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

Acute necrotizing pancreatitis in opossums after bile and pancreatic duct ligation (BPDL) is a useful experimental corollary of gallstone-induced acute pancreatitis in humans. In experimental and human acute pancreatitis, a loss of segregation of the lysosomal enzyme cathepsin B and the zymogen proenzyme trypsinogen (colocalization) is implicated as the triggering event of disease pathogenesis, as cathepsin B can activate trypsinogen. The object of this study was to quantitate acinar cell necrosis and to study subcellular distribution of cathepsin B in BPDL-induced acute necrotizing pancreatitis in opossums. Bile and pancreatic ducts were ligated separately (no bile reflux) in four opossums while ducts were dissected in four sham controls. Opossums were killed 24 hr after operation. Three equidistant cross-sectional portions of each opossum pancreas were submitted to histologic examination. In blinded fashion, each focus of acinar cell necrosis was photographed and quantitated with digitizing morphometry. Numerical density (foci/cm2) and areal density (x10(3) micron 2/cm2) of focal acinar cell necrosis were determined. Differentially centrifuged pancreatic homogenates were assayed for cathepsin B, the lysosomal marker enzyme N-acetylglucosaminidase, and amylase. Morphometric quantitation of acinar cell necrosis confirmed development of acute necrotizing pancreatitis after 24 hr of BPDL in opossums. However, colocalization was not observed after BPDL, as evidenced by an absence of subcellular shift of cathepsin B activity (and N-acetyl-glucosaminidase activity) from the lysosome-enriched to the zymogen-enriched subcellular fraction. Amylase activity was increased in subcellular fractions after BPDL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ligation-induced acute pancreatitis in opossums: acinar cell necrosis in the absence of colocalization. 753 Mar 9

Alcohol consumption i associated with pancreatitis, but the mechanism underlying this injury remains unclear. Alcohol consumption has recently been shown to increase the fragility of both rat pancreatic lysosomes and zymogen granules in vitro, which may predispose to autodigestion via the intracellular activation of digestive enzymes by lysosomal enzymes. Cerulein-induced pancreatitis is also associated with lysosomal fragility. To determine the effect of alcohol consumption on this form of pancreatic injury, the severity of pancreatitis was compared in three groups of rats following i.v. cerulein infusion: rats fed alcohol in a liquid diet, pair-fed dextrose controls, and chow-fed controls. The histological severity of pancreatitis induced by supramaximal cerulein infusion was not found to be increased by prior alcohol consumption. Since alcohol did not appear to increase the severity of pancreatic injury induced by cerulein, we sought to define biochemical parameters that might precede obvious injury. The subcellular distribution of cathepsin B activity and markers of lysosomal fragility were compared in the same groups of experimental animals. Cerulein infusion led to a marked redistribution of cathepsin B activity from the lysosomal to the zymogen-granule-enriched fractions.For animals killed in the fed state, a redistribution of cathepsin B activity toward the zymogen-granule-enriched fraction was also demonstrated in alcohol-fed animals compared to their pair-fed controls. However, chronic alcohol administration did not influence the effect of cerulein on subcellular cathepsin B distribution or lysosomal fragility. In this rat study, administration of alcohol did not increase the effects of supramaximal doses of cerulein on the pancreas.
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PMID:The effect of chronic alcohol administration on cerulein-induced pancreatitis. 759 67

The effects of single and repeated short-term (4 hr) obstruction of pancreaticobiliary duct (PBDO), with or without exocrine stimulation (intraductal hypertension) by cerulein infusion (0.2 micrograms/kg.hr), on the exocrine pancreas were evaluated in the rat. Single blockage of pancreaticobiliary duct for 4 hr caused a significant rise in serum amylase levels, pancreatic water content, and redistribution of lysosomal enzyme, cathepsin B from the lysosomal fraction to the zymogen fraction, which was considered to mean the colocalization of lysosomal enzymes with pancreatic digestive enzymes in the same subcellular compartment in acinar cells. In addition, the accelerated lysosomal and mitochondrial fragility was observed in the single pancreaticobiliary-duct-obstructed animals. Moreover, the repeated PBDO for 4 hr (2 hr in each obstruction and 1 hr of free flowing of pancreaticobiliary juice between two obstructions) caused more marked changes in almost the all parameters, and the repeated PBDO with intraductal hypertension caused an activation of trypsinogen in the pancreas, making more marked changes in almost the all parameters than the repeated PBDO only group. These results indicate that the present model of repeated PBDO with exocrine stimulation seems to be a pertinent model for gallstone pancreatitis in humans, and that redistribution of lysosomal enzymes and subcellular organellar fragility seem to play an important role in the pathogenesis of pancreatic injuries induced by PBDO, particularly by repeated PBDO with exocrine stimulation, probably via activation of trypsinogen to trypsin by lysosomal enzyme, cathepsin B.
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PMID:A possible mechanism for gallstone pancreatitis: repeated short-term pancreaticobiliary duct obstruction with exocrine stimulation in rats. 767 5

The redistribution of cathepsin B, a representative lysosomal enzyme, from the lysosomal pellet to the zymogen pellet in subcellular fractions and the colocalization of cathepsin B with digestive enzymes within acinar cells have been found during the early stage of caerulein-induced acute pancreatitis in the rat. This study investigated the protective effects of prostaglandins E1 and E2 on the exocrine pancreas in this experimental pancreatitis. Prostaglandin E2, but not E1, prevented the redistribution of cathepsin B along with the hyperamylasemia, and the increase in amylase and trypsinogen in the acinar cells in almost a dose-dependent manner, particularly at a dose of 100 micrograms/kg.hr of continuous infusion. These results suggest that subcellular organelle fragility is closely related to the pathogenesis of acute pancreatitis, and that prostaglandin E2 has an important cytoprotective effect on biological membranes as a stabilizer of lysosomal membrane.
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PMID:Effect of prostaglandin E on the redistribution of lysosomal enzymes in caerulein-induced pancreatitis. 768 11

Ethanol abuse is a well-known association of pancreatitis. The effects of chronic ethanol consumption on pancreatic digestive and lysosomal enzymes may be relevant to the pathogenesis of alcoholic pancreatitis, because pancreatic enzymes play an important role in the development of pancreatic injury. The aims of this study were to determine the effects of ethanol on gene expression and glandular content of pancreatic digestive enzymes and on gene expression of the lysosomal enzyme cathepsin B (known to be capable of activating trypsinogen). Pancreatic content and mRNA levels for lipase, trypsinogen, and chymotrypsinogen were determined in rats that were pair-fed a nutritionally adequate liquid diet with or without ethanol for 4 weeks. mRNA levels for the lysosomal enzyme cathepsin B were also assessed in this model. Ethanol significantly increased the content of lipase in the pancreas. There was a trend toward an increase in trypsinogen and chymotrypsinogen levels; however, these differences were not statistically significant. mRNA levels for lipase, trypsinogen, and chymotrypsinogen were raised in ethanol-fed rats. Ethanol feeding also increased mRNA levels for the lysosomal enzyme cathepsin B. Furthermore, there was a close, statistically significant correlation between changes in mRNA levels and tissue activities of pancreatic digestive and lysosomal enzymes after ethanol consumption. These results suggest that ethanol increases the capacity of the pancreatic acinar cell to synthesize digestive and lysosomal enzymes, thereby increasing the susceptibility of the gland to enzyme-related injury.
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PMID:Ethanol-induced alterations in messenger RNA levels correlate with glandular content of pancreatic enzymes. 773 27

The protective effect of an anti-ulcer agent, cetraxate hydrochloride [4-(2-carboxyethyl)phenyltrans-4-amino- methylcyclohexanecarboxylate hydrochloride], on the exocrine pancreas in caerulein-induced pancreatitis of rats was investigated. Hyperamylasaemia, pancreatic oedema and activation of trypsinogen in the pancreatic tissue, as well as subcellular redistribution of the lysosomal enzyme, cathepsin B, from the lysosomal fraction to the zymogen fraction, were prevented by infusion of 20 mg/kg.h cetraxate for 2 h before caerulein infusion and throughout the 3.5 h of caerulein infusion (5 micrograms/kg.h). The results indicate that cetraxate plays its protective roles against pancreatitis by inhibiting the redistribution of lysosomal enzyme and by activation of trypsinogen; such activities may be clinically useful in preventing pancreatic injuries, particularly in patients with chronic pancreatitis.
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PMID:Anti-ulcer agent, cetraxate hydrochloride (Neuer), prevents subcellular redistribution of lysosomal enzyme in caerulein-induced pancreatitis in the rat. 802 Jun 37

In order to reproduce what might occur during the initial phase in some cases of acute alcohol-induced pancreatitis, rabbits were infused with diluted ethanol and low-dose cerulein. The duct permeability was assessed by recovery of fluoresceinated dextran (molecular weight 19,500) in central venous blood following orthograde duct perfusion with this substance in the anesthetized animal. Serum ethanol, lipase, and amylase were measured; pancreatic duct morphology was examined by light microscopy and electron microscopy. ATP and glutathione were measured, as were amylase, trypsinogen/trypsin, cathepsin B, and DNA levels in differential centrifugates. As expected, acinar amylase and trypsinogen showed a significant decrease in the experimental group; cathepsin B activity was similarly diminished. Compared with the control group, the activity of serum amylase and lipase in the experimental group demonstrated a significant increase. However, no differences between saline-infused control animals and the treated group regarding pancreatic duct permeability, continuity of lumen-lining epithelium, ATP and glutathione levels, and the relative subcellular distribution of pancreatic digestive and lysosomal enzymes were observed. Thus, our findings do not support the relevance of some of the most common hypotheses on the pathophysiology of acute pancreatitis in its early stage for at least a certain subgroup of patients with acute alcohol-induced pancreatitis.
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PMID:Glutathione and ATP levels, subcellular distribution of enzymes, and permeability of duct system in rabbit pancreas following intravenous administration of alcohol and cerulein. 814 53

The effects of prostaglandin E2 on the fragility of cellular and subcellular organelles in caerulein-induced acute pancreatitis were investigated in rats. PGE2 at doses of 50 and 100 micrograms/kg/hr infused for 2 hours before and during caerulein (5 micrograms/kg/hr for 3.5 hours) infusion significantly prevented the increased discharge of both amylase and lactate dehydrogenase from dispersed acini, and the leakage of cathepsin B from lysosomes and of malate dehydrogenase from mitochondria in the subcellular fraction in vitro. These results suggest that PGE2 has a cytoprotective effect against caerulein-induced pancreatitis by stabilizing cell and lysosomal and mitochondrial membranes.
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PMID:Effect of prostaglandin E2 on cellular, lysosomal and mitochondrial fragility in caerulein-induced pancreatitis in rats. 827 Feb 35

The effects of short-termed (2 hours) obstruction of pancreatico-biliary duct (PBDO) and exocrine stimulation (IDH) by caerulein infusion (0.2 microgram/kg.hr) with systemic hypotension (SH) (30% reduction of mean arterial pressure for 30 min) on the exocrine pancreas were evaluated in the rat. PBDO and IDH with SH caused more significant rises in portal serum amylase, cathepsin B and malate dehydrogenase levels, and pancreatic water content as well as more significant redistribution of cathepsin B activity from the lysosomal fraction to the zymogen fraction in the subcellular fractionations than only PBDO, or PBDO with IDH, or PBDO with SH group. In addition, more accelerated lysosomal and mitochondrial fragility were observed in the PBDO and IDH with SH group. Moreover, PBDO and IDH with SH caused an activation of larger amount of trypsinogen in the pancreas compared with other groups (PBDO with IDH and PBDO with SH group). These results indicate that present model of short-termed PBDO and exocrine stimulation with systemic hypotension seems to be pertinent model for gallstone pancreatitis in humans, and that redistribution of lysosomal enzymes and subcellular organellar fragility seem to play an important role in the pathogenesis of pancreatic injuries by PBDO, particularly with exocrine stimulation and pancreatic ischaemia, probably via activation of trypsinogen to trypsin by lysosomal enzyme such as cathepsin B.
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PMID:A new experimental model for gallstone pancreatitis: short-termed pancreatico-biliary duct obstruction and exocrine stimulation with systemic hypotension in rats. 835 38

The role of infectious factors in the pathogenesis of acute pancreatitis and the protective effect of combined therapy with a new potent synthetic protease inhibitor, E3123, and a new potent synthetic cephalosporin, Shiomarin were examined in rat acute pancreatitis. Sodium taurocholate injection into the pancreatico-biliary duct of rats caused severe pancreatitis with a high mortality rate, characterized by hyperamylasaemia, high amylase activity in ascitic fluid, hyperendotoxaemia and a high serum level of fibrin degradation products (FDP) and redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction. Sodium taurocholate injection into the pancreatico-biliary duct also caused the bacterial growth in the pancreas. In rats with E3123 infusion almost all parameters were improved, including mortality rate, serum and ascitic fluid amylase levels, plasma endotoxin and serum FDP levels, and distribution of lysosomal enzyme. But combination therapy with E3123 and Shiomarin was significantly more protective than E3123 therapy alone. These results indicate that infection plays an important role in the development of severe pancreatitis and that combination therapy with a new synthetic protease inhibitor and a new potent antibiotic may be useful in the treatment of severe pancreatitis.
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PMID:Protective effect of a cephalosporin, Shiomarin, plus a new potent protease inhibitor, E3123, on rat taurocholate-induced pancreatitis. 843 63


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