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)

110 patients with proven chronic pancreatitis have been studied to assess the prevalence of the various Pi phenotypes of alpha1-antitrypsin in this disease compared with a control group of 116 blood-donors. The phenotype PiMZ (including Mweak) was significantly more prevalent and PiMM significantly less so in the patients with pancreatitis. It is possible that a heterozygous deficiency of this protease inhibitor renders the pancreas more vulnerable to aetiological agents (e.g., alcohol).
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PMID:Chronic pancreatitis and alpha-1-antitrypsin. 5 76

Aprotinin, a protease inhibitor, has been used in a wide variety of pathophysiological states thought to be associated with an increase in protease activity. Opinion differ with respect to the success of the therapy. This paper proposes a rationale for the therapeutic action of aprotinin based on biochemical and physiological evidence. In the kallikrein-kinin system, in addition to kallikrein, other serine-esterases such as trypsin, plasmin, etc. can generate kinin production. In certain disease states such as pancreatitis there is not only an increase in serine-protease activity but frequently these enzymes reach parts of the organism where they are not found in health. Thus in such circumstances increased production of kinins can result. The consequences of increased kinin generation are discussed in light of work indicating their role in metabolic and circulatory homeostasis. Aprotinin is specifically a serine-esterase inhibitor. It is suggested that perhaps the most important action of this compound is as an inhibitor of the kallikrein-kinin system. On this basis a therapeutic regime in various disease states for the use of aprotinin, which allows for control of kinin generation, is suggested.
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PMID:A rationale for the therapeutic action of aprotinin. 15 36

A survey of the main series in the world literature and personal data concerning injuries to the pancreas is followed by the suggestion that the risk of pseudocyst or pancreatitis means that in all cases where injury to the pancreas is suspected, and resolution is slow, laparotomy must be performed, coupled with careful exploration of the lesser omentum and precise evaluation of possible lesions, prior to suitable surgical management. Medical therapy is also of prime importance. Its main feature is the administration of a protease inhibitor to prevent pre- and post-operative enzymatic toxaemia.
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PMID:[Diagnosis and treatment of traumatic lesions of the pancreas]. 46 Jun 19

To study the degree of protease activation at reperfusion of a pancreatic allograft after cold storage for 24 hr, 18 porcine whole-organ pancreaticoduodenal allograft transplantations were performed. Twelve grafts were flushed with and stored in Perfadex. In six of these, a hyperosmotic salt solution was injected into the graft aorta at reperfusion. Six grafts were flushed and stored in UW solution. Eleven of twelve grafts in the Perfadex groups were functioning on the first postoperative day, compared with one of six in the UW solution group. There was a significantly more pronounced protease activation among grafts stored in UW solution than in the other groups, with a subsequent breakthrough of the local protease protection barrier made up of protease inhibitors. In surviving pigs (n = 14), biochemical signs of protease activation evolved in plasma, including formation of trypsin-protease inhibitor complexes, a decline in C3 and kininogen levels, and a decline in functionally active alpha 2-macroglobulin, functionally active antithrombin III, and plasma kallikrein inhibitory activity. These biochemical signs of pancreatitis correlated with a deteriorated graft function on the second postoperative day, indicating that graft tissue damage occurred due to protease activation.
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PMID:Protease activation following reperfusion of porcine pancreatic allografts. 127 75

To investigate the mechanism by which the pancreatic acinar cells are injured in animals with an obstructed common channel, we measured the amount of lysosomal enzymes and of amylase in the pancreatico-biliary juice in rats with pancreatico-biliary duct obstruction (PBDO). We tested the protective effect of a new potent synthetic protease inhibitor, E3123 (4-guanidinobenzoate methanesulfonate), on the exocrine pancreas in this model of PBDO and secretin infusion. Blockage of PBD for 4 hours and secretin (0.2 CU/kg.hr) infusion caused a significant rise in portal serum amylase and cathepsin B levels, pancreatic water content, and pancreatic amylase content, as well as redistribution of cathepsin B in acinar cells. These changes tended to continue for 12 hours after the removal of PBDO and disappeared at 24 hours. All the changes induced by PBDO with secretin infusion were no longer observed at 48 hours. The administration of 5 mg/kg.hr of E3123 during PBDO markedly attenuated all the parameters examined in this study. Thus, it had a significant protective effect on acinar cells in this model. E3123 in a dose of 2 mg/kg.hr had a partial, but significant, protective effect. These results indicate the possible usefulness of E3123 in the treatment of pancreatic duct obstructed pancreatitis.
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PMID:Effect of short-termed pancreatico-biliary duct obstruction on lysosomal enzyme in rats: protective effect of a potent new protease inhibitor, E-3123. 128 76

To clarify the relationship between the diminution of the serum protease inhibitor capacity and the severity of pancreatitis, the binding capacity of serum protease inhibitors for exogenous elastase 1 (E1) was investigated by gel filtration, the elastase activity of the alpha 2-macroglobulin (alpha 2-M)-elastase complex was measured, and the relationship between these findings and the severity of pancreatitis was studied in 13 patients with pancreatic disease and 6 healthy subjects. When 125I-labeled E1 was added to the sera of healthy subjects, it bound to alpha 2-M and alpha 1-protease inhibitor (alpha 1-PI) with a mean ratio of 72:28. In mild acute pancreatitis (n = 5), the binding capacity of alpha 2-M was less than that in healthy subjects. In severe pancreatitis (n = 4), most of the exogenous E1 bound to alpha 1-PI (alpha 2-M vs. alpha 1-PI, 13:87). This diminution in the binding capacity of alpha 2-M correlated well with the severity of acute pancreatitis. In the sera of patients (n = 4) with pancreatic cancer containing much immunoreactive E1, the proportion of exogenous E1 bound by alpha 2-M and alpha 1-PI (25:75) was similar to that seen in severe acute pancreatitis. A significant inverse relationship between the binding capacity of alpha 2-M and the activity of the endogenous elastase bound to alpha 2-M was seen in various pancreatic diseases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum protease inhibitor capacity for elastase and the severity of pancreatitis. 128 Mar 65

This in vivo and in vitro study demonstrates the protective effects of a new synthetic protease inhibitor--nafamostat mesilate, FUT-175--on increased cellular and lysosomal fragility within acinar cells during the early stage of cerulein-induced acute pancreatitis in rats. FUT-175 prevented hyperamylasemia, pancreatic edema, congestion owing to amylase, and lactic dehydrogenase (LDH) discharge from acini as well as cathepsin-B leakage from lysosomes dose-dependently in doses of 1-10 mg/kg.h. These results suggest that FUT-175 can protect against pancreatitis at subcellular levels in lysosomes and cellular or organelle membranes. Proteases may well play the important role in the pathogenesis of acute pancreatitis, and such a low molecular protease inhibitor may be useful clinically in the treatment of acute pancreatitis.
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PMID:Protective effect of nafamostat mesilate on cellular and lysosomal fragility of acinar cells in rat cerulein pancreatitis. 128 Dec 4

The redistribution of cathepsin B, a lysosomal enzyme, from the lysosomal pellet to the zymogen pellet in the subcellular fractionation, the colocalization of cathepsin B with digestive enzyme, and increased cellular, lysosomal, and mitochondrial fragility within acinar cells have been found during the early stages of caerulein-induced acute pancreatitis in rats. In the present study, the authors investigated the protective effects of prostaglandin E1 and E2, a combined therapy of these prostaglandins, and a new, synthetic, low molecular weight protease inhibitor, ONO3307, on the exocrine pancreas in this noninvasive model of experimental pancreatitis in vivo and in vitro. Prostaglandin E2, but not E1, prevented hyperamylasemia, congestion of amylase and trypsinogen in the acinar cells, redistribution of cathepsin B, and amylase and lactate dehydrogenase discharge from the dispersed acini. It also prevented cathepsin B leakage from the lysosomes and malate dehydrogenase leakage from the mitochondria in an almost dose-dependent manner, particularly at the dose of 100 micrograms/kg/hr continuous infusion. Furthermore, the combined therapy of prostaglandin E2 with ONO3307 strongly inhibited all the parameters tested in this study. This combination therapy seems to be the most effective against secretagogue-induced pancreatic injuries. These results indicate that cellular and subcellular organellar fragility seem to be closely involved in the pathogenesis of acute pancreatitis. Prostaglandin E2 seems to have important cytoprotective effects on the biologic membranes, such as a stabilizer of lysosomal or mitochondrial membranes. In addition, these findings also suggest the crucial roles of some unknown proteases in the etiology of acute pancreatitis, and indicate the clinical effectiveness of prostaglandins and this type of low molecular weight protease inhibitor for acute pancreatitis.
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PMID:Cytoprotective effects of prostaglandins and a new potent protease inhibitor in acute pancreatitis. 128 94

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 (SM) 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 hyperamylasemia, high amylase activity in ascitic fluid, and hyperendotoxemia and a high serum level of fibrin degradation products (FDP), redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction. 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 SM 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:Combined therapy of a cephalosporin, Shiomarin and a new potent protease inhibitor, E3123 in rat taurocholate-induced pancreatitis. 130 80

A supramaximal dose of caerulein (5 micrograms/kg.hr for 3.5 hours) caused an acute pancreatitis with marked hyperamylasemia and intense interstitial edema in rats. In this model of pancreatitis, the redistribution of lysosomal enzyme in acinar cells as well as the increased lysosomal and mitochondrial fragility were also observed. The combined therapy of a low molecular weight protease inhibitor, FOY, a synthetic platelet activating factor (PAF) antagonist, CV 6209, and a xanthine oxidase inhibitor, allopurinol produced more significant improvements in all the parameters examined than the therapy of any only one of these three agents, each only one therapy exerting a partial significant protective effect. These results indicate that several factors, such as unknown proteases activities, PAF and oxygen-derived free radicals may be involved in the pathogenesis of pancreatic injuries in this caerulein-induced pancreatitis. These results also suggest that such a combined therapy of different kinds of agents, whose therapeutic mechanisms are also different, is useful in the clinical treatment of acute pancreatitis.
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PMID:"Cocktail" therapy for acute pancreatitis: combined therapy of protease inhibitor, xanthine oxidase inhibitor and platelet activating factor antagonist in rat caerulein-induced pancreatis. 130 81


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