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<article article-type="research-article" dtd-version="1.2" xml:lang="ru" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><front><journal-meta><journal-id journal-id-type="issn">2658-6533</journal-id><journal-title-group><journal-title>Research Results in Biomedicine</journal-title></journal-title-group><issn pub-type="epub">2658-6533</issn></journal-meta><article-meta><article-id pub-id-type="doi">10.18413/2313-8955-2019-5-1-0-5</article-id><article-id pub-id-type="publisher-id">1609</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pharmacology</subject></subj-group></article-categories><title-group><article-title>Pharmacological correction of immune and metabolic disorders in acute biliary pancreatitis of varying severity</article-title><trans-title-group xml:lang="en"><trans-title>Pharmacological correction of immune and metabolic disorders in acute biliary pancreatitis of varying severity</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Mikaelyan</surname><given-names>Pavel K.</given-names></name><name xml:lang="en"><surname>Mikaelyan</surname><given-names>Pavel K.</given-names></name></name-alternatives><email>paul_keropoff@mail.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Loktionov</surname><given-names>Alexey L.</given-names></name><name xml:lang="en"><surname>Loktionov</surname><given-names>Alexey L.</given-names></name></name-alternatives></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Bystrova</surname><given-names>Natalya A.</given-names></name><name xml:lang="en"><surname>Bystrova</surname><given-names>Natalya A.</given-names></name></name-alternatives><email>konoplya51@mail.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Nazarenko</surname><given-names>Peter M.</given-names></name><name xml:lang="en"><surname>Nazarenko</surname><given-names>Peter M.</given-names></name></name-alternatives><email>nazarenko700pm@yandex.ru</email></contrib></contrib-group><pub-date pub-type="epub"><year>2019</year></pub-date><volume>5</volume><issue>1</issue><fpage>0</fpage><lpage>0</lpage><self-uri content-type="pdf" xlink:href="/media/medicine/2019/1/Биомедицинские_иссл-64-84.pdf" /><abstract xml:lang="ru"><p>Background: The incidence of acute pancreatitis is up to 40 cases per 100,000 adult population per year, including about 10-15% of patients with severe forms of this disease, and mortality reaching up to 80%. The aim of the study: to establish the pharmacological effectiveness of the combined use of immunomodulators, antioxidants and membrane protectors in acute biliary pancreatitis of varying severity in the experiment and clinic. Materials and methods: Acute pancreatitis was modeled in Wistar rats. Before and after the introduction of combinations of drugs, indicators of the immune status and parameters of the oxidative system were evaluated. 72 patients of Kursk City Hospital No. 4 were clinically examined and treated with minimally invasive surgical methods in combination with pharmacotherapy, using Polyoxidonium, Emoxipine and Essentiale N. The blood levels of cytokines, complement system parameters, and oxidant system were evaluated. Results: It was experimentally established that in relation to the mild form of acute pancreatitis, the changes were completely corrected by combinations of Ferrovir, Mexidol and Phosphogliv or Polyoxidonium, Emoxipine and Essentiale N, and with medium and high severity, pronounced immunometabolic disturbances were observed, which were not effectively corrected with the proposed combinations. Clinically, with mild, to a lesser extent, with a medium form of acute biliary pancreatitis, a more pronounced pharmacological efficacy of a combination of Polyoxidonium, Emoxipine and Essentiale N. was observed. Conclusion: The combination of Polyoxidonium, Emoxipine and Essentiale N in experimental acute pancreatitis of varying severity in the correction of immune and metabolic disorders was most effective. In patients with acute pancreatitis of biliary etiology of mild, to a greater extent with medium severity, in plasma, there was found an increase in the level of pro-, anti-inflammatory cytokines, metabolic activity of peripheral blood neutrophils, activation of lipid peroxidation, a decrease in the content of C3-and C4-complement components, phagocytic activity of blood neutrophils. In a medium degree of severity, a further increase in the content of IL-10, the activity of superoxide dismutase, catalase, a decrease in the levels of IL-2, IL-1Ra were observed. The inclusion in the treatment of patients with acute pancreatitis of biliary etiology of mild severity of a combination of polyoxidonium, emoxypine with Essentiale N has completely normalized changes in immune and oxidant parameters. In the medium severity the used scheme has corrected totally 78.4% of the laboratory immunometabolic parameters.</p></abstract><trans-abstract xml:lang="en"><p>Background: The incidence of acute pancreatitis is up to 40 cases per 100,000 adult population per year, including about 10-15% of patients with severe forms of this disease, and mortality reaching up to 80%. The aim of the study: to establish the pharmacological effectiveness of the combined use of immunomodulators, antioxidants and membrane protectors in acute biliary pancreatitis of varying severity in the experiment and clinic. Materials and methods: Acute pancreatitis was modeled in Wistar rats. Before and after the introduction of combinations of drugs, indicators of the immune status and parameters of the oxidative system were evaluated. 72 patients of Kursk City Hospital No. 4 were clinically examined and treated with minimally invasive surgical methods in combination with pharmacotherapy, using Polyoxidonium, Emoxipine and Essentiale N. The blood levels of cytokines, complement system parameters, and oxidant system were evaluated. Results: It was experimentally established that in relation to the mild form of acute pancreatitis, the changes were completely corrected by combinations of Ferrovir, Mexidol and Phosphogliv or Polyoxidonium, Emoxipine and Essentiale N, and with medium and high severity, pronounced immunometabolic disturbances were observed, which were not effectively corrected with the proposed combinations. Clinically, with mild, to a lesser extent, with a medium form of acute biliary pancreatitis, a more pronounced pharmacological efficacy of a combination of Polyoxidonium, Emoxipine and Essentiale N. was observed. Conclusion: The combination of Polyoxidonium, Emoxipine and Essentiale N in experimental acute pancreatitis of varying severity in the correction of immune and metabolic disorders was most effective. In patients with acute pancreatitis of biliary etiology of mild, to a greater extent with medium severity, in plasma, there was found an increase in the level of pro-, anti-inflammatory cytokines, metabolic activity of peripheral blood neutrophils, activation of lipid peroxidation, a decrease in the content of C3-and C4-complement components, phagocytic activity of blood neutrophils. In a medium degree of severity, a further increase in the content of IL-10, the activity of superoxide dismutase, catalase, a decrease in the levels of IL-2, IL-1Ra were observed. The inclusion in the treatment of patients with acute pancreatitis of biliary etiology of mild severity of a combination of polyoxidonium, emoxypine with Essentiale N has completely normalized changes in immune and oxidant parameters. In the medium severity the used scheme has corrected totally 78.4% of the laboratory immunometabolic parameters.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>biliary pancreatitis</kwd><kwd>immune disorders</kwd><kwd>oxidative disorders</kwd><kwd>immunomodulators</kwd><kwd>antioxidants</kwd><kwd>membrane protectors</kwd></kwd-group><kwd-group xml:lang="en"><kwd>biliary pancreatitis</kwd><kwd>immune disorders</kwd><kwd>oxidative disorders</kwd><kwd>immunomodulators</kwd><kwd>antioxidants</kwd><kwd>membrane protectors</kwd></kwd-group></article-meta></front><back><ref-list><title>Список литературы</title><ref id="B1"><mixed-citation>Karaulov AV. [Immunology, Microbiology, Immunopathology]. Moscow: Binom; 2012. Russian.</mixed-citation></ref><ref id="B2"><mixed-citation>Konoplya AI, Bushmina ON, LoktionovaAV, et al.[Immunomodulators, antioxidants, membrane protectors in correction of immunometabolic disturbances in experimental destructive acute pancreatitis in conditions of chronic alcoholic intoxication]. Belgorod State University Scientific bulletin. Medicine. Pharmacy. 2015;16(213):141-148. Russian.</mixed-citation></ref><ref id="B3"><mixed-citation>MB, Nazarenko PM, Ishunina TA, et al. [The use of roncoleukin for the correction of the secondary immunodeficiency in the elderly patients with acute cholecystitis]. The Russian Journal of Immunology. 2017;11(20)(3):470-471. Russian.</mixed-citation></ref><ref id="B4"><mixed-citation>Schmidt AI, K&amp;uuml;hlbrey C, Lauch R, et al. The predominance of a naive T helper cell subset in the immune response of experimental acute pancreatitis. Pancreatology. 2017;17(2):209-218. DOI: 10.1016/j.pan.2017.02.011</mixed-citation></ref><ref id="B5"><mixed-citation>Ermolov AS, Blagovestnov DA, Rogal ML, et al. [Long-term results of severe acute pancreatitis management]. Khirurgiya. Zhurnal imeni N.I. Pirogova. 2016;10:11-15. Russian. DOI: 10.17116/hirurgia20161011-15</mixed-citation></ref><ref id="B6"><mixed-citation>Bagnenko SF, Gol&amp;#39;tsov VP, Savello VE, et al. [Classification of acute pancreatitis: current state of the issue]. Vestnik khirurgii imeni I.I. Grekova. 2015;174(5):86-92. Russian. DOI: https://doi.org/10.24884/0042-4625-2015-174-5-86-92</mixed-citation></ref><ref id="B7"><mixed-citation>Razumova MS, Litvinova ES, Bystrova NA, et al. [Correction of metabolic activity of erythrocytes of a peripheric blood at an experimental acute toxic lesion of a liver]. Modern problems of science and education. 2016;5:51. Russian.</mixed-citation></ref><ref id="B8"><mixed-citation>Song L, W&amp;ouml;rmann S, Ai J, et al. PBCL3 Reduces the Sterile Inflammatory Response in Pancreatic and Biliary Tissues. Gastroenterology. 2016;150(2):499-512. DOI: 10.1053/j.gastro.2015.10.017.</mixed-citation></ref><ref id="B9"><mixed-citation>Konoplya AI. The relationship of immunometabolic and erythrocyte disorders in the etiology of acute pancreatitis. Kursk: Kursk State Medical University; 2013. Russian.</mixed-citation></ref><ref id="B10"><mixed-citation>Loktionov AL, Kozlova AI, Voropaev EV, et al. [Differential laboratory diagnostics of acute biliarny and nonbiliarny pancreatitis]. Belgorod State University Scientific Bulletin. Medicine. Pharmacy. 2015;31(16(213)):31-39. Russian.</mixed-citation></ref><ref id="B11"><mixed-citation>Pokrovsky MV. [Endothelioprotective effects of ademetionine in endothelial dysfunction]. The Journal of scientific articles &amp;quot;Health and Education millennium&amp;quot;. 2017;19(8):169-172. Russian.</mixed-citation></ref><ref id="B12"><mixed-citation>Lazarenko VA, Loktionov AL, Azarova YuE, et al. [Correction of cytokinsyntetic activity of peritoneal macrophages with longidaza in acute pancreatitis of various etiology]. Kursk Scientific and Practical Bulletin &amp;quot;Man and Health&amp;quot;. 2010;4:79-83. Russian.</mixed-citation></ref><ref id="B13"><mixed-citation>Kang R, Chen R, Xie M, et al. The Receptor for Advanced Glycation End Products Activates the AIM2 Inflammasome in Acute Pancreatitis. J Immunol. 2016;196(10):4331-4337. DOI: https://doi.org/10.4049/jimmunol.1502340</mixed-citation></ref><ref id="B14"><mixed-citation>Mikaelyan PK, Loktionov AL, Karaulov AV, et al. [Combined immunomodulatory, antioxidant and membrane-protective therapy in various forms of acute experimental pancreatitis]. Medical Immunology (Russia). 2017;19:48-49. Russian.</mixed-citation></ref><ref id="B15"><mixed-citation>Zinkin VYu. [A method of quantitative evaluation of oxygen-dependent metabolism of human neutrophil granulocytes]. Russian Clinical Laboratory Diagnostics. 2004;2:27-31. Russian.</mixed-citation></ref><ref id="B16"><mixed-citation>Gubler EV. [Application of nonparametric statistical criteria in biomedical research]. Moscow: Medicine; 1973. Russian.</mixed-citation></ref><ref id="B17"><mixed-citation>Zemskov AM, Zemskov VM, Kozlov VA, et al. [Clinical Immunology and Allergology]. Moscow: Istoki publishers; 2016. Russian.</mixed-citation></ref><ref id="B18"><mixed-citation>Sunyaikina OA, Konoplya AI, Loktionov AL, et al. [Indicators of immune and oxidative status in the diagnosis of acute pancreatitis of biliary and nonbiliary etiology]. Medical Immunology (Russia). 2015;17(4):385. Russian.</mixed-citation></ref><ref id="B19"><mixed-citation>Loktionov AL, Karaulov AV, Konoplya AI, et al. [Influence of refortane on cytokinoproduction activity of peritoneal macrophages at the acute pancreatitis]. Systems analysis and management in biomedical systemsRussian.</mixed-citation></ref><ref id="B20"><mixed-citation>Zhuang X, Shen J, Jia Z, et al. Anti-B7-H3 monoclonal antibody ameliorates the damage of acute experimental pancreatitis by attenuating the inflammatory response. Int Immunopharmacol. 2016;35:1-6. DOI: 10.1016/j.intimp.2016.03.013</mixed-citation></ref><ref id="B21"><mixed-citation>Bettac L, Denk S, Seufferlein T, et al. Complement in Pancreatic Disease &amp;ndash; Perpetrator or Savior? Front Immunol. 2017;17(8):15. DOI: https://doi.org/10.3389/fimmu.2017.00015</mixed-citation></ref><ref id="B22"><mixed-citation>Nazarenko PM, Nazarenko DP, Kanishchev YuV, et al. [Surgical Strategy in Acute Biliary Pancreatitis]. Annaly khirurgicheskoy gepatologii. 2011;16(3):71-76. Russian.</mixed-citation></ref><ref id="B23"><mixed-citation>Lazutkin MV. [Percutaneous puncture and endoscopic interventions in the treatment of complications of chronic pancreatitis]. Vestnik khirurgii imeni I.I.Grekova. 2014;173(2):118-121. Russian. DOI: https://doi.org/10.24884/0042-4625-2014-173-2-118-121</mixed-citation></ref><ref id="B24"><mixed-citation>Zemskov AM. [Clinical efficacy of immunostimulating drugs in treatment of purulent infections]. Khirurgiya. Zhurnal imeni N.I. Pirogova. 2011;2:4-10. Russian.</mixed-citation></ref><ref id="B25"><mixed-citation>Minkov GA, Halacheva KS, Yovtchev YP, et al. Pathophysiological mechanisms of acute pancreatitis define inflammatory markers of clinical prognosis. Pancreas. 2015;44(5):713-717. DOI: 10.1097/MPA.0000000000000329</mixed-citation></ref></ref-list></back></article>