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

Intraductal administration of enterokinase in rats produced hyperamylasemia and acute hemorrhagic pancreatitis. The experimental pancreatitis and hyperamylasemia could be prevented by the concomitant intraductal injection of fluorouracil, pituitrin, or chlorophyll-a. The clinical implication of the study is that these agents, if given intraductally, may be useful in the prevention of iatrogenic hyperamylasemia and acute pancreatitis that may occur after endoscopic retrograde pancreatocholangiography.
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PMID:Effect of chlorophyll-a, fluorouracil, and pituitrin on experimental acute pancreatitis. 8 61

Experimental pancreatitis (PT) is induced by proximal and distal duodenal closure in the bile-duct-ligated dog, by causing duodeno-pancreatic reflux of lumenal secretions. It has been postulated that trypsin and enterokinase (EK) in the secretions activate trypsinogen within the pancreas, producing PT. There is supporting evidence for trypsin, but EK has not previously been investigated. To determine whether EK alone could cause PT, we injected saline suspensions of partially purified EK, and other test materials, into the duct of Wirsung of dogs and after 24 hr examined their pancreases and estimated the increment in serum amylase. Following 0.5% EK, both PT and hyperamylasemia (HA) ensued; HA without PT occured when EK was inactivated by heat, administered with trypsin inhibitor (TI), or administered in more dilute solution. Injection of TI or of hog gastric mucin likewise leads to HA but not to PT. It is concluded that the PT observed was due to EK activity, and that therefore EK could contribute to the production of PT observed was due to EK activity, and that therefore EK could contribute to the production of PT in the closed-duodenal-loop model. The HA observed in the absence of PT is unexplained but appears to be related to the colloidal properties of the materials injected.
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PMID:Pancreatitis following the intraductal injection of partially purified enterokinase in dogs. 84 25

The trypsinogen and chymotrypsinogen contents of the pancreas were examined during acute experimental pacreatitiis of the rat. The proenzymes were activated with enterokinase and the amounts of active proteases were estimated with BAPNA (N-alfa-benzoyl-DL-arginin-4-nitroanilid hydrochlorid, Fluka AG) and SUPHEPA (succinyl-L-phenylalanine-p-nitroanilide, Schwarz/Mann, Division of Becton) as the substrates. The activation of chymotrypsinogen was more rapid than the activation of trypsinogen; maximal activation occurred in 3 hours. Under similar circumstances the activation of trypsinogen required 17 hours. Both trypsinogen and chymotrypsinogen content decreased significantly during the inflammation. In 8 hours the decline of trypsinogen content was 28.4 percent and that of chymotrypsinogen content 44.9 percent from the proenzyme content of the normal resting rat pancreas. This indicates that proenzymes and/or active proteases are liberated during the course of pancreatitis. No correlation was found between the trypsinogen and the chymotrypsinogen content of the normal pancreas, but during pancreatitis the proenzyme contents correlated clearly. The correlation during inflammation possibly reflects the amount of the viable pancreatic tissue and the rate of synthesis.
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PMID:The trypsinogen and chymotrypsinogen contents of the pancreas during acute experimental pancreatitis of the rat. 112 51

Precursors of proteolytic enzymes were demonstrated in the peritoneal inflammatory exudate during acute experimental pancreatitis of the rat. This was done by separating the proteinase inhibitors and proenzymes by gel filtration on Sephadex G-200. After elution the proenzymes could be demonstrated by activating them with enterokinase or with trypsin. The proenzymes were eluted after the main protein bulk and proteinase inhibitors. Enzyme precursors were absent from the exudate of formalin-induced peritonitis, which suggests that the proenzymes present in the exudate of pancreatitis are of pancreatic origin. The demonstration of proenzymes in perripheral blood during pancreatitis was tested with the several modifications of the same methods, but the results were not convincing, probably owing to the insensitivity of the methods used.
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PMID:The proteolytic proenzymes in the peritoneal exudate during acute experimental pancreatitis of the rat. 115 82

Trypsinogen activation peptides (TAP) were quantified by radioimmunoassay in blood, urine, and peritoneal exudate of rats with experimental pancreatitis. Forty-four animals were studied, comprising a control group and four different induction techniques (cerulein, cerulein plus either 2- or 10-min intraductal glycodeoxycholic acid [GDOC] infusion, and cerulein plus intraductal GDOC with enterokinase [EK]). Significantly higher TAP concentrations were found at 6 h (or at death) in plasma and ascites of all pancreatitis groups compared with controls. TAP quantitation in hourly urine samples demonstrated significantly higher concentrations from the third hour onward in the most severe groups and from the fourth hour onward in the cerulein-treated rats. All nonsurviving rats had a plasma TAP of greater than 2.5 nM/L, whereas only 1 of 34 surviving animals had such a concentration (p less than 0.001). A significant stepwise increase in total TAP in ascites was found when comparing the cerulein group, the two GDOC groups, and the EK group (p less than 0.001). Chromatography of samples with a high TAP content demonstrated comigration with synthetic TAP. We conclude that free TAP are present in blood, urine, and peritoneal exudate of rats with experimental pancreatitis of different pathogenesis and that the amount of TAP may be indicative of the severity of the disease process.
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PMID:Generation and possible significance of trypsinogen activation peptides in experimental acute pancreatitis in the rat. 137 47

Controlled intraduct infusion and peri-acinar dispersal of 100 microliter buffer containing sodium glycodeoxycholate (GDOC) at concentrations of 8.5, 17 and 34 mmol/l in rats caused a progressively severe acute pancreatitis from which none of the animals died over the experimental period. Infusion of affinity-purified active human enterokinase in buffer did not cause pancreatitis, presumably because of the inability of the macromolecule to gain access to its specific intracellular substrate trypsinogens. The addition of enterokinase 200 ng to GDOC 34 mmol/l in the infusate resulted in a severe systemic disturbance and a form of acute necrotizing pancreatitis which was uniformly and rapidly lethal. This effect was not seen when equimolar trypsin was substituted for enterokinase. These findings show that enterokinase specifically increases the lethality of experimental bile salt pancreatitis and suggest that this bile-borne enzyme may in some cases pose a significant clinical threat.
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PMID:Intraduct enterokinase is lethal in rats with experimental bile-salt pancreatitis. 354 76

The main pancreatic duct can be made permeable to molecules of up to 20,000 daltons by oral pretreatment with aspirin and ethanol. Because pancreatic enzymes have similar molecular weights, we hypothesized that activated pancreatic enzymes would leak from a permeable duct and produce pancreatitis. Four groups of cats were pretreated with either milk, aspirin, ethanol, or aspirin and ethanol for 48 hr. Then pancreatic juice (either activated by enterokinase or nonactivated) was perfused along the duct from tail to duodenum. Twenty-four hours later the animals were examined. Animals pretreated with aspirin, ethanol, or both, and in which ducts were perfused with activated juice, developed acute edematous pancreatitis. Animals that had perfusion with nonactivated enzymes had pancreases indistinguishable from control animals. Morphological studies on ductal permeability in animals pretreated with ethanol and aspirin showed electron-dense material (believed to be dextran) between the basal plasma membrane and basal lamina, and in the basal intercellular space.
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PMID:Effects of oral agents on pancreatic duct permeability. A model of acute alcoholic pancreatitis. 375 22

In a model of acute pancreatitis which requires that pancreatic enzymes leak from a permeable duct, we studied the role of intravenous enterokinase (195,000 daltons) in pancreatic enzyme activation. Anesthetized cats were given intravenous 16,16-dimethyl prostaglandin E2 to increase pancreatic blood flow and microvascular permeability. In some animals the permeability of the pancreatic duct was increased by perfusion of the duct with glycodeoxycholic acid (7.5 mM). Endogenous enzyme secretion was stimulated by IV CCK and secretin. Some cats also received enterokinase intravenously. Those animals that received PGE2, glycodeoxycholate, and enterokinase all developed pancreatitis. When any of these agents were not given the pancreases appeared normal. These findings were consistent with the hypothesis that intravenous enterokinase leaked from small pancreatic blood vessels into the pancreatic parenchyma and/or ducts where activation of pancreatic enzymes occurred. The development of pancreatitis appeared to require an increase in both microvascular and ductal permeability.
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PMID:Pancreatic duct and microvascular permeability to macromolecules. The relation to acute pancreatitis. 385 17

Ethanol-associated fatty liver was induced in rats fed a nutritionally deficient liquid diet containing 36% of total calories as ethanol. Control rats received the same diet with sucrose substituted isocalorically for ethanol. After 40 days, hepatic lipid content of the ethanol-maintained animals was four-fold greater than controls and ultrastructural changes in hepatocytes were well established. Clearance of intravenously administered human enterokinase from the circulation as well as bile flow were, however, the same in both groups. The proportion of enterokinase appearing in catalytically active form in bile after intravenous injection was substantially greater in the ethanol-maintained animals than the isocaloric controls; the difference was highly significant (p less than 0.001) and reached two- to four-fold after 70 days on the diet. These findings would suggest that the ability of hepatocytes to degrade enterokinase cleared from the blood may be bypassed or impaired by prolonged ethanol consumption and a deficient diet. Catalytically active enterokinase in bile may participate in the development of some types of acute necrotising pancreatitis.
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PMID:Biliary excretion of enterokinase in rats: studies in alcoholic rats with fatty liver. 633 13

The osmolality of contrast injected retrograde into the rat pancreatic duct did not affect the severity of the pancreatitis (Urografin, 1,300 mOsm/kg, and Hexabrix, 580 mOsm/kg). The severity of the pancreatitis induced in rats was assessed by survival rate, histologic grading, wet lung ratio, and serum levels of amylase, lipase, and trypsin-like activity. Rats with pancreatitis induced by retrograde injected Urografin, lipopolysaccharide, taurocholic acid plus enterokinase were treated with either intravenous (i.v.) FUT-175 (Nafamstat Mesilate), FUT-175 administered by retrograde pancreatic injection, i.v. terbutaline, i.v. piperacillin sodium, piperacillin sodium by retrograde pancreatic duct injection, or a combination of FUT-175 plus terbutaline and piperacillin. Survival among the rats was increased and the incidence of pancreatic infection reduced in rats treated with i.v. piperacillin or with a combination of FUT-175 plus i.v. terbutaline, plus i.v. piperacillin compared to controls.
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PMID:Therapeutic regimens in acute experimental pancreatitis in rats: effects of a protease inhibitor, a beta-agonist, and antibiotics. 747 69


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