Search

LITERATURE 1. Avtandylov H.G. Medical morphometry. Moscow. Medicine; 1990: 384 p. 2. Baevsky R.M., Kirillov O.I., Kletskin S.Z. Mathematical analysis of heart rate changes during stress. Moscow. Science; 1984: 221 p. 3. Baevsky R.M., Ivanov H.G. Variability of the heart rhythm: theoretical aspects and opportunities for clinical application. Ultrasound and functional diagnostics. 2001; 3: 106-127. 4. Bazarnova M.A. Cytological examination of punctate spleen. Guide to practical classes in clinical laboratory diagnostics. K.: Higher school; 1988: 263-264. 5. Balanovsky V.P., Popovych I.L., Karpynets SV. About the ambivalent-equilibrator nature of the influence of Naftusya medicinal water on the human body. ANU reports. Mat., prop., tech. science 1993; 3: 154-158. 6. Belousova OI, Fedotova MY. Comparative data on changes in the number of lymphocytes of the spleen, goiter and bone marrow in the early stages after irradiation in a wide range of doses. Radiobiology-radiotherapy. 1968; 9(3): 309-313. 7. Bilas V.R., Popovych I.L. The role of microflora and organic substances of Naftusya water in its modulating effect on the neuroendocrine-immune complex and metabolism. Medical hydrology and rehabilitation. 2009; 7(1): 68-102. 8. Biloshitsky P.V. Temperature, information, water, anabiosis, immortality. Health and longevity. Kyiv; 2007: 46-47. 9. Harkavy L.H., Kvakina E.B., Kuzmenko T.S. Antistress reactions and activating therapy. Moscow. Imedis; 1998: 654 p. 10. Harkavy L.H., Kvakina E.B., Ukolova M.A. Adaptation reactions and resistance of the body. Rostov-on-Don. Rostov University Publishing House, 3rd ed.; 1990: 224 p. 11. Harkavy L.H., Romasyuk S.I., Barantsev F.G., Kuzmenko T.S., Otkydach S.A., Tattsov O.V., Barantseva L.P. Activation therapy in the sanatorium-resort stage of rehabilitation of patients with internal organ diseases. Sochi; 2000: 94 p. 12. Gozhenko A.I. Theory of disease. Odesa. Phoenix; 2018: 236 p. 13. Gozhenko A.I. Dysregulation as the basis of the pathophysiology of homeostasis. Clinical and experimental pathology. 2004; 3 (2): 191-193. 14. Gozhenko A.I. Functional-metabolic continuum. The National Academy of Sciences of Ukraine. 2016; 22(1): 3-8. 15. Gozhenko A.I., Korda M.M., Popadynets O.O., Popovych I.L. Entropy, harmony, synchronization and their neuro-endocrine-immune correlates. Odesa. Phoenix; 2021: 232 p. 16. Horyachkovsky A.M. Clinical biochemistry. Odesa: Astroprint; 1998: 608 p. 17. Datsko O.R., Bubnyak A.B., Ivasivka S.V. The organic component of Naftusya mineral water. Development of an idea about its composition and origin. Medical hydrology and rehabilitation. 2008; 6(1): 168-174. 18. Ivasivka S.V., Popovych I.L., Aksentiychuk B.I., Flunt I.S. Physiological activity of uric acid and its role in the mechanism of action of Naftusya water. K. Computer Press; 2004: 163 p. 19. Lapovets L.Y., Lutsik B.D. Laboratory immunology. Kyiv. 2004. 173 p. 20. Perederiy V.G., Zemskov A.M., Bychkova N.G., Zemskov V.M. Immune status, principles of its evaluation and correction of immune disorders. K. Health; 1995: 211 p. 21. Popovych I.L. Informational effects of Naftusya bioactive water in rats: modulation of entropy, reversal of desynchronizing and limitation of disharmonizing effect of water-immersion stress on informational components of the neuro-endocrine-immune system and metabolism, which correlates with a gastroprotective effect. Medical hydrology and rehabilitation. 2007; 5(3): 50-70. 22. I.L. Popovych Concept of neuro-endocrine-immune complex. Medical hydrology and rehabilitation. 2009; 7(2): 9-18. 23. I.L. Popovych Stress-limiting adaptogenic mechanism of biological and therapeutic activity of Naftusya water. Kyiv. Computer press; 2011: 300 c. 24. Popovich I.L., Flunt I.S., Alekseev O.I. etc. Sanogenetic principles of rehabilitation at the Truskavets resort of urological patients of the Chernobyl contingent. Kyiv. Computer press; 2003: 192 p. 25. Popovich I.L., Flunt I.S., Nischeta I.V., Loboda M.V., Aksentiychuk B.I., Pryima B.G., Tserkovnyuk R.G. General adaptation reactions and resistance of the organism of liquidators of the Chernobyl accident. Kyiv. Computer press; 2000: 117 p. 26. Portnychenko A.G. Ukrainian balneology: scientific trends of the last decade (scientometric analysis). Medical hydrology and rehabilitation. 2015; 13(4): 41-52. 27. Smagliy V.S., Gozhenko A.I., Badyuk N.S., Popovych I.L. Variants of uric acid metabolism and their immune and microbial accompaniments in patients with complex neuro-endocrine-immune dysfunction. In: VIII National Congress of Pathophysiologists of Ukraine "Pathological Physiology - Health Care of Ukraine" (Odesa, May 13-15, 2020). Odesa; 2020: 314-315. 28. Khaitov R.M., Pinegin B.V., Istamov K.I. Ecological immunology. Moscow. INWARD; 1995: 219 p. 29. Khmelevsky Yu.V., Usatenko O.K. Basic biochemical constants of a person in normal and pathological conditions. Kyiv. Health; 1987: 160 p. 30. Efroimson V.P. Some biological factors of mental activity. VIET. 1987; 4: 74-84. 31. Yushkovska O.H. The use of information theory to study the adaptive reactions of athletes' bodies. Medical rehabilitation Spa therapy Physiotherapy. 2001; 1 (25): 40-43. 32. Abdel Aziz N., Tallima H., Hafez E.A., El Ridi R. Papain-based vaccination modulates Schistosoma mansoni infection-induced cytokine signals. Scand J Immunol. 2016;83(2):128–138. 33. Ahbap E., Sakaci T., Kara E., Sahutoglu T., Koc Y., Basturk T. Serum uric acid levels and inflammatory markers with respect to dipping status: a retrospective analysis of hypertensive patients with or without chronic kidney disease . Clin Exp Hypertens. 2016;38(6):555–563. 34. Akbar S.R., Long D.M., Hussain K., Alhajhusain A., Ahmed U.S., Iqbal H.I. Hyperuricemia: an early marker for severity of illness in sepsis. Int J Nephrol. 2015; 301021. 35. Alberti K.G., Eckel R.H., Grundy S.M., Zimmet P.Z., Cleeman J.I., Donato K.A. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; american heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation. 2009;120(16):1640–1645. 36. Aldenderfer M.S., Blashfield R.K. Cluster analysis (Second printing, 1985) [transl. from English in Russian]. In: Factor, Discriminant and Cluster Analysis. Moscow. Finance and Statistics; 1989: 139-214. 37. Alvarez-Lario B., Macarrón-Vicente J. Is there anything good in uric acid? QJM. 2011;104(12):1015–1024.] 38. Alvarez-Lario B., Macarron-Vicente J. Uric acid and evolution. Rheumatology. 2010;49(11):2010–2015. 39. Amaral F.A., Costa V.V., Tavares L.D., Sachs D., Coelho F.M., Fagundes C.T. NLRP3 inflammasome-mediated neutrophil recruitment and hypernociception depend on leukotriene B(4) in a murine model of gout. Arthritis Rheum. 2012;64(2):474–484. 40. Amaral K.B., Silva T.P., Malta K.K., Carmo L.A.S., Dias F.F., Almeida M.R. Natural Schistosoma mansoni infection in the wild reservoir Nectomys squamipes leads to excessive lipid droplet accumulation in hepatocytes in the absence of liver functional impairment. Plos One. 2016;11(11):e0166979. 41. Amaral L.M., Cunningham M.W., Jr, Cornelius D.C., LaMarca B. Preeclampsia: long-term consequences for vascular health. Vasc Health Risk Manage. 2015; 11: 403–415. 42. Ames B.N., Cathcart R., Schwiers E., Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A. 1981;78(11):6858–6862. 43. Amsellem V., Abid S., Poupel L., Parpaleix A., Rodero M., Gary-Bobo G., Latiri M., Dubois-Rande J.L., Lipskaia L., Combadiere C., et al. Roles for the CX3CL1/CX3CR1 and CCL2/CCR2 Chemokine Systems in Hypoxic Pulmonary Hypertension. Am. J. Respir. Cell. Mol. Biol. 2017; 56:597–608. 44. Ando K., Takahashi H., Watanabe T., Daidoji H., Otaki Y., Nishiyama S. Impact of serum uric acid levels on coronary plaque stability evaluated using integrated backscatter intravascular ultrasound in patients with coronary artery disease. J Atheroscler Thromb. 2016;23(8):932–939. 45. Andreadou E., Nikolaou C., Gournaras F., Rentzos M., Boufidou F., Tsoutsou A. Serum uric acid levels in patients with Parkinson's disease: their relationship to treatment and disease duration. Clin Neurol Neurosurg. 2009;111(9):724–728. 46. Annanmaki T., Muuronen A., Murros K. Low plasma uric acid level in Parkinson's disease. Mov Disord. 2007;22(8):1133–1137. 47. Anthony R.M., Rutitzky L.I., Urban J.F., Jr., Stadecker M.J., Gause W.C. Protective immune mechanisms in helminth infection. Nat Rev Immunol. 2007;7(12):975–987. Review. 48. Anzai N., Ichida K., Jutabha P., Kimura T., Babu E., Jin C.J. Plasma urate level is directly regulated by a voltage-driven urate efflux transporter URATv1 (SLC2A9) in humans. J Biol Chem. 2008;283(40):26834–26838. 49. Apasov S, Chen JF, Smith P, Sitkovsky M. A2A receptor dependent and A2A receptor independent effects of extracellular adenosine on murine thymocytes in the condition of adenosine deaminase deficiency. Blood. 2000; 95(12): 3859-3867. 50. Araya J., Rodrigo R., Videla L.A., Thielemann L., Orellana M., Pettinelli P. Increase in long-chain polyunsaturated fatty acid n - 6/n - 3 ratio in relation to hepatic steatosis in patients with non- alcoholic fatty liver disease. Clin Sci (Lond) 2004;106(6):635–643. 51. Aribas A., Kayrak M., Ulucan S., Keser A., Demir K., Alibasic H. The relationship between uric acid and erectile dysfunction in hypertensive subjects. Blood Press. 2014;23: 370–376. 52. Arvola L, Bertelsen G, Hassaf D, Ytrehus K. Positive inotropic and sustained anti-beta-adrenergic effect of diadenosine pentaphosphate in human and guinea pig hearts. Role of dinucleotide receptors and adenosine receptors. Acta Physiol Scand. 2004;182(3):277-285. 53. Arnold I.C., Mathisen S., Schulthess J., Danne C., Hegazy A.N., Powrie F. CD11c(+) monocyte/macrophages promote chronic Helicobacter hepaticus-induced intestinal inflammation through the production of IL-23. Mucosal Immunol. 2016; 9:352–363. 54. Auerbach A. Dose-ResponseAnalysis When There Is a Correlation between Affinity and Efficacy. Mol. Pharmacol. 2016; 89:297–302. 55. Babio N., Martínez-González M.A., Estruch R., Wärnberg J., Recondo J., Ortega-Calvo M. Associations between serum uric acid concentrations and metabolic syndrome and its components in the PREDIMED study. Nutr Metab Cardiovasc Dis. 2015;25(2):173–180. 56. Bakhtiari S., Toosi P., Samadi S., Bakhshi M. Assessment of uric acid level in the saliva of patients with oral lichen planus. Med Princ Pract. 2017;26(1):57–60. 57. Barabé F, Gilbert C, Liao N, Bourgoin SG, Naccache PH. Crystal-induced neutrophil activationVI. Involvement of FcgammaRIIIB (CD16) and CD11b in response to inflammatory microcrystals. FASEB J. 1998;12(2):209-220. doi:10.1096/fasebj.12.2.209 58. Barakat R., Abou El-Ela N.E., Sharaf S., El Sagheer O., Selim S., Tallima H. Efficacy and safety of arachidonic acid for treatment of school-age children in Schistosoma mansoni high-endemic regions. Am J Trop Med Hyg. 2015;92(4):797–804. 59. Bardin T., Richette P. Definition of hyperuricemia and gouty conditions. Curr. Opin. Rheumatol. 2014;26: 186–191. 60. Barikbin B., Yousefi M., Rahimi H., Hedayati M., Razavi S.M., Lotfi S. Antioxidant status in patients with lichen planus. Clin Exp Dermatol. 2011;36(8):851–854. 61. Bartáková V., Kuricová K., Pácal L., Nová Z., Dvořáková V., Švrčková M. Hyperuricemia contributes to the faster progression of diabetic kidney disease in type 2 diabetes mellitus. J Diabetes Complications. 2016;30(7):1300–1307. 62. Barylyak L.G., Malyuchkova R.V., Tolstanov O.B., Tymochko O.B., Hryvnak R.F., Uhryn M.R. Comparative estimation of informativeness of leukocytary index of adaptation by Garkavi and by Popovych. Medical Hydrology and Rehabilitation. 2013; 11(1): 5-20. 63. Basseville A., Bates S. Gout, genetics and ABC transporters. F1000 Biology Reports. 2011;3: 23. 64. Beck L.H. Requiem for gouty nephropathy. Kidney Int. 1986;30(2):280–287. 65. Becker B.F. Towards the physiological function of uric acid. Free Radical Biol Med. 1993;14(6):615–631. 66. Bellomo G., Venanzi S., Verdura C., Saronio P., Esposito A., Timio M. Association of uric acid with changes in kidney function in healthy normotensive individuals. Am J Kidney Dis. 2010;56(2):264–272. 67. Berntson GG, Bigger JT jr, Eckberg DL, Grossman P, Kaufman PG, Malik M, Nagaraja HN, Porges SW, Saul JP, Stone PH, Van der Molen MW. Heart Rate Variability: Origins, methods, and interpretive caveats. Psychophysiology. 1997; 34: 623-648. 68. Bianco C. Population of lymphocytes bearing a membrane receptor for antigen-antibody complex. J Exp Med. 1970; 134(4): 702-720. 69. Bjorkander S., Heidari-Hamedani G., Bremme K., Gunnarsson I., Holmlund U. Peripheral monocyte expression of the chemokine receptors CCR2, CCR5 and CXCR3 is altered at parturition in healthy women and in women with systemic lupus erythematosus. Scand. J. Immunol. 2013;77: 200–212. 70. Birch RE, Rosenthal AK, Polmer SH. Pharmacological modification of immunoregulatory T lymphocytes. II. Modulation of T lymphocyte cell surface characteristics. Clin Exp Immunol. 1982; 48(1): 231-238. 71. Bjornstad P., Lanaspa M.A., Ishimoto T., Kosugi T., Kume S., Jalal D. Fructose and uric acid in diabetic nephropathy. Diabetology. 2015;58(9):1993–2002. 72. Bjornstad P., Maahs D.M., Johnson R.J., Rewers M., Snell-Bergeon J.K. Estimated insulin sensitivity predicts regression of albuminuria in Type 1 diabetes. Diabetes Med. 2015;32(2):257–261. 73. Bjornstad P., Roncal C., Milagres T., Pyle L., Lanaspa M.A., Bishop F.K. Hyperfiltration and uricosuria in adolescents with type 1 diabetes. Pediatr Nephrol. 2016;(5):787–793. 74. Bjornstad P., Snell-Bergeon J.K., McFann K., Wadwa R.P., Rewers M., Rivard C.J. Serum uric acid and insulin sensitivity in adolescents and adults with and without type 1 diabetes. J Diabetes Complications. 2014;28(3):298–304. 75. Bobulescu I.A., Moe O.W. Renal transport of uric acid: evolving concepts and uncertainties. Adv Chronic Kidney Dis. 2012;19(6):358–371. 76. Bocarsly M.E., Powell E.S., Avena N.M., Hoebel B.G. High-fructose corn syrup causes characteristics of obesity in rats: increased body weight, body fat and triglyceride levels. Pharmacol Biochem Behav. 2010;97: 101–106. 77. Broz P., Dixit V.M. Inflammasomes: mechanism of assembly, regulation and signaling. Nat Rev Immunol. 2016;16(7):407–420. 78. Bruno C.M., Pricoco G., Cantone D., Elisa Marino E., Bruno F. Tubular handling of uric acid and factors influencing its renal excretion: a short review. EMJ Nephrol. 2016;4(1):92–97. 79. Busso N., Ea H.K. The mechanisms of inflammation in gout and pseudogout (CPP-induced arthritis) Rheumatismo. 2012;63(4):230–237. 80. Busso N., So A. Mechanisms of inflammation in gout. Arthritis Res Ther. 2010;12(2):206. 81. Busso N., So A. Microcrystals as DAMPs and their role in joint inflammation. Rheumatology (Oxford) 2012;51(7):1154–1160. 82. Cammalleri L., Malaguarnera M. Rasburicase represents a new tool for hyperuricemia in tumor lysis syndrome and in gout. International Journal of Medical Sciences. 2007;4(2):83–93. doi: 10.7150/ijms.4.83. 83. Campion E.W., Glynn R.J., DeLabry L.O. Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study. Am J Med. 1987; 82:421. 84. Carito V., Ceccanti M., Tarani L., Ferraguti G., Chaldakov G. N., Fiore M. Neurotrophins' modulation by olive polyphenols. Current Medicinal Chemistry. 2016;23(28):3189–3197. 85. Carvalho LAC, Lopes JPPB, Kaihami GH, Silva RP, Bruni-Cordoso A, Baldini RL, Meotti FC. Uric acid disrupts hypochlorous acid production and bactericidal activity of HL-60 cells. Redox Biology. 2018; 16: 179-188. 86. Chakraborti G., Biswas R., Chakraborti S., Sen P.K. Altered serum uric acid level in lichen planus patients. Indian J Dermatol. 2014;59(6):558–561. 87. Chang B.S. Ancient insights into uric acid metabolism in primates. Proc Natl Acad Sci USA. 2014;111(10):3657–3658. 88. Chaudhary K., Malhotra K., Sowers J., Aroor A. Uric Acid - key ingredient in the recipe for cardiorenal metabolic syndrome. Cardiorenal Med. 2013;3(3):208–220. 89. Chen CJ, Shi Y, Hearn A, et al. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Invest. 2006;116(8):2262-2271. 90. Chen H., Cao G., Chen D. Q., et al. Metabolomics insights into activated redox signaling and lipid metabolism dysfunction in chronic kidney disease progression. Redox Biology. 2016; 10:168–178. 91. Chen Y., Xu B., Sun W., Sun J., Wang T., Xu Y. Impact of the serum uric acid level on subclinical atherosclerosis in middle-aged and elderly Chinese. J Atheroscler Thromb. 2015;22(8):823–832. 92. Chen-Xu M., Yokose C., Rai S.K., Pillinger M.H., Choi H.K. Contemporary Prevalence of Gout and Hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 2007–2016. Arthritis Rheumatol. 2019; 71:991–999. 93. Cheung K.J., Tzameli I., Pissios P., Rovira I., Gavrilova O., Ohtsubo T. Xanthine oxidoreductase is a regulator of adipogenesis and PPARγ activity. Cell Metab. 2007; 5:115–128. 94. Cheungpasitporn W., Thongprayoon C., Harrison A.M., Erickson S.B. Admission hyperuricemia increases the risk of acute kidney injury in hospitalized patients. Clin Kidney J. 2016;9(1):51–56. 95. Chiquete E., Ruiz-Sandoval J.L., Murillo-Bonilla L.M., Arauz A., Orozco-Valera D.R., Ochoa-Guzmán A. Serum uric acid and outcome after acute ischemic stroke: PREMIER study. Cerebrovasc Dis. 2013;35(2):168–174. 96. Cho J., Kim C., Kang D.R., Park J. Hyperuricemia and uncontrolled hypertension in treated hypertensive patients: K-MetS study. Medicine (Baltimore) 2016;95(28): e4177. 97. Choi H.K., Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation. 2007;116(8):894–900. 98. Choi H.K., Ford E.S. Prevalence of the metabolic syndrome in individuals with hyperuricemia. Am J Med. 2007;120(5):442–447. 99.Choi Y.J., Shin H.S., Choi H.S., Park J.W., Jo I., Oh E.S. Uric acid induces fat accumulation via generation of endoplasmic reticulum stress and SREBP-1c activation in hepatocytes. Lab Invest. 2014;94(10):1114–1125. 100.Chou Y.C., Kuan J.C., Yang T., Chou W.Y., Hsieh P.C., Bai C.H. Elevated uric acid level as a significant predictor of chronic kidney disease: a cohort study with repeated measurements. J Nephrol. 2015;28(4):457–462. 101. Cicerchi C., Li N., Kratzer J., Garcia G., Roncal-Jimenez C.A., Tanabe K. Uric acid-dependent inhibition of AMP kinase induces hepatic glucose production in diabetes and starvation: evolutionary implications of the uricase loss in hominids FASEB J. 2014;(8):3339–3350. 102. Cicero A., Rosticci M., Tartagni E., Parini A., Grandi E., D'Addato S. Serum uric acid level, but not renal function or arterial stiffness, is associated to worse blood pressure control in general practice : data from the brisighella heart study. J Hypertens. 2015;33(Suppl 1):e22. 103. Cicero A.F., Rosticci M., Fogacci F., Grandi E., D'Addato S., Borghi C. High serum uric acid is associated with poorly controlled blood pressure and higher arterial stiffness in hypertensive subjects. Eur J Intern Med. 2017;37: 38–42. 104. Cinel I, Gür S. Direct inotropic effects of propofol and adenosine on rat atrial muscle: possible mechanisms. Pharmacol Res. 2000;42(2):123-128. 105. Clarson L.E., Chandratre P., Hider S.L., Belcher J., Heneghan C., Roddy E. Increased cardiovascular mortality associated with gout: a systematic review and meta-analysis. Eur J Prev Cardiol. 2015;22(3):335–343. 106. Clémençon B., Lüscher B.P., Fine M., Baumann M.U., Surbek D.V., Bonny O. Expression, purification, and structural insights for the human uric acid transporter, GLUT9, using the Xenopus laevis oocytes system. PLoS ONE. 2014;9(10):e108852. 107. Cleophas M. C., Joosten L. A., Stamp L. K., Dalbeth N., Woodward O. M., Merriman T. R. ABCG2 polymorphisms in gout: insights into disease susceptibility and treatment approaches. Ph. DArmacogenomics and Personalized Medicine. 2017; 10:129–142. 108. Conen D, Wietlisbach V, Bovet P, Shamlaye C, Riesen W, Paccaud F, et al. Prevalence of hyperuricemia and relationship of serum uric acid with cardiovascular risk factors in a developing country. BMC public health. 2004; 4:9. 109. Convento M.S., Pessoa E., Dalboni M.A., Borges F.T., Schor N. Pro-inflammatory and oxidative effects of noncrystalline uric acid in human mesangial cells: contribution to hyperuricemic glomerular damage. Urol Res. 2011;39(1):21–27. 110.Cristóbal-García M., García-Arroyo F.E., Tapia E., Osorio H., Arellano-Buendía A.S., Madero M. Renal oxidative stress induced by long-term hyperuricemia alters mitochondrial function and maintains systemic hypertension. Oxid Med Cell Longev. 2015; 535686. 111. Culleton B.F., Larson M.G., Kannel W.B., Levy D. Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study. Ann Intern Med. 1999;131(1):7–13. 112. Dalbeth N., Merriman T. Crystal ball gazing: new therapeutic targets for hyperuricemia and gout. Rheumatology (Oxford). 2009;48(3):222–226. 113. De Cosmo S., Viazzi F., Pacilli A., Giorda C., Ceriello A., Gentile S. Serum uric acid and risk of CKD in Type 2 diabetes. Clin J Am Soc Nephrol. 2015;10(11):1921–1929. 114. De Duve C, Wattiaux R. Functions of lysosomes. Annu Rev Physiol. 1966; 28:435–492. 115. De Vera M., Rahman M.M., Rankin J., Kopec J., Gao X., Choi H. Gout and the risk of Parkinson's disease: a cohort study. Arthritis Rheum. 2008 Nov 15;59(11):1549–1554. 116. Deci M.B., Ferguson S.W., Scatigno S.L., Nguyen J. Modulating Macrophage Polarization through CCR2 Inhibition and Multivalent Engagement. Mol. Pharm. 2018; 15:2721–2731. 117. Dehghan A., van Hoek M., Sijbrands E.J., Hofman A., Witteman J.C. High serum uric acid as a novel risk factor for type 2 diabetes. Diabetes Care. 2008;31(2):361–362.] 118. Denoble A.E., Huffman K.M., Stabler T.V., Kelly S.J., Hershfield M.S., McDaniel G.E. Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation. Proc Natl Acad Sci USA. 2011;108(5):2088–2093. 119. Desaulniers P, Fernandes M, Gilbert C, Bourgoin SG, Naccache PH. Crystal-induced neutrophil activation. VII. Involvement of Syk in the responses to monosodium urate crystals. J Leukoc Biol. 2001;70(4):659-668. 120. Desaulniers P., Marois S., Paré G., Popa-Nita O., Gilbert C., Naccache P.H. Characterization of an activation factor released from human neutrophils after stimulation by triclinic monosodium urate crystals. J Rheumatol. 2006;33(5):928–938. 121. DiBianco J.M., Jarrett T.W., Mufarrij P. Metabolic syndrome and nephrolithiasis risk: should the medical management of nephrolithiasis include the treatment of metabolic syndrome? Rev. Urol. 2015;17(3):117–128. 122. Doehner W., Jankowska E.A., Springer J., Lainscak M., Anker S.D. Uric acid and xanthine oxidase in heart failure – emerging data and therapeutic implications. Int J Cardiol. 2016;15(213):15–19. 123. Dogan M., Uz O., Aparci M., Atalay M. Confounders of uric acid level for assessing cardiovascular outcomes. J Geriatr Cardiol. 2016;13(2):197–198. 124. Döring A., Gieger C., Mehta D., Gohlke H., Prokisch H., Coassin S. SLC2A9 influences uric acid concentrations with pronounced sex-specific effects. Nat Genet. 2008;40(4):430–436. 125. Douglas SD, Quie PG. Investigation of Phagocytes in Disease. Churchill; 1981: 110 p. 126. Drulović J., Dujmović I., Stojsavljević N., Mesaros S., Andjelković S., Miljković D. Uric acid levels in sera from patients with multiple sclerosis. J Neurol. 2001;248(2):121–126. 127. Eisen A., Benderly M., Goldbourt U., Haim M. Is serum uric acid level an independent predictor of heart failure among patients with coronary artery disease? Clin Cardiol. 2013;36(2):110–116. 128. Eisenbarth SC, Colegio OR, O'Connor W, Sutterwala FS, Flavell RA. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminum adjuvants. Nature. 2008; 453(7198): 1122-1126. 129. Ejaz A.A., Alquadan K.F., Dass B., Shimada M., Kanbay M., Johnson R.J. Effects of serum uric acid on estimated GFR in cardiac surgery patients: a pilot study. Am J Nephrol. 2015;42(6):402–409. 130. Ejaz A.A., Mu W., Kang D.H., Roncal C., Sautin Y.Y., Henderson G. Could uric acid have a role in acute renal failure? Clin J Am Soc Nephrol. 2007;2(1):16–21. 131. Ekici B., Kütük U., Alhan A., Töre H.F. The relationship between serum uric acid levels and angiographic severity of coronary heart disease. Kardiol Pol. 2015;73(7):533–538. 132. El Ridi R, Tallima H. Physiological functions and pathogenic potential of uric acid: A review. J Adv Res. 2017;8(5):487-493. 133. El Ridi R., Aboueldahab M., Tallima H., Salah M., Mahana N., Fawzi S. In vitro and in vivo activities of arachidonic acid against Schistosoma mansoni and Schistosoma haematobium. Antimicrob Agents Chemother. 2010;54(8):3383–3389. 134. El Ridi R., Tallima H. Vaccine-induced protection against murine schistosomiasis mansoni with larval excretory-secretory antigens and papain or type-2 cytokines. J Parasitol. 2013;99(2):194–202. 135. El Ridi R., Tallima H., Dalton J.P., Donnelly S. Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases. Front Genet. 2014; 5:19 a.m. 136. El Ridi R., Tallima H., Migliardo F. Biochemical and biophysical methodologies open the road for effective schistosomiasis therapy and vaccination. Biochim Biophys Acta. 2016;1861(1 Pt B):3613–3620. 137. El Ridi R., Tallima H., Salah M., Aboueldahab M., Fahmy O.M., Al-Halbosiy M.F. Efficacy and mechanism of action of arachidonic acid in the treatment of hamsters infected with Schistosoma mansoni or Schistosoma haematobium. Int J Antimicrobial Agents. 2012;39(3):232–239. 138. El Ridi R., Tallima H., Selim S., Donnelly S., Cotton S., Gonzales Santana B. Cysteine peptidases as schistosomiasis vaccines with inbuilt adjuvanticity. PLoS One. 2014;9(1): e85401. 139. Elmas O., Elmas O., Aliciguzel Y., Simsek T. The relationship between hypertension and plasma allantoin, uric acid, xanthine oxidase activity and nitrite, and their predictive capacity in severe preeclampsia. J Obstet Gynecol. 2016;36(1):34–38. 140. Enomoto A., Kimura H., Chairoungdua A., Shigeta Y., Jutabha P., Cha S.H. Molecular identification of a renal urate anion exchanger that regulates blood urate levels. Nature. 2002;417(6887):447–452. 141. Erdogan D., Gullu H., Caliskan M., Yildirim E., Bilgi M., Ulus T. Relationship of serum uric acid to measures of endothelial function and atherosclerosis in healthy adults. Int J Clin Pract. 2005;59(11):1276–1282. 142. Erdogan D., Tayyar S., Ali Uysal B.A., Icli A., Karabacak M., Ozaydin M. Effects of allopurinol on coronary microvascular and left ventricular function in patients with idiopathic dilated cardiomyopathy. Can J Cardiol. 2012; 28: 721–727. 143. Erkmen Uyar M., Sezer S., Bal Z., Guliyev O., Tutal E., Kulah E. Post-transplant Hyperuricemia as a Cardiovascular Risk Factor. Transplant Proc. 2015;47(4):1146–1151. 144. Facchini F.1., Chen Y.D., Hollenbeck C.B., Reaven G.M. Relationship between resistance to insulin-mediated glucose uptake, urinary uric acid clearance, and plasma uric acid concentration. JAMA. 1992;266(21):3008–3011. 145. Fajda OI, Hrinchenko BV, Snihur OV, Barylyak LG, Zukow W. What Kerdoe’s Vegetative Index really reflects? Journal of Education, Health and Sport. 2015; 5(12): 279-288. 146. Fajda OI, Drach OV, Barylyak LG, Zukow W. Relationships between Ca/K plasma ratio and parameters of Heart Rate Variability in patients with diathesis urica. Journal of Education, Health and Sport. 2016; 6(1): 295-301. 147. Fang P., Li X., Luo J.J., Wang H., Yang X.F. A double-edged sword: uric acid and neurological disorders. Brain Disord Ther. 2013;2(2):109. 148. Feig D.I., Johnson R.J. Hyperuricemia in childhood primary hypertension. Hypertension. 2003; 42:247–252. 149. Fessel W.J. Renal outcomes of gout and hyperuricemia. Am J Med. 1979; 67:74. 150. Ficociello L.H., Rosolowsky E.T., Niewczas M.A., Maselli N.J., Weinberg J.M., Aschengrau A. High-normal serum uric acid increases risk of early progressive renal function loss in type 1 diabetes: results of a 6-year follow-up. Diabetes Care. 2010;33(6):1337–1343. 151. Fiddis RW, Vlachos N, Calvert PD. Studies of urate crystallization in relation to gout. Ann Rheum Dis. 1983;42 Suppl 1(Suppl 1):12-15. 152. Fields TR, Abramson SB, Weissmann G, Kaplan AP, Ghebrehiwet B. Activation of the alternative pathway of complement by monosodium urate crystals. Clin Immunol Immunopathol. 1983;26(2):249-257. 153. Franchi L., Eigenbrod T., Muñoz-Planillo R., Nuñez G. The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol. 2009;10(3):241–247. 154. Freitas H.S., Anhê G.F., Melo K.F., Okamoto M.M., Oliveira-Souza M., Bordin S. Na(+)-glucose transporter-2 messenger ribonucleic acid expression in kidney of diabetic rats correlates with glycemic levels: involvement of hepatocyte nuclear factor-1alpha expression and activity. Endocrinology. 2008;149(2):717–724. 155.Gaipov A., Solak Y., Turkmen K., Toker A., Baysal A.N., Cicekler H. Serum uric acid may predict development of progressive acute kidney injury after open heart surgery. Ren Fail. 2015;37(1):96–102. 156. Galluzzi L., Vitale I., Aaronson S. A., et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death & Differentiation. 2018;25(3):486–541. 157. Gao L, Jiang Y, Wang Y, Qu X, Li L, Lou X, Wang Y, GuoW, Liu Y. Male asymptomatic hyperuticemia patients display a lower number of NKG2D+ NK cells before and after a low-purine diet. Medicine (Baltimore). 2018; 97(50): e13668. 158. Geraci G., Mulè G., Mogavero M., Geraci C., Nardi E., Cottone S. Association between uric acid and renal hemodynamics: pathophysiological implications for renal damage in hypertensive patients. J Clin Hypertens (Greenwich) 2016;18(10):1007–1014. 159. Gerryng Z., Pearson J.F., Morrin H.R., Robinson B.A., Harris G.C., Walker L.C. Phosphohistone H3 outperforms Ki67 as a marker of outcome for breast cancer patients. Histopathology. 2015;67(4):538–547. 160. Gertler M.M., Garn S.M., Levine S.A. Serum uric acid in relation to age and physique in health and in coronary heart disease. Ann Intern Med. 1951;34(6):1421–1431. 161. Ghaemi-Oskouie F, Shi Y. The role of uric acid as an endogenous danger signal in immunity and inflammation. Curr Rheumatol Rep. 2011;13(2):160-166. 162.Giallauria F., Predotti P., Casciello A., Grieco A., Russo A., Viggiano A. Serum uric acid is associated with non-dipping circadian pattern in young patients (30–40 years old) with newly diagnosed essential hypertension. Clin Exp Hypertens. 2016;38(2):233–237. 163. Gille C., Spring B., Tewes L., Poets C.F., Orlikowsky T. A new method to quantify phagocytosis and intracellular degradation using green fluorescent protein-labeled Escherichia coli: Comparison of cord blood macrophages and peripheral blood macrophages of healthy adults . Cytom. A. 2006; 69:152–154. 164. Givertz M.M., Anstrom K.J., Redfield M.M., Deswal A., Haddad H., Butler J. Effects of xanthine oxidase inhibition in hyperuricemic heart failure patients: the xanthine oxidase inhibition for hyperuricemic heart failure patients (EXACT-HF) study. Circulation. 2015;131(20):1763–1771. 165. Glantzounis G.K., Tsimoyiannis E.C., Kappas A.M., Galaris D.A. Uric acid and oxidative stress. Curr Pharm Des. 2005;11(32):4145–4151. 166. Gold M.J., Hiebert P.R., Park H.Y., Stefanowicz D., Le A., Starkey M.R. Mucosal production of uric acid by airway epithelial cells contributes to particulate matter-induced allergic sensitization. Mucosal Immunol. 2016;9(3):809–820. 167. Góth L. The rasburicase therapy may cause hydrogen peroxide shock. Orvosi Hetilap. 2008;149(34):1587–1590. 168. Gozhenko AI, Smagliy SS, Korda IV, Badiuk NS, Zukow W, Popovych IL. Functional relationships between parameters of uric acid exchange and immunity in female rats. Actual problems of transport medicine. 2019; 4 (54): 123–131. 169. Gozhenko AI, Smagliy SS, Korda IV, Badiuk NS, Zukow W, Popovych IL. Features of immune status in different states of uric acid metabolism in female rats. Journal of Education, Health and Sport. 2019; 9(12): 167-180. 170. Gozhenko AI, Smagliy SS, Korda IV, Zukow W, Popovych IL. Cluster analysis of uric acid exchange parameters in female rats. Journal of Education, Health and Sport. 2019; 9(11): 277-286. 171. Gozhenko AI, Smagliy VS, Korda IV, Badiuk NS, Zukow W, Kovbasnyuk MM, Popovych IL. relationships between parameters of uric acid exchange and immunity as well as microbiota in patients with neuroendocrine-immune complex dysfunction. Journal of Education, Health and Sport. 2020; 10(1): 165-175. 172. Gozhenko AI, Smagliy VS, Korda IV, Badiuk NS, Zukow W, Popovych IL. Functional relationships between parameters of uric acid exchange and immunity in female rats. In: Rehabilitation Medicine and Health-Resort Institutions Development. Proceedings of the 19th International Applied Research Conference (Kyiv, December 11-12, 2019). Edited by O. Gozhenko, W. Zukow. Toruń, Kyiv. 2019: 23-24. 173. Gozhenko AI, Sydoruk NO, Babelyuk VYe, Dubkowa GI, Flyunt VR, Hubyts'kyi VYo, Zukow W, Barylyak LG, Popovych IL. Modulating effects of bioactive water Naftussya from layers Truskavets' and Pomyarky on some metabolic and biophysical parameters in humans with dysfunction of neuro-endocrine-immune complex. Journal of Education, Health and Sport. 2016; 6(12): 826-842. 174. Gozhenko AI, Zukow W, Polovynko IS, Zajats LM, Yanchij RI, Portnichenko VI, Popovych IL. Individual Immune Responses to Chronic Stress and their Neuro-Endocrine Accompaniment. RSW. UMK. Radom. Torun; 2019: 200 p. 175. Grebe A., Hoss F., Latz E. NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis. Circ. Res. 2018; 122:1722–1740. 176. Greenberg K., McAdams-DeMarco MA, Köttgen A., Appel L.J., Coresh J., Grams ME. Plasma urate and risk of a hospital stay with AKI: the atherosclerosis risk in communityitis study. Clin J Am Soc Nephrol. 2015;10(5):776–783. 177. Gutman A. B. Significance of uric acid as a nitrogenous waste in vertebrate evolution. Arthritis & Rheumatism. 1965;8(4):614–626. 178. Gwang H.B., Yang J.H., Park T.K., Song Y.B., Hahn J.Y., Choi J.H., Lee J.H., Lee S.H., Gwon H.C., Choi S.H. Uric acid level has a U-shaped association with clinical outcomes in patients with vasospastic angina. J Korean Med Sci. 2017; 32(8): 1275-1280/ 179. Haig A. J, Churchill A. Uric acid as a factor in the causation of disease. London. 1897. 180. Hall AP, Barry PE, Dawber TR, McNamara PM. Epidemiology of gout and hyperuricemia. A long-term population study. Am J Med. 1967; 42:27. 181. Hammad H., Lambrecht B.N. Barrier epithelial cells and the control of type 2 immunity. Immunity. 2015;43(1):29–40. 182. Hara K., Iijima K., Elias M.K., Seno S., Tojima I., Kobayashi T. Airway uric acid is a sensor of inhaled proteaseallergens and initiates type 2 immune responses in respiratory mucosa. J Immunol. 2014;192(9):4032–4042. 183. Harada K., Ohira S., Isse K., Ozaki S., Zen Y., Sato Y., Nakanuma Y. Lipopolysaccharide activates nuclear factor-kappaB through toll-like receptors and related molecules in cultured biliary epithelial cells. Lab. Investig. 2003; 83:1657–1667. 184. Harambat J., Dubourg L., Ranchin B., Hadj-Aïssa A., Fargue S., Rivet C. Hyperuricemia after liver transplantation in children. Pediatr Transplant. 2008;12(8):847–853. 185. Haryono A., Nugrahaningsih D.A.A., Sari D.C.R., Romi M.M., Arfian N. Reduction of Serum Uric Acid Associated with Attenuation of Renal Injury, Inflammation and Macrophages M1/M2 Ratio in Hyperuricemic Mice Model. Kobe. J. Med. Sci. 2018;64: E107–E114. 186. He Y., Franchi L., Nunez G. TLR agonists stimulate Nlrp3-dependent IL-1beta production independently of the purinergic P2X7 receptor in dendritic cells and in vivo. J. Immunol. 2013;190: 334–339. 187. Hediger M.A., Johnson R.J., Miyazaki H., Endou H. Molecular physiology of urate transport. Physiology. 2005;20: 125–133. 188. Heesen M., Renckens R., de Vos A.F., Kunz D., van der Poll T. Human endotoxemia induces down-regulation of monocyte CC chemokine receptor 2. Clin. Vaccine. Immunol. 2006;13: 156–159. 189. Henaut L, Candellier A, Boudot S, Grissi M, Mentaverri R, Choukroun G, Brazier M, Kamel S, Massy ZA. New insights into the roles of monocytes/macrophages in cardiovascular calcification associated with chronic kidney disease. Toxins (Basel). 2019; 11(9): 529. 190. Hjortnaes J., Algra A., Olijhoek J., Huisman M., Jacobs J., van der Graaf Y. Serum uric acid levels and risk for vascular diseases in patients with metabolic syndrome. J Rheumatol. 2007;34(9):1882–1887. 191. Hoffman HM, Scott P, Mueller JL, et al. Role of the leucine-rich repeat domain of cryopyrin/NALP3 in monosodium urate crystal-induced inflammation in mice. Arthritis Rheum. 2010;62(7):2170-2179. 192. Holme I., Aastveit A.H., Hammar N., Jungner I., Walldius G. Uric acid and risk of myocardial infarction, stroke and congestive heart failure in 417,734 men and women in the Apolipoprotein Mortality RISk study (AMORIS) J Intern Med . 2009;266(6):558–570. 193. Hooper D.C., Spitsin S., Kean R.B., Champion J.M., Dickson G.M., Chaudhry I. Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci USA. 1998;95(2):675–680. 194. Hornung V, Bauernfeind F, Halle A, et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008;9(8):847-856. 195. Hoskin D.W., Mader J.S., Furlong S.J., Conrad D.M., Blay J. Inhibition of T cell and NK cell function by adenosine and its contribution to immune evasion by tumor cells (Review). Int J Oncol. 2008; 32(3): 527-535. 196. Hosomi A., Nakanishi T., Fujita T., Tamai I. Extra-renal elimination of uric acid via intestinal efflux transporter BCRP/ABCG2. PLoS One. 2012;7(2): e30456. 197. Hovind P., Rossing P., Tarnow L., Johnson R.J., Parving H.H. Serum uric acid as a predictor for development of diabetic nephropathy in type 1 diabetes: an inception cohort study. Diabetes. 2009;58(7):1668–1671. 198. Heart Rate Variability. Standards of Measurement, Physiological Interpretation, and Clinical Use. Task Force of ESC and NASPE. Circulation. 1996; 93(5): 1043-1065. 199. Huang H., Huang B., Li Y., Huang Y., Li J., Yao H. Uric acid and risk of heart failure: a systematic review and meta-analysis. Eur J Heart Fail. 2014;16(1):15–24. 200. Huang S, Apasov S, Koshiba M, Sitkovski M. Role of A2A extracellular adenosine receptor mediated signaling in adenosine mediated inhibition of T-cell activation and expansion. Blood. 1997; 90(4): 1600-1610. 201.Huang W.M., Hsu P.F., Cheng H.M., Lu D.Y., Cheng Y.L., Guo C.Y. Determinants and prognostic impact of hyperuricemia in hospitalization for acute heart failure. Circ J. 2016;80(2):404–410. 202. Huls M., Brown C.D., Windass A.S., Sayer R., van den Heuvel J.J., Heemskerk S. The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane. Kidney Int. 2008;73(2):220–225. 203. Hyndman D., Liu S., Miner J.N. Urate handling in the human body. Current Rheumatology Reports. 2016;18(6):34. 204. Iso T., Kurabayashi M. Extremely low levels of serum uric acid are associated with endothelial dysfunction in humans. Circ J. 2015;79(5):978–980. 205. Iwata H, Nishio S, Yokoyama M, Matsumoto A, Takeuchi M. Solubility of uric acid and supersaturation of monosodium urate: why is uric acid so highly soluble in urine? J Urol. 1989 Oct;142(4):1095-8. 206. Jalal D.I. Hyperuricemia, the kidneys, and the spectrum of associated diseases: a narrative review. Curr Med Res Opin. 2016;26: 1–7. 207. Jalal D.I., Rivard C.J., Johnson R.J., Maahs D.M., McFann K., Rewers M. Serum uric acid levels predict the development of albuminuria over 6 years in patients with type 1 diabetesetes: findings from the Coronary Artery Calcification in Type 1 Diabetes study. Nephrol Dial Transplant. 2010;25(6):1865–1869. 208. Jayashankar C.A., Andrews H.P., Vijayasarathi Pinnelli V.B., Shashidharan B., Nithin Kumar H.N., Vemulapalli S. Serum uric acid and low-density lipoprotein cholesterol levels are independent predictors of coronary artery disease in Asian Indian patients with type 2 diabetes mellitus. J Nat Sci Biol Med. 2016;7(2):161–165. 209. Jeong J.H., Jung J.H., Lee J.S., Oh J.S., Kim Y.G., Lee C.K., Yoo B., Hong S. Prominent Inflammatory Features of Monocytes/Macrophages in Acute Calcium Pyrophosphate Crystal Arthritis: A Comparison with Acute Gouty Arthritis. Immune Netw. 2019;19: e21. 210. Jia L., Xing J., Ding Y., Shen Y., Shi X., Ren W., Wan M., Guo J., Zheng S., Liu Y., et al. Hyperuricemia causes pancreatic beta-cell death and dysfunction through NF-kappaB signaling pathway. PLoS ONE. 2013;8: e78284. 211. Johnson R. J., Titte S., Cade J. R., Rideout B. A., Oliver W. J. Uric acid, evolution and primitive cultures. Seminars in Nephrology. 2005;25(1):3–8. 212. Johnson R.J., Merriman T., Lanaspa M.A. Causal or noncausal relationship of uric acid with diabetes. Diabetes. 2015;64(8):2720–2722. 213. Johnson R.J., Nakagawa T., Jalal D., Sánchez-Lozada L.G., Kang D.H., Ritz E. Uric acid and chronic kidney disease: which is chasing which? Nephrol Dial Transplant. 2013;28(9):2221–2228. 214. Johnson R.J., Nakagawa T., Sanchez-Lozada L.G., Shafiu M., Sundaram S., Le M. Sugar, uric acid, and the etiology of diabetes and obesity. Diabetes. 2013;62(10):3307–3315. 215. Johnson R.J., Segal M.S., Srinivas T., Ejaz A., Mu W., Roncal C. Essential hypertension, progressive renal disease, and uric acid: a pathogenetic link? J Am Soc Nephrol. 2005;16(7):1909–1919. 216. Johnson RJ, Stenvinkel P, Martin SL, Jani A, Sánchez-Lozada LG, Hill JO. Redefining metabolic syndrome as a fat storage condition based on studies of comparative physiology. Obesity (Silver Spring) 2013;21(4):659–664. 217. Jondal M, Holm G, Wigzell H. Surface markers on human T and B lymphocytes. I. A large population of lymphocytes forming nonimmune rosettes with sheep red blood cells. J Exp Med. 1972; 136(2): 207-215. 218. Joosten L.A., Ea H.K., Netea M.G., Busso N. Interleukin-1β activation during acute joint inflammation: a limited role for the NLRP3 inflammasome in vivo. Joint Bone Spine. 2011;78(2):107–110. 219. Joosten L.A., Netea M.G., Mylona E., Koenders M.I., Malireddi R.K., Oosting M. Engagement of fatty acids with Toll-like receptor 2 drives interleukin-1β production via the ASC/caspase 1 pathway in monosodium urate monohydrate crystal-induced gouty arthritis. Arthritis Rheum. 2010;62(11):3237–3248. 220.Joung K.W., Choi S.S., Kong Y.G., Yu J., Lim J., Hwang J.H. Incidence and risk factors of acute kidney injury after radical cystectomy: importance of preoperative serum uric acid level. Int J Med Sci. 2015;12(7):599–604. 221. Kam M, Perl-Treves D, Caspi D, Addadi L. Antibodies against crystals. FASEB J. 1992;6(8):2608-2613. 222. Kam M, Perl-Treves D, Sfez R, Addadi L. Specificity in the recognition of crystals by antibodies. J Mol Recognit. 1994;7(4):257-264. 223. Kanbay M., Jensen T., Solak Y., Le M., Roncal-Jimenez C., Rivard C. Uric acid in metabolic syndrome: from an innocent bystander to a central player. Eur J Intern Med. 2016;29: 3–8. 224. Kanbay M., Segal M., Afsar B., Kang D.H., Rodriguez-Iturbe B., Johnson R.J. The role of uric acid in the pathogenesis of human cardiovascular disease. Heart. 2013;99(11):759–766. 225. Kanbay M., Solak Y., Afsar B., Nistor I., Aslan G., Çağlayan O.H. Serum uric acid and risk for acute kidney injury following contrast: an evaluation of epidemiology, clinical trials, and potential mechanisms. Angiology. 2017;68(2):132–144. 226. Kanbay M., Yilmaz M.I., Sonmez A., Turgut F., Saglam M., Cakir E. Serum uric acid level and endothelial dysfunction in patients with nondiabetic chronic kidney disease. Am J Nephrol. 2011;33: 298–304. 227. Kanellis J., Watanabe S., Li J.H., Kang D.H., Li P., Nakagawa T. Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2. Hypertension. 2003;41(6):1287–1293. 228. Kanevets U, Sharma K, Dresser K, Shi Y. A role of IgM antibodies in monosodium urate crystal formation and associated adjuvanticity. J Immunol. 2009;182(4):1912-1918. 229. Kang D.H., Chen W. Uric acid and chronic kidney disease: new understanding of an old problem. Semin Nephrol. 2011;31(5):447–452. 230. Kang D.H., Park S.K., Lee I.K., Johnson R.J. Uric acid-induced C-reactive protein expression: implication on cell proliferation and nitric oxide production of human vascular cells. J Am Soc Nephrol. 2005;16(12):3553–3562. 231. Kaplanov I., Carmi Y., Kornetsky R., Shemesh A., Shurin G.V., Shurin M.R., Dinarello C.A., Voronov E., Apte R.N. Blocking IL-1beta reverses the immunosuppression in mouse breast cancer and synergizes with anti-PD-1 for tumor abrogation. Proc. Natl. Acad. Sci. USA. 2019;116: 1361–1369. 232. Kato M., Hisatome I., Tomikura Y., Kotani K., Kinugawa T., Ogino K. Status of endothelial dependent vasodilation in patients with hyperuricemia. Am J Cardiol. 2005;96(11):1576–1578. 233. Kawabe M., Sato A., Hoshi T., Sakai S., Hiraya D., Watabe H. Gender differences in the association between serum uric acid and prognosis in patients with acute coronary syndrome. J Cardiol. 2016;67(2):170–176. 234. Keebaugh A. C., Thomas J. W. The evolutionary fate of the genes encoding the purine catabolic enzymes in hominoids, birds, and reptiles. Molecular Biology and Evolution. 2010;27(6):1359–1369. 235. Keenan T., Zhao W., Rasheed A., Ho W.K., Malik R., Felix J.F. Causal assessment of serum urate levels in cardiometabolic diseases through a Mendelian randomization study. J Am Coll Cardiol. 2016;67(4):407–416. 236. Kelkar A., Kuo A., Frishman W.H. Allopurinol as a cardiovascular drug. Cardiol Rev. 2011;19(6):265–271. 237. Kim S.M., Lee S.H., Kim Y.G., Kim S.Y., Seo J.W., Choi Y.W. Hyperuricemia-induced NLRP3 activation of macrophages contributes to the progression of diabetic nephropathy. Am J Physiol Renal Physiol. 2015;308(9): F993–F1003. 238. Kim Y.G., Huang X.R., Suga S., Mazzali M., Tang D., Metz C. Involvement of macrophage migration inhibitory factor (MIF) in experimental uric acid nephropathy. Mol Med. 2000;6(10):837–848. 239. Kippen I, Klinenberg JR, Weinberger A, Wilcox WR. Factors affecting urate solubility in vitro. Ann Rheum Dis. 1974;33(4):313-317. 240. Kırça M., Oğuz N., Çetin A., Uzuner F., Yeşilkaya A. Uric acid stimulates proliferative pathways in vascular smooth muscle cells through the activation of p38 MAPK, p44/42 MAPK and PDGFRβ J Recept Signal Transduct Res. 2016;12:1–7. 241. Kleber M.E., Delgado G., Grammer T.B., Silbernagel G., Huang J., Krämer B.K. Uric acid and cardiovascular events: a mendelian randomization study. J Am Soc Nephrol. 2015;26(11):2831–2838. 242. Klecka W.R. Discriminant Analysis [trans. from English in Russian] (Seventh Printing, 1986). In: Factor, Discriminant and Cluster Analysis. Moskva. Finance and Statistics; 1989: 78-138. 243. Kohagura K., Tana T., Higa A., Yamazato M., Ishida A., Nagahama K. Effects of xanthine oxidase inhibitors on renal function and blood pressure in hypertensive patients with hyperuricemia. Hypertension Res. 2016 Aug;39(8):593–597. 244. Kono H., Chen C.J., Ontiveros F., Rock K.L. Uric acid promotes an acute inflammatory response to sterile cell death in mice. J Clin Invest. 2010;120(6):1939–1949. 245. Kool M, Pétrilli V, De Smedt T, et al. Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. J Immunol. 2008;181(6):3755-3759. 246. Kool M, Soullié T, van Nimwegen M, et al. Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J Exp Med. 2008;205(4):869-882. 247. Kool M., Willart M.A., van Nimwegen M., Bergen I., Pouliot P., Virchow J.C. An unexpected role for uric acid as an inducer of T helper 2 cell immunity to inhaled antigens and inflammatory mediator of allergic asthma. Immunity. 2011;34(4):527–540. 248. Koratala A. Tumor lysis syndrome with massive hyperphosphatemia and hyperuricemia. Clinical Case Reports. 2017;5(12):2158–2159. 249. Köttgen A., Albrecht E., Teumer A., Vitart V., Krumsiek J., Hundertmark C. Genome-wide association analyzes identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013;45: 145–154. 250. Kozin F, McCarty DJ. Molecular orientation of immunoglobulin G adsorbed to microcrystalline monosodium urate monohydrate. J Lab Clin Med. 1980;95(1):49-58. 251. Kratzer JT, Lanaspa MA, Murphy MN, Cicerchi C, Graves CL, Tipton PA. Evolutionary history and metabolic insights of ancient mammalian uricases. Proc Natl Acad Sci USA. 2014;111(10):3763–3768. 252. Krishnan E., Pandya B.J., Chung L., Hariri A., Dabbous O. Hyperuricemia in young adults and risk of insulin resistance, prediabetes, and diabetes: a 15-year follow-up study. Am J Epidemiol. 2012;176(2):108–116. 253. Kul'chyns'kyi AB, Gozhenko AI, Zukow W, Popovych IL. Neuro-immune relationships in patients with chronic pyelonephritis and cholecystitis. Communication 3. Correlations between parameters EEG, HRV and Immunogram. Journal of Education, Health and Sport. 2017; 7(3): 53-71. 254. Kul'chyns'kyi AB, Kovbasnyuk MM, Kyjenko VM., Zukow W, Popovych IL. Neuro-immune relationships in patients with chronic pyelonephritis and cholecystitis. Communication 2. Correlations between parameters EEG, HRV and Phagocytosis. Journal of Education, Health and Sport. 2016; 6(10): 377-401. 255. Kul'chyns'kyi AB, Kyjenko VM, Zukow W, Popovych IL. Causal neuro-immune relationships in patients with chronic pyelonephritis and cholecystitis. Correlations between parameters EEG, HRV and white blood cell count. Open Medicine. 2017; 12(1): 201-213. 256. Kul'chyns'kyi AB, Zukow W, Korolyshyn TA, Popovych IL. Interrelations between changes in parameters of HRV, EEG and humoral immunity in patients with chronic pyelonephritis and cholecystitis. Journal of Education, Health and Sport. 2017; 7(9): 439-459. 257. Kumagai T., Ota T., Tamura Y., Chang W.X., Shibata S., Uchida S. Time to target uric acid to retard CKD progression. Clin Exp Nephrol. 2017;21(2):182–192. 258. Kunikullaya K.U., Purushottam N., Prakash V., Mohan S., Chinnaswamy R. Correlation of serum uric acid with heart rate variability in hypertension. Hipertens Riesgo Vasc. 2015;32(4):133–141. 259. Kushiyama A., Okubo H., Sakoda H., Kikuchi T., Fujishiro M., Sato H., Kushiyama S., Iwashita M., Nishimura F., Fukushima T., et al. Xanthine oxidoreductase is involved in macrophage foam cell formation and atherosclerosis development. Arterioscler. Thromb. Vasc. Biol. 2012;32: 291–298. 260. Lam RS, O'Brien-Simpson NM, Holden JA, Lenzo JC, Fong SB, Reynolds EC. Unprimed, M1 and M2 Macrophages Differentially Interact with Porphyromonas gingivalis. PLoS ONE. 2016;11: e0158629. 261. Lambrecht B.N., Hammad H. Allergens and the airway epithelium response: gateway to allergic sensitization. J Allergy Clin Immunol. 2014;134(3):499–507. 262. Lanaspa M.A., Cicerchi C., Garcia G., Li N., Roncal-Jimenez C.A., Rivard C.J. Counteracting roles of AMP deaminase and AMP kinase in the development of fatty liver. PLoS ONE. 2012;7(11): e48801. 263. Lanaspa M.A., Epperson L.E., Li N., Cicerchi C., Garcia G.E., Roncal-Jimenez C.A. Opposing activity changes in AMP deaminase and AMP-activated protein kinase in the hibernating ground squirrel. PLoS ONE. 2015;10(4): e0123509. 264. Lanaspa M.A., Sanchez-Lozada L.G., Choi Y.J., Cicerchi C., Kanbay M., Roncal-Jimenez C.A. Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress: potential role in fructose-dependent and -independent fatty liver. J Biol Chem. 2012;287(48):40732–40744. 265. Lanaspa M.A., Sanchez-Lozada L.G., Cicerchi C., Li N., Roncal-Jimenez C.A., Ishimoto T. Uric acid stimulates fructokinase and accelerates fructose metabolism in the development of fatty liver. PLoS ONE. 2012;7(10): e47948. 266. Landis RC, Haskard DO. Pathogenesis of crystal-induced inflammation. Curr Rheumatol Rep. 2001;3(1):36-41. 267. Langford H.G., Blaufox M.D., Borhani N.O., Curb J.D., Molteni A., Schneider K.A. Is thiazide-produced uric acid elevation harmful? Analysis of data from the hypertension detection and follow-up program. Arch Intern Med. 1987; 147: 645. 268. Lazzeri C., Valente S., Chiostri M., Gensini G.F. Long-term prognostic role of uric acid in patients with ST-elevation myocardial infarction and renal dysfunction. J Cardiovasc Med (Hagerstown) 2015;16(11):790–794. 269.Lee E.H., Choi J.H., Joung K.W., Kim J.Y., Baek S.H., Ji S.M. Relationship between serum uric acid concentration and acute kidney injury after coronary artery bypass surgery. J Korean Med Sci. 2015;30(10):1509–1516. 270.Lee J.J., Ahn J., Hwang J., Han S.W., Lee K.N., Kim J.B. Relationship between uric acid and blood pressure in different age groups. Clin Hypertens. 2015 Jul;15(21):14. 271. Lee M., Lee Y., Song J., Lee J., Chang S.Y. Tissue-specific Role of CX3CR1 Expressing Immune Cells and Their Relationships with Human Disease. Immune Netw. 2018;18: e5. 272. Leiba A., Vinker S., Dinour D., Holtzman E.J., Shani M. Uric acid levels within the normal range predict increased risk of hypertension: a cohort study. J Am Soc Hypertens. 2015;9(8):600–609. 273. Li G., Qiao W., Zhang W., Li F., Shi J., Dong N. The shift of macrophages toward M1 phenotype promotes aortic valvular calcification. J. Thorac. Cardiovasc. Surg. 2017;153: 1318–1327. 274. Li L., Yang C., Zhao Y., Zeng X., Liu F., Fu P. Is hyperuricemia an independent risk factor for new-onset chronic kidney disease? A systematic review and meta-analysis based on observational cohort studies. BMC Nephrol. 2014;27(15):122. 275.Li P., Zhang L., Zhang M., Zhou C., Lin N. Uric acid enhances PKC-dependent eNOS phosphorylation and mediates cellular ER stress: a mechanism for uric acid-induced endothelial dysfunction. Int J Mol Med. 2016;37(4):989–997. 276.Liang C.C., Lin P.C., Lee M.Y., Chen S.C., Shin S.J., Hsiao P.J. Association of serum uric acid concentration with diabetic retinopathy and albuminuria in Taiwanese patients with type 2 diabetes mellitus. Int J Mol Sci. 2016;17(8) 277. Liang J., Pei Y., Gong Y., Liu X.K., Dou L.J., Zou C.Y. Serum uric acid and non-alcoholic fatty liver disease in non-hypertensive Chinese adults: Cardiometabolic Risk in Chinese (CRC) study. Eur Rev Med Pharmacol Sci. 2015;19(2):305–311. 278. Liang J., Zhang P., Hu X., Zhi L. Elevated serum uric acid after injury correlates with the early acute kidney in severe burns. Burns. 2015 Dec;41(8):1724–1731. 279. Liang M.H., Fries J.F. Asymptomatic hyperuricemia: the case for conservative management. Ann Intern Med. 1978; 88:666. 280. Lieske J.C., de la Vega L.S., Gettman M.T., Slezak J.M., Bergstralh E.J., Melton L.J., 3rd Diabetes mellitus and the risk of urinary tract stones: a population-based case-control study. Am J Kidney Dis. 2006;48(6):897–904. 281.Limatibul S, Shore A, Dosch H.M., Gelfand E.W. Theophylline modulation of E-rosette formation: an indicator of T-cell maturation. Clin Exp Immunol. 1978; 33(3): 503-513. 282. Lin X., Kong J., Wu Q., Yang Y., Ji P. Effect of TLR4/MyD88 signaling pathway on expression of IL-1beta and TNF-alpha in synovial fibroblasts from temporomandibular joint exposed to lipopolysaccharide. Mediat. Inflamm. 2015; 329405. 283. Lin Y., Zhu J., Wang Y., Li Q., Lin S. Identification of differentially expressed genes through RNA sequencing in goats (Capra hircus) at different postnatal stages. PLoS One. 2017;12(8): e0182602. 284. Linnane J.W., Burry A.F., Emmerson B.T. Urate deposits in the renal medulla. Prevalence and associations. Nephron. 1981;29(5–6):216–222. 285. List J.F., Whaley J.M. Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans. Kidney Int Suppl. 2011;120: S20-S27. 286. Liu D, Yun Y, Yang D, et al. What Is the Biological Function of Uric Acid? An Antioxidant for Neural Protection or a Biomarker for Cell Death. Dis Markers. 2019; 4081962. 287. Liu P., Wang H., Zhang F., Chen Y., Wang D., Wang Y. The effects of allopurinol on the carotid intima-media thickness in patients with Type 2 diabetes and asymptomatic hyperuricemia: a three-year randomized parallel-controlled study. Intern Med. 2015;54(17):2129–2137. 288.Liu Z., Que S., Zhou L., Zheng S. Dose-response Relationship of Serum Uric Acid with Metabolic Syndrome and Non-alcoholic Fatty Liver Disease Incidence: A Meta-analysis of Prospective Studies. Sci. Rep. 2015;5: 14325. 289. Liu-Bryan R, Pritzker K, Firestein GS, Terkeltaub R. TLR2 signaling in chondrocytes drives calcium pyrophosphate dihydrate and monosodium urate crystal-induced nitric oxide generation. J Immunol. 2005;174(8):5016-5023. 290. Liu-Bryan R, Scott P, Sydlaske A, Rose DM, Terkeltaub R. Innate immunity conferred by Toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum. 2005;52(9):2936-2946. 291. Liu-Bryan R., Lioté F. Monosodium urate and calcium pyrophosphate dihydrate (CPPD) crystals, inflammation, and cellular signaling. Jt. Bone Spine. 2005;72: 295–302. 292. Lu N., Dubreuil M., Zhang Y., Neogi T., Rai S.K., Ascherio A. Gout and the risk of Alzheimer's disease: a population-based, BMI-matched cohort study. Ann Rheum Dis. 2016;75(3):547–551. 293. Lu W., Xu Y., Shao X., Gao F., Li Y., Hu J., Zuo Z., Shao X., Zhou L., Zhao Y., et al. Uric Acid Produces an Inflammatory Response through Activation of NF-kappaB in the Hypothalamus: Implications for the Pathogenesis of Metabolic Disorders. Sci. Rep. 2015;5: 12144. 294. Lv Q., Meng X.F., He F.F., Chen S., Su H., Xiong J. High serum uric acid and increased risk of type 2 diabetes: a systemic review and meta-analysis of prospective cohort studies. PLoS One. 2013;8(2): e56864. 295. Lyngdoh T., Marques-Vidal P., Paccaud F., Preisig M., Waeber G., Bochud M., Vollenweider P. Elevated serum uric acid is associated with high circulating inflammatory cytokines in the population-based Colaus study. PLoS ONE. 2011;6:e19901. 296. Ma D.W., Arendt B.M., Hillyer L.M., Fung S.K., McGilvray I., Guindi M. Plasma phospholipids and fatty acid composition differ between liver biopsy-proven nonalcoholic fatty liver disease and healthy subjects. Nutr Diabetes. 2016;6(7): e220. 297. Madero M., Rodríguez Castellanos F.E., Jalal D., Villalobos-Martín M., Salazar J., Vazquez-Rangel A. A pilot study on the impact of a low fructose diet and allopurinol on clinical blood pressure among overweight and prehypertensive subjects: a randomized placebo-controlled trial. J Am Soc Hypertens. 2015;9(11):837–844. 298. Maesaka J.K., Fishbane S. Regulation of renal urate excretion: a critical review. Am J Kidney Dis. 1998;32: 917–933. 299. Maesaka J.K., Wolf-Klein G., Piccione J.M., Ma C.M. Hypouricemia, abnormal renal tubular urate transport, and plasma natriuretic factor(s) in patients with Alzheimer's disease. J Am Geriatric Soc. 1993;41(5):501–506. 300. Mahomed F.A. On chronic Bright's disease, and its essential symptoms. Lancet. 1879;1: 399–401. 301. Maiuolo J., Oppedisano F., Gratteri S., Muscoli C., Mollace V. Regulation of uric acid metabolism and excretion. Int J Cardiol. 2016;213: 8–14. 302. Mallamaci F., Testa A., Leonardis D., Tripepi R., Pisano A., Spoto B. A polymorphism in the major gene regulating serum uric acid associates with clinical SBP and the white-coat effect in a family-based study. J Hypertens. 2014;32(8):1621–1628. 303. Mandel NS. The structural basis of crystal-induced membranolysis. Arthritis Rheum. 1976;19 Suppl 3:439-445. 304. Mantovani A., Rigolon R., Pichiri I., Pernigo M., Bergamini C., Zoppini G. Hyperuricemia is associated with an increased prevalence of atrial fibrillation in hospitalized patientsents with type 2 diabetes. J Endocrinol Invest. 2016;39(2):159–167. 305. Marchesini G., Bugianesi E., Forlani G., Cerrelli F., Lenzi M., Manini R. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37(4):917–923. 306. Marotta T., Liccardo M., Schettini F., Verde F., Ferrara A.L. Association of hyperuricemia with conventional cardiovascular risk factors in elderly patients. J Clin Hypertens (Greenwich). 2015;17(1):27–32. 307. Martinez F.O., Gordon S., Locati M., Mantovani A. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: New molecules and patterns of gene expression. J. Immunol. 2006;177: 7303–7311. 308. Martínez-Reyes CP, Manjarrez-Reyna AN, Méndez-García LA, et al. Uric Acid Has Direct Proinflammatory Effects on Human Macrophages by Increasing Proinflammatory Mediators and Bacterial Phagocytosis Probably via URAT1. Biomolecules. 2020;10(4):576. 309. Martinon F. Mechanisms of uric acid crystal-mediated autoinflammation. Immunol Rev. 2010;33(1):218–232. 310. Martinon F. Update on biology: uric acid and the activation of immune and inflammatory cells. Curr Rheumatol Rep. 2010;12(2):135–141. 311. Martinon F., Pétrilli V., Mayor A., Tardivel A., Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237–241. 312. Masuo K., Kawaguchi H., Mikami H., Ogihara T., Tuck M.L. Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension. 2003;42: 474–480. 313. Mazzali M., Hughes J., Kim Y.G., Jefferson J.A., Kang D.H., Gordon K.L. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension. 2001;38:1101–1106. 314. Mazzali M., Kanbay M., Segal M.S., Shafiu M., Jalal D., Feig D.I. Uric acid and hypertension: cause or effect? Curr Rheumatol Rep. 2010;12(2):108–117. 315. McCarty D.J., Hollander J.L. Identification of urate crystals in gouty synovial fluid. Ann Intern Med. 1961;54: 452–460. 316.McGeough M.D., Wree A., Inzaugarat M.E., Haimovich A., Johnson C.D., Pena C.A., Goldbach-Mansky R., Broderick L., Feldstein A.E., Hoffman H.M. TNF regulates transcription of NLRP3 inflammasome components and inflammatory molecules in cryopyrinopathies. J. Clin. Investig. 2017;127: 4488–4497. 317. Mehta T., Nuccio E., McFann K., Madero M., Sarnak M.J., Jalal D. Association of uric acid with vascular stiffness in the Framingham heart study. Am J Hypertens. 2015;28(7):877–883. 318. Mendi M.A., Afsar B., Oksuz F., Turak O., Yayla C., Ozcan F. Uric acid is a useful tool to predict contrast-induced nephropathy. Angiology. 2017;68(7): 627–632. 319. Mitroulis I., Kambas K., Chrysanthopoulou A., Skendros P., Apostolidou E., Kourtzelis I. Neutrophil extracellular trap formation is associated with IL-1β and autophagy-related signaling in gout. PLoS One. 2011;6(12): e29318. 320. Mitroulis I., Kambas K., Ritis K. Neutrophils, IL-1β, and gout: is there a link? Semin Immunopathol. 2013;35(4):501–512. 321. Mohamedali K. A., Guicherit O. M., Kellems R. E., Rudolph F. B. The highest levels of purine catabolic enzymes in mice are present in the proximal small intestine. Journal of Biological Chemistry. 1993;268(31):23728–23733. 322. Monahan TS, Sawmiller DR, Fenton RA, Dobson JG Jr. Adenosine A(2a)-receptor activation increases contractility in isolated perfused hearts. Am J Physiol Heart Circ Physiol. 2000;279(4):H1472-H1481. 323. Morelli M., Carta A.R., Kachroo A., Schwarzschild A. Pathophysiological roles for purines: adenosine, caffeine and urate. Prog Brain Res. 2010; 183: 183-208. 324. Mortada I. Hyperuricemia, type 2 diabetes mellitus, and hypertension: an emerging association. Current Hypertension Reports. 2017;19(9):69. 325. Murray P.J. Macrophage Polarization. Annu. Rev. Physiol. 2017;79: 541–566. 326. Naff GB, Byers PH. Complement as a mediator of inflammation in acute gouty arthritis. I. Studies on the reaction between human serum complement and sodium urate crystals. J Lab Clin Med. 1973;81(5):747-760. 327. Nagase M, Baker DG, Schumacher HR Jr. Immunoglobulin G coating on crystals and ceramics enhances polymorphonuclear cell superoxide production: correlation with immunoglobulin G adsorbed. J Rheumatol. 1989;16(7):971-976. 328. Nagayama D., Yamaguchi T., Saiki A., Imamura H., Sato Y., Ban N. High serum uric acid is associated with increased cardio-ankle vascular index (CAVI) in healthy Japanese subjects: a cross-sectional study. Atherosclerosis. 2015;239(1):163–168. 329. Nakagawa T., Hu H., Zharikov S., Tuttle K.R., Short R.A., Glushakova O. A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Renal Physiol. 2006;290(3): F625-631. 330. Nakagawa T., Kang D.H., Feig D., Sanchez-Lozada L.G., Srinivas T.R., Sautin Y. Unearthing uric acid: an ancient factor with recently found significance in renal and cardiovascular disease. Kidney Int. 2006;69(10):1722–1725. 331. Nakagawa T., Mazzali M., Kang D.H., Kanellis J., Watanabe S., Sanchez-Lozada L.G. Hyperuricemia causes glomerular hypertrophy in the rat. Am J Nephrol. 2003;23: 2–7. 332. Nakagawa T., Mazzali M., Kang D.H., Sánchez-Lozada L.G., Herrera-Acosta J., Johnson R.J. Uric acid – a uremic toxin? Blood Purif. 2006;24(1):67–70. 333. Nance DM, Sanders VM. Autonomic innervation and regulation of the immune system (1987-2007). Brain Behav Immun. 2007; 21(6): 736-745. 334. Navalta J.W., Fedor E.A., Schafer M.A., Lyons T.S., Tibana R.A., Pereira G.B., Prestes J. Caffeine affects CD8+ lymphocyte differently in naive and familiar individuals following moderate intensity exercise. Int J Immunopathol Pharmacol. 2016; 29(2): 288-294. 335. Nawaz A., Aminuddin A., Kado T., Takikawa A., Yamamoto S., Tsuneyama K., Igarashi Y., Ikutani M., Nishida Y., Nagai Y., et al. CD206(+) M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors. Nat. Commun. 2017;8: 286. 336. Nery R.A., Kahlow B.S., Skare T.L., Tabushi F.I., do Amaral e Castro A. Uric acid and tissue repair. Arq Bras Cir Dig. 2015;28(4):290–292. 337. Ng G, Sharma K, Ward SM, et al. Receptor-independent, direct membrane binding leads to cell-surface lipid sorting and Syk kinase activation in dendritic cells. Immunity. 2008;29(5):807-818. 338. Nogi S., Fujita S., Okamoto Y., Kizawa S., Morita H., Ito T. Serum uric acid is associated with cardiac diastolic dysfunction among women with preserved ejection fraction. Am J Physiol Heart Circ Physiol. 2015;309(5) H986-994. 339. Oberbach A., Neuhaus J., Jehmlich N., Schlichting N., Heinrich M., Kullnick Y. A global proteome approach in uric acid stimulated human aortic endothelial cells revealed regulation of multiple major cellular pathways. Int J Cardiol. 2014;176(3):746–752. 340. Obermayr R.P., Temml C., Gutjahr G., Knechtelsdorfer M., Oberbauer R., Klauser-Braun R. Elevated uric acid increases the risk for kidney disease. J Am Soc Nephrol. 2008;19(12):2407–2413. 341. Ogino K., Kato M., Furuse Y., Kinugasa Y., Ishida K., Osaki S. Uric acid-lowering treatment with benzbromarone in patients with heart failure: a double-blind placebo-controlled crossover preliminary study. Circ Heart Fail. 2010;3: 73–81. 342. Okazaki H., Shirakabe A., Kobayashi N., Hata N., Shinada T., Matsushita M. The prognostic impact of uric acid in patients with severely decompensated acute heart failure. J Cardiol. 2016;68(5):384–391. 343. Ortiz-Bravo E, Sieck MS, Schumacher HR Jr. Changes in the proteins coating monosodium urate crystals during active and subsiding inflammation. Immunogold studies of synovial fluid from patients with gout and of fluid obtained using the rat subcutaneous air pouch model. Arthritis Rheum. 1993;36(9):1274-1285. 344. Otomo K., Horino T., Miki T., Kataoka H., Hatakeyama Y., Matsumoto T. Serum uric acid level as a risk factor for acute kidney injury in hospitalized patients: a retrospective database analysis using the integrated medical information system at Kochi Medical School hospital. Clin Exp Nephrol. 2016;20(2): 235–243. 345. Pachot A., Cazalis M.A., Venet F., Turrel F., Faudot C., Voirin N., Diasparra J., Bourgoin N., Poitevin F., Mougin B., et al. Decreased expression of the fractalkine receptor CX3CR1 on circulating monocytes as a new feature of sepsis-induced immunosuppression. J. Immunol. 2008;180: 6421–6429. 346. Palazzuoli A., Ruocco G., Pellegrini M., Beltrami M., Giordano N., Nuti R. Prognostic significance of hyperuricemia in patients with acute heart failure. Am J Cardiol. 2016;117(10):1616–1621. 347. Pan M., Gao H., Long L., Xu Y., Liu M., Zou J. Serum uric acid in patients with Parkinson's disease and vascular parkinsonism: a cross-sectional study. Neuroimmuno-modulation. 2013;20(1):19–28. 348. Park B.S., Lee J.O. Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp. Mol. Med. 2013;45:e66. 349. Park J.H., Jin Y.M., Hwang S., Cho D.H., Kang D.H., Jo I. Uric acid attenuates nitric oxide production by decreasing the interaction between endothelial nitric oxide synthase and calmodulin in human umbilical vein endothelial cells: a mechanism for uric acid -induced cardiovascular disease development. Nitric oxide. 2013;32: 36–42. 350. Parsa A., Brown E., Weir M.R., Fink J.C., Shuldiner A.R., Mitchell B.D. Genotype-based changes in serum uric acid affect blood pressure. Kidney Int. 2012;81(5):502–507. 351. Patel H.J., Patel B.M. TNF-alpha and cancer cachexia: Molecular insights and clinical implications. Life Sci. 2017;170: 56–63. 352. Peden DB, Hohman R, Brown ME, Mason RT, Berkebile C, Fales HM. Uric acid is a major antioxidant in human nasal airway secretions. Proc Natl Acad Sci USA. 1990;87(19):7638–7642. 353. Peden D.B., Swiersz M., Ohkubo K., Hahn B., Emery B., Kaliner M.A. Nasal secretion of the ozone scavenger uric acid. Am Rev Respir Dis. 1993;148(2):455–461. 354. Peracoli M.T., Bannwart C.F., Cristofalo R., Borges V.T., Costa R.A., Witkin S.S., Peracoli J.C. Increased reactive oxygen specieses and tumor necrosis factor-alpha production by monocytes are associated with elevated levels of uric acid in pre-eclamptic women. Am. J. Reprod. Immunol. 2011;66: 460–467. 355. Perheentupa J., Raivio K. Fructose-induced hyperuricemia. Lancet. 1967; 2(7515): 528–531. 356. Petsyukh S.V., Petsyukh M.S., Kovbasnyuk M.M., Barylyak L.G., Zukow W. Relationships between Popovych's Adaptation Index and parameters of ongoing HRV and EEG in patients with chronic pyelonephritis and cholecystitis in remission. Journal of Education, Health and Sport. 2016; 6(2): 99-110. 357. Pfister R., Barnes D., Luben R., Forouhi N.G., Bochud M., Khaw K.T. No evidence for a causal link between uric acid and type 2 diabetes: a Mendelian randomization approach. Diabetology. 2011;54(10):2561–2569. 358. Popadynets' OO, Gozhenko AI, Zukow W, Popovych IL. Relationships between the entropies of EEG, HRV, immunocytogram and leukocytosis. Journal of Education, Health and Sport. 2019; 9(5): 651-666. 359. Popa-Nita O., Naccache P.H. Crystal-induced neutrophil activation. Immunol Cell Biol. 2010;88(1):32–40. 360. Popovych AI. Features of the immunotropic effects of partial components of the balneotherapeutic complex of spa Truskavets'. Journal of Education, Health and Sport. 2018; 8(12): 919-935. 361. Popovych AI. Features of the neurotropic effects of partial components of the balneotherapeutic complex of spa Truskavets'. Journal of Education, Health and Sport. 2019; 9(1): 396-409. 362. Popovych IL, Kozyavkina OV, Kozyavkina NV, Korolyshyn TA, Lukovych YuS, Barylyak LG. Correlation between Indices of the Heart Rate Variability and Parameters of Ongoing EEG in Patients Suffering from Chronic Renal Pathology. Neurophysiology. 2014; 46(2): 139-148. 363. Popovych IL, Kul'chyns'kyi AB, Gozhenko AI, Zukow W, Kovbasnyuk MM, Korolyshyn TA. Interrelations between changes in parameters of HRV, EEG and phagocytosis in patients with chronic pyelonephritis and cholecystitis. Journal of Education, Health and Sport. 2018; 8(2): 135-156. 364. Popovych IL, Kul'chyns'kyi AB, Korolyshyn TA, Zukow W. Interrelations between changes in parameters of HRV, EEG and cellular immunity in patients with chronic pyelonephritis and cholecystitis. Journal of Education, Health and Sport. 2017; 7(10): 11-23. 365. Popovych IL, Lukovych YuS, Korolyshyn TA, Barylyak LG, Kovalska LB, Zukow W. Relationship between the parameters heart rate variability and background EEG activity in healthy men. Journal of Health Sciences. 2013; 3(4): 217-240. 366. Pousti A, Deemyad T, Malihi G. Mechanism of inhibitory effect of citalopram on isolated guinea-pig atria in relation to adenosine receptor. Hum Psychopharmacol. 2004;19(5):347-350. 367. Price KL, Sautin YY, Long DA, et al. Human vascular smooth muscle cells express a urate transporter. J Am Soc Nephrol. 2006;17(7):1791-1795. 368. Raijmakers M.T., Dechend R., Poston L. Oxidative stress and pre-eclampsia: rationale for antioxidant clinical trials. Hypertension. 2004;44(4):374–380. 369. Rasheed H., McKinney C., Stamp L.K., Dalbeth N., Topless R.K., Day R., Kannangara D., Williams K., Smith M., Janssen M., et al. The Toll-Like Receptor 4 (TLR4) Variant rs2149356 and Risk of Gout in European and Polynesian Sample Sets. PLoS ONE. 2016;11: e0147939. 370. Rentzos M., Nikolaou C., Anagnostouli M., Rombos A., Tsakanikas K., Economou M. Serum uric acid and multiple sclerosis. Clin Neurol Neurosurg. 2006;108(6):527–531. 371. Reschke L.D., Miller E.R., 3rd, Fadrowski J.J., Loeffler L.F., Holmes K.W., Appel L.J. Elevated uric acid and obesity-related cardiovascular disease risk factors among hypertensive youth. Pediatr Nephrol. 2015;30(12):2169–2176. 372. Rocha D.M., Caldas A.P., Oliveira L.L., Bressan J., Hermsdorff H.H. Saturated fatty acids trigger TLR4-mediated inflammatory response. Atherosclerosis. 2016;244: 211–215. 373. Roch-Ramel F., Werner D., Guisan B. Urate transport in brush border membrane of human kidney. Am J Physiol Renal Physiol. 1994;266:F797–F805. 374. Roncal-Jimenez C.A., Ishimoto T., Lanaspa M.A., Milagres T., Andres-Hernando A., Jensen T. Aging-associated renal disease in mice is fructokinase dependent. Am J Physiol Renal Physiol. 2016;311(4): F722–F730. 375. Roncal-Jimenez C.A., Lanaspa M.A., Rivard C.J., Nakagawa T., Sanchez-Lozada L.G., Jalal D. Sucrose induces fatty liver and pancreatic inflammation in male breeder rats independent of excess energy intake. Metabolism. 2011;60: 1259–1270. 376. Roy D., Perreault M., Marette A. Insulin stimulation of glucose uptake in skeletal muscles and adipose tissues in vivo is NO dependent. Am J Physiol. 1998; 274(4 Pt 1): E692-699. 377. Ryu E.-S., Kim M.J., Shin H.-S., Jang Y.H., Choi H.S., Jo I. Uric acid-induced phenotypic transition of renal tubular cells as a novel mechanism of chronic kidney disease. Am J Physiol Renal Physiol. 2013;304 F471-80. 378. Salahudeen M.S., Nishtala P.S. An overview of pharmacodynamic modeling, ligand-binding approach and its application in clinical practice. Saudi. Pharm. J.2017;25: 165–175. 379. Sánchez-Lozada L.G., Lanaspa M.A., Cristóbal-García M., García-Arroyo F., Soto V., Cruz-Robles D. Uric acid-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP concentrations. Nephron Exp Nephrol. 2012; 121(3–4): e71-78. 380. Sánchez-Lozada L.G., Nakagawa T., Kang D.H., Feig D.I., Franco M., Johnson R.J. Hormonal and cytokine effects of uric acid. Curr Opin Nephrol Hypertens. 2006; 15(1): 30–33. 381. Sanchez-Lozada L.G., Tapia E., Santamaria J., Avila-Casado C., Soto V., Nepomuceno T. Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int. 2005;67: 237–247. 382. Sautin Y.Y., Johnson R.J. Uric acid: the oxidant-antioxidant paradox. Nucleosides Nucleotides Nucl Acids. 2008;27(6):608–619. 383. Sautin Y.Y., Nakagawa T., Zharikov S., Johnson R.J. Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. Am. J. Physiol. Cell Physiol. 2007;293:C584–C596. 384. Schett G., Dayer J.M., Manger B. Interleukin-1 function and role in rheumatic disease. Nat Rev Rheumatol. 2016;12(1):14–24. 385. Schlesinger I., Schlesinger N. Uric acid in Parkinson's disease. Mov Disord. 2008; 23(12): 1653–1657. 386. Schlesinger N, Norquist JM, Watson DJ. Serum urate during acute gout. J Rheumatol. 2009; 36(6): 287-1289. 387. Schorn C., Frey B., Lauber K., Janko C., Strysio M., Keppeler H. Sodium overload and water influx activate the NALP3 inflammasome. J Biol Chem. 2011;286(1):35–41. 388. Schroder K., Zhou R., Tschopp J. The NLRP3 inflammasome: a sensor for metabolic danger? Science. 2010;327(5963):296–300. 389. Schwarzmeier J.D., Marktl W., Moser K., Lujf A. Fructose-induced hyperuricemia. Effects of fructose on the de novo synthesis of adenine nucleotides in the liver and skeletal muscles of rats. Res Exp Med (Berl) 1974;162(4):341–346. 390. Scott P, Ma H, Viriyakosol S, Terkeltaub R, Liu-Bryan R. Engagement of CD14 mediates the inflammatory potential of monosodium urate crystals. J Immunol. 2006; 177(9): 6370-6378. 391. Seet RC, Kasiman K, Gruber J, et al. Is uric acid protective or deleterious in acute ischemic stroke? A prospective cohort study. Atherosclerosis. 2010;209(1):215-219. 392. Selim S., El Sagheer O., El Amir A., Barakat R., Hadley K., Bruins M.J. Efficacy and safety of arachidonic acid for treatment of Schistosoma mansoni-infected children in Menoufiya, Egypt. Am J Trop Med Hyg. 2014;91(5):973–981. 393.Shafiu M., Johnson R.J., Turner S.T., Langaee T., Gong Y., Chapman A.B. Urate transporter gene SLC22A12 polymorphisms associated with obesity and metabolic syndrome in Caucasians with hypertension. Kidney Blood Press Res. 2012;35(6):477–482. 394. Shani M., Vinker S., Dinour D., Leiba M., Twig G., Holtzman E.J. High normal uric acid levels are associated with an increased risk of diabetes in lean, normoglycemic healthy women. J Clin Endocrinol Metab. 2016;101(10):3772–3778. 395. Shannon C.E. Works on the theory of informatics and cybernetics [transl. from English to Russian]. Moskva: Inostrannaya literatura; 1963: 329 p. 396. Sharaf El Din UAA, Salem MM, Abdulazim DO. Uric acid in the pathogenesis of metabolic, renal, and cardiovascular diseases: A review. J Adv Res. 2017;8(5):537-548. 397. Shi Y., Chen W., Jalal D., Li Z., Chen W., Mao H. Clinical outcome of hyperuricemia in IgA nephropathy: a retrospective cohort study and randomized controlled trial. Kidney Blood Press Res. 2012;35(3):153–160. 398. Shi Y., Evans J.E., Rock K.L. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature. 2003;425(6957):516–521. 399. Shih M.H., Lazo M., Liu S.H., Bonekamp S., Hernaez R., Clark J.M. Association between serum uric acid and nonalcoholic fatty liver disease in the US population. J Formos Med Assoc. 2015;114(4):314–320. 400. Shimizu T., Yoshihisa A., Kanno Y., Takiguchi M., Sato A., Miura S. Relationship of hyperuricemia with mortality in heart failure patients with preserved ejection fraction. Am J Physiol Heart Circ Physiol. 2015;309: H1123–H1129. 401. Sluijs I., Holmes M.V., van der Schouw Y.T., Beulens J.W., Asselbergs F.W., Huerta J.M. A Mendelian randomization study of circulating uric acid and type 2 diabetes. Diabetes. 2015;64(8):3028–3036. 402. Smárason A.K., Allman K.G., Young D., Redman C.W. Elevated levels of serum nitrate, a stable end product of nitric oxide, in women with pre-eclampsia. Br J Obstet Gynaecol. 1997;104(5):538–543. 403. Smyth CJ, Holers VM. Gout, Hyperuricemia, and Other Crystal-Associated Arthropathies. New York: Marcel Dekker; 1998. 404. Snigdha S., Smith E. D., Prieto G. A., Cotman C. W. Caspase-3 activation as a bifurcation point between plasticity and cell death. Neuroscience Bulletin. 2012;28(1):14–24. 405. Sofaer JA, Emery AE. Genes for super-intelligence? J Med Genet. 1981;18(6):410-413. 406. Soletsky B., Feig D.I. Uric acid reduction rectifies prehypertension inobese adolescents. Hypertension. 2012; 60(5): 1148–1156. 407. Sotgiu S., Pugliatti M., Sanna A., Sotgiu A., Fois M.L., Arru G. Serum uric acid and multiple sclerosis. Neurol Sci. 2002; 23(4):183–188. 408. Spahis S., Alvarez F., Dubois J., Ahmed N., Peretti N., Levy E. Plasma fatty acid composition in French-Canadian children with non-alcoholic fatty liver disease: effect of n-3 PUFA supplementation. Prostaglandins Leukot Essential Fatty Acids. 2015;99: 25–34. 409. Spilberg I. Current concepts of the mechanism of acute inflammation in gouty arthritis. Arthritis Rheum. 1975;18(2):129–134. 410.Stack A.G., Hanley A., Casserly L.F., Cronin C.J., Abdalla A.A., Kiernan T.J. Independent and joint associations of gout and hyperuricemia with total and cardiovascular mortality. QJM. 2013;106(7):647–658. 411. Steele TH. Hyperuricemic nephropathies. Nephron. 1999;81 Suppl 1:45-49. 412. Struk ZD, Mel'nyk OI, Zukow W, Popovych IL. The diversity of immune reactions to balneotherapy and their accompaniments. Journal of Education, Health and Sport. 2019; 9(11): 349-373. 413. Sugihara S., Hisatome I., Kuwabara M., Niwa K., Maharani N., Kato M. Depletion of uric acid due to SLC22A12 (URAT1) loss-of-function mutation causes endothelial dysfunction in hypouricemia. Circ J. 2015;79(5):1125–1132. 414.Sun H.L., Pei D., Lue K.H., Chen Y.L. Uric acid levels can predict metabolic syndrome and hypertension in adolescents: a 10-year longitudinal study. PLoS ONE. 2015;10(11): e0143786. 415. Sydoruk NO, Zukow W. Differences between the effects of water Naftussya from fields of Truskavets' and Pomyarky on the parameters of the EEG, HRV, immunity and metabolism. Journal of Education, Health and Sport. 2019; 9(1): 287-293. 416. Szabo G., Csak T. Inflammasomes in liver diseases. J Hepatol. 2012;57(3):642–654. 417. Tak HK, Cooper SM, Wilcox WR. Studies on the nucleation of monosodium urate at 37 degrees c. Arthritis Rheum. 1980;23(5):574-580. 418. Takae K., Nagata M., Hata J., Mukai N., Hirakawa Y., Yoshida D. Serum uric acid as a risk factor for chronic kidney disease in a Japanese community – the Hisayama study. Circ J. 2016;80(8):1857–1862. 419.Takir M., Kostek O., Ozkok A., Elcioglu O.C., Bakan A., Erek A. Lowering uric acid with allopurinol improves insulin resistance and systemic inflammation in asymptomatic hyperuricemia. J Investig Med. 2015;63(8):924–929. 420. Talbott J.H., Terplan K.L. The kidney in gout. Medicine. 1960;39: 405–467. 421. Tallima H, Dvořák J, Kareem S, et al. Protective immune responses against Schistosoma mansoni infection by immunization with functionally active gut-derived cysteine peptidases alone and in combination with glyceraldehyde 3-phosphate dehydrogenase. PLoS Negl Trop Dis. 2017;11(3): e0005443. 422. Tallima H., Dalton J.P., El Ridi R. Induction of protective immune responses against Schistosomiasis haematobium in hamsters and mice using cysteine peptidase-based vaccine. Front Immunol. 2015; 6:130. 423. Tan P.K., Ostertag T.M., Miner J.N. Mechanism of high affinity inhibition of the human urate transporter URAT1. Sci. Rep. 2016;6: 34995. 424. Tang L., Xu Y., Wei Y., He X. Uric acid induces the expression of TNFalpha via the ROSMAPKNFkappaB signaling pathway in rat vascular smooth muscle cells. Mol. Med. Rep. 2017;16: 6928–6933. 425. Tani S., Nagao K., Hirayama A. Effect of febuxostat, a xanthine oxidase inhibitor, on cardiovascular risk in hyperuricemic patients with hypertension: a prospective, open-label, pilot study. Clin Drug Investig. 2015;35(12):823–831. 426. Taniguchi K., Tamura Y., Kumagai T., Shibata S., Uchida S. Stimulation of V1a receptor increases renal uric acid clearance via urate transporters: insight into pathogenesis of hypouricemia in SIADH. Clin Exp Nephrol. 2016;20(6):845–852. 427. Terkeltaub R, Tenner AJ, Kozin F, Ginsberg MH. Plasma protein binding by monosodium urate crystals. Analysis by two-dimensional gel electrophoresis. Arthritis Rheum. 1983;26(6):775-783. 428. Terkeltaub R. Update on gout: new therapeutic strategies and options. Nat Rev Rheumatol. 2010; 6(1): 30-38. 429. Testa A., Mallamaci F., Spoto B., Pisano A., Sanguedolce M.C., Tripepi G. Association of a polymorphism in a gene encoding a urate transporter with CKD progression. Clin J Am Soc Nephrol. 2014; 9(6):1059–1065. 430. Thayer JF, Sternberg EM. Neural aspects of immunomodulation: Focus on the vagus nerve. Brain Behav Immun. 2010; 24(8): 1223-1228. 431. Tian H., Ye X., Hou X., Yang X., Yang J., Wu C. SVCT2, a potential therapeutic target, protects against oxidative stress during ethanol-induced neurotoxicity via JNK/p38 MAPKs, NF-κB and miRNA125a-5p. Free Radical Biology and Medicine. 2016; 96: 362–373. 432.Torres-Castro I., Arroyo-Camarena U.D., Martinez-Reyes C.P., Gomez-Arauz A.Y., Duenas-Andrade Y., Hernandez-Ruiz J., Bejar Y.L., Zaga-Clavellina V., Morales-Montor J., Terrazas L.I., et al. Human monocytes and macrophages undergo M1-type inflammatory polarization in response to high levels of glucose. Immunol. Lett. 2016;176:81–89. 433. Tracey K.J. Understanding immunity requires more than immunology. Nature Immunology. 2010; 11(7): 561-564. 434. Tramontini N, Huber C, Liu-Bryan R, Terkeltaub RA, Kilgore KS. Central role of complement membrane attack complex in monosodium urate crystal-induced neutrophilic rabbit knee synovitis. Arthritis Rheum. 2004;50(8):2633-2639. 435. Trapnell C., Williams B. A., Pertea G., et al. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nature Biotechnology. 2010;28(5):511–515. 436. Tschopp J., Schroder K. NLRP3 inflammasome activation: The convergence of multiple signaling pathways on ROS production? Nat Rev Immunol. 2010;10(3):210–215. 437. Uchida S., Chang W.X., Ota T., Tamura Y., Shiraishi T., Kumagai T. Targeting uric acid and the inhibition of progression to end-stage renal disease – a propensity score analysis. PLoS ONE. 2015;10(12): e0145506. 438. Viazzi F., Rebora P., Giussani M., Orlando A., Stella A., Antolini L. Increased serum uric acid levels blunt the antihypertensive efficacy of lifestyle modifications in children at cardiovascular risk. Hypertension. 2016;67(5):934–940. 439. Vigano S, Alatzoglou D, Irving M, Menetrier-Caux Ch, Caux Ch, Romero P, Coukos G. Targeting adenosine in cancer immunotherapy to enhance T-cell function. Front Immunol. 2019; 10: 925. 440. Vitart V, Rudan I, Hayward C, et al. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat Genet. 2008;40(4):437-442. 441. Von Lueder T.G., Girerd N., Atar D., Agewall S., Lamiral Z., Kanbay M. Serum uric acid is associated with mortality and heart failure hospitalizations in patients with complicated myocardial infarction: findings from the High-Risk Myocardial Infarction Database Initiative. Eur J Heart Fail. 2015;17(11):1144–1151. 442. Wang J., Qin T., Chen J., Li Y., Wang L., Huang H. Hyperuricemia and risk of incident hypertension: a systematic review and meta-analysis of observational studies. PLoS ONE. 2014;9(12): e114259. 443. Wang L., Hu W., Wang J., Qian W., Xiao H. Low serum uric acid levels in patients with multiple sclerosis and neuromyelitis optica: an updated meta-analysis. Mult Scler Relat Disord. 2016;9: 17–22. 444.Wang W., Wang C., Ding X.Q., Pan Y., Gu T.T., Wang M.X. Quercetin and allopurinol reduce liver thioredoxin-interacting protein to alleviate inflammation and lipid accumulation in diabetic rats. Br J Pharmacol. 2013;169(6):1352–1371. 445. Wang Y, Ma X, Su Ch, Peng B, Du J, Jia H, Luo M, Fang Ch, Wei Y. Uric acid enhanced the antitumor immunity of dendritic cell-based vaccine. Sci Rep. 2015; 5: 16427. 446. Wang Z., Lin Y., Liu Y., Chen Y., Wang B., Li C. Serum uric acid levels and outcomes after acute ischemic stroke. Mol Neurobiol. 2016;53(3):1753–1759. 447. Watanabe S, Kang DH, Feng L, et al. Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity. Hypertension. 2002;40(3):355-360. 448. Wei F., Sun N., Cai C., Feng S., Tian J., Shi W. Associations between serum uric acid and the incidence of hypertension: a Chinese senior dynamic cohort study. J Transl Med. 2016;14(1):110. 449. Willart M.A., Poulliot P., Lambrecht B.N., Kool M. PAMPs and DAMPs in allergy exacerbation models. Meth Mol Biol. 2013;1032: 185–204. 450.Wu A.H., Gladden J.D., Ahmed M., Ahmed A., Filippatos G. Relation of serum uric acid to cardiovascular disease. Int J Cardiol. 2016;15(213):4–7. 451.Wu C.Y., Hu H.Y., Chou Y.J., Huang N., Chou Y.C., Lee M.S. High serum uric acid levels are associated with all-cause and cardiovascular, but not cancer, mortality in elderly adults. J Am Geriatric Soc. 2015;63(9):1829–1836. 452.Wu H., Jia Q., Liu G., Liu L., Pu Y., Zhao X. Decreased uric acid levels correlate with poor outcomes in acute ischemic stroke patients, but not in cerebral hemorrhage patients. J Stroke Cerebrovasc Dis. 2014;23(3):469–475. 453.Wu J., Qiu L., Cheng X.Q., Xu T., Wu W., Zeng X.J., Ye Y.C., Guo X.Z., Cheng Q., Liu Q., et al. Hyperuricemia and clustering of cardiovascular risk factors in the Chinese adult population. Sci. Rep. 2017;7: 5456. 454. Wynn T.A., Chawla A., Pollard J.W. Macrophage biology in development, homeostasis and disease. Nature. 2013; 496: 445–455. 455. Xia X., Luo Q., Li B., Lin Z., Yu X., Huang F. Serum uric acid and mortality in chronic kidney disease: a systematic review and meta-analysis. Metabolism. 2016;65(9):1326–1341. 456. Xiao J., Fu C., Zhang X., Zhu D., Chen W., Lu Y. Soluble monosodium urate, but not its crystal, induces toll-like receptor 4-dependent immune activation in renal mesangial cells. Mol Immunol. 2015;66(2):310–318. 457. Xiao J., Zhang X.L., Fu C., Han R., Chen W., Lu Y. Soluble uric acid increases NALP3 inflammasome and interleukin-1β expression in human primary renal proximal tubule epithelial cells through the Toll-like receptor 4 -mediated pathway. Int J Mol Med. 2015; 35(5):1347–1354. 458. Xu W., Huang Y., Li L., Sun Z., Shen Y., Xing J. Hyperuricemia induces hypertension through activation of renal epithelial sodium channel (ENaC). Metabolism. 2016;65(3):73–83. 459. Xu X., Hu J., Song N., Chen R., Zhang T., Ding X. Hyperuricemia increases the risk of acute kidney injury: a systematic review and meta-analysis. BMC Nephrol. 2017;18(1):27. 460. Yakoob M.Y. Vitamin D deficiency during pregnancy and the risk of preeclampsia. J Pak Med Assoc. 2011;61(8):827–828. 461. Yan D., Tu Y., Jiang F., Wang J., Zhang R., Sun X. Uric acid is independently associated with diabetic kidney disease: a cross-sectional study in a Chinese population. PLoS ONE. 2015;10(6): e0129797. 462. Yano H., Tamura Y., Kobayashi K., Tanemoto M., Uchida S. Uric acid transporter ABCG2 is increased in the intestine of the 5/6 nephrectomy rat model of chronic kidney disease. Clin Exp Nephrol. 2014;18(1):50–55. 463. Yin H., Hou X., Tao T., Lv X., Zhang L., Duan W. Neurite outgrowth resistance to rho kinase inhibitors in PC12 Adh cells. Cell Biology International. 2015;39(5):563–576. 464. Yokoi Y., Kondo T., Okumura N., Shimokata K., Osugi S., Maeda K. Serum uric acid as a predictor of future hypertension: stratified analysis based on body mass index and age. Prev Med. 2016;9(90):201–206. 465. Yokokawa H., Fukuda H., Suzuki A., Fujibayashi K., Naito T., Uehara Y. Association between serum uric acid levels/hyperuricemia and hypertension among 85,286 Japanese workers. J Clin Hypertens (Greenwich). 2016; 18(1): 53–59. 466. Yoshitomi R., Fukui A., Nakayama M., Ura Y., Ikeda H., Oniki H. Sex differences in the association between serum uric acid levels and cardiac hypertrophy in patients with chronic kidney disease. Hypertension Res. 2014;37(3):246–252. 467. Yousefi M., Rahimi H., Barikbin B., Toossi P., Lotfi S., Hedayati M. Uric acid: a new antioxidant in patients with pemphigus vulgaris. Indian J Dermatol. 2011;56(3):278–281. 468. Yu K. H., Chen D. Y., Chen J. H., et al. Management of gout and hyperuricemia: multidisciplinary consensus in Taiwan. International Journal of Rheumatic Diseases. 2018; 21(4): 772–787. 469. Yu M., Ling K., Teng Y., Li Q., Mei F., Li Y. Serum uric acid is associated with increased risk of idiopathic venous thromboembolism in high HDL-C population: a case-control study. Exp Ther Med. 2016; 11(6): 2314–2320. 470.Yu M.A., Sánchez-Lozada L.G., Johnson R.J., Kang D.H. Oxidative stress with an activation of the renin-angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction. J Hypertens. 2010;28(6):1234–1242. 471. Yu S., Yang H., Guo X., Zheng L., Sun Y. Hyperuricemia is independently associated with left ventricular hypertrophy in post-menopausal women but not in pre-menopausal women in rural Northeast China. Gynecol Endocrinol. 2015;31(9):736–741. 472.Yu T.Y., Jee J.H., Bae J.C., Jin S.M., Baek J.H., Lee M.K., Kim J.H. Serum uric acid: A strong and independent predictor of metabolic syndrome after adjusting for body composition. Metabolism. 2016;65: 432–440. 473. Yu X., Shi J., Jiang C., Xu J., You S., Cao Y. Association study of serum uric acid levels with clinical outcome and hemorrhagic transformation in stroke patients with rt-PA intravenous thrombolysis. Zhonghua Yi Xue Za Zhi. 2015;95(29):2351–2354. 474. Yuan H., Yu C., Li X., Sun L., Zhu X., Zhao C. Serum uric acid levels and risk of metabolic syndrome: a dose-response meta-analysis of prospective studies. J Clin Endocrinol Metab. 2015;100(11):4198–4207. 475. Yun Y., Yin H., Gao Z., et al. Intestinal tract is an important organ for lowering serum uric acid in rats. PLoS One. 2017;12(12): e0190194. 476. Zakharova I., Sokolova T., Vlasova Y., Bayunova L., Rychkova M., Avrova N. α-Tocopherol at nanomolar concentration protects cortical neurons against oxidative stress. International Journal of Molecular Sciences. 2017;18(1):216. 477. Zhang B., Duan M., Long B., Zhang B., Wang D., Zhang Y., Chen J., Huang X., Jiao Y., Zhu L., et al. Urate transport capacity of glucose transporter 9 and urate transporter 1 in cartilage chondrocytes. Mol. Med. Rep. 2019; 20: 1645–1654. 478. Zhang J., Diao B., Lin X., Xu J., Tang F. TLR2 and TLR4 mediate an activation of adipose tissue renin-angiotensin system induced by uric acid. Biochimie. 2019;162: 125–133. 479. Zhang M., Hutter G., Kahn S.A., Azad T.D., Gholamin S., Xu C.Y., Liu J., Achrol A.S., Richard C., Sommerkamp P., et al. Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages in vivo. PLoS ONE. 2016;11: e0153550. 480. Zhang W., Iso H., Murakami Y., Miura K., Nagai M., Sugiyama D. Serum uric acid and mortality form cardiovascular disease: EPOCH-JAPAN study. J Atheroscler Thromb. 2016;23(6):692–703. 481. Zhang X., Zhang J.H., Chen X.Y., Hu Q.H., Wang M.X., Jin R. Reactive oxygen species-induced TXNIP drives fructose-mediated hepatic inflammation and lipid accumulation through NLRP3 inflammasome activation. Antioxid Redox Signal. 2015;22(10):848–870. 482.Zhao J., Zheng D.Y., Yang J.M., Wang M., Zhang X.T., Sun L. Maternal serum uric acid concentration is associated with the expression of tumor necrosis factor-α and intercellular adhesion molecule-1 in patients with preeclampsia. J Hum Hypertens. 2016; 30(7): 456–462. 483. Zhou Y., Hu W., Chen P., et al. Ki67 is a biological marker of malignant risk of gastrointestinal stromal tumors: a systematic review and meta-analysis. Medicine. 2017; 96(34): e7911. 484. Zhou Y., Yang Y., Warr G., Bravo R. LPS down-regulates the expression of chemokine receptor CCR2 in mice and abolishes macrophage infiltration in acute inflammation. J Leukoc Biol. 1999; 65: 265–269. 485. Zhu L., Wang J., Wang Y., Jia L., Sun K., Wang H. Plasma uric acid as a prognostic marker in patients with hypertrophic cardiomyopathy. Can J Cardiol. 2015; 31(10):1252–1258. 486. Zoccali C., Maio R., Mallamaci F., Sesti G., Perticone F. Uric acid and endothelial dysfunction in essential hypertension. J Am Soc Nephrol. 2006;17: 466–1471. 487. Zurlo A., Veronese N., Giantin V., Maselli M., Zambon S., Maggi S. High serum uric acid levels increase the risk of metabolic syndrome in elderly women: the PROVA study. Nutr Metab Cardiovasc Dis. 2016; 26(1): 27–35. У монографії висвітлені результати пріоритетних експериментальних і клініко-фізіологічних досліджень зв’язків урикемії і урикозурії з параметрами обміну сечовини, креатиніну і електролітів та нейро-ендокринно-імунного комплексу. В руслі авторських концепцій функціонально-метаболічного континууму і нейроендокринно-імунного комплексу з використанням методів дискримінантного і канонічного кореляційного аналізів продемонстровано, що молекула сечової кислоти проявляє відчутну фізіологічну активність і може вважатися четвертою ендогенною сигнальною молекулою поряд з NO, CO і H2S. Для біохіміків, патофізіологів, ендокринологів, імунологів. The monograph highlights the results of priority experimental and clinical-physiological studies of the relationship between uricemia and uricosuria with the parameters of urea, creatinine and electrolyte metabolism and the neuro-endocrine-immune complex. In line with the author's concepts of the functional-metabolic continuum and the neuroendocrine-immune complex using the methods of discriminant and canonical correlation analyses, it was demonstrated that the uric acid molecule exhibits significant physiological activity and can be considered the fourth endogenous signal molecule along with NO, CO and H2S. For biochemists, pathophysiologists, endocrinologists, immunologists. Аннотація В експерименті на здорових щурах виявлено широкий діапазон параметрів обміну сечової кислоти і вперше показано, що з ними значуще корелюють 34 імунні параметри із 41 зареєстрованого. Урикозурія (більшою мірою) і урикемія (меншою мірою), взяті разом, детермінують стан імунітету на 71%. Сечова кислота стимулює фагоцитоз Staph. aureus нейтрофілами (але не моноцитами) крові, збільшує відносний вміст лімфоцитів загалом і В-лімфоцитів зокрема в крові, Т-лімфоцитів і макрофагів в тимусі та фібробластів в селезінці, а також нарощує ентропію імуноцитограми крові. З іншого боку, сечова кислота зменшує ентропію лейкоцитограми крові, загальний вміст в крові лейкоцитів і відносний вміст в лейкоцитограмі моноцитів і паличкоядерних нейтрофілів, натуральних кілерів в імуноцитограмі, а також ентропію тимоцитограми і вміст в ній епітеліоцитів і ретикулоцитів. Вперше показано, що з-поміж нейро-ендокринних факторів адаптації урикозурія і урікемія негативно корелюють з ВРС-маркерами симпатичного тонусу і циркулюючих катехоламінів, рівнем в плазмі кортикостерону і товщиною фасцикулярної зони кори наднирників, а також рівнем в плазмі трийодтироніну і Са-Р-маркером кальцитонінової активності, натомість позитивно корелюють з ВРС-маркером вагального тонусу і екскрецією з сечею 17-кетостероїдів. Міра детермінації сечовою кислотою нейро-ендокринних факторів адаптації становить 62%. Сукупний детермінуючий вплив параметрів обміну сечової кислоти (за значної переваги урикозурії над урикемією) на констеляцію метаболічних параметрів становить 56%. Максимальній позитивній детермінації з боку сечової кислоти підлеглі діурез і екскреція фосфатів та калію, меншою мірою детермінуються екскреція кальцію, креатиніну і сечовини, ще меншою – рівні креатиніну, сечовини і калію в плазмі, а мінімальній детермінації підлегла магнійурія. У людей обох статей, хворих на хронічний пієлонефрит в фазі ремісії, виявлено чотири варіанти обміну сечової кислоти. У 34% помірна гіпоурикозурія поєднується з нижньопограничною урикемією. У 24% помірно підвищена урикозурія асоціюється із нормальною урикемією. У 17% помірно підвищена урикозурія поєднується з вираженою гіпоурикемією. Нарешті, у 25% пацієнтів нижньопогранична урикемія супроводжується вираженою гіперурикозурією. З-поміж усіх зареєстрованих параметрів в якості розпізнавальних щодо чотирьох варіантів обміну сечової кислоти виявлено 28. У дискримінантну модель включено, окрім урикозурії і урикемії за визначенням, 6 нейроендокринних параметрів адаптації (кортизол, трийодтиронін, тестостерон, кальцитонін, вегетативний індекс Кердьо і Са/К-маркер симпато-вагального балансу), 8 параметрів імунітету (активність і завершеність фагоцитозу нейтрофілами грампозитивних і грамнегативних бактерій, рівень в крові загальних лімфоцитів, інтерлейкіну-1β, IgG та IgA в слині), два інформаційні параметри (індекс напруження лейкоцитограми Поповича і ентропія імуноцитограми), 7 параметрів метаболізму електролітів (магній, калій, фосфати) і неелектролітів (глюкоза, сечовина і креатинін), а також маркери хронічного пієлонефриту (бaктерійурія і лейкоцитурія) і мікробіоти (Bifidobacteria). Вперше показано, що динаміка урикозурії позитивно детермінує динаміку діурезу і екскреції сечовини, креатиніну, кальцію, фосфатів, магнію, хлориду і калію та калійемії, рівня Т-гелперів, ВРС-маркерів вагального тонусу і симпато-вагального балансу. Натомість негативній детермінації підлеглі зміни вегетативного індексу Кердьо та інтенсивності фагоцитозу Staph. aureus. Динаміка такої констеляції параметрів організму детермінується динамікою сечової кислоти на 97%. Динаміка урикемії детермінує динаміку вегетативного індексу Кердьо, кортизолу і кальцитоніну негативно, натомість електролітних маркерів паратироїдної активності і симпато-вагального балансу та тестостерону – позитивно. З-поміж імунних параметрів негативній сечокислій детермінації підлеглі зміни Т-гелперів і TNF-α, натомість позитивній – ЦІК, моноцитів і IgG. Стосовно параметрів метаболізму спостерігається лише позитивна сечокисла детермінації їх динаміки. Метаболічна констеляція включає кальційемію, хлоридемію, магнійемію, а також діурез та екскрецію хлориду, натрію, сечовини і креатиніну. В цілому сечокисла детермінація динаміки перелічених параметрів організму становить 80%. Одержані результати розвивають і доповнюють концепцію, що ендогенна сечова кислота володіє фізіологічною активністю, яка проявляється у модуляції параметрів нейроендокринно-імунного комплексу і метаболізму. Gozhenko AI, Korda MM, Smagliy VS, Badiuk NS, Zukow W, Klishch MI, Korda IV, Bombushkar IS, Popovych IL. Uric Acid, Metabolism, Neuro-Endocrine-Immine Complex. Odesa. Feniks; 2023: 266 p. Annotation In an experiment on healthy rats, a wide range of parameters of uric acid metabolism was revealed, and it was shown for the first time that 34 immune parameters out of 41 registered were significantly correlated with them. Uricosuria (to a greater extent) and uricemia (to a lesser extent), taken together, determine the state of immunity by 71%. Uric acid stimulates the phagocytosis of Staph. aureus by neutrophils (but not monocytes) of the blood, increases the relative content of lymphocytes in general and B-lymphocytes in particular in the blood, T-lymphocytes and macrophages in the thymus and fibroblasts in the spleen, and also increases the entropy of the blood immunocytogram. On the other hand, uric acid reduces the entropy of the blood leukocytogram, the total content of leukocytes in the blood and the relative content of monocytes and rod-shaped neutrophils in the leukocytogram, natural killers in the immunocytogram, as well as the entropy of the thymocytogram and the content of epitheliocytes and reticulocytes in it. For the first time, it was shown that among the neuro-endocrine factors of adaptation, uricosuria and uricemia are negatively correlated with HRV-markers of sympathetic tone and circulating catecholamines, the plasma level of corticosterone and the thickness of the fascicular zone of the adrenal cortex, as well as the plasma level of triiodothyronine and the Ca-P marker calcitonin activity, on the other hand, are positively correlated with HRV-marker of vagal tone and urinary excretion of 17-ketosteroids. The rate of determination of neuro-endocrine adaptation factors by uric acid is 62%. The cumulative determining influence of parameters of uric acid metabolism (due to the significant advantage of uricosuria over uricemia) on the constellation of metabolic parameters is 56%. Diuresis and excretion of phosphates and potassium are subject to the maximum positive determination by uric acid, excretion of calcium, creatinine and urea are determined to a lesser extent, levels of creatinine, urea and potassium in plasma are even less determined, and magnesiumuria is subject to the minimum determination. In people of both sexes, patients with chronic pyelonephritis in the phase of remission, four variants of uric acid metabolism were found. In 34%, moderate hypouricosuria is combined with lower borderline uricemia. In 24%, moderately increased uricosuria is associated with normal uricemia. In 17%, moderately increased uricosuria is combined with pronounced hypouricemia. Finally, in 25% of patients, subliminal uricemia is accompanied by marked hyperuricosuria. Among all the registered parameters, 28 were identified as identifying four variants of uric acid metabolism. In addition to uricosuria and uricemia by definition, the discriminant model included 6 neuroendocrine parameters of adaptation (cortisol, triiodothyronine, testosterone, calcitonin, Kerdoe’s autonomic index and Ca/K-marker of sympatho-vagal balance), 8 parameters of immunity (activity and completion of phagocytosis by neutrophils of gram-positive and gram-negative bacteria, the levels of total lymphocytes, interleukin-1β, IgG in the blood and IgA in saliva), two informational parameters (the Popovych’s leukocytogram strain index and the entropy of the immunocytogram), 7 parameters of electrolyte metabolism (magnesium , potassium, phosphates) and non-electrolytes (glucose, urea and creatinine), as well as markers of chronic pyelonephritis (bacteriuria and leukocyturia) and microbiota (Bifidobacteria). It was shown for the first time that the dynamics of uricosuria upregulates the dynamics of diuresis and excretion of urea, creatinine, calcium, phosphates, magnesium, chloride and potassium and plasma potassium, the level of T-helpers, HRV-markers of vagal tone and sympatho-vagal balance. Instead, changes in the Kerdoe’s vegetative index and the intensity of Staph. aureus phagocytosis are subject to downregulation. The dynamics of such a constellation of body parameters is determined by the dynamics of uric acid by 97%. The dynamics of uricemia determines the dynamics of the Kerdoe’s autonomic index, cortisol and calcitonin negatively, instead of the electrolyte markers of parathyroid activity and sympatho-vagal balance and testosterone - positively. Among the immune parameters, changes in T-helpers and TNF-α are subject to negative uric acid determination, while positive ones include CIC, monocytes, and IgG. Regarding metabolic parameters, only positive uric acid determination of their dynamics is observed. The metabolic constellation includes calciumemia, chlorideemia, magnesiumemia, as well as diuresis and excretion of chloride, sodium, urea, and creatinine. In general, uric acid determines the dynamics of the listed parameters of the body by 80%. The obtained results develop and complement the concept that endogenous uric acid has physiological activity, which is manifested in the modulation of the parameters of the neuroendocrine-immune complex and metabolism.

Rat liver lysosomes, isolated from metrizamide gradients by the method of Wattiaux et al. (Wattiaux, R., Wattiaux-de Coninck, S., Ronveaux-Dupol, M.F., and Dubois, F. (1978) J. Cell Biol. 78, 349-368) took up from the medium and degraded several marker protein preparations, viz. 125I-asialofetuin, [35S]methionine-labeled hemoglobin, and [3H]leucine-labeled rat liver cytosol proteins. Rates were indistinguishable for all the markers, indicating that uptake was by a nonspecific process analogous to fluid pinocytosis. No effect of added MgATP or K+ was observed. Lysosomal degradation of all the markers was inhibited by 10(-4) M chloroquine. Swainsonine, on the other hand, at 10(-5) M, inhibited the breakdown only of the glycoprotein, 125I-asialofetuin. In the presence of the inhibitors, there was an accumulation of markers in the lysosomes in amount corresponding to the decreased breakdown, indicating that uptake was unaffected. Degradation and inhibition were measured at pH 7.0, 6.0, and 5.0 with both intact lysosomes and with lysosomes disrupted by the addition of 0.2% Triton X-100. Degradation with intact lysosomes was relatively independent of pH. On the other hand, activity with disrupted lysosomes was negligible at pH 7.0 and rose rapidly with decreasing pH. Inhibition by 10(-4) M chloroquine and 10(-5) M swainsonine with intact lysosomes decreased sharply with decreasing pH and did not occur with disrupted lysosomes.

Rat liver lysosomes, isolated from metrizamide gradients by the method of Wattiaux et al. (Wattiaux, R., Wattiaux-de Coninck, S., Ronveaux-Dupol, M.F., and Dubois, F. (1978) J. Cell Biol. 78, 349-368) took up from the medium and degraded several marker protein preparations, viz. 125I-asialofetuin, [35S]methionine-labeled hemoglobin, and [3H]leucine-labeled rat liver cytosol proteins. Rates were indistinguishable for all the markers, indicating that uptake was by a nonspecific process analogous to fluid pinocytosis. No effect of added MgATP or K+ was observed. Lysosomal degradation of all the markers was inhibited by 10(-4) M chloroquine. Swainsonine, on the other hand, at 10(-5) M, inhibited the breakdown only of the glycoprotein, 125I-asialofetuin. In the presence of the inhibitors, there was an accumulation of markers in the lysosomes in amount corresponding to the decreased breakdown, indicating that uptake was unaffected. Degradation and inhibition were measured at pH 7.0, 6.0, and 5.0 with both intact lysosomes and with lysosomes disrupted by the addition of 0.2% Triton X-100. Degradation with intact lysosomes was relatively independent of pH. On the other hand, activity with disrupted lysosomes was negligible at pH 7.0 and rose rapidly with decreasing pH. Inhibition by 10(-4) M chloroquine and 10(-5) M swainsonine with intact lysosomes decreased sharply with decreasing pH and did not occur with disrupted lysosomes.

In order to study the intracellular localization of the proteolytic processing steps in the maturation of alpha-glucosidase and cathepsin D in cultured human skin fibroblasts we have used incubation with glycyl-L-phenylalanine-beta-naphthylamide (Gly-Phe-NH-Nap) as described by Jadot et al. [Jadot, M., Colmant, C., Wattiaux-de Coninck, S. & Wattiaux, R. (1984) Biochem. J. 219,965-970] for the specific lysis of lysosomes. When a homogenate of fibroblasts was incubated for 20 min with 0.5 mM Gly-Phe-NH-Nap, a substrate for the lysosomal enzyme cathepsin C, the latency of the lysosomal enzymes alpha-glucosidase and beta-hexosaminidase decreased from 75% to 10% and their sedimentability from 75% to 20-30%. In contrast, treatment with Gly-Phe-NH-Nap had no significant effect on the latency of galactosyltransferase, a marker for the Golgi apparatus, and on the sedimentability of glutamate dehydrogenase and catalase, markers for mitochondria and peroxisomes, respectively. The maturation of alpha-glucosidase and cathepsin D in fibroblasts was studied by pulse-labelling with [35S]methionine, immunoprecipitation, polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate and fluorography. When homogenates of labelled fibroblasts were incubated with Gly-Phe-NH-Nap prior to immunoprecipitation, 70-80% of all proteolytically processed forms of metabolically labelled alpha-glucosidase and cathepsin D was recovered in the supernatant. The earliest proteolytic processing steps in the maturation of alpha-glucosidase and cathepsin D appeared to be coupled to their transport to the lysosomes. Although both enzymes are transported via the mannose-6-phosphate-specific transport system, the velocity with which they arrived in the lysosomes was consistently different. Whereas newly synthesized cathepsin D was found in the lysosomes 1 h after synthesis, alpha-glucosidase was detected only after 2-4 h. When a pulse-chase experiment was carried out in the presence of 10 mM NH4Cl there was a complete inhibition of the transport of cathepsin D and a partial inhibition of that of alpha-glucosidase to the lysosomes. Leupeptin, an inhibitor of lysosomal thiol proteinases, had no effect on the transport of labelled alpha-glucosidase to the lysosomes. However, the early processing steps in which the 110-kDa precursor is converted to the 95-kDa intermediate form of the enzyme were delayed, a transient 105-kDa form was observed and the conversion of the 95-kDa intermediate form to the 76-kDa mature form of the enzyme was completely inhibited.(ABSTRACT TRUNCATED AT 400 WORDS)

In order to study the intracellular localization of the proteolytic processing steps in the maturation of alpha-glucosidase and cathepsin D in cultured human skin fibroblasts we have used incubation with glycyl-L-phenylalanine-beta-naphthylamide (Gly-Phe-NH-Nap) as described by Jadot et al. [Jadot, M., Colmant, C., Wattiaux-de Coninck, S. & Wattiaux, R. (1984) Biochem. J. 219,965-970] for the specific lysis of lysosomes. When a homogenate of fibroblasts was incubated for 20 min with 0.5 mM Gly-Phe-NH-Nap, a substrate for the lysosomal enzyme cathepsin C, the latency of the lysosomal enzymes alpha-glucosidase and beta-hexosaminidase decreased from 75% to 10% and their sedimentability from 75% to 20-30%. In contrast, treatment with Gly-Phe-NH-Nap had no significant effect on the latency of galactosyltransferase, a marker for the Golgi apparatus, and on the sedimentability of glutamate dehydrogenase and catalase, markers for mitochondria and peroxisomes, respectively. The maturation of alpha-glucosidase and cathepsin D in fibroblasts was studied by pulse-labelling with [35S]methionine, immunoprecipitation, polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate and fluorography. When homogenates of labelled fibroblasts were incubated with Gly-Phe-NH-Nap prior to immunoprecipitation, 70-80% of all proteolytically processed forms of metabolically labelled alpha-glucosidase and cathepsin D was recovered in the supernatant. The earliest proteolytic processing steps in the maturation of alpha-glucosidase and cathepsin D appeared to be coupled to their transport to the lysosomes. Although both enzymes are transported via the mannose-6-phosphate-specific transport system, the velocity with which they arrived in the lysosomes was consistently different. Whereas newly synthesized cathepsin D was found in the lysosomes 1 h after synthesis, alpha-glucosidase was detected only after 2-4 h. When a pulse-chase experiment was carried out in the presence of 10 mM NH4Cl there was a complete inhibition of the transport of cathepsin D and a partial inhibition of that of alpha-glucosidase to the lysosomes. Leupeptin, an inhibitor of lysosomal thiol proteinases, had no effect on the transport of labelled alpha-glucosidase to the lysosomes. However, the early processing steps in which the 110-kDa precursor is converted to the 95-kDa intermediate form of the enzyme were delayed, a transient 105-kDa form was observed and the conversion of the 95-kDa intermediate form to the 76-kDa mature form of the enzyme was completely inhibited.(ABSTRACT TRUNCATED AT 400 WORDS)

The intracellular localization of diamine oxidase (EC 1.4.3.6) in rabbit kidney cortex was studied. The distribution of diamine oxidase in the subcellular fractions, obtained by modifying the classical method of Wattiaux-De Coninck, S., Rutgeerts, M.T. and Wattiaux, R. (Biochim. Biophys. Acta (1965) 105, 446-459) demonstrated that this activity is concentrated (greater than 60%) in the microsomal fraction. Biochemical and morphological data indicate a 20-30% contamination of this fraction by plasma membrane and brush border fragments. Subfractionation of the microsomes, obtained by centrifuging in a continuous sucrose-Ficoll gradient (d 1.038-1.064) for 75 min, showed that diamine oxidase is concentrated in membrane deriving from the endoplasmic reticulum. In fact the bulk of diamine oxidase activity was recovered in a subfraction of the gradient which was shown both biochemically and morphologically to derive from the endoplasmic reticulum. The possible significance of this result is discussed.

The subcellular localization of the ω-hydroxylase of Saccharomycopsis lipolytica was assessed by the analytical fractionation technique, originally described by de Duve C., Pressman, B.C., Gianetto, R., Wattiaux, R. and Appelmans, F., and hitherto little, if at all, applied to yeast. Protoplasts were separated in six fractions by differential centrifugation. Some of these fractions were further fractioned by density gradient centrifugation. The distribution of ω-hydroxylase and 15 other constituents chosen as possible markers of its subcellular membranes has been established. ω-Hydroxylase resulted in being bound to a membrane that containes also cytochrome P-450 and NADPH-cytochrome c reductase. This membrane clearly differs from five other subcellular entities. (1) Mitochondria were characterized by particulate malate dehydrogenase, particulate Antimycin A-insensitive NADH-cytochrome c reductase, oligomycin-sensitive and K+-stimulated ATPase pH 9. (2) Most if not all of the catalase and urate oxidase is peroxisomal. (3) Free ribosomes account for most RNA. (4) Nucleoside diphosphatase is for the first time reported in a yeast and appears to belong to an homogeneous population of small membranes. (5) The soluble compartment contains magnesium pyrophosphatase, alkaline phosphatase, 5′-nucleotidase and part of the NADH-cytochrome c reductase. Latent arylesterase and ATPase pH7 have an unspecific distribution. Alkaline phosphodiesterase I has not been detected.