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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the effects of acute pancreatitis on the energy metabolism of the liver and on the fragility of hepatic cells and subcellular organelles, we studies (1) the arterial blood ketone body ratio (BKBR) (aceto acetate/beta-hydroxy butyrate), which is in equilibrium with the free NAD+/NADH ratio in liver mitochondria; (2) the hepatic energy charge (EC) = (ATP + 1/2 ADP)/(ATP + ADP + AMP); (3) the cathepsin B leakage from hepatic lysosomes and the malate dehydrogenase leakage from hepatic mitochondria in vitro; and (4) the protective effects of prostaglandin E2 (PGE2) and a new synthetic protease inhibitor ONO 3307 on hepatic injury in acute pancreatitis induced in rats by a supramaximal dose of caerulein. Decreased BKBR and hepatic EC as well as increased hepatic lysosomal and mitochondrial fragility were observed in rats with this type of acute pancreatitis, and both PGE2 and ONO 3307 had a significant protective effect against hepatic injury in these rats, especially ONO 3307. These results suggest that impaired hepatic energy metabolism is closely related to increased hepatic lysosomal and mitochondrial fragility and that some proteases, which are derived from pancreatitis and are susceptible to inhibition by ONO 3307, seem to play an important pathological role in this liver injury induced by pancreatitis. Therefore, it is important to take care of the liver in patients with acute pancreatitis.
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PMID:Impaired hepatic energy metabolism in rat acute pancreatitis: protective effects of prostaglandin E2 and synthetic protease inhibitor ONO 3307. 152 49

The aim of this study was to investigate the effect of Nafamostat mesilate (FUT-175) on some blood platelet properties during the first hours of acute experimental pancreatitis (AEP) in dogs. A significant decrease in platelet count, hyperaggregability of platelets by ADP and PAF as well as an increased level of TXB2, were found in the early stage of AEP. No changes in platelet aggregation induced with AA were demonstrated. FUT-175 prevented a decrease in platelet number and inhibited platelet aggregation induced with ADP, PAF and AA when it was given immediately after induction of AEP. No evident changes in TXB2 levels in dogs treated with FUT-175 were found. Our results indicate that the positive effect of FUT-175 in AEP in part depends on its antiaggregatory action.
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PMID:Blood platelet function in canine acute pancreatitis with reference to treatment with Nafamostat mesilate (FUT-175). 157 98

In this study, changes of hepatic cellular ATP, ADP, and AMP, concentrations and mitochondrial oxidative phosphorylation were investigated in rats with experimental acute necrotizing pancreatitis (ANP). It was found that energy change (ATP + 1/2 ADP)/(ATP + ADP + AMP) of the liver decreased from 0.866 to 0.806 (P less than 0.05) 24 h after ANP, and to 0.769 (P less than 0.01) at 48 h. On the other hand, mitochondrial phosphorylative activity increased to 130% and 157% over the control at 12 h and 24 h respectively, and then rapidly dropped to 62% of normal value at 48 h. Blood ketone body ratio was positively correlated with hepatic energy charge level in ANP. The authors came to the following conclusions that: (1) In ANP, mitochondrial function damage resulted in decreased hepatic energy charge, which, in turn, led to hepatocellular impairment; (2) the measurement of blood ketone body ratio was a reliable indicator by which to assess the energy status of the liver in ANP.
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PMID:[Changes in hepatic energy metabolism in rats with acute necrotizing pancreatitis]. 208 1

The damage to the liver during acute pancreatitis (AP) could be partly dependent on depressive action of pancreatitis associated ascitic fluid (PAAF) on the energy metabolism of hepatocytes. The aim of the study was to assess the effect of PAAF from dogs with acute experimental pancreatitis (AEP) and from humans with AP on the respiratory function of isolated rat liver mitochondria (RLM). The mitochondrial oxygen consumption rate in state 3 respiration (with ADP) and in state 4 (without ADP) using sodium succinate as substrate and oxygen Clark's electrode was estimated. Respiratory control ratio (RCR) and P/O ratio were calculated. PAAF was collected after 6 h of AEP induced by Elliott's method in 8 dogs, and from 4 patients with AP, intraoperatively. Both animal and human PAAFs increase the oxygen consumption rate by RLM in state 4 dose dependently (by 65% with 50 microL to 150% with 200 microL of canine PAAF). This uncoupling effect of human PAAF was twice more potent than the canine. Dialysis of PAAF reduced this effect almost completely. The mitochondrial ATPase activity in RLM treated with PAAF was stimulated and this effect was also reduced by dialysis. The conclusion was that the damage to the liver in AEP could be partly dependent on the toxicity of dializable component(s) of PAAF on the energy metabolism of mitochondria. These findings may partly explain the beneficial effects of peritoneal lavage in acute pancreatitis.
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PMID:The effect of pancreatitis associated ascitic fluid on some functions of rat liver mitochondria. A possible mechanism of the damage to the liver in acute pancreatitis. 248 Sep 84

The role of blood platelets in the disturbed haemostasis in acute pancreatitis is not fully elucidated. The aim of this study was to evaluate the blood platelet function during the first hours of acute experimental pancreatitis (AEP) in dogs. AEP was induced by the retrograde injection of bile and trypsin into the main pancreatic duct. Platelet count, platelet aggregation induced with ADP, PAF, AA as well as plasma Beta-TG and TXB2 levels were determined. At 30 min after induction of AEP a significant decrease of platelet count was noted; these changes were observed until 4 th hr. At 30 min as well as at 60 min of AEP increased sensitivity of platelet aggregation to ADP was found. After that time evident decrease of platelet aggregation to ADP was shown. Platelets sensitivity to PAF was higher at 30 min of AEP whereas 60 min, 2 and 4 hrs after AEP normalization of platelet aggregation by PAF was observed. The significant increase of plasma Beta-TG and TXB2 concentrations corresponded well to changes of platelet aggregation. These results indicate that AEP affects blood platelet function with the drop of their count.
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PMID:Does acute experimental pancreatitis affect blood platelet function? 252 19

Evidence suggests that changes in prostaglandins and disseminated intravascular coagulation accompany pancreatitis. Both may induce changes in platelet function. We wished to determine if experimentally induced pancreatitis in the dog was associated with altered platelet number and function, and whether there were concomitant changes in prostaglandins. Evidence for disseminated intravascular coagulation in the dogs with pancreatitis were red blood cell fragmentation, increased platelet turnover indicated by macro-platelets and the transient presence of fibrin degradation products in urine. There were no significant changes in platelet count. The platelets from dogs with pancreatitis showed a functional defect characterized by significantly decreased aggregation in response to adenosine diphosphate, arachidonic acid, and collagen. Release of adenosine triphosphate from platelets was reduced in collagen-stimulated aggregation. There were no changes in the plasma concentrations of thromboxane B2, 6-Keto-PGF1a, and PGE2. This defect may have been due to the generation of fibrin degradation products and platelet "exhaustion".
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PMID:Platelet function in experimentally induced pancreatitis in the dog. 308 2

In 1981, a new low-molecular-weight protease inhibitor, FUT-175 (nafamstat mesilate), was synthesized. Its preventive action against acute experimental pancreatitis (AEP) was detected. We studied the effect of FUT-175 on the blood count and aggregability of platelets in AEP in dogs. At 30 min after induction of AEP, the sensitivity to ADP increased more than two times in untreated animals. An evident decrease in platelet count of about 37% was noted in these dogs at 6 h after AEP induction. Treatment of AEP with FUT-175 prevented these changes. We assume that the positive effect of FUT-175 against AEP depends at least in part on its influence on platelet aggregation.
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PMID:Effect of FUT-175 (nafamstat mesilate) on platelets in canine acute experimental pancreatitis. 323 15

Acute hemorrhagic pancreatitis (AHP) involves multiple organ failure probably caused by the toxic factor(s) released in pancreatitis-associated ascitic fluid (PAAF). We found that PAAF interferes with hepatic mitochondrial respiration resulting in severe disturbances in respiratory control (RCR) and ADP/O ratios. Pancreatitis was induced in dogs by retrograde pancreatic duct infusion and the resultant PAAF was centrifuged, filtered, and frozen until used. Two human PAAFs collected from AHP patients were treated in a similar manner. Rat liver mitochondrial oxygen uptake was measured at 30 degrees C before and after addition of ADP and PAAF. Paired control runs were made using pooled heat-inactivated dog serum. Tests with nine canine PAAFs showed a mean increase of 120% in state 4 respiration (P less than 0.0001). After exposure to PAAF, addition of ADP to previously coupled mitochondria did not induce state 3 respiration. The human PAAFs both showed significant increases in state 4 respiration (P less than 0.01) and a marked decrease in RCR. Dose-response tests with human and canine PAAFs showed a positive correlation between percentage increase in state 4 respiration and the concentration of PAAF used. These results confirm the presence in PAAF of mitotoxic substance(s) which cause irreversible mitochondrial damage. Inhibition of coupled mitochondrial respiration by PAAF with the resultant fall in ATP may be the causative agent for the tissue and organ damage observed in AHP.
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PMID:Mitochondrial dysfunction induced by pancreatitis-associated ascitic fluid. 684 50

Lazaroids, 21-aminosteroids without gluco- and mineralocorticoid activity, protect against oxidative injury in nervous system cells and may therefore also have a potential for treatment of pancreatitis, where oxidative stress contributes to cell injury. The present study evaluates the protective potential of the lazaroids U-78518F, U-74500A, and U-74389F against damage to isolated pancreatic acinar cells exposed to two models of oxidative stress: (a) a XOD/HX model, consisting of xanthine oxidase, hypoxanthine, and chelated FeCl3; and (b) an ADP/Fe model, consisting of FeSO4 and the reducing agent ADP. Both models caused time-dependent cell injury as assessed by uptake of trypan blue and release of lactate dehydrogenase. Short-term peak production of free radicals in the XOD/HX model--as monitored by the deoxyribose assay--was more injurious to cells than continuous radical generation at lower levels in the ADP/Fe model. In general, lazaroids at 1-10 microM reduced oxidative damage and deoxyribose oxidation in both models. The degree of reduction of cell damage and deoxyribose oxidation depended on the type and concentration of the lazaroid and the model used. Lazaroid concentrations < 0.1 microM were ineffective, and concentrations > 50 microM even accelerated cell injury, although lazaroids still served as scavengers at high concentrations. At least part of the noxious effects of high lazaroid concentrations is due to nonspecific membrane damage because these concentrations caused cell injury also in the absence of oxidative stress. The limited range of protective concentrations has to be observed in further in vivo studies. Interestingly, acinar cells in the absence of lazaroids also reduced radical-induced deoxyribose degradation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lazaroids protect isolated rat pancreatic acinar cells against damage induced by free radicals. 747 66

The purpose of this study was to evaluate the effect of free radical ablation therapy in acute hemorrhagic pancreatitis. Acute pancreatitis was induced in 64 rats by retrograde injection of 5% sodium taurocholate. Thirty animals were pretreated with 100,000 units/kg/hr of superoxide dismutase (SOD) and 400,000 units/kg catalase within the first 3 hr. After 0.5, 3.5, and 12 hr of observation time, serum enzymes and the tissue content of conjugated dienes, malondialdehyde, reduced and oxidized glutathione, as well as ATP, ADP and AMP were measured. In addition, tissue samples were examined by light microscopy. Untreated rats (N = 34) developed within 12 hr an acute hemorrhagic necrotizing pancreatitis with a concomitant increase in serum enzyme levels and a decrease in reduced glutathione and ATP. Within the 12-hr observation period, 57% of the animals died. Scavenger treatment improved the tissue damage and attenuated the increase of the serum enzyme levels and the decrease in reduced glutathione and ATP. Moreover, the lethality rate was significantly lower. Oxygen radicals seem to be instrumental for the development of acute hemorrhagic pancreatitis. Thereby, antioxidant treatment reduces tissue damage, biochemical alterations and extrapancreatic complications, thus improving the final outcome.
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PMID:Effect of antioxidant treatment in rats with acute hemorrhagic pancreatitis. 817 16


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