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)

The effect of new CCK receptor antagonist, lorglumid on taurocholate AEP in rats was studied. Lorglumid was applied intraperitoneally at a dose of 5.6 mg/kg BW immediately after taurocholate injection into choledochopancreatic duct. Activity of amylase, antithrombin III (AT III), alpha 1 protease inhibitor (alpha 1 PI), alpha 2 antiplasmin (alpha 2 AP) and alpha 2 M) in plasma, trypsin and chymotrypsin in pancreata were measured after 1, 3, 6 h of AEP. In AEP treated by lorglumid serum amylase activity and pancreatic wet weight was significantly reduced. The use of lorglumid prevented the increase of alpha 1 PI and alpha 2 AP compared to not treated animals. AT III and alpha 2 M in plasma and trypsin and chymotrypsin activity in pancreata did not change significantly in all groups. The mortality of the lorglumid treated rats was significantly lower in comparison with control group. It is concluded that lorglumid in taurocholate AEP moderates the changed plasma proteinase-antiproteinase balance. Our results indicate a protective effect of lorglumid in this model of acute experimental pancreatitis.
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PMID:The effect of a cholecystokinin receptor antagonist lorglumid on the proteinase-antiproteinase balance in taurocholate acute experimental pancreatitis (AEP) in rats. 130 47

Activation of pancreatic digestive zymogens within the pancreatic acinar cell may be an early event in the development of pancreatitis. To detect such activation, an immunoblot assay has been developed that measures the relative amounts of inactive zymogens and their respective active enzyme forms. Using this assay, high doses of cholecystokinin or carbachol were found to stimulate the intracellular conversion of at least three zymogens (procarboxypeptidase A1, procarboxypeptidase B, and chymotrypsinogen 2) to their active forms. Thus, this conversion may be a generalized phenomenon of pancreatic zymogens. The conversion is detected within ten minutes of treatment and is not associated with changes in acinar cell morphology; it has been predicted that the lysosomal thiol protease, cathepsin B, may initiate this conversion. Small amounts of cathepsin B are found in the secretory pathway, and cathepsin B can activate trypsinogen in vitro; however, exposure of acini to a thiol protease inhibitor (E64) did not block this conversion. Conversion was inhibited by the serine protease inhibitor, benzamidine, and by raising the intracellular pH, using chloroquine or monensin. This limited proteolytic conversion appears to require a low pH compartment and a serine protease activity. After long periods of treatment (60 minutes), the amounts of the active enzyme forms began to decrease; this observation suggested that the active enzyme forms were being degraded. Treatment of acini with E64 reduced this late decrease in active enzyme forms, suggesting that thiol proteases, including lysosomal hydrolases, may be involved in the degradation of the active enzyme forms. These findings indicate that pathways for zymogen activation as well as degradation of active enzyme forms are present within the pancreatic acinar cell.
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PMID:Intracellular proteolysis of pancreatic zymogens. 134 58

The study investigated the protective effect of a new synthetic protease inhibitor, E-3123, a 4-guanidinobenzoate methanesulphonate, on the exocrine pancreas in caerulein-induced pancreatitis of rats both in vivo and in vitro. Hyperamylasaemia, pancreatic oedema and congestion of amylase, as well as cathepsin B leakage from lysosomes and malate dehydrogenase leakage from mitochondria, were prevented by infusion of 5 mg/kg.h E-3123 particularly when infused for 2 h before and during 5 micrograms/kg.h caerulein infusion for 3.5 h. The results indicate that E-3123 plays its protective roles against pancreatitis in the subcellular compartments such as lysosomes and mitochondria, and that such a low molecular weight protease inhibitor as E-3123 may be clinically useful in the treatment of acute pancreatitis.
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PMID:A new synthetic protease inhibitor, E-3123, prevents lysosomal and mitochondrial fragility in rat caerulein-induced pancreatitis. 138 65

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

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

Assessment of the degree of severity of acute pancreatitis by means of biochemical parameters is still a subject of extensive studies. The purpose of the present study was a trial of evaluation of the diagnostic usefulness and prognostic value of certain tests for proteinase-anti-proteinase equilibrium and acute phase indices in acute pancreatitis in 52 patients (36 women and 16 men aged 22 to 83 years). The control group compared 29 healthy volunteers. The patients were classified according to the aetiology of the disease: pancreatitis connected with bile duct disease, alcoholic and non-classifiable, and another classification was based on the clinical course (medium severe, severe). Significantly higher concentration of immunoreactive trypsin (TLI) was found in the first two weeks in the group of severe disease as compared to the group with medium severe pancreatitis (p less than 0.01). TLI was significantly higher than in controls for 2 months after clinical recovery. The serum inhibitory capacity was significantly reduced in severe cases in relation to medium severe ones, particularly between 3 and 7 days of the disease (p less than 0.001). Similarly as trypsin concentration, reduced inhibitory capacity in relation to controls persisted for up to 2 months after pancreatitis. No significant differences were noted in the concentration of alpha 1 protease inhibitor and C3 and C4 complement components, in the studied groups. The serum alpha 2 macroglobulin level was significantly decreased between days 3 and 7 (p less than 0.05). The values of alpha 2 macroglobulin were correlated in that time with the values of the inhibitory capacity.
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PMID:[Diagnostic usefulness and prognostic value of inhibitory capacity and other biochemical parameters of plasma in acute pancreatitis in humans]. 170 53

Earlier studies have reported that interstitial oedematous pancreatitis characterized by hyperamylasaemia can be seen during the early stage of stimulation of supramaximal dose of caerulein. The present study investigated the changes in both cellular and lysosomal fragility and the protective effects of a synthetic protease inhibitor gabexate mesilate (FOY) on this non-invasive model of experimental pancreatitis. The infusion of FOY (50 mg/kg/h) prevented the caerulein-induced increase in serum amylase and pancreatic oedema formation and reduced the elevated amylase content significantly. The administration of FOY with caerulein also reduced the increased lactic dehydrogenase (LDH) discharge significantly and inhibited the cathepsin B leakage from lysosomes in an in vitro incubation system. These results indicate that FOY plays its protective role at the subcellular level--that is, in lysosomes by inhibiting some proteases such as phospholipase A2. The importance of esterases in the pathogenesis of acute pancreatitis is demonstrated. This type of esterase inhibitor may be valuable clinically in the treatment of acute pancreatitis and these results also suggest the role of lysosomal fragility in the pathogenesis of progression of acute pancreatitis.
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PMID:Protection by gabexate mesilate (FOY) of the exocrine pancreas in rats with acute pancreatitis induced by a supramaximal dose of caerulein. 171 33

Graft pancreatitis and allograft rejection were both accompanied by increased serum levels of immunoreactive anionic trypsin (irAT) in a porcine pancreatic allograft transplantation model. Characterization of this immunoreactivity by gel filtration revealed different elution profiles in these conditions that can be helpful in the differentiation between them. During graft pancreatitis, a major part of the immunoreactivity was found within the high-molecular-weight fraction corresponding to the formation of complexes between trypsin and protease inhibitors. During allograft rejection, virtually all serum irAT increase could be attributed to the release of anionic trypsinogen without any evidence of activation. Since this transplantation model includes urinary diversion of the exocrine secretions, irAT and immunoreactive cationic trypsin (irCT) can also be measured in the urine. Characterization of this immunoreactivity showed that most of both irAT and irCT was found as active trypsin but a minor part was probably complexed with some protease inhibitor (possibly pancreatic secretory trypsin inhibitor [PSTI]).
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PMID:Characterization of immunoreactive trypsin as a means of differentiating graft pancreatitis and allograft rejection after porcine pancreatic transplantation. 173 80

The present study investigated the protective effect of a new potent synthetic protease inhibitor, E-3123 (4-guanidinobenzoate methanesulfonate) on the exocrine pancreas in the caerulein induced experimental pancreatitis both in-vivo and in-vitro at 3 different doses (1, 2, and 5 mg/kg.hr). This protease inhibitor prevented hyperamylasemia, pancreatic edema, congestion of amylase, and both amylase and lactic dehydrogenase (LDH) discharge from dispersed acini, as well as cathepsin B leakage from lysosomes and malate dehydrogenase (MDH) leakage from mitochondria in a dose-dependent manner, particularly in doses of 2 and 5 mg/kg.hr. Furthermore, the combined prophylactic and therapeutic use of this agent seems to be very effective in preventing caerulein induced pancreatitis. These results indicate that E-3123 plays its protective roles against pancreatitis in the subcellular compartment: lysosomes, mitochondria, cellular or organella membranes. It is hoped that such a low molecular weight protease inhibitor as E-3123 will be clinically useful in the treatment of acute pancreatitis.
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PMID:A new synthetic protease inhibitor, E-3123, reduces organelle fragility of acinar cells in rat caerulein pancreatitis. 182 13

The effect on endogenous beta-endorphins of a new synthetic protease inhibitor was studied in acute pancreatitis. Pancreatitis was induced by the injection of autologous bile mixed with trypsin into the main pancreatic duct after ligation of the accessory duct. Plasma beta-endorphin concentrations and cardiovascular function were measured. Ten dogs (control group) were given 10 ml/kg/h of lactate Ringer's solution intravenously beginning 1 h before the induction of pancreatitis and continuing throughout the experiments. Six dogs received an intravenous infusion of 3 mg/kg/h of a new synthetic protease inhibitor, E-3123 (4-(2-succinimidoethylthio)4-geranidinobenzoate methanesuLfonate), in lactate Ringer's solution soon after the induction of pancreatitis. Plasma beta-endorphin concentrations in the control group increased significantly. However, plasma beta-endorphin levels in the protease inhibitor group did not increase as in the control group. The protease inhibitor infusion improved hypotension, myocardial depression, and plasma lactate, suggesting that the inhibitory effect of the protease inhibitor on beta-endorphin release contributed to the improvement.
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PMID:Effect of a new synthetic protease inhibitor on beta-endorphin release during acute pancreatitis in dogs. 187


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