Sulaieva O.N., Deliy V.Yu.

THE ROLE OF ACUTE INFLAMMATORY RESPONSE IN THE DEVELOPMENT OF ULCER BLEEDING

---

About the author:	Sulaieva O.N., Deliy V.Yu.
Heading	CLINICAL MEDICINE
Type of article	Scentific article
Annotation	The goal of this study was to estimate the severity of the acute inflammatory response in patients with primary and recurrent bleeding under peptic ulcers of stomach and duodenum. Evaluation of peripheral blood and biopsies of the marginal zone of ulcers was conducted among patients with acute ulcer bleeding who were subdivided into two groups according the outcome: with effective hemostasis (group 1, n = 35) and in the development of rebleeding (group 2, n = 40). There were no differences between patients of the 1st and 2nd groups with respect to age, male sex, and previous ulcer disease. A comparison of peripheral blood reaction to acute ulcer bleeding did not demonstrate differences in terms of erythrocyte, platelet and hemoglobin concentrations, total white blood cell count. Despite the increase of neutrophil count in peripheral blood of bleeders comparing with control (P=0,031), there were not significant differences between 1st and 2nd groups. However, plasma fibrinogen concentration in rebleeders was significantly higher than in 1st group patients (P=0,01) A comparison of histological changes in the ulcer margin and intact mucosa has revealed that the development of bleeding is associated with ischemic injury and acute inflammatory reaction in the ulcer margin, regardless of the ulcer location. Compared with patients from the 1st group, rebleeders exhibited more severe neutrophilic infiltration that was associated with secondary damage and an expansion in width of the necrosis area that might be one of the reasons for rebleeding. However, there were no correlation between peripheral blood leukocytes or neutrophils and severity of local PMNs infiltration in ulcer margin. The morphometric analysis of immunohistochemical stains showed an increased representation of macrophages at the ulcer margin compared to the intact mucosa (P<0,01). We found that the tissue infiltration of macrophages in the ulcer margin derived from rebleeders was significantly increased at the time of admission when compared with that of patients with sustained hemostasis (P<0,001). The macrophages number correlated with the neutrophil recruitment (P<0,001), the intensity of edema (P<0,01) and the severity of the ulcer margin injury (P<0,01). In addition, we compared the aggregation of platelets alone and in combination with leukocytes. It was found that the coincubation of platelets with leukocytes significantly decreased the collageninduced aggregation(P=0,008). Thus, the histological investigation showed the link between the local macrophages’ reaction and the increased recruitment of neutrophils in the margin of ulcers. In addition, the realization of exaggerated acute inflammatory reaction in the ulcer margin, which is considered to be one of the sources of healing, was associated with a progressive damage of tissues in width and depth resulting in rebleeding. In addition it was shown that leukocytes modulate platelet reactivity leading to hemostasis failure due to inhibition of platelets’ response to collagen.
Tags	peptic ulcer, acute bleeding, inflammation, neutrophils, macrophages
Bibliography	Barinov Je. F. Gastrointestinal'nye miofibroblasty – rol' v reguljacii fiziologicheskoj aktivnosti i reparacii zheludochno-kishechnogo trakta / Je.F. Barinov, O. N. Sulaeva // RZhGGK. – 2010. – T. 20. – №. 3. – S. 9-18. Barinov Je.F. Mehanizmy trombogeneza / Je. F. Barinov, O. N. Sulaeva // Kardiologija. – 2012. – T. 52. – № 2. – S. 45-56. Barinov Je.F. Rol' serotonina v fiziologii i patologii zheludochno-kishechnogo trakta / Je. F. Barinov, O. N. Sulaeva // RZhGGK. – 2012. – №2. – S. 4-13. Kondratenko P.G. Ostroe krovotechenie v prosvet organov pishhevaritel'nogo kanala / P.G. Kondratenkoju – D.– 2006.– 420 s. Kononov A.V. Vospalenie kak osnova Helicobacter pylori-associirovannyh zabolevanij / A.V. Kononov // Arh. Patol. – 2006. – № 5. – S. 3-10. Sulaєva O. M. Dinamіka funkcіonal'nogo stanu nejtrofіlіv u pacієntіv z virazkovimi krovotechami / O.M. Sulaєva // Tavr. med.-biol. estnik. – 2011. – № 14, Ch. 2. – S. 56-60. Barinov E.F. Blood monocytic L-arginine metabolic changes in diabetic foot syndrome / E.F. Barinov, O.N. Sulaeva, M.E. Barinova // Klin Lab Diagn. -2010. – № 5. – R. 16-19. Barinov E. F. Gastric and duodenal mucosa protection and defense / E. F. Barinov, O. N. Sulaieva // Curr. Gastroenterol. – 2011. – T. 61(5). – S. 36-43. Barinov E. Platelet aggregation measurement for assessment of hemostasis failure mechanisms in patients with gastroduodenal ulcer bleeding / E. Barinov, O. Sulaieva, Y. Lyakch // Clin. Exp. Gastroenterol. – 2013. – T. 6. – S. 139-148. Mills C.D. M1 and M2 macrophages: oracles of health and disease / C. D. Mills // Crit. Rev. Immunol. – 2012. – Vol. 32. – R. 463-488. Mantovani A. Macrophage plasticity and polarization in tissue repair and remodeling. / A. Mantovani, S.K. Biswas, M.R. Galdiero // J. Pathol. – 2013. – Vol. 229. – R. 176-185. Petrie A. Medical Statistics at a Glance / A. Petrie, S. Sabin // 2nd ed. Malden, MA: Blackwell Publishing; -2005. Sulaieva O. Vagus Nerve Versus Helicobacter pylori: New View on Old Secrets of Gastroduodenal Pathology / O. Sulaieva // Ann. Rev. Res. Biol. – 2014. – T. 4. – №. 22. – P. 3392-3408. Sulaieva O. Gaseous mediator-based anti-inflammatory drugs / O. Sulaieva, J.L. Wallace // Curr. Opin. Pharmacol. – 2015. – Vol. 25. – P. 1-6. Tarnawski A.S. Cellular and molecular mechanisms of gastrointestinal ulcer healing / A.S. Tarnawski // Dig. Dis. Sci. – 2005. – Vol. 50(1). – P. 24-33. Wallace J.L. Inflammatory mediators in gastrointestinal defense and injury / J.L. Wallace, L. Ma // Exp. Biol. Med. – 2001. – Vol. 11. – P. 1003-1015. Wallace J. L. Toward More GI-Friendly Anti-Inflammatory Medications / J. L. Wallace, G. de Nucci, O. Sulaieva // Curr. Treat. Opt. Gastroenterol. – 2015. – Vol. 13 (4). – R. 64-69
Publication of the article	«World of Medicine and Biology» №4(53) 1 part 2015 year, 073-077 pages, index UDK 616.32/.33-002.44-005.1