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)

We examined the protective effect of human pancreatic secretory trypsin inhibitor (PSTI), a specific trypsin inhibitor secreted from pancreatic acinar cells into the pancreatic duct, on cerulein-induced acute pancreatitis in conscious rats. The protective effect of human PSTI-RS, an analogue of PSTI with Arg-44 to Ser substitution which has a longer half-life in vitro, was also examined. Intraperitoneal administration of a pharmacological dose of cerulein to conscious rats induced acute pancreatitis, characterized by light microscopy as cellular disorganization of the acini and interstitial edema. Intravenous infusion of human PSTI (10, 50 or 250 micrograms/rat/h) into rats with cerulein-induced acute pancreatitis decreased their pancreatic wet weight and plasma amylase concentration. It also caused a dose-dependent decrease in vacuoles in acinar cells and interstitial edema. Human PSTI-RS, which has a longer half-life in vivo, was more effective than native PSTI at the same dose rate (10 micrograms/rat/h) in reducing pancreatitis. These results suggest that human PSTI may have a beneficial effect on acute pancreatitis.
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PMID:Protective effect of human pancreatic secretory trypsin inhibitor on cerulein-induced acute pancreatitis in rats. 145 47

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

Tumor-associated trypsin inhibitor (TATI) is a 6,000 Daltons peptide, which is synthesized by several tumors and cell lines. TATI is identical to pancreatic secretory trypsin inhibitor (PSTI). This peptide is also produced by the mucosa of the gastrointestinal tract, where it is thought to protect the mucosal cells from proteolytic breakdown. Elevated serum and urine levels of TATI occur in connection with many types of cancer, especially mucinous ovarian cancer. Elevated levels may also occur in nonmalignant diseases, e.g. in pancreatitis, severe infections and tissue destruction. Thus TATI may behave as an acute phase reactant. Tumors producing TATI often express tumor-associated trypsinogen. Elevation of TATI in cancer and pancreatic disease is therefore associated with expression of trypsin, but such a connection has not been demonstrated in inflammatory disease. TATI can inhibit trypsin-mediated degradation of extracellular matrix by tumor cells. Therefore its role may be to control the activation of tumor-associated trypsinogen. TATI has also been shown to possess growth factor activity in vitro, but it is not known whether this is a physiological function.
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PMID:Biology and function of tumor-associated trypsin inhibitor, TATI. 178 Jun 91

Serum pancreatic enzymes (amylase, trypsin, pancreatic elastase 1, pancreatic phospholipase A2) and serum pancreatic secretory trypsin inhibitor (PSTI) were measured in 22 patients with moderate or severe acute pancreatitis. Serum levels of all pancreatic enzymes were elevated at the initial determination, but they fell rapidly to normal in both moderate and severe pancreatitis. In contrast, PSTI in severe pancreatitis increased after admission and reached the maximum on the second to the forth day after onset. There was a significant positive correlation between the level of PSTI and that of acute phase reactant (fibrinogen, alpha 1-antitrypsin), and serum PSTI in severe acute pancreatitis changed as if it was one of acute phase reactants. There was also a significant negative correlation between the level of serum PSTI and that of alpha 2-macroglobulin.
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PMID:[Changes in serum pancreatic enzymes and pancreatic secretory trypsin inhibitor in patients with severe acute pancreatitis]. 241 44

The clinical usefulness of serum pancreatic secretory trypsin inhibitor (PSTI) in pancreatic disease and gastric and colorectal cancer has been examined. The results showed that serum PSTI in acute pancreatitis was significantly higher than in normal subjects and it was also raised in acute exacerbations of chronic pancreatitis. Although the sensitivities of serum PSTI, amylase and elastase I were similar, serum PSTI in necrotizing hemorrhagic pancreatitis was 2.7 times higher than in mild acute pancreatitis. Only a few patients with chronic pancreatitis showed increased concentrations and the mean value was near normal. The mean PSTI in patients with pancreatic and colorectal cancer was higher than normal, although that of gastric cancer was within normal limits. The sensitivity of serum PSTI measurements in patients with these three malignant diseases was only about 30%. The results suggested that the measurement of serum PSTI could be useful in the diagnosis of acute pancreatitis, but of limited value in the diagnosis of other disease which we examined.
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PMID:The measurement of serum immunoreactive pancreatic secretory trypsin inhibitor in gastrointestinal cancer and pancreatic disease. 245 73

The objective of this investigation was to test the capacity of recombinant human pancreatic secretory trypsin inhibitor (rhPSTI) to provide prophylaxis against experimental pancreatitis. Acute hemorrhagic pancreatitis was induced by intraductal injection of sodium taurocholate in rats and by intraductal injection of bile in dogs. In one treatment group of rats the injection of taurocholate was preceded by injection of rhPSTI. In a second group of rats the rhPSTI was given intraperitoneally starting 15 min after the induction of acute pancreatitis. The survival rate in a control group of rats was 13%. In contrast, the survival rate in groups receiving rhPSTI intraductally or intraperitoneally was 80% and 63%, respectively. The survival rate in a control group of dogs was 40% at 24 h and 0% at 48 h. In contrast, all the dogs receiving a single intraductal dose of rhPSTI, either immediately before the bile injection or mixed with the bile, survived for up to 6 weeks. Detailed biochemical and immunohistologic studies in the dog indicate that, whereas rhPSTI cannot prevent the initial bile-induced injury, it does prevent the subsequent development of that injury to the point where there is massive damage to the pancreas and the surrounding tissues, and changes in blood chemistry. The development of the initial injury is, therefore, presumed to involve activation of trypsinogen. Since rhPSTI prevents the serious consequences of experimental pancreatic injury by blocking the action of trypsin, and since the pathobiochemistry of human acute pancreatitis also implies an important role for trypsin, it is possible that rhPSTI could protect humans from the pancreatitis that complicates endoscopic retrograde cholangiopancreatography and endoscopic papillotomy.
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PMID:Local administration of human pancreatic secretory trypsin inhibitor prevents the development of experimental acute pancreatitis in rats and dogs. 281 37

Pancreatic secretory trypsin inhibitor (PSTI) is a 6000-dalton peptide, that occurs in high concentrations in the pancreas and in pancreatic juice. It is thought to be synthesized by pancreatic acinar cells. We have recently reported the findings of an identical trypsin inhibitor at high concentrations in the urine of patients with gynecological malignancy. Therefore, we have named the inhibitor tumor-associated trypsin inhibitor (TATI). We have now studied patients who have undergone total pancreatoduodenectomy for pancreatic cancer or chronic pancreatitis. By radioimmunoassay (RIA), we found normal levels of this inhibitor in the serum and urine of pancreatectomized patients. The absence of pancreas was confirmed by measuring serum trypsin. By gel filtration and HPLC it was found that PSTI/TATI occurring in pancreatectomized patients was indistinguishable from that found in connection with pancreatitis and ovarian cancer.
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PMID:Pancreatic secretory trypsin inhibitor-like immunoreactivity in pancreatectomized patients. 393 45

A reliable radioimmunoassay (RIA) for human pancreatic secretory trypsin inhibitor (PSTI) has been developed. The method is highly sensitive (0.4 ng/ml), reproducible and specific. A good parallel relationship was observed between the standard curve and dilution curves for serum and urine. The PSTI bound to trypsin-alpha 2-macroglobulin complexes was found not to be immunoreactive, whereas a part of the psti-trypsin complex was immuno-reactive. In healthy individuals, serum PSTI level ranged from 5.4 ng/ml to 16.0 ng/ml, the average being 11.3 ng/ml (S.D. +/- 2.7). Elevated values were observed in patients with acute pancreatitis (highest value 3200 ng/ml), and in some patients with chronic relapsing pancreatitis.
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PMID:Radioimmunoassay for human pancreatic secretory trypsin inhibitor: measurement of serum pancreatic secretory trypsin inhibitor in normal subjects and subjects with pancreatic diseases. 615 49

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

In earlier studies we reported the finding of a tumor-associated peptide that also occurred at high concentrations in early amniotic fluid. Determination of the N-terminal sequence of this peptide revealed that it is closely related or identical to the pancreatic secretory trypsin inhibitor. Therefore, the peptide is called tumor-associated trypsin inhibitor (TATI). The concentration of TATI was determined by radioimmunoassay in the urine of 148 patients with various forms of gynecologic malignancy and in a reference population consisting of 98 patients with non-malignant gynecologic disease, and also in 40 patients with severe infections or inflammatory disease. In the reference population, the median urinary concentration of TATI was 22 micrograms/g creatinine and the central 95% reference interval was 7-50 micrograms/g creatinine. Elevated urinary levels were observed in 53% of all patients with gynecologic cancer, in 63% of those with active disease and 26% of those in clinical remission. The highest urinary TATI level (11,000 micrograms/g creatinine) was over 200 times the upper limit of the reference range. Patients with cervical cancer had the highest frequency of elevated values. Increased excretion of TATI was also observed in patients with severe bronchopulmonary infections and pancreatitis. Although increased excretion of TATI is not cancer-specific, the distinction by elevated levels of TATI between malignant and nonmalignant gynecologic disease is better than by most other putative tumor markers, and the increased excretion of TATI in patients with active disease can be important for the understanding of tumor biology.
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PMID:Excretion of a tumor-associated trypsin inhibitor (TATI) in urine of patients with gynecological malignancy. 619 Jul 63


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