Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 12 dogs with acute experimental pancreatitis (AEP) and 6 control animals the "free", "latent" and "total" activity of acid phosphatase, beta-glucuronidase and cathepsins in whole homogenates of the pancreas, in a lysosomal-enriched subfraction and the supernatant of pancreatic tissue was estimated. AEP was induced by injection of bile salts and thrombin solution into the pancreatic duct. In 6 dogs the protection with heparin (1.5 mg/kg/body weight) immediately after producing AEP was applied. In AEP without any protection the free activity of hydrolases in the whole homogenate (80--90%) and in the lysosomal enriched subfraction (75--90%) was higher than in the controls (60--70% and 55--75% respectively), suggesting an augmented lysosomal fragility during the course of AEP. Heparin depressed the free activity of hydrolases to 60--80% in whole homogenates, and 64--75% in the lysosomal enriched subfraction. The release of cathepsins during incubation of the lysosomal-enriched subfraction in acidic medium was lower in the group with heparin treatment. The data obtained suggest the stabilising effect of heparin on the lysosomes of the pancreas during acute experimental pancreatitis in dogs.
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PMID:The effect of heparin on lysosomes of the dog pancreas during acute experimental pancreatitis. 47 25

In dogs with acute experimental pancreatitis (AEP) induced according to Elliotts method the total, free and latent activity of lysosomal hydrolases (acid phosphatase, beta-glucuronidase and cathepsins) in whole homogenates and some subfractions of pancreas were studied. The animals were divided into three groups of 6 dogs each: I. control healthy dogs. II. AEP-treated with glucagon (0.33 mg of glucagon in drop infusion 3 times every six hours). III. AEP without any drug treatment. In dogs treated with glucagon the significant decrease of relative free activity of all tested hydrolases (66-80%) in comparison with the group without any treatment (III/80-90%) was found. Moreover significant decrease of total catheptic activity (about 1/3) in the former group was demonstrated. Incubation of lysosomal enriched fraction taken from group II/in medium buffered to pH 5.0 caused decreasing release of catheptic activity (60% of total) in comparison with the group III (75%). The histochemical reaction for acid phosphatase according to Gomoris method in pancreatic acinar cells of dogs treated with glucagon was less intensive than reaction in untreated animals. These results indicate on the less impairment of pancreatic lysosomes in AEP treated with glucagon in comparison with that in untreated animals.
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PMID:The lysosomal hydrolases in acute experimental pancreatitis in dogs treated with glucagon. 84 47

Acute pancreatitis was studied by electron microscopy after retrograde infusion of either trypsin, and/or beta-glucuronidase into the canine pancreatic duct. Marked changes were induced by the mixture of trypsin and beta-glucuronidase. (1) The acinar cells were initially excavated from the acinar lumen and formed cystic bodies in themselves. The cystic bodies were then disrupted at their marginal membranes, and the acinar cells were filled with a large amount of fibrillar materials which originated from the contents of the cystic bodies. At this time, the luminal margin of the acinar cells completely disappeared. (2) The cellular organellas and the intracellular fibrillar materials in the acinar cells were discharged into the interstitial space through the disrupted basal lamina. Infection in the pancreatic ductal system was considered to play an important role in the pathogenesis of acute hemorrhagic pancreatitis.
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PMID:Ultrastructural studies of experimental acute pancreatitis. 97 83

To evaluate the effects of acute pancreatitis on hepatic function and hepatic cellular and subcellular organellar fragility, we studied 1) the hepatic secretion of lysosomal enzymes (beta-glucuronidase, beta-galactosidase, and N-acetyl-beta-glucosaminidase) into bile in the isolated perfused rat liver model; 2) the aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and lysosomal enzyme levels in the effluent in an isolated liver model; 3) hepatic lysosomal fragility in an in vitro incubation study; and 4) protective effects of a new low molecular weight synthetic protease inhibitor, ONO 3307, against hepatic injury in doses of 2 and 5 mg/kg.h in acute pancreatitis induced by a supramaximal dose of cerulein in rats. Decreased hepatic secretion of lysosomal enzymes into bile and accelerated hepatic lysosomal fragility were observed in acute pancreatitis induced by cerulein. ONO 3307 showed a significant protective effect against this hepatic injury in acute pancreatitis, the dose of 5 mg/kg.h showing a more potent effect than the dose of 2 mg/kg.h. These results suggest that the impaired hepatic function, including depressed hepatic secretion of lysosomal enzymes, seems to be closely related to accelerated hepatic fragility and that some unknown protease, which is present in pancreatitis and is susceptible to inhibition by ONO 3307, plays a crucial pathologic role in the development of this liver injury during acute pancreatitis.
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PMID:Effects of acute pancreatitis on hepatic secretion of lysosomal enzymes into bile and hepatic lysosomal fragility: protective effects of a new synthetic protease inhibitor, ONO 3307. 150 86

Acute necrotizing pancreatitis induced by infusion of bile salt into the pancreatic duct in rats is consistently associated with acute lung injury similar to the adult respiratory distress syndrome. The role of platelet-activating factor (PAF) in this pancreatitis-associated remote organ failure (lung injury) was investigated. Pulmonary tissue levels of PAF were increased gradually and reached a level of 1345 +/- 455 pg/g (6 times the control level) at 12 hours after induction of pancreatitis, whereas pancreatic PAF levels were undetectable and blood PAF remained unchanged. This local pulmonary PAF accumulation occurred at approximately the same time as the progression of lung injury. Pulmonary responses detected (i.e., eicosanoid production, leukocytic infiltration, Evan's blue extravasation, beta-glucuronidase release) were attenuated to varying degrees by treatment of rats in which pancreatitis was initiated with the PAF receptor antagonists (WEB2170 and BN52021). Rat lung lavages were examined after a 12-hour course of pancreatitis and no changes in PAF concentration, surfactant content, and phospholipase A2 (PLA2) activity were noted. Intravenous administration of PLA2 promoted pulmonary PAF production in experimental rats with pancreatitis but not in normal rats. This observation indicates that PLA2, which was determined to be elevated in plasma during pancreatitis, may be responsible for the accumulation of PAF in the lung. In conclusion, pancreatitis-associated lung injury appears to result from an endogenous inflammatory response in which PAF may play an important role.
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PMID:Role of platelet-activating factor in pancreatitis-associated acute lung injury in the rat. 156 55

Black and brown pigment gallstones are morphologically, compositionally, and clinically distinct. Black stones form primarily in the gallbladder in sterile bile and are associated with advanced age, chronic hemolysis, alcoholism, cirrhosis, pancreatitis, and total parenteral nutrition. Brown stones form not only within the gallbladder but also within the intrahepatic and extrahepatic ducts; they are uniformly infected with enteric bacteria and are usually associated with ascending cholangitis. Brown stones are related to juxtapapillary duodenal diverticula and are the predominant type of de novo common bile duct stones. Cholecystectomy is usually curative in black pigment stone disease, whereas stones often recur after cholecystectomy for brown stone disease. The pathogenesis of black stones is probably related to nonbacterial, nonenzymatic hydrolysis of bilirubin conjugates. At the pH of bile, this results in two monohydrogenated bilirubin anions that precipitate with calcium ions. Bilirubin monoconjugates that are increased in several conditions, such as Gilbert's syndrome and chronic hemolysis, may play a pivotal role in black stone formation as a source of unconjugated monohydrogenated bilirubin and as a possible co-precipitant with calcium. The precipitation of calcium carbonate and phosphate is influenced by local gallbladder factors. Brown pigment stones are formed in bile infected with enteric bacteria that elaborate hydrolytic enzymes: beta-glucuronidase, phospholipase A, and conjugated bile acid hydrolase. The resulting anions of bilirubin and fatty acids form insoluble calcium salts. We used nb/nb mice with a chronic hemolytic anemia as a model of hemolysis-induced black stone disease. The presence of 40% bilirubin monoconjugates in mouse gallstones indicated the importance of this moiety in the pathogenesis of black stones. Other data obtained by marrow transplantation experiments in mice revealed the relative importance of genotype versus the hemolytic anemia on determinants such as biliary bile acid composition and mucin secretory glands in the mouse gallbladder neck. Additional physical chemical studies of the interaction of unconjugated bilirubin in model bile solutions will be helpful in further delineating the pathogenesis of both black and brown pigment gallstones.
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PMID:Pigment gallstone disease. 202 17

Intracellular localization and enzymatic activities of lysosomal enzymes (cathepsin B, N-acetyl-beta-glucosaminidase, and beta-glucuronidase) were studied in control rats and after induction of caerulein pancreatitis. In control rats high enzymatic activities were found in the postnuclear 1000 g fraction (purified zymogen granules). The corresponding subcellular fraction in pancreatitis animals additionally contained larger secretory vacuoles and autophagosomes and revealed a marked increase in lysosomal enzyme activities. Immunolabelling studies at the ultrastructural level for trypsinogen and cathepsin B demonstrated a colocalization of lysosomal and digestive enzymes in zymogen granules in healthy controls. After induction of pancreatitis immunolabelling still demonstrated a colocalisation of cathepsin B and trypsinogen in secretory granules and newly formed Golgi-derived secretory vacuoles. Concomitantly appearing autophagosomes were, however, only labelled for cathepsin B. It is concluded that segregation of lysosomal and digestive enzymes is incomplete in normal acinar cells resulting in a colocalization in zymogen granules. In pancreatitis colocalization in secretory granules is maintained, whereas only lysosomal enzymes were sufficiently transferred into autophagic vacuoles. No indication for impaired mechanisms of molecular sorting of lysosomal and digestive enzymes in caerulein-induced pancreatitis was found.
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PMID:Localization of lysosomal and digestive enzymes in cytoplasmic vacuoles in caerulein-pancreatitis. 235 74

Both ethanol abuse and protein deficiency result in pancreatic injury. Moreover, these two variables frequently coexist. As lysosomal enzymes may play a role in the initiation of pancreatic injury, the aim of this study was to determine the effects of ethanol consumption and protein deficiency on pancreatic lysosomal stability. For 3 weeks, male Sprague-Dawley rats were match-fed (in groups of four) isocaloric amounts of one of the following liquid diets: (1) protein-sufficient diet, (2) protein-sufficient diet containing ethanol as 36% of the total energy, (3) protein-deficient diet, and (4) protein-deficient diet containing ethanol as 36% of energy. Pancreatic lysosomal stability was assessed by determining (a) latency, as indicated by the percentage increase in lysosomal enzyme activity in pancreatic homogenate induced by Triton X-100, and (b) by the percentage of lysosomal enzyme remaining in the supernatant after sedimentation of the lysosomal pellet from the pancreatic homogenate. Protein deficiency was associated with a decrease in latency and an increase in supernatant enzyme. Ethanol administration was associated with a decreased latency. Both protein-deficient and ethanol-fed animals exhibited higher pancreatic activities of cathepsin B, a lysosomal protease capable of activating trypsinogen. In addition, protein-deficient animals exhibited higher pancreatic activities of acid phosphatase, N-acetyl-glucosaminidase, and beta-glucuronidase. As lysosomal enzymes are postulated to play a role in the initiation of pancreatitis, these results suggest that ethanol consumption and protein deficiency may at least partly exert their toxic effects on the pancreas by altering pancreatic lysosomal stability and increasing the glandular content of cathepsin B.
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PMID:Both ethanol consumption and protein deficiency increase the fragility of pancreatic lysosomes. 236 35

In acute pancreatitis, damage to the liver is an important aspect of multiorgan failure. In 28 dogs (20 with bile-trypsin induced acute experimental pancreatitis (AEP], 'total' and 'free' activity of lysosomal hydrolases: beta-glucuronidase, cathepsins and acid phosphatase in mitochondrial and lysosomal subfraction of the liver were determined 12 h or 24 h after the induction of AEP. The respiratory control ratio with sodium succinate as a substrate, using Clarck's electrode and uncoupler-dependent ATP-ase activity in mitochondrial subfraction, was assayed. Groups of dogs were treated or pretreated with prostacyclin (PGI2), 20 ng.kg-1.min-1 i.v. for 12 or 13 h. The relative free activity of hydrolases was significantly elevated in untreated AEP after 12 h and was partially normalized in AEP after 24 h or after 12 h followed by treatment and pretreatment with PGI2. Respiratory control ratio was twice lower than normal in AEP after 12 h and partially normalized after 24 h post PGI2 treatment. The relative free activity of lysosomal hydrolases was highly negatively correlated with respiratory control ratio. It was concluded, that during AEP in dogs the function of liver mitochondria and lysosomal stability are impaired. The significant correlation found between the mitochondrial and lysosomal lesions points to lysosomal-mitochondrial interactions in liver damage in AEP. Prostacyclin in the investigated dose partially prevents the mitochondrial and lysosomal lesions in liver in this disease.
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PMID:Lysosomal-mitochondrial interrelationships in damage to the liver in acute experimental pancreatitis in dogs. Treatment with prostacyclin (PGI2). 304 48

This paper presents a review of the clinical significance of juxtapapillary duodenal diverticula in man. The incidence of such diverticula varies considerably in the literature, and possibly depends on the methods of investigation used. Studies show that the incidence of biliary calculi is significantly higher in patients with juxtapapillary diverticula as compared with patients without such diverticula. The assumed higher rate of diverticula in patients with pancreatitis is probably due to the presence of biliary calculi in these patients. Studies have shown that there is an insufficient choledochoduodenal sphincter in patients with diverticula, and also a higher rate of bacterial contamination of the duodenum and bile ducts in these patients. Fecal type flora has been found in most patients with juxtapapillary duodenal diverticula. Further, pigment gallstones have been found in most patients with diverticula, and analyses of these calculi showed that calcium bilirubinate was the main component. Further studies in our laboratory have shown that bacterial cultures produced beta-glucuronidase, a fact which may be connected with the increased frequency of pigment gallstones. Other studies have shown that there is a higher rate of diverticula in patients with recurrent biliary calculi who had undergone cholecystectomy. Recent data have also shown that there is a higher rate of common bile duct calculi in patients with diverticula, than in those without diverticula and without prior cholecystectomy--a fact supporting the theory on the pathogenesis of biliary calculi in patients with juxtapapillary diverticula. Other, and rare complications due to such diverticula are also mentioned.
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PMID:Juxtapapillary duodenal diverticula. 313 98


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