholinergic, i.e. peptidergic system development of inflammatory processes [email protected]; ORCID iD: https://orcid. of functioning of the lungs. in many organs, including the gastroin- org/0000-0002-9986-8840. Later it was proved that certain im- testinal tract and BPS [23, 29, 30]. They 98 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

are produced in the central nervous sys- inflammatory process in the bronchial periphery, mainly in the respiratory tract tem and peripheral tissues, including in wall. Substance P affecting the vessels and gastrointestinal tract [19, 23]. the BPS. They are synthesized in the causes their dilatation, affecting the gob- Among proinflammatory neuropep- BPS by epithelial cells of the mucous let cells of the respiratory tract and sub- tides, the peptide of the tachykinin fam- membrane of the bronchi, endothelial mucosal cells causes hypersecretion and ilies, chemokinin-1, has been actively cells, endocrine and endocrine-active stimulation of mucociliary clearance, af- studied in recent years, which, like sub- immune-competent cells of the lamina of fecting the smooth muscles of the bron- stance P, interacts through NK1 recep- the bronchial mucous membrane (mast chi causing bronchospasm. Substance tors. It is synthesized predominantly by cells, eosinophils, neutrophils, lympho- P activates inflammation of the bronchi leukocytes, as well as by immunocom- cytes, monocytes, macrophages), bron- through the activation of immune-competent cells of the bronchial mucosa, chial smooth muscle cells, neurons. It petent cells (mast cells, eosinophils, neu- including macrophages and causes a has been established that the BPS of BA trophils, lymphocytes, monocytes, mac- reduction in the bronchi in humans. In ex- patients is more sensitive to tachykinins rophages), chemotaxis of lymphocytes, perimental mice, it has been established than the BPS of healthy individuals [22]. neutrophils and eosinophils, as well as that it is generated by activated mast Tachykinins act through neurokinin re- degranulation of target cells of allergies, cell allergens and contributes to experi- ceptors: NK1 (substance P), NK2 (neu- predominantly mast cells [5, 22, 23]. mental chronic allergic inflammation of rokinin-A, neurokinin B) and NK3. Tachy- Neurokinin-A, which has been active- the airways [34]. Chemokine-1-induced kinins are important in the regulation of ly studied in recent years, is a product bronchial contraction can be mainly as- the peptidergic mechanisms of asthma of the preprotakhinin-A gene. As well as sociated with NK2 receptors in humans and are by far the most studied neuro- substance P, it is synthesized by immune, and with NK1 receptors in the guinea peptides in pulmonology. inflammatory, endothelial and epithelial pig [15]. Chemokinin-1 800 times more Allergic sensitization of the respiratory cells, as well as by the smooth muscle powerful effect on the bronchi of people tract of guinea pigs leads to the induction cells of the bronchi in various immune than neurokinin-A [22]. It has been es- of tachykinins (substance P, neurokinin inflammatory processes in the bronchi. It tablished that chemokine-1 increases in A) and a peptide related to the calci- participates in the activation of immune patients with asthma and causes mast tonin gene (PRCG) by sensory neurons, cells, prolonging the inflammatory pro- cell degranulation, an immune inflamma- which is one of the pathogenetic mecha- cess in the bronchi [22]. There is an in- tory process in the bronchial mucosa and nisms of inflammation in the bronchi and crease in its content in sensory neurons, bronchospasm [34]. bronchoconstruction [30]. Through NK1 as well as in endocrine and endocrine-ac- As can be seen from the literature data receptors, tachykinins lead to the devel- tive BPS cells of patients with BA. It caus- presented, tachykinins are considered as opment of powerful inflammation in the es contraction of smooth muscles, mainly possible mediators of asthma, and tachy- mucous membrane of the bronchi caus- in the BPS and gastrointestinal tract [13, kinin receptor antagonists can be consid- ing vasodilation, an increase in vascular 23, 31]. ered as a new class of drugs in the treat- permeability, hypersecretion, stimulation In patients with physical asthma, ex- ment of patients with asthma [13, 23]. For of mast cells, lymphocytes, and chemo- ercise-induced sputum was collected at example, it was established that bron- taxis of neutrophils and eosinophils, and the beginning and 30 minutes after ex- chospasm induced by inhalation of neu- through NK2 receptors they cause bron- ercise. In the induced sputum, secreted rokinin-A in patients with BA is blocked by chospasms. Bronchial hyperreactivity mucin 5AC, eicosanoids, cysteinyl leu- the double antagonist of NK1/NK2 recep- (BGR) develops as a result of the isola- kotrienes, 15S-hydroxyethylisatetraenoic tors of the tachykinin DNK333 [13] and tion of tachykinins from capsaicin-sensi- acid and tachykinins (neurokinin-A, sub- the antagonist of NK2 receptors of the tive centripetal nerves via the NK1/NK2 stance P) were determined. At the same tachykinin MEN11420 (nepadutant) [32]. receptors [30]. time, there was a twofold increase in the It has been proven that dual NK1/NK2 The substance P, which was discov- induced sputum of asthma patients in the receptor antagonists (DNK-333, AVE- ered in 1931, is the most studied of the physical effort of mucin 5AC, as well as 5883 and MEN11420) have the property tachykinin family. Substance P is encod- tachykinins: neurokinin A and substance of weakening bronchial hypersensitivity ed by the preprotachikinin-A gene and is P. The authors assumed that the release (BHS) [13, 14, 32]. expressed predominantly in sensory neu- of mucin 5AC after exercise may occur The NK2 receptor antagonist SR rons sensitive to capsaicin. Receptors, through activation of sensory nerves of 48968 (saredutant) also prevents bron- through which substance P functions, the respiratory tract associated with cys- choconstriction caused by neurokinin-A were found in the lamina propria of the teinyl leukotrienes tachykinins and the in patients with BA [5]. The NK2 recep- bronchial mucosa, the smooth muscles development of bronchial obstruction. tor antagonist SR 144190 selectively in- of the bronchi, near blood vessels, gan- Exercise-induced pathogenesis of bron- hibits the binding of neurokinin A to NK2 glia and nerve bundles of the submuco- chial obstruction involves the release of receptors in humans and various animal sa. They are absent in the submucous mediators (including tachykinins) in re- species. It prevented BHS in guinea pigs glands and alveolar septa [12]. sponse to physical exertion. However, caused by citric acid to acetylcholine [6]. The substance P is actively synthe- the mechanism that prevents airflow ob- The NK3 receptor antagonist osan- sized in various immune inflammatory struction during exercise is not fully un- etant (SR142801) reduces the level of processes in the bronchi. It has been derstood [28]. TNF-α and interleukin-6, as well as the established that the content of sub- The bronchoconstrictive effect of activity of matrix metalloproteinase-9 stance P increases in serum, sputum, neurokinin-B has also been proven. in the inflammation of the respirato- bronchoalveolar lavage, endocrine and This peptide is derived from the preprot- ry tract caused by mouse endotoxin. A endocrine-active BPS cells and sensory achikin-B gene and is acted upon by the high anti-inflammatory activity in airway neurons of patients with BA [5, 22, 27]. NK3 receptors. Neurokinin-B and NK3 inflammation was observed in the com- The latter implies the direct participation receptors are predominantly found in the bination of the NK1 receptor antagonist of substance P in the development of the central nervous system, as well as on the SR140333 and NK2 SR48968 [19]. 3’ 2019 99

The bronchoconstrictive effect of spasm is not blocked by histamine, ace- nervous system, cardiovascular, respira- chemokine-1 is blocked by the NK2 re- tylcholine and leukotriene antagonists [4]. tory, urogenital and immune systems, as ceptor antagonist SR 48968, while the re- Endothelin-1, refers to peptides with well as in the thyroid gland. VIP receptors ceptor antagonist SR 140333 only slightly pro-inflammatory, profibrotic, bron- are found in the smooth muscles of the reduced the effects of chemokinin-1 [22]. cho-and vasoconstrictive effects. It plays pulmonary vessels, large bronchi, on the The triple antagonist of the NK1/NK2/ an important role in the development of surface of epithelial and glandular cells, NK3 receptor CS-003 reduced BGR and airway inflammation and remodeling in and are practically absent in the bronchi bronchoconstriction caused by neuroki- asthma [17]. of small caliber. The latter is due to the nin-A in BA patients [31]. Bombesins are synthesized by the lack of its influence on their tone. Their The presented data are convincing nervous system, as well as various types receptors are also present in the nerve evidence of inhibition of bronchoconstric- of neuroendocrine cells, including lung fibers of normal lungs [8, 11] tion by selective antagonists of tachykinin cells. In the lungs, bombesins contribute In order to determine the VIP in the receptors in patients with BA, and open to the differentiation of epithelial cells and lungs in patients with BA, the lung tissue up broad prospects for their use. play an important role in modulating the obtained during autopsy and lobectomy The role of nonapeptide bradykinin in physiology of the respiratory tract. They in 5 patients with BA and 9 without BA the development of inflammation has also cause hypersecretion of mucus and was examined. Conducted immunohis- been studied. It is established that he is marked bronchial obstruction and are tochemical staining of lung tissue for the one of the mediators of inflammation in one of the main mediators of inflamma- detection of VIP and histological exam- asthma. Its content increases in the bron- tion in patients with asthma. Broncho- ination of at least 80 sections of lung tis- choalveolar lavage of patients with BA. spasm develops due to the direct effect sue of each patient. VIP was detected in Bradykinin affects vascular tone and per- of Bombesin on the receptors of the more than 92% of the sites from the lungs meability, causes hypersecretion and re- smooth muscles of the bronchi. At the of patients without BA. It was not found duces the smooth muscles of the bronchi same time, bronchial obstruction caused in any of the 468 sections of lung tissue through cholinergic mechanisms. By ac- by Bombesin is not affected by atropine, of patients with BA. It was noted a signif- tivating fibroblasts, it is directly involved hexametonium, propranolol, triprolidine, icant decrease in the number of VIP in in the remodeling of the bronchi. It has methysergide, Ro 19-3704 [10]. the nerves in the tissue from the lungs in been proven that NK2 (SR48968) and In recent years, interest in facets has all patients with asthma. According to the NK3 receptor antagonists (SR142801 or revived, mainly chromium granules A and authors, patients with asthma have a loss SB223412) suppress cough caused by B. The study of serum granules today is of VIP from the pulmonary nerve fibers. bradykinin in guinea pigs [25]. used to diagnose lung tumors. Some re- At the same time, it is unclear whether PRCG also belong to pro-inflammato- searchers have reported that chromogr- this loss is a cause or a result of BA [2]. ry peptides. The main sources of PRCG anin A is increased in patients with bron- A number of authors have established in the respiratory tract are believed to be cho-obstructive diseases, including those that IL-5, which is a key cytokine for BA, unmyelinated and fine myelin sensory with asthma. The relationship between acts directly on the nociceptors of the nerve fibers and neuroendocrine cells. the amount of serum chromogranin A, respiratory tract and causes the release PRСG receptors, as well as substance smoking, respiratory symptoms and spi- of VIP. VIP, in turn, stimulates CD4+ lym- P, are found in the lamina propria of the rometry indicators has been studied. phocytes, resulting in a Th2 response and bronchial mucosa, near blood vessels, as Studies were conducted on smokers with allergic inflammation of the bronchi. Noci- well as in the ganglia and nerve bundles normal lung function and bronchial ob- ceptors are believed to enhance patho- of the submucosa [12]. In its own plastic struction. At the same time, high figures logical adaptive immune responses [29]. of the bronchial mucosa, PRCG is local- of serum chromogranin A were detected It has been established that im- ized predominantly on CD3 + / CD4 + and in smokers with bronchial obstruction mune-competent cells involved in the CD68 + cells [4]. In the smooth muscles confirmed spirometrically, in contrast to development of inflammation in the mu- of the bronchi, in contrast to substance P, smokers with a normal spirogram. At the cous membrane of the bronchi (eosino- very few PRCG receptors are detected, same time, the increase in chromogranin phils, mast cells, macrophages, neutro- and in the glands and alveolar septa they A correlated with the degree of bronchial phils) have the ability to release peptide are absent [12]. obstruction. The latter, according to the substances that block the secretion of It has been established that the con- authors, suggests neuroendocrine acti- VIP [11]. Some authors suggest that in tent of PRCG increases in bronchoalve- vation in inflammatory and remodeling patients with BA, active peptidases, re- olar lavage, sputum, peptidergic nerves processes in the lungs [18]. leased in a BPS, result in the destruction and sensory neurons of the lower respi- The role of anti-inflammatory peptides of some peptides, including VIP. It has ratory tract of patients with asthma [27]. in the functioning of the bronchopulmo- also been proven that persistent respira- PRCG may contribute to the late phases nary system tory syncytial infection causes significant of asthmatic reactions after provocation Among the anti-inflammatory pep- changes in the peptidergic innervation of by respiratory allergens [5]. This peptide tides, the most studied is the VIP, which the respiratory tract, namely, in this cate- enhances the effect of substance P, caus- causes vasodilation, has a pronounced gory of patients, VIP-reactive nerve fibers es potent vasodilation, hypersecretion, bronchodilatory effect, has a positive ef- decreased [27]. bronchial edema and bronchial smooth fect on bronchial secretion and mucocili- VIP may be considered as a new an- muscle spasm, more pronounced than in ary clearance. The bronchodilation activ- ti-asthma drug due to its bronchodilating substance R. In addition, it contributes to ity of the latter is 100 times higher than activity, vasodilation and immunomod- the release of inflammatory mediators, in- that of isoproterenol. It has been proven ulating and anti-inflammatory effects [9, cluding histamine from mast cells, which that VIP has a powerful anti-inflamma- 11]. When systemic injection of VIP has increases inflammatory reaction of the tory effect and inhibits the migration of its drawbacks, such as hypotension, bronchi and bronchospasm. It has been eosinophils [5, 11]. It is detected in the heart rate reduction. There have been established that in this case the broncho- intestine, in the central and peripheral attempts to use VIP as a drug in patients 100 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

with asthma, however, its only and seri- tidergic nerves of the lower respiratory an effective vasoactive peptide. It is de- ous drawback, restraining its use in these tract and sensory neurons. In the smooth tected in the blood, heart, blood vessels, patients, is a very short half-life after in- muscles of the bronchi, their number de- lungs, kidneys, endocrine glands, cere- travenous administration [9]. These pep- creases. The effect of the neuropeptide brospinal fluid. Its main properties are: tide effects are minimized by inhalation "Y" is closely related to the sympathetic vasodilation, diuretic and natriuretic ef- administration. The development of high- nervous system. In patients with asthma, fects, positive inotropic effect, inhibition ly active analogues of VIP and systems an increase in serum adrenaline, norepi- of endothelial cell apoptosis, induction of for their delivery to the respiratory tract nephrine and neuropeptide "Y" was de- angiogenesis, inhibition of cardiomyocyte is a promising direction for the pharma- tected. Apparently, this peptide having a apoptosis, suppression of aldosterone cotherapy of broncho-obstructive dis- neuronal origin leads to the release of formation, anti-inflammatory effect and eases, including BA. Confirmation of the vasopressors, which is accompanied by antioxidant activity. The physiological latter is the successful use of inhalation vasoconstriction and bronchodilation. It effects of adrenomedullin are mediated administration of the powder derivative plays an important role in the regulation by the participation of type 1 receptors - VIP - [Arg 15, 20, 21, Leu17] - VIP-GRR of airway blood flow, smooth muscle con- PRCG. The amount of peptide increases (IK312532). The drug showed its high an- traction and modulation of the immune during an attack of asthma. The peptide ti-inflammatory efficacy on the bronchi in response. Its content increases in the air- also acts as a bronchodilator. The effect the experiment [8]. ways of patients with asthma. According of adrenomedullin on bronchoconstric- PACAP-38 as well as VIP has anti-in- to the authors, the neuropeptide "Y" can tion induced by histamine and / or ace- flammatory and bronchodilating effects. participate in the regulation of cytokines tylcholine in anesthetized guinea pigs in Its effects are mediated by three recep- and the cellular activity of immune cells vivo was studied. At the same time, the tors associated with G-protein: PAC1R, in asthma. At the same time, it remains peptide inhibited bronchoconstriction VPAC1 and VPAC2, which have similar- unclear whether such an increase in it is caused by acetylcholine and induced a ities with VIP. PACAP-38 and its recep- a protective or compensatory mechanism prolonged bronchodilation response [3]. tors are present in the central nervous [24]. Although some authors suggest a Conclusion. As the literature data system and peripheral organs, including protective role of the peptide in patients show, the connection between the ner- the endocrine system (adrenal glands, with asthma. A decrease in its quantity vous, endocrine and immune systems is pancreas, ovaries, testicles), gastrointes- contributes to the hypersecretion of mu- carried out by means of neuropeptides tinal tract, BPS, cardiovascular system, cus in patients with asthma. The content [22]. The classical definition of neuropep- urinary system, and immune competent of neuropeptide "Y" is increased in the tides has been changed in recent years, cells [21]. In the BPS, it is localized in the bronchoalveolar lavage. There was an since they are not produced exclusively nerve fibers innervating the lungs. PA- increase in the content of neuropeptide by neurons, but are also synthesized by CAP-38 released from peripheral nerve “Y” in the serum of experimentally aller- endocrine and immunocompetent cells. endings with neurogenic inflammation. genic mice. An inflammatory reaction They are considered as neuroendocrine Plays an important role in the functioning of the respiratory tract was detected in immune modulators and play an import- of the lungs. It is a powerful bronchodila- these mice, which was confirmed by an ant role in the functioning of the gener- tor and causes marked dilatation of the increase in the content of neutrophils al neuroimmune-endocrine system [23]. pulmonary vessels. It plays the role of and eosinophils in bronchoalveolar la- Thus, the discoveries of recent years the regulator of respiration with the cat- vage. A direct strong correlation was not- make it possible to isolate the neuroim- echolaminergic system in the medulla ed between the content of neuropeptide mune-endocrine mechanisms of the de- oblongata [21]. It has been established “Y” in the serum and an increase in the velopment of BA, i.e. combine neurogen- that PACAP-38 reduces the release of bronchoalveolar lavage of experimental ic, immune and endocrine mechanisms inflammatory neuropeptides from nerve mice of neutrophils and eosinophils. An into one. endings. Agonists PACAP-38 can also increase in the level of neuropeptide “Y” Many peptide substances in animal be considered as possible drugs for the in peripheral blood was attributed by the experiments have proven their anti-in- treatment of asthma. authors to increased inflammation of the flammatory and bronchodilation effects. The effect of PHM on BPS was stud- airways in allergenized mice [20]. This allows us to consider them as pos- ied. It resembles the action of VIP. How- In recent years, the role of ANP has sible drugs for the treatment of BA. A ever, its bronchodilating activity is sever- been studied. Its receptors are found number of proinflammatory peptides, al times higher than that of the VIP, the in the lung tissue, expressed by type II lead to the activation of the inflammato- vasodilating activity is somewhat weaker. pneumocytes. Its concentration in the ry process in the bronchi and bronchial Secretory function is more pronounced blood plasma increases with severe ex- obstruction through exposure through as well. This peptide can also be consid- acerbations of asthma. Intravenous ad- various receptors. The search for antag- ered as a drug for the treatment of BA. ministration of it to experimental animals onists acting on these receptors is a new The neuropeptide "Y" was first isolat- significantly reduced bronchospasm pro- direction of anti-inflammatory and bron- ed from the pig hypothalamus in 1982. voked by inhalation administration of his- chodilatory therapy of asthma. Its abnormal regulation is associated tamine. It has been proven that ANP has It is known that many anti-inflamma- with the development of a wide range a powerful bronchodilator effect. The dis- tory neuropeptides reduce the inflamma- of diseases, including obesity, hyperten- advantage of this peptide is the short half- tory response by reducing inflammatory sion, atherosclerosis, epilepsy, metabol- life, in connection with which the possibil- and regulating anti-inflammatory media- ic disorders, and many cancers [26]. At ities of inhalation administration of ANP tors. Anti-inflammatory neuropeptide re- the end of the twentieth century, began for the purpose of bronchodilation and ceptors can also be promising targets in to be widely studied in pulmonology. It is bronchoprotection are considered [7, 33]. the treatment of BA [23]. synthesized both in the peripheral and Adrenomedullin was isolated in 1993 Sometimes contradictory, but encour- central nervous systems. The content of from human pheochromocytoma cells. aging data on the possibility of using neuropeptide “Y” increases in the pep- It belongs to the family of PRCG and is peptides as drugs in pulmonology open 3’ 2019 101

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European icsonline.org/open-access/multifaces-of-pitu- Authors’ information: Journal of Pharmaceutical Sciences. 2013; 49(3): itary-adenylate-cyclaseactivating-polypeptide-pa- Chamsutdinov Nabi U., MD, Professor, Head 382-389. DOI: 10.1016/j.ejps.2013.04.009. cap-2167-0943.1000162.pdf (access date: of the Faculty Therapy Department, Dagestan 9 Athari SS., Pourpak Z., Folkerts G [et al.]. 30.09.2018). DOI: 10.4172/2167-0943.1000162. State Medical University, Makhachkala, Republic Conjugated alpha-alumina nanoparticle with va- 22. Groneberg DA., Quarcoo D., Frossard of Dagestan, Russian Federation, E-mail: nauch- soactive intestinal peptide as a Nano-drug in N. [et al.]. Neurogenic mechanisms in bron- [email protected]; mobile phone: 89604094661 treatment of allergic asthma in mice. European chial inflammatory diseases. URL: https:// (contact with editorial staff); ORCID iD: https:// Journal of Pharmacology. 2016; 791: 811-820. onlinelibrary.wiley.com/doi/full/10.1111/j.1398- orcid.org/0000-0002-3124-0272; DOI: 10.1016/j.ejphar.2016.10.014. 9995.2004.00665.x (access date: 29.10.2018). Guseynov Ali A., MD, assoc., Professor, De- 10. Lach E., Haddad EB., Gies JP. Contractile DOI: 10.1111/j.1398-9995.2004.00665.x. partment of Faculty Therapy, Dagestan State effect of bombesin on Guinea pig lung in vitro: in- 23. Pinter E., Pozsgai G., Hajna Z [et al.]. Medical University, Makhachkala, Republic of volvement of gastrin-releasing peptide-preferring Neuropeptide receptors as potential drug targets Dagestan, Russian Federation, E-mail: ajub@ receptors. URL: https://www.ncbi.nlm.nih.gov/ in the treatment of inflammatory conditions. Brit- inbox.ru; ORCID iD: https://orcid.org/0000-0002- pubmed/8381599 (access date: 17.10.2018). ish Journal of Clinical Pharmacology. 2014; 77(1): 1829-9077. DOI: 10.1152/ajplung.1993.264.1.l80. 5–20. DOI: 10.1111/bcp.12097. Abdulmanapova Jariyat N., PhD, assis- 11. Delgado M., Ganea D. Vasoactive intes- 24. Makinde TO., Steininger R., Agrawal DK. tant Department of Faculty Therapy, Dagestan tinal peptide: a neuropeptide with pleiotropic im- NPY and NPY receptors in airway structural and State Medical University, Makhachkala, Repub- mune functions. Amino Acids. 2013; 45(1): 25-39. inflammatory cells in allergic asthma. Experimen- lic of Dagestan, Russian Federation, E-mail: DOI: 10.1007/s00726-011-1184-8. tal and Molecular Pathology. 2013; 94 (1): 45-50. [email protected]; ORCID iD: https://orcid. 12. Komatsu T., Yamamoto M., Shimoka- DOI: 10.1016/j.yexmp.2012.05.009. org/0000-0002-9986-8840. 102 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

POINT OF VIEW

B.O. Shcheglov, I.V. Galkina, S.N. Shcheglova, M.Yu. Shchelkanov EFFECTIVENESS OF 3D-MODELLING LABORATORY IMPLEMENTATION INTO THERAPEUTIC AND DIAGNOSTIC MEDICAL DOI 10.25789/YMJ.2019.67.30 INSTITUTIONS

The article presents the analysis of 3D modeling laboratory efficiency after its introduction in the departments of radio diagnostics. Prospects and risks of the work of this unit is presented in the study. The calculation of economic indicators shows that the payback is around 2 years, the breakeven point is 60 – 70 clients per month. Results obtained economically and technologically justify active deployment labs 3D simulation in medical institutions. Keywords: healthcare, economy, 3D modeling.

Using of 3D-modeling in medical in- cant increase in the volume of work [8, tics into full-fledged three-dimensional stitutions has not yet become a routine 13, 14]. It should be noted that the trend models, so the doctor has a chance to procedure, but it is in this direction that of increasing volumes of medical activi- carry out preliminary surgical preparation a qualitative breakthrough in the field of ty using medical imaging, and data pro- and choose the most effective and opti- personalized medicine is the most likely cessing technologies with an ever-grow- mal tactics for performing surgical opera- [11, 16] since a technological basis has ing consumer market has been observed tions with minimal risk for the patient and already been formed for this and in the everywhere in the last decade [18]. For a decrease in the trauma of healthy tis- process of its practical testing it should example, steady increase in mortality sues. Successful high-quality recognition additionally take shape relevant organi- from malignant neoplasms of the brain of diseases of various origins in the ra- zational, economic and ethical standards. and spinal cord recorded in Russia re- diation laboratory complex also reduces In this regard, a systematic analysis of quires significant optimization of their the need for repetition of studies and time the effectiveness of the implementation diagnosis and treatment [1]. Due to the saving, leading to an increase in the effi- of these decisions in medical practice is rapidly improving Big Data technologies, ciency of staff and the medical institution necessary [7, 8]. increasing the productivity of electronic as a whole [3, 10, 12, 17]. The department of radiation diagnos- computing power, it is possible to over- The main threats to the work of the 3D tics, which is standard for Russian med- come the lack of radiation diagnostic data modeling laboratory are hacking and theft ical institutions [2], could be the most and accelerate digital processing [15]. of information by hackers (Table 1). This suitable unit for the implementation of High quality hardware / software com- problem can be solved by using more ad- 3D modeling and printing. Firstly, a 3D plex, management and good work orga- vanced cryptography algorithms, using modeling group is better positioned as an nization aimed at achieving continuous specialized security software, Blockchain independent technological unit bearing improvement of preanalytical, analytical, technologies and integrated security sys- in mind its transformation into a sepa- and postanalytic phases in diagnosis are tems for user authentication [4, 5, 9]. rate laboratory in the event of a signifi- an integral guarantee of making a correct The introduction of the laboratory with diagnosis (Table 1). the addition of information processing of SHCHEGLOV Bogdan Olegovich, Head Today, it has already become possible data can improve the organization of la- of the Student Association “3D-Modeling in to qualitatively supplement and improve bor, save time and more carefully control Biomedicine” of the Center for Project Activi- the differentiation of diseases of various of the research process [6, 19]. At the first ties, Far Eastern Federal University (Vladivo- genesis with the help of slicer programs stage, this new technology requires addi- stok); e-mail: [email protected]; mobile: that convert 2D data of radiation diagnos- tional investments, the financial viability 89147189825. GALKINA Irina Vyachesla- vovna, PhD in medicine, Leader Researcher of the International Scientific and Educational Table 1 Center of Molecular Technologies, School of Biomedicine, Far Eastern Federal University (Vladivostok); e-mail: [email protected]; Analysis of prospects for the implementation of 3D modeling laboratory mobile: 89031705864. SHCHEGLOVA Svet- lana Nikolaevna, PhD in pedagogy, Head of Opportunities Threats the Department of Higher Mathematics, North- eastern State University (Magadan); e-mail: Increased productivity and lower costs resulting from using of machine Certified software and integrated [email protected]; mobile: 89148624028. Strengths SHCHELKANOV Mikhail Yurievich, Doctor learning, categorization, artificial security systems of Biological Sciences, Head of the Interna- intelligence algorithms tional Scientific and Educational Center of Molecular Technologies, School of Biomed- Dependence on electronic computing Imperfection of authentication and icine, Far Eastern Federal University (Vlad- Weaks power and access to specialized personification systems when working ivostok); e-mail: [email protected]; mobile: databases with databases 89032689098. 3’ 2019 103

of which can be characterized by comparing the expected costs and revenues 0 0 0 24 73 2500 1500 5000 [13]. The time variation of these econom- 5000 50000 75200 10000 35800 33040 91700 90800 83810 Table 2 Table 182500 146700 259270 ic values in relation to the economic con- 365040 ditions of the Primorsky Krai is presented in Fig.: for the 3D modeling laboratory, 0 0 0 22 73 2500 1500 5000 5000 8381 50000 75200 10000 35800 33040 76770 91700 the payback period is about 2 years, 90800 182500 146700 182540 the break-even point is 60-70 clients per month; the net present value with a rate of 10% and an investment of 500,000 ru- 0 0 0 20 43 40 2500 1500 5000 5000 50000 75200 10000 91700 15800 bles is 187,734 rubles (Table 2). 14580 -39200 -36180 107500 146700 The creation of a 3D modeling labora- -105730 tory in medical institutions as an additional module to the department of radiation 0 0 0 18 73 2500 1500 5000 5000 50000 75200 diagnostics or autonomous education 10000 35800 33040 91700 90800 83810 182500 146700 -213230 allows us to significantly expand existing -107460 methods of non-invasive examination and use them in the areas of preopera- 0 0 0 16 63

tive planning and prosthetics. The results 2500 1500 5000 5000 9970 50000 75200 10000 10800 91700 65800 60730 157500 146700 -395730 obtained during the work economically -289960 substantiate the creation of this laboratory in hospitals and clinics to improve the 0 0 0 14 quality of medical services to the popu- 53 2500 1500 5000 5000 50000 75200 10000 91700 40800 37660 -13110 -14200 132500 146700 -553230 lation. -447460

References 0 0 0 12 73 2500 1500 5000 5000 50000 75200 10000 35800 33040 91700 90800 83810 182500 1. Каприн А.Д., Старинский В.В., Петрова 146700 -685730 -579960 Г.В. (ред.) Злокачественные новообразования в России в 2017 году (заболеваемость и смерт- ность). М.: Московский научно-исследователь- 0 0 0 10 ский онкологический институт им. П.А. Герце- 73 2500 1500 5000 5000 50000 75200 10000 35800 33040 91700 90800 на, 2018: 250. [Kaprin AD, Starinsky VV, Petrova 83810 182500 146700 -868230 GV (eds.) Malignant neoplasms in Russia in 2017 -762460 (morbidity and mortality). Moscow: PA Herzen Moscow Scientific-Research Institute; 2018: 250 8 0 0 (In Russ.).] 0 43 2500 1500 5000 5000 50000 75200 10000 91700 15800 2. О совершенствовании службы лучевой 14580 -39200 -36180 107500 146700 -944960 диагностики. Приказ Министерства здравоох- -1050730 ранения РСФСР № 132 от 02.08.1991 с изме- нениями от 05.04.1996. [About the improvement of service for radiation diagnostics. The order of 6 0 0 0 70 2500 1500 5000 RSFSR Ministry of Public Health № 132 dated at 5000 50000 75200 10000 28300 26120 91700 83300 76890 175000 146700 -1158230 August 02, 1991 with changes dated at April 5, -1052460 1996. (In Russ.).] 3. Юрьев В.К. , Пузырев В.Г., Глущенко

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P.I. Kudrina, S.I. Sofronova, O.V. Tatarinova ETHNIC AND AGE-RELATED CHARACTERISTICS OF NEUROLOGICAL SYMPTOMS AND FUNCTIONAL STATE OF THE KIDNEYS IN ELDERLY AND SENILE DOI 10.25789/YMJ.2019.67.31 AGE PEOPLE OF YAKUTIA

The study was conducted in patients of elderly and senile age, representatives of the indigenous and non-indigenous ethnic group. It has been established that the development and progression of chronic cerebral ischemia occurs in parallel with the progression of chronic kidney disease. At the same time, representatives of the non-indigenous population showed more severe neurological symptoms due to structural changes in the cerebral vascular bed due to hypertension and atherosclerosis, as well as severe renal dysfunction. Evens had milder clinical symptoms of chronic cerebral ischemia and lower renal abnormalities. Keywords: ethnos, elderly and senile age, chronic brain ischemia, chronic kidney disease.

The problem of cerebro-renal interac- progression of CCI associated with ath- of neurological symptoms and functional tions in elderly and senile age patients erosclerosis and arterial hypertension state of the kidneys in elderly and senile suffering from chronic cerebral ischemia [1]. The high prevalence of CCI is ex- age people of Yakutia. (CCI) in modern medicine is relevant pri- plained not only by demographic chang- Materials and research methods. marily due to the large medical and social es in modern society with an increase in This study was performed in the con- significance. This is due to the fact that the proportion of elderly and senile age fines of the neurological department of impaired renal function plays a significant people, but also by an increase in the the Geriatric Center of the Republican role in accelerating the development and prevalence of risk factors, which include Hospital of Sakha (Yakutia) "Republican arterial hypertension, atherosclerosis, Hospital №3". 522 patients from 60 to diabetes and obesity [3]. It is known that 89 years, of comparable age and sex, Yakutsk, Republic Sakha (Yakutia), Russia: each ethnic group of the population de- were examined. CCI was diagnosed ac- KUDRINA Polina Ivanovna - PhD, neurolo- termines its own characteristics in the cording to the Classification of Vascular gist of the Republican Hospital No. 2 - Cen- epidemiology of a disease. CCI in combi- Brain Lesions of the Institute of Neurol- ter for Emergency Medicine, [email protected]; nation with chronic kidney disease (CKD) ogy, Russian Academy of Medical Sci- SOFRONOVA Sargylana Ivanovna - PhD, is no exception. ences (1985), the diagnosis was worded chief researcher, head of Department of YSC The aim of the study was to research in accordance with ICD-10. The criterion CMP, ORCID the ethnic and age-related characteristics for the diagnosis was instrumentally con- 3’ 2019 105

firmed lesion of cerebral vessels with the Table 1 corresponding clinical picture of the stages of CCI in accordance with the classi- Distribution of patients with chronic cerebral ischemia by ethnicity and age groups fication of E.V. Schmidt (1985) - patients with chronic cerebral ischemia stage I Evens Yakuts Russians (CCI I) and patients with chronic cerebral Age group n=174 n=177 n=171 ischemia stage II (CCI II). n % n % n % The following diseases were excluded: - identified malignant neoplasms or CCI I operations for such pathology in the pa- 60-74 years 42 48.3 61 67.8 54 62.8 tient’s medical history; 75-89 years 45 51.7 29 32.2 32 37.2 - diseases of the blood system, includ- CCI II ing anemia; 60-74 years 46 52.9 58 66.7 40 47.1 - angina pectoris of the 4th FC, as well 75-89 years 41 47.1 29 33.3 45 52.9 as acute myocardial infarction (up to 40 days), the presence of congestive heart tration rate was determined by two com- As shown in table 2, manifestations failure of the 3rd and more functional putational methods with the subsequent of renal dysfunction with glomerular fil- class (NYHA, New York, 1964); determination of the stages of chronic tration rate from 58.78 to 77.87 are ob- - Alzheimer's disease and vascular de- kidney disease: served in all patients with CCI, a more mentia; Cockcroft&Gault pronounced decrease in renal func- - chronic renal failure >3rd stage ac- GFR (ml/min) = (140-age) × body tion is observed in the representatives cording to M.A. Ratner; weight (kg) × Е blood creatinine (µmol/l), of the 3rd group in both computational - acute inflammatory pathology of the where Е-1,23 for men and 1,04 for formulas. In patients of the 1st group, articular apparatus; women the glomerular filtration rate is higher - chronic obstructive diseases of the MDRD: than in patients of the 2nd and 3rd bronchopulmonary apparatus with res- GFR (ml/min/1.73 м2) = 186 x (serum piratory failure (RF) stage II-III and mani- creatinine (mg/dL)-1.154 x (age)-0.203 x festations of chronic pulmonary heart (0.742 for women). ya-r 0.895 0.005 0.687 P disease; 0.895 The stages of chronic kidney disease 2 Table - obliterating arteriopathy of the lower were determined in accordance with limbs stages III-IV according to Fontaine. the classification of the National Kidney e-r 0.416 0.001 0.991 P Strict elimination criteria are justified Foundation of the USA [4]. 0.652 by the fact that the clinical manifesta- Statistical processing of the research tions of the diseases listed above come results was performed using the SPSS e-ya P 0.194 0.121 0.669 to the forefront, changing the clinical pic- 19.0 software package. To describe the 0.536 ture and the course of chronic cerebral quantitative data, an average value with

ischemia. a standard deviation was calculated. m 2.25 2.63 2.57 All patients were divided into three Qualitative attributes are presented in 10.00 ethnic groups: the form of frequency tables containing

1st group - 174 patients of the Even Russians absolute values and the relative share М 67.87 58.78 73.93 nationality (representatives of small in- of the attribute (percentage). Verification 72.64 digenous peoples of the North), living in of the laws of distribution of quantitative the Arctic zone. 87 people were in the traits for compliance with the normal law m 2.29 2.22 2.23 subgroup of CCI I, CCI II - 87. was performed using the Kolmogorov- 2.26 2nd group - 177 patients of the Yakut Smirnov test. The test results showed nationality (CCI I - 90, CCI II - 87), Yakuts

that the distribution of the studied param- М rd 66.52 65.05 72.54 3 group - 171 patients of the Russian eters differs from the normal distribution. 72.19 nationality (CCI I - 86, CCI II - 85). The Mann-Whitney paired test was used The age of the examined patients

to compare the average values of the m 7.17 2.31 2.48 ranged from 60 to 89 years; the aver- studied parameters. In all statistical crite- 2.34 age age of the examined was 72.7 ± 7.2 ria used, the value of p <0.05 was taken years, for men - 72.9 ± 7.2, for women as the threshold level of significance. Evens М 77.87 70.06 77.97 - 72.6 ± 7.2 years. The age groups were Results and discussion. The main 74.21 formed based on the WHO classification: objective of our work was to study the early elderly people - 60-74 years, late el- functional state of the kidneys, which was derly people - 75-89 years. determined by the decrease in the glo- CCI I In order to study the functional state merular filtration rate, a parameter that CCI II The average value of glomerular filtration rate by calculation formulas (unit) The average value of glomerular of the kidneys and assess the severity of most correctly (as one specific numerical Subgroup chronic kidney disease (stage) in patients value) reflects global kidney function, and with different stages of CCI, depending an assessment of the severity of chronic on ethnicity, the level of glomerular filtra- kidney disease (stage) by the glomeru- tion rate was calculated, the parameter lar filtration rate [2]. The value was de- MDRD most correctly (in the form of one specific MDRD

termined by two computational methods Formula numerical value) reflecting global kidney with subsequent determination of the Cockroft&Gault function. The speed of the glomerular fil- Cockroft&Gault stages of chronic kidney disease. Note: M - average value, m standard error of the mean 106 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

of CCI, is less pronounced in Table 3 Evens, more in Russians, Yakuts occupy an intermediate position. The average values of glomerular filtration rate, depending on age and ethnicity Evaluation of the functional state of the kidneys in patients Calculation Evens Yakuts Russians P P P using the computational formu- formula M m M m M m e-ya e-r ya-r las revealed a high incidence of 60-74 years the formation of chronic kidney Cockroft&Gault 91.81 2 81.72 2.29 86.54 2.08 0.002 0.078 0.127 disease in patients with CCI. In

CCI I MDRD 90.25 2.96 81.89 2.25 85.87 2.29 0.025 0.521 0.66 our opinion, the cause of such 75-89 years relationships may be the parallel- Cockroft&Gault 57.79 2.15 53.13 2.40 49.18 2.81 0.092 0.016 0.434 ism of atherogenesis processes. MDRD 58.78 2.19 52.88 2.41 50.40 2.71 0.083 0.018 0.501 Thus, in patients with CCI, 60-74 years both in stage I and stage II, in the Cockroft&Gault 78.10 2.86 70.67 2.57 70.79 2.96 0.057 0.81 0.976 elderly and the senile, the best MDRD 78.27 2.89 74.44 2.68 69.9 20.65 0.145 0.552 0.319 indicators of kidney function are 75-89 years

CCI II observed in Evens rather than in Cockroft&Gault 61.04 3.21 53.80 3.44 48.10 2.43 0.136 0.002 0.169 Yakuts and Russians. Moreover, MDRD 77.42 14.97 54.88 3.43 48.29 2.42 0.213 0.048 0.123 with age, the severity of chronic kidney disease increases in par- groups. Statistically significant differenc- with Evens in the elderly (60-74 y/o) age allel with the stage of chronic es were observed in patients with CCI II group and in Russians compared with the cerebral ischemia in each ethnic group. in Evens and Yakuts compared with Rus- Evens in the senile (75-89 y/o) age group We also carried out a comparative sians. according to the two computational for- analysis of the dependence of the neu- Old age and CCI increasing severity mulas. In patients with CCI II, statistically rological symptoms of chronic cerebral decreases GFR in all ethnic groups (ta- significant differences were noted only in ischemia on the mean value of the glo- ble 3). In Yakuts and Russians with CCI I Russians aged 75-89 years compared merular filtration rate in the elderly and and CCI II of all age groups GFR is lower with the Evens in the same group. De- senile, taking into account national iden- compared with the Evens. Significant crease in GFR, depending on the stage tity and age group (Table 4). We have differences were noted in patients with CCI I of the Yakut nationality compared Table 4

Neurological symptoms in the studied patients by age depending on the magnitude of the glomerular filtration rate

Evens Yakuts Russians Neurological symptoms P P P M m M m M m e-ya e-r ya-r 60-74 years Vestibulopathy 74.81 4.26 70.83 3.63 71.83 3.54 0.083 0.595 0.844 CCF 82.28 2.29 76.04 1.91 78.53 2.05 0.039 0.225 0.377 Extrapyramidal syndrome 85.95 9.47 65.86 9.45 51.56 11.34 0.19 0.083 0.381 MCI 76.11 4.55 71.10 3.39 71.50 4.17 0.384 0.462 0.941 POR 41.04 2.96 39.09 4.83 54.45 17.87 0.753 0.589 0.544 Ataxia 77.62 4.03 73.30 3.67 72.52 4.18 0.432 0.385 0.889 Pyramidal syndrome 77.32 4.19 71.79 3.23 71.95 3.52 0.303 0.334 0.973 Pathological reflexes 50.00 9.12 36.77 2.20 43.32 3.65 0.282 0.552 0.209 Vegetative symptoms 84.07 3.92 78.20 5.04 82.87 2.48 0.368 0.798 0.418 Sensory disorders 85.04 5.14 76.45 4.99 80.01 3.86 0.238 0.441 0.575 Reflex asymmetry 89.35 5.51 85.24 3.70 85.48 3.78 0.544 0.570 0.965 Vestibular-ataxic disorders 95.55 4.31 85.57 3.21 92.50 3.74 0.078 0.60 0.172 Changes in muscle tone 102.09 5.50 86.95 7.56 84.66 5.04 0.141 0.044 0.807 75-89 years Vestibulopathy 59.87 4.36 54.78 7.64 47.78 2.71 0.576 0.026 0.417 CCF 59.20 2.39 53.13 2.26 49.71 1.95 0.069 0.003 0.256 Extrapyramidal syndrome 79.85 6.69 37.28 1.05 52.29 5.27 0.125 0.235 0.035 MCI 60.47 6.31 55.02 4.14 48.75 3.41 0.408 0.124 0.250 POR 41.41 2.29 38.79 6.04 54.83 6.77 0.742 0.101 0.152 Ataxia 56.33 4.74 52.92 4.08 48.10 3.23 0.590 0.161 0.361 Pyramidal syndrome 62.93 4.52 54.34 5.50 44.89 2.41 0.239 0.001 0.134 Pathological reflexes 39.29 1.25 38.23 1.43 40.97 2.29 0.588 0.537 0.335 Vegetative symptoms 54.54 4.23 50.07 4.12 41.93 3.02 0.457 0.022 0.429 Sensory disorders 61.68 5.93 51.54 4.61 49.69 3.50 0.192 0.098 0.751 Reflex asymmetry 56.81 6.23 52.44 3.15 51.38 5.95 0.547 0.540 0.879 Vestibular-ataxic disorders 54.05 5.20 53.47 3.33 55.20 4.36 0.926 0.818 0.756 Changes in muscle tone 49.55 4.21 50.24 1.87 45.66 8.78 0.809 0.846 0.657 3’ 2019 107

identified changes in the clinical picture, cept for the extrapyramidal syndrome, tained a calmer, more traditional lifestyle neurological status. Persons of Russian it is mild cognitive impairment (MCI), and nutrition of the peoples of Yakutia, nationality had more pronounced chang- pyramidal syndrome, and sensory dis- had lighter clinical symptoms of chronic es in the clinical picture of neurological orders. A more pronounced decrease cerebral ischemia and lower renal abnor- symptoms. in GFR is also observed in representa- malities. At the same time, according to the tives of all nations with POR, pathological symptoms, high numbers of GFR are reflexes, in addition, in Evens, with the References observed in elderly Evens, except for changes of the muscle tone, in Yakuts 1. Арьев А.Л., Чесноков А.А., Дзахова primitive oral reflexes (POR). Yakuts with extrapyramidal syndrome, ataxia, С.Д. [и др.]. Мультиморбидность как один из have low GFR, except for extrapyrami- in Russians with vestibulopathy, CCF предикторов развития контраст–индуциро- dal syndrome, ataxia and changes in (craniocerebral failure), MCI, ataxia, py- ванной нефропатии в гериатрической практике. Нефрология. 2017; 21 (1):.34-37. muscle tone. Russians have a high GFR ramidal syndrome, and sensitive disor- [Ariev AL, Chesnokov AA, Dzakhova SD et al. with POR, a low with extrapyramidal syn- ders, change in muscle tone. Multimorbidity as one of the predictors of the de- drome, ataxia. Thus, the presence of chronic kidney velopment of contrast-induced nephropathy in Among the senile, the Evens have disease was associated with the most geriatric practice. Nefrologiya. 2017; 21 (1): 34- a more favorable clinical picture, with pronounced cognitive and neurological 37. (In Russ.)] 2. Мухин Н.А. Снижение скорости the exception of POR, pathological re- disorders, and a worsening of symptoms клубочковой фильтрации – общепопуляцион- flex, vestibular-ataxic disorders (VAD), with the severity of CCI was noted. ный маркер неблагоприятного прогноза. changes in muscle tone. Renal dysfunc- Conclusion. Based on our study, it Терапевтический архив. 2007; 6: 5-10. [Mukhin tion is expressed in Russians, apart from can be stated that in the studied elder- NA. Decrease in glomerular filtration rate - general population marker of unfavorable prognosis. extrapyramidal syndrome, POR, patho- ly and senile age patients, the develop- Terapevticheskij arhiv. 2017; 6: 5-10. (In Russ.)] logical reflexes, VAD. Late elderly Yakuts ment and progression of chronic cere- http://www.fesmu.ru/elib/Article.aspx?id=166933 occupy an intermediate position, except bral ischemia occurs in parallel with the 3. Мякотных В.С. Некоторые проблемы for the extrapyramidal syndrome, POR, progression of chronic kidney disease. современной геронтологии и гериатрии pathological reflexes, VAD, where there At the same time, more severe neuro- в Российской Федерации: взгляд врача- клинициста. Успехи геронтологии. 2012; 2(25): are lower rates of GFR. logical symptoms were discovered in the 197-204. [Myakotnykh VS. Some problems of An interesting fact is that in the elderly representatives of the non-indigenous modern gerontology and geriatrics in the Russian the low rate of GFR is observed in repre- population due to structural changes in Federation: a view of a clinician. Uspekhi geron- sentatives of all nationalities with POR and the cerebral vascular bed due to arteri- tologii. 2012; 2(25): 197-204. (In Russ.)] https:// elibrary.ru/item.asp?id=17830261 pathological reflexes, which explains the al hypertension and atherosclerosis, as 4. National Kidney Foundation. K/DOQI Clini- parallelism of the stages of CKD and CCI. well as severe renal dysfunction. The cal practice guidelines for chronic kidney disease: In the senile Evens, GFR is reduced Evens, the indigenous inhabitants of evaluation, classification, and stratification. Am J with all objective symptoms of CCI, ex- the northern regions of Yakutia, who re- Kidney Dis 2002; 39 (Suppl 1): SI-266.

I.P. Gouriev DISTRIBUTION OF CARRIERS OF “INDO- EUROPEAN” HAPLOTYPES OF HLA SYSTEM DOI 10.25789/YMJ.2019.67.32 ON THE TERRITORY OF EURASIA

The age of the “Indo-European” haplotypes HLA-A1/B17 and HLA-A1/B8 is calculated for different populations of Eurasia. The obtained data are compared with historical events. The results show that the most ancient carriers of the HLA-A1/B17 haplotype are Latvians, and the HLA-A1/ B8 haplotype are the Turks. The distribution of the HLA-A1/B17 haplotype in populations is consistent with the migration patterns of Indo-European tribes. This is not observed for HLA-A1/B8; therefore, it has been suggested that the majority of Indo-European tribes did not have this haplotype. A definition of allele frequencies is proposed by directly counting the number of haplotypes by alleles without using the Bernstein formula. Keywords: Inlo-Europeans, HLA system, haplotype, population, founder effect.

Since the 70-s of the last century, anti- to the study of haplotypes, since it can the HLA-A1 and HLA-B8 genes, also gens of the HLA system have been wide- provide more specific information about HLA-A1/B8 haplotype are Indo-Europe- ly used for genetic characterization of some population events. an, since they appeared in Europe to- populations along with other polymorphic For the new approach, the HLA sys- gether with Indo-European tribes. At the systems. On the basis of allele frequen- tem with highly polymorphic and closely time, Indo-Europeans in Siberia distrib- cies, similarities or differences between linked loci is a very convenient tool for uted the haplotype HLA-A1/B17. There- individual populations were identified, studying the genetic history of popula- fore, this paper discusses the distribution and phylogenetic trees were constructed. tions. From the literature data on the fre- of haplotypes HLA-A1/B17 and HLA-A1/ At the end of the 20th century, a new ap- quencies of alleles and haplotypes of the B8 over the territory Eurasia. proach to the study of population genet- HLA system from different populations, To calculate the age of the haplotype ics appeared, called genetic archeology. one can determine the critical moments in population, the formula according to [3] The new approach pays great attention in their history, the age of expansion of is used: 1/n those or other haplotypes, and associate S1/2 = 1 – p , them with a specific historical event. where S is the genetic distance be- GURYEV Innokenty Pavlovich - Candidate According to V.V. Fefelova [23] L. tween the loci under study, p is the level of Agricultural Sciences, [email protected] Degos and J. Dausset believed that stability (the proportion of chromosomes 108 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

that preserve the founder chromosome), from Russian merchants as a result of The arrival of theHLA-A1/B8 haplo- n is the number of generations between the development of trade. type in ancestors of Germans in the VII the founder chromosome and modern HLA antigens in Turks were studied century AD due to the seizure of land chromosomes. by two group of authors. Albert et al. [22] by the Slavs east of Elbe with the partial The genetic distance (S) between the investigated 162 Turkish workers and assimilation of German population. This HLA-A and HLA-B loci is 0,8 cM. To determine the level stability (p) of the hap- Table 1 lotype under consideration, one should first find out its initial (maximum) equal Age of haplotypes HLA-A1/B17 и HLA-A1/B8 in different populations of Eurasia to the square root of its theoretically alive frequency, that is h = (h h )1/2, where h А1/В17 А1/В8 1 А В А Population A source is the allele frequency, component of the n years ago n years ago Latvians 368 9196 40 995 [14] haplotype from locus A, hВ is the frequency of allele, component of the haplotype Russians (Moscow) 341 8525 78 1950 [15] from locus B. The value of h1 can also be Russians (Nizhny Novgorod) 247 6187 78 1950 [10] calculated using the linkage disequilibri- Ukrains (southeast) 283 7064 206 5140 [9] um value of the haplotype D as follows: Germans (Munich) 185 4625 54 1350 [22] 1/2 h1 = (h2 - D) , where h2 is modern, that is, Belorusians (Мinsk) 174 4350 117 2933 [5] the observed frequency of the haplotype, Кomi 173 4325 114 2854 [16] D is the delta value or magnitude of the Тurks а) 161 4020 314 7820 [22] linkage disequilibrium. The level of stabil- b) 144 3600 235 5870 [18] ity (p) will be equal to the fraction of the Buryats 156 3900 no В8 allele [23]. [11] modern, that is, the observed frequency Spanish 147 3675 - - [23] of the haplotype h from its initial frequen- 2 Тоfs 129 3225 - - [23] cy h1. The ages of the studied haplotypes calculated in this way in a number of pop- Тurkмеn 128 3200 - - [23] French People 126 3150 89 2215 [13] ulations are shown in Table 1. As can be seen Table 1, of the pop- Pakistanis 108 2696 no А1/В8 [20] ulation examined here, the first haplo- Ashkenazi Jews 106 2650 - - [23]. [19] type HLA-A1/B17 began to split from the Sherpa 104 2606 no В8 allele [21] ancestors of Latvians about 9200 years Indiaan Hindu 82 2050 - - [23] ago and from them fell to the ancestors Yakuts а) 63 1572 no А1/В8 [12] of Russians and Ukrainians and further б) 59 1489 no А1/В8 [23] spread to other peoples. The haplotype Basque 40 1000 - - [23] HLA-A1/B8 first appeared among the Khanty 34 850 no А1/В8 [7] ancestors of the Turks 7846 years ago and spread exclusively throughout Eu- students working in Germany, and as a was facilitated by the great migration of ropeans. The Mongoloids and Pakistanis control group – 442 Germans. The group peoples. This is the name of the combi- do not have this haplotype, and Latvians of Turks was from different regions of nation of ethnic movements in Europe in began to multiply only 40 generation ago. Turkey, most of them were from rural ar- the IV – VII centuries, caused mainly by Buryats and Sherpas have no HLA-B8 eas. The persons included in study of A. the general cooling of the climate. Peo- allele. Svejgaard were also from different places ple from areas with continental climate According to current calculation, the in Turkey, but from urban areas. In total rushed to areas with a milder climate. haplotype HLA-A1/B8 in Latvians began there were 119 samples, of which 117 Wars, frequent floods, crop failures, fam- to multiple about 1000 years ago. In the were not relatives. ine epidemics greatly reduced the popu- history it is just noted that at the end of At first glance, the results of the two lation of Western Europe in VI, VII cen- the first millennium AD as a result of the groups of authors seemed to differ, but turies. wars between the stronger western and due to the small samples analyzed, The studied I.G. Udina and G.S. Rau- eastern neighbors of the Latvians, very these differences turned out to be unreli- tian three Komi groups here are com- little remained, and their number began able. According Albert et al. HLA-A1/B17 bined into one population. As a result, to increase after partial assimilation by haplotype is estimated to be 4020±870 the Komi haplotype ages turned out to be the Belarusians and the Russians. years old, and according to A.Svejgaard very close with the corresponding hap- At the end of the I millennium AD ma- et al. 3600±900; HLA-A1/B8 age – like lotype age in Belorusians. This suggest jor changes took place in the life of the 7800±1900 and 5870±1400 years ago, that the Komi and Belorusians have com- ancient Latvian tribes: feudalism, a new respectively. mon ancestors 3-4 thousand years ago. socio-economic formation, began to The splitting of the HLA-A1/B17 hap- According to historical data, the first take shape, while the territory of Latvia lotype in the ancestors of Belorusians, Indo-European tribes invaded the territo- became the crossroads of trade routes. Komi, Germans, Pakistanis and Turks ry of modern Pakistan in the late II and Russian merchants walked along the coincides with the movements of the early I Millennium BC, therefore the stud- Daugava up to its lower reaches and by first nomads of Europe – Indo-European ied population is Caucasian. Therefore land from Pskov and Novgorod. Conse- tribes in III millennium BC. Iranian tribes B.G. Solheim et al. [20] were surprised quently, it is quite legitimate to assume went to Iran, Afghanistan, Indo-Arians by the absence of haplotype HLA-A1/ that the impetus for an increase in num- went to India, the Hittites invaded Asia B8 in Caucasian population and highest bers after a strong decline was their ac- Minor, and the Celts moved to Western frequency of non-Caucasian haplotype quisition of the HLA-A1 / B8 haplotype Europe [4]. HLA-A10/B8 with a very high D-value. 3’ 2019 109

Сalculation from the data of B.G. Kingdom of Israel – Samaria-was defeat- the antigen A1 was found in 97 people Solheim et al. [20] showed that with the ed by the warriors of Assyria, and its pop- and B17-in 96, and the sum of chromo- invasion of the Indo-Europeans in Paki- ulation was resettled by the Assyrians in somes with such alleles turned out only stan, the haplotypes HLA-A1/B5 (since media and there was lost among the sur- 92. It is clear that 5 people have haplo- 980 BC) and HLA-A1B17 (since 724 BC) rounding peoples. In 586 BC the Babylo- type A1/Bx and 4 people – Ax / B17. In spread, and haplotype began to multiply nians conquered the Kingdom of Judah, the same way, it can be understood that later, since 312 BC. At the time, Pakistan destroyed the temple of Jerusalem, and 12 people are carriers of the haplotype was ruled by Persian Sassanid dynasty, took the color of its population to Baby- Ax/B27 (Table 2) which ruled from Asia Minor to Central lon (the Babylonian captivity). 70 years Layout by haplotypes shows that the Asia. At the end of III, beginning of the later, due to the generous Cyrus of Per- actual frequency of alleles in the work of IV century a number of regions in East sia, who broke the power of Babylon, the V. V. Fefelova other than that specified dis appeared from the Empire. These Jews were able to return to their land and in article, for example, the frequency of territories were conquered during the build a new Temple in Jerusalem, which A1 is 01414, not 0,1531, frequency B17 reign of Shapur II in 309-372 BC. There- helped to restore the number of Jews. – 0,1399, not 0,1514. With the correction fore, due to coincidence of time, Shapur In 1972, the Sherpas had a popula- of data, the age of the haplotype HLA-A1/ II is supposed to be founder in Pakistan tion of approximately 13,000 living in B17 in Yakuts changes from 70 genera- of the chromosome with the haplotype solu Khumbu in the Eastern Nepal re- tions to 59. From this we can conclude HLA-A10/B8. gion. Sherpas come from a small group that in such works a more accurate re- From the data of Table 1 it is seen that of families who, according to historical sult will come out when the frequencies the first Indo – European influence of the documents, came from the city of Salmo of alleles and haplotypes will be derived Siberian peoples were the Buryats - at Ganges in the Eastern Tibetan province by direct counting after the layout of hap- the beginning of the II Millennium BC. of Han and who migrated West to settle lotypes in the lattice, without the use of Probably the ancestors of the Buryats in the high valleys near Everest. This mi- Bernstein's formula h = 1 – . gained haplotype HLA-A1/B17 with pen- gration occurred around 1530 A.D. the In the paper “About the Yakuts ori- etrated into Western Mongolia Indo-Euro- Sherpas ' Single families established gin…” (Genetics, 2004), we hypothesized peans who inhabited this region in D. E. so-called tribal villages where only mem- that the haplotype HLA-A1/B17 fell to the Eremeev [4] at the turn of III-II Millennium bers of the clan's family, not foreigners, Yakuts, as well as to the Indians, from the BC, the ancestors of Turkmens Tofs and are allowed to live. Clans of Sherpas Saks. You can still add the hypothesis this haplotype came seven centuries af- was established in strictly patrilineal that the introduction of this haplotype with ter drilled. fashion, which in the genealogies record the Huns. When comparing the English The emergence of the haplotype the names of only through the male line. language belonging to the German group HLA-A1 / B17 in Western Europe – 3675 Sherpas marry only members of other of languages and the Yakut language be- years ago in Spain and 3150 years ago in Sherpas clans, but do not mix with other longing to the Turkic group, the matches France, in all probability, due to the Celts. populations. The rule of exogamy is very of the words of the compared languages They caused a great genetic change in strictly enforced. Therefore, inbreeding in sound and meaning were revealed. Spain – with their conquest, the men be- does not occur in the Sherpa population Therefore, linguists express the ancient fore them in the Iberian Peninsula com- [21]. As can be seen from table1, Cauca- historical connection of the Huns (Tur- pletely disappeared from the gene pool, sian haplotype HLA-A1/B17 introduced kic-speaking tribes) with the Germanic as can be seen from the Y-chromosome Sherpa 104 generations ago in 624 BC, tribes. It is known that the Huns in the 70s [“New Scientist”]. that is, in the Eastern Tibetan. of the IV century, subordinated a number The Celts were called Gauls by the The expansion of the haplotype of Germanic tribes. Among turkologists Romans. Apparently, they gave the HLA-A1 / B17 in Hindus (2050 years ago) there is an opinion that the direct descen- French the haplotype HLA-A1/B8 – 236 historically coincides with the formation dants of the Hun substrate of those times BC during the first Millennium BC the of the Indo-Saka state, which began with are modern Yakuts, as part of the Huns Greeks, Romans and Carthaginians had king Maues. According to numismatic migrated to the East, to Central Asia and established colonies on the Mediter- data, beginning his rule applies no later further [17]. ranean coast and coastal Islands. The than the middle of the I century BC. After Basques – a people that lives in the Roman Empire captured the southern Maues there were five kings in this dy- mountains and the Atlantic ocean between part of Gaul and turned it into a province nasty [2]. Spain and France and speaks in cryptic called Norbonne Gaul.at the end of the II Previously it was published that the language eskuara. The strange thing is century BC. Yakuts have mainly Mongoloid antigen that the Indo-European haplotype HLA-A1/ The population of Ashkenazi Jews frequencies of the HLA system, and the B17 was introduced to the Spaniards 3675 passed through the "bottleneck" of a Indo-European haplotype HLA-A1/B17 years ago, the French 3150 years ago, small number 106 generations ago, after began to split them 70 generations ago. and the Basques only 1000 years ago. In- which the haplotype HLA-A1/B17 began This result was obtained from the work deed, in history it is noted that the Basques to multiply. At this time, the Kingdom of of V. V. Fefelova [23] by calculating the did not submit to any invader and kept Israel was greatly weakened by the divi- frequency of genes from the frequen- their language and traditions, although sion into two kingdoms – Jewish and Is- cy of antigens according to the formula they were pushed to the mountains and raeli, and by rivalry between them. This h = 1 – . But in the Table 3 in clamped to the ocean. According to the cal- was not slow to take advantage of the Fefelova there is no blank graph and culations of haplotype HLA-A1/B17 got to neighbors. the sum of haplotype frequencies by al- the Basque population in the period of the First, the Egyptian Pharaoh Shes- leles. Because of this, it is impossible to Reconquista. So called the process of win- honk II raided Judea, took Jerusalim and understand whether the number of chro- ning the Iberian Peninsula from the yoke of robbed many other cities of the country. mosomes corresponds to the number of Mauritania, which lasted from 718 to 1492. In 722 BC, the capital of the Northern people in alleles. The article shows that In 905-925 Basque king Sancho Garc- 110 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

Table 2 References

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[Bon- Bw22 2 0 0 0 1 0 1 0 0 0 2 gard-Levin GV, Ilyin GF. India in antiquity. Mos- cow: Nauka, 1985: 738. (In Russ.)]. B27 59 3 7 2 30 1 4 0 0 12 59 3. Евграфов О.В. Генетическая археология: B35 53 7 23 4 25 3 0 0 0 0 62 новый подход к исследованию генетической B40 139 8 59 2 67 11 5 2 0 0 154 истории популяций. Докл. РАН, 1994; 6 (338): 822-826. [Evgrafov OV. Genetic archeology: a Bx 5 0 0 0 0 0 0 0 54 59 new approach to the study of the genetic history Total 97 209 36 206 26 22 10 2 78 686 of populations. Dokl. RAS. 1994; 6 (338): 822- 826. (In Russ.)]. Note: the number of samples is written in italics, otherwise the number of haplotypes. 4. Еремеев Д.Е. На стыке Азии и Европы. Очерки о Турции и турках. М.: Nauka, 1980: 238. [Yeremeev DE. At the junction of Asia and es strengthens the Kingdom of Pamplona mestic horse found in the southern Urals Europe. Essays on Turkey and the Turks. Mos- and proclaims the Kingdom of Navarra. in the Parking lots of Mullino and Dav- cow: Nauka, 1980: 238. (In Russ.)]. It was one of the outposts of the Re- lekanovo. They are dated by C-14 by the 5. Семенов Г.В., В.И. Левин В.И., Гошко conquista. Under Sancho III the Great turn of VII-VI millennia BC [6]. This is also Н.Н. и др. Иммуногенетические параметры (970-1035) the Kingdom expanded the consistent with the opinion of most sci- HLA (локусы С и DR) жителей Минска. Анти- гены гистосовместимости и заболевания: Сб. borders of their possessions in the South entists who consider the black sea and науч. тр., СПб; 1991; 9-16. [Semenov GV, Levin and distributed the authority over all of Caspian steppes to be the probable an- VI, Goshko NN et al. Immunogenetic parameters Christian Spain. At this point, the Basque cestral home of Indo-Europeans. Then, of HLA (C and DR loci) of Minsk residents. Sb. haplotype HLA-A1/B17 appeared. There- at the beginning of the VI Millennium BC nauch. tr. Histocompatibility antigens and diseases. Sat scientific works. St-Peterburg; 1991: 9-16. fore, Sancho III the Great can be consid- Indo-Europeans could conquer Eastern (In Russ.)]. ered to have spread in the Basque stud- Anatolia. 6. Матюшин Г.Н. Археологический словарь. ied haplotype from Spanish Christians. Haplotype HLA-A1/B17 spread to all М.: Просвещение: АО «Учеб. лит.», 1996; 304. V.P. Alekseev points out that the reset- populations conquered by Indo-Europe- [Matyushin GN. Archeological dictionary. M.: En- tlement of Indo-Europeans began in the an tribes, and the time of its appearance lightenment: AO “Teaching. lit.”; 1996: 304. (In Russ.)]. south-east of Europe rushing west, they coincides with historical events, but the 7. Абрамов В.Ю., Зарецкая Ю.М., Кривцо- occupied all of Europe as far as the Atlan- appearance of haplotype HLA – A1/B8 - ва Л.А., Оточева Л.А. Особенности полимор- tic. Part of the Indo-European tribes that not quite often. The fact that the repre- физма генетической системы HLA в популя- spread to the north and east did not go sentatives of the Indo – Aryan people-Pa- ции хантов. Генетика. 1990; 26(6): 1087-1091. [Abramov VYu, Zarethkaya YuM, Krivthova LA, further than the Ural Mountains. In this re- kistanis this haplotype is absent, and mi- Otocheva LA. Feature of the polymorphism of the gard, the age of the HLT-A1 / B17 in Khanty grated to Western Europe Celts spread genetic system HLA in the population of Khanty. is only 850 years old, showing the acqui- there only haplotype HLA-A1/B17, indi- Genetics; 1990; 26(6): 1087-1091(In Russ.)]. sition of the haplotype in the XII century. cates that neither the Arians nor the Celts 8. Хаитов Р.М. и др. Полиморфизм генов им- Since the turn of the X-XI centuries, haplotype HLA-A1/B8 was not. мунного ответа и его роль в противоинфекци- онной защите Иммунология. 2013; 3:132-144. the role of fur hunting, acquiring com- Probably it arose by mutation only [Khaitov RM et al. Polymorphism of genes of the mercial value, has been growing. In the arrived in Asia Minor and the Hittites, immune response and its role in anti-infective pro- X-XIII centuries, Komi-Zyryan and Rus- and from them came the ancestors of tection. Immunology. 2013; 3:132-144(In Russ)]. sian Novgorod merchants, “industrial the Ukrainians. The rest of the Europe- 9. Тимошенко Л.И., Бурка Н.И., Бай Е.Н., Минченко Ж.Н. Популяционно-генетическое people” (fur hunters) penetrated to the ans this haplotype spread much later. изучение лейкоцитарных антигенов системы north of the Urals and Western Siberia. Probably, the frequency of HLA-B8 hap- HLA у жителей юго-восточной географической In this regard, it is assumed the appear- lotype and the HLA-A1/B8 Europeans зоны УССР. Проблемы гематологии и перели- ance of the European haplotype HLA-A1 increased, as suggested by V. Bodmer, вания крови. 1992; 27(1): 37-40. [Timoshenko / B17 among the Khanty from Russian or after the pandemics of plague, smallpox LI, Burka NI, Bay EN, Minchenko ZhN. Genetic study of the leucocytic HLA system antigens in Komi-Zyrian traders. and cholera. It was later found that car- the population of the south-eastern geno-geo- Perhaps, the ancestors of the Rus- riers of haplotype HLA-A1/B8/DR3 were graphicl zone of the Ukrainian SSR. Problems of sians were Indo-Europeans or faced In- highly resistant to infections regardless of hematology and blood transfusion. 1982 27(1): do-Europeans in the 7th millennium BC the nature of their pathogens [8]. If this 37-40. (In Russ)]. 10. Казакова И.М., Сидорова Т.И. Козло- in the steppes of the Black Sea or Cas- is the case, it is not the founder's effect, ва Н.Л. и др. Распределение лейкоцитарных pian region. They could come on horse- but the natural selection that changed антигенов и частота аллосенсибилизации к back from the Urals, as there at that time the immunogenetic profile of Europeans различным антигенам системы HLA среди жи- the horse was domesticated. in antiquity, the Middle Ages and the Re- телей Нижнего Новгорода. Антигены гистосов- Тhe most ancient remains of a do- naissance as a result of epidemics. местимости и заболевания: Сб. науч. тр. СПб; 3’ 2019 111

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CLINICAL CASE A. A Shevchenko, E. A Kashkarov, N. G Zhila., A.V Koshevoy CLINICAL CASE OF SUCCESSFUL APPLICATION OF REOSTEOSYNTHESIS STERNUM IN CHRONIC POSTOPERATIVE DOI 10.25789/YMJ.2019.67.33 STERNOMEDIASTINITIS

The authors described the clinical observation of postoperative sternomediastinitis. The feasibility of a two-stage surgical treatment of this pathology was noted: the first stage is the removal of ligatures and necrectomy of the sternum, the second is the resection of the sternum with plastic replacement of the wound defect. At the integrity of the sternum, the authors propose to perform surgical intervention, including the preservation of bone tissue, sternal rheosteosynthesis. Keywords: osteomyelitis of the sternum, sternomediastinitis.

Postoperative sternal wound infec- ated with high mortality [2, 4]. Clinical ex- tion of the sternum with plastic replace- tions is a severe threatening complication perience of postoperative sternal wound ment of the chest wall wound defect. of open cardiac surgery and it is associ- infections treatment [1, 3, 5, 6] indicates However, it should be noted that it does the need for two-stage treatment of this not always achieve a positive result in the pathology, due to the severe general con- form of primary healing. In this regard, SHEVCHENKO Alexander Alexandrovich, dition of patients in the onset of the dis- in our view, this clinical case of the reos- candidate of medical Sciences, associate Pro- ease, the severity of concomitant chron- teosynthesis execution in the process of fessor of the Department of Surgery FESMU, ic pathology and the inability to perform two-stage treatment of the patient with Far Eastern State Medical University, 680000, wound plastic operation in purulent ne- postoperative sternal wound infections 35 Muravyov-Amursky St, phone 8-914-770- crotic infection conditions. with a positive outcome would be inter- 34-77, e-mail: [email protected]; KASH- KAROV Evgeniy Alexandrovich, the head of According to the accepted technique esting to experts. the department of Thoracic Surgery Regional of treatment in the Regional Clinical Hos- 18.04.18 Patient K. aged 70, first Clinical Hospital No.1, 680000, 9 Krasno- pital №1 in Khabarovsk [5], the first stage entered the Thoracic Department of darskaya St., e-mail: [email protected]; is the wound surgical treatment, including the Regional Clinical Hospital №1 in ZHILA Nikolai Grigorievich, doctor of medi- the removal of foreign bodies, necrecto- Khabarovsk. At the time of admission, he cal Sciences, Professor of department of sur- my of infected bone fragments of the complained of pain in the lower third of gical diseases of childhood Saint Petersburg sternum. Due to the inflammatory nature the sternum, the presence of fistulas in state pediatric medical University, 194100, of the wound, it is not sutured and open the middle third of the scar with purulent Saint Petersburg, 2 Litovskaya St, e-mail: [email protected]; KOSHEVOY Alexander Vlad- treatment is carried out by bandaging. As discharge. During examination: the chest imirovich, a thoracic surgeon of the depart- the wound is cleaned, which is controlled in the region of the median line had the ment of Thoracic Surgery Regional Clinical macroscopically and microbiologically, sternotomy immature scar in the lower Hospital No. 1680000, 9 Krasnodarskaya St. the second stage is the extensive resec- third of which there was a fistula sized 0.2 112 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

x 0.5 cm with purulent discharge. There was redness of the skin and swelling of the edges of the tissues around the fistula. At palpation moderate soreness in the lower third of the sternum was determined. SCT showed the features of the sternum subtotal osteomyelitis. From the history of the disease: 2.04.2018 in the Federal Center of Car- diovascular Surgery in Khabarovsk, the sternotomic access surgery mammaro- coronary bypass of the anterior descend- а b ing artery, autovenous bypass of the Fig. 2. a) Mobilized half of the sternum artery of the blunt edge, posterior inter- b) Fixation of the sternum ventricular artery were performed. In the Fig. 1. Patient K., 70 years old: the appear- postoperative period, after discharging, ance of a wound in the sternum area before the second stage of surgical treatment remove foreign bodies and sequesters 12.04.2018 there was redness of the of the sternum; the second stage is skin on the sternal scar, the occurrence the implementation of resection of the the integrity of the sternum (there was an of pain, and 17.04.2018 in the lower third sternum with plastic replacement of the isolated fracture of the left half of the ster- of the scar fistula with purulent discharge wound defect of the chest wall. In the num) and absence of purulent changes opened. He was examined by a thorac- case of the sternum integrity, the absence in the bone tissue we decided to perform ic surgeon and then sent to the Thoracic of pus and adequate microbiological sternal rheosteosynthesis. Department in Regional Clinical Hospital purity of the wound the implementation of 20.07.2018 there was the operation №1 for treatment. Anamnesis of life: Cor- sternal rheosteosynthesis is justified as - mediastinotomy excision, the sternal onary heart disease: Stable angina of FC the second stage. III. Postinfarction cardiosclerosis (2008). rheosteosynthesis. In the process of Atherosclerosis of the coronary arteries: surgery, the edges of the mediastinotomy the defeat of several vessels. Hyperten- were cut; the skin wound was expanded References sion, stage III, degree 2, risk 4. CH2 A, II in the cranial direction to the edge of the sternal hilt. Fragments of the 1. Вишневский А.А., Печетов А.А. Совре- FC by NYHA. Prostate cancer T2NxM0, менное многоэтапное хирургическое лечение II CL. gr.. ICD (DT 2016). CKD 2 st. (GFR sternum were mobilized from the anterior больных хроническим послеоперационным 68 ml/min). Chronic cholecystitis, adi- mediastinum, while the right pleural медиастинитом. Практическая медицина. pose hepatosis, chronic obstructive pul- cavity in the lower third of the sternotomy 2010;8(47):4-8. [Vishnеvskiy AA, Pechetov AA. monary disease, remission phase. was opened. The drainage of the right Modern multi-stage surgical treatment of patients with chronic postoperative mediastinitis. Praktich- The patient was hospitalized in the pleural space was performed in the eskaya medicina. 2010; 8(47):4-8. (In Russ.). ] Thoracic Surgery Department with the 5th intercostal space along the middle 2. Корымасов Е.А, Пушкин С.Ю., Бенян acute postoperative sternal wound infec- clavicle line of the PVC drainage valve А.С., Медведчиков-Ария М.А. Стратегия и так- tions diagnosis (fistula formation). At the along the Bulau. The revision revealed a тика хирургического лечения инфекционных transverse fracture of the upper third of осложнений после стернотомии. Раны и ране- first stage of the treatment (18.04.18 - вые инфекции. 2015;2(4):15-25. [Korimasov EA, 25.05.18) a surgical revision of the wound the left half of the sternum. The thorough Pushkin CU, Benyan AS, Medvedchikov-Ariya was performed (24.04.18), the sternal curettage of the surface of the sternal M.A. Strategy and tactics of surgical treatment of ligatures were removed, the sanation of fragments with partial edge resection of infectious complications after sternotomy. Rani i the protruding edges, the scraping of the ranevie infekcii. 2015; 2(4):15-25 (In Russ.). ] the mediastinum was performed. In the 3. Национальные клинические рекомен- process of surgical intervention the con- granulation tissue were conducted. The дации. Торакальная хирургия / под ред. П.К. solidation of the sternum was not stated, mediastinum was sanitized. The sternum Яблонского. – М.: ГЭОТАР-Медиа, 2014:160. the severe acute sternal wound infection fragments were fixed with three 8-shaped [National clinical guidelines. Thoracic surgery. was observed. In the postoperative pe- and one U-shaped sutures. The wound PK Yablonsky, editor. Moscow: GEOTAR-Media; 2014:160. riod, open wound care was performed. was sutured tightly. The postoperative 4. Вишневский А.А., Рудаков С.С., Ми- The patient got a course of antibacterial period passed without complications, ланов Н.О. и др Хирургия грудной стенки. (cefepime, ciprofloxacin, vancomycin), the patient got vancomycin, metrogil, Руководство. – М.: Издательский дом Видар anti-inflammatory and cardiotropic ther- kvamatel and cardiac medications. The – М, 2005:312. [Vishnevsky AA, Rudakov SS, Milanov NA, Surgery of the chest wall. Moscow: apy, bandages with antiseptics, includ- pleural drainage was removed on the Publishing house Vidar; 2005]. ing vacuum bandages, were used. As a fifth day. The wound was healed by 5. Шевченко А.А., Жила Н.Г., Кашкаров Е.А. result of the therapeutic measures, the the primary intention. On the 14th the Анализ лечения послеоперационного остео- patient’s condition was stabilized, the patient was discharged with detailed миелита грудины и стерномедиастинита Даль- discharge from the wound decreased, recommendations for further outpatient невосточный медицинский журнал 2017;1:30- 33. [Shevchenko A. A., Zhila N. G., Kashkarov E. became meager and mucous. The micro- treatment. A. Analysis of postoperative osteomyelitis of the biological spectrum of the wound allowed Conclusion. In the treatment of sternum and sternomediastinitis. Dalnevostochnij to continue further surgical treatment. sternomediastinitis, in our opinion, it is medicinskij zhurnal. 2017; 1:30-33 (In Russ.). ] The patient returned to the hospital for advisable to use a two-stage method of 6. Yue-Dong Shi, Fa-Zhi Qi, Yong Zhang. Treatment of sternal wound infections after open- the second stage (02.07.18 – 03.08.18) the surgical treatment: on the first stage heart surgery. Asian Journal of Surgery. 2014; of the surgical treatment (Fig. 1). Taking it is necessary to perform a resternotomy, 37:24 – 29. 3’ 2019 113

EXPERIENCE EXCHANGE

V.A. Ivanov, K.N. Bolshev, R.Z. Alekseev, A.S. Andreev DETERMINATION OF THE THERMAL CHARACTERISTICS OF THE MATERIAL

DOI 10.25789/YMJ.2019.67.34 OF THE INSULATING SHEATH FOR THE TREATMENT OF COLD INJURIES

In the treatment of cold injuries for maximum tissue recovery is very important temperature. The frostbitten area must be warmed up due to the natural heat exchange by the blood circulation, for this the condition of maximum thermal insulation of the affected area must be observed. The article describes the method and provides data on the laboratory determination of thermal conductivity and heat transfer resistance of the material from which the heat-insulating sheaths are made for treatment frostbitten limbs. The results were obtained by the method of stationary thermal conditions at the facility assembled in the department of heat and mass transfer processes of the IPTPN SB RAS. In this paper, a climate chamber, a precision “Tercon” signal converter and non-standard heat flux transducers of the PTP-1B type with integrated temperature sensors are used. Keywords: climatic chamber, frostbite, low temperatures, heat insulation, thermal conductivity.

The Republic Sakha (Yakutia) is fa- the maximum possible tissue repair, it is chamber of -30 °C, and the other side is mous for its extremely low temperatures, necessary to observe the condition of at room temperature + 22 °C. it is here that the so-called “Pole of Cold” slow and gradual warming of frostbitten The temperature and heat flux were is located - Oymyakon village, where tissues due to natural heat exchange by recorded using a multichannel, preci- the air temperature in winter falls to the blood circulation. To this end, the in- sion Terсon signal converter. Converter -71.2°C. In severe climatic conditions, the jured limb is thermally insulated as much is coupled with IBM PC through a seri- problems associated with frostbite and as possible and various means are used al interface type RS -232 C , and allows hypothermia of people is of indisputable to accelerate blood circulation [1]. One of you to record measurement data of heat relevance. During the winter, about 200 the original solutions is "Hotutent" devel- fluxes and temperatures in the form of a people come to hospitals in the Republic oped and produced by the Yakut devel- table or graph. of Sakha (Yakutia) with frostbite of the ex- oper’s multilayer insulating material. PTP-1B converters, developed by the tremities and in a state of profound hypo- The purpose of the work is to deter- Institute of engineering thermophysics thermia. Proper, timely provision of medi- mine the thermal conductivity of a heat- of the National academy of sciences of cal care in the regions of the Far North is insulating material “Hotutent”, which is Ukraine (Kiev), were used to measure the largely ensured by qualitative preliminary used as thermal insulation for extremities heat flux. The PTP-1B sensor is a round clinical and technical research [2]. of people, who received frostbite under thin plate made of a PCB with a diameter The vast majority of cold injuries conditions of low climatic temperatures. of 100 mm and a thickness of 2 mm with cause frostbite of the extremities. In case A rectangular sample of material “Ho- six leads. The PTP-1B sensor also con- of severe frostbite of the extremities, for tutent” with dimensions of 29.5 cm by tains a resistance thermometer, where 26 cm was examined. The material is the Pt 100 platinum thermometer with a

stitched through the seams and has a nominal static characteristic W100 = 1.385 IVANOV Vasiliy Alekseevich, doctor of layered structure. is used as sensitive element. The nomi- technical sciences, leading researcher of the The structure of the material consists nal value of the resistance thermometer heat and mass transfer department Institute of physical and technical problems of the North of 8 layers: at 0 °C is 100 Ω. The limit of permissible named after V.P. Larionov Siberian branch 1. Outer layer: oxford fabric. basic relative error of heat flux measure- of the Russian academy of sciences, v.ivan- 2. Bamboo heating insulation filler. ment is ± 4%, and the limit of permissible [email protected] Yakutsk, 677000, Russia. BOL- 3. Insulation №1. Fuzz absolute error of temperature measure- SHEV Konstantin Nikolaevich, candidate of 4. Insulation number 2: Deer wool. ment is ± 0.5 K [3]. technical sciences, head of the department 6. Bamboo heating insulation filler. Such combined sensors are very con- of heat and mass transfer, Institute of physical 7. Oxford fabric. venient for use in the experimental de- and technical problems of the North named 8. Inner layer: heat reflective mate- termination of resistance to heat transfer after V.P. Larionov Siberian branch of the Rus- sian academy of sciences, [email protected] rial (foil). and thermal conductivity of materials, Yakutsk, 677000, Russia. ALEKSEEV Revo Thermal conductivity was determined since when placing them on both sides of Zakharovich, doctor of medical sciences, by the stationary method at the facility the sample under study, we obtain a com- professor, senior researcher of the depart- assembled in the department of heat and plete set of initial data for the calculation. ment for the study of adaptation mechanisms, mass transfer processes of the IPTPN To place the sample in the boundary Yakut science Centre of Complex medical SB RAS. To create a constant tempera- plane between the chamber and the problems, [email protected] Yakutsk, 677000, ture difference across the sample thick- room, an extruded polystyrene foam Russia. ANDREEV Aleksandr Semenovich, ness, the BINDER MK-53 climate cham- screen with a size of 550 × 550 × 100 mm lead engineer of the heat and mass transfer department, Institute of physical and technical ber was used. The working temperature was made with an opening in the center problems of the North named after V.P. Lari- range of this chamber is from -40 to +180 for the dimensions of the sample plate. onov Siberian branch of the Russian academy °C. Thermostat accuracy in a chamber After reaching the specified negative of sciences, [email protected] Yakutsk, is ± 1 °C. One side of the plate is main- temperature in the climate chamber, the 677000, Russia. tained at a negative temperature in the value of which was chosen as - 30 °C, 114 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

and the establishment of a stationary ductivity is below the tabulated values of mode, data recording continues for an- thermal conductivity of materials such as other 5 minutes for calculations, we took mineral wool and low density polystyrene the values of fluxes and temperatures av- insulation (0.045 W/(m*K)) [5]. eraged over this stationary period. The value of thermal resistance to References heat transfer is determined by the formu- 1. Алексеев Р.З., Большев К.Н., Томский la 1 [4]: М.И., Пугач В.Н., Андреев А.С. Внедрение (1) автоматизированного прибора для монито- ринга температуры конечностей человека при лечении хладотравм. Якутский медицинский журнал. 2017; 4(60):60-62. [Alekseev RZ, Bol- Where t2, t1, are temperatures on the shev KN, Tomsky MI, Pugach VN, Andreev AS. warm and cold surfaces of the plate, °C; Introduction of an automated device for monitor- - the average density of the heat flux ing the temperature of human extremities in the W / m2, determined by the formula 2: treatment of cold traumas. Yakut Medical Journal. 2017; 4(60): 60-62 (In Russ.).] 2. Алексеев Р.З., Стручков Н.А., Нифонтов К.Р., Андреев А.С. Изменение общих (2) Fig.1. Installation for measuring thermal con- клинических параметров и показателей сер- ductivity дечно сосудистой системы при холодовой травме у собак. Якутский медицинский журнал. Where u2, u1 , – voltage signals from 2017; 1(57): 54-56. [Alekseev RZ, Struchkov NA, two heat meters, mV; K2, K1, – the corre- Nifontov KR, Andreev AS. Changes in general sponding values of the conversion coeffi- clinical parameters and indices of the cardiovas- cients, W / (m2 · mV). cular system during cold injury in dogs. Yakut medical journal. 2017; 1(57): 54-56 (In Russ.).] The value of thermal conductivi- 3. Малышев А.В., Степанов А.В. ty λ plate, W / (m·°C) is determined by Определение термического сопротивления the formula 3: теплопередаче слоя жидкого керамического теплоизоляционного покрытия «Броня». (3) Евразийский союз ученых IV международная научно-практическая конференция «Совре- менные концепции научных исследований». Where - h is the plate thickness, m; 26-27сентября. Москва. 2014; 6. Часть 6:40-43. [Malyshev AV, Stepanov AV. Determination of the RK – calculated by the formula (1) thermal resistance to heat transfer, (m2 ·°C) / thermal resistance of the heat transfer layer of liquid ceramic insulation coating "Armor". Eurasian W. The thickness h was taken as the av- Fig.2. Diagram of the measurement setup Union of Scientists IV International Scientific and erage profile of about 3 centimeters. Practical Conference "Modern Concepts of Sci- In fig. 3 and fig. 4 shows the graphs entific Research". September 26-27. Moscow. of the development of the density of the 2014; 6. Part 6: 40-43 (In Russ.).]. 4. ГОСТ 7076-99 Материалы и изделия heat flux and temperatures on the surfac- строительные. Метод определения теплопро- es of the sample. водности и термического сопротивления при Thermal resistance to heat transfer of стационарном тепловом режиме. Госстрой the heat-insulating material for isolation России. - М., 2000; 23 с. [GOST 7076-99 Build- ing materials and products. Method for determin- of frostbitten extremities is equal to 1.050 ing thermal conductivity and thermal resistance (m 2 ∙ K) / W. Thermal conductivity of the under stationary thermal conditions. Gosstroy of material corresponding to the given thick- Russia. – M., 2000; 23 p. (In Russ.)]. ness is 0.028 W / (m · K). 5. Ivanov VA, Bolshev KN, Stepanov AA, Malyshev AV, Andreev AS. Estimation of the These results confirm declared ther- basalt-reinforced material of thermal resistance. mal insulation properties of the mate- Fig. 3. Graphs of change in the density of East European Scientific Journal. 2017; 9 (25): rial. The obtained value of thermal con- the heat flux on the warm and cold sides of 62-64. the sample on time

Fig. 4. The graphs change the temperature of the warm and cold sides of the sample over time 3’ 2019 115

R.A. Saleev, A.B. Abdrashitova COMPARATIVE ANALYSIS OF MAXILLOFACIAL AREA DISEASES, WHICH LED TO TEMPORARY DISABILITY DOI 10.25789/YMJ.2019.67.35 IN DENTAL MEDICAL ORGANIZATIONS

In this article the authors studied the temporary disability cases in patients with the maxillofacial area diseases that received treatment and rehabilitation in the dental medical organizations in the period of 2007-2016. Methods.The groups of the maxillofacial area diseases that lead to restriction and/or loss of capacity for work of the adult population in the Re- public of Tatarstan: inflammatory (of odontogenic and neodontogenic genesis), traumatic, benign and malignant lesions, secondary jaw edentulism (full or partial), as well as tooth eruption diseases. Results. The odontogenic inflammatory processes made the largest share in the causes of temporary disability in patients of dental medical organizations (66.1% of cases), the injuries took a second place (13.9%), the secondary jaw edentulism observed in 7.4% of cases took the third place. Conclusions. The authors found that during the period under study, the statistically significant changes in the duration of temporary disability cases with odontogenic inflammatory processes, tooth eruption diseases, secondary jaw edentulism, injuries and neoplasms were noted. The analysis showed statistically significant differences in the structure of temporary disability cases by nosological groups, depending on sex, age and year of observation. Keywords: stomatology, dental medical organization, treatment and rehabilitation of patients, examination of temporary disability, maxillofacial area diseases.

Introduction. The examination of musculoskeletal system diseases [1,2]. tal medical organizations of the Republic temporary disability (ETD) is a type of When appealing to a dental medical or- of Tatarstan served as a source of the medical activity aimed at assessing the ganization, the patient is given a tempo- information was (analysis of accounting patient’s health status, the quality and rary sheet of disability based on the pa- and reporting forms 16-ВН, 036/у, 035/у, effectiveness of the treatment, the possi- tient’s testimony, the duration of which is 043/у for the period 2007-2016). The ma- bility of professional activities, determin- determined by the time of treatment and terial of the study was subjected to sta- ing the timing of temporary disability [3]. the patient rehabilitation for a full return tistical processing using the methods of The examination of temporary disability to the work process. Many authors in parametric and nonparametric analysis in the Russian Federation is regulated their studies assert that the case of tem- in accordance with the results of testing by the following orders: On approval of porary or total disability with the disease the compared populations for the normal Procedure for Issuing Sheets of Disability of any organs and systems of the body distribution. The accumulation, updating, No. 624н dated June 29, 2011; On Intro- leads to the patient’s somatic and mental systematization of the initial information duction of Changes in Procedure for Is- imbalance [4,5,6]. The person of working and visualization of the obtained results suing Sheets of Disability No. 31н dated age: women - up to 55 years, men - up were carried out in Microsoft Office Excel January 24, 2012; On Approval of Proce- to 60 years makes the main category 2016. The statistical analysis was carried dure for Examination of Temporary Dis- of patients seeking medical dental care. out using the IBM SPSS Statistics 23. ability No. 625н dated August 23, 2016; Most patients almost always present a Results and discussion. The maxil- On Introduction of Form for Registration temporary sheet of disability to the social lofacial area is an important element of of Clinical and Expert Work in Treatment insurance fund for the payment of corre- the anatomical and functional unity of the and Prevention Institutions No. 154 dat- sponding allowance. human body. Taking into account the pe- ed May 21, 2002. Among the nosologies Duration of disability by a patient may culiarities of the structure of soft tissues, with temporary disability, the digestive depend on various factors, such as the maxillofacial bones, their blood supply system diseases occupy the sixth place type and course of the maxillofacial area and innervation, we have defined the after the respiratory and circulatory organ disease, seasonality, individual charac- groups of the maxillofacial area diseases diseases, injuries and poisonings, and teristics of the organism. The estimated that lead to the limitation and/or loss of periods of temporary disability for diges- the working capacity of the adult popu- tive diseases (class XI according to ICD- lation: inflammatory (of odontogenic and SALEEV Rinat Akhmedullovich, Doctor of 10) are established relative to the group non-dontogenous genesis), traumatic, Medical Science, Dean of Faculty of Dentist- ry of Kazan State Medical University Federal of the maxillofacial area diseases in the benign and malignant lesions, secondary State Budgetary Educational Institution of Russian Federation. However, we have jaw edentulism (full or partial), as well as Higher Education of the Ministry of Health of not revealed any data on the effect of var- tooth eruption diseases. When appealing Russia, 49 Butlerov St, 420012 Kazan, Rus- ious factors on the duration of temporary to a dental medical organization, as a sia, e-mail: [email protected]._ ORCID: disability in the patient with maxillofacial rule, in most cases, the sheet of disability 0000-0003-3604-7321. ABDRASHITOVA area disease during treatment in dental is issued by a dentist-surgeon, somewhat Alena Borisovna, Candidate of Medical Sci- medical organizations. less often by a dentist-therapist. ence, Associate Professor of Pediatric Den- The purpose of the study is to analyze The total number of temporary disabil- tistry of Kazan State Medical University Fed- temporary disability cases in the maxil- ity cases studied by us in dental medical eral State Budgetary Educational Institution of Higher Education of the Ministry of Health of lofacial area diseases in dental practice organizations of the Republic of Tatarstan Russia, 49 Butlerov St, 420012 Kazan, Rus- over a period of 10 years. for 2007-2016 totaled 12,891 units, which sia, e-mail: [email protected]. ORCID: Material and methods. The temporary we accepted as the general population. 0000-0002-3315-7560 disability cases, established by the den- The statistical analysis was carried out by 116 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

the method of a sample, in which, based maining years the fluctuations of the in- statistically significant (p<0.001). For on mathematical calculations, the num- dicator were insignificant, ranging from this indicator, a gradual decrease from ber was 5,204 cases. The distribution 4.68 days in 2010 to 6.54 days in 2008. 14.89 to 7.88 days, observed from 2008 of temporary disability cases in the Re- The results of the comparison of the to 2015, was characteristic. However, in public of Tatarstan by years is shown in duration of cases of temporary disability 2016 the average duration of the case Figure 1. due to secondary jaw edentulism in the increased significantly, reaching 15.92 According to the presented figure, the dynamics from 2009 to 2016 (in 2007- days. The growth of this indicator we as- greatest number of temporary disability 2008 there was a small number of cases sociate with the increase of cases of joint cases due to dental diseases was regis- of this pathology) are shown in Figure 4. treatment and rehabilitation of patients tered in 2013 (904 cases), the smallest The analysis made it possible to reveal with the maxillofacial area injuries in the - in 2009 (253 cases). At this stage of our statistically significant differences in the dental medical organization in 2016 and study, we estimated the time dependence duration of cases of temporary disability the conditions of the maxillofacial depart- of the incidence of temporary disability at secondary jaw edentulism in dynamics ment of the profile hospital. from various factors, including the no- (p<0.001). When comparing the values The next nosological group, for which sological group of the disease, sex, age, of the indicator, the significantly differ- the dynamics of the average duration of and doctor’s experience. ent average duration of the case in 2015 cases of temporary disability was studied, The results of the comparison of the came under our notice, which was 17.29 were the maxillofacial area neoplasms. In duration of temporary disability cases, days, which was almost twice as high as this section of our study, we consider the depending on the nosological group to the next largest indicator of 2013, equal maxillofacial area neoplasms of only be- which the underlying disease was relat- to 9.36 days. We associate the growth of nign genesis, treatment and rehabilitation ed, are presented in Table 1. this indicator with an insignificant number of these patients was performed in the According to the study, the duration of of cases of temporary disability at jaw dental medical organizations or the max- temporary disability cases in maxillofacial edentulism in the structure of the maxil- illofacial department of the profile hospi- area diseases had statistically significant lofacial area diseases leading to the oc- tal according to indications. The resulting differences, depending on the nosologi- currence of the case of temporary loss of graph is shown in Figure 6. cal group to which the underlying disease capacity for work by the patient, hence, In accordance with the data obtained, belonged (p<0.001). The mean duration in this case, the median fluctuation was the average duration of the case was of the case was greatest in patients with minimal. characterized by statistically significant abnormalities of maxillofacial area de- The average levels of the duration positive dynamics, increasing during the velopment and with injuries, amounting of cases of temporary disability caused study period from 4 to 17 days (p<0.001). to 12.18±1.26 and 11.79±0.36 days, re- by maxillofacial area injuries were com- According to the results of the analy- spectively. The lowest values were taken pared in dynamics in Figure 5. sis, the differences in the duration of cas- in the case of odontogenic inflammatory As in the case of other studied diseases of temporary disability with non-dental processes in the maxillofacial area and es, the changes in the duration of cases inflammatory diseases and maxillofacial tooth eruption diseases (5.61±0.08 and of temporary disability due to maxillo- anomalies, depending on the year of ob- 6.13±0.35 days, respectively). facial area injuries in 2007-2016 were servation, were statistically insignificant Comparison of the duration of tem- (p=0.125 and 0.257, respectively). porary disability cases corresponding to In the study, we also revealed the ef- certain nosological groups was also per- fect of the patient’s sex on the duration formed in dynamics. The following dia- of temporary disability in various nosol- gram was obtained for the group of odon- ogies of maxillofacial area diseases. The togenic inflammatory processes (Fig. 2). results are shown in Table 2. In accordance with the results of a According to the presented Table, single-factor analysis of variance, the the statistically significant differences in statistically significant differences in the the duration of cases of temporary dis- duration of cases of odontogenic inflam- ability, depending on sex were noted in matory processes in dynamics over 10 Distribution of temporary disability cases in a most nosological groups. The index took years were established (p<0.001). During sample during the period under study significantly higher values among men in the study period, there was a significant increase in the average from 2008 to Table 1 2013 from 4.88 to 6.47 days. In 2015, the average duration of cases fell sharply to Comparison of duration of temporary disability cases, depending on affiliation of 5.29 days, and in 2016 it fell to 5.05 days. disease to particular nosological group When comparing the duration of cases of temporary disability caused by tooth Duration of cases, days eruption diseases, the data presented in Nosological groups Figure 3 were obtained in the dynamics. M±m Based on the data obtained, the statis- Odontogenic inflammatory processes of maxillofacial area 5.61±0.08 tically significant differences in the dura- Tooth eruption diseases 6.13±0.35 tion of cases of tooth eruption diseases, Secondary jaw edentulism 8.57±0.36 depending on the year of observation, Maxillofacial area injuries 11.79±0.36 were noted (p=0.006). At the same time, Neodontogenic inflammatory processes of maxillofacial area 7.61±0.46 the average duration of cases took the Maxillofacial area neoplasms 7.83±0.63 maximum values in 2009 and 2012 (8.0 Anomalies in maxillofacial area development 12.18±1.26 and 9.36 days, respectively), in the re- Polypathia 8.15±0.8 3’ 2019 117

tooth eruption diseases, secondary jaw Table 2 edentulism, injuries and neoplasms were The duration of cases of temporary disability, depending on patients’ sex of in noted. The statistically significant differ- nosological groups of maxillofacial area diseases ences in the structure of cases of temporary disability on nosological groups of Duration of cases of temporary maxillofacial area diseases were estab- Nosological group disability (M±m) p lished depending on sex, age, and year Men Women of observation. Odontogenic inflammatory processes 5.88±0.15 5.52±0.09 0.039* There is no conflict of interest. of maxillofacial area Tooth eruption diseases 7.04±1.05 5.88±0.32 0.296 Secondary jaw edentulism 10.77±0.79 7.38±0.3 <0.001* References Maxillofacial area injuries 13.37±0.54 9.07±0.43 <0.001* Neodontogenic inflammatory processes 1. Ushnitsky I.D., Ivanov A.V., Ivanova A.A., 8.17±0.79 6.36±0.46 0.051 of maxillofacial area Yurkevitch A.V., Seydalova E.M., Novogodin A.A. Maxillofacial area neoplasms 8.89±0.97 5.89±0.44 0.007* Clinical-epidemiological characteristics of patho- Anomalies in maxillofacial area logical processes of periodontal tissues of inflam- 15.07±2.01 9.82±1.58 0.043* development matory-destructive nature. Yakut medical journal. Polypathia 10.81±2.04 6.92±0.76 0.083 2018; 1 (61):79—82. 2. Naygovzina N.B., Luchinsky A.V. State * - differences in indicators are statistically significant (p<0.05) guarantees for medical dental care provided to the outpatients setting. Stomatology. 2015; case of odontogenic inflammatory pro- and 33 years of age, respectively). Later, 4:12-15. (In Russ.). https://doi.org/10.17116/ stomat201594412-15. cesses in the maxillofacial are (p=0.039), other causes were secondary jaw eden- 3. Federal Law No. 323-ФЗ dated November secondary jaw edentulism (p<0.001), in- tulism (38 years of age) and odontogenic 21, 2011 On the Fundamentals of Public Health juries (p<0.001), neoplasms (p=0.007), inflammatory processes of maxillofacial Protection in the Russian Federation. The link developmental abnormalities (p=0.007). area (37 years of age). is active as of April 19, 2017. (in Russ.). https:// The average duration of temporary in- www.rosminzdrav.ru/documents/7025. Conclusion. Taking into account the 4. Shamsiyarov N.N., Galiullin A.N. Clinical capacity in patients with non-pediatric peculiarities of the structure of soft tis- and statistical analysis of the economically ac- inflammatory processes and associated sues, maxillofacial bones, their blood tive population of Kazan city. Vestnik sovremen- diseases was also increased in men, the supply and innervation, we have identi- noi klinicheskoi medicine. 2015; 8(2):74-81. (In significance level was very close to the fied groups of maxillofacial area diseases Russ.). 5. Rreeuwijk K.G., Robroek S.J.W., Burdorf A., critical level (p=0.051 and p=0.083, re- that lead to the limitation and/or loss of Hakkaart L. How work impairments and reduced spectively). capacity for work of the adult population work ability are associated with health care use Another factor, whose influence on the in the Republic of Tatarstan: inflammatory in workers with musculoskeletal disorders, cardio- nosological structure of cases of tempo- (of odontogenic and neodontogenic gen- vascular disorders or mental disorders. Journal of rary disability was studied, was the pa- esis), traumatic, benign and malignant Occupational Rehabilitation; 2014;24;4;631-639. https://doi.org/10.1007/s10926-013-9492-3. tients’ age. As the analysis showed, the lesions, secondary jaw edentulism (full or 6. Caroline H. van Dongen, Paulien H. Goos- patients’ age had statistically significant partial), as well as tooth eruption diseas- sens, Inge E. van Zee, Kirsten N. Verpoort, Thea differences depending on the nosological es. We established that during the study P.M. Vliet Vlieland, Judith M. van Velzen. Short- group (p<0.001). The lowest values of period, the statistically significant chang- Term Outcomes of a Vocational Rehabilitation the median age were observed in tooth Program for Patients with Acquired Brain Injury in es in the duration of cases of temporary the Netherlands. Journal of Occupational Reha- eruption diseases (29 years of age), in- disability due to odontogenic inflamma- bilitation, 2017/ https://doi.org/10.1007/s10926- juries and developmental anomalies (32 tory processes in the maxillofacial area, 017-9738-6. 118 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

M.S. Savvina, S.A. Evseeva, T.I. Nelunova, T. Е. Burtseva M.P. Slobodchikova RISK FACTORS INFLUENCING THE PERSISTENCE OF PATENT DUCTUS ARTERIOSUS IN NEONATES WITH CHD DOI 10.25789/YMJ.2019.67.36 IN THE REPUBLIC SAKHA (YAKUTIA)

The authors present their research of factors, possibly influencing the duration of persistent patent ductus arteriosus (PDA) in the neonates with congenital heart defects (CHDs) in the Republic Sakha (Yakutia). Such factors as multiple pregnancy, operative delivery, gestational arterial hypertension, preeclampsia, fetoplacental insufficiency, anemia in pregnancy, threatened miscarriage, congenital heart defects in future mother, and ethnicity of a mother or a father are examined. A retrospective clinical research work was based on the data of the Perinatal Centre of the Republican hospital No1, National Centre of medicine. A research work is based on clinical results of medical tests, taken from 162 medical records of the patients with a diagnosed “Congenital heart disease” (CHD). According to the results of statistical analysis there were revealed most significant risk factors for long-term persistent arterial ducts among the neonate population of the Republic Sakha (Yakutia). They may be associated with: complicated course of pregnancy, i.e. gestational arterial hypertension with or without proteinuria, pregnancy edema associated with presence or absence of proteinuria, fetoplacental insufficiency, anemia of the current pregnancy and presence of CHD in the mother’s past history. Keywords: congenital heart defect, arterial duct, hemodinamically insignificant patent ductus arteriosus.

Introduction. The prevalence of the intake etc., are known. A number of sev- of CHDs was divided into groups: the 1st patent ductus arteriosus (PDA) in the eral factors which can be associated with group consists of the patients with non-re- newborns remains unknown as there are high risk of long-term persistence of PDA vealed shunting according to the Doppler no distinct criteria from what period of in neonates are not well studied in the ter- monitoring of the vessel with pulmonary gestation PDA is considered pathologic. ritory of the Republic of Sakha (Yakutia). artery projection, non-functioning arteri- Nominally it is supposed to close with- Objectives: The factors that are pos- al flow; the nd2 group consists of the pain the first two weeks after birth. Under sibly associated with the long-term per- tients with revealed systolic and diastolic such criteria the prevalence of the isolat- sistence of PDA in neonates with CHDs disorders or systolic shunting, according ed pathology is 0.14-0.3 per 1,000 live- are studied. to the Doppler monitoring of the vessel born children, 7% among all the CHDs Methods and materials: A retrospec- with pulmonary artery projection, func- and 3% among all the critical defects [7]. tive clinical research work was based on tioning arterial flow; the 3rd group con- Persistence of the arterial duct consid- the data of the Perinatal Centre of the sists of all cases of CHD. The research erably depends on the term of gestation Republican hospital No1, National Cen- was performed from 2001 to 2003 on the besides that the data that some factors of tre of medicine. A research work is based base of ATL-HDI-3000 Philips, from 2013 the mother, such as intrauterine hypoxia, on clinical results of medical tests, taken to 2015 on the base of EPIQ-7 Philips. non-steroid anti-inflammatory medication from 162 medical records of the patients The age of the neonates included in with a diagnosed “Congenital heart dis- the selective group was from 17 to 40 for ease” (CHD). The time distance of the mothers and from 17 to 48 for fathers. SAVVINA Maya Semyonovna – Ph.D., se- medical records is registered two times, The period of gestation at the moment of nior staff scientist of the laboratory of pediatric thus from 2001 to 2003 and from 2013 birth of a child with CHD was from 25 to health level monitoring, Yakut science Centre to 2015. The CHD is recorded according 41 weeks. The body weight at moment of complex medical problems, Yakutsk, Rus- to Q20-Q28 (ICD-10, chapter XVII: Con- of the birth was from 564 gr to 4,500 gr. sia, e-mail: [email protected]; NELUN- genital malformations, deformations and The height at the moment of the birth was OVA Tuyara Ivanovna – cardiologist of the chromosomal abnormalities). The deliv- from 30 cm to 58cm. Perinatal Center of the Republican hospital ery case reports (#010u) and patient’s The family history of the both parents No1, postgraduate, St. Petersburg state pe- discharge statistic card (#066/u-02) were was retrospectively evaluated. Thus, the diatric medical university, St. Petersburg, the initial documentations for analysis. following factors were included: 1) the fac- Russia; EVSEYEVA Sardana Anatolievna – Ph.D., senior staff scientist of the laborato- All the neonates had experienced ul- tors complicating pregnancy (gestational ry of pediatric health level monitoring, Yakut trasound examination (Doppler echocar- hypertension with or without proteinuria, science Centre of complex medical problems, diography) of the heart to evaluate the edema with or without proteinuria for the Yakutsk, Russia; BURTSEVA Tatiana Egor- anatomical structure and cardiovascular current pregnancy, preeclampsia, feto- ovna – MD, professor of the department of pe- function. The selection is based on the placental insufficiency, anemia during the diatrics and pediatric surgery, Medical institute cases with bypass through interatrial current pregnancy, multiple pregnancy, of the North-Eastern federal university, a head septum according to the results of ultra- threatened miscarriage, operative deliv- of the laboratory of the Yakut science Centre of sound investigation. The functioning ac- ery of the current pregnancy); 2) CHD in complex medical problems, Yakutsk, Russia; tivity of the arterial duct was evaluated by the mother’s past history; 3) ethnicity of SLOBODCHIKOVA Maya Pavlovna – a senior lecturer of the department of foreign lan- colour Doppler test to define additional the parents (was registered by self-deter- guages with the course of Russian language, flow in the vessel projection, i.e. pulmo- mination of the survey). St. Petersburg state pediatric medical univer- nary trunk. According to the results of the On data processing χ2 criteria were sity, St. Petersburg, Russia. ultrasound investigation, all the selection used (comparing binary / nominal vari- 3’ 2019 119

ables) and the Mann-Whitney U test arterial duct (p=0.157), the revealed data erably higher in both groups and were of (comparing continuous variables). When are not statistically confirmed. The feto- the same degree (Table 1). p<0.05 the intergroup accuracy was con- placental insufficiency of the current preg- Threatened miscarriage of the current sidered significant. The initial data were nancy was registered in 36.4% of all cases pregnancy in the past history of the neo- accumulated in the database by means of born with CHDs (n=162). A higher asso- nates as a possible predictor of a long- Microsoft® Excel software, all the statistic ciation of the fetoplacental insufficiency term persistence of the arterial duct was operations were conducted by means of with a risk of persistence of PDA (p=0.157) also studied. According to the common SPSS® Statistics software (IBM® USA). in comparison with closure of PDA are data, threatened miscarriage was re- Results and discussion. The statis- noticed, but not confirmed statistically. vealed in 38.3% of all the selected groups tical analysis of the repeated ultrasound Anemia in pregnancy was most com- of the arterial duct. The results of this re- investigations of one and the same child mon for the group of HIS-PDA (n=86), in search show that threatened miscarriage with CHD confirming the presence or ab- the group of the patent ductus arteriosus most commonly occurred in groups of sence of PDA was carried out. 162 cases (n=76), it composed 56.6% and 50.0% HIS-PDA (n=86)-45.3% than in groups of were selected. A possible association of respectively. The revealed data were not PDA (n=76) – 30.3%. The results are not multiple pregnancy with the risk of long- statistically confirmed (p=0.402), but they statistically verified (p=0.049) and show term persistence of the ductus arteriosus showed possible association of anemia the association of the threatened miscar- during the medical reexaminations was with a risk of persistence of PDA, never- riage with a risk of persistence of PDA as analyzed (Table 1). theless a part of anemic turned consid- well as closure of PDA. The following factors aggravating pregnancy were investigated, i.e. gesta- Table 1 tional arterial hypertension and edema The proportion of factors aggravating the course of pregnancy in groups of newborns with or without proteinuria, preeclampsia, with HIS-PDA and PDA fetoplacental insufficiency, anemia of the current pregnancy and threatened miscarriage, as well as operative delivery. Group No factor multiple pregnancy p According to the research statistically 1 n=86 94.2 5.8 0.130 unconfirmed results were obtained, i.e. 2 n=76 98.7 1.3 0.130 the results were higher for multiple preg- Total n=162 96.3 3.7 0.130 nancies among hemodinamically insignif- Gestational arterial hypertension icant patent ductus arteriosus (HIS-PDA) No factor with or without proteinuria (n=86) – 5.8% than in groups with the hemodinamically significant patent duc- 1 n=86 66.3 33.7 0.948 tus arteriosus (HS-PDA) (n=76) – 1.3%. 2 n=76 65.8 34.2 0.948 Multiple pregnancy as a predictor of long- Total n=162 66.0 34.0 0.948 term persistence of the patent ductus ar- No factor Preeclampsia teriosus among all the selections became 1 n=86 20.9 73.1 0.058 statistically unsatisfactory. 2 n=76 34.2 65.8 0.058 The association of the gestational ar- Total n=162 27.2 72.8 0.058 terial hypertension with or without proteinuria of the current pregnancy with a No factor Fetoplacental insufficiency risk of persistence of PDA (p=0.948) was 1 n=86 68.6 31.4 0.157 revealed, but the results are not statistically verified. In 34% of all cases of re-ex- 2 n=76 57.9 42.1 0.157 amination of the arterial duct (n=162) the Total n=162 63.6 36.4 0.157 following factors were registered. The No factor Anemia prevalence of the gestational arterial 1 n=86 50.0 50.0 0.402 hypertension with or without proteinuria, 2 n=76 43.4 56.6 0.402 and edema of the pregnancy with or Total n=162 46.9 53.1 0.402 without proteinuria in the structure of the No factor Threatened miscarriage arterial duct was equal in both groups: 1 n=86 54.7 45.3 0.049 HIS-PDA– 33.7% (n=86) and HS-PDA – 34.2% (n=76). 2 n=76 63.7 30.3 0.049 According to the results, preeclampsia Total n=162 61.7 38.3 0.049 of the current pregnancy was registered No factor Mothers with CHD in 72.8% of all cases of CHDs and was 1 n=86 93.0 7.0 0.075 more significantly associated with the risk 2 n=76 84.2 15.8 0.075 of long-term persistence of the ductus Total n=162 88.9 11.1 0.075 arteriosus. A part of preeclampsia in the No factor Operative delivery groups of HIS-PDA (n=86) was higher – 73.1%, (in a case of the patent ductus ar- 1 n=86 53.5 46.5 0.821 teriosus (n=76) – 65.8%). These results 2 n=76 55.3 44.7 0.821 were statistically unverified (p=0.058). Total n=162 54.3 45.7 0.821 The results show an equal association Note. In the Tables 1-2 1st group - there were no signs of the functioning of the ductus of fetoplacental insufficiency with the risk of arteriosus during re-examination (HIS-PDA); 2nd group - signs of the functioning of the persistence arterial duct and closure of the arterial duct (PDA) were revealed. 120 ЯКУТСКИЙ МЕДИЦИНСКИЙ ЖУРНАЛ

Also the cases of CHD in the mother’s in PDA group rather than in HIS-PDA 2. The association of a risk of per- past history of a CHD neonate as a pos- group (16.1% and 8% respectively). In a sistent PDA and PDA closure with such sible predictor of long-term persistence group of HIS-PDA 4.7% corresponded to factors as gestational hypertension with of PDA are also studied. The research the peoples of Caucasus (1.3% in PDA or without proteinuria, pregnancy edema data show that mother’s CHD was reg- group). associated with presence or absence of istered in 11.1% of all selected groups. Among the fathers of the CHD neo- proteinuria, anemia in pregnancy and Statistically unconfirmed data showed nates it was most common for Yakuts and threatened miscarriage was statistically association of mother’s CHD in PDA Russian 73.51% and 17.3% respectively. unconfirmed. groups (p=0.075). In PDA groups (n=76) There were 14.9% for Evenks, 2.5% for 3. The association of fetoplacental this factor far doubled than in groups of peoples of Caucasus and other nations insufficiency with risk of persistent PDA HIS-PDA (n=76), it was 15.8% and 7.0% (Ukrainians, Polishes, Germans, Tatars, was unconfirmed statistically. respectively. Buryats, Kumyks and Khakasses) – 0.6% 4. The association of mother’s CHD The operative delivery of the current for each group. Statistically unconfirmed in a group of PDA was also unconfirmed pregnancy as a factor of possible long- results show that the ethnicity of the fa- statistically. term persistence of the ductus arteriosus ther is associated with groups of arterial According to the results of statistical turned to be statistically unsatisfactory, it ducts (p=0.565). The research revealed analysis there were revealed most signif- was common for HIS-PDA group of neo- that PDA group was most common for icant risk factors for long-term persistent nates – 46.5% (Table 1). Yakuts (75%). Russian and Evenks com- arterial ducts among the neonate popu- The ethnicity of the mothers and fa- monly occurred in the groups of HIS-PDA lation of the Republic Sakha (Yakutia). thers in children with PDA and HIS-PDA (n=86) – 18.6% and 5.8%, and in a group They may be associated with complicat- was investigated (Table 2). PDA (n=76) – 15.8% and 3.9%. Other na- ed course of pregnancy, i.e. gestational Among all the cases of reexaminations (Evens, peoples of the Caucasus, arterial hypertension with or without proteinuria, pregnancy edema associated Table 2 with presence or absence of proteinuria, fetoplacental insufficiency, anemia of the Ethnicity of Parents of Newborns with HIS-PDA and PDA current pregnancy and presence of CHD in the mother’s past history. Mother ethnicity, % The reported study was funded by Groups of arterial duct 1 2 3 4 5 6 7 8 P= RFBR according to the research project 1 n=86 72.1 15.1 0.0 8.1 0.0 4.7 0.0 0.0 0.601 #18-05- 60035_Arctica. 2 n=76 71.1 17.1 1.2 9.2 0.0 1.3 0.0 0.0 0.601 Total n=162 71.6 16.0 0.6 8.6 0.0 3.1 0.0 0.0 0.601 References Father ethnicity. % 1 2 3 4 5 6 7 8 P= 1. Володин Н.Н. Протокол ведения недоно- шенных детей с гемодинамически значимым 1 n=86 72.1 18.6 0.0 5.8 1.3 0.0 0.0 0.0 0.585 функционирующим артериальным протоком. 2 n=76 75.0 15.8 1.3 3.9 1.3 1.3 0.0 1.3 0.585 Российский государственный медицинский Total n=162 73.5 17.3 0.6 4.9 0.6 2.5 0.0 0.6 0.585 университет Росздрава. 2009. [Volodin NN. Preterm infants with hemodynamically significant Note. 1 – Yakuts, 2 – Russians, 3 – Evens, 4 – Evenks, 5 – other indigenous small-numbered patent ductus arteriosus guidelines. Rossiiskii go- peoples of the North, Siberia and the Far East: Dolgans, Yukaghirs, Chukchis, 6 – peoples of sudarstvennii medicinskii universitet Roszdrava. 2009. (In Russ.).] the Caucasus, 7 – peoples of the Central Asia, 8 – others: Ukranians, Polishes, Germans, Tatars, 2. Гераськин А.В. Детская хирургия. Клини- Buryats, Kumyks and Khakasses. ческие разборы. ГЭОТАР – Медиа. 2011. [Ger- askin AV. Pediatric surgery. Clinical examinations. tion of the arterial ducts (n=162), it was Ukranians, Polishes, Germans, Tatars, Geotar-Media. 2011. (In Russ.).] most common for the Yakut and Russian Buryats, Kumyks and Khakasses) were 3. Детская хирургия: национальное руко- водство. ГЭОТАР – Медиа. 2009. [Pediatric mothers 71.6% and 16.0% respectively, present only in a group of PDA. surgery: national guideline. Geotar-Media. 2009. Evenks - 8.6%, peoples of the Caucasus Conclusions: (In Russ.).] – 3.1%. Statistically unconfirmed data 1. Multiple pregnancy as a predictor 4. Гриффин Б. Кардиология. Практика. (p=0.601) of the distribution according of long-term persistence of arterial ducts 2008; 150-152. [Griffin B. Cardiology. Practica. to mothers’ ethnicity were received when on reexamination, according to current 2008; 150-152. (In Russ.).] 5. Прахов А.В. Неонатальная кардиология. comparing the groups of arterial ducts. research, occurred statistically unreli- НГМА. 2008. [Prakhov AV. Neonatal cardiology. According to the results of the research able. Preeclampsia and operative deliv- NGMA. 2008. (In Russ.).] there were Yakut mothers in both groups ery of the current pregnancy as factors 6. Руководство по перинатологии. Информ almost equally – 72.2% and 71.1% re- of possible association with long-term – Навигатор. 2015. [Perinatology guidelines. In- form-Navigator. 2015; 22. (In Russ.).] spectively. Evens were only in PDA persistence of PDA turned statistically 7. Шарыкин А.С. Кардиология. Бином, 2009; group (n=76), 1.2%. It was most common unreliable, and most commonly occurred 50-51. [Sharykin AS. Cardiology. Binom. 2009; for Russian 17.1% and Evenks 9.2% in groups of HIS-PDA. 50-51. (In Russ.).]