No abstract

In experimental models of pancreatitis lipid peroxidation products are increased possibly because of an enhanced generation of oxygen radicals. The purpose of this study was to determine whether lipid peroxidation products are increased in pancreatic tissue and serum of patients suffering from chronic or acute pancreatitis. In 20 patients undergoing operative treatment for chronic ( n = 11) and acute pancreatitis ( n = 9) the levels of malondialdehyde, conjugated dienes, and reduced and oxidized glutathione were determined in resected tissue samples. The excised tissue was examined and evaluated by light microscopy. Shortly before operation the serum concentrations of malondialdehyde, a-amylase, and lipase were measured. Pancreatic tissue from eight organ donors who had no abdominal trauma or pancreatic disease served as control. In chronic pancreatitis, conjugated dienes as well as malondialdehyde concentrations in the tissue were significantly elevated. Reduced glutathione was significantly decreased, suggesting glutathione depletion due to oxidative stress. In acute pancreatitis only the tissue and serum malondialdehyde levels were significantly high, whereas conjugated dienes remained within the normal range. Serum malondialdehyde levels correlated significantly with tissue concentrations (r = 0.76; p < 0.05) but not with the clinical course or the enzyme levels. In chronic pancreatitis, the increased tissue levels of lipid peroxidation products and the changes in glutathione metabolism suggest ongoing peroxidation of lipids due to an enhanced generation of oxygen radicals. In hemorrhagic necrotizing pancreatitis, however, oxygen radical-induced lipid peroxidation cannot be proven. Apparently, other pathomechanisms are involved in the development of the severe tissue damage.

Low arterial blood pH and sustained nitric oxide (NO) production are critical parameters in inflammatory events such as sepsis, and appropriate treatment is still under debate. Because the stability of nitrogen and oxygen intermediates is dependent on the surrounding pH, we investigated whether the relationship among NO, peroxynitrite (ONOO−), and reactive oxygen species production also depends on the pH value, particularly with respect to their effects on hepatocellular damage. Our studies demonstrate that the extracellular pH influences NO and hydroxyl radical (OH) production in hepatocytes. Acidification (pH 7.0) of the medium revealed a significant increase ( P < 0.05) of OH-like radicals, enhanced hepatocellular damage, and a sharp drop in cellular glutathione (GSH) content compared with levels measured at physiological or alkaline pH conditions. Furthermore, inhibition of NO synthesis at all pH conditions resulted in decreased NO production and cellular GSH levels but a simultaneous increase of OH-like radicals and hepatocellular damage with a maximum seen at pH 7.0. Our results suggest that hepatocellular damage is in part regulated by the surrounding pH and that inhibition of NO synthesis at acidic conditions (e.g., in sepsis) leads to increased reactive oxygen-mediated cell injury.

A newly developed modification of the limulus amebocyte lysate test for quantification of endotoxin levels in blood is described. The chromogenic peptide carbobenzoxy-Gly-Gly-Arg-4-methyl-cumarinyl-7-arnid proved to be most suitable. The liberated fluorescent dye is diazotized with N(1-naphtyl-)-ethylen-diamin-dihydrochloride. Using this statistically proved reliable and sensitive test, endotoxin serum levels of healthy persons and patients undergoing major surgical treatment were compared. In the postoperative phase endotoxin serum levels up to 0.5 ng/ml can be detected without clinical signs of septicemia. Healthy persons show endotoxin serum levels up to 0.08 ng/ml. In rats no difference of endotoxin serum levels was detected in the portal vein, and in arterial and venous blood. So a physiological endotoxin resorption from the intestine followed by a clearance during the liver passage seems to be doubtful in this species.

Hemorrhagic mucosal lesions are produced during intestinal ischemia and after reperfusion due at least in part to the accumulation and activation of polymorphonuclear leukocytes in the tissue. It has been shown in vitro that adenosine is instrumental in attenuating this pathophysiological process. Acadesine [5-amino-4-imidazolecarboxamide (AICA) riboside], a purine nucleoside analogue, increases the availability of adenosine in the tissue. The aim of the study was therefore to assess the influence of acadesine treatment on neutrophil accumulation, purine metabolism, and mucosal damage after intestinal ischemia and reperfusion. Intestinal ischemia was induced in cats by partial occlusion of the superior mesenteric artery for 2 h. Samples of the small intestine were exercised before and at the end of the hypotensive period as well as 10 and 60 min after reperfusion. Conjugated dienes, myeloperoxidase, and reduced and oxidized glutathione, as well as the purine metabolites, were determined in the tissue samples. The tissue was also examined histologically. Six cats received saline, and six cats were treated initially before ischemia with acadesine (2.5 mg/kg body wt i.v.) over 5 min as a bolus. Thereafter, acadesine (0.5 mg.kg-1.min- i.v.) was given continuously during ischemia and 30 min after reperfusion. Acadesine treatment significantly attenuated the mucosal lesions seen during reperfusion. This improvement was due at least in part to the inhibition of neutrophil accumulation, as judged by low myeloperoxidase levels. The prevention of neutrophil activation resulted most likely from increased adenosine concentrations in the intestinal tissue in the early reperfusion period.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum KYN seems to be a reliable diagnostic tool for the assessment of post-transplant inflammatory complications, already in an early stage, and for monitoring the efficacy of therapeutic interventions. Prospective studies are recommended.

Serum reductive potential at the site of accident or at admission allows the stratification of trauma patients with respect to lethal outcome in severe trauma when severity scores fail to do so.

The generation of free oxygen radicals is presumed to be a pathogenetic principle in various conditions, primarily in postischemic reperfusion injury. Their assessment is difficult. ESR is an excellent tool to assess free radicals directly. In an experimental model of rat liver ischemia and reperfusion the increased generation of free radicals during reperfusion in liver tissue could be demonstrated after 60 min of liver ischemia. Elevated production rates of radicals could be detected after 5 min of reperfusion for at least 45 min with a maximum after 15 min of reperfusion. Scavenging of these radicals has to start in the very beginning of reperfusion.