Medicni perspektivi, 2022;27(4)
2022 Vol. XXVII N 4
Tsymbalyuk V.I., Vadzyuk S.N., Tolokova T.I., Pankiv I.B. Reproductive health under global warming
Authors and affiliations
Tsymbalyuk V.I. National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
Vadzyuk S.N. I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
Tolokova T.I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine,
Pankiv I.B. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
Key words: global warming, premature birth, reproductive health, adverse effects of pregnancy
Abstract. Reproductive health under global warming. Tsymbalyuk V.I., Vadzyuk S.N., Tolokova T.I., Pankiv I.B. Reproductive health problems are attracting the attention of biomedical scientists in connection with changes in the environment. Climate change in the direction of rising temperatures is an urgent threat to human health with negative long-term effects. Under conditions of global warming, the number of negative consequences of pregnancy is increasing, namely idiopathic premature termination of pregnancy with the birth of premature newborns. The priority to reduce the negative health effects of climate change is to identify most sensitive risk groups to the negative impacts of climate change on health, which include pregnant women and newborns. The strategy to prevent and reduce changes in reproductive health is based on the recognition of global warming as a risk factor that contributes to the growth of premature birth and the associated adverse effects of pregnancy.
- Moiseienko RA, Mokretsov SY, Dudina OO, Kryzyna NP. [Reproductive health of the population of Ukraine as the main criterion for the effectiveness of socio-economic policy]. Zdorovia natsii. 2012;2(3):86-91. Ukrainian. Available from: http://nbuv.gov.ua/UJRN/Uzn_2012_2-3_17
- Joshua P Vogel, Saifon Chawanpaiboon, Ann-Beth Moller, Kanokwaroon Watananirun, Mercedes Bonet, Pisake Lumbiganon. The global epidemiology of preterm birth. Best Practice & Research Clinical Obstetrics & Gynaecology. 2018;52:3-12. doi: https://doi.org/10.1016/j.bpobgyn.2018.04.003
- Sara McElroy, Sindana Ilango, Anna Dimitrova, Alexander Gershunov, Tarik Benmarhnia. Extreme heat, preterm birth, and stillbirth: A global analysis across 14 lower-middle income countries. Environment International.2022;158:106902. doi: https://doi.org/10.1016/j.envint.2021.106902
- Dalugoda Y, Kuppa J, Phung H, Rutherford S, Phung D. Effect of Elevated Ambient Temperature on Maternal, Foetal, and Neonatal Outcomes: A Scoping Review. International Journal of Environmental Research and Public Health. 2022;19(3):1771. doi: https://doi.org/10.3390/ijerph19031771
- Blencowe H, Cousens S, Oestergaard M, Chou D, Moller AB, Narwal R, et al. National, regional and worldwide estimates of preterm birth. The Lancet. 2012 June 9;379(9832):2162-72. doi: https://doi.org/10.1016/S0140-6736(12)60820-4
- Radzinskii VE. [Premature birth and prospects for the use of progesterone for their prevention]. Health of woman. 2013;(3):96-98. Available from: http://nbuv.gov.ua/UJRN/Zdzh_2013_3_22
- Lakatosh VP, Narytnyk TT, Bila VV, Aksonova AV, Tkalich VO. [Premature birth: contradictions and modern realities]. Health of woman. 2014;7(93):10-18. Ukrainian. Available from: http://nbuv.gov.ua/UJRN/Zdzh_2014_7_3
- Young N, Dugas E. Representations of Climate Change in Canadian National Print Media: The Banalization of Global Warming / Canadian Review of Sociology / Revue canadienne de sociologie. 2011 Feb. 01;48:1-22.
- Masson-Delmotte V, Zhai P, Pörtner H-O, Roberts D, Skea J, Shukla PR, et al. An IPCC Special Report on the impacts of global warming of 1.5°C above pre-industrial levels and related global greenhouse gas emission pathways, in the context of strengthening the global response to the threat of climate change, sustainable development, and efforts to eradicate poverty. Waterfield T, editor. Intergovernmental Panel on Climate Change; 2019. Available from:https://report.ipcc.ch/sr15/pdf/sr15_spm_final.pdf
- Jeremiah Bohr. Reporting on climate change: A computational analysis of U.S. newspapers and sources of bias, 1997-2017. Global Environmental Change. 2020 march;61:102038. doi: https://doi.org/10.1016/j.gloenvcha.2020.102038
- Potts M, Henderson CE. Global warming and reproductive health. International Journal of Gynecology and Obstetrics. 2012;119:S64-S67. doi: https://doi.org/10.1016/j.ijgo.2012.03.020
- Masson-Delmotte V, Zhai P, Pörtner HO, Roberts D, Skea J, Shukla PR, et al. An IPCC Special Report on the impacts of global warming of 1.5°C above pre-industrial levels and related global greenhouse gas emission pathways, in the context of strengthening the global response to the threat of climate change, sustainable development, and efforts to eradicate poverty. In Press: Intergovernmental Panel on Climate Change [Internet]; 2019 [cited 2022 May 27]. Available from: https://www.ipcc.ch/report/ar6/wg2/
- Holovatch YV. [The whole is more than the sum of the parts]. Visnyk of the National Academy of Sciences of Ukraine. 2021;12:18-26. doi: https://doi.org/10.15407/visn2021.12.018
- Masson-Delmotte V, Zhai P, Pirani A, Connors SL, Péan C, Berger S, et al, editors. IPCC, 2021: Climate Change 2021: The Physical Science Basis. Contribution of Working Group I to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change [Internet]. In Press: Cambridge University Press.; 2021 [cited 2022 May 27]. Available from: https://www.ipcc.ch/report/ar6/wg1/
- Szopa S, Naik V, Adhikary B, ArtaxoP, Berntsen T, Collins WD, et al. 2021: Short-Lived Climate Forcers. In Climate Change 2021: The Physical Science Basis. Contribution of Working Group I to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change. Masson-Delmotte V, Zhai P, Pirani A, Connors SL, Péan C, Berger S, et al, editors. In Press: Cambridge University Press; Available from: https://www.ipcc.ch/report/ar6/wg1/downloads/report/IPCC_AR6_WGI_Full_Report.pdf
- gov.ua [Internet]. 2021 [cited 2022 May 27]. Available from: https://meteo.gov.ua/ua/33345/zmi/articles/read/61
- [On the approval of the Implementation Concept state policy in the field of change climate for the period until 2030]. Order of 2016, Pub. No. 932. (Dec. 7, 2016). Ukrainian. Available from: https://www.kmu.gov.ua/npas/249573705
- ua [Internet]. [The European Parliament has declared a climate emergency]; 2019 [cited 2022 May 20]. Available from: https://www.rbc.ua/ukr/news/evroparlament-obyavil-klimaticheskoe-chrezvychaynoe-1574945815.html
- ipcc.ch [Internet]. Geneva: Climate Change 2007: Synthesis Report. World Meteorological Organization; 2007 [cited 2022 May 20]. Available from: http://www.ipcc.ch/pdf/assessment-report/ar4/syr/ar4_syr.pdf
- Menezo Y, Dale B, Elder K. The negative impact of the environment on methylation/epigenetic marking in gametes and embryos: A plea for action to protect the fertility of future generations. Mol Reprod Dev. 2019;86:1273-82. doi: https://doi.org/10.1002/mrd.23116
- Taha Z, Hassan Ahmed A, Wikkeling-Scott L, Papandreou D. Factors Associated with preterm birth and Low Birth Weight in Abu Dhabi, the United Arab EmiratesInt. J. Environ. Res. Public Health 2020;17:1382. doi: https://doi.org/10.3390/ijerph17041382
- Wang Q, Zhang H, Huang C. Chapter 12 - Air pollution, climate change, and reproductive health in China. In: Meng Gao, Zifa Wang, Gregory Carmichael, editors. Air Pollution, Climate, and Health. Elsevier; 2021. p. 249-71. doi: https://doi.org/10.1016/B978-0-12-820123-7.00020-6
- Barreca A, Schaller J. The impact of high ambient temperatures on delivery timing and gestational lengths. Nat. Chang. 2020;10:77-82. doi: https://doi.org/10.1038/s41558-019-0632-4
- ua [Internet]. [Climate change negatively affects childbirth – scientists]. 2019 [cited 2022 Jun 20]. Ukrainian.Available from: https://tsn.ua/nauka_it/zmina-klimatu-negativno-vplivaye-na-pologi-vcheni-1453239.html
- Shanshan Lia, Gongbo Chena, Jouni J K Jaakkolab, Gail Williamsc, Yuming Guoa. Temporal change in the impacts of ambient temperature on preterm birth and stillbirth: Brisbane, 1994-2013. Science of the Total Environment. 2018;634:579-85 doi: https://doi.org/10.1016/j.scitotenv.2018.03.385
- Avalos LA, Chen H, Li DK, Basu R. The impact of high apparent temperature on spontaneous preterm delivery: a case-crossover study. Environ Health. 2017;16(5). doi: https://doi.org/10.1186/s12940-017-0209-5
- Tansey EA, Johnson CD. Recent advances in thermoregulation. Adv Physiol Educ. 2015;39:139-48. doi: https://doi.org/10.1152/advan.00126.2014
- Eiden LE, Gundlach AL, Grinevich V, Lee MR, Mecawi AS, Chen D, et al. Regulatory peptides and systems biology: A new era of translational and reverse-translational neuroendocrinology. Journal of Neuroendocrinology. 2020;32(5):e12844. doi: https://doi.org/10.1111/jne.12844
- Strand LB, Barnett AG, Tong S. Maternal exposure to ambient temperature and the risks of preterm birth and stillbirth in Brisbane, Australia. Am. J. Epidemiol. 2012;175:99-107. doi: https://doi.org/10.1093/aje/kwr404
- Patil AS, Gaikwad NW, Grotegut CA, Dowden SD, Haas DM. Alterations in endogenous progesterone metabolism associated with spontaneous very preterm delivery. Human Reproduction Open. 2020;2020(2):1-10. doi: https://doi.org/10.1093/hropen/hoaa007
- Gabbe SG, Niebil JR, Simpson JL, editors. Obstetrics: normal and problem pregnancies. Philadelphia: Churchill Livingstone, Elsevier. 2007. ISBN: 9780443069307, ISBN: 0443069301.
- Guo T, Wang Y, Zhang H, Zhang Y, ZhaoJ, Wang Y, et al. The association between ambient temperature and the risk of preterm birth in China. Science of the Total Environment. 2018;613-614:439-46. doi: https://doi.org/10.1016/j.scitotenv.2017.09.104
- ZhangY, Yu C, Wang L. Temperature exposure during pregnancy and birth outcomes: An updated systematic review of epidemiological evidence. Environmental Pollution. 2017 June;225:700-12 doi: https://doi.org/10.1016/j.envpol.2017.02.066
- Tsymbaliuk V, VadziukS, Tolokova T, Tabas Prevalence of premature birth in conditions of global warming. Medicni perspektivi. 2021 Sep 30;26(3):152-61. doi: https://doi.org/10.26641/2307-0404.2021.3.242167
- An R, Ji M, Zhang S. Global warming and obesity: a systematic review. Obesity Etiology/Public2018 Feb;19(2):150-63. doi: https://doi.org/10.1111/obr.12624
- Metwally M, Li TC, Ledger WL. The impact of obesity on female reproductive function. Complications of Obesity. 2007 Nov;8(6):515-23. doi: https://doi.org/10.1111/j.1467-789X.2007.00406.x
- Larsen EC, Christiansen OB, Kolte AM, Macklon N. New insights into mechanisms behind miscarriage. BMC Med. 2013;11:154. doi: https://doi.org/10.1186/1741-7015-11-154
- Frey HA, Klebanoff MA. The epidemiology, etiology, and costs of preterm birth.Semin. Fetal Neonatal Med. 2016;21(2):68-73. doi: https://doi.org/10.1016/j.siny.2015.12.011
- Vogel JP, Chawanpaiboon S, Moller AB, Watananirum K, Bonet M, Lumbiganon P. The global epidemiology of preterm birth. Best Practice & Research Clinical Obstetrics and Gynaecology. 2018 Oct;52:3-12. doi: https://doi.org/10.1016/j.bpobgyn.2018.04.003
- Barreca A, Schaller J. The impact of high ambient temperatures on delivery timing and gestational lengths. NatureClimate Change, 2020 Jan;10:77-82. doi: https://doi.org/10.1038/s41558-019-0632-4
- Marushko RV, Dudina ОО. Modern aspects of perinatal mortality in Ukraine. Ukrainian Journal of Perinatology and Pediatrics. 2020;2(82):76-85. doi: https://doi.org/10.15574/PP.2020.82.76
- Flouris AD, Spiropoulos Y, Sakellariou GJ, Koutedakis Y. Effect of seasonal programming on fetal development and longevity: Links with environmental temperature. American Journal of Human Biology. 2009;21(2):214-16. doi: https://doi.org/10.1002/ajhb.20818
- Weng YH, Yang CY, Chiu YW. Adverse neonatal outcomes in relation to ambient temperatures at birth: A nationwide survey in Taiwan. Archives of Environmental & Occupational Health. 2018;73(1):48-55. doi: https://doi.org/10.1080/19338244.2017.1299084
- Stepanenko SM, Polovyi AM, Loboda NS. [Climate change and their impact on the economy of Ukraine]. Stepanenko SM, Polovyi AM, editors. Odesa: TES; 2015. Ukrainian. Available from: http://eprints.library.odeku.edu.ua/id/eprint/2269
- Johanzon M, Odesjo H, Jacobsson B, Sandberg K, Wennerholm Ulla_Britt. Extreme Preterm Birth: Onset of Delivery and Its Effect on Infant Survival and Morbidity. Obstetrics & Gynecology. 2008;111(1):42-50. doi: https://doi.org/10.1097/01.AOG.0000295866.97499.35
- Blencowe H, Cousens S, Oestergaard M, Chou D, Moller AB, Narwal R, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. The Lancet. 2012 June;9;379(9832):2162-72. doi: https://doi.org/10.1016/S0140-6736(12)60820-4
- Schifano P, Lallo A, Asta F, De Sario M, Davoli M, Michelozzi P. Effect of ambient temperature and air pollutants on the risk of preterm birth, Rome 2001-2010. Environ 2013;61:77-87. doi: https://doi.org/10.1016/j.envint.2013.09.005
- Kent ST, McClure LA, Zaitchik BF, Smith TT, Gohlke JM. Heat waves and health outcomes in Alabama (USA): the importance of heat wave deﬁnition. Environ Health 2014;122(2):151-8. doi: https://doi.org/10.1289/ehp.1307262
- Wyrobek AJ, Gordon LA, Burkhart JG, Francis MW, Kapp RW, Letz G, et al. An evaluation of human sperm as indicators of chemically induced alterations of spermatogenic function: A report of the U.S. environmental protection agency Gene-Tox program. Mutation Research/Reviews in Genetic Toxicology. 1983;115(1):73-148. ISSN 0165-1110. doi: https://doi.org/10.1016/0165-1110(83)90015-5
- Niels E. Skakkebaek, Ewa Rajpert-De Meyts, Germaine M Buck Louis, Jorma Toppari, et al. Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility. Physiol Rev. 2016;96(1):55-97. doi: https://doi.org/10.1152/physrev.00017.2015
- Kyung-Taek Rim. Reproductive Toxic Chemicals at Work and Efforts to Protect Workers' Health: A Literature Review. Safety and Health at Work. 2017 June;8(2):143-50. doi: https://doi.org/10.1016/j.shaw.2017.04.003
- World Health Organization. Health topics: infertility. Geneva: Department of Reproductive Health and Research, WHO [Internet]; 2013. Available from: https://www.who.int/
Yavorovsky O.P., Zazuliak T.S., Ostapiv D.D., Riabovol V.M., Demetska O.V. Comparative assessment of the effect of titanium dioxide – based nanoparticles on boar germ cells in vitro
Authors and affiliations
Yavorovsky O.P. Bogomolets National Medical University, Kyiv, Ukraine
Zazuliak T.S. Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
Ostapiv D.D. Institute of Animal Biology NAAS of Ukraine, Lviv, Ukraine
Riabovol V.M. Bogomolets National Medical University, Kyiv, Ukraine,
Demetska O.V. SI “Yu. Kundiiev Institute for Occupational Health of the NAMS of Ukraine”, Kyiv, Ukraine
Key words: nanoparticles of titanium dioxide, nanocomposite of titanium dioxide with silver, nanotoxicology, succinate dehydrogenase, cytochrome oxidase, boar germ cells
Abstract. Comparative assessment of the effect of titanium dioxide – based nanoparticles on boar germ cells in vitro. Yavorovsky O.P., Zazuliak T.S., Ostapiv D.D., Riabovol V.M., Demetska O.V. Modern titanium dioxide nanomaterials, in particular modified with nanosilver, have antiviral, antibacterial, antifungal activity, cytotoxic effects in vitro experiments and can affect germ cells of warm-blooded laboratory animals. The research aims to study the effect of different types of titanium dioxide nanoparticles on the physiological and biochemical characteristics of wild boar germ cells in vitro. When applying the maximum dose (LD50) of the studied nanopowders in all samples, sperm survival was probably lower than in the control: by 41.9% (р<0.001) ‒ under the action of TiO2 nanoparticles (hereinafter NPs) (Frantsevich Institute for Problems of Materials Science of NAS of Ukraine, hereinafter IPM), by 28.0% (р<0.05) ‒ under the action of TiO2 NPs (Acros Organics), by 53.5% (р<0.001) ‒ under the action of 4% Ag-TiO2 NPs (IPM) and by 55.9% (р<0.001) ‒ are the action of NPs 8% Ag-TiO2 (IPM). Nanopowders of different based on titanium dioxide manufacturers, characterized by similar morphological characteristics and varying degrees of nanosilver addition (Ag content from 0 to 8%), starting from a dose of 1/10 LD50, can have a damaging effect on the germ cells of wild boars, which is manifested by a decrease in the respiratory activity of sperm and cytochrome oxidase activity, by increasing succinate dehydrogenase activity. The most sensitive marker was the sperm survival rate, the value of which significantly decreased under the action of 8% Ag-TiO2 nanoparticles (IPM) at a dose of 1/100 LD50, which is a consequence of disruption of the activity of mitochondrial enzymes and, accordingly, resynthesis of ATP. Our results confirm and extend the data on the nature of the damaging effect of titanium dioxide-based nanoparticles on germ cells of warm-blooded animals due to oxidative stress. The obtained experimental data will be taken into account in the hygienic regulation of the investigated nanopowders.
- Waghmode MS, Gunjal AB, Mulla JA, et al. Studies on the titanium dioxide nanoparticles: biosynthesis, applications and remediation. SN Appl. Sci. 2019;1:310. doi: https://doi.org/10.1007/s42452-019-0337-3
- Zahornyi M, Tyschenko N, Shyrokov O, et al. The Effect of Ag Content on the Structural, Optical, and Cytotoxicity Properties of TiO2 Nanopowders Grown from TiO(OH)2 Precursor by the Chemical Deposition Method. Nanosistemi, Nanomateriali, Nanotehnologii. 2021;19(4):923-40. doi: https://doi.org/10.15407/nnn.19.04.923
- Zahornyi MM, Yavorovsky OP, Riabovol VM, et al. [Morphological, spectral and toxicological features of new composite material of titanium nanodioxide with nanosilver for use in medicine and biology]. Medicni perspektivi. 2022;27(1):152-9. Ukrainian. doi: https://doi.org/10.26641/2307-0404.2022.1.254381
- Pankivska YuB, Biliavska LO, Povnitsa OYu, et al. [Antiadenoviral activity of titanium dioxide nanoparticles]. Mikrobiolohichnyi zhurnal. 2019;81(5):73-84. Ukrainian. doi: https://doi.org/10.15407/microbiolj81.05.073
- Kermani SA, Salari S, Nejad Almani PG. Comparison of antifungal and cytotoxicity activities of titaniumdioxide and zinc oxide nanoparticles with amphotericin Bagainst different Candida species: In vitro evaluation. J Clin Lab Anal. 2021;35(1):e23577. doi: https://doi.org/10.1002/jcla.23577
- de Dicastillo CL, Correa MG, Martínez FB, et al. Antimicrobial Effect of Titanium Dioxide Nanoparticles. In: Mareș M, Lim SHE, Lai K, Cristina R, editors. Antimicrobial Resistance – A One Health Perspective [Internet]. London: IntechOpen; 2020 [cited 2022 Jul 12]. doi: https://doi.org/10.5772/intechopen.90891
- Riabovol VM, Kozar TI. [Investigation of acute toxic effects of nanopowders of titanium dioxide and its composites with nanosilver in laboratory mice. Ecological and hygienic problems of the sphere of human life]. Collection of materials of the scientific-practical conference with international participation; Kyiv; 2022. p. 160-2. Ukrainian.
- Alaee S, Ilani M. Effect of Titanium Dioxide Nanoparticles on Male and Female Reproductive Systems. Journal of Advanced Medical Sciences and Applied Technologies. 2017;3(1):3-8. doi: https://doi.org/18869/nrip.jamsat.3.1.3
- Guerreiro DD, Mbemya GT, Bruno JB, et al. Invitro culture systems as an alternative for female reproductive toxicology studies. Zygote. 2019;27(2):55-63. doi: https://doi.org/10.1017/S0967199419000042
- Demetska OV, Didenko MM, Movchan VO, et al. [Screening assessment of the damaging effect of nanomaterials using bovine spermatozoa as a test object]. Pivdennoukrainskyi medychnyi naukovyi zhurnal. 2021;29:12-15. Ukrainian.
- [Express method for determining the toxicity of nanomaterials in in vitro solutions using bovine spermatozoa as a test object]: pat. 101308 Ukraine. No. u201412531; appl. 19.12.2014; publ. 10.09.2015, bull. No. 17. 2 p. Ukrainian. Available from: http://www.medfoundation.od.ua/zhurnaly/29_2021.pdf
- Vlizlo VV, Fedoruk RS, Ratych IB, et al. [Laboratory research methods in biology, animal husbandry and veterinary medicine]. Vlizlo VV, edotir. Lviv: Spolom; 2012. Ukrainian. ISBN 976-966-665-677-6.
- Antomonov MYu. [Mathematical processing and analysis of medical and biological data]. Кyiv: Medinform. 2018. Russian.
Feshchenko Yu.I., Iashyna L.A., Opimakh S.G., Gumeniuk G.L., Ignatieva V.I., Polianska M.A., Zvol I.V., Moskalenko S.M. Features of lung impairment due to COVID-19 in patients of the first wave of the pandemic (literature review)
Authors and affiliations
Feshchenko Yu.I. SI “National institute of phthisiology and pulmonology named after F.G. Yanovsky NAMS of Ukraine”, Kyiv, Ukraine
Iashyna L.A. SI “National institute of phthisiology and pulmonology named after F.G. Yanovsky NAMS of Ukraine”, Kyiv, Ukraine
Opimakh S.G. SI “National institute of phthisiology and pulmonology named after F.G. Yanovsky NAMS of Ukraine”, Kyiv, Ukraine, e-mail:
Gumeniuk G.L. SI “National institute of phthisiology and pulmonology named after F.G. Yanovsky NAMS of Ukraine”, Kyiv, Ukraine
Ignatieva V.I. SI “National institute of phthisiology and pulmonology named after F.G. Yanovsky NAMS of Ukraine”, Kyiv, Ukraine
Polianska M.A. SI “National institute of phthisiology and pulmonology named after F.G. Yanovsky NAMS of Ukraine”, Kyiv, Ukraine
Zvol I.V. SI “National institute of phthisiology and pulmonology named after F.G. Yanovsky NAMS of Ukraine”, Kyiv, Ukraine
Moskalenko S.M. SI “National institute of phthisiology and pulmonology named after F.G. Yanovsky NAMS of Ukraine”, Kyiv, Ukraine
Key words: COVID-19, lung impairment, inflammation, fibrosis, thrombosis
Abstract. Features of lung impairment due to COVID-19 in patients of the first wave of the pandemic (literature review). Feshchenko Yu.I., Iashyna L.A., Opimakh S.G., Gumeniuk G.L., Ignatieva V.I., Polianska M.A., Zvol I.V., Moskalenko S.M. During the COVID-19 pandemic number of patients suffering from symptoms, decreased work ability and the deterioration in quality of life for several weeks and even months after the onset of the disease is increasing. The aim of the literature review is to search and study the existing literature data regarding the lung impairment features in COVID-19, as well as the morphological and pathophysiological prerequisites for the long-term respiratory disorders in patients who have had this disease. The most common complaints of patients after acute COVID-19 are fatigue, dyspnea, cough and chest discomfort. In these cases restrictive pattern in the pulmonary function test, a reduced gas transfer and persistent changes in computed tomography often in the form of fibrosis are observed, less often in the form of bullous-emphysematous changes, bronchiectasis and pleural effusion. The main pathophysiological mechanisms of acute lung impairment in COVID-19 are direct viral toxicity, impaired function of the immune system, hyperinflammatory response, endotheliopathy, microcirculatory disorders and increased blood clotting with small and large vessels thrombosis, which can lead to pneumonia or acute respiratory distress syndrome. After the acute phase of COVID-19 the pathology of the lung can be caused by an immunogenic and hyperinflammatory response, hypercoagulability and lead to pulmonary fibrosis. The possible mechanisms of the pulmonary fibrosis are thrombotic processes, hemosiderosis, necrotic capillaritis, angiogenesis, hypoxia, cytokine storm. Thus abnormal immune response, hyperinflammation, endothelial dysfunction and excessive coagulation not only cause pneumonia or acute respiratory distress syndrome in acute COVID-19, but also may persist for a long time and contribute to pulmonary fibrosis in some patients. The causes of a longer duration and increased severity of the lung impairment in some people compared to others are the subject of current investigations.
- Pertseva TA, Konopkina LI, Koval DS, Guba YuV. [The processes of inflammation and fibrosis in patients with chronic obstructive pulmonary disease]. Medicni perspektivi. 2020;25(4):59-65. Ukrainian. doi: https://doi.org/10.26641/2307-0404.2020.4.221229
- Feshchenko YuI, Golubovska OA, Dziublyk AYa, Gavrysyuk VK, Dziublyk YaA, Liskina IV. [Pulmonary disease in COVID-19]. Ukr Pulmonol J. 2021;1:5-14. Ukrainian. doi: https://doi.org/10.31215/2306-4927-2021-29-1-5-14
- Feshchenko YI, Lynnyk МІ, Gumeniuk МІ, Kalabukha IA, Іgnatieva VІ, Gumeniuk GL, et al. [Diagnosis of disappearing lung syndrome as a complication of non-hospital pneumonia of viral etiology (COVID-19)]. Infusion & Chemotherapy. 2021;3:5-11. Ukrainian. doi: https://doi.org/10.32902/2663-0338-2021-3-5-11
- Ambardar SR, Hightower SL, Huprikar NA, Chung KK, Singhal A, Collen JF. Post-COVID-19 Pulmonary Fibrosis: Novel Sequelae of the Current Pandemic. Journal of Clinical Medicine. 2021;10(11):2452. doi: https://doi.org/10.3390/jcm10112452
- Bellan M, Soddu D, Balbo PE, et al. Respiratory and Psychophysical Sequelae Among Patients With COVID-19 Four Months After Hospital Discharge. JAMA Netw Open. 2021;4(1):e2036142. doi: https://doi.org/10.1001/jamanetworkopen.2020.36142
- Borczuk AC, Salvatore SP, Seshan SV, Patel SS, Bussel JB, et al. COVID-19 pulmonary pathology: a multi-institutional autopsy cohort from Italy and New York City. Mod Pathol. 2020;33(11):2156-68. doi: https://doi.org/10.1038/s41379-020-00661-1
- Chun HJ, Coutavas E, Pine A, et al. Immuno-fibrotic drivers of impaired lung function in post-acute sequelae of SARS-CoV-2 infection (PASC). Preprint. medRxiv. 2021;2021.01.31.21250870. doi: https://doi.org/10.1101/2021.01.31.21250870
- Fahriani M, Ilmawan M, Fajar JK, et al. Persistence of long COVID symptoms in COVID-19 survivors worldwide and its potential pathogenesis – A systematic review and meta-analysis. Narra J. 2021;1(2):e36. doi: http://doi.org/10.52225/narraj.v1i2.36
- Faverio P, Luppi F, Rebora P, Busnelli S, Stainer A, et al. Six-Month Pulmonary Impairment after Severe COVID-19: A Prospective, Multicentre Follow-Up Study. Respiration. 2021;100:1078-87. doi: https://doi.org/10.1159/000518141
- Fogarty H, Townsend L, Morrin H, et al; the Irish COVID-19 Vasculopathy Study (iCVS) investigators. Persistent endotheliopathy in the pathogenesis of long COVID syndrome. J Thromb Haemost. 2021;19:2546-3. doi: https://doi.org/10.1111/jth.15490
- Grosse C, Grosse A, Salzer HJF, Dünser MW, Motz R, Langer R. Analysis of cardiopulmonary findings in COVID-19 fatalities: High incidence of pulmonary artery thrombi and acute suppurative bronchopneumonia. Cardiovasc Pathol. 2020;49:107263. doi: https://doi.org/10.1016/j.carpath.2020.107263
- Jiang DH, Roy DJ, Gu BJ, Hassett LC, McCoy RG. Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A State-of-the-Art Review. J Am Coll Cardiol Basic Trans Science. 2021;9-10:796-811. doi: https://doi.org/10.1016/j.jacbts.2021.07.002
- Konopka KE, Perry W, Huang T, Farver CF, Myers JL. Usual Interstitial Pneumonia is the Most Common Finding in Surgical Lung Biopsies from Patients with Persistent Interstitial Lung Disease Following Infection with SARS-CoV-2. eClinicalMedicine; 2021. doi: https://doi.org/10.1016/j.eclinm.2021.101209
- Lombardi F, Calabrese A, Iovene B. et al. Residual respiratory impairment after COVID-19 pneumonia. BMC Pulm Med. 2021;21:241. doi: https://doi.org/10.1186/s12890-021-01594-4
- Maltezou HC, Pavli A, Tsakris A. Post-COVID Syndrome: An Insight on Its Pathogenesis. Vaccines (Basel). 2021;9(5):497. doi: https://doi.org/10.3390/vaccines9050497
- Marik PE, Iglesias J, Varon J, Kory P. A scoping review of the pathophysiology of COVID-19. International Journal of Immunopathology and Pharmacology. 2021;35:1-16. doi: https://doi.org/10.1177/20587384211048026
- Meizlish ML, Pine AB, Bishai JD, Goshua G, Nadelmann ER, et al. A neutrophil activation signature predicts critical illness and mortality in COVID-19. Blood Adv. 2021;5(5):1164-1177. doi: https://doi.org/10.1182/bloodadvances.2020003568
- Mittal A, Sabharwal S, Foley R. Bullous lung disease complicating COVID-19 pneumonia. Chest. 2021;160(4):A908. doi: https://doi.org/10.1016/j.chest.2021.07.846
- Myall KJ, Mukherjee B, Castanheira AM, et al. Persistent Post-COVID-19 Interstitial Lung Disease. An Observational Study of Corticosteroid Treatment. Ann Am Thorac Soc. 2021;18(5):799-806. doi: https://doi.org/10.1513/AnnalsATS.202008-1002OC
- Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27:601-15. doi: https://doi.org/10.1038/s41591-021-01283-z
- Pandey P, Agarwal S, Rajkumar. Lung pathology in COVID-19: A systematic review. Int J App Basic Med Res. 2020;10:226-3. doi: https://doi.org/10.4103/ijabmr.IJABMR_381_20
- Rendeiro AF, Ravichandran H, Bram Y, et al. The spatial landscape of lung pathology during COVID-19 progression. Nature. 2021;593:564-9. doi: https://doi.org/10.1038/s41586-021-03475-6
- Reno C, Sanmarchi F, Stoto MA, Fantini MP, Lenzi J, Golinelli D. The impact of health policies and vaccine rollout on the COVID-19 pandemic waves in Italy. Health Policy and Technology. 2022;100604. doi: https://doi.org/10.1016/j.hlpt.2022.100604
- Salem AM, Al Khathlan N, Alharbi AF, Alghamdi T, AlDuilej S, Alghamdi M, et al. The Long-Term Impact of COVID-19 Pneumonia on the Pulmonary Function of Survivors. Int J Gen Med. 2021;14:3271-80. doi: https://doi.org/10.2147/IJGM.S319436
- Shah W, Hillman T, Playford ED, Hishmeh L. Managing the long term effects of COVID-19: summary of NICE, SIGN, and RCGP rapid guideline. BMJ. 2021;372:n136. doi: https://doi.org/10.1136/bmj.n136
- Siddiqui S, Brightling CE. Pathological disease in the lung periphery after acute COVID-19. Lancet Respir Med. 2021;9(10):1089-90. doi: https://doi.org/10.1016/S2213-2600(21)00378-7
- Solomon JJ, Heyman B, Ko JP, Condos R, Lynch DA. CT of Post-Acute Lung Complications of COVID-19. Radiology. 2021;301(2):E383-95. doi: https://doi.org/10.1148/radiol.2021211396
- Stockley JA, Alhuthail EA, Coney AM, et al. Lung function and breathing patterns in hospitalised COVID-19 survivors: a review of post-COVID-19 Clinics. Respir Res. 2021;22:255. doi: https://doi.org/10.1186/s12931-021-01834-5
- Wild JM, Porter JC, Molyneaux PL, et al. Understanding the burden of interstitial lung disease post-COVID-19: the UK Interstitial Lung Disease-Long COVID Study (UKILD-Long COVID). BMJ Open Respir Res. 2021;8(1):e001049. doi: https://doi.org/10.1136/bmjresp-2021-001049
- Wu Q, Zhong L, Li H, Guo J, Li Y, et al. A Follow-Up Study of Lung Function and Chest Computed Tomography at 6 Months after Discharge in Patients with Coronavirus Disease 2019. Canadian Respiratory Journal. 2021;6692409. doi: https://doi.org/10.1155/2021/6692409
- Zawbaa HM, Osama H, El-Gendy A, et al. Effect of mutation and vaccination on spread, severity, and mortality of COVID-19 disease. J Med Virol. 2021;94:197-204. doi: https://doi.org/10.1002/jmv.27293
- Zayet S, Zahra H, Royer P-Y, Tipirdamaz C, Mercier J, Gendrin V, et al. Post-COVID-19 Syndrome: Nine Months after SARS-CoV-2 Infection in a Cohort of 354 Patients: Data from the First Wave of COVID-19 in Nord Franche-Comté Hospital, France. Microorganisms. 2021;9(8):1719. doi: https://doi.org/10.3390/microorganisms9081719
- Zhang S, Bai W, Yue J, et al. Eight months follow-up study on pulmonary function, lung radiographic, and related physiological characteristics in COVID-19 survivors. Sci Rep. 2021;11:13854. doi: https://doi.org/10.1038/s41598-021-93191-y
Sokolova K.V., Stavytskyi V.V., Konovalova S.О., Podpletnya O.A., Kovalenko S.I., Avdeenko A.P. Design and search for prospective diuretics (CA II Inhibitors) among aroylhydrazones of esters quinone oxime using in silico and in vivo methodology
Authors and affiliations
Sokolova K.V. Dnipro State Medical University, Dnipro, Ukraine,
Stavytskyi V.V. Oles Honchar Dnipro National University, Dnipro, Ukraine
Konovalova S.О. Donbass State Engineering Academy, Kramatorsk, Ukraine
Podpletnya O.A. Dnipro State Medical University, Dnipro, Ukraine
Kovalenko S.I. Zaporizhzhia State Medical University, Zaporizhzhia, Ukraine
Avdeenko A.P. Donbass State Engineering Academy, Kramatorsk, Ukraine
Key words: design, molecular docking, carbonic anhydrase inhibitors, synthesis, aroylhydrazones of esters quinone oximes, diuretic activity, SAR analysis
Abstract. Design and search for prospective diuretics (CA II Inhibitors) among aroylhydrazones of esters quinone oxime using in silico and in vivo methodology. Sokolova K.V., Stavytskyi V.V., Konovalova S.О., Podpletnya O.A., Kovalenko S.I., Avdeenko A.P. The design and search for new selective inhibitors of CA II with a better pharmacological profile, which would cause minimal electrolyte disturbances in the body, remains an urgent problem of medical chemistry and pharmacology today. It is important that the discovered new classes of inhibitors do not always contain the main “pharmacophoric” function (sulfamide), which is characteristic of “classic” drugs (Acetazolamide, Methazolamide, Ethoxzolamide, Dorzolamide and others), but are derivatives of phenols, polyamines, coumarins/thiocoumarins, ureas, thioureas, hydroxamates, etc. These molecules also bind in the active site of the enzyme, but do not interact directly with the catalytic zinc ion or interact through zinc-coordinated water molecules/hydroxide ion. However, this leads to an increase in their selectivity and, as a result, pharmacological action. Continuing the search for compounds that affect urination, we were interested in aroylhydrazones of esters of quinone oxime. Firstly, they are characterized by certain structural features (dynamic and geometric isomerism); secondly, they exhibit redox properties; thirdly, the presence of aromatic fragments makes it possible to create a voluminous combinatorial library for analysis. These compounds are ligands in complexation reactions, and an additional increase in the number of hydrogen acceptors in the molecule due to structural modification will improve ligand-enzymatic interactions with carbonic anhydrase (CAII) and, as a result, reveal new promising diuretics. The aim – design and search for potential diuretics (CA II inhibitors) among aroylhydrazones of esters of quinone oxime using in silico, traditional synthesis and in vivo methodologies. Methods of organic synthesis, physico-chemical methods of analysis of organic compounds (NMR 1H-spectroscopy, elemental analysis). Prediction of affinity to the biological target, prediction of toxicity and lipophilicity of the combinatorial library of benzohydrazides O-aroyl esters of quinone oxime using computer services. The study of compounds affecting the excretory function of rat kidneys was carried out according to the generally accepted method of E.B.Berkhin with water load. The investigation of the probable mechanism was carried out using flexible molecular docking, as an approach to search for molecules that have affinity for human carbonic anhydrase type II (CA II). Macromolecular data of the crystal structure of CA II (PDB ID – 3HS4) were downloaded from the Protein Data Bank (PDB). The design was developed and the search for diuretic agents among benzohydrazides of O-aroyl esters of quinone oximes was developed using in silico methods (prediction of affinity, lipophilicity, toxicity and enzyme-ligand interactions), traditional organic synthesis, and in vivo methods (effect on excretory function of rat kidneys). The synthesis of benzohydrazides of O-aroyl esters of quinone oxime was carried out by the interaction of aroylhydrazines with 4-[(aroylimino)]cyclohexa-2,5-dien-1-ones. The structure of the synthesized compounds was confirmed by elemental analysis and 1H NMR spectra. Studies of the effect of synthesized compounds on the excretory function of rat kidneys allowed us to identify a number of promising compounds among aroylhydrazones of quinonexime esters, which increase daily diuresis by 54.2-352.8% compared to the control group. At the same time, it was established that the most active was N'-(4-[(2-chlorobenzoyloxy)imino]cyclohexa-2,5-dien-1-ylidene)-3-nitrobenzohydrazide, which increased daily diuresis by 352.8% in comparison with the control group, while exceeding the effect of “Hydrochlorothiazide” (170.8%). The developed and implemented strategy for the search for diuretics among benzohydrazides of O-aroylesters of quinone oxime allowed the identification of an effective compound, which in terms of diuretic effect exceeds the comparison drug “Hydrochlorothiazide”. Visualization of the molecular docking of the active compounds showed that their geometry makes it difficult to place them in the pocket of the active site of CA II, but the pronounced diuretic effect can also be associated with their ability to form coordination bonds with the zinc cation. The obtained results justify the further targeted search for potential diuretics among this class of compounds for a more detailed understanding and study of the mechanism of action.
- Ellison DH. Clinical Pharmacology in Diuretic Use. Clinscal Journal of the Americal Society of Nephrology (CJASN). 2019;14(8):1248-57. doi: https://doi.org/10.2215/CJN.09630818
- Supuran CT. How many carbonic anhydrase sinhibition mechanisms exits? Jornal of Enzyme Inhibitoin and Medical Chemistry. 2016;31(3):345-60. doi: https://doi.org/10.3109/14756366.2015.1122001
- Alterio V, Di Fiore A, D’Ambrosio K, Supuran CT, De Simone G. Multiple Binding Modes of Inhibitors to Carbonic Anhydrases: How to Design Specific Drugs Targeting 15 Different Isoforms? Chemical Reviews. 2012;112(8):4421-68. doi: https://doi.org/10.1021/cr200176r
- Mishra CB, Tiwari M, Supuran CT. Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today? Med Res Rev. 2020:1‐81. doi: https://doi.org/10.1002/med.21713
- Doretta Cuffaro, Elisa Nuti, Armando Rossello. An overview of carbohydrate-based carbonic anhydrase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry. 2020;35(1):1906-22. doi: https://doi.org/1080/14756366.2020.1825409
- Kumari D, Bansal H. Benzohydrazides: As potential bio-active agents. The Pharma Innovation Journal. 2018;7(8):543-50. doi: https://doi.org/10.22271/tpi
- de Oliveira Carneiro Brum Juliana, França Tanos CC, LaPlante Steven R, Villar José Daniel Figueroa. Synthesis and Biological Activity of Hydrazones and Derivatives: A Review. Mini Reviews in Medicinal Chemistry. 2020;20(5):342-68. doi: https://doi.org/10.2174/1389557519666191014142448
- Patil M, Bendre R. Synthesis, Characterization and Antioxidant Potency of Naturally Occurring Phenolic Monoterpenoids Based Hydrazide Motifs. Medicinal Chemistry. 2018;8(7):177-80. doi: https://doi.org/10.4172/2161-0444.1000509
- Taha M, Shah SAA, Khan A, Arshad F, Ismail NH, et al. Synthesis of 3,4,5-trihydroxybenzohydrazone and evaluation of their urease inhibition potential. Arabian Journal of Chemistry. 2019;12:2973-82. doi: http://doi.org/10.1016/j.arabjc.2015.06.036
- Alisi IO, Uzairu A, Abechi SE. In silico design of hydrazone antioxidants and analysis of their free radical-scavenging mechanism by thermodynamic studies. Beni-Suef University Journal of Basic and Applied Sciences. 2019;8:11. doi: https://doi.org/10.1186/s43088-019-0011-2
- Taha M, Sultan S, Herizal M, Fatmi MQ, Selvaraj M, Ramasamy K, et al. Synthesis, anticancer, molecular docking and QSAR studies of benzoylhydrazone. Journal of Saudi Chemical Society. 2019;23:1168-79. doi: https://doi.org/10.1016/j.jscs.2019.07.007
- Maniak H, Talma M, Matyja K, Trusek A, Giurg M. Synthesis and Structure-Activity Relationship Studies of Hydrazide-Hydrazones as Inhibitors of Laccase from Trametes versicolor. Molecules. 2020;25:1255. doi: https://doi.org/10.3390/molecules25051255
- Martínez MJA, Benito PB. Biological Activity of Quinones. Studies in Natural Products Chemistry. 2005:303-66. doi: https://doi.org/10.1016/s1572-5995(05)80036-5
- Madeo J Zubair А, Marianne F. A review on the role of quinones in renal disorders. SpringerPlus. 2013;2:139. Available from: http://www.springerplus.com/content/2/1/139
- Bolton JL, Dunlap T. Formation and Biological Targets of Quinones: Cytotoxic versus Cytoprotective Effects. Chemical Research in Toxicology. 2016;30(1):13-37. doi: https://doi.org/10.1021/acs.chemrestox.6b00256
- El-Najjar N, Gali-Muhtasib H, Ketola RA, Vuorela P, Urtti A, Vuorela H. The chemical and biological activities of quinones: overview and implications in analytical detection. Phytochemistry Reviews. 2011;10(3):353-70. doi: https://doi.org/10.1007/s11101-011-9209-1
- org [Internet]. USA: Protein Data Bank; 2022 [cited 2022 Nov 6].Available from: http://www.rcsb.org/pdb/home/home
- MarvinSketch version 20.20.0. ChemAxon. [Internet]. [cited 2022 Nov 6].
Available from: http://www.chemaxon.com
- Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455-61.
- Discovery Studio Visualizer v19.1.018287. [Internet]. Accelrys Software Inc. 2022 [cited 2022 Nov 6]. Available from: https://www.3dsbiovia.com
- ProTox-II – Prediction of Toxicity of Chemicals. [Internet]. 2021 [cited 2022 Nov 6]. Available from: https://tox-new.charite.de/protox_II/index.php?site=home
- European convention for the protection of vertebrate animal used for experimental and other scientific purposes. Council of Europe, Strasbourg; 1986.
- Bryukhanov VM, Zverev YuF, Lampatov VV, Zharikov AYu. [Methodological approaches to the study of kidney function in animal experiments]. Nefrologiia. 2009;13(3):52-62. Russian.
- Stefanov OV. [Preclinical studies of drugs]. Kyiv: Avitsena; 2001. Ukrainian. Available from: https://cryo.net.ua/xmlui/bitstream/handle/123456789/77/Руководство%20Стефанов%2C%202001.pdf?sequence=1&isAllowed=y
- Lapach SN, Chubenko AV, Babich PN. [Statistical methods in biomedical research using EXCEL]. Kyiv: Morion; 2000. Russian.
- Breitmaier E. Structure Elucidation by NMR in Organic Chemistry: A Practical Guide’, Eberhard Breitmaier, 3rd Revised Edition, Wiley; 2002.
Ivanov V.S., Makarenko O.A., Dienha O.V. Correction of metabolic changes in the tissues of oral cavity of rats using a complex of drugs under the conditions of pathological factors
Authors and affiliations
Ivanov V.S. SE «The Institute of stomatology and maxillo-facial surgery National academy of medical sciences of Ukraine», Odesa, Ukraine
Makarenko O.A. SE «The Institute of stomatology and maxillo-facial surgery National academy of medical sciences of Ukraine», Odesa, Ukraine
Dienha O.V. SE «The Institute of stomatology and maxillo-facial surgery National academy of medical sciences of Ukraine», Odesa, Ukraine, e-mail:
Key words: intrauterine tissue hypoxia, cariogenic diet, caries-prophylactic effect, plant polyphenols, rats
Abstract. Correction of metabolic changes in the tissues of oral cavity of rats using a complex of drugs under the conditions of pathological factors. Ivanov V.S., Makarenko O.A., Dienha O.V. Hypoxia is a typical pathological process that occurs when tissues are insufficiently supplied with oxygen or when its utilization is impaired. One of the most important pathogenetic factors in the development of tissue hypoxia is the disintegration of the structure of mitochondrial membranes which occurs under the influence of various etiological factors. In children who suffered hypoxia in the antenatal period, the frequency of developmental delays is significantly increased, and the incidence of caries is also shown to increase as compared to healthy children. Based on the above, this work is relevant for modern dentistry. The work is devoted to the study of the state of the maxillofacial system and tissues of the oral cavity of rats under the influence of the complex of drugs under the conditions of intrauterine hypoxia, cariogenic diet, thyroid insufficiency and fluorine deficiency. The subjects of the study were 25 female white rats of the Wistar line of herd breeding from the vivarium of the SE “ISMFS NAMS” kept on a standard vivarium diet. The animals were divided into three groups – intact (7 rats), pathology model (8 rats), pathology model and drug complex (8 rats). Animals were removed from the experiment under thiopental anesthesia (40 mg/kg). Lower jaws and pulp were removed. As a result of the research, it was established that the proposed treatment-prophylactic complex has a pronounced caries-prophylactic and periodontoprotective effect. The caries-preventive effectiveness of the complex was due to its ability to stimulate the mineralizing function of the dental pulp, namely, to increase the activity of alkaline phosphatase of the pulp, as an indicator of the activation of osteoblasts, against the background of a decrease in the activity of acid phosphatase, a marker of osteoclasts.
- Zarubina IV [Modern ideas about the pathogenesis of hypoxia and its pharmacological correction]. Obzory po klinicheskoi farmakologii i lekarstvennoi terapii. 2011;9(3):31-48. Russian.
- Maksimov AL, Averjanova IV. [Informative value of the test with respiration to assess the resistance of the body of young men to the combined effects of hypoxia and hypercapnia]. Fiziologicheskii zhurnal im. IM Sechenova. 2017;103(9):1057-68. Russian.
- Gridin LA. [Modern ideas about the physiological and therapeutic and prophylactic effects of hypoxia and hypercapnia]. Medicina. 2016;4(3):45-68. Russian. Available from: https://www.fsmj.ru/download/15/06.pdf
- European convention for the protection of vertebrale animals used for experimental and other scientific purposes. [Internet]. Strasburg: Council of Europe; 1986 [cited 2022 Oct 20]. Available from: http://www.worldlii.org/int/other/treaties/COETSER/1986/1.html
- [Order of the Ministry of Education and Science of Ukraine dated March 16, 2012, No. 249 "On the approval of the Procedure for carrying out experiments and experiments on animals by scientific institutions"]. (2012). Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/z0416-12#Text
- Shnaider SA, Levitsky AP. [Experimental Dentistry. Pt.1. Experimental models of dental diseases]. Odesa: KP «Odeska miska drukarnia»; 2017. Russian.
- Tkachenko YeK, Nikolaeva AV, Novoselskaya NG. [The effect of preparations of plant polyphenols and vitamin-mineral complex on the state of the intercellular matrix of the periodontium and the oral mucosa of rats with hypoestrogenism]. Visnyk stomatolohii. 2014;1(86):16-20. Russian. Available from: http://www.visnyk.od.ua/index.php/mainjournal/issue/view/13
- Tsviakh OO. [The influence of stress on the state of the pro-oxidant-antioxidant system of the stomach of rats with a lack and excess of melatonin]. Visnyk problem biolohii i medytsyny. 2013;1(102):254-258. Ukrainian. Available from: http://www.irbis-nbuv.gov.ua/cgi-bin/irbis_nbuv/cgiirbis_64.exe?C21COM=2&I21DBN=UJRN&P21DBN=UJRN&IMAGE_FILE_DOWNLOAD=1&Image_file_name=PDF/Vpbm_2013_3(1)__57.pdf
- Yelins’ka AM, Kostenko VO. [Mechanisms of disorganization of rat periodontal connective tissue under conditions of systemic inflammation]. Aktualni problemy suchasnoi medytsyny: Visnyk ukrainskoi medychnoi stomatolohichnoi akademii. 2018;1(61):175-7. Ukrainian. Available from: http://repository.pdmu.edu.ua/bitstream/123456789/11328/1/Mechanisms_of_connective_tissue_disruption.pdf
- Granchuk A, Granchuk G, Gudumak VS. [Activity of metabolic processes in the mandibular bone tissues of albino rats using zinc coordination compounds (experimental study, stage 1)]. Mezhdunarodnyi nauchno-issledovatelskii zhurnal. 2019;12-2(90):196-200. doi: https://doi.org/10.23670/IRJ.2019.90.12.041
Koval T.I., Syzova L.M., Pryimenko N.O., Sydorenko A.Н., Kulіsh M.V., Ilchenko V.I., Lymarenko N.P. The role of TLR-4 gene in the functioning of the natural human immune system and the immunopathogenesis of chronic hepatitis C (literature review)
Authors and affiliations
Koval T.I. Poltava state medical university, Poltava, Ukraine
Syzova L.M. Poltava state medical university, Poltava, Ukraine,
Pryimenko N.O. Poltava state medical university, Poltava, Ukraine
Sydorenko A.Н. Poltava state medical university, Poltava, Ukraine
Kulіsh M.V. Poltava state medical university, Poltava, Ukraine
Ilchenko V.I. Poltava state medical university, Poltava, Ukraine
Lymarenko N.P. Poltava state medical university, Poltava, Ukraine
Key words: TLR-4 gene, polymorphism, Asp299Gly, chronic hepatitis C, immunopathogenesis
Abstract. The role of TLR-4 gene in the functioning of the natural human immune system and the immunopathogenesis of chronic hepatitis C (literature review). Koval T.I., Syzova L.M., Pryimenko N.O., Sydorenko A.Н., Kulіsh M.V., Ilchenko V.I., Lymarenko N.P. To date, despite significant advances in the study of the immunopathogenesis of chronic hepatitis C (CHC), many open questions remain in the diagnosis, prediction and course of treatment. In the context of the study of this infection, the Toll-like gene family of innate immune system receptors (TLRs) is of considerable interest. The article analyzes and summarizes the data of professional scientific sources on the role of the TLR-4 gene in the functioning of the natural human immune system, as well as Asp299Gly polymorphism of this gene in the immunopathogenesis of CHC. The relevance of the study is due to the fact that the innate immune system is crucial in the primary protection of the macroorganism from pathogens, the recognition of which largely depends on the TLRs receptor gene family, and genetic analysis is a modern and promising direction in personalized medicine. The importance of determining genetic markers lies in the fact that regardless of age and other factors of the external and internal environment, they carry information about the predisposition to various diseases, which can be used in the formation of a genetic passport. The data concerning the influence of the Asp299Gly polymorphism of the TLR4 gene on the immunopathogenesis of CHC are contradictory and require further investigation. An in-depth study of this issue will improve the therapeutic and diagnostic tactics of this disease based on a comprehensive assessment of the features of the immune response, which are caused by the carriage of the indicated polymorphism in the human genome.
- Dubynska GM, Koval TI, Sizova LM, Izyumska OM, Kotelevska TM, Svyrydenko NP, etal. [Analysis of antiviral therapy effectiveness for chronic hepatitis C patients in Poltava region]. Klinicheskaia infektologiia i parazitologiia. 2016;5(4):440-48. Russian. Available from: http://repository.pdmu.edu.ua/bitstream/123456789/413/1/anails.pdf
- Dmytiiev DV, Nazarchuk OA. [Modern views on the role of Toll-like receptors in immune and physiological homeostasis and pathology]. Aktualni Problemy Suchasnoi Medytsyny: Visnyk Ukrainskoi medychnoi stomatolohichnoi akademii. 2015;15,3(51):313-19. Ukrainian. Available from: https://cyberleninka.ru/article/n/suchasni-uyavlennya-pro-rol-toll-podibnih-retseptoriv-v-imunofiziologichnomu-gomeostazi-ta-pri-patologiyi/pdf
- Lebedeva ОР, Qirko R. [Expression of Toll-like receptors in the female reproductive tract and its hormone regulation (review)]. Research Results in Biomedicine. 2018;4(3):3-17. doi: https://doi.org/10.18413/2313-8955-2018-4-3-0-1
- Petrov RV, Haitov RM, Chereshnev VA. [Physiology of the immune system: cellular and molecular-biological mechanisms]. Vestnik RFFI. 2017;1:96-119. Russian.
- Sizovа L, Koval T, Kaidashev I, Ilchenko V, Dubinskaya G. [The role of genetic polymorphisms Toll-like receptor 4 and 7 in the chronic hepatitis C and gender features of their distribution]. GMN. 2016;1(250):51-56. Russian.
- Rudenko KA, Tuguz AR, Anokhina EN, Muzhenya DV. [Toll-like receptor gene polymorphisms, associated with a hereditary history and age of bronchial asthma manifestation]. Vestnik AGU. 2014;1(133):64-69. Russian. Available from: https://cyberleninka.ru/article/n/polimorfizmy-genov-toll-podobnyh-retseptorov-assotsiirovannye-s-nasledstvennoy-otyagoschennostyu-i-vozrastom-manifestatsii-1/viewer
- Sizova LM. [Peculiarities of clinical and laboratory characteristics of chronic hepatitis C in patients with polymorphism Asp299Gly of TLR4 gene and Gln11Leu of TLR7 gene]. Aktualni problemy suchasnoi medytsyny: Visnyk Ukrainskoi medychnoi stomatolohichnoi akademii. 2016;16.4(56).1:182-87. Ukrainian.
- Chaiwiang N, Poyomtip T. The associations between Toll-like receptor 4 gene polymorphisms and hepatitis C virus infection: a systematic review and meta-analysis. Biosci Rep. 2019;39(2). doi: https://doi.org/10.1042/BSR20182470
- Dubinskaya G, Sizova L, Koval Т, Kovalyova Е, Kaydashev I. Clinical and genetic predictors and prognostic model of rapidly progressive hepatic fibrosis in chronic hepatitis C. GMN. 2016; 7-8(256-257):37-45.
- Nieto JC, Sánchez E, Román E, Vidal S, Oliva L, Guarner-Argente C, et al. Cytokine production in patients with cirrhosis and TLR4 polymorphisms. WJG. 2014;20(46):17516-524. doi: https://doi.org/10.3748/wjg.v20.i46.17516
- David SP. Genomic and precision medicine: primary care: Third Edition. London: Academic Press; 2017. doi: https://doi.org/10.1016/B978-0-12-800685-6.00001-1
- Pettengill MA, van Haren SD, Li N, Dowling DJ, Bergelson I, Jans J, et al. Distinct TLR-mediated cytokine production and immunoglobulin secretion in human newborn naive B cells. Innate Immun. 2016;22(6):433-43. doi: https://doi.org/10.1177/1753425916651985
- Dowling JK, Mansell A. Toll-like receptors: the swiss army knife of immunity and vaccine development. ClinTransl 2016;5(5). doi: https://doi.org/10.1038/cti.2016.22
- Emonts M. Polymorphisms in immune response genes in infectious diseases and autoimmune diseases. Rotterdam: Erasmus University Rotterdam; 2008.
- Stewart EA, Wei R, Branch MJ, Sidney LE, Amoaku WM. Expression of Toll-like receptors in human retinal and choroidal vascular endothelial cells. Exp Eye Res.2015;138:114-23. doi: https://doi.org/10.1016/j.exer.2015.06.012
- Guo J, Loke J, Zheng F, Hong F, Yea S, Fukata М, et al. Functional linkage of cirrhosis-predictive single nucleotide polymorphisms of Toll-like receptor 4 to hepatic stellate cell responses. Hepatology. 2009;49(3):960-68. doi: https://doi.org/10.1002/hep.22697
- Funk E, Kottilil S, Gilliam B, Talwani R. Tickling the TLR7 to cure viral hepatitis. J Transрl Med. 2014;12(1). doi: https://doi.org/10.1186/1479-5876-12-129
- Gesuete R, Kohama SG, Stenzel-Poore MP. Toll-like receptors and ischemic brain injury. J Neuropathol Exp 2014;73(5):378-86. doi: https://doi.org/10.1097/NEN.0000000000000068
- Guo J, Friedman SL. Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis. Fibrogenesis Tissue 2010;3(1):21. doi: https://doi.org/10.1186/1755-1536-3-21
- Howell J, Angus P, Gow P, Visvanathan K. Toll-like receptors in hepatitis C infection: Implications for pathogenesis and treatment. J Gastroenterol Hepatol. 2013;28(5):766-76. doi: https://doi.org/10.1111/jgh.12170
- Zhu Q, Zou L, Jagavelu K, Simonetto DA, Huebert RC, Jiang ZD, et al. Intestinal decontamination inhibits TLR4 dependent fibronectin-mediated cross-talk between stellate cells and endothelial cells in liver fibrosis in mice. J Hepatol. 2012;56(4):893-99. doi: https://doi.org/10.1016/j.jhep.2011.11.013
- Izmailova O. Analysis of association between the polymorphic variants of the TLR2 (RS5743708) and TLR4 (RS4986790, RS4986791) genes with the health status of apparently healthy individual. The Medical and Ecological Problems. 2018;22(1-2):17-22. doi: https://doi.org/10.31718/mep.2018.22.1-2.03
- Jiménez-Dalmaroni MJ, Gerswhin ME, Adamopoulos IE. The critical role of toll-like receptors − from microbial recognition to autoimmunity: a comprehensive review. Autoimmun 2016;15(1):1-8. doi: https://doi.org/10.1016/j.autrev.2015.08.009
- Kawai Т, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity.2011;34(5):637-50. doi: https://doi.org/10.1016/j.immuni.2011.05.006
- Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol [Internet]. 2014 [cited 2022 Feb 02];5:461. doi: https://doi.org/10.3389/fimmu.2014.00461
- Khakpour S, Wilhelmsen K, Hellman J. Vascular endothelial cell Toll-like receptor pathways in sepsis. Innate 2015;21(8):827-46. doi: https://doi.org/10.1177/1753425915606525
- Pires-Neto ODS, de SáKSG, Santana BB, Tatielle Monteiro Gomes S, da Silva Graça Amoras , da Silva Conde SR, et al. Lack of association between polymorphisms of the TLR4 gene and infection with the hepatitis B and C viruses. Mediators of inflammation. 2015. doi: https://doi.org/10.1155/2015/150673
- LesterSN, Li Toll-like receptors in antiviral innate immunity. J Mol Biol. 2014;426(6):1246-64. doi: https://doi.org/10.1016/j.jmb.2013.11.024
- Medvedev Toll-like receptor polymorphisms, inflammatory and infectious diseases, allergies, and cancer. J Interferon Cytokine Res. 2013;33(9):467-84. doi: https://doi.org/10.1089/jir.2012.0140
- MukherjeeS, Huda S, Sinha Babu Toll-like receptor polymorphism in host immune response to infectious diseases: A review. Scand J Immunol. 2019;90(1). doi: https://doi.org/10.1111/sji.12771
- WangS, Charbonnier LM, Rivas MN, Georgiev P, Li N, Gerber G, et al. MyD88 adaptor-dependent microbial sensing by regulatory T cells promotes mucosal tolerance and enforces commensalism. Immunity. 2015;43(2):289-303. doi: https://doi.org/10.1016/j.immuni.2015.06.014
- NeteaMG, Wijmenga C, O'neill Genetic variation in Toll-like receptors and disease susceptibility. Nat Immunol. 2012;13(6):535-42. doi: https://doi.org/10.1038/ni.2284
- LeeCM, Hu TH, Lu SN, Wang JH, Hung CH, Chen CH, Yen Peripheral blood toll-like receptor 4 correlates with rapid virological response to pegylated-interferon and ribavirin therapy in hepatitis C genotype 1 patients. BMC gastroenterology. 2016;16(1):73. doi: https://doi.org/10.1186/s12876-016-0492-6
- Perić M, Bošnjak Z, Šarkanj B, Barbić J, Antolović-Požgain A, Ružman N, et al. Polymorphisms of Toll-like receptors 2 and 4 in chronically infected hepatitis C patients from north-east Croatia. Arch Virol. 2015;160(1):297-304. doi: https://doi.org/10.1007/s00705-014-2283-0
- Sghaier I, Mouelhi L, Ghazoueni E, Brochot E, Almawi WY, Yacoubi-Loueslati B. Role of TLRs and IL-6 in the outcome of chronic hepatitis C treatment in Tunisian population. Cytokine. 2017;99:297-304. doi: https://doi.org/10.1016/j.cyto.2017.08.010
- Kordjazy N, Haj-Mirzaian A, Haj-Mirzaian A, Rohani MM, Gelfand EW, Rezaei N, et al. Role of toll-like receptors in inflammatory bowel disease. Pharmacol Res. 2018;129:204-15. doi: https://doi.org/10.1016/j.phrs.2017.11.017
- Sasai M, Yamamoto М. Pathogen recognition receptors: ligands and signaling pathways by Toll-like receptors. Int Rev Immunol. 2013;3(2):116-33. doi: https://doi.org/10.3109/08830185.2013.774391
- Saxena M, Bhardwaj N. Re-emergence of dendritic cell vaccines for cancer treatment. Trends Сancer. 2018;4(2):119-37. doi: https://doi.org/10.1016/j.trecan.2017.12.007
- Skevaki C, Pararas M, Kostelidou K., Tsakris A, Routsias JG. Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious diseases. ClinExp 2015;180(2):165-77. doi: https://doi.org/10.1111/cei.12578
- Takeda K, Akira S. Toll-like receptors’. Curr Protoc Immunol, 2015;109(1). doi: https://doi.org/10.1002/0471142735.im1412s109
- Tartey S, Takeuchi O. Pathogen recognition and Toll-like receptor targeted therapeutics in innate immune cells. IntRev 2017;36(2):57-73. doi: https://doi.org/10.1080/08830185.2016.1261318
- Al-Qahtani AA, Al-Anazi R, Al-Zoghaibi F, Abdo AA, Sanai FM, Khan MQ, et al. The association of toll-like receptor 4 polymorphism with hepatitis C virus infection in Saudi Arabian patients. BioMed research international; doi: https://doi.org/10.1155/2014/357062
- Syzova LM, Koval TI, Ilchenko VI, Zviaholska IM, Iziumska OM. The impact of Toll-like receptors on the immune system functioning and on the immunopathogenesis of chronic hepatitis C: a modern view (literature review). Pathologia. 2020;17(1):114-21. doi: https://doi.org/10.14739/2310-1237.2020.1.203859
- Mohamed SY, Mostafa EF, Hanafy AS, Atia H, Metwally A, Marei AM. The relationship between expression of Toll-like receptor 4 in chronic hepatitis C patients and different stages of liver fibrosis. Gastroenterol Hepatol Bed Bench. 2017;10(4):278-83. doi: https://doi.org/10.31219/osf.io/6pj56
- Ziakas PD, Prodromou ML, El Khoury J, Zintzaras E, Mylonakis E. The role of TLR4 896 A> G and 1196 C>T in susceptibility to infections: a review and meta-analysis of genetic association studies. PloS one. 2013;8(11). doi: https://doi.org/10.1371/journal.pone.0081047
- Tizaoui K, Kaabachi W, Hamzaoui K, Hamzaoui A. Association of single nucleotide polymorphisms in Toll-like receptor genes with asthma risk: a systematic review and meta-analysis. Allergy Asthma Immuno Res. 2015;7(2):130-40. doi: https://doi.org/10.4168/aair.2015.7.2.130
- Elefanti L, Sacco G, Stagni C, Rastrelli M, Menin C, Russo I, et al. TLR7 Gln11Leu single nucleotide polymorphism and susceptibility to cutaneous melanoma. Oncol 2016;12 (1):275-80. doi: https://doi.org/10.3892/ol.2016.4584
- Alvarado-Tapias E, Guarner-Argente C, Oblitas E, Sánchez E, Vidal S, Román E, et al. Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites.World J Hepatol. 2018;10(1):124-33. doi: https://doi.org/10.4254/wjh.v10.i1.124
- Iqbal MS, Ashfaq UA, Khaliq S, Masoud MS, Qasim M, Haque A, et al. Toll-like receptor 4 polymorphism as pretreatment predictor of response to HCV genotype 3a interferon-based treatment. Future Virol. 2017;12(12):739-46.
- Alvarado-Tapias E, Guarner-Argente C, Oblitas E, Sánchez E, Vidal S, Román E, et al. Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites. World J Hepatol. 2018;10(1):123-24. doi: https://doi.org/10.4254/wjh.v10.i1.124
- Chen Yi, Me SG, Burchell J, Skinner N, Millen R, Matthews G, Hellard M, et al. Toll-like receptor expression and signaling in peripheral blood mononuclear cells correlate with clinical outcomes in acute hepatitis C virus infection. JID.2016;214(5):739-47. doi: https://doi.org/10.1093/infdis/jiw235
- Piñero P, Juanola O, Caparrós E, Zapater P, Giménez P, González-Navajas JM, et al. Toll-like receptor polymorphisms compromise the inflammatory response against bacterial antigen translocation in cirrhosis. Sci Rep. 2017;7. doi: https://doi.org/10.1038/srep46425
- Hacine-Gherbi H, Denys A, Carpentier M, Heysen A, Duflot P, Lanos P, et al. Use of Toll-like receptor assays for the detection of bacterial contaminations in icodextrin batches released for peritoneal dialysis. Toxicol 2017;4:566-73. doi: https://doi.org/10.1016/j.toxrep.2017.10.004
- Vesnina LE, Izmailova OV, Shlykova OA, Kidashev I. Features of NF-kB-mediated signaltransduction and development of systemic inflammation in patients with diseases of internal organs are determined by microbial factor and individual reactivity of the body (review of own research findings). Problemy ekologii ta medytsyny. 2015;19(3-4):30-37. Available from: https://ecomed-journal.org/index.php/journal/article/view/49
- Vijay K. Toll-like receptors in immunity and inflammatory diseases: past, present, and future. Int Immunopharmacol.2018;59:391-412. doi: https://doi.org/10.1016/j.intimp.2018.03.002
- Volchenkov R, Sprater F, Vogelsang P, Appel S. The 2011 Nobel Prize in physiology or medicine. Scand J Immunol. 2012;75(1):1-4. doi: https://doi.org/10.1111/j.1365-3083.2011.02663.x
Shtrygol’ S.Yu., Koiro O.O., Kudina O.V., Yudkevych T.K., Gorbach T.V. Comparative analysis of the effect of diclofenac sodium and etoricoxib on energy metabolism in rat liver in the acute general cooling model
Authors and affiliations
Shtrygol’ S.Yu. National University of Pharmacy, Kharkiv, Ukraine,
Koiro O.O. National University of Pharmacy, Kharkiv, Ukraine
Kudina O.V. National University of Pharmacy, Kharkiv, Ukraine
Yudkevych T.K. National University of Pharmacy, Kharkiv, Ukraine
Gorbach T.V. Kharkiv National Medical University, Kharkiv, Ukraine
Key words: nonsteroidal anti-inflammatory drugs, acute general cooling, energy metabolism, liver
Abstract. Comparative analysis of the effect of diclofenac sodium and etoricoxib on energy metabolism in rat liver in the acute general cooling model. Shtrygol’ S.Yu., Koiro O.O., Kudina O.V., Yudkevych T.K., Gorbach T.V. When the ambient temperature decreases, physiological mechanisms that prevent heat loss are activated. However, under cold stress hypothermia develops, which significantly disrupts the functioning of the body and can be transformed into life-threatening. Preventive use of nonsteroidal anti-inflammatory drugs, especially diclofenac sodium and etoricoxib, has been found to reduce the severity of cold trauma. Given that their frigoprotective effect can accompany the impact on the synthesis of eicosanoids when exposed to low temperatures, it is advisable to study mechanisms for preventing hypothermia independent of cyclooxygenase, particularly the influence on energy metabolism. The aim of the study was to figure out the effect of diclofenac sodium and etoricoxib on the indicators of energy metabolism in the liver of rats after acute general cooling. Experiments were carried out on 28 sexually mature male rats, which were given diclofenac sodium (7 mg/kg), etoricoxib (5 mg/kg), or solvent 30 minutes before cold trauma intragastrically (in the intact control and pathology control groups). Acute hypothermia was caused by exposure of animals for 2 hours at a temperature of -18°C. Rectal temperature was measured before and after acute general cooling. The content of lactate, pyruvate and adenosine triphosphate in the liver was measured and the lactate/pyruvate ratio was calculated. Diclofenac sodium, unlike etoricoxib, was found to significantly reduce the severity of hypothermia. Both nonsteroidal anti-inflammatory drugs prevent energy metabolism disorders caused by exposure to cold, namely, reducing the concentration of lactic acid and the ratio of lactate/pyruvate, increasing the content of pyruvate and adenosine triphosphate in the liver of animals. Etoricoxib normalizes the content of energy metabolism intermediates to their levels in intact animals. Diclofenac sodium has a similar effect, the expression of which is inferior to the selective cyclooxygenase-2 inhibitor. Therefore, when administered prophylactically before acute general cooling, diclofenac sodium effectively prevents hypothermia in rats, surpassing etoricoxib. Etoricoxib completely prevents a decrease in the content of pyruvate and adenosine triphosphate, as well as the accumulation of lactic acid in the liver. Diclofenac sodium is inferior to etoricoxib in its effect on energy metabolism, which indicates other mechanisms of frigoprotective action of a non-selective cyclooxygenase inhibitor. The frigoprotective and energotropic properties of nonsteroidal anti-inflammatory drugs dissociate.
- Biem J, Koehncke N, Classen D, Dosman J. Out of the cold: management of hypothermia and frostbite. Canadian Medical Association Journal. 2003;168(3):305-11. PMID: 12566336. PMCID: PMC140473.
- Centers for Disease Control and Prevention. QuickStats: Death Rates Attributed to Excessive Cold or Hypothermia Among Persons Aged ≥15 years, by Urban-Rural Status and Age Group - National Vital Statistics System, United States, 2019. MMWR Morb Mortal Wkly Rep; 2021:70(7):258. doi: https://doi.org/10.15585/mmwr.mm7007a6
- Fudge J. Exercise in the Cold: Preventing and Managing Hypothermia and Frostbite Injury. Sports Health.2016;№8(2):133-9. doi: https://doi.org/10.1177/1941738116630542
- Charkoudian N. Mechanisms and modifiers of reflex induced cutaneous vasodilation and vasoconstriction in humans. J Appl Physiol. 2010;109(4):1221-8. doi: https://doi.org/10.1152/japplphysiol.00298.2010
- Haman F, Blondin DP. Shivering thermogenesis in humans: Origin, contribution and metabolic requirement. Temperature (Austin). 2017 May 22;4(3):217-26. PMID: 28944268; PMCID: PMC5605160. doi: https://doi.org/10.1080/23328940.2017.1328999
- W van Marken Lichtenbelt. Brown adipose tissue and the regulation of nonshivering thermogenesis. Curr Opin Clin Nutr Metab Care. 2012 Nov;15(6):547-52. PMID: 23037904. doi: https://doi.org/10.1097/MCO.0b013e3283599184
- Duong H, Patel G. [Updated 2021 Jan 27]. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK545239/
- McIntosh SE, Hamonko M, Freer L, Grissom CK, Auerbach PS, Rodway GW, et al. Wilderness Medical Society Practice Guidelines for the Prevention and Treatment of Frostbite: 2014 Update. Wilderness & Environmental Medicine. 2014;2(22):156-66. PMID: 21664561. doi: https://doi.org/10.1016/j.wem.2011.03.003
- Imray C, Grieve A, Dhillon S. Cold damage to the extremities: frostbite and non-freezing cold injuries. Postgraduate medical journal. 2009;85:481-8. PMID: 19734516. doi: https://doi.org/10.1136/pgmj.2008.068635
- Kapelka IG, Shtrygol’ SYu. [The comparative research of frigoprotective properties of nonsteroidalanti-inflammatory drugs оn the model of acute general cooling]. Pharmacology and Drug Toxicology. 2019;13(5):338-43. Ukrainian.
- Kapelka IG, Shtrygol` SYu, Lesyk RB, Lozynskyi AV, Khomyak SV, Novikov VP. [The comparative research of arachidonic acid cascade inhibitors for frigoprotective activity]. Pharmacology and Drug Toxicology.2020;14(2):122-8. doi: https://doi.org/10.33250/14.02.122
- Shtrygol SYu, Kapelka IG, Mishchenko MV, Mishchenko OYa. [Non-obvious effects of montelukast – leukotriene receptor blocker: frigoprotective and anticonvulsant properties]. Medicni perspektivi. 2021;26(2):19-25. doi: https://doi.org/10.26641/2307-0404.2021.2.234486
- Shtrygol’ S, Koiro O, Kudina O, Tovchiga O, Yudkevich T, Oklei D. The influence of non-steroidal anti-inflammatory drugs with different mechanisms of action on the course of stress reaction, the functional state of kidneys, liver, and heart on the model of acute general cooling ScienceRise: Pharmaceutical Science. 2022;2(36):46-55. doi: https://doi.org/10.15587/2519-4852.2022.255797
- Kapelka I, Shtrygol S, Koiro O, Merzlikin S, Kudina O, Yudkevych T. Effect of arachidonic acid cascade inhibitors on body temperature and cognitive functions in rats in the Morris water maze after acute cold injury. Pharmazie. 2021 Jul 1;76(7):313-6.
- Kapelka IG, Shtrygol’ SYu. [The characteristics of the anti-inflammatory action of sodium diclofenac in cold and normal environment]. News of Pharmacy. 2020;2(100):106-12. doi: https://doi.org/10.24959/nphj.20.37
- Bondarev EV, Shtrygol’ SYu. Drogovoz SM, Shchokіna KG. [Cold injury: preclinical study of drugs with frigoprotective properties. Methodical recommendations of the Ministry of Health of Ukraine]. Kharkiv: National University of Pharmacy; 2018. Ukrainian.
- Danilovа LA, editor. [Handbook of laboratory research methods]. Sankt-Peterburg: Piter; 2003. Russian.
- Kamyshnikova VS, editor. [Handbook of clinical biochemical research and laboratory diagnostics]. Moskva: MEDpress-inform; 2009. Russian.
- Eshchenko ND. [Measurement of ATP content in tissues]. In: Prokhorova MI, editor. [Methods of biochemical research (lipid and energy metabolism)]. Leningrad: izdatelstvo leningradskogo universiteta; 1982. p. 210-212. Russian.
- Hao L, Kearns J, Scott S, Wu D, Kodani SD, Morisseau C, et al. Indomethacin Enhances Brown Fat Activity. J Pharmacol Exp Ther. 2018;365(3):467-75. doi: https://doi.org/10.1124/jpet.117.246256
- Abumrad NA. The Liver as a Hub in Thermogenesis. Cell Metab. 2017 Sep 5;26(3):454-5. PMID: 28877451. doi: https://doi.org/10.1016/j.cmet.2017.08.018
- Yao R, Yang Y, Lian S, Shi H, Liu P, Liu Y, et al. Effects of Acute Cold Stress on Liver O-GlcNAcylation and Glycometabolism in Mice. Int. J. Mol. Sci. 2018;19(9). doi: https://doi.org/10.3390/ijms19092815
- Brychta RJ, and Chen KY. Cold-induced Thermogenesis in Humans. Eur. J. Clin. Nutr. 2017;71(3):345-52. doi: https://doi.org/10.1038/ejcn.2016.223
- Fosslien E. Review: Cardiovascular Complications of Non-Steroidal Anti-Inflammatory Drugs. Annals of Clinical & Laboratory Science. 2005;4(35):347-85. PMID: 16254252.
- Romanovsky AA, Garami A. Prostaglandin riddles in energy metabolism: E is for excess, D is for depletion. Focus on "Food deprivation alters thermoregulatory responses to lipopolysaccharide by enhancing cryogenic inflammatory signaling via prostaglandin D2". Am J Physiol Regul Integr Comp Physiol. 2010;298(6):R1509-R1511. doi: https://doi.org/10.1152/ajpregu.00253.2010
- Shi H, Yao R, Lian S, Liu P, Liu Y, Yang YY, Yang H, Li S. Regulating glycolysis, the TLR4 signal pathway and expression of RBM3 in mouse liver in response to acute cold exposure. Stress. 2019 May;22(3):366-76. Epub 2019 Mar 1.PMID: 30821572. doi: https://doi.org/10.1080/10253890.2019.1568987
- Gottfried E, Lang SA, Renner K, Bosserhoff A, Gronwald W, Rehli M, et al. New aspects of an old drug – diclofenac targets MYC and glucose metabolism in tumor cells. PLoS One. 2013 Jul 9;8(7):e66987. PMID: 23874405; PMCID: PMC3706586. doi: https://doi.org/10.1371/journal.pone.0066987
Kuzminov B.P., Zazulyak T.S. Medicinal products as a causative agent of occupational diseases in pharmaceutical workers (literature review)
Authors and affiliations
Kuzminov B.P. Lviv national medical university named after Danylo Halytskyi, Lviv, Ukraine
Zazulyak T.S. Lviv national medical university named after Danylo Halytskyi, Lviv, Ukraine, e-mail:
Key words: medicinal products, occupational diseases, pharmaceutical companies
Abstract. Medicinal products as a causative agent of occupational diseases in pharmaceutical workers (literature review). Kuzminov B.P., Zazulyak T.S. The issue of occupational diseases in chemical and pharmaceutical workers is urgent because it stems from the rapid pace of development, the functional features, and the high biological activity of raw materials used by that industry. The study is aimed at summarizing the information on preconditions and nature of occupational diseases among chemical and pharmaceutical workers based on the analysis of literature data. An important prerequisite for the emergence of occupational diseases is the shortcomings in the production process, leading to pollution of surfaces and workspace air with chemicals through the use of semi-automatic equipment in particular. The harmful substances then enter the bodies of workers through the respiratory system, which is the main and most harmful way. The most dangerous processes are the production and processing of substances with high pharmacological activity, and thus the active pharmaceutical ingredients maybe considered to be the leading causative agents of occupational diseases in the industrial production of medicinal products. The range of diseases diagnosed in pharmaceutical workers is diverse and includes acute intoxication, effects on internal organs, reproductive function, changes in hormonal status, and changes in the hemic system and nervous system. The most common are diseases of respiratory organs and diseases of allergic origin. As a result, influential international organizations and many authors emphasize the need to develop criteria and methods for assessing the harmful effects of medicinal products on the health of workers when authorizing their production.
- Vitiuk AV, Trachenko KR. [Contradictory trends in the development of the pharmaceutical industry of Ukraine]. Visnyk Vinnytskoho politekhnichnoho instytutu. 2018;6:35-43. doi: https://doi.org/10.31649/1997-9266-2018-141-6-35-43
- Horokhova LH, Martynova NA, Kizichenko NV, Lohunova TD. [Hygienic aspects of the state of health of workers in chemical and pharmaceutical production]. Medytsyna v Kuzbasse. 2017;16(3):11-5. Russian.
- Horokhova LH, Ulanova EV, Shavtsova HM, Erdeeva SV, Blazhina ON. [The state of health of workers in the chemical and pharmaceutical industry]. Medytsyna truda i promyshlennaia ekolohiia. 2018;6:38-42. Russian. doi: https://doi.org/10.31089/1026-9428-2018-6-38-42
- [State Register of Medicines of Ukraine] [Internet]. Kyiv: State Service of Medicines and Drug Control of Ukraine; 2021 [updated 2021 March 31; cited 2021 April 9]. Available from: https://www.dls.gov.ua/
- [Economic statistics] [Internet]. Kyiv: State Statistics Service of Ukraine; 2021 [updated 2021 March 12; cited 2021 April 9]. Available from: http://www.ukrstat.gov.ua.
- Zahorii HV, Ponomarenko MS, Trokhymchuk VV, Drozdova AO, Hryhoruk YuM. [Comparative structural and statistical analysis of morbidity with temporary disability of personnel of CJSC “Pharmaceutical firm “Darnytsia” in connection with reengineering processes in the strategy of accelerated development of the enterprise (1996-2000 and 2006-2010)]. Upravlinnia, ekonomika ta zabezpechennia yakosti v farmatsii. 2012;1:38-44. Ukrainian.
- Zazuliak TS. [Harmful chemical factors in the production of medicines]. Aktualni problemy profilaktychnoi medytsyny. 2021;22:94-109. Ukrainian.
- Trakhtenberh IM, editors. [Medical toxicology. Preclinical studies]. Kyiv: Avitsena; 2020. Ukrainian.
- Nahorna AM, Sokolova MP, Kononova IH. [Occupational morbidity of medical workers in Ukraine as a medical and social problem]. Ukrainskyi zhurnal z problem medytsyny pratsi. 2016;2(47):3-16. Ukrainian. doi: https://doi.org/10.33573/ujoh2016.02.003
- Nahorna AM, Sokolova MP, Kononova IH. [Epidemiological studies of occupational health in Ukraine]. Ukrainskyi zhurnal z problem medytsyny pratsi. 2018;4(57):3-20. Ukrainian. doi: https://doi.org/10.33573/ujoh2018.04.003
- Nahorna OK. [Occupational safety of workers in the pharmaceutical industry]. In: Problemy okhorony pratsi, promyslovoi ta tsyvilnoi bezpeky. Proceedings of the eighteenth all-Ukrainian scientific-methodical Сonference; 2018 May15-16; Kyiv: KPI im. Ihoria Sikorskoho; 2018. p. 190-3. Ukrainian.
- [About medicines. Pub. L. No. 123/96-VR, 1996. Information of the Verkhovna Rada of Ukraine No. 22, Stat. 86. (Apr 04, 1996).
- Trakhtenberh IM, Dmytrukha NM. [Industrial toxicology: main directions, results and prospects of scientific activity]. Ukrainskyi zhurnal z problem medytsyny pratsi. 2019;5(2):87-101. Ukrainian. doi: https://doi.org/10.33573/ujoh2019.02.087
- Tymoshyna DP, Lubianova IP. [Health problems of medical workers in Ukraine]. Upravlinnia zakladamy okhorony zdorovia. 2015;8:54-58. Ukrainian.
- Shafran LM, Tretiakova OV. [The concept of “TOXICITY TESTING-21” in modern toxicology]. Aktualni problemy profilaktychnoi medytsyny. 2021;22:8-42. Ukrainian.
- Albert F, Bassani R, Coen D, Vismara A. Hypoglycaemia by inhalation. Lancet. 1993;342:47-8. doi: https://doi.org/10.1016/0140-6736(93)91906-3
- Allian AD, Shah NP, Ferretti AC, Brown DB, Kolis SP, Sperry JB. Process safety in the pharmaceutical industry – part I: thermal and reaction hazard evaluation processes and techniques. Organic Process Research & Development. 2020;24(11):2529-48. doi: https://doi.org/10.1021/acs.oprd.0c00226
- Baxter PJ, Samuel AM, Aw TC, Cocker J. Exposure to quinal barbitone sodium in pharmaceutical workers. Br Med J (Clin Res Ed). 1986;292:660-61. doi: https://doi.org/10.1136/bmj.292.6521.660-a
- Bhusnure OG, Dongare RB, Gholve SB, Giram PS. Chemical hazards and safety management in pharmaceutical industry. Journal of Pharmacy Research. 2018;12(03):357-69.
- Conde-SalazarL, Blancas-Espinosa R, Pérez-Hortet Occupational airborne contact dermatitis from omeprazole. Contact Dermatitis. 2007 Jan;56(1):44-6. doi: https://doi.org/10.1111/j.1600-0536.2007.00921.x
- European competition authorities working to gether for affordable and innovative medicines: Report from the commission to the council and the European Parliament. Competition enforcement in the pharmaceutical sector (2009-2017). [Internet]. Brussels; 2019 Jan 28 [cited 2021 April 15]. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:52019DC0017
- Fung VSWC. Risk Assessment and Communication in Pharmaceuticals: Recognizing the Differences in Occupational Health and Medication Safety. J Toxicol Risk 2019;5:019. doi: https://doi.org/10.23937/2572-4061.1510019
- Gathuru IM, Buchanich JM, Marsh GM, Dolan DG. Health Hazards in the Pharmaceutical Industry. Pharmaceut Reg Affairs. 2015;4(3):1-15. doi: https://doi.org/10.4172/2167-7689.1000145
- Gomez Torrijos E, Borja J, Galindo PA, et al. Allergic contact dermatitis from mitomycin C. Allergy. 1997;52:687.
- Goon ATJ, McFadden JP, McCann M, Royds C, Rycroft RJG. Allergic contact dermatitis from melphalan and chlorambucil: cross-sensitivity or cosensitization? Contact 2000;47:309. doi: https://doi.org/10.1034/j.1600-0536.2002.4705101.x
- Gunnarsson L, Jason R. Snape JR, Verbruggen B, Owen SF, Kristiansson E, et al. Pharmacology beyond the patient – the environmental risks of human drugs. Environment International. 2019 Aug;129:320-32. doi: https://doi.org/10.1016/j.envint.2019.04.075
- Heron RJL, Pickering FC. Health effects of exposure to active pharmaceutical ingredients (APIs). Occupational 2003;53:357-62. doi: https://doi.org/10.1093/occmed/kqg115
- Jeebhay M, Mbuli S, Uebel Assessment of exposure to chloramphenicol and azathioprine among workers in a South African pharmaceutical plant. Int Arch Occup Environ Health. 1993;65(1 Suppl):119-22. doi: https://doi.org/10.1007/BF00381321
- Kiffmeyer ТК, Drrernat, Schmidt KG, Paul JM, Sessink PJM. Vapourpressures, evaporation behaviour and airborne concentrations of hazardous drugs: implications for occupational safety. The pharmaceutical journal. 2002;268:331-7.
- Kuzminov BP, Zazulyak TS, Hrushka OI, Kuzminov AB, Shvets IA, Brejdak AA. System Approach to Regulation of the Harmful Influence of Medicines in the Conditions in the Manufacturing Process and Environment. Eksperymentalna ta klinichna fiziolohiia i biokhimiia. 2018;2(82):15-20. doi: https://doi.org/10.25040/ecpb2018.02.015
- Milković-KrausS, Jelena Macan J, Bozica Kanceljak-Macan Occupational allergic contact dermatitis from azithromycin in pharmaceutical workers: a case series. Contact Dermatitis. 2007 Feb;56(2):99-102. doi: https://doi.org/10.1111/j.1600-0536.2007.00999.x
- Neumark M, Arieh Ingber A, Michael Levin M, Dan Slodownik Occupational airborne contact dermatitis caused by pantoprazole. Contact Dermatitis. 2011 Jan;64(1):60-1.
- Park HS, Nahm New occupational allergen in a pharmaceutical industry: serratial peptidase and lysozyme chloride. Ann Allergy Asthma Immunol. 1997 Feb;78(2):225-9.
- PrasadMH, Pushpavathi K, Devi GS, Reddy Reproductive epidemiology in sulfonamide factory workers. J Toxicol Environ Health. 1996 Feb 9;47(2):109-14. doi: https://doi.org/10.1080/009841096161816
- Reichard JF, Maiera MA, NaumannBD, Pecquet AM, Pfister T, Sandhu R, et al. Toxicokinetic and toxicodynamic considerations when deriving health-based exposure limits for pharmaceuticals. Regulatory Toxicology and Pharmacology. 2016;79(1,15):67-78. doi: https://doi.org/10.1016/j.yrtph.2016.05.027
- Romanowska-Słomka I, Szołkowski A. [Dangers of chemical substances in the pharmaceutical industry]. Zeszyty naukowe wyższej szkoły zarządzania ochroną pracy w Katowicach. 2019;1(15):43-57. Polish. doi: https://doi.org/10.32039/WSZOP/1895-3794-2019-01
- RyanPJJ, Rycroft RJG, Aston Allergic contact dermatitis from occupational exposure to ranitidine hydrochloride. Contact Dermatitis. 2003 Feb;48(2):67-8. doi: https://doi.org/10.1034/j.1600-0536.2003.480202.x
- SahuRK, Yadav R, Prasad P, Roy, Chandrakar S. Adverse drug reactions monitoring: prospects and impending challenges for pharmacovigilance. Springerplus. 2014 Nov;3:695.
- Sarkis M, Bernardi A., Shah N, Papathanasiou MM. Emerging Challenges and Opportunities in Pharmaceutical Manufacturing and Distribution. Processes. 2021;9(3):457. doi: https://doi.org/10.3390/pr9030457
- Schenk L, Johanson G. Use of uncertainty factors by the European Commission Scientific Committee on Occupational Exposure Limits: a follow-up. Crit Rev Toxicol.2018;48(7):513-21. doi: https://doi.org/10.1080/10408444.2018.1483891
- Scott Occupational health in the pharmaceutical industry: an overview. Occup Med (Lond). 2003 Sep;53(6):354-6. doi: https://doi.org/10.1093/occmed/kqg114
- Shuai Deng, Yige Sun, Tianyi Zhao, Yang Hu, Tianyi Zang. A Review of Drug Side Effect Identification Methods. Current Pharmaceutical Design. 2020;26(26):3096-104. doi: https://doi.org/10.2174/1381612826666200612163819
- Singal M, Patnode R. Health Hazard Evaluation Report 81-322-1228. [Internet]. Mylan Pharmaceuticals, Morgantown, West Virginia. National Institute for Occupational Safety and Health, Cincinnati, OH: Report No. HETA 81-322-1228; 1982 Nov. [cited 2021 April 15]. Available from: https://www.cdc.gov/niosh/hhe/reports/pdfs/81-322-1228.pdf.
- TaskinenH, Lindbohm ML, Hemminki Spontaneous abortions among women working in the pharmaceutical industry. Br J Ind Med. 1986 Mar;43(3):199-205. doi: https://doi.org/10.1136/oem.43.3.199
- Thomson KF, Sheehan-Dare RA, Wilkinson SM. Allergic contact dermatitis from topical carmustine. Contact Dermatitis. 2000;42:112. PMID: 10703643.
- TomeiF, Iavicoli S, Iavicoli A, Papaleo B, Baccolo Liver damage in pharmaceutical industry workers. Arch Environ Health. 1995 Jul-Aug;50(4):293-7. doi: https://doi.org/10.1080/00039896.1995.9935957
- Whitaker P. Occupational allergy to pharmaceutical products. Current Opinion in Allergy and Clinical Immunology. 2016 April;16(2):101-6. doi: https://doi.org/10.1097/ACI.0000000000000248
- Yan BB, Ma YY, Guo J, Wang YC. Self-microemulsifying delivery system for improving bioavailability of water insoluble drugs. Journal of nanoparticle research. 2020 Jan 4;22(1):1-14. doi: https://doi.org/10.1007/s11051-019-4744-6
- Zuskin E, Mustajbegovic J, Schachter NE, Kern J, Deckovic-Vukres V, Pucarin-Cvetkovic J, Nola-Premec IA. Respiratory findings in pharmaceutical workers. Am J Ind Med. 2004 Nov;46(5):472-9. doi: https://doi.org/10.1002/ajim.20085
Menekse Oksar, Hasibe G. Baytan, Selim Turhanoglu, Tayfun Aybek, Nazife Y. Ardicoglu, Oguzhan Ozcan Changes in tryptase levels during cardiac surgery in patients at low risk for allergic reactions
Authors and affiliations
Menekse Oksar Hatay Mustafa Kemal University, Antakya, Hatay Province, Turkey,
Hasibe G. Baytan Private TOBB ETU Hospital, Ankara, Turkey
Selim Turhanoglu Hatay Mustafa Kemal University, Antakya, Hatay Province, Turkey
Tayfun Aybek Private TOBB ETU Hospital, Ankara, Turkey
Nazife Y. Ardicoglu Private TOBB ETU Hospital, Ankara, Turkey
Oguzhan Ozcan Hatay Mustafa Kemal University, Antakya, Hatay Province, Turkey
Key words: hypersensitivity, anaesthesia, cardiac procedures, protamines, adverse effects, tryptases
Abstract. Changes in tryptase levels during cardiac surgery in patients at low risk for allergic reactions. Menekse Oksar, Hasibe G. Baytan, Selim Turhanoglu, Tayfun Aybek, Nazife Y. Ardicoglu, Oguzhan Ozcan. Tryptase test can be used as a clinical marker of mast cell activation. The present study is was aimed to identify variations in serum tryptase levels and their possible relationships with allergic reactions to protamine in low-risk patients undergoing cardiac bypass surgery. Thirty patients according to American Society of Anesthesiologists physical status III who underwent cardiac bypass surgery were enrolled. This prospective, non-randomised, clinical study was conducted in an operating room. Venous blood samples for tryptase measurements were obtained from cardiac bypass surgery patients upon admission to the operating room and immediately before and 30 min after the initiation of protamine administration. Signs of allergic reactions were recorded and management steps based on rapid effect response-based clinical assessments for diagnosis and treatment decisions during protamine administrations were described. Serum tryptase levels and clinical signs of allergic reactions, primarily mean arterial pressure (MAP), were recorded. Serum tryptase levels increased significantly and progressively during the bypass procedure (study power, 80%; sample size, 28; power of analysis, 99.8% with α=0.05); however, tryptase levels did not reach a sufficiently high level to confirm an allergic reaction. The MAP and heart rate decreased in 50% of the patients. Although tryptase increased significantly when compared with baseline levels, protamine-associated increases were not significant and failed to provide an unequivocal indication of an allergic response to protamine.
- Benoit R, Nougier C, Desmurs-Clavel H, Simon M, Dargaud Y. The modification of the thrombin generation assay for the clinical assessment of hypercoagulability in patients receiving heparin therapy. International Journal of Laboratory Hematology. 2022;44(2):371-8. doi: https://doi.org/10.1111/ijlh.13735
- Zhao Y-C, Zhao X, Fu G-W, Liu Q-L, Li H-B. Heparin-free after 3000 IU heparin loaded in veno-venous ECMO supported acute respiratory failure patients with hemorrhage risk: a novel anti-coagulation strategy. Thrombosis 2022;20(1):36. doi: https://doi.org/10.1186/s12959-022-00396-w
- Guo F, Zhu X, Wu Z, Wu J, Zhang F. Clinical applications of machine learning in the survival prediction and classification of sepsis: coagulation and heparin usage matter. Journal of Translational Medicine. 2022;20(1):265. doi: https://doi.org/10.1186/s12967-022-03469-6
- Chen Y, Phoon PHY, Hwang NC. Heparin Resistance During Cardiopulmonary Bypass in Adult Cardiac Surgery. Journal of Cardiothoracic and Vascular Anesthesia.2022;36(11):4150-60. doi: https://doi.org/10.1053/j.jvca.2022.06.021
- To L, Attar D, Lines B, Coba V, Lekura J. Incidence of Heparin-Induced Thrombocytopenia in Patients With Newly Implanted Mechanical Circulatory Support Devices. Annals of Pharmacotherapy. 2022;56(5):565-71. doi: https://doi.org/10.1177/10600280211038705
- Tian L, Liu Y, Fei Y, Li L, Shi J. Effect of Clemastine Fumarate on Perioperative Hemodynamic Instability Mediated by Anaphylaxis During Cardiopulmonary Bypass Surgery. Medical Science Monitor. 2022;28:e936367. doi: https://doi.org/10.12659/MSM.936367
- Chiba Y, Otsuka Y, Lefor AK, Sanui M. Efficacy of point-of-care thromboelastography 6s to evaluate platelet function in a patient with pseudothrombocytopenia undergoing cardiopulmonary bypass: a case report. JA Clinical 2022;8(1):8. doi: https://doi.org/10.1186/s40981-022-00496-6
- He Y-Y, Huang Y-P, Wang L, Song B. A case with no administration of protamine to neutralize heparin in aortic valve replacement with cardiopulmonary bypass. Transplant 2022;73:101601. doi: https://doi.org/10.1016/j.trim.2022.101601
- Asai H, Yamamoto R, Kuromiya K, Kurosaki H, Fukuishi N. A Rapid and Sensitive Determination of Histamine in Mast Cells Using a Didansyl Derivatization Method. International Archives of Allergy and Immunology.2022;183(10):1050-5. doi: https://doi.org/10.1159/000525588
- Huang W, Zhou X. Anti-histamine effects of dipotassium glycyrrhizinate on lung fibroblasts, implicating its therapeutic mechanism for pulmonary fibrosis. The Journal of pharmacy and pharmacology. 2022;74(9):1241-50. doi: https://doi.org/10.1093/jpp/rgac030
- De Almeida AD, Silva IS, Fernandes-Braga W, Cassali GD, Klein A. A role for mast cells and mast cell tryptase in driving neutrophil recruitment in LPS-induced lung inflammation via protease-activated receptor 2 in mice. Inflammation Research. 2020;69(10):1059-70. doi: https://doi.org/10.1007/s00011-020-01376-4
- Schwartz LB, Metcalfe DD, Miller JS, Earl H, Sullivan T. Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis. The New England Journal of Medicine. 1987;316:622-6. doi: https://doi.org/10.1056/NEJM198706253162603
- Schwartz LB, Min HK, Ren S, Xia HZ, Hu J, Zhao W. Tryptase precursors are preferentially and spontaneously released, whereas mature tryptase is retained by HMC-1 cells, Mono-Mac-6 cells, and human skin-derived mast cells. Journal of Immunology. 2003;170:5667-73. doi: https://doi.org/10.4049/jimmunol.170.11.5667
- Xie H, Chen L, Zhang H, Wang S, He S. Increased expressions of CD123, CD63, CD203c, and Fc epsilon receptor I on blood leukocytes of allergic asthma. Frontiers inMolecular 2022;9:907092. doi: https://doi.org/10.3389/fmolb.2022.907092
- Krishna MT, York M, Chin T, Gnanakumaran G, Heslegrave J, Derbridge C. Multi-center retrospective analysis of anaphylaxis during general anesthesia in the United Kingdom: etiology and diagnostic performance of acute serum tryptase. Clinical and Experimental Immunology.2014;178:399-404. doi: https://doi.org/10.1111/cei.12424
- Fellinger C, Hemmer W, Wohrl S, Sesztak-Greinecker G, Jarisch R, Wantke F. Clinical characteristics and risk profile of patients with elevated baseline serum tryptase. Allergologia et Immunopathologia. 2014;42:544-52. doi: https://doi.org/10.1016/j.aller.2014.05.002
- Antunes J, Kochuyt AM, Ceuppens JL. Perioperative allergic reactions: experience in a Flemish referral center. Allergologia et Immunopathologia. 2014;42:348-54. doi: https://doi.org/10.1016/j.aller.2013.08.001
- Sokolowska E, Kalaska B, Miklosz J, Mogielnicki A. The toxicology of heparin reversal with protamine: past, present and future. Expert Opinion on Drug Metabolism and Toxicology. 2016;12(8):897-909. doi: https://doi.org/10.1080/17425255.2016.1194395
- Chooriyil N, Jom D, Panattil P, Sreedharan S. Protamine-induced hypotension and pulmonary arterial hypertension. Journal of Pharmacology and Pharmacotherapeutics. 2021;12(1):23-25.
- Bircher AJ, Hauser C, Pichler W, Varonier H, Wüthrich B. Importance and indication of specific IgE and IgG antibody determination in allergy diagnostics. Allergologie.2002;25(6):338-40. doi: https://doi.org/10.5414/ALP25338
- Dewachter P, Savic L. Perioperative anaphylaxis: pathophysiology, clinical presentation and management. BJA 2019;19(10):313-20. doi: https://doi.org/10.1016/j.bjae.2019.06.002
- Mo Y, Qian Y. Successful re-treatment in a patient with protamine allergy by a slow intravenous injection method. Adverse Drug Reactions Journal. 2020;22(2):117-9.
- Pastorello EA, Farioli L, Scibilia G. Baseline tryptase levels are related to age, total IgE, and anti-rPru p 3 IgE levels in peach-allergic patients. Journal of Allergy and Clinical Immunology. 2013;23:127-8.
- Blum S, Gunzinger A, Muller UR, Helbling A. Influence of total and specific IgE, serum tryptase, and age on severity of allergic reactions to Hymenoptera stings. Allergy.2011;66:222-8. doi: https://doi.org/10.1111/j.1398-9995.2010.02470.x
- Borer-Reinhold M, Haeberli G, Bitzenhofer M. An increase in serum tryptase even below 11.4 ng mL−1 may indicate a mast cell-mediated hypersensitivity reaction: a prospective study in Hymenoptera venom allergic patients. Clinical and Experimental Allergy. 2011;41:1777-83. doi: https://doi.org/10.1111/j.1365-2222.2011.03848.x
- Laroche D, Gomis P, Gallimidi E, Malinovsky JM, Mertes PM. Diagnostic value of histamine and tryptase concentrations in severe anaphylaxis with shock or cardiac arrest during anaesthesia. Anaesthesiology. 2014;121:272-9. doi: https://doi.org/10.1097/ALN.0000000000000276
- BaimbetovA, Bizhanov K, Yakupova I, Bairamov B, Medeubekov U, Madyarov Long-term results of simultaneous hybrid ablation of therapy-resistant atrial fibrillation. European Heart Journal. 2020;41:626.
- Baimbetov A, Bizhanov K, Yergeshov K, Bayramov B, Yakupova I, Bozshagulov T. One year continuously monitoring follow up results after single procedure atrial fibrillation ablation using cryoballoon second generation. European Heart Journal. 2018;39:1225. doi: https://doi.org/10.1093/eurheartj/ehy566.P5772
Zabolotnyi D.I., Zabolotna D.D., Babkina T.V., Tsvirinko I.R., Telukha K.I., Kizim Ya.V., Valchyshyn S.V. Radiological research methods in the diagnosis and treatment of patients with the parapharyngeal space tumors
Authors and affiliations
Zabolotnyi D.I. SI "Institute of Otolaryngology named after prof. O.S. Kolomiychenko National Academy of Sciences of Ukraine", Kyiv, Ukraine
Zabolotna D.D. SI "Institute of Otolaryngology named after prof. O.S. Kolomiychenko National Academy of Sciences of Ukraine", Kyiv, Ukraine
Babkina T.V. SI "Institute of Otolaryngology named after prof. O.S. Kolomiychenko National Academy of Sciences of Ukraine", Kyiv, Ukraine
Tsvirinko I.R. SI "Institute of Otolaryngology named after prof. O.S. Kolomiychenko National Academy of Sciences of Ukraine", Kyiv, Ukraine, e-mail:
Telukha K.I. SI "Institute of Otolaryngology named after prof. O.S. Kolomiychenko National Academy of Sciences of Ukraine", Kyiv, Ukraine
Kizim Ya.V. SI "Institute of Otolaryngology named after prof. O.S. Kolomiychenko National Academy of Sciences of Ukraine", Kyiv, Ukraine
Valchyshyn S.V. SI "Institute of Otolaryngology named after prof. O.S. Kolomiychenko National Academy of Sciences of Ukraine", Kyiv, Ukraine
Key words: parapharyngeal space tumors, diffusion-weighted magnetic resonance imaging, perfusion magnetic resonance imaging, transoral surgical approach
Abstract. Radiological research methods in the diagnosis and treatment of patients with the parapharyngeal space tumors. Zabolotnyi D.I., Zabolotna D.D., Babkina T.V., Tsvirinko I.R., Telukha K.I., Kizim Ya.V., Valchyshyn S.V. The parapharyngeal space is a complex structure, being narrow and difficult for surgical approach. Surgical treatment is the main treatment for parapharyngeal space (PPS) tumors, it is performed on the basis of information obtained from imaging methods (computed tomography (CT) and magnetic resonance imaging (MRI)). Objective – to investigate the effectiveness of advanced visualization of radiological research methods in the diagnosis of the parapharyngeal space tumors in order to select the necessary tactics of surgical treatment. This retrospective study included 43 patients who underwent surgery for primary parapharyngeal space tumors from 2010 to 2021. 32 patients were treated in previous 10 years, 11 – patients who underwent examination and surgical treatment over the past 2 years with advanced methods of MRI and CT to select a safe surgical approach. Patients of the 2nd group underwent advanced MRI and CT studies in order to choose the correct method of surgical approach and prevent postoperative complications and recurrence. The histological conclusion in 90.1% of the operated patients confirmed the preliminary data of MRI perfusion regarding the probable histological structure of the neoplasm. Due to a comprehensive preoperative study, in 81.8% of patients in this group transoral approach was used. Our experience confirms the necessity for a thorough preoperative diagnostic procedure that should take advantage of imaging modalities (CT, MRI), especially new techniques (MRI-perfusion and diffusion weighted imaging).
- Dimitrijevic MV, Jesic SD, Mikic AA, Arsovic NA, Tomanovic NR. Parapharyngeal space tumors: 61 case reviews. Int J Oral Maxillofac Surg. 2010;39:983-9. doi: https://doi.org/10.1016/j.ijom.2010.06.005
- Horowitz G, Ben-Ari O, Wasserzug O, Weizman N, Yehuda M, Fliss DM. The transcervical approach for parapharyngeal space pleomorphic adenomas: Indications and technique. PLoS One. 2014;9:e90210. doi: https://doi.org/10.1371/journal.pone.0090210
- Chen H, Sun G, Tang E, Hu Q. Surgical treatment of primary parapharyngeal space tumors: a single-institution review of 28 cases. J Oral Maxillofac Surg. 2019;77(7):1520.e1-e16. doi: https://doi.org/10.1016/j.joms.2019.03.001
- Razek A, Khalek AA, Sieza S, Germeen AA. Characterization of Parotid Tumors With Dynamic Susceptibility Contrast Perfusion-Weighted Magnetic Resonance Imaging and Diffusion-Weighted MR Imaging. Comput Assist 2017;41:131-6. doi: https://doi.org/10.1097/RCT.0000000000000486
- Lien KH, Young CK, Chin SC, Liao CT, Huang SF. Parapharyngeal space tumors: a serial case study. J Int Med Res. 2019 Aug;47(8):4004-13. Epub 2019 Jul 29. PMID: 31353995; PMCID: PMC6726805. doi: https://doi.org/10.1177/0300060519862659
- Fermi M, Serafini E, Ferri G, Alicandri-Ciufelli M, Presutti L, Mattioli F. Management of parapharyngeal space tumors with transparotid-transcervical approach: analysis of prognostic factors related with disease-control and functional outcomes. Eur Arch Otorhinolaryngol. 2022 May;279(5):2631-9. Epub 2021 Sep 16. PMID: 34529157.
- Patadia S, Keshri A, Shah S, Shrivastava A. Benign Parapharyngeal Tumours: Surgical Intricacies by Transcervical Approach. Otolaryngology. 2016;6:219. doi: https://doi.org/10.4172/2161-119X.1000219
- Arnason T, Hart RD, Taylor SM, Trites JR, Nasser JG, Bullock MJ. Diagnostic accuracy and safety of fine-needle aspiration biopsy of the parapharyngeal space. Diagn 2012;40:118-23. doi: https://doi.org/10.1002/dc.21508
- Jichi K, Murakami S. Surgical treatment of parapharyngeal space tumors: A report of 29 cases. Oncol Lett. 2017;14(3):3249-54. doi: https://doi.org/10.3892/ol.2017.6480
- Chen Z, Chen YL, Yu Q, Zhou SH, Bao YY, Shang DS, Ruan LX. Excision of tumors in the parapharyngeal space using an endoscopically assisted transoral approach: a case series and literature review. J Int Med Res.2019;47(3):1103-13. doi: https://doi.org/10.1177/0300060518816190
- Vallabhaneni AC, Mandakulutur SG, Vallabhaneni S, Prabha A, Banavara RK. True parapharyngeal space tumors: case series from a teaching oncology center. Indian J Otolaryngol Head Neck Surg. 2017;69(2):225-9. doi: https://doi.org/10.1007/s12070-017-1099-0
- Tryggvason G, Barnett A, Kim J, Soken H, Maley J, Hansen MR. Radiographic association of schwannomas with sensory ganglia. Otol Neurotol. 2012;33:1276-82. doi: https://doi.org/10.1097/MAO.0b013e318263d315
- Bulut OC, Giger R, Alwagdani A, Aldabal N, Stenzinger A, Heimgartner S, et al. Primary neoplasms of the parapharyngeal space: diagnostic and therapeutic pearls and pitfalls. Eur Arch Otorhinolaryngol. 2021 Dec;278(12):4933-41. Epub 2021 Mar 19. PMID: 33740083; PMCID: PMC8553685. doi: https://doi.org/10.1007/s00405-021-06718-4
- Sun F, Yan Y, Wei D, Li W, Cao S, Liu D, et al. Surgical management of primary parapharyngeal space tumors in 103 patients at a single institution. Acta Otolaryngol.2018;138(1):85-89. doi: https://doi.org/10.1080/00016489.2017.1378433
- Rzepakowska A, Osuch-Wójcikiewicz E, Żurek M, Durmaj A, Niemczyk K. Tumor, host and surgery related factors predisposing to cranial nerve deficits after surgical treatment of parapharyngeal space tumors. Eur Arch Otorhinolaryngol. 2021 Jun;278(6):1973-81. Epub 2020 Aug 10. doi: https://doi.org/10.1007/s00405-020-06261-8
- López F, Suárez C, Vander Poorten V, Mäkitie A, Nixon IJ, Strojan P, et al. Contemporary management of primary parapharyngeal space tumors. Head Neck. 2019;41(2):522-35. doi: https://doi.org/10.1002/hed.25439
- Pool CD, Goyal N. Parapharyngeal Space Tumors Treatment & Management. MedScape [internet]. 2017 Nov [cited 2022 Jun 12]. Avaliable from: https://emedicine.medscape.com/article/849385-overview
- van Hees T, van Weert S, Witte B, et al. Tumors of the parapharyngeal space: the VU University Medical Center experience over a 20-year period. Eur Arch Otorhinolaryngol. 2018;275:967-72. doi: https://doi.org/10.1007/s00405-018-4891-x
- Lajud SA, Aponte-Ortiz JA, Garraton M, et al. A novel combined transoral and transcervical surgical approach for recurrent metastatic medullary thyroid cancer to the parapharyngeal space. J Robotic Surg. 2019;14(1):233-6.
- Meng L, Zhong Q, Fang J, et al. Early experience in endoscopic transoral resection for parapharyngeal space tumors. Ear Nose Throat J. 2018;97(4-5):E5-9. doi: https://doi.org/10.1177/0145561318097004-501
- Larson AR, Ryan WR. Transoral Excision of Parapharyngeal Space Tumors. Otolaryngol Clin N Am. 2021;54:531-41. doi: https://doi.org/10.1016/j.otc.2021.03.001
- Nornadiah R, Wah, Yap Bee. Power comparisons of Shapiro–Wilk, Kolmogorov–Smirnov, Lilliefors and Anderson–Darling tests. Journal of Statistical Modeling and Analytics. 2011;2(1):21-33. Retrieved 30 March 2017.
Sirko A.H., Dziak L.A., Perepelytsia V.A., Cherednychenko Yu.V. Compensation pathways for venous drainage of the brain in superior sagittal sinus occlusion by parasagittal meningioma
Authors and affiliations
Sirko A.H. Dnipro State Medical University; Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikova, Dnipro, Ukraine
Dziak L.A. Dnipro State Medical University, Dnipro, Ukraine
Perepelytsia V.A. Dnipro State Medical University; Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikova, Dnipro, Ukraine , e-mail:
Cherednychenko Yu.V. Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikova, Dnipro, Ukraine, e-mail:
Key words: superior sagittal sinus, occlusion of superior sagittal sinus, cerebral collateral flow, parasagittal veins, meningioma, parasagittal meningioma, cerebral digital subtraction angiography
Abstract. Compensation pathways for venous drainage of the brain in superior sagittal sinus occlusion by parasagittal meningioma. Sirko A.H., Dziak L.A., Perepelytsia V.A., Cherednychenko Yu.V. This study aims to determine the existing pathways of collateral cerebral circulation in parasagittal meningiomas that cause superior sagittal sinus occlusion based on literature review and analysis of own clinical observations. Results of clinical and instrumental examination of 221 patients treated in Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov from 2000 to 2021 were subjected to retrospective and prospective analysis. Inclusion criteria were: patient age of 18+, parasagittal extracerebral tumor according to computed tomography/magnetic resonance imaging, histologically verified meningioma, superior sagittal sinus occlusion (type V-VI according to M.P. Sindou and J.E. Alvernia) according to selective cerebral angiography. This study is based on the analysis of examination of 43 patients who met the inclusion criteria. The selected patients were analyzed for demography (sex, age), brain computed tomography/magnetic resonance imaging before and after intravenous contrast enhancement, and computed tomography angiography and selective cerebral angiography data. Transformed venous drainage pathways were analyzed depending on the location of superior sagittal sinus occlusion by parasagittal meningioma: anterior, middle, or posterior third of the superior sagittal sinus. It was determined that preoperative diagnosis of parasagittal meningiomas that, based on brain computed tomography/magnetic resonance imaging, has signs of type V or VI superior sagittal sinus invasion according M.P. Sindou and J.E. Alvernia, must include selective cerebral angiography. Dynamic images of selective cerebral angiography in the venous phase allows to fully assess the established pathways of collateral blood flow and the blood flow direction. Information on collateral venous circulation in case of superior sagittal sinus occlusion by parasagittal meningioma is extremely important in a surgery planning. It helps avoiding iatrogenic damage to eloquent veins, which increases radical tumor removal with maintaining/improving a patient’s functional state in the early postoperative period and improving long-term treatment outcomes.
- Antomonov MYu. [Mathematical processing and analysis of biomedical data]. Kyiv: Medinform. 2018. Ukrainian.
- Wang X, Wang MY, Qian K, Chen L, Zhang FC. Classification and Protection of Peritumoral Draining Veins of Parasagittal and Falcine Meningiomas. World Neurosurg. 2018;117:362-70. doi: https://doi.org/10.1016/j.wneu.2018.06.037
- Wang S, Ying J, Wei L, Li S, Jing J. Effects of parasagittal meningiomas on intracranial venous circulation assessed by the virtual reality technology. Int J Clin Exp Med. 2015;8(8):12706-15.
- Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro-Oncology.2021:23(8);1231-51. doi: https://doi.org/10.1093/neuonc/noab106
- Yin T, Zhang H, Wang W, Zhang L, Wang S. Falcine Sinus and Parafalcine Collateral Veins in Meningiomas Invading the Superior Sagittal Sinus. World Neurosurg.2019;132:434-42. doi: https://doi.org/10.1016/j.wneu.2019.08.120
- Giordan E, Sorenson TJ, Lanzino G. Optimal surgical strategy for meningiomas involving the superior sagittal sinus: a systematic review. Neurosurg Rev. 2020;43(2):525-35. doi: https://doi.org/10.1007/s10143-018-1026-1
- Mathiesen T. Parasagittal meningiomas. Handb Clin 2020;170:93-100. doi: https://doi.org/10.1016/B978-0-12-822198-3.00031-8
- Gatterbauer B, Gevsek S, Höftberger R, Lütgendorf-Caucig C, Ertl A, Mallouhi A, et. Multimodal treatment of parasagittal meningiomas: a single-center experience. J Neurosurg. 2017;127(6):1249-56. doi: https://doi.org/10.3171/2016.9.JNS161859
- Ricci A, Di Vitantonio H, De Paulis D, Del Maestro M, Gallieni M, Dechcordi SR, et. al. Parasagittal meningiomas: Our surgical experience and the reconstruction technique of the superior sagittal sinus. Surg Neurol Int. 2017 Jan;8:1.
- Zeeshan Q, Patel A, Cheng CY, Zhao NH, Barber J, Ghodke BV, et al. Resection of Meningiomas Involving Major Dural Venous Sinuses: Classification, Technique, and Long-Term Results. World Neurosurg. 2019;125:521-36. doi: https://doi.org/10.1016/j.wneu.2019.01.128
- Ottavio Tomasi S, Umana GE, Scalia G, Raudino G, Graziano F, Palmisciano P, et. al. The Superficial Anastomosing Veins of the Human Brain Cortex: A Microneurosurgical Anatomical Study. Front. Surg. 2022;8:817002. doi: https://doi.org/10.3389/fsurg.2021.817002
Radchenko A.O, Kolesnikova O.V. Evaluation of metabolic disorders and aging rates depending on SIRT1 polymorphism in patients with arterial hypertension and subclinical hypothyroidism
Authors and affiliations
Radchenko A.O. L.T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine, Kharkiv, Ukraine, e-mail:
Kolesnikova O.V. L.T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine, Kharkiv, Ukraine, e-mail:
Key words: arterial hypertension, subclinical hypothyroidism, aging, metabolic diseases, SIRT1
Abstract. Evaluation of metabolic disorders and aging rates depending on SIRT1 polymorphism in patients with arterial hypertension and subclinical hypothyroidism. Radchenko A.O., Kolesnikova O.V. There is an increase in the frequency and severity of metabolic disorders in patients with arterial hypertension (AH) in combination with subclinical hypothyroidism (SH), that is accompanied by accelerated aging rates, but the research findings on the aging rates in this category of patients are extremely few in number. Therefore, the aim of our study was to assess metabolic disorders and the aging rates depending on the SIRT1 rs7069102 polymorphism in patients with AH and SH. A total of 132 patients with a median age of 47.6 years were included in the study and divided into 3 groups: a control group (n=30), a group of patients with AH without SH (n=49) and patients with AH in combination with SH (n=53). Anthropometric parameters, biochemical parameters, pro-inflammatory and oxidative states were evaluated in all patients. The aging rates were assessed using two different methods. The frequencies of SIRT1 rs7069102 genotypes carriers in the study sample of patients were 8% for the CC genotype, 51% for the CG genotype and 41% for the GG genotype. There was a significant difference in the incidence of CC homozygosity and carriers of the G allele between groups of patients with AH depending on the SH presence (p<0.001). We showed that carriers of the G allele and GG genotype of the SIRT1 gene (rs7069102) polymorphic marker with AH and SH had significantly higher (p<0.05) insulin resistance, higher levels of low-density lipoprotein cholesterol, alkaline phosphatase, C-reactive protein and lower glomerular filtration rate, which negatively affected the aging processes in this category of patients. In addition, patients with AH had a marked effect of carrying the G allele on the lipid profile and biological age of patients. Therefore, timely detection of a polymorphic variant of the SIRT1 gene may be effective in premature aging prevention in patients with AH and SH.
- Kolesnikova OV, Radchenko AO. [Modern view on the mechanisms of oxidative stress and its biomarkers in a larger number of non-communicable diseases]. Ukrain. Therap. J. 2020;1:51-61. Ukrainian.
- Delitala AP, Scuteri A, Maioli M, Mangatia P, Vilardi L, Erre GL. Subclinical hypothyroidism and cardiovascular risk factors. Minerva medica. 2019 Nov 11;110(6):530-45. doi: https://doi.org/10.23736/S0026-4806.19.06292-X
- Kilic U, Gok O, Bacaksiz A, Izmirli M, Elibol-Can B, Uysal O. SIRT1 gene polymorphisms affect the protein expression in cardiovascular diseases. PloS one. 2014 Feb 28;9(2):e90428. doi: https://doi.org/10.1371/journal.pone.0090428
- Peeters AV, Beckers S, Verrijken A, Mertens I, Roevens P, et al. Association of SIRT1 gene variation with visceral obesity. Human genetics. 2008 Nov 1;124(4):431. doi: https://doi.org/10.1371/journal.pone.0115339
- Alamdari DH, Paletas K, Pegiou T, Sarigianni M, Befani C, Koliakos G. A novel assay for the evaluation of the prooxidant–antioxidant balance, before and after antioxidant vitamin administration in type II diabetes patients. Clinical biochemistry. 2007 Feb 1;40(3-4):248-54. doi: https://doi.org/10.1016/j.clinbiochem.2006.10.017
- Voitenko VP, Tokar AV, Rudaia ES. [Method of determining biological age]. Voprosy gerontologii. 1989;11:9. Russian.
- Levine ME, Lu AT, Quach A, Chen BH, Assimes TL, Bandinelli S, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018 Apr;10(4):573. doi: https://doi.org/10.18632/aging.101414
- Antomonov MYu. [Mathematical processing and analysis of biomedical data]. Kyiv: Medinform; 2017. Russian.
- Habieb MS, Abdel-Aziz WF, Ismail AH, Sallam KM, El-Shafie MK. Sirtuin1 and Sirtuin3 gene polymorphisms and acute myocardial infarction susceptibility. Meta Gene. 2021 Dec 1;30:100965. doi: https://doi.org/10.1016/j.mgene.2021.100965
- Shimoyama Y, Mitsuda Y, Tsuruta Y, Suzuki K, Hamajima N, Niwa T. SIRTUIN 1 gene polymorphisms are associated with cholesterol metabolism and coronary artery calcification in Japanese hemodialysis patients. Journal of Renal Nutrition. 2012 Jan 1;22(1):114-9. doi: https://doi.org/10.1053/j.jrn.2011.10.025
- Kilic U, Gok O, Erenberk U, Dundaroz MR, Torun E, Kucukardali Y, et al. A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human. PloS one. 2015 Mar 18;10(3):e0117954. doi: https://doi.org/10.1371/journal.pone.0117954
- Letonja J, Završnik M, Makuc J, Šeruga M, Peterlin A, Cilenšek I, Petrovič D. Sirtuin 1 rs7069102 polymorphism is associated with diabetic nephropathy in patients with type 2 diabetes mellitus. Bosnian Journal of Basic Medical Sciences. 2021 Oct;21(5):642. doi: https://doi.org/10.17305/bjbms.2020.5368
- Ji JS, Liu L, Shu C, Yan LL, Zeng Y. Sex Difference and Interaction of SIRT1 and FOXO3 Candidate Longevity Genes on Life Expectancy: A 10-Year Prospective Longitudinal Cohort Study. The Journals of Gerontology: Series A. 2021 Dec 20;2021:glab378. doi: https://doi.org/10.1093/gerona/glab378
Stepanov Yu.M., Didenko V.I., Klenina I.A., Tatarchuk O.M., Petishko O.P. Improvement of liver fibrosis verification using new minimally invasive markers in patients with chronic diffuse liver diseases
Authors and affiliations
Stepanov Yu.M. SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro, Ukraine
Didenko V.I. SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro, Ukraine,
Klenina I.A. SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro, Ukraine
Tatarchuk O.M. SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro, Ukraine
Petishko O.P. SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro, Ukraine
Key words: non-alcoholic fatty liver disease, chronic hepatitis associated with virus C, alcoholic liver disease, toxic drug-induced hepatitis, cytokines, biochemical markers of fibrosis
Abstract. Improvement of liver fibrosis verification using new minimally invasive markers in patients with chronic diffuse liver diseases. Stepanov Yu.M., Didenko V.I., Klenina I.A., Tatarchuk O.M., Petishko O.P. The aim of our research was to obtain new minimally invasive serum markers of fibrotic changes of liver in patients with chronic diffuse liver diseases of different etiology and compare them with traditional markers. 364 patients aged 30 to 66 years were examined: 221 women (60.7%) and 143 men (39.3%). Depending on the etiological factors, all patients were divided into 4 groups: group I consisted of 108 patients with non-alcoholic fatty liver disease (NAFLD), group II – 143 patients with chronic hepatitis associated with virus C (CHC), group III – 56 patients with alcoholic liver disease (ALD), group IV – 57 patients with toxic drug-induced hepatitis (TH). The control group consisted of 30 practically healthy people. Using correlation and ROC-analyzes, we obtained minimally invasive diagnostics markers that show the risk of developing liver fibrosis. For patients with NAFLD these were the levels of HOMA-IR, TNFα/IL-10 and α1-acid glycopeptide content, which are better in quality of the diagnostic model than the traditional Forns index, APRI, FIB-4, AAR. For patients with CHC, these were the protein-bound hydroxyproline (HPp/b) /HPf ratio, phospholipids content, and IL-6, CD4+ levels, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. The following markers were obtained for patients with ALD – TNFα levels, HPp/b and glycosaminoglycans content, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. For patients with TH, these were medium molecular weight peptides content, IL-6/IL-10 ratio and CD4+/CD8+, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. Thus, new minimally invasive markers of fibrosis in patients with chronic diffuse liver diseases have been obtained.
- Younossi ZM, Stepanova M, Younossi Y, Golabi P, Mishra A, Rafiq N, et al. Epidemiology of chronic liver diseases in the USA in the past three decades. Gut. 2020;69(3):564-8.
- Petta S, Ting J, Saragoni S, Degli Esposti L, Shreay S, Petroni ML, et al. Healthcare resource utilization and costs of nonalcoholic steatohepatitis patients with advanced liver disease in Italy. Nutrition, metabolism, and cardiovascular diseases. 2020;30(6):1014-22. doi: https://doi.org/10.1016/j.numecd.2020.02.016
- Durazzo M, Ponzo E, Bonetto S, Fagoonee S, Pellicano R. Liver diseases in the elderly. Minerva medica. 2019;110(1):35-51.
- Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. J. Hepatol. 2019;70:151-71.
- Pimpin L, Cortez-Pinto H, Negro F, Corbould E, Lazarus JV, Webber L, et al. Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies. Journal of hepatology. 2018;69(3):718-35. doi: https://doi.org/10.1016/j.jhep.2018.05.011
- Park SH, Plank LD, Suk KT, Park YE, Lee J, Choi JH, et al. Trends in the prevalence of chronic liver disease in the Korean adult population, 1998-2017. Clinical and molecular hepatology. 2020;26(2):209-15. doi: https://doi.org/10.3350/cmh.2019.0065
- Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. Journal of hepatology.2019;70(1):151-71. doi: https://doi.org/10.1016/j.jhep.2018.09.014
- Paik JM, Golabi P, Younossi Y, Mishra A, Younossi ZM. Changes in the Global Burden of Chronic Liver Diseases From 2012 to 2017: The Growing Impact of NAFLD. Hepatology (Baltimore, Md.). 2020;72(5):1605-16. doi: https://doi.org/10.1002/hep.31173
- Roehlen N, Crouchet E, Baumert TF. Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives. Cells.2020;9(4):875. doi: https://doi.org/10.3390/cells9040875
- Stepanov Y, Didenko V, Konenko I, Tatarchuk O, Petishko O. [The characteristics of immune status and carbohydrate metabolism at different stages of liver fibrosis in patients with hepatitis C virus-related chronic hepatitis]. Gastroenterology. 2021;54(1):18-23. Ukrainian. doi: https://doi.org/10.22141/2308-2097.54.1.2020.199137.
- Niederreiter L, Til H. Cytokines and fatty liver diseases. Liver Research. 2018;2(1):14-20. doi: https://doi.org/10.1016/j.livres.2018.03.003
- Caballería L, Pera G, Arteaga I, Rodríguez L, Alumà A, Morillas RM, et al. High prevalence of liver fibrosis among European adults with unknown liver disease: a population-based study. Clin Gastroenterol Hepatol.2018;16(7):1138-45. doi: https://doi.org/10.1016/j.cgh.2017.12.048
- Stepanov YM, Didenko VI, Konenko IS, Yahmur VB, Petishko OP. [Method for diagnosing hepatic steatosis in patients with non-alcoholic fatty liver disease]. Patent 136479 Ukraina: A61B8/00, A61B8/12. №u201900966, 30.01.2019. 27.08.2019. Ukrainian.
- [Unified clinical protocol of primary, secondary (specialized) medical care for alcoholic hepatitis. Order of the Ministry of Health of Ukraine dated November 6, 2014 No. 826]. (2014). Ukrainian.
- Danan G, Teschke R. RUCAM in Drug and Herb Induced Liver Injury: The Update. International Journal of Molecular Sciences. 2015;17(1):14. doi: https://doi.org/10.3390/ijms17010014
- Zayadeen AR, Hijazeen S, Smadi M, Fayyad L, Halasa M, AlQusous S. et al. Comparing shear wave elastography with liver biopsy in the assessment of liver fibrosis at King Hussein Medical Center. Egypt Liver Journal. 2022;12(24). doi: https://doi.org/10.1186/s43066-022-00186-z
- Stepanov YuM, Didenko VI, Konenko IS, Klenina IA, Yagmur VB, Petishko OP. [Role of biochemical and hemodynamic indicators in assessing the progression of liver fibrosis of various origins]. Suchasna gastroenterolohiia. 2019:5:5-13. Ukrainian. doi: https:// doi.org/10.30978/MG-2019-5-5
- Strakhova OP, Androsov OI. [Statistical methods of processing the results of medical and biological research: educational and methodological manual]. Ryzhova OA, editor. Lviv: Vydavets Marchenko T.V.; 2021. Ukrainian.
- Zviahintseva TD, Chernobai AI. [Metabolically associated fatty liver disease: focus on metabolic disorders and their correction]. Zdorovia Ukrainy. 2021;4(62). Ukrainian.
- Zhang D, Huang J, Luo D, Feng X; Liu Y, Liu Y. Glycosylation change of alpha1-acid glycoprotein as a serum biomarker for hepatocellular carcinoma and cirrhosis. Biomark Med. 2017;11(15):423-30. doi: https://doi.org/10.2217/bmm-2016-0284
- Tanabe K, Kitagawa K, Kojima N, Iijima S. Multifucosylated alpha-1-acid glycoprotein as a novel marker for hepatocellular carcinoma. J Proteome Res. 2016;15(9):2935-44. doi: https://doi.org/10.1002/hep.21242
- Hastings KL, Green MD, Gao B, Ganey PE, Roth RA, Burleson GR. Beyond metabolism: role of the immune system in hepatic toxicity. Int J Toxicol. 2020;39(2):151-64. doi: https://doi.org/10.1177/109158181989839914
- Tatarchuk OM, Didenko VI, Melanich SL, Kudryavtseva VYe. [Immunological reactivity in patients with chronic diffuse liver diseases]. Hastroenterolohiia. 2018;52(4):222-6. Ukrainian. doi: https://doi.org/10.22141/2308-2097.52.4.2018.154142.
Klygunenko O.M., Kravets O.V., Marzan O.O. Albumin solution as an important component of intensive infusion therapy in women with preeclampsia
Authors and affiliations
Klygunenko O.M. Dnipro State Medical University, Dnipro, Ukraine
Kravets O.V. Dnipro State Medical University, Dnipro, Ukraine
Marzan O.O. Dnipro State Medical University, Dnipro, Ukraine,
Key words: albumin solution, preeclampsia, infusion therapy, body water compartments, hemodynamics, markers of inflammation
Abstract. Albumin solution as an important component of intensive infusion therapy in women with preeclampsia. Klygunenko O.M., Kravets O.V., Marzan O.O. The aim of the study is to determine the efficiency and effectiveness of albumin solution in intensive infusion therapy for pregnant women with preeclampsia based on measuring indicators of central and peripheral hemodynamics, body water compartments, and markers of inflammation. 60 women were divided into two groups and examined. The first group (n=30) included women whose average age was 30.06±5.13 years, gestation period – 260.18±6.34 days. 16.7% of women in this group had moderate preeclampsia, 83.3% – severe preeclampsia. Patients of this group received standard intensive infusion therapy according to approved treatment protocols. The second group (n=30) included women, whose average age was 30.62±6.02 years, and pregnancy period 258.75±5.74 days. The patients of this group received intensive infusion therapy, like the women of the first group but in combination with a continuous infusion of a 20% albumin solution (8 ml/h – on the 1 st day; 4 ml/h – on the 2nd and 3rd day) and furosemide (0.05 mg/kg/h – on the 1st day; 0.025 mg/kg/h – on the 2nd and 3rd day) for 72 hours starting from the moment of the end of vaginal delivery or Cesarean section surgery. The comparative analysis showed that the dynamics of changes in the main indicators of homeostasis, hemodynamics, body water compartments and markers of inflammation in parturient women with preeclampsia strongly depend on the type of intensive infusion therapy. In women with preeclampsia, continuous administration of a 20% albumin solution immediately after delivery ensures the normalization of body water compartments till the 7th day of the postpartum period. It is the result of a rapid decrease in the total volume of fluid (by 17.2%, p<0.001 from the baseline) and interstitium (by 31.8%, p<0.001 from the prenatal level). The provided treatment in parturient women with preeclampsia helps to ensure a eukinetic type of blood circulation from the 5th day of the postpartum period already. It is also accompanied by the restoration of adaptation mechanisms that participate in maintaining the proper functioning of the cardiovascular system. The use of albumin and furosemide solution infusion reduces the degree of the background inflammatory process by 3.8 times (according to the index of inflammatory activity IL-6/IL-10) which comes along with preeclampsia.
- Gestational Hypertension and Preeclampsia ACOG Practice Bulletin, Number 222. Obstetrics & Gynecology.2020 June;135(6). doi: https://doi.org/10.1097/AOG.0000000000003891
- Cater JH, Kumita JR, Zeineddine Abdallah R, Zhao G, Bernardo-Gancedo A, Henry A, et al. Human pregnancy zone protein stabilizes misfolded proteins including preeclampsia- and Alzheimer's-associated amyloid beta peptide. Proc Natl AcadSciUSA. 2019;116:61016110. doi: https://doi.org/10.1073/pnas.1817298116
- Süleyman Serkan Karaşin, Tayfur Çift. The Role of Ischemia-modified Albumin as a Biomarker in Preeclampsia. Rev Bras Ginecol Obstet. 2020 Mar;42(3):133-9. doi: https://doi.org/10.1055/s-0040-1709662
- Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy. Eur. Heart J. 2018;39(34):3165-241. doi: https://doi.org/10.1093/eurheartj/ehy340
- Burton GJ, Redman CW, Roberts JM, et al. Preeclampsia: pathophysiology and clinical implications. BMJ.2019;366:l2381. doi: https://doi.org/10.1136/bmj.l2381
- Ridder A, Giorgione V, Khalil A, et al. Preeclampsia: the relationship between uterine artery blood flow and trophoblast function. Int. J. Mol. Sci. 2019;20(13):3263. doi: https://doi.org/10.3390/ijms20133263
- Staff AC, Fjeldstad HE, Fosheim IK, et al. Failure of physiological transformation and spiral artery atherosis: their roles in preeclampsia. Am. J. Obstet. Gynecol. 2020;S0002-9378(20):31116-9. doi: https://doi.org/10.1016/j.ajog.2020.09.026
- Alnaes-Katjavivi P, Roald B, Staff AC. Uteroplacental acute atherosis in preeclamptic pregnancies: rates and clinical outcomes differ by tissue collection methods. Pregnancy Hypertens. 2020;19:11-17. doi: https://doi.org/10.1016/j.preghy.2019.11.007
- Than NG, Romero R, Tarca AL, Kekesi KA, Xu Y, Xu Z, et al. Integrated systems biology approach identifies novel maternal and placental pathways of preeclampsia. Front Immunol. 2018;9(1661). doi: https://doi.org/10.3389/fimmu.2018.01661
- McCarthy FP, Adetoba A, Gill C, Bramham K, Bertolaccini M, Burton GJ, et al. Urinary congophilia in women with hypertensive disorders of pregnancy and preexisting proteinuria or hypertension. Am J Obstet Gynecol. 2016;215:464.e1-e7. doi: https://doi.org/10.1016/j.ajog.2016.04.041
- Aouache R, Biquard L, Vaiman D, Miralles F. Oxidative stress in preeclampsia and placental diseases. Int J Mol Sci. 2018;19(1496). doi: https://doi.org/10.3390/ijms19051496
- Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2018;13:291-310. doi: https://doi.org/10.1016/j.preghy.2018.05.004
- Francisco C, Wright D, Benkő Z, Syngelaki A, Nicolaides KH. Competing-risks model in screening for pre-eclampsia in twin pregnancy according to maternal factors and biomarkers at 11-13 weeks' gestation. Ultrasound Obstet Gynecol. 2017;50:589-95. doi: https://doi.org/10.1002/uog.17531
- Poon LC, Shennan A, Hyett JA, Kapur A, Hadar E, Divakar H, et al. The international federation of gynecology and obstetrics (FIGO) initiative on preeclampsia: A pragmatic guide for first-trimester screening and prevention. Int J Gynaecol Obstet. 2019;145(Suppl 1):S1-S33. doi: https://doi.org/10.1002/ijgo.12802
- Webster K, Fishburn S, Maresh M, Findlay SC, Chappell LC. Diagnosis and management of hypertension in pregnancy: Summary of updated NICE guidance. BMJ. 2019;366(l5119). doi: https://doi.org/10.1136/bmj.l5119
- Artiomenko VV, Berlinskaya LI. [Risk factors of preeclampsia development]. Visnyk morskoi medytsyny. 2018;1(78):108-114. Ukrainian. doi: https://doi.org/5281/zenodo.1240781
- Klygunenko EN, Zozulya ОА. [Human serum albumin (past and future)]. Meditsina neotlozhnykh sostoianii. 2017;5(84):26-30. Russian. doi: https://doi.org/10.22141/2224-05188.8.131.527.109356
- Klygunenko EN, Volkov AO. [Correlation of pro- and anti-inflammatory cytokines in pregnant women in the third trimester]. Meditsina neotlozhnykh sostoianii. 2013;6(53):162-4. Russian.
- Klygunenko EN, Marzan OO. [The influence of pregnancy that is complicated by preeclampsia on the main parameters of central and peripheral hemodynamics and body water compartments volume]. Ukrainskyi medychnyi chasopys. 2021;2(142):71-73. Ukrainian. doi: https://doi.org/32471/umj.1680-3051.142.203830
- [On approval of the protocol «Hypertensive disorders during pregnancy, childbirth and the postpartum period»]. Order of the Ministry of Health of Ukraine from 2022, Pub. No. 151. (Jan 24, 2022). Ukrainian. Available from: https://www.dec.gov.ua/mtd/gipertenzyvni-rozlady-y-vagitnyh/
- Whittier N, Wildhagen T, Gold H. Statistics for Social Understanding With Stata and SPSS. Rowman & Littlefield Pub. 2019;(17):210-45.
Khaskhachikh D.A., Potapov V.O. Molecular mechanisms of resistance of endometrial hyperplasia to progestogen therapy based on the study of the expression of estrogen and progesterone receptors and paracrine cellular markers of cellular interaction
Authors and affiliations
Khaskhachikh D.A. Dnipro State Medical University, Dnipro, Ukraine,
Potapov V.O. Dnipro State Medical University, Dnipro, Ukraine
Key words: endometrial hyperplasia, estrogen receptors, progesterone receptors, E-cadherin, β-catenin, progesterone resistance
Abstract. Molecular mechanisms of resistance of endometrial hyperplasia to progestogen therapy based on the study of the expression of estrogen and progesterone receptors and paracrine cellular markers of cellular interaction. Khaskhachikh D.A., Potapov V.O. The problem of resistance of non atypical endometrial hyperplasia (NEH) to traditionally accepted, pathogenetically sound therapy with different types of progestins is currently an unsolved problem. In about 17-20% of cases there is a recurrence or even progression of atypical forms of endometrial hyperplasia (AEH), which required the use of surgical treatments. The aim of the study was to investigate the results of hormone therapy with different types of progestins for the treatment of endometrial hyperplasia in women with different types of expression of estrogen and progesterone receptors in combination with the expression of intercellular adhesion molecules E-cadherin and β-catenin to determine the cause of hormonal resistance, formation of groups of women with progestogen-sensitive endometrial hyperplasia (EH) non atypical type NEH (+), which can use progestogens for treatment, and progestogen-resistant forms of endometrial hyperplasia with non atypical NEH (-), which should be offered alternative therapy. The study was performed on the morphological material of the endometrium obtained by diagnostic biopsy in women with abnormal uterine bleeding who were diagnosed with NEH by histological examination. For immunohistochemical study, 80 endometrial samples were taken from women with abnormal uterine bleeding (AUВ) and in the same women after treatment of endometrial hyperplasia without atypia in 3 and 6 months of therapy. The control group (CG) consisted of a group of 20 women who were followed-up without treatment tactics. All women were divided into 3 groups in which different types of progestins were used for treatment: group I – continuous intake of 100 mg of micronized progesterone per os twice a day for 6 months, group II – 20 mg of dihydrogesterone per os twice a day for 6 months, group III – in which LNG-IUD was used. The state of proliferation and differentiation in the studied tissues was assessed by the expression of their key molecular participants – estrogen receptors (ERα) and progesterone (PGR), transmembrane glycoproteins of E-cadherin and β-catenin. ERα and PGR expression were determined by immunohistochemistry and calculated by the semi-quantitative H-index method. Evaluation of the expression of E-cadherin and β-catenin was performed by determining the percentage of IHH-positive cells to these antigens depending on the degree of their color. The criterion for the effectiveness of NEH treatment was considered to be a biopsy in 3 and 6 months of treatment in the absence of pathological changes in the endometrium. The results showed that after the use of progestogens in group I there was a change in the endometrium to the secretory type in 45% of cases, in group II with dydrogesterone therapy – in 55% there was a reduction of EH to normal histological picture. The intrauterine system with levonorgestrel (LNG-IUD) showed the greatest efficiency, with the use of which in 75% of cases normalization of the endometrial structure was observed. In the control group in 32% of cases the structure of the endometrium normalized. After 6 months of treatment with gestagens, both oral forms (micronized progesterone, dydrogesterone) and the use of LNG-IUDs showed a positive effect from their use; the therapeutic form of gestagens for therapy is not significant in reducing excessive endometrial proliferation. In the control group of patients who did not receive therapy or discontinued therapy for various reasons, it was shown that 47% of patients had spontaneous regression of EH. The overall percentage of no effect from treatment was 20% in groups I, II and III. Determination of ERα expression in all groups showed a pronounced expression in glands and stroma, which did not differ significantly in the group with NEH (+) and in NEH (-). Analysis of PGR expression of NEH in endometrium (-) showed that in glandular cells (50.82±0.73) and in the stroma (47.34±0.82) it was lower than in the endometrium of women with NEH (+) (gland 187±3.1; stroma 166.4±2.3; p<0.05), as well as in the unchanged endometrium in the proliferative phase (glands 193.2±8.5; stroma 178.7±6.3; p<0.05) and the secretory phase (glands 140.2±4.4; stroma 116.6±3.1; p<0.05). A study of E-cadherin expression in women with EH (-) showed that in 86.4% of cases the expression was absent and in 13.6% it decreased. In NEH (+) women, 49.2% of E-cadherin expression was weak, in 34.4% – moderate, and in 16.4% – negative, indicating an association between PGR and E-cadherin expression. In women with NEH (-) there was marked cytoplasmic expression of β-catenin up to 80%, which can be interpreted as potentially threatening the progression of NEH in atypical forms and relapses. Thus, the study of molecular mechanisms of resistance of endometrial hyperplasia to progestogen therapy will help to develop a differential approach to its diagnosis and treatment.
- Nees LK, Heublein S, Steinmacher S, Juhasz-Böss I, Brucker S, Tempfer CB, Wallwiener M. Endometrial hyperplasia as a risk factor of endometrial cancer. Arch Gynecol Obstet. 2022 Aug;306(2):407-21. PMID: 35001185; PMCID: PMC9349105. doi: https://doi.org/10.1007/s00404-021-06380-5
- Sanderson PA, Critchley HO, Williams AR, Arends MJ, Saunders PT. New concepts for an old problem: the diagnosis of endometrial hyperplasia. Hum Reprod Update. 2017 Mar 1;23(2):232-54. PMID: 27920066; PMCID: PMC5850217. doi: https://doi.org/10.1093/humupd/dmw042
- Raffone A, Travaglino A, Saccone G, Insabato L, Mollo A, De Placido G, Zullo F. Endometrial hyperplasia and progression to cancer: which classification system stratifies the risk better? A systematic review and meta-analysis. Arch Gynecol Obstet. 2019 May;299(5):1233-42. Epub 2019 Feb 27.PMID: 30810881. doi: https://doi.org/10.1007/s00404-019-05103-1
- Nees LK, Heublein S, Steinmacher S, Juhasz-Böss I, Brucker S, Tempfer CB, Wallwiener M. Endometrial hyperplasia as a risk factor of endometrial cancer. Arch Gynecol Obstet. 2022 Jan 10. Epub ahead of print. PMID: 35001185.
- Al Nemer AM, Al Bayat MI, Al Qahtani NH. The accuracy of endometrial sampling for the diagnosis of patterns of endometrial pathology in women presenting with abnormal uterine bleeding. More conservative therapeutic approaches. Saudi Med J. 2019 Aug;40(8):815-9. PMID: 31423519; PMCID: PMC6718861. doi: https://doi.org/10.15537/smj.2019.8.24449
- Lax SF. Vorläuferläsionen der Endometriumkarzinome [Precursor lesions of endometrial carcinoma]. Pathologe. 2019 Feb;40(1):13-20. Deutsch.
- Sobczuk K, Sobczuk A. New classification system of endometrial hyperplasia WHO 2014 and its clinical implications. Prz Menopauzalny. 2017 Sep;16(3):107-11. Epub 2017 Oct 12. PMID: 29507578; PMCID: PMC5834925. doi: https://doi.org/10.5114/pm.2017.70589
- Khaskhachikh DA, Potapov VO, Kukina GO. Differentiated approach to the treatment of endometrial hyperplasia without atypia in women of reproductive age. Current issues of pediatrics, obstetrics and gynecology. 2019;2(24):149-54. Ukranian. doi: https://doi.org/10.11603/24116-4944.2019.2.10935
- Sanderson PA, Critchley HO, Williams AR, Arends MJ, Saunders PT. New concepts for an old problem: the diagnosis of endometrial hyperplasia. Hum Reprod 2017;23(2):232-54. PMCID: PMC5850217. PMID: 27920066.
- Gromova OL, Potapov VO, Khaskhachykh DA, Finkova OP, Gaponova OV, Kukina GO, Penner KV. Epigenetic profile of endometrial proliferation in the different morphotypes of endometrial hyperplasia. Reproductive Endocrinology.2021;57:68-78. doi: https://doi.org/10.18370/2309-4117.2021.57.68-78
- Hassan WA, Ibrahim R. Expression of CD117, CD34, and VEGF proteins in progression from endometrial hyperplasia to endometrioid carcinoma. Int J Clin Exp Pathol. 2020 Aug 1;13(8):2115-22. PMID: 32922608; PMCID: PMC7476947.
- Huvila J, Pors J, Thompson EF, Gilks CB. Endometrial carcinoma: molecular subtypes, precursors and the role of pathology in early diagnosis. J Pathol. 2021 Apr;253(4):355-65. Epub 2021 Feb 6. PMID: 33368243. doi: https://doi.org/10.1002/path.5608
- Craciunas L, Gallos I, Chu , Bourne T, Quenby S, Brosens JJ, Coomarasamy A. Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis. Hum Reprod Update. 2019 Mar 1;25(2):202-23. PMID: 30624659. doi: https://doi.org/10.1093/humupd/dmy044
- Uysal G, Acmaz G, Madendag Y, Cagli F, Akkaya H, Madendag I, Karakilic EU. The Efficacy of Dienogest in the Treatment of Simple Endometrial Hyperplasia without Atypia. Gynecol Obstet Invest. 2018;83(2):151-5. Epub 2017 Jul 15. PMID: 28715800. doi: https://doi.org/10.1159/000477618
- MacLean JA, Hayashi K. Progesterone Actions and Resistance in Gynecological Disorders. Cells. 2022 Feb 13;11(4):647. PMID: 35203298; doi: https://doi.org/10.3390/cells11040647
- Sletten E, Arnes L, Lyså М, Larsen M, Orbo A. Significance of progesterone receptors (PR-A and PR-B) expression as predictors for relapse after successful therapy of endometrial hyperplasia: a retrospective cohort study. BJOG.2019;126(7):936-43. doi: https://doi.org/10.1111/1471-0528.15579
- Tanos V, Balami S, Lingwood L. Junctional zone endometrium alterations in gynecological and obstetrical disorders and impact on diagnosis, prognosis and treatment. Curr Opin Obstet Gynecol. 2019 Dec;31(6):418-27. PMID: 31573995. doi: https://doi.org/10.1097/GCO.0000000000000572
- Yu J. Hormone Resistance. Adv Exp Med Biol. 2021;1187:391-401. PMID: 33983590. doi: https://doi.org/10.1007/978-981-32-9620-6_20
- Maciel LFS, Silva ESM, Oliveira-Filho JP, Fritsch SC, Rossi RS, Lourenção JAC, Meira C. Endometrial expression of estrogen and progesterone receptors in non-cyclic mares treated only with long-acting progesterone. [Internet]. Theriogenology. 2018 Mar 1;108:185-91. Epub 2017 Dec 2. PMID: 29223656. doi: https://doi.org/10.1016/j.theriogenology.2017.11.037
- Gromova OL, Potapov VO, Khaskhachikh DA, Kukina GO, Gaponova OV, Penner KV. [Receptor status of the endometrium in hyperplastic processes in premenopausal women]. Neonatology, surgery and perinatal medicine. 2021;1(39):33-38. Ukranian. doi: https://doi.org/10.24061/2413-4260.XI.1.39.2021.5
- Gallos ID, Alazzam M, Clark T, Faraj R, Rosenthal A, Smith PGJ. Management of Endometrial Hyperplasia. Royal College of Obstetricians & Gynaecologists. Retrieved from. [Internet]. RCOG/BSGE Green-top Guideline; 2016 [cited 2022 Apr 14]. Available from: https://rcog.org.uk/en/guidelines-research-services/guidelines/
- Campo G, Rebecchi A, Vanni VS, Pagliardini L, Patruno C, Papaleo E, et al. Levonorgestrel-releasing intrauterine system versus oral medroxyprogesterone acetate in infertile women with endometrial hyperplasia without atypia. Reprod Biomed Online. 2021 Nov;43(5):864-70. Epub 2021 Aug 30. PMID: 34629315. doi: https://doi.org/10.1016/j.rbmo.2021.08.022
- Luo L, Luo B, Zheng Y, Zhang H, Li J, Sidell N. Oral and intrauterine progestogens for atypical endometrial hyperplasia. [Internet]. Cochrane Database Syst Rev; 2018 Dec 4;12(12):CD009458 [cited 2022 Apr 14]. PMID: 30521671; PMCID: PMC6517239. doi: https://doi.org/10.1002/14651858.CD009458.pub3
- Clark K, Westberg SM. Benefits of Levonorgestrel Intrauterine Device Use vs. Oral or Transdermal Progesterone for Postmenopausal Women Using Estrogen Containing Hormone Therapy. Innov Pharm. 2019 Jul 22;10(3):10.24926/iip.v10i3.2002. PMID: 34007573; PMCID: PMC8127097. doi: https://doi.org/10.24926/iip.v10i3.2002
- Doherty MT, Sanni OB, Coleman HG, Cardwell CR, McCluggage WG, Quinn D, McMenamin UC. Concurrent and future risk of endometrial cancer in women with endometrial hyperplasia: A systematic review and metaanalysis. PloS 2020;15(4):e0232231. doi: https://doi.org/10.1371/ journal.pone.0232231
- Khaskhachikh DA, Potapov VO, Kukina GO. [Differentiated approach to the treatment of endometrial hyperplasia without atypia in women of reproductive age]. Actual Problems of Pediatrics, Obstetrics and Gynecology. 2019;2(24):149-54. Ukranian. doi: https://doi.org/10.11603/24116-4944.2019.2.10935
- Maker A, Gumbiner BM. Reconstitution of the full transmembrane cadherin-catenin complex. Protein Expr Purif [Internet]. 2022 May;193:106056 [cited 2022 Apr 14]. Epub 2022 Jan 18. PMID: 35063654. doi: https://doi.org/10.1016/j.pep.2022.106056
- Gul IS, Hulpiau P, Saeys Y, van Roy F. Evolution and diversity of cadherins and catenins. Exp Cell Res. 2017 Sep 1;358(1):3-9. Epub 2017 Mar 6. PMID: 28268172. doi: https://doi.org/10.1016/j.yexcr.2017.03.001
- Blaschuk OW. Potential Therapeutic Applications of N-Cadherin Antagonists and Agonists. Front Cell Dev Biol [Internet]. 2022 Mar 3;10:866200 [cited 2022 Feb 02]. PMID: 35309924. PMCID: PMC8927039. doi: https://doi.org/10.3389/fcell.2022.866200
- Chatzipantelis P, Koukourakis M, Balaska K, Giatromanolaki A. Endometrial Stromal Expression of ER, PR, and B-Catenin Toward Differentiating Hyperplasia Diagnoses. Int J Surg Pathol. 2022 Aug;30(5):492-8. Epub 2021 Dec 6. PMID: 34866456. doi: https://doi.org/10.1177/10668969211065110
- Auclair MH, Yong PJ, Salvador S, Thurston J, Colgan TTJ, Sebastianelli A. Guideline No. 390-Classification and Management of Endometrial Hyperplasia. J Obstet Gynaecol Can. 2019 Dec;41(12):1789-800. doi: https://doi.org/10.1016/j.jogc.2019.03.025
- Antomonov MYu. [Mathematical processing and analysis of biomedical data]. Kyiv: Medinform; 2018. Russian.
- [Decree of the Ministry of Health of Ukraine dated 05.05.2021 No. 869 "On the approval of the Unified Clinical Protocol for Primary, Secondary (Specialized), Tertiary (Highly Specialized) Medical Assistance "Hyperplasia Endometriya"]. [Internet]. (2021). [cited 2022 Feb 02]. Ukrainian. Available from: https://moz.gov.ua/article/ministry-mandates/nakaz-moz-ukraini-vid-05052021--869-pro-zatverdzhennja-unifikovanogo-klinichnogo-protokolu-pervinnoi-vtorinnoi-specializovanoi-tretinnoi-visokospecializovanoi-medichnoi-dopomogi-giperplazija-endometrija
Yuryeva L.M., Shusterman T.Y., Podolska L.V. Clinical and psychometric study of asthenia in foreign applicants for medical education at different stages of training
Authors and affiliations
Yuryeva L.M. Dnipro State Medical University, Dnipro, Ukraine
Shusterman T.Y. Dnipro State Medical University, Dnipro, Ukraine,
Podolska L.V. Dnipro State Medical University, Dnipro, Ukraine,
Key words: foreign applicants, asthenia, asthenic syndrome, adaptation disorders, psychometry
Abstract. Clinical and psychometric study of asthenia in foreign applicants for medical education at different stages of training. Yuryeva L.M., Shusterman T.Y., Podolska L.V. This article analyzes the results of the clinical and psychometric study of asthenia in foreign applicants for higher medical education at different stages of training. The study involved 110 applicants of the preparatory department (group 1) and 44 applicants of the I-II course (group 2). They were trained at Dnipro State Medical University. Duration of training was from 1 to 2 months and from 6 months to 2 years, respectively (at the time of participation in the study). The clinical and psychopathological examination was conducted using the semi-structured interview method and the psychometric investigation of the level of asthenia with using the Multidimensional Fatigue Inventory scale (MFI-20). It was found that the investigated group 2 had the significantly higher frequency of detection of both complaints/symptoms and nosological forms (by 1.8 times) than group 1. The analysis of the MFI-20 scale data confirmed the clinically obtained results: the normal (24,5%) and moderate level (23,5%) of asthenia was significantly more often observed in group 1. The high level (32%) of asthenia was in group 2 that proves the maladaptive process deepening. The obtained result indicates the necessity to develop preventive, differential and corrective measures to improve the quality of life of this contingent.
- Antomonov MY. [Mathematical processing and analysis of biomedical data]. 2nd ed. Kyiv: Medinform; 2018.
- Yuryeva LM, Ogorenko VV, Gnenna OM, Kokashinskii VO. [The influence of the level of self-esteem of medical students on the confidence in choosing a future specialization]. Modern engineering and innovative technologies [Internet]. 2020;13(5):49-53. Russian.
- Gutnik VV, Chepelev SN. [The prevalence of signs of asthenic syndrome in medical students]. Fundamentalnaia nauka v sovremennoi meditsine [Іnternet]. 2021:388-92. Available from: http://rep.bsmu.by:8080/handle/BSMU/31642
- Zhurakovskaya L. [Educational (educational) migration to Ukraine: state, problems and prospects]. Moldoscopie. 2017;4(79):127-43. Russian.
- Leshhenko TO, Yufimenko VG. [The Ukrainian language as a tool for professional adaptation of foreign students in Ukraine. Actual issues of medical (pharmaceutical) education of foreign citizens: problems and prospects]. Conference. 2018 Nov 22; Poltava. 2018. p. 54-56. Ukrainian.
- Trofimov EA, Trofimova TI. [Features of educational migration in the context of globalization. In: Trends and problems in the Russian economy: theoretical and practical aspects]. Materials of the All-Russian scientific and practical conference; 2017 March 23. Irkutsk: Baikal State University. 2017. p. 219-24. Russian. doi: https://doi.org/10.17223/978-5-94621-954-9-2020-1
- Haustov MM. [Medico-psychological view on the problem of adaptation disorders in students]. Medytsyna sohodni i zavtra. 2020 Dec 19;83(2). Ukrainian. doi: https://doi.org/10.35339/msz.2019.83.02.06
- Osório FL, Loureiro SR, Hallak JE, Machado‐de‐Sousa JP, Ushirohira JM, Baes CV, et al. Clinical validity and intrarater and test–retest reliability of the Structured Clinical Interview for DSM‐5 – Clinician Version (SCID‐5‐CV). Psychiatry and Clinical Neurosciences [Internet]. 2019 Oct 14;73(12):754-60. doi: https://doi.org/10.1111/pcn.12931
- Smets EM, Garssen B, Bonke B, De Haes JC. The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. Journal of Psychosomatic Research [Internet]. 1995;39(3):315-25. doi: https://doi:10.1016/0022-3999(94)00125-o
- The Universal Declaration on Bioethics and Human Rights. International Social Science Journal [Internet]. 2005 Dec [cited 2021 Oct 29];57(186):745-53. doi: https://doi.org/10.1111/j.1468-2451.2005.00592
- Zdun-Ryżewska A, Nadrowska N, Basiński K, Walkiewicz M, Błażek M. Who is a tired student? Fatigue and its predictors from a gender perspective. Journal of University Teaching & Learning Practice. 2021;18(6):139-54. doi: https://doi.org/10.53761/184.108.40.206
- World Medical Association Declaration of Helsinki. JAMA [Internet]. 2013 Nov 27 [cited 2021 Oct 29];310(20):2191. doi: https://doi.org/10.1001/jama.2013.281053
Ogorenko V.V., Shornikov A.V., Zavalko Yu.М. The structure of non-psychotic mental disorders, alexithymia and anxiety in patients with aseptic necrosis of the femoral head
Authors and affiliations
Ogorenko V.V. Dnipro State Medical University, Dnipro, Ukraine
Shornikov A.V. Dnipro State Medical University, Dnipro, Ukraine,
Zavalko Yu.М. KP "Dnipro Multidisciplinary Clinical Hospital for Psychiatric Care"DOR", Dnipro, Ukraine, е-mail:
Key words: alexithymia, avascular necrosis, neurotic disorders, anxiety
Abstract. The structure of non-psychotic mental disorders, alexithymia and anxiety in patients with aseptic necrosis of the femoral head. Ogorenko V.V., Shornikov A.V., Zavalko Yu.М. Aseptic necrosis of the femoral head (ANFH) is a severe chronic poliaethiologic disease of the hip joint which is prevalent mainly in young people with a loss of professional and social skills. It is known that the non-psychotic mental disorders appearance in patients with ANFH can lead to the increasing disability, the decreasing in the quality of life, and difficulties in organizing the rehabilitation period. Current researches prove that the preoperative mental state assessment in patients can lead to the statistically significant decrease of the pain intensity in the postoperative period, an improvement in the quality of life related to health, a decrease in anxiety, depression and behavioural problems in the postoperative period. The aim of this research was to study the syndromic features of non-psychotic mental disorders, alexithymia and anxiety levels in patients with ANFH at the preoperative stage. The study involved 137 people aged 25 to 75 years, who were diagnosed with ANFH and identified non-psychotic mental disorders. Clinical-psychopathological and psychodiagnostic methods of examination were used (AUDIT test, Toronto alexithymia scale-20, Taylor manifest anxiety scale). The patients were divided into two groups depending on the ANFH duration. The results of the study revealed the main leading syndromes: asthenic-depressive – in 35.8%, depressive-hypochondriac – in 18.2%, anxious-phobic – in 16.1%, anxious-depressive - in 15.3% and astheno-apathetic – in 14.6% of cases. The average anxiety score was 26 (19; 37), which indicates the presence of a medium-high level of anxiety in the examined, while 52.5 percent of patients had high and very high levels of anxiety. A multivariate logistic regression analysis was performed and as a result, the duration of the disease (OR: 2.23; 95% [CI]: 1.11-4.47; p<0.05), estimates of alexithymia (OR: 2.52; 95% [CI]: 1.00-6.36; p<0.05) and female sex (OR: 2.16; 95% [CI]: 1.03-4.50; p<0.05) were found to be independent risk factors associated with the level of anxiety in persons with ANFH at the preoperative stage.
- Lespasio MJ, Sodhi N, Mont MA. Osteonecrosis of the Hip: A Primer. The Permanente journal. 2019;23:18-100. doi: https://doi.org/10.7812/TPP/18-100
- Pidlubnyi VL. [Prognostic and socio-economic significance of using the mental health assessment system model]. ZaporozhyeMedical 2021 Apr 16;23(2):286-92. doi: https://doi.org/10.14739/2310-1210.2021.2.205344
- Osawa Y, Seki T, Takegami Y, Kasai T, Higuchi Y, Ishiguro N. Do femoral head collapse and the contralateral condition affect patient-reported quality of life and referral pain in patients with osteonecrosis of the femoral head? International Orthopaedics (SICOT). 2018;42(7):1463-8. doi: https://doi.org/10.1007/s00264-018-3867-1
- He D, Xue Y, Li Z, Tang Y, Ding H, Yang Z, et al. Effect of Depression on Femoral Head Avascular Necrosis From Femoral Neck Fracture in Patients Younger Than 60 Years. Orthopedics.2014;37(3):e244-51. doi: https://doi.org/10.3928/01477447-20140225-56
- Chen S-B, Hu H, Gao Y-S, He H-Y, Jin D-X, Zhang C-Q. Prevalence of Clinical Anxiety, Clinical Depression and Associated Risk Factors in Chinese Young and Middle-Aged Patients with Osteonecrosis of the Femoral Head. PLOS ONE. 2015;10(3):e0120234. doi: https://doi.org/10.1371/journal.pone.0120234
- Richard HM, Cerza SP, De La Rocha A, Podeszwa DA. Preoperative mental health status is a significant predictor of postoperative outcomes in adolescents treated with hip preservation surgery. Journal of Children's Orthopaedics.2020;14(4):259-65. doi: https://doi.org/10.1302/1863-2548.14.200013
- Wouters RM, Vranceanu A-M, Slijper HP, Vermeulen GM, et al. Patients With Thumb-base Osteoarthritis Scheduled for Surgery Have More Symptoms, Worse Psychological Profile, and Higher Expectations Than Nonsurgical Counterparts: A Large Cohort Analysis. Clinical Orthopaedics and Related Researches. 2019;477(12):2735-46. doi: https://doi.org/10.1097/CORR.0000000000000897
- Takemoto G, Seki T, Osawa Y, Takegami Y, Kusano T, Imagama S. Preoperative Risk Factors for Dissatisfaction After Total Hip Arthroplasty Among Patients With Osteonecrosis of the Femoral Head. Research Square [Internet];
- Atula S. [Guideline 00708. Mental disorders due to somatic disease]. The Finnish Medical Society Duodecim. [Internet]; 2017 [cited 2022 Jun 16]. Available from: https://guidelines.moz.gov.ua/documents/3503.
- Laukkala T. [Guideline 01068. Psychiatric examination of adults]. The Finnish Medical Society Duodecim. [Internet]; 2017 [cited 2022 Jun 16]. Ukrainian. Available from: https://guidelines.moz.gov.ua/documents/3785.
- Leppävuori A, Räsänen А. [Guideline 00708. Patient with psychosomatic symptoms]. The Finnish Medical Society Duodecim. [Internet]; 2017 [cited 2022 Jun 16]. Ukrainian. Available from: https://guidelines.moz.gov.ua/documents/3504
- Ivanchuk M, Polishchuk O. [Features of statistical analysis of medical and psychological research]. PMGP. 2020;5(3):e0504255. Ukrainian. Available from: https://uk.e-medjournal.com/index.php/psp/article/view/255
Basanets A.V., Gvozdetskyi V.A. Functional state of the peripheral nervous system in miners suffering from chronic lumbosacral radiculopathy of occupational origin
Authors and affiliations
Basanets A.V. SE "Scientific center of preventive toxicology, food and chemical safety named after Academician L.I. Medved of the Ministry of Health of Ukraine", Kyiv, Ukraine,
Gvozdetskyi V.A. SI "Institute of Otolaryngology named after prof. O.S. Kolomiychenko National Academy of Sciences of Ukraine", Kyiv, Ukraine, e-mail:
Key words: chronic lumbosacral radiculopathy, musculoskeletal system, occupational pathology, electroneuromyography
Abstract. Functional state of the peripheral nervous system in miners suffering from chronic lumbosacral radiculopathy of occupational origin. Basanets A.V., Gvozdetskyi V.A. Exercise is a major factor in the development of occupational pathology of the connective tissue and musculoskeletal system, including chronic lumbosacral radiculopathy (LSRP), which accounts for 20% of occupational diseases in Ukraine. Some problems remain insufficiently studied despite a significant number of scientific works devoted to the study of issues of etiology, pathogenesis, features of clinical manifestations, the use of diagnostic and prophylactic measures in LSRP. The criteria for diagnosing changes in the peripheral nervous system need to be clarified and systematized by in-depth study of the functional state of the nervous apparatus in patients with LSRP of professional genesis. The research was carried out in a group of 60 miners of the main professions (coal-cutter, mining worker of a clearing pit (MWCP), drifter) suffering from LSRP. The activity of the neuromuscular apparatus was assessed according to the indices of electroneuromyography (ENMG), namely: the amplitude of the M-response during stimulation at the distal point of the right and left m. Abductor Hallucis, n. Plantar Medial, S1, S2 (mV), as well as indicators of terminal and residual latencies (ms), the speed of the impulse along the indicated nerves (m/s). It was found that the average amplitude of the M-response during stimulation at the distal point m. Abductor Hallucis, n. Plantar Medial in the MWCF group was at 6.37 mV (with a reference value of 4-5.8 mV), the average pulse conduction velocity was 38.46 m/s (with a reference value of 40.00 -50.00 m/s), it was found that most often in the group of coal-cutters (64.2%), a pathological indicator of terminal latency was recorded, while in a group of drifter, it did not go beyond the normal range in one of the surveyed miners suffering from LSRP of occupational genesis. Thus, ENMG of the long nerves of the lower extremities is a useful tool of objectifying the diagnosis of LSRP of ocupational genesis, it allows to determine the degree of impairment of the functional activity of peripheral nerves, neuromuscular synapses and the contractility of the striated muscles.
- Nahorna AM, Sokolova MP, Vitte PM. [State of occupational morbidity in the period of legislation changes]. Ukrainian Journal of Occupational Health. 2016;46(1):3-15. Ukrainian. doi: https://doi.org/10.33573/ujoh2016.01.003
- Cameron Barton, Piyush Kalakoti, Nicholas A Bedard, Nathan R Hendrickson, Comron Saifi, Andrew J Pugely. What are the aosts of LSR Radiculopathy prior to surgical treatment. Spine (Phila Pa 1976). 2019 Jul 1;44(13):937-42. doi: https://doi.org/10.1097/BRS.0000000000002983
- Sadaf Shafique, Shakeel Ahmad, Syed Shakil-Ur-Rehman. Effect of Mulligan spinal mobilization with arm movement along with neurodynamics and manual traction in LSRP patients: a randomized controlled trial. J Pak Med Assoc. 2019 Nov;69(11):1601-4.
doi: https://doi.org/ 10.5455/JPMA.297956
- John-Michael Li, Jinny Tavee. Electrodiagnosis of radiculopathy. Handb Clin Neurol. 2019;161:305-16. doi: https://doi.org/10.1016/B978-0-444-64142-7.00056-4
- Selkirk SM, Ruff Low back pain, radiculopathy. Handb Clin Neurol. 2016;136:1027-33. doi: https://doi.org/10.1016/B978-0-444-53486-6.00053-3
- Jae Hyeon Park, Sun G Chung, Keewon Kim. Electrodiagnostic characteristics of upper lumbar stenosis: Discrepancy between neurological and structural levels. Muscle 2020 May;61(5):580-6. doi: https://doi.org/10.1002/mus.26844
- Antomonov MY. [Mathematical processing and analysis of biomedical data]. Kyiv: Medinform; 2018;2:31-45. Ukrainian.
- Gorblyanskiy YuYu, Yakovleva NV, Kosorotova NS, Bulavina MV. [Prevention of lumbosacral radiculopathy in coal miners]. Med Tr Prom Ekol. 2016;(9):5-10. Russian.
- Arash Babaei-Ghazani, Bina Eftekharsadat, Bahram Samadirad, Vida Mamaghany, Saeed Abdollahian. Traumatic lower extremity and lumbosacral peripheral nerve injuries in adults: Electrodiagnostic studies and patients symptoms. J Forensic Leg Med. 2017 Nov;52:89-92. doi: https://doi.org/10.1016/j.jflm.2017.08
- Stålberg E, van Dijk H, Falck B, Kimura J, Neuwirth C, Pitt M, et al. Standards for quantification of EMG and neurography. Clin Neurophysiol. 2019 Sep;130(9):1688-729. Epub 2019 Jun 10. PMID: 31213353. doi: https://doi.org/10.1016/j.clinph.2019.05.008
- Battakova S, Shraimanov B. Neurophysiological changes in the afferent somatosensory system indices in the case of vertebrogenic spine pathology in miners. Int J Occup Med Environ Health. 2013 Apr;26(2):230-4. Epub 2013 Jun 15. PMID: 23771862. doi: https://doi.org/10.2478/s13382-013-0109-z
Isaiev O.A., Serdiuk V.M. Prediction of the rate of progression of primary open-angle glaucoma depending on gender and polymorphism of the endothelial NO-synthase (NOS3) gene
Authors and affiliations
Isaiev O.A. Dnipro State Medical University; KP "Dnipropetrovsk Regional Clinical Ophthalmological Hospital", Dnipro, Ukraine, e-mail:
Serdiuk V.M. Dnipro State Medical University; KP "Dnipropetrovsk Regional Clinical Ophthalmological Hospital", Dnipro, Ukraine, e-mail:
Key words: primary open-angle glaucoma, NOS3, rs1799983, rs2070744, prognosis
Abstract. Prediction of the rate of progression of primary open-angle glaucoma depending on gender and polymorphism of the endothelial NO-synthase (NOS3) gene. Isaiev O.A., Serdiuk V.M. Relevance – it is promising to develop a system for the diagnosis and prevention of primary open-angle glaucoma (POAG), which would be based on the determination of constitutive propensity factors and would be able to predict the onset and progression of the disease. The aim of the study was to develop a model for predicting the rate of progression of primary open-angle glaucoma depending on gender and endothelial NO-synthase (NOS3) gene polymorphism. There were genotyped 153 patients with POAG aged 36-84 years. Genotypes rs1799983 and rs207074 were determined in the blood of patients by real-time polymerase chain reaction (amplifier Gene Amp® PCR System 7500; USA) using the TaqMan Mutation Detection Assays Life-Technology test system (USA). For mathematical processing of the obtained results, the Statistica 10 program (StatSoft, Inc., USA) was used. The rate of progression of POAG was higher in the presence of risk alleles in the haplotype of the NOS3 gene polymorphisms: T rs1799983 and C rs2070744 (haplotypes TT-CC, GT-CC and GT-CT), which, when distributed by gender, was more pronounced in women than in men of each of the possible haplotypes. The maximum difference was noted for carriers of the TT-SS haplotype, in whom the rate of progression of POAG in women exceeded that in men by 1.4 times (p<0.001). A regression model was built with satisfactory prediction indicators (multiple correlation coefficient R=0.963; coefficient of determination R2=0.928; p<0.001). The probable “hereditary” age of patients in which one or another stage of POAG should be expected is calculated. Gender and haplotypes rs1799983 and rs2070744 of the NOS3 gene were shown to be associated with the onset and rate of progression of POAG, which was implemented in the prognostic model of the disease. Separately for men and women, carriers of different haplotypes, the rate of progression and the possible age of POAG development by stages were calculated.
- Ling JD, Bell NP. Role of cataract surgery in the management of glaucoma. Int Ophthalmol Clin. 2018;58(3):87-100. doi: https://doi.org/10.1097/IIO.0000000000000234
- Cieza A, Keel S, Kocur I, Mccoy M, Mariotti SP. World report on vision. Geneva: World Health Organization. [Internet]; 2019. Available from: https://www.who.int/health-topics/blindness-and-vision-loss#tab=tab_1
- Wang W, He M, Li Z, Huang W. Epidemiological variations and trends in health burden of glaucoma worldwide. Acta Ophthalmol. 2019;97(3):e349-e355. doi: https://doi.org/10.1111/aos.14044
- Flaxman SR, Bourne RR, Resnikoff S, Ackland P, Braithwaite T, Cicinelli MV, et al. Vision loss expert group of the global burden of disease study. Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(12):e1221-e34. doi: https://doi.org/10.1016/S2214-109X(17)30393-5
- Bourne RR. Vision 2020: where are we? Curr Opin Ophthalmol. 2020;31(2):81-84. doi: https://doi.org/10.1097/ICU.0000000000000647
- Torres LA, Hatanaka M. Correlating structural and functional damage in glaucoma. J Glaucoma. 2019;28(12):1079-85. doi: https://doi.org/10.1097/IJG.0000000000001346
- Hymes J. Glaucoma. American Optometric Association. [Internet]; 2020. Available from: https://www.aoa.org/healthy-eyes/eye-and-visionconditions/glaucoma?sso=y
- Mudassar IB, Yew KK, Thambiraja R, Sulong S, Ghulam RA, Ahmad TL. Microvascular endothelial function and primary open angle glaucoma. Ther Adv Ophthalmol. 2019;11:2515841419868100. doi: https://doi.org/10.1177/2515841419868100
- Vargas-Valderrama A, Messina A, Mitjavila-Garcia MT, Guenou H. The endothelium, a key actor in organ development and hPSC-derived organoid vascularization. JBiomed 2020;27(1):67. doi: https://doi.org/10.1186/s12929-020-00661-y
- Krüger-Genge A, Blocki A, Franke RP, Jung F. Vascular endothelial cell biology: an update. Int J Mol Sci. 2019;20(18):4411. doi: https://doi.org/10.3390/ijms20184411
- Picciano AL, Crane BR. A nitric oxide synthase-like protein from Synechococcus produces NO/NO3- from l-arginine and NADPH in a tetrahydrobiopterin- and Ca2+-dependent manner. J Biol Chem. 2019;294(27):10708-19. doi: https://doi.org/10.1074/jbc.RA119.008399
- Liu Y, Allingham RR. Major review: Molecular genetics of primary open-angle glaucoma. Exp Eye Res. 2017;160:62-84. doi: https://doi.org/10.1016/j.exer.2017.05.002
- Salari N, Bokaee S, Farshchian N, Mohammadi M, Kazeminia M. The role of polymorphisms rs2070744 and rs1799983 eNOS gene in patients with POAG: a systematic review and meta-analysis. Int Ophthalmol. 2021 Apr 10. doi: https://doi.org/10.1007/s10792-021-01832-y
- Terminology and Guidelines for Glaucoma. 4th Edition. European Glaucoma Society. Available on: eugs.org
- Antomonov M.Yu. [Mathematical processing and analysis of medical and biological data]. 2 ed. Kyiv: Malyi druk. 2017.
- Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow 2013 Mar;48(3):452-8. doi: https://doi.org/10.1038/bmt.2012.244
- Magalhães da Silva T, Rocha AV, Lacchini R, Marques CR, Silva ES, Tanus-Santos JE, et al. Association of polymorphisms of endothelial nitric oxide synthase (eNOS) gene with the risk of primary open angle glaucoma in a Brazilian population. Gene. 2012;502(2):142-6. doi: https://doi.org/10.1016/j.gene.2012.04.047
- Kang JH, Wiggs JL, Haines J, Abdrabou W, Pasquale LR. Reproductive factors and NOS3 variant interactions in primary open-angle glaucoma. Mol. Vis. 2011;17:2544-51. PMCID: PMC3198482. PMID: 22025889.
- Emam WA, Zidan HE, Abdulhalim BE, Dabour SA, Ghali MA, Kamal AT. Endothelial nitric oxide synthase polymorphisms and susceptibility to high-tension primary open-angle glaucoma in an Egyptian cohort. Mol. Vis.2014;20:804-11. PMID: 24940036; PMCID: PMC4057245.
- Xiang Y, Dong Y, Li X, Tang X. Association of Common Variants in eNOS Gene with Primary Open Angle Glaucoma: A Meta-Analysis. J Ophthalmol. 2016;2016:1348347. doi: https://doi.org/10.1155/2016/1348347
- Kondkar AA, Azad TA, Sultan T, Osman EA, Almobarak FA, Al-Obeidan SA. Association of endothelial nitric oxide synthase (NOS3) gene polymorphisms with primary open-angle glaucoma in a Saudi cohort. PLoS ONE. 2020;15(1):e0227417. doi: https://doi.org/10.1371/journal.pone.0227417
Gavrylyak I.V., Grebin N.K., Bilous V.L., Korsa V.V., Zhaboedov D.G., Ağca C.A., Tykhomyrov A.O. The levels of hypoxia- and angiogenesis-related regulators and matrix metalloproteinase 9 activity in tear fluid of patients with non-penetrating ocular traumas
Authors and affiliations
Gavrylyak I.V. Bogomolets National Medical University, Kyiv, Ukraine,
Grebin N.K. Bogomolets National Medical University, Kyiv, Ukraine
Bilous V.L. Palladin Institute of Biochemistry of NAS of Ukraine, Kyiv, Ukraine
Korsa V.V. Palladin Institute of Biochemistry of NAS of Ukraine, Kyiv, Ukraine
Zhaboedov D.G. Bogomolets National Medical University, Kyiv, Ukraine
Ağca C.A. Bingol University, Bingol, Turkey, e-mail:
Tykhomyrov A.O. Palladin Institute of Biochemistry of NAS of Ukraine, Kyiv, Ukraine, e-mail:
Key words: tear fluid, corneal trauma, D-dimer, HIF-1α, angiostatins, matrix metalloproteinase 9
Abstract. The levels of hypoxia- and angiogenesis-related regulators and matrix metalloproteinase 9 activity in tear fluid of patients with non-penetrating ocular traumas. Gavrylyak I.V., Grebin N.K., Bilous V.L., Korsa V.V., Zhaboedov D.G., Ağca C.A., Tykhomyrov A.O. This article was focused on the evaluation of protein biomarkers related to thrombosis, hypoxia, angiogenesis, and tissue remodeling in tear fluid of patients with non-penetrating corneal trauma. 32 patients with non-penetrating corneal injures were enrolled in the study, the control group consisted of 15 healthy patients. Samples of tear fluid were collected from the patients and control volunteers with the use of a disposable end micropipette. Protein levels of D-dimer, hypoxia-inducible factor 1α (HIF-1α), angiostatins, and matrix metalloproteinase 9 (MMP-9) in tear fluids were determined by western blot analysis. Proteolytic activity values of MMP-9 were measured by gelatin zymography. Results of western blot and zymography assay were calculated by densitometry analysis and expressed as arbitrary units. Significant increase of D-dimer and HIF-1α levels in tear fluid of patients with injured cornea by 7.3 (p<0.05) and 56 (p<0.001) folds, respectively, was shown compared with control, indicating thrombotic events and hypoxia condition to be involved in pathogenesis of ocular trauma. Dramatically elevated levels/activity of MMP-9 enzyme (by 105 folds vs. control, p<0.001) suggest intense tissue remodeling and degradation of extracellular matrix in the damaged cornea. Up-regulation of angiostatin level, products of proteolytical cleavage of plasminogen, in tear fluid collected from patients with traumatic eye in comparison with healthy volunteers (by 7.3 folds, p<0.05), could represent an adaptive mechanism, which counteracts excessive hypoxia-induced neovascularization in injured cornea. It is summarized that there was a strong association between elevation of D-dimer, HIF-1α, angiostatins, and MMP-9 levels suggesting thrombosis- and hypoxia-mediated mechanisms triggering wound healing of injured cornea. The findings of this study are novel and provide a basis for further investigations of the reparation mechanisms during non-penetrating ocular trauma. Studied proteins of the tear fluid can serve as relevant biomarkers of corneal wound healing and are appropriate for diagnostic and prognostic purposes.
- Ljubimov AV, Saghizadeh M. Progress in corneal wound healing. Prog Retin Eye Res. 2015 Nov; 49:17-45. doi: https://doi.org/10.1016/j.preteyeres.2015.07.002
- Willmann D, Fu L, Melanson SW. Corneal Injury. 2022 May 2. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. PMID: 29083785.
- Jones G, Lee TJ, Glass J, Rountree G, Ulrich L, Estes A, et al. Comparison of different mass spectrometry workflows for the proteomic analysis of tear fluid. Int J Mol Sci. 2022 Feb 19;23(4):2307. doi: https://doi.org/10.3390/ijms23042307
- Pang K, Lennikov A, Yang M. Hypoxia adaptation in the cornea: current animal models and underlying mechanisms. Animal Model Exp Med. 2021 Nov 28;4(4):300-10. doi: https://doi.org/10.1002/ame2.12192
- Voelter K, Tappeiner C, Riond B, Nuss K, Bruetsch D, Pot SA. Evaluation of D-dimer levels in aqueous humor of rabbit eyes with and without induced intraocular fibrin and fibrinolytic treatment. Vet Ophthalmol. 2020 Mar;23(2):212-8. doi: https://doi.org/10.1111/vop.12706
- Lee D, Miwa Y, Kunimi H, Ibuki M, Shoda C, Nakai A, Kurihara T. HIF inhibition therapy in ocular diseases. Keio J Med. 2022 Mar 25;71(1):1-12. doi: https://doi.org/10.2302/kjm.2021-0004-IR
- Wolf M, Clay SM, Oldenburg CE, Rose-Nussbaumer J, Hwang DG, Chan MF. Overexpression of MMPs in corneas requiring penetrating and deep anterior lamellar keratoplasty. Invest Ophthalmol Vis Sci. 2019 Apr 1;60(5):1734-47. doi: https://doi.org/10.1167/iovs.18-25961
- Singh A, Maurya OP, Jagannadhan MV, Patel A. Matrix metalloproteinases (MMP-2 and MMP-9) activity in corneal ulcer and ocular surface disorders determined by gelatin zymography. J Ocul Biol Dis Infor. 2012 Dec 29;5(2):31- doi: https://doi.org/10.1007/s12177-012-9096-8
- Waszczykowska A, Podgórski M, Waszczykowski M, Gerlicz-Kowalczuk Z, Jurowski P. Matrix metalloproteinases MMP-2 and MMP-9, their inhibitors TIMP-1 and TIMP-2, vascular endothelial growth factor and sVEGFR-2 as predictive markers of ischemic retinopathy in patients with systemic sclerosis-case series report. Int J Mol Sci. 2020 Nov 18;21(22):8703. doi: https://doi.org/10.3390/ijms21228703
- Petrenko OM, Tykhomyrov AA. Levels of angiogenic regulators and MMP-2, -9 activities in Martorell ulcer: a case report. Ukr Biochem J. 2019 Jan-Feb;91(1):100-7. doi: https://doi.org/10.15407/ubj91.01.100
- Stoscheck CM. Quantitation of protein. Methods Enzymol. 1990;182:50-68. doi: https://doi.org/10.1016/0076-6879(90)82008-P
- Taylor SC, Posch A. The design of a quantitative western blot experiment. Biomed Res Int. 2014;2014:361590. doi: https://doi.org/10.1155/2014/361590
- Ranganathan P. An introduction to statistics: choosing the correct statistical test. Indian J Crit Care Med. 2021 May;25(Suppl 2):S184-S186. doi: https://doi.org/10.5005/jp-journals-10071-23815
- Fu R, Klinngam W, Heur M, Edman MC, Hamm-Alvarez SF. Tear proteases and protease inhibitors: potential biomarkers and disease drivers in ocular surface disease. Eye Contact Lens. 2020 Mar;46(Suppl 2):S70- doi: https://doi.org/10.1097/ICL.0000000000000641
- Coppini LP, Visniauskas B, Costa EF, Filho MN, Rodrigues EB, Chagas JR, et al. Corneal angiogenesis modulation by cysteine cathepsins: In vitro and in vivo studies. Exp Eye Res. 2015 May;134:39-46. doi: https://doi.org/10.1016/j.exer.2015.03.012
- Hagan S, Martin E, Enríquez-de-Salamanca A. Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine. EPMA J. 2016 Jul 13;7(1):15. doi: https://doi.org/10.1186/s13167-016-0065-3
- Zhan X, Li J, Guo Y, Golubnitschaja O. Mass spectrometry analysis of human tear fluid biomarkers specific for ocular and systemic diseases in the context of 3P medicine. EPMA J. 2021 Dec 3;12(4):449-75. doi: https://doi.org/10.1007/s13167-021-00265-y
- Bukowiecki A, Hos D, Cursiefen C, Eming SA. Wound-healing studies in cornea and skin: parallels, differences and opportunities. Int J Mol Sci. 2017 Jun 12;18(6):1257. doi: https://doi.org/10.3390/ijms18061257
- Nishida T, Kojima T, Kataoka T, Isogai N, Yoshida Y, Nakamura T. Comparison of corneal biomechanical properties and corneal tomography between customized and accelerated corneal crosslinking in eyes with keratoconus. Cornea. 2021 Jul 1;40(7):851-8. doi: https://doi.org/10.1097/ICO.0000000000002572
- Sugioka K, Fukuda K, Nishida T, Kusaka S. The fibrinolytic system in the cornea: a key regulator of corneal wound healing and biological defense. Exp Eye Res. 2021 Mar;204:108459. Epub 2021 Jan 23. doi: https://doi.org/10.1016/j.exer.2021.108459
- Bitirgen G, Korkmaz C, Zamani A, Ozkagnici A, Zengin N, Ponirakis G, Malik RA. Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID. Br J Ophthalmol. 2021 Jul 26:bjophthalmol-2021-319450. doi: https://doi.org/10.1136/bjophthalmol-2021-319450
- Hashimoto T, Shibasaki F. Hypoxia-inducible factor as an angiogenic master switch. Front Pediatr. 2015 Apr 24;3:33. doi: https://doi.org/10.3389/fped.2015.00033
- Peral A, Mateo J, Domínguez-Godínez CO, Carracedo G, Gómez JA, Crooke A, Pintor J. Therapeutic potential of topical administration of siRNAs against HIF-1α for corneal neovascularization. Exp Eye Res. 2022 Jun;219:109036. doi: https://doi.org/10.1016/j.exer.2022.109036
- Lee YH, Bang SP, Shim KY, Son MJ, Kim H, Jun JH. Association of tear matrix metalloproteinase 9 immunoassay with signs and symptoms of dry eye disease: a cross-sectional study using qualitative, semiquantitative, and quantitative strategies. PLoS One. 2021 Oct 18;16(10):e0258203. doi: https://doi.org/10.1371/journal.pone.0258203
- Bilous VL, Kapustianenko LG, Tykhomyrov AA. Production and application of angiostatins for the treatment of ocular neovascular diseases. Biotech Acta. 2021;14(1):5-24. doi: https://doi.org/10.15.407/biotech14.01.005
- Sack RA, Beaton AR, Sathe S. Diurnal variations in angiostatin in human tear fluid: a possible role in prevention of corneal neovascularization. Curr Eye Res. 1999 Mar;18(3):186-93. doi: https://doi.org/10.1076/ceyr.220.127.116.1167
- Wu P, Duan F, Luo C, et al. Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol 2020;138:575-8. doi: https://doi.org/10.1001/jamaophthalmol.2020.1291
- Jiang L, Yang Y, Gandhewar J. Bilateral corneal endothelial failure following COVID-19 pneumonia. BMJ Case Rep. 2021 Sep 20;14(9):e242702. doi: https://doi.org/10.1136/bcr-2021-242702
Svyatenko T.V., Starostina O.A., Zakharov S.V., Solovyiova S.V. The results of using Blue cap® foam for skin care with signs of xerosis
Authors and affiliations
Svyatenko T.V. Dnipro State Medical University, Dnipro, Ukraine
Starostina O.A. Dnipro State Medical University, Dnipro, Ukraine
Zakharov S.V. Dnipro State Medical University, Dnipro, Ukraine
Solovyiova S.V. Dnipro State Medical University, Dnipro, Ukraine
Key words: xerosis, atopic dermatitis, acne, seborrheic dermatitis, rosacea, correction of skin dryness, emollients
Abstract. The results of using Blue cap® foam for skin care with signs of xerosis. Svyatenko T.V., Starostina O.A., Zakharov S.V., Solovyiova S.V. A significant increase in the severity of clinical manifestations of various dermatoses accompanied by dry skin often increases the feeling of discomfort and itching of the skin, significantly reducing the patient's quality of life. This leads to the search for effective ways to correct the dryness of the skin and maintain the proper functioning of the epidermal barrier of the skin in various dermatoses. The aim of the study was to study the effect of using a combined emollient, which includes components of a classic emollient (with the inclusion of ceramides and substances with moisturizing and softening effects), as well as substances with antiseptic and fungistatic effects. The results of treatment of 100 patients with skin diseases and conditions accompanied by dry skin and itching were analyzed. The study group included patients with acne undergoing treatment with retinoids and external preparations with an irritating effect, patients with atopic dermatitis in remission, patients with seborrheic dermatitis, rosacea, follicular hyperkeratosis, and skin xerosis. Using the method of corneometry, the dynamics of changes in skin hydration during the use of a combined moisturizer and changes in the indicators of the dermatological index of the quality of life of patients were studied. The data obtained showed a pronounced increase in skin hydration in terms of corneometry after 2 weeks of using an emollient (by an average of 31.6 units or 160%), and after a month of observation, the changes amounted to 36.7 conv. units, i.e. increased by 185%, which proves the effectiveness of using Blue cap® foam to normalize skin hydration. The level of the dermatological index of quality of life during this period decreased from 9.9±0.2 to 7.2±0.2 points, i.e. by 2.7 points or 27%,what also indicates an improvement in the subjective attitude of patients and promotion quality of life of patients. In the course of the study, a significant improvement in skin hydration when using the combined Blue cap® foam to correct signs of skin xerosis was proven. In the case of dermatoses accompanied by itching associated with dry skin, a marked reduction in itching was noticed, as well as a significant improvement in the quality of life of the patient after a month of using the combined moisturizer.
- Vyumvuhore RR, Michael-Jubeli R, Verzeaux L, Boudier D, Le Guillou M, BordesS, et al. Lipid organization in xerosis: the key of the problem? Int J Cosmet Sci. 2018;40(6):549-54. doi: https://doi.org/10.1111/ics.12496
- Kovalova TM, Polovko NP. [Xerosis: Causes and Review of the Progressive Correction]. Collection of scientific works of NMAPE named after PL Shupyk. 2015;24(2):405-09. Ukrainian.
- Kaliuzhnaia LD. [Modern external therapy for dry aging skin]. Ukr. J. dermatol., venerol., kosmetol. 2005;18(3):33-35. Ukrainian.
- Sviatenko TV, Kharitonova OG, Starostina OA. [Complex therapy and rehabilitation of patients with rosacea]. Dermatolohiia ta venerolohiia. 2014;(4):93-99. Ukrainian.
- Sviatenko TV, Starostina OA. [Analysis of the antipruritic effect of the combined use of desloratadine and dimethindemaleate in the treatment of allergic dermatosis in children]. Health of Ukraine. 2021;16(4):46-52. Ukrainian.
- Arora D, Garg S. Skin Care of Acne Vulgaris in Sensitive Skin. The Sensitive Skin: Treatment Modalities and Cosmeceuticals. 2019:3.
- Guanti MB, Bonzano L, Rivi M, Alicandro T, Liberati S, Hebert AA, et al. Efficacy and Safety of an Antioxidant-Enriched Medical Device for Topical Use in Adults with Eczematous Dermatitis. Dermatology and Therapy. 2022;12(4):1015-25. doi: https://doi.org/10.1371/journal.pone.0231078
- Huang Y-x, Li J, Zhao Z-x, Zheng B-l, Deng Y-x, Shi W, et al. Effects of skin care habits on the development of rosacea: a multi-center retrospective case-control survey in Chinese population. PLoS ONE. 2020;15(4):e0231078. doi: https://doi.org/10.1371/journal.pone.0231078
- Stettler H, Crowther JM, Brandt M, Lu B, Boxshall A, de Salvo R, et al. Targeted dry skin treatment using a multifunctional topical moisturizer. International Journal of Cosmetic Science. 2021;43(2):191-200. doi: https://doi.org/10.1111/ics.12680
- Yosipovitch G, Misery L, Proksch E, Metz M, Ständer S, Schmelz M. "Skin Barrier Damage and Itch: Review of Mechanisms, Topical Management and Future Directions." Acta Derm Venereol 2019;99:1201-9. doi: https://doi.org/10.2340/00015555-3296
- Sutton E, Shaw AR, Ridd MJ, Santer M, Roberts A, Baxter H, et al. How parents and children evaluate emollients for childhood eczema: a qualitative study. British Journal of General Practice. 2022;72(719):e390-e7. doi: https://doi.org/10.3399/BJGP.2021.0630
- Koliadenko VG, Chernyshov PV. [Indicators of the quality of life in dermatological ailments]. Ukr. J. dermatol., venerol., kosmetol. 2005;2:11-14. Ukrainian.
- Peacock J. Peacock P. Oxford Handbook of Medical Statistics. Oxford medical handbook; 2010. doi: https://doi.org/10.1093/med/9780199551286.001.0001
- Cekiera A, Popiel Ja, Siemieniuch M, Jaworski Z, Slowikowska M, Siwinska N, et al. The examination of biophysical parameters of the skin in Polish Konik horses. PloS ONE. 2021;16(6):e0250329. doi: https://doi.org/10.1371/journal.pone.0250329
- Moore DJ, Rawlings AV. The chemistry, function and (patho) physiology of stratum corneum barrier ceramides. International journal of cosmetic science. 2017;39(4):366-72. doi: https://doi.org/10.1111/ics.12399
- Zelenkova H, Pavlickova D. Effectiveness of activated piroctone olamine in the treatment of psoriasis and seborrheic dermatitis. Dermatology DOST Svidnik. 2022;1:43.
- Baurecht H, et al. Epidermal lipid composition, barrier integrity, and eczematous inflammation are associated with skin microbiome configuration. Journal of Allergy and Clinical Immunology. 2018;141(5):1668-76.e16 doi: https://doi.org/10.1016/j.jaci.2018.01.019
- Lefèvre-Utile A, Braun C, Haftek M, Aubin F. Five functional aspects of the epidermal barrier. International Journal of Molecular Sciences. 2021;22(21):11676. doi: https://doi.org/10.3390/ijms222111676
- [Expert conclusion No. K-486]. Kyiv: Chamber of Commerce and Industry [Internet]. 2021 April 27. Ukrainian. Available from: https://kiev-chamber.org.ua/
- Batpenova GR, Tsoi NO. [The results of a clinical study and assessment of the effectiveness of the casting of Blue Cap® Foam]. Theses of Astana cal University. 2022:4-6. Ukrainian.
Pechkovskyi K.E., Kolotilov M.M., Pechkovska I.M., Timokhina T.O. Systemic correction of osteoporosis of the alveolar processes of the jaw in complex treatment of patients with generalized periodontitis
Authors and affiliations
Pechkovskyi K.E. Bogomolets National Medical University, Kyiv, Ukraine,
Kolotilov M.M. Bogomolets National Medical University, Kyiv, Ukraine
Pechkovska I.M. PHEI «Kyiv Medical University», Kyiv, Ukraine, e-mail:
Timokhina T.O. Bogomolets National Medical University, Kyiv, Ukraine
Key words: generalized periodontitis, melatonin, vitamin D, alveolar process
Abstract. Systemic correction of osteoporosis of the alveolar processes of the jaw in complex treatment of patients with generalized periodontitis. Pechkovskyi K.E., Kolotilov M.M., Pechkovska I.M., Timokhina T.O. Generalized periodontitis is accompanied by progressive bone atrophy of the alveolar process of the jaws. The first signs of osteoporosis appear in the alveolar process already in the early stages. Complex treatment of generalized periodontitis includes, first of all, an etiopathogenetic approach. The object of the study is to investigate the effectiveness of biotherapeutic correction of osteoporosis of the alveolar processes of the jaws in the complex treatment of patients with generalized periodontitis adding melatonin and vitamin D. The study involved 121 patients aged from 26-40 years with generalized periodontitis of initial-I and I stages with a chronic course, and 45 apparently healthy volunteers from the control group. All patients gave voluntary informed consent to participate in the study. Groups of patients were randomized approximately by same age and gender. Before onset of treatment and 6 months after the complex treatment the level of vitamin D and melatonin level was measured and examined for osteoporosis using a cone-beam computed tomography. In order to give a qualitative and quantitative assessment of the state of mineralization of the spongy and compact bone tissue of the alveolar processes of the jaws histographic analysis of computed tomography was used. 55 patients in addition to traditional local treatment were added vitamin D intake of 4000 IU/d with meals and melatonin intake of 1.5 mg at bedtime for 1 month. It was stated, that level of melatonin in saliva is inversely proportional to the level of vitamin D in the blood serum in patients with generalized periodontitis and patients from the group with clinically healthy periodontium. Using melatonin and vitamin D in the complex of treatment of patients with generalized periodontitis leads to an increase X-ray density of bone tissue of the alveolar processes of the jaws, which allows to achieve restoration of bone density of alveolar processes and longer stabilization of dystrophic – inflammatory process in the periodontium. To strengthen the bone tissue of the alveolar processes of the jaws in patients with generalized periodontitis, it is advisable to use melatonin and vitamin D in a complex treatment.
- Antomonov MYu. [Mathematical processing and analysis of biomedical data]. Kyiv: Medynform; 2018. ISBN 978-966-409-202-6.
- Amrein K, Scherkl M, Hoffmann M. Vitamin D deficiency 2.0: an update on the current status worldwide. EurJ Clin 2020;74:1498-513. doi: https://doi.org/10.1038/s41430-020-0558-y
- Balaji TM, Vasanthi HR, Rao SR. Gingival, Plasma and Salivary Levels of Melatonin in Periodontally Healthy Individuals and Chronic Periodontitis Patients: A Pilot Study. Journal of Clinical and Diagnostic Research. 2015;9(3):ZC23. doi: https://doi.org/10.7860/JCDR/2015/11311.5652
- Balaji TM, Varadarajan S, Jagannathan R, Mahendra J, Fageeh HI, Fageeh HN, et al. Melatonin as a Topical/Systemic Formulation for the Management of Periodontitis: A Systematic Review. Materials (Basel). 2021;14(9):2417. doi: https://doi.org/10.3390/ma14092417
- Borysenko AV. Periodontal and Oral Mucosa Diseases. In 2 volumes. Kyiv: AUS Medicine Publishing; 2018. p. 224-253.
- Cashman KD. Vitamin D Deficiency: Defining, Prevalence, Causes, and Strategies of Addressing. Calcif Tissue 2020;106:14-2. doi: https://doi.org/10.1007/s00223-019-00559-4
- Ferlazzo N, Andolina G, Cannata A, Costanzo MG, Rizzo V, Currò M, et al. Is Melatonin the Cornucopia of the 21st Century? Antioxidants (Basel). 2020;9(11):1088. doi: https://doi.org/10.3390/antiox9111088
- Ghallab NA, Hamdy E, Shaker OG. Malondialdehyde, superoxide dismutase and melatonin levels in gingival crevicular fluid of aggressive and chronic periodontitis patients. Australian Dental Journal. 2016;61(1):53-61. doi: https://doi.org/10.1111/adj.12294
- Hassan RS, Salman SA. Evaluation of salivary melatonin and periodontal parameters in type II diabetic patients with chronic periodontitis: A comparative study. Indian J of Public Health Research and Development. 2019;10(10):2740-5. doi: https://doi.org/10.5958/0976-5506.2019.03283.2
- Konečná B, Chobodová P, Janko J, Baňasová L, Bábíčková J, Celec P, Tóthová Ľ. The Effect of Melatonin on Periodontitis. Int J Mol Sci. 2021;22(5):2390. doi: https://doi.org/10.3390/ijms22052390
- Lodhi K, Saimbi CS, Khan MA, Nath C, Shukla R. Evaluation of melatonin levels in saliva in gingivitis and periodontitis cases: A pilot study. Contemp Clin Dent. 2016;7(4):519-23. doi: https://doi.org/10.4103/0976-237X.194115
- Permuy M, López-Peña M, González-Cantalapiedra A, Muñoz F. Melatonin: A Review of Its Potential Functions and Effects on Dental Diseases. Int J Mol Sci. 2017 Apr 19;18(4):865. PMID: 28422058; PMCID: PMC5412446. doi: https://doi.org/10.3390/ijms18040865
- Ramesh A, Prakash A, Thomas B, Shetty M. Salivary melatonin and total antioxidant capacity in reproductive and postmenopausal women. Journal of the International Clinical Dental Research Organization. 2016;8(1):39. doi: https://doi.org/10.4103/2231-0754.176249
- Sharan K, Lewis K, Furukawa T, Yadav VK. Regulation of bone mass through pineal-derived melatonin-MT2 receptor pathway. J. Pineal Res. 2017;4:63. doi: https://doi.org/10.1111/jpi.12423
- Shariq N, Zohaib K, Sana Z, Muhammad S. Therapeutic potential of melatonin in oral medicine and periodontology. The Kaohsiung Journal of Medical Sciences. 2016;32(8):391-6. doi: https://doi.org/10.1016/j.kjms.2016.06.005
- Ternovoy NK, Drobotun OV, Kolotilov NN. Polymorbidity and heterogeneity of intact bone tissue in patients with malignant and metastatic bone tumors. Radiation Diagnostics, Radiation Therapy. 2019;3:25-29. doi: https://doi.org/10.37336/2707-0700-2019-3-3
Omelchenko E.M., Yelizarova O.T., Polka N.S., Polka O.O., Hozak S.V. Heritability of body mass index and physical activity in Ukrainian adolescents
Authors and affiliations
Omelchenko E.M. SI “O.M. Marzieiev Institute for Public Health NAMSU”, Kyiv, Ukraine, e-mail:
Yelizarova O.T. SI “O.M. Marzieiev Institute for Public Health NAMSU”, Kyiv, Ukraine, e-mail:
Polka N.S. SI “O.M. Marzieiev Institute for Public Health NAMSU”, Kyiv, Ukraine, e-mail:
Polka O.O. SI “O.M. Marzieiev Institute for Public Health NAMSU”, Kyiv, Ukraine, e-mail:
Hozak S.V. SI “O.M. Marzieiev Institute for Public Health NAMSU”, Kyiv, Ukraine, e-mail:
Key words: adolescents, physical activity, body mass index, heritability, familial aggregation
Abstract. Heritability of body mass index and physical activity in Ukrainian adolescents. Omelchenko E.M., Yelizarova O.T., Polka N.S., Polka O.O., Hozak S.V. The article analyzed the lifestyle and physical development of Ukrainian adolescents and their parents and estimated the familial aggregation and heritability of body mass index and physical activity. 408 nuclear families were examined (1216 people with complete information). Anthropometric measures such as weight, height were measured following standardized procedures of WHO. Questionnaires were used to estimate the levels of physical activity. The method of genetic epidemiology research was used to explore heritability (h2) and family aggregation (ρ). Analysis was performed using the software product S.A.G.E. The study showed that 12.0±1.6% of children were overweight or obese, 6.4±1.2% were underweight and 81.6±1.9% with normal weight. It was found that among adolescents aged 12-15 years, 17.5±3.1% of boys and 32.7±2.9% of girls were physically inactive. Body mass index values higher than 25.0 kg/m2 were found in 34.3±2.4 mothers and in 70.6±2.3% of fathers. The proportion of physically inactive persons was 45.7±2.5% among mothers and 51.1±2.7% among fathers. Heritability values were significant for both body mass index (h2 =0.41±0.09; p<0.001) and physical activity (h2 =0.23±0.07; p<0.001). Significant familial correlations were obtained between parents-offspring for physical activity (ρ=0.20±0.04; p<0.001) and body mass index (ρ=0.25±0.03; p<0.001). The study estimated that the familial correlations for physical activity between mother-son and mother-daughter pairs were higher than in father-son and father-daughter pairs. The highest is the mother-daughter aggregation (ρ = 0.29 ± 0.06; p <0.001), the lowest is the father-son (ρ=0.19±0.08; p<0.05) by body mass index. As physical inactivity and overweight increase the risk of non-communicable diseases development, the data obtained should be taken into account while planning preventive measures.
- Roth GA, Mensah GA, Johnson CO, et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019. Update From the GBD 2019 Study. J Am Coll Cardiol.2020 Dec 22;76(25):2982-3021. doi: https://doi.org/10.1016/j.jacc.2020.11.010
- Dempsey PC, Matthews CE, Dashti SG, et al. Sedentary Behavior and Chronic Disease: Mechanisms and Future Directions. J Phys Act Health. 2020 Jan 1;17(1):52-61. doi: https://doi.org/10.1123/jpah.2019-0377
- World Health Organization. The impact of the COVID-19 pandemic on noncommunicable disease resources and services: results of a rapid assessment. World Health Organization [Internet]; 2020. Available from: https://apps.who.int/iris/handle/10665/334136.
- Andrieieva O, Kashuba O, Yarmak O, et al. Efficiency of children's fitness training program with elements of sport dances in improving balance, strength and posture. Journal of Physical Education and Sport. 2021;21(5):2872-9. doi: https://doi.org/10.7752/jpes.2021.s5382
- Che WI, Westerlind H, Lundberg IE, et al. Familial aggregation and heritability: a nationwide family-based study of idiopathic inflammatory myopathies. Ann Rheum Dis.2021 Nov;80(11):1461-6. doi: https://doi.org/10.1136/annrheumdis-2021-219914
- Barbosa J, Basso L, Bartholomeu T, et al. Familial aggregation and heritability of markers of metabolic risk, physical activity, and physical fitness in nuclear families from Muzambinho (Minas Gerais, Brazil). Arch Endocrinol 2019 May-Jun;63(3):215-21. doi: https://doi.org/10.20945/2359-3997000000137
- Blomquist GE. Unpacking the heritability of body mass index and other ratios. Am J Hum Biol. 2019 Sep;31(5):e23289. doi: https://doi.org/10.1002/ajhb.23289
- Bull FC, Al-Ansari SS, Biddle S, et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med. 2020 Dec;54(24):1451-62. doi: https://doi.org/10.1136/bjsports-2020-102955
- Piercy KL, Troiano RP, Ballard RM, et al. The Physical Activity Guidelines for Americans. JAMA. 2018 Nov 20;320(19):2020-8. doi: https://doi.org/10.1001/jama.2018.14854
- Yelizarova O, Stankevych T, Parats A, et al. Specific Features of the Ukrainian Urban Adolescents' Physical Activity: A Cross-Sectional Study. J Environ Public 2020 Apr 9;2020:3404285. doi: https://doi.org/10.1155/2020/3404285
- Bouchard C, Malina RM, Pérusse L. Genetics of Fitness and Physical Performance. Champaign, IL: Human Kinetics; 1997.
- Lezhenko G. [Features of obesity in adolescents]. Dytiachyi likar. 2017;1(52):20-26. Ukrainian. Available from: https://d-l.com.ua/uploads/issues/2016/2(47)/DL16-2_20-26_b71a6779e2e6263607fd9f142171edcf.pdf.
- Lembryk I, Cycjura O, Pryjmak R. [Clinical course and prevalence of obesity in combination with Oddi's sphincter dysfunction in adolescents]. Child`s health. 2019;14(3):159-64. doi: https://doi.org/10.22141/2224-0518.104.22.1689.168767
- Ogniev VA, Pomohaibo KG. [Medico-social substantiation of the model of quality management of obesity of children]. Visnyk socialnoi hihiieny ta organizatsii ohorony zdorovia Ukrainy. 2018;1(75):52-60. Ukrainian. Availablefrom: http://repo.knmu.edu.ua/handle/123456789/21046
- Sorokman TV, Popeliuk OM, Ushakova KJu. [Prognostic criteria for the development of metabolic syndrome in children]. Child`s health. 2016;2:29-32. Ukrainian. Available from: http://nbuv.gov.ua/UJRN/Zd_2016_2_6
Lebets I.S., Dynnik V.O., Matkovska T.M., Medvedovska N.V., Kashkalda D.A. Рrevention and rehabilitation of health problems of schoolchildren from the zone of military conflict in Ukraine
Authors and affiliations
Lebets I.S. SI “Institute for Children and Adolescents Health Care of the NAMS of Ukraine”, Kharkiv, Ukraine, e-mail:
Dynnik V.O. SI “Institute for Children and Adolescents Health Care of the NAMS of Ukraine”, Kharkiv, Ukraine, e-mail:
Matkovska T.M. SI “Institute for Children and Adolescents Health Care of the NAMS of Ukraine”, Kharkiv, Ukraine, e-mail:
Medvedovska N.V. SI “Institute for Children and Adolescents Health Care of the NAMS of Ukraine”, Kharkiv; National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine,
Kashkalda D.A. SI “Institute for Children and Adolescents Health Care of the NAMS of Ukraine”, Kharkiv, Ukraine, e-mail:
Key words: school-age children living in the zone of military conflict, сhildren-migrants, rehabilitation, medical and psychological support
Abstract. Рrevention and rehabilitation of health problems of schoolchildren from the zone of military conflict in Ukraine. Lebets I.S., Dynnik V.O., Matkovska T.M., Medvedovska N.V., Kashkalda D.A. The purpose of the research is to justify the necessity for rehabilitative medical and psychological support of schoolchildren from the zone of military conflict with psychosomatic disorders, psychological divergences in conditions of post-traumatic stress of different levels. There were surveyed 286 children of school age who suffered as a result of military conflict in the East of Ukraine. Anxiety, the level of stress, psychological, emotional internal health, the intensity of stress-realizing systems (cortisol, adrenaline, norepinephrine, diene conjugates, thiobarbituric acid-active products) and stress-limits of systems (serotonin, methlorinate, recovered glutathione, glutathionoperoxidase, superoxide-midase) were assessed. It is established that in the majority (59.52%) of schoolchildren from the Joint Forces Operation (JFO) zone in both boys and girls an increased level of emotional tension was recorded. It was found that the past stress provokes the activation of stress-regulating systems, the severity of which depends on the intensity of stress. Cortisol, diene conjugates, thiobarbituric acid-active products, reduced glutathione, melatonin play a special role in these processes. Children-migrants have a higher level of certain indices of the stress-realizing system (adrenaline) compared to schoolchildren from the military zone, which confirms the influence of a place of living as an additional stress factor on the child's body. It was found that most of the surveyed children have numerous somatic and psychosomatic complaints, and clinical symptoms are characterized by polymorphism. Among organic and functional disorders, diseases of the digestive, endocrine system, neurotic and non-psychotic disorders of residual-organic genesis dominate. The problem of deteriorating health status of schoolchildren from the zone of military conflict was revealed, a possibility of systematic impact on preservation and strengthening the health of this contingent was justified. The revealed disorders of the psychosomatic health of children from the zone of military conflict require a multidisciplinary approach (consulting and follow-up of specialist-doctors of various profiles) to prevent their progression.
- Diab M, Peltonen K, Qouta SR, Palosaari E, Punamäki RL. Can functional emotion regulation protect children's mental health from war trauma? A Palestinian study. Int J Psychol. 2019;54(1):42-52. Epub 2017 Apr 19. PMID: 28421608. doi: https://doi.org/10.1002/ijop.12427
- Jayuphan J, Sangthong R, Hayeevani N, et al. Mental health problems from direct vs indirect exposure to violent events among children born and growing up in a conflict zone of southern Thailand. Soc Psychiatry Psychiatr 2020;55:57-62. doi: https://doi.org/10.1007/s00127-019-01732-8
- Kadir A, Shenoda S, Goldhagen J, Pitterman S. Section On International Child Health. The Effects of Armed Conflict on Children. Pediatrics. 2018;142(6):e20182586. PMID: 30397168. doi: https://doi.org/10.1542/peds.2018-2586
- Karam EG, Fayyad J, Karam AN, Melhem N, Mneimneh Z, Dimassi H, Tabet CC. Outcome of depression and anxiety after war: a prospective epidemiologic study of children and adolescents. J Trauma Stress. 2018;27(2):192-9.PMID: 24740870. doi: https://doi.org/10.1002/jts.21895
- Slone M, Mann S. Effects of War, Terrorism and Armed Conflict on Young Children: A Systematic Review. Child Psychiatry Hum Dev. 2016;47(6):950-65. PMID: 26781095.
- Veronese G, Pepe A, Almurnak F, Jaradah A, Hamdouna H. Quality of life, primary traumatisation, and positive and negative affects in primary school students in the Gaza Strip. Lancet. 2018;21:391. Epub 2018 Feb 21. doi: https://doi.org/10.1016/S0140-6736(18)30380-5
- Veronese G, Pepe A, Jaradah A, Al Muranak F, Hamdouna H. Modelling life satisfaction and adjustment to trauma in children exposed to ongoing military violence: An exploratory study in Palestine. Child Abuse Negl. 2017;63:61-72. Epub 2016 Nov 28. PMID: 27907846. doi: https://doi.org/10.1016/j.chiabu.2016.11.018
- Davydov VV, Kashkalda DA, Goloborod'ko AV. [The norms of the content of biologically active substances in children and adolescents: Handbook]. Kharkov: Fedorko, 2008; Russian.
- Calam R. Public health implications and risks for children and families resettled after exposure to armed conflict and displacement. Scand J Public Health. 2017;45(3):209-11. Epub 2016 Oct 30. PMID: 27799420. doi: https://doi.org/10.1177/1403494816675776
- Garry S, Checchi F. Armed conflict and public health: into the 21st century. Journal of Public Health. 2020;42(3):e287-98. doi: https://doi.org/10.1093/pubmed/fdz095
- Sánchez-Villegas M, et al. Mental health problems, family functioning and social support among children survivors of Colombia’s armed conflict. Journal of aggression, conflict and peace research. 2021;1:61-72. doi: https://doi.org/10.1108/JACPR-08-2020-0535
- Gómez-Restrepo C, Cruz-Ramírez V, Medina-Rico M, Rincón CJ. Mental health in displaced children by armed conflict - National Mental Health Survey Colombia 2015. Actas Esp Psiquiatr. 2018;46(2):51-7. Epub 2018 Mar1. PMID: 29616713.
- Marroquín Rivera A, Rincón Rodríguez CJ, Padilla-Muñoz A, Gómez-Restrepo C. Mental health in adolescents displaced by the armed conflict: findings from the Colombian national mental health survey. Child Adolesc Psychiatry Ment Health. 2020;14:23. PMID: 32467726; PMCID: PMC7236943. doi: https://doi.org/10.1186/s13034-020-00327-5
- Piñeros-Ortiz S, Moreno-Chaparro J, Garzón-Orjuela N, Urrego-Mendoza Z, Samacá-Samacá D, Eslava-Schmalbach J. [Mental health consequences of armed conflicts in children and adolescents: An overview of literature reviews]. Biomedica. 2021;41(3):424-448. Spanish. PMID: 34559491; PMCID: PMC8525875. doi: https://doi.org/10.7705/biomedica.5447
- Ichanska OM., Kliuzko KIe. [Dynamics of experiencing a crisis during psycho-rehabilitation of children affected by the armed conflict in Donbas. Individuality in the psychological dimensions of communities and professions: a collection of scientific papers]. Kyiv; 2018;145-50. Ukraine.
- Ihnatenko K. [Social protection of children in the activities of state organizations in eastern Ukraine]. Social Work and Education. 2021;8(3):329-40. Ukraine. doi: https://doi.org/10.25128/2520-622.214.171.124
- Rudenko TP. [Social protection of victims of armed conflicts: summary of lectures]; 2021. Ukraine.
Korobchanskyi V.O., Sarkis-Ivanova V.V., Bohachova O.S., Oliinyk Y.O., Biеleсka S.V. Implementation of the principles of the scientific concept “Medicine of borderline states” regarding donosological diagnosis and overcoming the risks of health deterioration in student youth
Authors and affiliations
Korobchanskyi V.O. Kharkiv National Medical University, Kharkiv, Ukraine
Sarkis-Ivanova V.V. Kharkiv National Medical University, Kharkiv, Ukraine,
Bohachova O.S. Kharkiv National Medical University, Kharkiv, Ukraine
Oliinyk Y.O. Kharkiv National Medical University, Kharkiv, Ukraine
Biеleсka S.V. Dnipro state medical university, Dnipro, Ukraine; Medical center for refugees from Ukraine "Luxmed", Krakow, Poland, e-mail:
Key words: medicine of borderline states, donosological diagnosis, overcoming the risks, health deterioration in student youth
Abstract. Implementation of the principles of the scientific concept “Medicine of borderline states” regarding donosological diagnosis and overcoming the risks of health deterioration in student youth. Korobchanskyi V.O., Sarkis-Ivanova V.V., Bohachova O.S., Oliinyk Y.O., Biеleсka S.V. Today, the methodological basis of disease prevention among various categories of the population, including students, is an innovative area of medical science and health care practice, namely medicine of borderline conditions. The development of a system of prenosological diagnosis of pathological conditions in young students and their hygienic correction for disease prevention are important both from a scientific and practical point of view. The study was conducted in the conditions of a natural experiment on the basis of three types of educational institutions, at the place of study of representatives of both sexes aged 14 to 23 years, adolescents and yound adults. In order to achieve the relevant objectives, the study used the following methods: analytic addressed at the study of educational programs, curricula, schedules, profile and regulatory documents; sanitary-hygienic; psychophysiological; psychological, statistic. Set of risk factors related to the educational process among young people studying in three types of educational institutions – secondary educational institutions, higher educational institution, Professional Agrarian Lyceum was analyzed. It is established that unfavorable living conditions affect donosological mental states of asthenic, hypochondriac and depressive nature.
- Antomonov MYu. [Mathematical processing and analysis of medical and biological data]. Kyiv: Medinform; 2018. Russian.
- Bohachova OS. [Hygienic assessment and optimization of learning conditions in professional agricultural lyceums]. Kharkiv: Kharkiv National Medical University; 2019. Ukrainian. Available from: http://repo.knmu.edu.ua/handle/123456789/24532
- Bogachova OS, Korobchanskiy VO. [Donosological diagnostics of pre-pathological mental states in students of Professional Agrarian Lyceum using the «Agrotest» computer program]. Medicni perspektivi. 2019;23(4):95-100. doi: https://doi.org/10.26641/2307-0404.2018.4.153010
- Korobchanskyi PO. [Hygienic aspects of the impact of physical training on the formation of health and professional success of medical students]. Extended abstract of candidate’s thesis. Kharkiv: Kharkiv National Medical University; 2014. Ukrainian. Available from: http://www.irbis-nbuv.gov.ua/cgi-bin/irbis_nbuv/cgiirbis_64.exe?Z21ID=&I21DBN=EC&P21DBN=EC&S21STN=1&S21REF=10&S21FMT=fullwebr&C21COM=S&S21CNR=20&S21P01=0&S21P02=0&S21P03=I=&S21COLORTERMS=1&S21STR=%D0%A0%D0%90407594$
- Korobchanskyi VO, Vasilchenko IO, Staruseva VV, et al. [Lifestyle questionnaire as a method of assessing risk factors in adolescents]. Kyiv: Information letter of the Ministry of Health of Ukraine; 2005.
- Korobchansky VO, Padavalenko OV, Vasilchenko IO, Vitrishchak SV. [Psychodiagnostic questionnaire for high school students as a method of assessing pre-nosological mental states of adolescents: textbook]. Kyiv; 2005. Ukrainian.
- BogachovaОС et al. [Medicine of border states: 30-year experience of psychohygienic research: monograph]. Odessa; 2016. Ukrainian.
- Oliinyk YuO. [Psychohygienic assessment and correction of vital activity of high school students in the industrial and agricultural region]. Extended abstract of candidate’s thesis. Donetsk: Donetsk National Medical University; 2010. Ukrainian. Available from: http://www.irbis-nbuv.gov.ua/cgi-bin/irbis_nbuv/cgiirbis_64.exe?C21COM=2&I21DBN=ARD&P21DBN=ARD&Z21ID=&Image_file_name=DOC/2010/10oyopar.zip&IMAGE_FILE_DOWNLOAD=1
- Reznichenko OH. [Hygienic assessment of the impact of the nature and conditions of learning on the functional state and health of medical students]. Extended abstract of candidate’s thesis. Kharkiv: Kharkiv National Medical University; 2013. Ukrainian. Available from: http://irbis-nbuv.gov.ua/cgi-bin/irbis_nbuv/cgiirbis_64.exe?&I21DBN=EC&P21DBN=EC&S21STN=1&S21REF=10&S21FMT=fullwebr&C21COM=S&S21CNR=20&S21P01=0&S21P02=0&S21P03=I=&S21COLORTERMS=0&S21STR=%D0%A0%D0%90401364
- Boda Z, Elmer T, Vörös A, Stadtfeld C. Short-term and long-term effects of a social network intervention on friendships among university students. Sci Rep. 2020 Feb 19;10(1):2889. PMID: 32076003; PMCID: PMC7031228. doi: https://doi.org/10.1038/s41598-020-59594-z
- de PaulaW, Breguez GS, Machado EL, Meireles Prevalence of anxiety, depression, and suicidal ideation symptoms among university students: A systematic review. Brazilian Journal of Health Review. 2020;3(4):8739-56. doi: https://doi.org/10.34119/bjhrv3n4-119
- da Silva AW, Huckins JF, Wang R, Wang W, Wagner DD, Campbell AT. Correlates of Stress in the College Environment Uncovered by the Application of Penalized Generalized Estimating Equations to Mobile Sensing Data. JMIR Mhealth Uhealth. 2019 Mar 19;7(3):e12084. doi: https://doi.org/10.2196/12084
- Gruzieva TS, Galiienko LI, Pelo IM, Omelchuk ST, Antonuk OY. Health and lifestyle of students' youth: status, problems and ways of solution. Wiad Lek. 2018;71(9):1753-8. PMID: 30737935.
- Liu RT. The microbiome as a novel paradigm in studying stress and mental health. American Psychologist. 2017;72(7):655-67. doi: https://doi.org/10.1037/amp0000058
- Liu Y, Wu S, Li Y, Shao F, Su J, Liu A survey of mental symptoms of Chinese population based on SCL-90. Chinese Mental Health Journal. 2018;32(5):437-41.
- Twenge JM, Joiner TE, Rogers ML, Martin GN. Increases in Depressive Symptoms, Suicide-Related Outcomes, and Suicide Rates Among U.S. Adolescents After 2010 and Links to Increased New Media Screen Time. Clin Psychol 2017 Nov 14;6(1):3-17. doi: https://doi.org/10.1177/2167702617723376
- Ye L, Posada A, Liu Y. A review on the relationship between Chinese adolescents’ stress and academic achievement. New directions for child and adolescent development. 2019;2019(163):81-95. doi: https://doi.org/10.1002/cad.20265
Shevchenko O.A., Sheviakov O.V., Kornienko V.V., Burlakova I.A., Slavska Y.A., Sizov V.V., Dorohan S.B. Psychologial components of the rehabilitation potential of specialists of low enforcement forces structures
Authors and affiliations
Shevchenko O.A. Dnipro state medical university, Dnipro, Ukraine,
Sheviakov O.V. Dnipropetrovsk State University of Internal Affairs, Dnipro, Ukraine,
e-mail: [email protected]in.ua
Kornienko V.V. Dnipropetrovsk State University of Internal Affairs, Dnipro, Ukraine
Burlakova I.A. Dnipropetrovsk State University of Internal Affairs, Dnipro, Ukraine
Slavska Y.A. Dnipropetrovsk Academy of Music named after M. Hlinka, Dnipro, Ukraine
Sizov V.V. Dnipropetrovsk Academy of Music named after M. Hlinka, Dnipro, Ukraine
Dorohan S.B. Dnipro state medical university, Dnipro, Ukraine,
e-mail: [email protected]com
Key words: rehabilitation potential, psychological state, specialists of law enforcement forces, development, methodological approach, social support, psychological support
Abstract. Psychologial components of the rehabilitation potential of specialists of low enforcement forces structures. Shevchenko O.A., Sheviakov O.V., Kornienko V.V., Burlakova I.A., Slavska Y.A., Sizov V.V., Dorohan S.B. To study the rehabilitation potential of law enforcement officers and the process of its development, a verbal-communicative diagnostic method was used to collect information about subjects with depressive disorders using "Google Form". The study was conducted on the social network Facebook during 2020-2021. The study involved 452 people from the Central, Southern and Eastern regions of Ukraine aged 20 to 49 years with depressive disorders of the neurotic spectrum and 182 subjects without affective disorders. Socio-demographic features of the subjects with depressive disorders of different genesis are analyzed. It was found that women (54.51%) and subjects aged 30-49 years (70.0%) predominated among the surveyed. The majority of respondents are city dwellers (58.51%), with incomplete higher education (33.33%), mostly working and having family (with neurotic depression (54.95% and 51.65% respectively) and organic depression) (51.16% and 55.81%, respectively) and mostly unemployed and single (with endogenous depression) (59.14% and 58.06%, respectively). It was determined that among the factors of mental trauma in subjects with neurotic depression factors related to family and personal relationships (DC=3.32) dominated, in organic depression – with their own health (DC=2.08), in endogenous depression – factors of socio-psychological nature (DC=2.75). It was found that such factors as young age (20-29 years), higher education, living in the city, having a family, can be favorable factors for the formation of the rehabilitation potential of people with depressive disorders of various genesis. It was also determined that according to many socio-demographic indicators, subjects with neurotic disorders coincided with the respondents of the control group, which may indicate a higher level of rehabilitation potential of people with neurotic depression.
- Arshava I, Kornienko V, Baratynska A. Influence of personal and pathophychological characteristics on adaptation possibilities of patients with depression in the process of medical-psychological rehabilitation. Psychological perspectives on health and disease: collective monograph. Malgorzata Tatala. Rīga: Baltija Publishing; 2019. p. 1-18. doi: https://doi.org/10.5709/PPHD-2-5
- Global Action Plan for the Prevention and Control of Noncommunicable Diseases 2013-2020. World Health Organization, [Internet]. 2020[cited 2022 May 02]. Available from: http://www.who.int/disabilities/world_report/2020/summary_ru.pdf?ua=1
- Yevdokimova O. [The personality of the police in a transformational society. Mental health of the individual in a crisis society: Proceedings of the 4 All-Ukrainian science and practice conference]; 2019 Oct 18; Lviv, Ukraine. Lviv: Lviv State University of Internal Affairs; 2019. p. 85-89. Ukrainian.
- Zelenska KO, Koltsova GG. [Clinical and psychopathological analysis of modern depressive disorders associated with suicidal behavior in women]. ScienceRise. Medical science [Internet]. 2017;12:39-42 [cited 2022 Apr 01].
- Kim TK. A test as parametric statistic. Korean J Anasthesiol. 2015;68(6):540-6. doi: https://doi.org/10.4097/kjae.2015.68.6.540
- Kornienko VV. [Conceptualization of the study of the problem of socio-psychological foundations of the rehabilitation potential of the individual. In: Kornienko VV, editor. Theoretical and applied problems of psychology and social work: collection of science Proceedings of the Eastern Ukrainian National University named after Volodymyr Dahl]. Severodonetsk: Publishing house of SNU named after V. Dahl; 2021. p. 36-45.
- Kornienko VV. [System of social and psychological support of the process of development of rehabilitation potential of personality. In: Kornienko VV, editor. Theoretical and applied problems of psychology and social work: collection of science. Proceedings of the Volodymyr Dahl East Ukrainian National University]. Severodonetsk: Publishing house of SNU named after V. Dahl; 2021. p. 15-24.
- Panina N. Structure of Political Success Factors as an Indicator of political direction in electoral system development. In Y. Golovakha, editor. Ukrainian Sociological Review 2002-2003 [Internet]. Kyiv: Institute of Sociologyof the National Academy of Sciences of Ukraine; 2005 p. 27-53 [cited 2022 Jun 29]. Available from: https://nbn-resolving.org/urn:nbn:de:0168-ssoar-104845
- Popovych V, Ragimov F, Kornienko V, Ivanova I, Buryk Z. Development of social and communicative paradigm of the field of social networks. International Journal of Data and Network Science. 2020;4:319-28. doi: https://doi.org/10.5267/j.ijdns.2020.6.001
- Fetisov V.S. [Package of statistical data analysis STATISTICA]. Nizhin: NSU named after M. Gogol; 2018. p. 100-114.
- Shevchenko PF. [Criteria for assessing the severity of depression. Proceedings of the IV International Scientific and Practical Conference "Personality in Crisis and Critical Situations"]. Sumy: Sumy State Pedagogical University named after A.S. Makarenko; 2018. p. 312-4.
- Shevchenko O, Burlakova I, Sheviakov O, Agarkov O, Shramko I. Psychological foundations of occupational health of specialists in the economic sphere. Medicni perspektivi.2020;25(2):163-7. doi: https://doi.org/10.26641/2307-0404.2020.2.206890
- Sheviakov OV, Doroshenko EYu, Mykhaliuk YeL, Prykhodko VV, Liakhova IM, Nikanorov OK, et al. [Features of social-psychological rehabilitation of sportsmen-paralympians specialized in powerlifting]. Zaporozhye medical journal. 2020;22(1):96-102. Ukrainian. doi: https://doi.org/10.14739/2310-1210.2020.1.194632
- Sheviakov O, Korniienko V, Shu Gao Han. System of psychological support for the development of rehabilitation potential of power structures specialists. Phylosophy, Economics and Law Review. 2022;2(1):7-15. doi: https://doi.org/10.31733/2786-491X-2022-1-7-15
Bezverkhniuk T.M., Babova I.K. Ensuring of rehabilitation care quality provision: organizational-methodological aspect
Authors and affiliations
Bezverkhniuk T.M. SI «Ukrainian Research Institute of Medical Rehabilitation and Resort Therapy of the Ministry of Health of Ukraine», Odesa, Ukraine, e-mail:
Babova I.K. SI «South Ukrainian National Pedagogical University named after K.D. Ushynsky», Odesa, Ukraine, e-mail:
Key words: rehabilitation in health care, standards, quality, recommended rehabilitation program
Abstract. Ensuring of rehabilitation care quality provision: organizational-methodological aspect. Bezverkhniuk T.M., Babova I.K. Introduction of international treatment protocols into medical care determines the need for scientific substantiation of the mechanisms of their adaptation in rehabilitation care. On the basis of a systemic approach we substantiated the organizational model of quality assurance for the provision of rehabilitation care in health care system in Ukraine, which consists of four interacting subsystems: management, functional, monitoring (resultative) and supply (process) subsystems. The state of rehabilitation care provision in Ukraine at the expense of the Social Insurance Fund of Ukraine and the National Health Service of Ukraine was analyzed. Need to renovate medical and technological documentation of rehabilitation care for the main groups of socially significant diseases that lead to disability of the population was grounded. Recommended program of rehabilitation at the health-resort stage of patients after coronavirus disease (COVID-19) is proposed for health-resort institutions as a methodical basis for the introduction of updated medical-technological standardization documents, which will contribute to improving the quality of rehabilitation care in Ukraine. Typical (recommended) rehabilitation program consists of general provisions on the organization of rehabilitation care, in particular the existing documentary base; indications, contraindications and criteria for admission to the health-resort stage of rehabilitation (in the post-acute or long-term period); diagnostic plan; regulation of actions in case of deterioration of the patient's clinical condition; approximate duration of the rehabilitation course; tasks of the rehabilitation stage; general characteristics of the resort and available natural healing resources; list of rehabilitation procedures; indicators of the effectiveness of rehabilitation care. The program was implemented in a number of health-resort institutions of Ukraine.
- [Fundamentals of Ukrainian legislation on health care]. Law of Ukraine of 1992, renovation 2020, Pub. L. No. 2802-ХІІ. (2020). Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/2801-12#Text
- [About rehabilitation in health care sphere]. Law of Ukraine of 2020, Pub. L. No. 103-IX. (Dec 03, 2020). Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/1053-20#Text
- [Methodology for development and implementation of medical standards of medical care based on evidence-based medicine]. Order of the Ministry of Health of Ukraine of 2012, Pub. No. 751. (Sep 28, 2012). Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/z2001-12#Text
- Diachuk D, Zyukov O, Lishchyshyna O. [Rationale of perspective directions of standardization of medical care of the population of Ukraine at the turn of 2020]. Clinichna ta profilactychna medycyna. 2020;3(13):4-11. Ukrainian. doi: https://doi.org/10.31612/2616-4868.3(13).2020.01
- Golik V, Syvak O. Assessment of national disability, health and rehabilitation system in Ukraine. Reflections disability and rehabilitation subcluster meeting. Ukraynskyi visnyk mediko-sotsialnoi ekspertyzy. 2016 March 11;1(19):26-62.
- International classification of functioning, disability and health: ICF. World Health Organization; 2001.
- Situation assessment of rehabilitation in Ukraine. Copenhagen: WHO Regional Office for Europe; 2021.
- [About state financial guarantees of medical care for the population]. Law of Ukraine of 2017, Pub. L. No. 2168-VІІІ. (Oct 19, 2017). Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/2168-19#Text
- [On the approval of licensing conditions for conducting business activities in medical practice]. Resolution of the CMU of 2016, Pub. No. 285. (March 02, 2016).Available from: https://zakon.rada.gov.ua/laws/show/285-2016-%D0%BF#Text
- [The procedure for reimbursement of expenses for the provided social services for the treatment of insured persons and their family members after diseases and injuries in the rehabilitation departments of health-resort institutions at the expense of the funds of the Social Insurance Fund of Ukraine]. Resolution of the Board of the FSS of Ukraine of 2017, Pub. No. 39. (Jun 13, 2017). Ukrainian. Available from: https://zakon.rada.gov.ua/rada/show/v0039890-17#Text
- gov [Internet]. [Health-resort and health facilities]. c1998 [cited 2022 Aug 11]. Ukrainian. Available from: www.ukrstat.gov.ua
- [About recognizing some orders of the Ministry of Health of Ukraine as having lost their validity]. Order of the Ministry of Health of Ukraine of 2019, Pub. No. 448. (Feb 22, 2019). Ukrainian. Available from: http://search.ligazakon.ua/l_doc2.nsf/link1/MOZ31142.html
- [The efficiency index of medical rehabilitation at the expense of the Social Insurance Fund reached 81.8%]. Uriadovyi portal [Internet]. 2022 [cited 2022 Aug 11). Ukrainian. Available from: https://www.kmu.gov.ua/news/pokaznik-efektivnosti-medichnoyi-reabilitaciyi-za-koshti-fondu-socialnogo-strahuannya-syagnuv-818
- Donabedian A. Evaluating the quality of medical care. The Milbank quarterly. 2005;83(4):691-729. doi: https://doi.org/10.1111/j.1468-0009.2005.00397.x
- [About the procedure for quality control of the provision of medical care]. Order of the Ministry of Health of Ukraine of 2012, Pub. No. 752. (Sep 28, 2012). Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/z1996-12#Text
- Lobas VМ, Slabkyi GА, Kravets ОА. [Model of management of the medical rehabilitation process at the primary level of medical care providing]. Pytannia eksperymentalnoi ta klinichnoi medycyny: zbirnyk statei. 2013;1(17):158-63. Ukrainian.
- White Book on Physical and Rehabilitation Medicine in Europe. European Physical and Rehabilitation Medicine Bodies Alliance. Eur J Phys Rehabil Med. 2018;54(2). Available from: http://www.whitebookprm.eu/2019/03/21/white-book-iii-ed-complete-pdf-version/
- Stepanenko АV, Parii VD, Morozov АМ, et al. [Unified methodology for the development of local medical care protocols for health care institutions of Ukraine: methodological recommendations]. Kyiv; 2012. Ukrainian.
- [Multidisciplinary working groups and topics]. [Internet]. Kyiv: State expert center. c1990-2022 [cited 2022 Aug 11]. Ukrainian. Available from: https://www.dec.gov.ua/mtd/multydysczyplinarni-robochi-grupy/
- Babova ІК, Rozkov VS. [Health-resort rehabilitation of servicemen in Ukraine: public-administration aspect]. Publichne upravlinnia i administruvannia v Ukraini. 2020;19:21-26.
- [List of health-resort facilities in terms of medical rehabilitation profiles for reimbursement of costs for rehabilitation treatment services provided to insured persons]. [Internet]. Kyiv: Social Insurance Fund of Ukraine. c2014 [cited 2022 Aug 11]. Ukrainian. Available from: http://www.fssu.gov.ua/fse/control/main/uk/publish/article/952253
- [Requirements PMG 2022]. [Internet]. Kyiv: National Health Service of Ukraine. 2022 [cited 2022 Aug 11].Available from: https://contracting.nszu.gov.ua/vimogi-pmg-2022
- [The tariff for rehabilitation medical services has been increased in PMG]. [Internet]. Kyiv: National Health Service of Ukraine. 2021 Marсh 09 [cited 2022 Aug 11]. Ukrainian. Available from:
- Rehabilitation needs of people recovering from COVID-19. [Internet]. WHO: Scientific brief. 20212 Nov 09 [cited 2022 Aug 11]. Available from: https://WHO/2019-nCoV/Sci_Brief/Rehabilitation/2021.1
- [In case of complications from COVID-19, employees can undergo rehabilitation at the Fund's expense]. Kyiv: Social Insurance Fund of Ukraine. c2014 [cited 2022 Aug 11]. Ukrainian. Available from: http://www.fssu.gov.ua/fse/control/main/uk/publish/article/972583
- [Coronavirus disease 2019 (COVID-19)]. [Internet]. Kyiv: State expert center. c1990-2022 [cited 2022 Aug 11]. Ukrainian. Available from: https://www.dec.gov.ua/mtd/koronavirusna-hvoroba-2019-covid-19/
Kodynets A.O., Doroshenko O.F., Volynets I.P., Dorozhko G.K., Petrenko V.O., Belitsky V.V. Protection from unfair competition on the pharmaceutical market in the conditions of the COVID-19 pandemic
Authors and affiliations
Kodynets A.O. Taras Shevchenko National University of Kyiv; Intellectual Property Scientific Research Institute of National Academy of Legal Sciences of Ukraine, Kyiv, Ukraine,
Doroshenko O.F. Intellectual Property Scientific Research Institute of National Academy of Legal Sciences of Ukraine, Kyiv, Ukraine, e-mail:
Volynets I.P. Intellectual Property Scientific Research Institute of National Academy of Legal Sciences of Ukraine, Kyiv, Ukraine
Dorozhko G.K. Intellectual Property Scientific Research Institute of National Academy of Legal Sciences of Ukraine, Kyiv, Ukraine
Petrenko V.O. Ukrainian State University of Science and Technologies, Institute of Industrial and Business Technologies, Dnipro, Ukraine, e-mail:
Belitsky V.V. Dnipro State Medical University, Dnipro, Ukraine,
Key words: medicines, unfair advertising, intellectual property, COVID-19, legal protection, unfair competition
Abstract. Protection from unfair competition on the pharmaceutical market in the conditions of the COVID-19 pandemic. Kodynets A.O., Doroshenko O.F., Volynets I.P., Dorozhko G.K., Petrenko V.O., Belitsky V.V. The article reveals the problems and prospects of combating dishonest advertising of medicinal products in the conditions of the COVID-19 pandemic. Using the example of the USA and Ukraine, the criteria for banning the advertising of medicinal products by researching scientific sources, international and domestic legal acts, prescriptions and instructions of state bodies, etc. were analyzed. The differences and specifics of the regulatory requirements for the advertising of medicinal products in Ukraine and the USA have been determined. It has been established that in the USA it is allowed to advertise prescription drugs, and in Ukraine a ban has been introduced to advertise "antiviral drugs of direct action". Attention was drawn to the qualification of the division of advertising slogans in the USA, which made it possible to draw an analogy with Ukrainian advertising of medicinal products. It has been proven that individual pharmaceutical manufacturers, by providing advertisers with incomplete information about the drug, can mislead consumers about its effectiveness. The Antimonopoly Committee of Ukraine has demonstrated cases of countering the spread of false information about the properties of medicinal products, which became more frequent in connection with the emergence of the strain (SARS-CoV-2) in 2019. The advantages and disadvantages of a complete ban on medicines on television and radio, as well as other mass media are indicated in connection with the entry into force of the decision of the National Security and Defense Council of Ukraine "On the state of the national health care system and urgent measures to ensure the protection of citizens of Ukraine with medical assistance" dated July 30, 2021. As an alternative to the complete rejection of drug advertising it is proposed, the introduction of the mechanism of "corrective advertising", which is actively used in the USA and consists in correcting or making amendments to already published drug advertising and eliminating statements that mislead consumers, contain incomplete, inaccurate, false information about the medicinal product.
- Prescription Drugs: Medicare Spending on Drugs with Direct-to-Consumer Advertising [Internet]. Washington: U.S. Government Accountability Office (U.S. GAO); 2021 [cited 2022 Aug 12]. Available from: https://www.gao.gov/products/gao-21-380/
- [During the year, drug manufacturers spent 7.2 billion hryvnias on advertising]. [Internet]. Ekonomichna pravda. 2016 Mar 14 [cited 2022 Aug 12]. Ukrainian. Available from: https://www.epravda.com.ua/news/2016/03/14/585194/
- media [Internet]. [The company Ocean Media Plus pointed out the risks for the Ukrainian media market due to the introduction of a moratorium on the advertising of medicinal products]; 2021 Aug 19 [cited 2022 Aug 12]. Ukrainian. Available from: https://detector.media/infospace/article/191295/2021-08-19-kompaniya-ocean-media-plus-vkazala-na-ryzyky-dlya-ukrainskogo-mediarynku-cherez-vvedennya-moratoriyu-na-reklamu-likarskykh-zasobiv/
- Volynets I. [Protection against unfair advertising on the drug market. Creation, protection, protection and commercialization of objects of intellectual property rights]. 5th All-Ukrainian scientific and practical conference with international participation; 2022 Apr 26; Kyiv, Ukraine. Kyiv: KPI im. I. Sikorskoho; 2022. p. 358-63. Ukrainian. Available from: https://km.kpi.ua/wp-content/uploads/Zbirnyk-IV-2022.pdf
- [On protection against unfair competition: Law of Ukraine of 1996, Pub. No. 236/96-VR. (Oct 16, 2020). Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/236/96-vr#Text.
- [About advertising: Law of Ukraine of July 3, 1996,No. 270/96-VR. (Aug 3, 2022). Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/270/96-vr#Text
- [About some issues of prohibition of advertising of medicinal products: Order of the Ministry of Health of Ukraine of Juny 06, 2012, Pub. No. 422. (Feb 18, 2022). Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/z1189-12#Text
- [On making changes to the Criteria used in the determination of medicinal products, the advertising of which is prohibited: Order of the Ministry of Health of Ukraine of Nov 23, 2021, Pub. No. 2593. (2021). Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/z0092-22#Text
- Chabarai H. [How to wean Ukrainians from Google therapy. Analytics, security, economics, international politics, culture. Content matters!] [Internet]. Kyiv: Tyzhden. 2018 May 18 [cited 2022 Aug 12]. Ukrainian. Available from: https://tyzhden.ua/Society/214112
- Lapii F, Lavrovskyi N, Denysenko A, Shcherban O. [Money on the wind: which drugs with dubious effectiveness spend billions of hryvnias in Ukraine and what to do about it]. Ukrainska pravda [Internet]. 2021 Oct 13 [cited 2022 Aug 12]. Ukrainian. Available from: https://life.pravda.com.ua/health/2021/10/13/246197/
- Most advertised drugs on U.S. TV 2021. Statista Research Department [Internet]. 2022 Sep 5 [cited 2022 Aug 12]. Available from: https://www.statista.com/statistics/639356/tv-advertise-drugs-usa/
- Guttmann Pharmaceutical industry TV ad spend in the U.S 2016-2020. Statista [Internet]. 2021 [cited 2022 Aug 12]. Available from: https://www.statista.com/statistics/953104/pharma-industry-tv-ad-spend-us/
- Lee B. How Is Consumer Drug Advertising Regulated in the United States? GoodRx Health [Internet]. 2022 July 1 [cited 2022 Aug 12]. Available from: https://www.goodrx.com/healthcare-access/patient-advocacy/prescription-drug-advertising-regulation-united-states
- Kracov D, Davar M. International Comparative Legal Guides International Business Reports. Pharmaceutical Advertising Laws and Regulations Report 2022 USA [Internet]; 2022 [cited 2022 Aug 12]. Available from: https://iclg.com/practice-areas/pharmaceutical-advertising-laws-and-regulations/usa
- Faerber AE, Kreling DH. Content Analysis of False and Misleading Claims in Television Advertising for Prescription and Nonprescription Drugs. Journal of General Internal Medicine. 2013 Sep 13;29(1):110-8. doi: https://doi.org/10.1007/s11606-013-2604-0
- [According to the results of the study on the detection and termination of unfair practices in the field of advertising of medicinal products, biologically active additives, medical procedures, antiseptics and disinfectants: Report of the Antimonopoly Committee of Ukraine. Office of Unfair Competition Investigations]. [Internet]. Kyiv; 2020. [cited 2022 Aug 14]. Ukrainian. Available from: https://amcu.gov.ua/storage/app/uploads/public/5ff/5b9/766/5ff5b976685ac541795869.pdf
- [On violation of the legislation on protection against unfair competition: Decision of the Antimonopoly Committee of Ukraine of October 22, 2020, Pub. No. 654-r]. [Internet]; (Oct 22, 2020). Ukrainian. Available from: https://amcu.gov.ua/storage/app/uploads/public/5f9/fd7/08d/5f9fd708dd9f7819532980.pdf
- [On violation of the legislation on protection against unfair competition and imposition of a fine: Decision of the Antimonopoly Committee of Ukraine of July 2, 2020, Pub. No. 421-r]. [Internet]; (Jul 02, 2020). Ukrainian. Available from: https://amcu.gov.ua/storage/app/uploads/public/5f0/852/ae6/5f0852ae6c6f2854410852.pdf
- [On violation of the legislation on protection against unfair competition and the imposition of a fine: Decision of the Antimonopoly Committee of Ukraine of July 2, 2020, Pub. No. 430-r]. [Internet]; (Jul 02 2020). Ukrainian. Available from: https://amcu.gov.ua/npas/pro-porushennya-zakonodavstva-pro-zahist-vid-nedobrosovisnoyi-konkurenciyi-ta-nakladennya-shtrafu-5
- [Regarding the application of the provisions of Article 151 of the Law of Ukraine "On Protection from Unfair Competition" in relation to the advertising of medicinal products: Recommendation clarifications of the Antimonopoly Committee of Ukraine of March 16, 2021, Pub. No.13-rr]. [Internet]; (2021). Ukrainian. Available from: https://amcu.gov.ua/npas/shchodo-zastosuvannya-polozhen-statti-151-zakonu-ukrayini-pro-zahist-vid-nedobrosovisnoyi-konkurenciyi-stosovno-reklami-likarskih-zasobiv
- [On the state of the national health care system and urgent measures to provide citizens of Ukraine with medical aid: Decision of the National Security and Defense Council of Ukraine of July 30, 2021]. [Internet]; (2021). Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/n0052525-21#Text
- [Do self-medication now and then: in Ukraine, antibiotics will be sold by electronic prescription]. Vikna [Internet]; 2022 [cited 2022 Aug 12]. Ukrainian. Available from: https://vikna.tv/styl-zhyttya/zdorovia-ta-krasa/z-1-serpnya-v-ukrayini-antybiotyky-prodavatymut-lyshe-za-elektronnym-reczeptom/
- [From August 2022, patients will start receiving electronic prescriptions for antibiotics]. [Internet]. Kyiv: Ministry of Health; 2022 [cited 2022 Aug 12]. Ukrainian. Available from: https://moz.gov.ua/article/news/z-serpnja-2022-roku-pacienti-pochnut-otrimuvati-elektronni-recepti-na-antibiotiki.
- Aikin KJ, Southwell BG, Paquin RS, Rupert DJ, O'Donoghue AC, Betts KR, Lee PK. Correction of misleading information in prescription drug television advertising: The roles of advertisement similarity and time delay. Research in Social and Administrative Pharmacy. 2017 Mar;13(2):378-88. doi: https://doi.org/10.1016/j.sapharm.2016.04.004
- Corrective advertising [Internet]. Multitran dictionary; 2022 [cited 2022 Aug 12]. Available from: https://www.multitran.com/m.exe?l1=1&l2=2&s=corrective+advertising\&langlist=2
Lytovchenko V.P. Medical interview in the system of dental care providing to patients with special needs
Authors and affiliations
Lytovchenko V.P. Ukrainian Military Medical Academy, Kyiv, Ukraine,
Key words: dental care, doctor-patient relationship, universal design in dentistry, patients with hearing impairment, medical interview model/ guide to the medical interview
Abstract. Medical interview in the system of dental care providing to patients with special needs. Lytovchenko V.P. Among the leading trends in the field of medicine – improving the quality of various services; focus on individually targeted care, experience and needs of patients; creating equal opportunities and favorable treatment conditions. Relevant in this context is the “Cambridge guide to the medical interview” designed to identify effective communication skills between physician and patient and to provide a sound framework for their analysis. To solve the two leading tasks, an adapted interview model for dentists was developed and tested, taking into account the communicative needs of patients with severe hearing impairment (to the general tasks of “providing structure”, “building the relationship”), which are cross-cutting for each stage of medical interview, “ensuring a universal design of the environment” included, before the stage of “initiating the session” an additional “selection of priority means of communication/necessary adaptations”, etc.) was proposed. Based on the described modern approaches to building trusting relationships in medical practice, taking into account the adapted version of the interview, the key components of working with patients with special needs (hearing impairment) in dentistry are identified.
- Bronіkova S. [Practices of communicative culture in a medical institution: patient-centered approach: textbook]; 2020. Ukrainian.Available from: http://ekmair.ukma.edu.ua/handle/123456789/21027
- [Universal Declaration on Bioethics and Human Rights of the General Conference of UNESCO: adopted by the resolution of the General Conference of UNESCO on the report of Commission III at the 18th plenary meeting of 19 October 2005]. Russian. Available from: http://portal.unesco.org/en/ev.php-URL_ID=31058&URL_DO=DO_TOPIC&URL_SECTION=201.html
- [Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects: The World Medical Association; Declaration, International document of June 1, 1964] [Internet]. Kyiv; 2008 Oct 1. Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/990_005#Text
- [Convention on the Rights of Persons with Disabilities, Pub. L. No. 1767-VI]. (Dec 16, 2009). Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/995_g71#Text
- Lytovchenko VP, Lytovchenko SV. [Availability of dental services for people with hearing impairments: communication between doctor and patient]. Ukrainskyi naukovo-medychnyi molodіzhnyi zhurnal. 2021;125(3):52-63. Ukrainian. doi: https://doi.org/10.32345/USMYJ.3(125).2021.52-63
- Cohen M. [Interdisciplinary planning of dental treatment. Principles, goals, practical application. Illustrated lectures]. Moskva: Azbuka; 2012. Russian. Available from: https://www.dental-azbuka.ru/books/raznoe/kniga_120.html
- Bottaev NA, Diachenko EV, Samoilenko NV, et al. [Skills of effective communication for rendering patient-oriented medical care: scientific and methodical edition]. Moskva: ROSOMED; 2018. Russian. Available from: https://rosomed.ru/system/documents/files/000/000/102/original/
- [On approval of the Procedure for conducting clinical trials of medicinal products and examination of clinical trial materials and standard regulations on ethics commissions: Order of the Ministry of Health of Ukraine No. 690]. (Sep 23, 2009). Ukrainian. Available from: https://zakon.rada.gov.ua/laws/show/z1010-09#Text
- Becker C, Hunziker S. [The importance of communication between physicians and patients]. Ther Umsch. 2019;76(5):231-238. PMID: 31577188. doi: https://doi.org/10.1024/0040-5930/a001095
- Berger R, Bulmash B, Drori N, Ben-Assuli O, Herstein R. The patient-physician relationship: an account of the physician's perspective. Isr J Health Policy Res. 2020 Jun 30;9(1):33. PMID: 32605635. PMCID: PMC7325021. doi: https://doi.org/10.1186/s13584-020-00375-4
- Bird J, Cohen-Cole SA. The three-function model of the medical interview. An educational device. Adv Psychosom Med. 1990;20:65-88. PMID: 2239506. doi: https://doi.org/10.1159/000418260
- Bokhour BG, Fix GM, Mueller NM, Barker AM, Lavela SL, Hill JN, et al. How can healthcare organizations implement patient-centered care? Examining a large-scale cultural transformation. BMC Health Serv Res. 2018 Mar 7;18(1):168. PMID: 29514631; PMCID: PMC5842617. doi: https://doi.org/10.1186/s12913-018-2949-5
- Burt J, Abel G, Elmore N, Campbell J, Roland M, Benson J, Silverman J. Assessing communication quality of consultations in primary care: initial reliability of the Global Consultation Rating Scale, based on the Calgary-Cambridge Guide to the Medical Interview. BMJ Open. 2014 Mar 6;4(3):e004339. PMID: 24604483; PMCID: PMC3948635. doi: https://doi.org/10.1136/bmjopen-2013-004339
- Dalaya M, Ishaquddin S, Ghadage M, Hatte G. An interesting review on soft skills and dental practice. J Clin Diagn Res. 2015 Mar;9(3):ZE19-21. PMID: 25954720; PMCID: PMC4413170. doi: https://doi.org/10.7860/JCDR/2015/12725.5719
- DeCamp M, Dukhanin V, Hebert LC, Himmelrich S, Feeser S, Berkowitz SA. Patients' Views About Patient Engagement and Representation in Healthcare Governance. J Healthc Manag. 2019 Sep-Oct;64(5):332-46. PMID: 31498210; PMCID: PMC6865800. doi: https://doi.org/10.1097/JHM-D-18-00152
- Edwards A, Elwyn G. Understanding risk and lessons for clinical risk communication about treatment preferences. Qual Health Care. 2001 Sep;10(Suppl 1):i9-13. PMID: 11533431; PMCID: PMC1765742. doi: https://doi.org/10.1136/qhc.0100009
- Feletti G, Firman D, Sanson-Fisher R. Patient satisfaction with primary-care consultations. J Behav Med. 1986 Aug;9(4):389-99. PMID: 3746905. doi: https://doi.org/10.1007/BF00845122
- Hashiyama DT, Mori N. Osler's nodes: dialogue with Sir William Osler. QJM. 2021 Nov 13;114(9):667-68. doi: https://doi.org/1093/qjmed/hcab139
- Hofhansl A, Horn W, Kainberger F, Zlabinger G, Rieder A. ["To be a good doctor": how are medical students prepared for the future]. Wien Med Wochenschr. 2015 Mar;165(5-6):83-5. PMID: 25786601. Deutsch. doi: https://doi.org/1007/s10354-015-0349-6
- Krot K, Rudawska I. The Role of Trust in Doctor-Patient Relationship: Qualitative Evaluation of Online Feedback from Polish Patients. Econom. & Sociology. 2016;9(3):76-88.
- Krzikallová K, Střílková Labour-intensive services and changes in value added tax revenue. Journal of Competitiveness.2016 Mar;8(1):5-18. doi: https://doi.org/10.7441/joc.2016.01.01
- Kurtz S, Silverman J, Benson J, Draper J. Marrying content and process in clinical method teaching: enhancing the Calgary-Cambridge guides. Acad Med. 2003Aug;78(8):802-9. PMID: 12915371. doi: https://doi.org/10.1097/00001888-200308000-00011
- Łakomy-Zinowik M, Horváthová Z. Public-private partnerships as a way of financing in the healthcare system (based on the examples of Poland and the United Kingdom). Journal of International Studies. 2016 Nov;9(3):150-8.
- Machan TR. Rights, values, regulation and health care: to be well is not a fundamental right but a value. American Journal of Medical Research. 2016;3(2);115-125. doi: https://doi.org/10.22381/AJMR3220165
- Naseribooriabadi T, Sadoughi F, Sheikhtaheri A. Barriers and Facilitators of Health Literacy among D/deaf Individuals: A Review Article. Iran J Public Health. 2017 Nov;46(11):1465-74. PMID: 29167764; PMCID: PMC5696685. Available from: https://pubmed.ncbi.nlm.nih.gov/29167764/
- Novack DH, Dubé C, Goldstein MG. Teaching medical interviewing. A basic course on interviewing and the physician-patient relationship. Arch Intern Med. 1992 Sep;152(9):1814-20. PMID: 1520048. doi: https://doi.org/10.1001/archinte.152.9.1814
- Patient experience in adult NHS services: improving the experience of care for people using adult NHS services. London: National Institute for Health and Care Excellence (NICE); 2021 Jun 17. PMID: 34260162. Availablefrom: https://pubmed.ncbi.nlm.nih.gov/34260162/
- Peters L, Pressey A, Gilchrist AJP, Johnson W. Involving customers in innovation: knowledgability and agency as process variables. Journal of Business and Industrial Marketing. 2018 Mar 5;33(2):164-73. doi: https://doi.org/10.1108/JBIM-04-2016-0083
- Riccardi V, Kurtz S. Communication and counseling in health care. Springfield: C.C. Thomas; 1983. Available from: https://ur.booksc.eu/book/320139/798c7a
- Silverman J, Kurtz S, Draper J. Skills for Communicating with Patients. 3rd ed. CRC Press; 2013. Available from: https://www.routledge.com/Skills-for-Communicating-with-Patients/Silverman-Kurtz-Draper/p/book/9781846193651
- Smith AJE. [Series: Communication in the dental practice. Building a good dentist-patient relationship with communication]. Ned Tijdschr Tandheelkd. 2019 Jan;126(1):37-44. Deutsch. PMID: 30636264. doi: https://doi.org/10.5177/ntvt.2019.01.18212
- Stillman PL, Sabers DL, Redfield DL. The use of paraprofessionals to teach interviewing skills. Pediatrics. 1976 May;57(5):769-74.PMID: 940718. doi: https://doi.org/10.1542/peds.57.5.769
- Tosyalı H, Sütçü CS, Tosyalı F. Patient Loyalty in the Hospital Patient Relationship: The Mediating Role of Social Media. Erciyes İletişim Dergisi. 2019;6(1):783-804. doi: https://doi.org/10.17680/erciyesiletisim.454347
- Towle A, Godolphin W. Framework for teaching and learning informed shared decision making. BMJ. 1999 Sep 18;319(7212):766-71.PMID: 10488010. doi: https://doi.org/10.1136/bmj.319.7212.766.
- Ustrell-Torrent JM, Buxarrais-Estrada MR, Ustrell-Torrent Riutord-Sbert P. Ethical relationship in the dentist-patient interaction. J Clin Exp Dent. 2021 Jan 1;13(1):e61-e66. PMID: 33425233. doi: https://doi.org/10.4317/jced.57597
- Van Den Assem B, Dulewicz V. Doctors' trustworthiness, practice orientation, performance and patient satisfaction. Int J Health Care Qual Assur. 2015;28(1):82-95. PMID: 26308405. doi: https://doi.org/10.1108/IJHCQA-04-2013-0037
- Van Dalen J, Bartholomeus P, Kerkhofs E, Lulofs R, Van Thiel J, Rethans JJ, Scherpbier AJ, Van Der Vleuten CP. Teaching and assessing communication skills in Maastricht: the first twenty years. Med Teach. 2001 May;23(3):245-51.PMID: 12098395. doi: https://doi.org/10.1080/01421590120042991
- Watkins DA, Jamison DT, Mills T., Atun T., Danforth K, Glassman A, et al. Universal Health Coverage and Essential Packages of Care. In: Jamison DT, Gelband H, Horton S, Jha P, Laxminarayan R, Mock CN, Nugent R, editors. Disease Control Priorities: Improving Health and Reducing Poverty. 3rd ed. Washington (DC): The International Bank for Reconstruction and Development / The World Bank; 2017 Nov 27(Chapter 3). PMID: 30212154. doi: https://doi.org/1596/978-1-4648-0527-1_ch3
- Weeber JE. Ronald L Mace. Encyclopedia Britannica [Internet]; 2021 [cited 2001 Jan 01]. Available from: https://www.britannica.com/biography/Ronald-L-Mace
- Zulman DM, Haverfield MC, Shaw JG, Brown-Johnson CG, Schwartz R, Tierney AA, et al. Practices to Foster Physician Presence and Connection With Patients in the Clinical Encounter. JAMA. 2020 Jan 7;323(1):70-81. doi: https://doi.org/10.1001/jama.2019.19003
Kapustynska O.A. Ischemic heart disease in the evacuated adult population as a cause of health loss in the long term after the Chernobyl accident. Results of epidemiological studies 1988-2016
Authors and affiliations
Kapustynska O.A. SI "National Research Center of Radiation Medicine of the National Academy of Medical Sciences of Ukraine", Kyiv, Ukraine, е-mail:
Key words: Chernobyl accident, adult evacuated population, morbidity, disability, mortality, coronary heart disease
Abstract. Ischemic heart disease in the evacuated adult population as a cause of health loss in the long term after the Chernobyl accident. Results of epidemiological studies 1988-2016. Kapustynska O.A. Ischemic heart disease (CHD) is one of the most common diseases of the circulatory system, which is the main cause of death in Ukraine. The purpose of this study was to analyze the incidence, disability, mortality from ischemic heart disease, its individual nosological forms in the adult population evacuated from the 30 km zone of the Chernobyl nuclear power plant in the post-accident period, taking into account the age at the date of the accident, sex and time after the accident for further improving the system of dispensary observation evacuees and reducing the risk of cardiovascular complications. The study used epidemiological surveillance data (1988-2016) for the category of the adult evacuated population (18-60 years old as of the date of the accident) with a population of 42 982 people, of which 58.7% are women according to the data of the State Register of Ukraine of persons injured in as a result of the Chernobyl disaster (GRU). The research results were assessed both in general for ischemic heart disease and the main nosological forms according to ICD-9 and ICD-10. In the study, epidemiological, analytical, mathematical and statistical methods were used, as well as the method of internal comparison (with indicators of 1988-1992). As the results of the study have shown, in the structure of the causes of morbidity, disability and mortality of the adult evacuated population from diseases of the circulatory system, IHD takes a leading place. The statistically significant influence of age, calendar observation period, gender was established. Among nosological forms, chronic CHD is in the lead. Evacuees at the age of 18–39 years show an increase in the incidence of coronary artery disease with a maximum rate after 17 years, and at the age of 40-60 years – at the beginning of the observation with a subsequent noticeable decrease since 2003. In recent years (2013-2016), there has been a significant decrease in the incidence of coronary artery disease at the age of 40-60 years by 9.3 times, and at the age of 18-39 years, on the contrary, an increase by 3.8 times. During the post-accident period, the level of disability and mortality of the studied contingents from ischemic heart disease has significantly increased. High rates of growth of disability in recent years in persons aged 18-39 at the date of the accident. The mortality rate of the evacuees in recent years has increased in comparison with the early observation period by 5.8 times, higher mortality rates in men compared to women. Further more in-depth studies are required to assess the contribution of non-cancer diseases to the total radiation damage to human health.
- Kovalenko VM, Dorohoi AP. [Cardiovascular diseases: medical and social significance and strategy for the development of cardiology in Ukraine]. Ukrainian Journal of Cardiology. 2016;3:5-14. Ukrainian.
- Drozdova IV, Babets AA, Stepanova LG, Omelnytska LV. [Diseases of the circulatory system in Ukraine as one of the characteristics of public health]. Ukrainian therapeutic journal. 2017;(1):5-14. Ukrainian. Available from: http://nbuv.gov.ua/UJRN/UTJ_2017_1_3
- Diachuk DD, Moroz GZ, Gidzinska IM. [Prevention of cardiovascular diseases: theoretical principles and practical implementation]. DNU: "NPC PKM" DUS; 2019. Ukrainian.
- Terenda NO, Panchyshyn NYa, Lytvynova ON, Petrashyk YuM. [Risk factors in the development of myocardial infarction and ways of their correction]. The health of the nation. 2017;3(44):266-8. Ukrainian.
- Townsend N, Wilson L, Bhatnagar P, Wickramasinghe K, Rayner M, Nichols M. Cardiovascular disease in Europe: epidemiological update 2016. European Heart Journal.2016;37(42):3232-45. doi: https://doi.org/10.1093/eurheartj/ehw334
- Serdiuk AM, Bazyka DA, Los IP, Prysiazhniuk AE, Chumak VV. [Problems of radiation medicine and safety of Ukraine in the 21st century: historical past and modern tasks]. Scientific journal of the Ministry of Health of Ukraine. 2013;(1):7-17. Ukrainian.
- Sushko VO, Kolosynska OO, Tatarenko OM, Nezhovorova GA, Berestiana ZhM. [Medical examination of diseases that led to the loss of working capacity and death as a result of exposure to ionizing radiation in the conditions of the Chornobyl disaster (remote post-accident period)]. Journal of the National Academy of Sciences of Ukraine. 2019;25(1):5-12. Ukrainian.
- Huskova AK. [30 years of the accident at the Chornobyl nuclear power plant: the experience of liquidating medical consequences]. Meditsinskaia radiologiia i radiatsionnaia bezopasnost. 2016;(3):30-35. Russian.
- Onishchenko GG, Popova AYu, Romanovych IK. [Radiological consequences and lessons of radiation accidents at the Chornobyl NPP and Fukushima-1 NPP]. Radiatsionnaia gigiena. 2021;14(1):6-16. Russian. doi: https://doi.org/10.21514/1998-426X-2021-14-1-6-16
- Gurachevskii VL. [Consequences of the Chornobyl accident in Belarus and their overcoming]. Minsk: BGATU; 2017. ISBN 978-985-519-854-4. Russian.
- Bazika DA, Sushko VO, Lohanovskyi KM, Prysiazhniuk AYe, Bilyi DO, Fedirko PA. [Radiation medicine of Ukraine - a quarter of a century of progress and priorities for the future]. Journal of the National Academy of Sciences of Ukraine. 2018;24(1-2):26-42. Ukrainian.
- Buzunov VA, Pirogova EA, Tereshchenko VM. [Epidemiology of non-neoplastic diseases of participants in the liquidation of the aftermath of the Chornobyl accident]. Problemy radiatsiinoi medytsyny ta radiobiolohii. 2004;(10):187-207. Russian.
- Buzunov VA, Pirogov EA, Tsuprikov VA. [Non-tumor morbidity and mortality of the evacuated population. Twenty-five years of the Chornobyl disaster. Future safety]. Natsionalnyi doklad Ukrainy. Kyiv: KIM; 2011. p. 163-74. Russian.
- Prykashchikova KYe, Pavlovskyi YeYe, Kostiuk GV, Kapustynska OA, Yaroshenko ZhS, Lukianiuk VO, et al. [Changes in the structures of non-tumor morbidity and mortality in residents of radioactively contaminated areas: epidemiological monitoring for 1988–2015]. Dovkillia ta zdorovia. 2017;84(4):8-13. Ukrainian.
- Chekin SYu, Maksiutov MA, Kashcheev VV. [Assessment of radiation risks of non-oncological diseases among Russian participants in the liquidation of the consequences of the accident at the Chornobyl nuclear power plant]. Radiatsiia i risk. 2021;30(1):78-93. Russian.
- Pirogova Oya, Buzunov VO, Domashevska TE. [Cardiovascular morbidity of the population evacuated from the 30-km zone of the Chornobyl nuclear power plant in the post-evacuation period (epidemiological study)]. Problemy radiatsiinoi medytsyny ta radiobiolohii. 2011;16:50-58. Ukrainian.
- Khomaziuk IM, et al. [Peculiarities of diseases of the circulatory system in participants in the liquidation of the consequences of the Chornobyl accident 25 years later]. Serdiuk AM, Bebeshka VG, Bazyky DA, editors. [Medical consequences of the Chornobyl: 1986–2011]. Ternopil: TDMU; 2011. p. 411-59. Ukrainian.
- Chekin SYu, Maksiutov MA, Kashcheev VV, Tumanov KA, Korelo AM, Kochergina EV, et al. [Determination of the group of radiation risk of mortality from circulatory system diseases among Russian participants in the liquidation of the accident at the Chornobyl NPP]. Radiatsiia i risk. 2016;25(3):24-34. Russian. doi: https://doi.org/10.12737/25050
- Bilyi DO, Nastina OM, Gabulavichene ZhM, et al. [Radiation and non-radiation factors and their influence on the course of coronary heart disease in participants in the liquidation of the consequences of the Chornobyl accident]. Problemy radiatsiinoi medytsyny ta radiobiolohii. 2014;19:213-22. Ukrainian.
- Buzunov VO, Fedirko PA, Strii NI. [Assessment of the risk of ischemic heart disease and hypertension in participants in the liquidation of the consequences of the accident at the Chornobyl NPP]. Ukrainian Journal of Cardiology. 2006;6:101-5. Ukrainian.
- Buzunov VA, Pirogova EA, Krasnikova LI, et al. [Indicators and methods of their calculation in the epidemiology of non-infectious diseases: educational and methodological manual]. Kyiv: Avitsena; 2014. Russian.
- Antomonov MYu. [Mathematical processing and analysis of medical and biological data]. Kyiv: Medinform; 2018.
- Khomaziuk IM, et al. [Peculiarities of chronic ischemic heart disease in participants in the liquidation of the consequences of the Chornobyl accident who suffered a myocardial infarction]. Serdiuk AM, Bebeshka VG, Bazika DA, editors. [Medical consequences of the Chornobyl disaster: 1986-2011]. Ternopil: TDMU, Ukrmedknyga; 2011. p. 436-45. Ukrainian.
- Bilyi DO, Pleskach GV, Nastina OM, Sydorenko GV, Kursina NV, Bazika OD, et al. [Features of the development of coronary heart disease in liquidation participants consequences of the Chornobyl accident depending on the effect of radiation and non-radiation risk factors and the carrier of genotypes according to the polymorphism Rs966221 of the phosphodiesterase 4D gene]. Problemy radiatsiinoi medytsyny ta radiobiolohii. 2016;21:204-17. Ukrainian. Available from: http://nbuv.gov.ua/UJRN/Prmtr_2016_21_17
- Ivanov VK, Meniailo AN, Kashcheev VV. [Medical radiological consequences among the participants in the liquidation of the accident at the Chornobyl NPP. Part 1. Prognostic estimates]. Radiatsiia i risk. 2011;20(3):16-39. Russian.
- Chekin SYu, Maksiutov MA, Kascheev VV, Karpenko SV, Tumanov KA, et al. [Assessment of radiation risks of non-oncological diseases among Russian participants in the liquidation of the consequences of the Chornobyl accident]. Radiatsiia i risk. 2021;30(1):78-93. Russian.
A CASE FROM PRACTICE
Shkrobot S.I., Milevska-Vovchuk L.S., Duve Kh.V., Naumova L.V., Budarna O.Yu. A Clinical Case report: stroke in a young patient with systemic lupus erythematosus on the background of secondary antiphospholipid syndrome
Authors and affiliations
Shkrobot S.I. I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
Milevska-Vovchuk L.S. I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine, e-mail:
Duve Kh.V. I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
Naumova L.V. I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
Budarna O.Yu. I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
Key words: antiphospholipid syndrome, ischemic stroke, antiphospholipid antibodies
Abstract. A clinical case report: stroke in a young patient with systemic lupus erythematosus on the background of secondary antiphospholipid syndrome. Shkrobot S.I., Milevska-Vovchuk L.S., Duve Kh.V., Naumova L.V., Budarna O.Yu. The article describes a clinical case report of a young patient with ischemic stroke on the background of antiphospholipid syndrome (APLS). The uniqueness of this case lies in the complex diagnostic search that we performed. On admission, the patient had general cerebral, general infectious and focal syndromes. We suspected encephalitis due to the peculiarities of the onset of the disease and the results of computed tomography. However, after the results of lumbar puncture, the diagnosis of encephalitis required careful differential diagnosis. We performed an extensive diagnostic search. Based on clinical-laboratory, instrumental and immunological data the patient had the following final diagnosis: “Ischemic cardioembolic stroke in the right middle cerebral artery pool (15.10.17) (ICD 11: 8B11.5). Acute period with left pyramidal reflex insufficiency and changes in magnetic resonance imaging. Systemic lupus erythematous (ICD 11: 4A40.0), subacute course, activity II, with the lesion of skin (transient erythematous rash), kidneys (proteinuria, transient impaired renal function), lungs (bilateral pleurisy with immunological disorders). Secondary APLS (ICD 11: 4A45) (Acute iliofemoral thrombosis, May 2017; chronic thrombosis of the inferior vena cava, iliac veins, positive IgG to cardiolipin, beta 2 glycoproteins). Thus, we have to link thrombotic complications in young patients with APLS and to examine the patients for antiphospholipid antibody presence.
- Shkrobot S, Sokhor N, Milevska-Vovchuk L, Yasnii O, Shkrobot L. [Clinical and hemodynamic features of the course of the acute period of ischemic hemodynamic stroke]. Georgian medical news. 2017;2(263):35-44. Russian.
- Chaturvedi S, McCrae KR. Diagnosis and management of the antiphospholipid syndrome. Blood Rev. 2017 Nov;31(6):406-17. PMID: 28784423. doi: https://doi.org/10.1016/j.blre.2017.07.006
- Garcia D, Erkan D. Diagnosis and management of the antiphospholipid syndrome. N Engl J Med. 2018;378:2010-21. doi: https://doi.org/10.1056/NEJMra1705454
- Krytskyy T, Pasyechko N, Yarema N, Naumova L, Mazur l. Influence of age-related androgen deficiency on the risk factors for cardiovascular diseases in men with hypothyroidism. Georgian medical news. 2020;298:105-9. doi: https://doi.org/10.1530/endoabs.73.EP219
- Lin Z, Liu Y, Chen L, Cao S, Huang Y, Yang X, et al. Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets.Sci China Life Sci. 2021 Jan 19. PMID: 33481164.
- Saccone G, Berghella V, Maruotti GM, Ghi T, Rizzo G, Simonazzi G, et al. PREGNANTS (PREGNancy in women with ANTiphospholipid Syndrome) working group. Am J Obstet Gynecol. 2017 May; 216(5):525.e1-e12. PMID: 28153662. doi: https://doi.org/10.1016/j.ajog.2017.01.026
- Sayar Z, Moll R, Isenberg D, Cohen. Thrombotic antiphospholipid syndrome: A practical guide to diagnosis and management.Thromb Res. 2021 Feb;198:213-21. PMID: 33485122. doi: https://doi.org/10.1016/j.thromres.2020.10.010
- Schreiber K, Hunt Managing antiphospholipid syndrome in pregnancy. Thromb Res. 2019 Sep;181(Suppl 1):S41-S46. PMID: 31477227 Review. doi: https://doi.org/10.1016/S0049-3848(19)30366-4
- Shkrobot SI, Sokhor NR, Milevska-Vovchuk LS, Krynytska IYa, Marushchak MI, Shkrobot LV, Yasnii OR. Clinical neurological characteristics of ischemic stroke subtypes in acute phase. Zaporozhye medical journal. 2018;20(1):41-46. doi: https://doi.org/10.14739/2310-1210
- Stack Christopher A, Cole John W, Ischemic stroke in young adults Curr Opin Cardiol. 2018 Nov;33(6):594-604. doi: https://doi.org/10.1097/HCO.0000000000000564