[ACUTE PANCREATITIS IN FAMILY PHYSICIAN PRACTICE].

Acute pancreatitis (AP) is a serious illness, defined as acute inflammation of the pancreas, which can result in damage to the surrounding tissue and other organ systems. It is considered as a set of dynamic, local and systemic pathophysiological changes, caused by sudden rush of lithic pancreatic enzymes into glandular parenchyma. AP is an inflammatory process caused by auto-digestion of pancreatic tissue due to early activation of the zymogen into the active proteolytic enzyme. The most common causes are biliary disease and alcohol abuse. Clinical presentation is predominated by severe upper abdominal pain. Depending on the disease severity, it may be associated with systemic complications and damage to distant organs. The majority of patients have multiply elevated serum concentrations of pancreatic enzymes, amylase and lipase. AP may have a variable course and prognosis, from mild to severe forms and potentially lethal disease; therefore, early assessment using different prognostic parameters is of utmost importance. Clinical signs vary from mild interstitial pancreatitis to severe pancreatitis with necrosis and associated multiple organ failure. The clinical course of mild AP is generally without complications and full recovery is expected. Treatment is conservative and/or surgical, and consists of pain control, fluid replacement, nutritional support, and prevention of complications. Key words:

Analysis of the mechanism by which melatonin inhibits human eosinophil peroxidase.

BACKGROUND AND PURPOSE: Eosinophil peroxidase (EPO) catalyses the formation of oxidants implicated in the pathogenesis of various respiratory diseases including allergy and asthma. Mechanisms for inhibiting EPO, once released, are poorly understood. The aim of this work is to determine the mechanisms by which melatonin, a hormone produced in the brain by the pineal gland, inhibits the catalytic activity of EPO. EXPERIMENTAL APPROACH: We utilized H2O2-selective electrode and direct rapid kinetic measurements to determine the pathways by which melatonin inhibits human EPO. KEY RESULTS: In the presence of plasma levels of bromide (Br-), melatonin inactivates EPO at two different points in the classic peroxidase cycle. First, it binds to EPO and forms an inactive complex, melatonin-EPO-Br, which restricts access of H2O2 to the catalytic site of the oxidation enzyme. Second, melatonin competes with Br- and switches the reaction from a two electron (2e-) to a one electron (1e-) pathway allowing the enzyme to function with catalase-like activity. Melatonin is a bulky molecule and binds to the entrance of the EPO haem pocket (regulatory sites). Furthermore, Br- seems to enhance the affinity of this binding. In the absence of Br-, melatonin accelerated formation of EPO Compound II and its decay by serving as a 1e- substrate for EPO Compounds I and II. CONCLUSIONS AND IMPLICATIONS: The interplay between EPO and melatonin may have a broader implication in the function of several biological systems. This dual regulation by melatonin is unique and represents a new mechanism for melatonin to control EPO and its downstream inflammatory pathways.