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MINISTRY OF HEALTH OF UKRAINE DU UKRAINIAN RESEARCH INSTITUTE OF TRANSPORT MEDICINE TERNOPIL NATIONAL MEDICAL UNIVERSITY AND I. ГОРБАЧЕВСКОГО UNIVERSITY NAMED AFTER M. COPERNIK, TORUN, POLAND M.V. HRYTSAK N.S. BADIUK D.V. POPOVYCH W. ZUKOW MINERAL WATERS MYROSLAVA AND KHRYSTYNA Monograph Torun 2022 Recommended for publication by the Academic Council State Enterprise Ukrainian Research Institute of Transport Medicine, Ministry of Health of Ukraine (Protocol№ 2 of February 23, 2022) Reviewers: Vastyanov Ruslan Sergeevich, Doctor of Medical Sciences, Professor, Honored Worker of Science and Technology of Ukraine, Head of the Department of General and Clinical Physiology. V.V. Podvysotsky Odessa National Medical University Savitsky Ivan Volodymyrovych, Doctor of Medical Sciences, Professor, Vice-Rector for Scientific and Pedagogical Work, Head of the Department of Medical and Biological Disciplines of Odessa International Medical University Hrytsak MV [etc.]. Mineral waters “Myroslava” and “Khrystyna”: monograph / M.V. Hrytsak, N.S. Badiuk, D.V. Popovych, W. Zukow. Torun. UMK; 2022: 214 p. ISBN 978-1-4717-5172-1 DOI https://doi.org/10.5281/zenodo.6334934 The monograph highlights the results of priority experimental and clinical-physiological studies of the impact of newly created sulfate-chloride sodium-magnesium mineral waters "Myroslava" (5 g / l) and "Khrystyna" (10 g / l) Truskavets resort on neuro-endocrine regulation, metabolism, cholekinetics and immunity of healthy rats and patients of the resort in the process of restorative treatment of chronic pyelonephritis and cholecystitis in remission. In line with the concepts of functional-metabolic continuum and neuroendocrine-immune complex using discriminant and canonical correlation analyzes, it is demonstrated that mineral waters have both similar and specific physiologically favorable modulating effects on the parameters of the studied body systems. For specialists in medical rehabilitation, endocrinologists, immunologists, biochemists, pathophysiologists. ISBN 978-1-4717-5172-1 © M.V. Hrytsak, N.S. Badiuk, D.V. Popovych, W. Zukow, 2022 © UkrNDI of medicine of transport, 2022 © Ternopil NMU named after A.I. Gorbachevsky, 2022 © University named after M. Copernicus, Torun, 2022 ISBN 978-1-4717-5172-1 CONTENT SUMMARY 5 CHAPTER 1 EFFECT OF DRINKING MINERAL WATERS ON METABOLISM AND NEUROENDOCRIN-IMMUNE COMPLEX (literature review) 1.1. Metabolism 16 1.2. Immune system 26 1.3. Neuro-hormonal regulation 36 1.4. Gastroentero-pancreatic endocrine system 62 SECTION 2 MATERIAL AND METHODS OF RESEARCH 2.1. Experiment on rats 70 2.2. Clinical and physiological observations 76 EXPERIMENTAL RESEARCH SECTION 3 NEUROENDOCRIN-METABOLIC AND NEUROENDOCRIN-IMMUNE RELATIONSHIPS IN HEALTHY RATS 3.1. Canonical correlation analysis of neuroendocrine-metabolic relationships 81 3.2. Canonical correlation analysis of neuroendocrine-immune relationships 89 SECTION 4 NEURO-ENDOCRINE AND METABOLIC EFFECTS OF MIROSLAVA AND CHRISTINA MINERAL WATERS 4.1. Common neuroendocrine and metabolic effects 94 4.2. Specific neuroendocrine and metabolic effects 104 SECTION 5 IMMUNOTROPIC EFFECTS OF MYROSLAVA AND CHRISTINA MINERAL WATERS 5.1. Joint immunotropic effects 114 5.2. Specific immunotropic effects 122 5.3. Patterns of specific immunotropic effects 129 SECTION 6 INTEGRAL EFFECTS OF MYROSLAVA AND CHRISTINA MINERAL WATERS ON NEUROENDOCRIN-IMMUNE COMPLEX AND METABOLISM 6.1. Discriminant analysis of specific integral effects 133 6.2. Patterns of common and specific integral effects 140 CLINICAL AND PHYSIOLOGICAL OBSERVATIONS SECTION 7 NON-SPECIFIC INFLUENCE OF COMPLEX DRINKING BALNEOTHERAPY ON NEUROENDOCRIN-IMMUNE COMPLEX, MICROBIOTIS AND METABOLISM OF PATIENTS IN PATIENTS IN PATIENTS 7.1. Screening of parameters subject to balneotherapy 143 7.2. Discriminant analysis of nonspecific balneological effects 146 7.3. Canonical correlation analysis of the relationships between the effects of balneo-factors on neuroendocrine and immune and metabolic parameters SECTION 8 COMPARATIVE STUDY OF THE EFFECT ON THE NEURO-ENDOCRINE-IMMUNE COMPLEX AND METABOLISM OF DRINKING MONOTHERAPY WITH “NAFTUSYA” WATER FOUNDATION AND SUPPLEMENTARY 8.1. Discriminant analysis of balneoeffects on the autonomic nervous, endocrine and immune systems and metabolism 157 8.2. Modeling of partial effects of mineral waters on the autonomic nervous, endocrine and immune systems and metabolism 164 8.3. Discriminant analysis of balneoeffects on the EEG 166 8.4. Modeling of partial effects of mineral waters on electroencephalogram 173 8.5. Discriminant analysis of balneoeffects on neuroendocrine-immune complex and metabolism 174 8.6. Modeling of partial effects of mineral waters on the neuro-endocrine-immune complex and metabolism 181 SECTION 9 SPECIFIC BALNEOEFFECTS OF MYROSLAVA AND CHRISTINA MINERAL WATERS 9.1. Screening of parameters whose changes are different under the influence of two balneotherapy regimens 184 9.2. Discriminant analysis of specific balneoeffects 185 9.3. Canonical analysis of the neuro-endocrine mechanism of specific balneological effects 192 REFERENCES 198 INFORMATION ABOUT THE AUTHORS 213 RESUME Priority experimental and clinical-physiological study of the influence of newly created sulfate-chloride sodium-magnesium mineral waters "Myroslava" (5 g / l) and "Khrystyna" (10 g / l) of Truskavets resort on neuro-endocrine regulation, metabolism, cholekinetics and cholekinetics healthy rats and patients of the resort in the process of restorative treatment of chronic pyelonephritis and cholecystitis in remission. In line with the concepts of functional-metabolic continuum and neuroendocrine-immune complex using discriminant and canonical correlation analyzes, it is demonstrated that mineral waters have both similar and specific physiologically favorable modulating effects on the parameters of the studied body systems. An experiment on 50 healthy female rats divided into 4 groups (intact, control tap and two main) showed that both mineral waters consumed for 6 days were equally effective in preventing aversion stress-induced increase in glomerular adrenal cortex thickness and non-adrenal mineralocorticoid activity, as well as glycemia and amylasuria, thymus mass and content in the thymocytogram of endothelial cells and macrophages in the splenocytogram and phagocytic index of blood neutrophils. Significantly increased levels of testosterone and plasma catalase, thymocytogram plasma cells and immunocytogram entropy under the influence of mineral waters are reduced to the upper zone of normal due to stress. On the other hand, both mineral waters equally prevent stress-induced decrease in adrenal reticular thickness, triiodothyronemia, parathyroid activity, calciumemia, urinary excretion of sodium and chloride, urinary concentrations of malonic dialdehyde, and relative activity in blood and monocyte. intensity of phagocytosis by bacterial monocytes. However, differences in the integrated effects of mineral waters were identified. Myroslava water deepens the stress-induced decrease in plasma corticosterone levels, erythrocyte superoxide dismutase activity, lymphoblast content in thymocytogram, splenocytogram plasma cells and spleen mass, and total leukocytes in in blasts under the influence of PHA. On the other hand, Khrystyna water does not affect this constellation of parameters. Stress-insensitive parameters (amylasemia, erythrocyte natrigy, magniuria, lymphoblast and reticulocyte content in the splenocytogram, T-cytolytic lymphocyte content in the immunocytogram, and the neutrophil-killing index parameters. In contrast, Myroslava water, in contrast to Khrystyna water, initiates an increase in the entropy of the leukocytogram and thymocytogram, the content of epitheliocytes, macrophages and reticulocytes in the thymocytogram, as well as eosinophils in the splenocytogram and natural killers in the blood. In the clinical and physiological observation of 34 men with chronic pyelonephritis and cholecystitis in remission, who received three options for drinking balneotherapy (only bioactive water "Naftusya"; water "Naftusya" in combination with mineral water "Myroslava" or "Christina”), the same physiologically favorable changes were revealed: a) electroencephalogram parameters: increase within the norm of initially normal levels of spectral power density (BMD) of beta rhythm in loci Fp2 and T4, theta rhythm in locus F7 and entropy of SHSP in locus T5 in combination with decrease within normal normal levels of SHSP and entropy at the Fp2 locus, as well as the left-hand shift of initially symmetric theta and beta rhythms; b) normalization of moderately elevated plasma testosterone levels; c) metabolic parameters: increase in moderately increased daily diuresis, transfer of phosphaturia from the lower normal zone to the upper, reduction of hypocreatininuria and hypercreatininemia, decrease within the normal concentration of sodium in the urine; d) immune parameters: increase to the lower zone of the norm of reduced bactericidal neutrophils against Staphylococcus aureus and Escherichia coli and increase the normal level of serum IgG; e) increase to the lower zone of the norm of reduced content in the feces of lactic acid Bifidobacter and Lactobacillus in combination with a decrease in the increased content of the strain Escherichia coli with weakened enzymatic activity, ie reduction of dysbacteriosis; e) reduction of moderate bacteriuria; g) normalization of reduced gallbladder reactivity to standard cholekinetics. Complex balneotherapy by interval use of sulfate-magnesium mineral water together with Naftusya water causes significant changes in the constellation of neuroendocrine, metabolic and immune parameters, which are different from the effects of monotherapy with Naftusya water. In particular, initially reduced neuro-endocrine (VLF and ULF bands HRV, calcitonin, triiodothyronine, aldosterone), metabolic (urinary concentrations of phosphates, calcium, magnesium and creatinine, phosphaturia, potassium, calciumemia and cholecystokinetic activity and cholecystokinetic activity staphylococci grow, as a rule, to the zone of norm. On the other hand, initially increased urinary excretion and sodium concentration and plasma creatinine and urea levels are reduced. However, there is an increase in initially normal levels of vagal tone, parathyroid activity, plasma testosterone, excretion of magnesium and chloride and plasma interleukins 1 and 6, as well as a decrease in initially normal levels of uric acid in urine and glucose and cholesterol and low lipoprotein cholesterol. , as well as the intensity of phagocytosis of Staphylococcus aureus. The latter pattern is formed by initially reduced levels of sodium, phosphate and plasma chloride, chloride and potassium of urine, as well as active T-lymphocytes, which continue to decline. EEG analysis revealed two patterns of multidirectional neurotropic effects of mineral waters. The first pattern reflects a more or less pronounced activation of generating delta-rhythm neurons projected on loci O2 and F7, alpha-rhythm of generating neurons projected on loci P3, F4, T4 and C3 and beta-rhythm of generating neurons projected on loci F8, Fp2 and F4, as well as the right shift of symmetry of beta and alpha rhythms. Instead, the pattern antipode reflects the inhibition of the delta-rhythm of generating neurons projected at loci T5, P3, C4, and F8, the alpha-rhythm of generating neurons projected at locus F8, and the theta-rhythm of generating neurons projected at loci T2 , F7, F8, O2 and T4, as well as the left shift of symmetry of theta rhythm and decrease the entropy of the EEG at loci T5, T4, O2, T6, P3 and F7. Screening of differences in balneal effects of mineral waters revealed 37 parameters grouped into 5 patterns. The first pattern combines 11 parameters that decrease under the influence of Myroslava water and increase under the influence of Khrystyna water. In particular, it is the beta-rhythm of the beta-rhythm in the loci Fp1, F4, F8, C4, T6 and O2, as well as the LF of the HRV range; diastolic but not systolic blood pressure; plasma aldosterone, potassium excretion and relative monocytes in the blood. Regarding the other 7 parameters of the second pattern (T5-β and F4-α; sodium and plasma chloride; active blood T-lymphocytes, as well as both variants of Popovich's leukocyte stress index), Myroslava water works similarly, while Khrystyna water is ineffective. . Both mineral waters have a stimulating effect on 8 parameters, while Myroslava is inferior to Khrystyna. In particular, it is diuresis and urinary excretion of creatinine, uric acid and magnesium; serum IgG level, completion of E. coli phagocytosis by blood neutrophils; the content in the feces of a common strain of E. coli, as well as cholecystokinetic index. It should be noted that the content in the feces of E. coli strains with hemolytic and impaired enzymatic ability, as well as Klebsiela & Proteus is reduced to the same extent. Myroslava water has a stimulating effect on 9 parameters of the fourth pattern, while Khrystyna water has a braking effect. In particular, it is the delta rhythm RMS in loci Fp1, F4, C3 and C4, as well as the VLF component of HRV and the vegetative Kerdio index; serum cortisol and IgM levels. Finally, sodium excretion and leukocyturia decrease under the influence of both mineral waters, but to a greater extent under the influence of water “Christina". Thus, Myroslava and Khrystyna mineral waters have both similar and different effects on the body. It is important that the differences are manifested not only in the severity of changes in the registered parameters, but also in their direction. Since the chemical composition of both mineral waters is qualitatively identical, the difference in physiological effects is obviously due to their total mineralization (5 g / l and 10 g / l, respectively). In addition, it should be borne in mind that patients used these waters in combination with biologically active water "Naftusya". However, the specificity of physiological effects was confirmed in an experiment on rats. Based on previous research of Truskavets Scientific School of Balneology, the authors put forward and confirmed the hypothesis that the primary effect of mineral waters is to modulate the activity of the autonomic and central nervous and endocrine systems, which in turn have regulatory modulating effects on the immune system, microbio metabolism, cholekinetics, blood pressure and, apparently, other, not yet registered parameters of the body. The materials of the monograph are reflected in the following publications 1. Hrytsak MV, Barylyak LG, Usyns’kyi RS, Mysula IR. Endocrine and metabolic effects of sulfate chloride sodium-magnesium mineral waters "Myroslava" and "Khrystyna" of Truskavets ’spa in healthy female rats. In: Proceedings of the XII All-Ukrainian scientific-practical conference "Topical issues of pathology under the influence of extraordinary factors on the body". Galician Readings II (Ternopil ’, October 29-30, 2020). Ternopil '; 2020: 125-127. 2. Mel’nyk OI, Zukow W, Hrytsak MV, Popovych DV, Zavidnyuk YV, Bilas VR, Popovych IL. Canonical analysis of neuroendocrine-metabolic and neuroendocrine-immune relationships at female rats. Journal of Education, Health and Sport. 2021; 11 (5): 356-369. 3. Hrytsak MV, Popovych DV, Badiuk NS, Hrytsan II, Zukow W. Similar neuroendocrine and metabolic effects of sulfate-chloride sodium-magnesium mineral waters "Myroslava" and "Khrystyna" of Truskavets ’spa in healthy female rats. Journal of Education, Health and Sport. 2021; 11 (6): 320-334. 4. Hrytsak MV, Popovych DV, Badiuk NS, Hrytsan II, Zukow W. Peculiaritias of neuroendocrine and metabolic effects of sulfate-chloride sodium-magnesium mineral waters "Myroslava" and "Khrystyna" of Truskavets ’spa in healthy female rats. Journal of Education, Health and Sport. 2021; 11 (9): 862-875. 5. Badiuk NS, Popovych DV, Hrytsak MV, Ruzhylo SV, Zakalyak NR, Kovalchuk GY, Mel'nyk OI, Zukow X. Similar and specific immunotropic effects of sulfate-chloride sodium-magnesium mineral waters "Myroslava" and "Khrystyna" of Truskavets' spa in healthy female rats. Journal of Education, Health and Sport. 2021; 11 (11): 314-353. 6. Popovych DV, Badiuk NS, Hrytsak MV, Ruzhylo SV, Mel’nyk OI, Zukow X. Sulfate-chloride sodium-magnesium mineral waters modulate neuroendocrine-immune complex and metabolism in healthy female rats. Journal of Education, Health and Sport. 2021; 11 (12): 455-466. 7. Hrytsak MV, Popovych DV, Badiuk NS, Hrytsan II, Zukow X. Comparative study of the effect on the neuroendocrine-immune complex and metabolism of drinking monotherapy with Naftussya water and therapy supplemented with “Myroslava” and “Khrystyna” mineral waters. Journal of Education, Health and Sport. 2022; 12 (1): 355-367. 8. Popovych IL, Gozhenko AI, Hrytsak MV, Popovych DV, Korolyshyn TA, Kovbasnyuk MM, Zukow W. General non-specific effects of balneofactors of Truskavets' spa on parameters of neuroendocrine regulation, metabolism, immunity and microbiota in patients with chronic pyelonephritis and cholecystitis. Journal of Education, Health and Sport. 2022; 12 (1): 368-384. 9. Hrytsak MV, Popovych DV, Badiuk NS, Hrytsan II, Zukow X. Comparative study of the effects on the EEG of drinking monotherapy with Naftussya water and therapy supplemented with “Myroslava” and “Khrystyna” mineral waters. Journal of Education, Health and Sport. 2022; 12 (2): 141-150. 10. Gozhenko AI, Hrytsak MV, Popovych DV, Badiuk NS, Zukow X. “Myroslava” and “Khrystyna” drinking mineral waters modulate the state of neuroendocrine-immune complex and metabolism in patients of Truskavets ’spa. Journal of Education, Health and Sport. 2022; 12 (3): 11-23. 11. Hrytsak MV, Popovych DV, Ruzhylo SV, Zakalyak NR, Zukow W. Neuro-endocrine mechanism of specific balneoeffects of sulfate-chloride sodium-magnesium mineral waters. Journal of Education, Health and Sport. 2022; 12 (3): 274-282. МІНІСТЕРСТВО ОХОРОНИ ЗДОРОВ’Я УКРАЇНИ ДУ УКРАЇНСЬКИЙ НАУКОВО-ДОСЛІДНИЙ ІНСТИТУТ МЕДИЦИНИ ТРАНСПОРТУ ДНЗ ТЕРНОПІЛЬСЬКИЙ НАЦІОНАЛЬНИЙ МЕДИЧНИЙ УНІВЕРСИТЕТ ІМ. І.Я. ГОРБАЧЕВСЬКОГО УНІВЕРСИТЕТ ІМ. М. КОПЕРНИКА, ТОРУНЬ, ПОЛЬЩА М.В. ГРИЦАК Н.С. БАДЮК |
