THE ROLE OF THE NEUROENDOCRINE AND IMMUNE COMPLEX IN THE MECHANISM OF ACTION OF BALNEOTHERAPY (experimental and clinical studies) = РОЛЬ НЕЙРОЕНДОКРИННО-ІМУННОГО КОМПЛЕКСУ В МЕХАНІЗМІ ДІЇ БАЛЬНЕОТЕРАПІЇ (експериментальні і клінічні дослідження)
Creators: name: Popovych, Ihor Lvovych
Publisher: name: Zenodo
Year: 2023
Subjects: neuroendocrine and immune complex
balneotherapy
нейроендокринно-імунний комплекс
бальнеотерапія

description: Machine Translated by Google MINISTRY OF HEALTH PROTECTION OF UKRAINE Ihor Lvovych Popovych UDC 615.327.015.4[615.838 THE ROLE OF THE NEUROENDOCRINE-IMMUNE COMPLEX IN THE MECHANISM OF ACTION OF BALNEOTHERAPY (experimental and clinical studies) 14.03.04 - pathological physiology Scientific report based on a set of monographs and articles for obtaining the scientific degree of Doctor of Medical Sciences 2023 Machine Translated by Google The work was performed at the SE "Ukrainian Research Institute of Transport Medicine of the Ministry of Health of Ukraine", Odesa; Institute of Physiology named after O.O. Bogomolets National Academy of Sciences of Ukraine, Kyiv Scientific consultant: Doctor of Medical Sciences, Professor, Honored Worker of Science and Technology of Ukraine Anatoly Ivanovich Gozhenko, SE "Ukrainian Research Institute of Transport Medicine of the Ministry of Health of Ukraine", Director Official opponents: 2 Machine Translated by Google GENERAL CHARACTERISTICS OF THE RESEARCH Actuality of theme. The human body is a supersystem, and therefore his Adaptation reactions in normal and pathological conditions are always complex and include both specific and numerous non-specific reactions [A.I. Gozhenko, 2015]. To the most important non-specific reactions include reactions of the neuroendocrine immune complex. Since the epoch-making discovery of H. Selye [1936], it is known that it is non-specific the pathogenetic basis of many chronic diseases is stress (general adaptation syndrome). This concept is developed by its numerous followers [Horizontov P.D. and others, 1983; Meerson F.Z., 1986, 1993; L.H. Garkavy and others, 1990, 1998; Chrousos GP, 1992-2005; Stress of Life, 1998; O.M. Radchenko, 2004; Reznikov O.G. et al., 2004; Dhabhar FS, 2009-2018; Baraboy V.A., Reznikov O.G., 2013; Reznikov O.G., 2019]. Physiological antipode of stressors are adaptogens, which act stress-limiting effect by induction of anti-stress general adaptation reactions The level of resistance of the organism is determined by the quality of its general adaptation reaction [L.H. Harkavy and others, 1990, 1998; O.M. Radchenko, 2004]. By L.H. Garkavy et al. [1990], all stimuli and influences should be considered adaptogens (electric stimulation of the hypothalamus, carbon dioxide as an irritant reticular formation and interoreceptors, magnetic fields, neurotropic agents, immunomodulators, antioxidants, muscle strain, biostimulants of plant and animal origin), which are capable of acting on the body cause an anti-stressor general adaptation reaction. However, the majority authors include only substances capable of causing a condition as adaptogens "non-specifically increased resistance" of the organism to the influence of adverse factors environmental factors of a physical, chemical and biological nature [N.V. Lazarev, 1958; I.I. Brehman, 1957, 1987; I.V. Dardymov, 1976; Saratykov A.S., Krasnov E.A., 1987; Kaplan E.A. and others, 1990; Yakovlev G.M. and others, 1990; I.L. Popovych, 2011; Panossian AG et al, 2022]. They are another form of adaptogenic effect of the means regulatory [Saratikov A.S., Krasnov E.A., 1987] ambivalent-equilibrator [Balanovsky V.P. et al., 1993] effect, that is, normalization abnormal body parameters regardless of their orientation. One of the long-known and widely used adaptogenic means is ball attendants The theoretical basis of balneotherapy and balneorehabilitation is the concept of sanogenesis Gozhenka A.I. and Gozhenko O.A. [2007]. Their main task is to increase the body's resistance, both general and immune, with the goal prevention of aggravation of aseptic inflammation by infection, metaphylaxis relapses in patients in the phase of remission, deepening and prolongation of the latter, suppression of the latent inflammatory process [Cmiyan I.S., 1967, 1973, 2008; I.L. Popovych et al., 2003; Kostyuk P.K. et al., 2006; Babov K.D. et al., 2009; I.L. Popovych, 2011]. 3 Machine Translated by Google Back in 1993, Korneva E.A. [1993; 2020] introduced the term "a single immune-neuro- endocrine complex that participates in ensuring the stability internal environment of the body". I. L. Popovych, barely changing the term to "neuroendocrine-immune complex" [I.L. Popovich, 2009], initiated large-scale studies of immediate and long-term (course) effects on it the famous Naftusya bioactive water, which is a combination non-antigenic (oil-like substances and products of their microbial transformation, primarily fatty acids) and antigenic (indigenous microflora) irritants and fully meets the recently accepted International Scientific criteria Association for Probiotics and Prebiotics (ISAPP) to refer the product to synbiotics: "a mixture containing living microorganisms and substrates selectively used by host microorganisms that provides benefits for the health of the host" [Swanson KS et al., 2020]. The results were published in a number of monographs [Dranovsky A.L., Popovych I.L., 2010; I.L. Popovych, 2011; Chebanenko O.I., Popovych I.L., 2011; 2012; 2013; 2015; I.L. Popovych et al., 2014; Kozyavkina O.V. et al., 2015; Sydoruk N.O. et al., 2018; Gozhenko AI et al., 2019; Popovych IL et al., 2020; Gozhenko A.I. and others, 2021; Popovych IL et al., 2022; Korda M.M. et al., 2023] and numerous articles Truskavet Scientific School of Balneology, which aroused great interest in specialists and were recognized by experts as the main trend of the last decade in Ukrainian balneology [A.G. Portnichenko, 2015]. At the same time, in the process of studying the impact of transdermal devices electrostimulation on the human body, it was found that changes in parameters neuroendocrine-immune complex and metabolome also have adaptogenic character [Popovych IL, 2022; Babelyuk VE and Popovych IL, 2023]. So, the mentioned authors of the concept of anti-stress general adaptive reactions were still right about the wide spectrum of the nature of adaptogens. Connection of work with scientific programs, plans, topics. The research was carried out along the lines of: programs of the Institute of Physiology named after O.O. Bogomolets National Academy of Sciences of Ukraine "Study of the mechanisms of regulation of the body's functional systems in conditions of normality and pathology" (No. DR 0102U002064), fragments of which are topics Department of Experimental Balneology "Influence of factors of the Truskavets resort on vegetative and vascular tone and heart activity"; "Mechanisms of induction of the body's protective systems by spa attendants of the Truskavets resort"; "Immunological aspects of balneotherapy at the Truskavets resort of diseases organs of the urinary system" (order No. 104/1–142 of the Institute dated February 25, 1998 p); of the general resort theme of the Association of Scientists of the city "Integral Quantitative assessment of the general state of health (vitality) of various categories of persons who arrive at the Truskavets resort, the impact on it is standard 4 Machine Translated by Google balneotherapy complex and the search for methods of increasing efficiency of balneotherapy, balneo-rehabilitation and balneosanitation" (No. DR 0104U007397). The aim of the study. Find out the role of the neuroendocrine-immune complex in the mechanism of therapeutic and prophylactic action of adaptogens of different nature (phyto- balneo-, electrogenic) and to evaluate the contributions of the components of the composition of adaptogens (polyphenols, fatty acids, bacteria) in their influence on parameters neuroendocrine-immune complex. Research tasks. To achieve the goal, it is necessary solve the following problems. 1. In the clinical and physiological observations, register short-term (within 1.5 hours) reactions of the parameters of the neuroendocrine-immune complex on the use of Naftusya bioactive water and phytoadaptogen and related changes parameters of gastric and pancreatic secretion, cholekinetics, urination and hemodynamics. Identify predictors of options for short-term reactions on adaptogens. 2. Investigate changes in the parameters of the neuroendocrine-immune complex under by the influence of the course of drinking Naftusya bioactive water, the use of phytoadaptogens or transcutaneous electrical stimulation of nerve plexuses by the author device "VEB". To find out which changes in parameters of the neuroendocrine immune complex are the same for adaptogens of different nature (common), and which specific 3. Based on specific effects, evaluate the contributions of individual components adaptogens (aryl hydrocarbons, fatty acids and bacteria) in their effects on neuro-endocrine-immune complex. 4. To analyze the correlation relationships between the parameters of the central and autonomous nervous, endocrine and immune systems as components neuroendocrine-immune complex. Find out the relationship between the parameters neuroendocrine-immune complex and their changes, as factors signs, and microbiota of urine and feces, metabolism of lipids, electrolytes and nitrogenous metabolites, hemodynamics, cholekinetics, gastric and pancreatic secretion, acupuncture and gas discharge visualization - as effective signs 5. In experiments on rats, conduct a comparative study of preventive effects of phytoadaptogen and Naftusya bioactive water on changes in the neuroendocrine immune complex, metabolome and markers of myocardial damage and gastric mucosa under the influence of acute immobilization-cold factors stress Analyze neuroendocrine-immune interrelationships and find out the role of the neuroendocrine-immune complex in minimizing stressors damage to the myocardium and gastric mucosa. 6. Identify options for reactions of the neuroendocrine-immune complex of rats to chronic immobilization stress and analyze neuroendocrine immune relationships. 5 Machine Translated by Google 7. Identify general and specific changes in neuroendocrine-immune parameters complex of animals with their course load of fresh and mineral waters of different chemical composition. Analyze the connections between the content of tested waters of organic substances, microelements and electrolytes, with on the one hand, and the parameters of the neuroendocrine-immune system exposed to them of the complex - on the other hand. 8. Assess the contributions of autochthonous microflora and bioactive organic substances of Naftusya water in its effects on neuroendocrine-immune parameters of the complex The object of research is the neuroendocrine-immune complex, microbiota, metabolome, hemodynamics, cholekinetics, gastric and pancreatic secretion, biophysical parameters. Subject of research in humans: Amplitude-frequency and spectral parameters of the electroencephalogram: average amplitude (ÿV), average frequency (Hz), frequency deviation (Hz), index rhythm (%), asymmetry coefficient (%), lateralization coefficient (%), absolute (ÿV2 /Hz) and relative (%) spectral power density (SPD) of the main rhythms: ÿ (35÷13 Hz), ÿ (13÷8 Hz), ÿ (8÷4 Hz) and ÿ (4÷0.5 Hz) in 16 loci (Fp1, Fp2, F3, F4, F7, F8 , C3, C4, T3, T4, P3, P4, T5, T6, O1, O2). Entropy is relative SHSP in these loci. Temporal and spectral parameters of heart rate variability (HRV): HR, Mo, AMo, MxDMn, TNN, SDNN, RMSSD, pNN50, absolute (msec 2) and relative (%) spectral power of HRV components: HF (0.4÷0.15 Hz), LF (0.15÷0.04 Hz), VLF (0.04÷0.015 Hz), ULF (0.015÷0.003 Hz) and their entropy. Adaptation hormones: cortisol, aldosterone, triiodothyronine, testosterone, calcitonin Hormones of the gastroentero-pancreatic neuroendocrine system (GEPES): gastrin, glucagon, insulin. Parameters of immune status: leukocytes and leukocytogram; relative the content in the blood of lymphocytes that express CD3, CD4, CD8, CD22, CD25 and CD56 receptors and T-lymphocytes with a high affinity for CD2 receptors, as well as sensitive and resistant to theophylline; serum content of immunoglobulins G, A, M, circulating immune complexes, C-RP, IL-1, IL-6, TNF-ÿ; activity, intensity and completeness of phagocytosis by neutrophils of blood cultures Staphylococcus aureus (ATCC N 25423 F49) and Escherichia coli (O55 K59); entropy leukocytograms and immunocytograms; author's leukocyte indices of adaptation and tension; content of lysozyme, sIgA, IgA, IgG in saliva. Fecal microbiota: normal, hemolyzing and weakened E. coli enzymatic activity, Klebsiella, Proteus, Bifidobacteria, Lactobacilli. Bacteriuria, leukocyturia and erythrocyturia. Parameters of the metabolome: the content of triglycerides and cholesterol in the plasma composition of lipoproteins of high, low and very low density, in plasma and urine - 6 Machine Translated by Google creatinine, urea, uric acid, phosphates, chloride, sodium, potassium, calcium and magnesium. Hemodynamic parameters: EDV, ESV, SV, ET, HR, BPs, BPd, GPRV, the author's index of the contractile activity of the heart. Cholekinetics parameters: gallbladder volumes on an empty stomach and after 5÷60 min after standard cholekinetics and/or Naftusya water. Parameters of gastric secretion: intragastric pH-metry and/or gastric probing on an empty stomach and after the introduction of Naftusya water with determination of the titrated acid and pepsin. Parameters of pancreatic secretion: duodenal probing on an empty stomach and after introduction of Naftusya water with determination of bicarbonate, amylase, lipase and trypsin. Biophysical parameters: electrical conductivity of acupuncture points, area, shape, entropy and symmetry of the gas discharge image, energy and asymmetry virtual chakras. Subject of research in rats ECG and variation cardiointervalogram parameters (Mo, AMo and MxDMn). The mass of the adrenal glands and the thickness of their glomerular, fascicular, reticular and medullary zones. Plasma levels of adaptation hormones (corticosterone, triiodothyronine and testosterone). Excretion with daily urine 17-ketosteroids. + The concentration of electrolytes in the blood (Na K+, Mg 2+, Ca 2+, Cl -, phosphates), nitrogenous metabolites (creatinine, urea, uric acid, bilirubin), medium molecular weight polypeptides, glucose, amylase, cholesterol alpha- and non-alpha-lipoproteins, products of lipoperoxidation (diene conjugates and malondialdehyde), activity of antioxid
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3: 22-24. 7.\u041f\u0435\u0440\u0447\u0435\u043d\u043a\u043e \u0412\u041f, \u041f\u043e\u043f\u043e\u0432\u0438\u0447 \u0418\u041b, \u0421\u0442\u0435\u0446\u0435\u043d\u043a\u043e \u0413\u0418, \u041f\u0435\u0442\u0440\u043e\u0432\u0430 \u0421\u041c, \u0424\u043b\u044e\u043d\u0442 \u0418\u0421, \u041c\u043e\u0434\u0440\u0438\u0446\u043a\u0438\u0439 \u042f\u041c. \u0412\u043b\u0438\u044f\u043d\u0438\u0435 \u043c\u0438\u043d\u0435\u0440\u0430\u043b\u044c\u043d\u043e\u0439 \u0432\u043e\u0434\u044b \u043d\u0430\u0444\u0442\u0443\u0441\u044f \u043d\u0430 \u0436\u0435\u043b\u0443\u0434\u043e\u0447\u043d\u043e\u0435 \u043a\u0438\u0441\u043b\u043e\u0442\u043e\u043e\u0431\u0440\u0430\u0437\u043e\u0432\u0430\u043d\u0438\u0435. \u0412\u043e\u043f\u0440 \u043a\u0443\u0440\u043e\u0440\u0442\u043e\u043b. 1991; 2: 48-52. 8.\u041f\u043e\u043f\u043e\u0432\u0438\u0447 \u0418\u041b, \u041f\u0435\u0440\u0447\u0435\u043d\u043a\u043e \u0412\u041f, \u0411\u0443\u0442\u0443\u0441\u043e\u0432\u0430 \u0418\u0410, \u041f\u0430\u0441\u0442\u0435\u0440\u043d\u0430\u043a \u0410\u0411. \u0412\u043b\u0438\u044f\u043d\u0438\u0435 \u043a\u0443\u0440\u0441\u043e\u0432\u043e\u0433\u043e \u043f\u0440\u0438\u0435\u043c\u0430 \u0432\u043e\u0434\u044b \u043d\u0430\u0444\u0442\u0443\u0441\u044f \u043d\u0430 \u0433\u0430\u0441\u0442\u0440\u043e\u044d\u043d\u0442\u0435\u0440\u043e-\u043f\u0430\u043d\u043a\u0440\u0435\u0430\u0442\u0438\u0447\u0435\u0441\u043a\u0443\u044e \u044d\u043d\u0434\u043e\u043a\u0440\u0438\u043d\u043d\u0443\u044e \u0441\u0438\u0441\u0442\u0435\u043c\u0443. \u0412\u043e\u043f\u0440 \u043a\u0443\u0440\u043e\u0440\u0442\u043e\u043b. 1991; 3: 33-38. 9.\u041f\u043e\u043f\u043e\u0432\u0438\u0447 \u0418\u041b, \u0411\u0443\u0442\u0443\u0441\u043e\u0432\u0430 \u0418\u0410, \u0418\u0432\u0430\u0441\u0438\u0432\u043a\u0430 \u0421\u0412. \u0413\u0430\u0441\u0442\u0440\u043e\u043f\u0440\u043e\u0442\u0435\u043a\u0442\u0438\u0432\u043d\u043e\u0435 \u0434\u0435\u0439\u0441\u0442\u0432\u0438\u0435 \u043b\u044e\u043c\u0438\u043d\u0430\u043b\u044c\u043d\u043e\u0433\u043e \u0433\u0430\u0441\u0442\u0440\u0438\u043d\u0430. \u0424\u0438\u0437\u0438\u043e\u043b \u0436\u0443\u0440\u043d. 1991; 37(5): 117-120. 10.\u041f\u043e\u043f\u043e\u0432\u0438\u0447 \u0418\u041b, \u0411\u0443\u0442\u0443\u0441\u043e\u0432\u0430 \u0418\u0410, \u0418\u0432\u0430\u0441\u0438\u0432\u043a\u0430 \u0421\u0412, \u042f\u0440\u0435\u043c\u0435\u043d\u043a\u043e \u041c\u0421. \u041e\u0441\u043e\u0431\u0435\u043d\u043d\u043e\u0441\u0442\u0438 \u0440\u0435\u0430\u043a\u0446\u0438\u0438 \u0433\u0430\u0441\u0442\u0440\u0438\u043d\u0430 \u0443 \u043a\u0440\u044b\u0441 \u0441 \u0440\u0430\u0437\u043b\u0438\u0447\u043d\u043e\u0439 \u043f\u043e\u0434\u0432\u0435\u0440\u0436\u0435\u043d\u043d\u043e\u0441\u0442\u044c\u044e \u043f\u043e\u0432\u0440\u0435\u0436\u0434\u0435\u043d\u0438\u044f\u043c \u0441\u043b\u0438\u0437\u0438\u0441\u0442\u043e\u0439 \u0436\u0435\u043b\u0443\u0434\u043a\u0430 \u043f\u0440\u0438 \u0438\u043c\u043c\u043e\u0431\u0438\u043b\u0438\u0437\u0430\u0446\u0438\u043e\u043d\u043d\u043e-\u0445\u043e\u043b\u043e\u0434\u043e\u0432\u043e\u043c \u0441\u0442\u0440\u0435\u0441\u0441\u0435. \u0411\u044e\u043b \u044d\u043a\u0441\u043f \u0431\u0438\u043e\u043b \u043c\u0435\u0434\u0438\u0446. 1992; 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