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M. Gorky Donetsk National Medical University . Macrophages dysfunction and recurrent gastric ulcer bleeding . Ground. Diagnostics an prediction of outcome Location of ulcer Size of ulcer Forrest class Age and sex Comorbifities Ulcer anamnesis Number of erythrocytes
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M. Gorky Donetsk National Medical University Macrophages dysfunction and recurrent gastric ulcer bleeding
Ground Diagnostics an prediction of outcome • Location of ulcer • Size of ulcer • Forrest class • Age and sex • Comorbifities • Ulcer anamnesis • Number of erythrocytes • Hematocrite • Hemoglobine • Gastric ulcer bleeding M. Gorky Donetsk National Medical University Antonina Kalmykova
Ulcer bleeding risk factors 1 Age 2 Comorbid pathology (portal hypertension, cancer, diabetes mellitus etc.) 3 Size of ulcer more than 2 sm 4 Low hemoglobine concentration at hospital admission M. Gorky Donetsk National Medical University Antonina Kalmykova
Research questions: Why? Why? Why? Reasons of un-sustained hemostasis? Mechanisms of insufficient regeneration? Determinants of recurrent bleeding development? M. Gorky Donetsk National Medical University Antonina Kalmykova
Solving th problem Inflammation Injury Regeneration M. Gorky Donetsk National Medical University Antonina Kalmykova
Targets for investigation Pathogen-associated inflammation Reactivity of organism Epinephrine 5-HT Thrombine LPS Alternative mechanisms Classic mechanisms iNOS of Macrophages M. Gorky Donetsk National Medical University Antonina Kalmykova
GOAL Estimate the role and some mechanisms of macrophage dysfunction in gastric ulcer bleeing M. Gorky Donetsk National Medical University Antonina Kalmykova
APPROACH Clinical and laboratoty data Pathomorphology of ulcer margin Endoscopy (size, location, hemostasis) State of monocytes-macrophage lineage OUTCOME OF ULCER BLEEDING M. Gorky Donetsk National Medical University Antonina Kalmykova
Desighn of investigation 1st group Groups 2nd group Age Sex Comorbidity Preliminary treatment Endoscopic features Laboratory tests data Clinical criteria M. Gorky Donetsk National Medical University Antonina Kalmykova
Materials and methods • Morphological investigation • Histological specimens • Staning: hematoxylin and eosin Ishemia Infiltration • Immunohistochemistry Number anddistributionof CD68 positive cell • Biochemical analysis of iNOS activity in monocytes Monocytes + 0 Monocytes + LPS Monocytes + alternative regulators (thrombin and epinephrine). M. Gorky Donetsk National Medical University Antonina Kalmykova
Results of investigation M. Gorky Donetsk National Medical University Antonina Kalmykova
Results of investigation M. Gorky Donetsk National Medical University Antonina Kalmykova
Results of investigation M. Gorky Donetsk National Medical University Antonina Kalmykova
Results Nitrites concentration in supernatant of un-stimulated monocytes (nmol NO2-/ml) M. Gorky Donetsk National Medical University Antonina Kalmykova
Results Basal and LPS-stimulated activity of iNOS in intact and of stimulated monocytes (nmol NO2-/ml) M. Gorky Donetsk National Medical University Antonina Kalmykova
Results Nitrites concetntration in supernatant of stimulated monocytes (nmol NO2-/ml) Gastric bleeding Healthy volontiers M. Gorky Donetsk National Medical University Antonina Kalmykova
Conclusion Gastric ulcer bleeding is accompanied with proinflammatory activation of peripheral blood monocytes and increase of macrophages recruitment into the gastric mucosa. 2. This changes are associated with desregulation of monocytes-macrophages activity and disbalance in L-arginine metabolism. 3. Hyperactivation of these cells can be concidered is one of the reason of recurrent bleeding M. Gorky Donetsk National Medical University Antonina Kalmykova
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