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 long-term ethanol intake on pancreatic digestive enzyme secretion was determined in Sprague-Dawley rats. Weight-matched triplets were fed Lieber-DeCarli diet containing 5% w/v concentration of ethanol, isocaloric amounts of Lieber-DeCarli diet, or rat chow ad libitum for 6, 12, and 18 months. Basal and bethanechol-stimulated secretion of amylase, lipase, trypsinogen, chymotrypsinogen, and pancreatic secretory trypsin inhibitor (PSTI) was determined. In the ethanol-fed group, basal secretion of trypsinogen and chymotrypsinogen was increased at 6, 12, and 18 months. In addition, basal secretion of amylase and lipase was increased and that of PSTI was decreased at 12 and 18 months. Secretion of PSTI was stimulated by bethanechol (10(-4)M), whereas the secretion of digestive enzymes was not stimulated in the ethanol-fed versus two control groups. At 12 months the dose-response curve of amylase and lipase secretion was shifted upwards in the ethanol-fed group with increase in ED50. These data are suggestive of membrane perturbations leading to increased basal secretion and a subsensitivity of the cholinergic receptors in the ethanol-fed group. Increased basal secretion of proteases in the presence of diminished trypsin inhibitor indicates that premature activation of proenzymes could occur resulting in pancreatitis.
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PMID:Effect of chronic ethanol feeding on pancreatic enzyme secretion in rats in vitro. 618 44

A decrease in renal blood flow is believed to be important in the genesis of the acute renal failure of acute pancreatitis. In some instances, this decrease is undoubtedly due to hypovolemia, whereas in other instances, a circulating vasotoxic agent, possibly trypsin, has been incriminated. Using a canine model of pancreatitis induced by retrograde injection of bile along the pancreatic duct, the effects on renal blood flow of correcting the hypovolemia or administering aprotinin (a trypsin inhibitor) were studied using externally applied flow probes. Correcting the hypovolemia with N saline solution had no effect; the renal blood flow continued to decrease (p less than 0.05). When dextran 40 or dextran 75 was employed, the decrease in renal blood flow was prevented. After the administration of aprotinin, the renal blood flow actually increased (p less than 0.025) compared with preadministration values. It appears that aprotinin may have played a role in preventing this serious complication of pancreatitis.
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PMID:Effectiveness of normal saline solution, dextran 40 or dextran 75, and aprotinin (Trasylol) on renal blood flow preservation during acute canine pancreatitis. 620 98

Therapeutic effects of human urinary trypsin inhibitor (MTI) on acute pancreatitis were examined. MTI potently inhibited not only proteases such as trypsin or alpha-chymotrypsin, but also inhibited lipase or creatine phosphokinase which are considered to be related to pancreatitis. Although gabexate mesilate (gabexate) and aprotinin also strongly inhibited trypsin, their inhibition spectra against pancreatic enzymes were narrower and aprotinin also strongly inhibited trypsin, their inhibition against pancreatic enzymes were narrower than MTI. MTI inhibited proteases released from pancreatic slice by trypsin more potently than gabexate or aprotinin. The therapeutic effects of MTI on experimental acute trypsin-induced pancreatitis in dogs or rats were stronger than those of gabexate or aprotinin. These results suggest that MTI may suppress pathogenesis and development of pancreatitis in several ways, for example, by directly inhibiting trypsin and by inhibiting tissue-damaging enzymes released from the pancreas by stimulation with trypsin.
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PMID:[Therapeutic effects of human urinary trypsin inhibitor on acute experimental pancreatitis]. 634 4

Therapeutic effect and the mechanism of the action of human urinary trypsin inhibitor (MTI) on experimental acute pancreatitis were studied. MTI significantly increased survival rate of animals with experimental acute pancreatitis induced by the infusion of trypsin or phospholipase A2 into pancreas or by a closed duodenal loop. The efficacy of MTI on these types of pancreatitis were higher than those of aprotinin. Pancreatic enzymes were released from pancreatic slice by trypsin or phospholipase A2, and this release was inhibited by MTI. Further, these pancreatic enzymes caused a secondary release of enzymes from other pancreatic slice, suggesting that these enzymes injured pancreatic tissue and that a chain reaction of pancreatic enzyme activation may play an important role in the pathogenesis of acute pancreatitis. MTI suppressed the secondary enzyme-induced pancreatic injury more strongly than aprotinin. These results suggest that MTI may suppress pathogenesis and development of pancreatitis by inhibiting the chain reaction of pancreatic enzyme activation.
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PMID:Effects of urinary trypsin inhibitor on pancreatic enzymes and experimental acute pancreatitis. 636 18

Excretion of adrenaline was increased in patients with chronic recurrent pancreatitis, excretion of noradrenaline tended to decrease although the content of this amine exceeded 1.5-2-fold its normal concentration in individual patients; excretion of DOPA was unaltered. Hyperlipoproteinemia was found in the majority of the patients. Maximal level of the adrenaline excretion was mainly observed in the patients with high activity of the trypsin inhibitor in blood serum as well as with the high ratio trypsin inhibitor/trypsin. An increase in the adrenaline excretion correlated with hypercholesterolemia and to a lesser extent--with hypertriglyceridemia. The most pronounced hypertriglyceridemia was typical for the patients with alcoholic abuse. Relationship between catecholamines and extrasecretory functions of pancreatic gland as well as with hyperlipoproteinemia in pancreatitis is discussed. An increase in the total antitryptic activity might be caused by activation of the sympathoadrenal system or by hyperproduction of adrenaline.
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PMID:[Excretion of catecholamines and lipid composition of blood in patients with chronic pancreatitis]. 640

Chromatography of human pancreatic juice has allowed the isolation of an inactive protein of 14,000 Mr (protein X) and the determination of its amino acid composition and N-terminal sequence. Protein X was found to be immunologically identical to the protein extracted from precipitates present in the pancreatic juices of patients with chronic calcifying pancreatitis and recently shown to be a degradation product of trypsinogen 1. The same chromatography performed in the presence of lima bean trypsin inhibitor has permitted the isolation of precursors of approximately congruent to 19,000 Mr which can be transformed into protein X "in vitro" by chymotrypsin hydrolysis. These results emphasize the easy activation of human pancreatic zymogens and the possible consequences due to proteolysis in pancreatic disease.
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PMID:Characterization and N-terminal sequence of a degradation product of 14,000 molecular weight isolated from human pancreatic juice. 644 May 59

The activity of trypsin, common trypsin inhibitor and elastase was evaluated in the blood serum of children with chronic diseases of the digestive organs. The activity of trypsin and its inhibitor was shown to be elevated in most children with both concomitant pancreatitis and without it. Increased activity of the trypsin inhibitor reflects a positive compensatory response of the body to excess trypsin supply to the blood. The activity of serum elastase rises only with exacerbation of chronic pancreatitis.
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PMID:[Change in proteolytic enzymatic activity in the blood serum in children with chronic diseases of the digestive organs]. 699 29

To determine the role alcohol might play in altering pancreatic function, we have examined pure pancreatic juice, obtained by endoscopic cannulation of the pancreatic duct, from a group of 10 chronic alcoholic subjects without history or clinical or laboratory evidence of pancreatic disease and compared the results with those obtained from 15 healthy, non-alcoholic subjects. These findings confirm observations in experimental animals made by others and support the hypothesis that chronic alcohol abuse may damage the pancreas via a sequence of events involving protein hypersecretion. Increase in concentration was not uniform for all proteins measured. Unexpectedly, chronic alcoholics exhibited a highly significant elevation (two- to three-fold over normal) in trypsinogen, in contrast to statistically insignificant increases of other zymogens and trypsin inhibitor. The strikingly increased ratio of trypsinogen to trypsin inhibitor observed in all our alcoholic patients may indicate a weakening of the defence mechanism provided by the trypsin inhibitor against premature intraductal activation of zymogens and explain the predisposition of these patients to pancreatitis.
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PMID:Studies of pure pancreatic secretions in chronic alcoholic subjects without pancreatic insufficiency. 738 47

The effect of a novel synthetic trypsin inhibitor, 4-(2-succinimidoethylthio)-phenyl 4-guanidinobenzoate methanesulfonate (E3123), on severe acute pancreatitis was studied in trypsin-taurocholate-induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of subdivided doses of E3123 with fixing the total dose at 3 mg/kg body weight. Group A: 1.5 mg/kg of E3123 subcutaneously (SC) each at 1 h before and after induction of pancreatitis. Group B: 1 mg/kg SC each at 1 h before, 1 and 3 h after induction. Group C: 1.5 mg/kg SC each at 1 and 3 h after induction. Group D: 1.5 mg/kg SC each at 3 and 5 h after induction of pancreatitis. The survival rate at 24 h was significantly improved in group B (77% in group B, vs. 36% in paired control; p < 0.01) and in group C (70 vs. 38%; p < 0.05), but not in group A or D. Residual tryptic activity of serum alpha 2-macroglobulin trypsin complex (alpha 2M-TRY) was reduced after the injection of E3123 though immunoreactive trypsin remained unchanged in the early phase of pancreatitis. The reduction of alpha 2M-TRY reflected the inhibitory capacity of E3123 in plasma. E3123 showed favorable effects on the initial stage of severe acute pancreatitis and the effects were probably based on the inhibition of alpha 2M-TRY activity in serum.
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PMID:Monitoring serum tryptic activity and effect of trypsin inhibitor on rat acute pancreatitis. 751 53

We evaluated the protective effect and the mechanism of action of the trypsin inhibitor, urinastatin, extracted from human urine, in experimental acute pancreatitis induced by a supramaximal dose of cerulein (5 micrograms/kg/hr for 3.5 hr). Urinastatin in a dose of 10,000 units/kg/hr was given by three different methods of continuous infusion: (1) 2 hr before and during cerulein infusion, (2) only during cerulein infusion, and (3) starting 1 hr after the beginning of cerulein infusion and continued for 3.5 hr. In protocol 1 and 2 urinastatin was significantly more protective than in 3. In protocol 1 urinastatin was very protective in all parameters tested (serum amylase level, pancreatic water and amylase content, distribution of lysosomal enzymes, cellular and lysosomal fragility). These results suggest that the administration of urinastatin before and during cerulein infusion may suppress the pathogenesis and evolution of pancreatitis by inhibiting the chain reaction of pancreatic enzyme activation closely related to redistribution of lysosomal enzyme and lysosomal fragility.
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PMID:Effect of urinary trypsin inhibitor on pancreatic cellular and lysosomal fragility in cerulein-induced acute pancreatitis in rats. 768 48


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