RESULTS

1. Natalia Obraztsova, Oksana Sulaieva, StanislavZharikov and Victoria Delii Donetsk national medical university of M. Gorky, Ukraine EFFECTS OF PROTON PUMP INHIBITORS AND H2-ANTAGONISTS ON NEUTROPHIL OXIDATIVE METABOLISM IN PATIENTS WITH GASTRIC AND DUODENAL ULCER BLEEDING RESULTS INTRODUCTION NBT reduction rate was significantly higher in patients with active bleeding (F1a) than that in patients with sustained haemostasis (p<0.05). It has been shown that intensity of superoxide radicals’ production by Nph was higher in patients who were admitted after 12-24 hours than at 3-6 hours after clinical manifestation of hemorrhage (p<0.05). Administration of PPIs was associated with decreaseof the NBT-reaction (p<0.01), whereas H2A administration led to stimulation of NADPH-oxidase activity (p<0.05) in Nph. The administration of PPIs was also accompanied by an increased proliferation of epithelium and angiogenesis. Despite the progress in pharmacotherapy and endoscopic management of bleeding 20-30% of patients demonstrate the recurrent bleeding. One of the reasons of it may be inflammation propagation related with dysfunction of neutrophils (Nph). 
 The goal of this research was to estimate the effects of the most common antisecretory drugs as proton pumps inhibitors (PPI) and H2 antagonists (H2A) on Nph oxidative metabolism. Sp. density of Nphs in the marginal zone of ulcer in patients hospitalized at different terms The defining of Nph status, which were isolated from blood of patients with ulcer bleedings, after 3 days of treatment revealed some interesting facts. The most important was the opposite effect of PPIs and H2As on sNBT. While in the 1st group was registered a substantial restriction of sNBT level, in the 2nd group it was much higher. The interpretation of this phenomenon goes back to the cause and effect events, that overall determine the effectiveness of a drug. High NphNADPH-oxidase activity in patients treated with H2As not only represents the status of oxygen-dependent processes, but can also be accompanied by increased production of arachidonic acid metabolites, proinflammatory cytokines and chemokines. On the other hand, pro-inflammatory activation of Nph usually is associated with increasing of their adhesive and migratory activity, which in it’s turn can explain increased recruitment to the affected area and the severity of secondary alteration in patients of 2nd group. Not surprisingly, that negative effect of H2Aswas registered in patients hospitalized during the 24 hours after the first bleeding signs. At this time already are activated own mechanisms of acute inflammatory response, and taking H2Ascan potentiate the process leading to amplified alteration. In contrast to this, blocking the proton pump, analogues of which are also working in lysosomes of phagocytes, was accompanied by a significant decrease the intensity of sNBT reaction, as well as iNBT. It is likely that this effect represents anti-inflammatory effect of PPIs. In addition, the decrease in the intensity of NBT reaction, in fact, represents lower NADPH-oxidase activity, and so the severity of oxidative damage of structures (at the ulcer margin and restriction of acute inflammatory reaction) . DISCUSSION 1st group PPIs 2nd group H2As 1st group PPIs 2nd group H2As CONCLUSIONS • Thus, the analysis of morphological and cytochemical results leads to the following conclusions: • 1. The administration of anti-secretory drugs not only affects the secretory activity and gastric acidity, but also modulates the inflammation, and status of gastro-intestinal barrier. • 2. The administration of PPIs is accompanied by the decrease of proinflammatoryactivation of neutrophils, and as a result has an anti-inflammatory effect in the marginal zone of the ulcer. However, PPIs didn’t influence the severity of lymphocytic infiltration. • 3. The adverse effect of PPIs treatment considers the following change in gastrointestinal barriers of gastroduodenal area such as an increased proliferation of epithelium, that was not accompanied by effective differentiation of the cells.Thus the status of mucus-bicarbonate barrier can be affected. • 4. The treatment of patients with H2Aswas associated with the maintenance of inflammatory infiltration in GDA or with the enhancement of it during the 1st day from the beginning of bleeding. • 5. The potentiating effect of H2Ason the acute phase of inflammation is caused by stimulation of the oxygen dependent metabolism in Nph from peripheral blood and by their recruitment to the marginal zone of ulcer and supporting an acute inflammatory response there. • Administration of PPI and H2A not only affect gastric acid production but also change innate immunity mechanisms since NADPH-oxidase activity of Nph is related with phagocytosis and lifespan. So antisecretory drugs can change the acute inflammatory reaction by modulation of leukocytes kinetics in ulcer region. METHODS AND MATERIALS Characteristics of bleeding were defined in 124 patients by clinical, laboratory and endoscopic criteria according to Forrest class. In total, 63 patients were treated with PPI, and 61 with H2A. To assess Nph oxidative metabolism, superoxide production was measured using the nitrobluetetrazolium reduction test (NBT) in isolated neutrophils at 1st, 3d and 7th day of therapy. Morphologically in the marginal zone of ulcers were assessed intensity of infiltration and its cellular composition. To asses cell proliferation and angiogenesis were measured the expression of Ki-67 and CD131 2 4 3 1 5 Lamina propria of the piloric portion of stomach in patients with duodenal ulcers. Infiltration of lamina propria with lymphocytes, plasmocytes, neutrophils and eosinophils. Hypersecretion of pyloric glands. H & E. High magnification (x 400). Cell proliferation in the marginal zone of ulcer of duodenum in patient at the moment of admission. Immunohistochemical staining using mAb to Ki-67 High magnification (x 400) Enhanced proliferation of gastric epithelium in patients of group 1.Immunohistochemical staining using mAbto Ki-67 High magnification (x 400) Angiogenesis in the marginal zone of ulcer of duodenum in patients of group 1. Immunohistochemical staining using mAbto CD-131. High magnification (x 400) Enchanced rescrutmet ofleukocytestomuscalarismucosae in marginal zone of ulcer under the treatment in patients of 2nd group H & E. High magnification (x 400) CONTACT OBRAZTSOVA NATALIA email: natalionus@gmail.com M. Gorky DONETSK NATIONAL MEDICAL UNIVERSITY, UKRAINE