Urinary Trypsinogen-2 Research Articles

Urinary trypsinogen-2 test strip for acute pancreatitis

SummaryBackground A simple, rapid test that is specific and sensitive enough to distinguish, in patients with clinically suspected acute pancreatitis, those whose abdominal pain is indeed of pancreatic origin has proved elusive.Methods In two consecutive series of surgical patients in a teaching hospital, whose acute abdominal pain turned out to be due to acute pancreatitis (n=57) or extrapancreatic in origin (n=40), we studied urinary trypsinogen-2 in two ways. A test strip, incorporating monoclonal antibodies to two epitopes on trypsinogen-2, recorded a blue line when concentrations exceeded 50 μg/L; we also measured trypsinogen-2 concentrations in the laboratory.Findings In the patients with acute pancreatitis the test strip was positive in 52 and negative in five, whereas in the 40 extrapancreatic controls there were four false positives. In a further set of 57 orthopaedic controls, one urine was strip-test positive. Concentrations of urinary trypsinogen-2 and the test-strip results were in good agreement and in only three of the 154 patients were the two approaches discrepant, at the 50 μg/L cut-off.Interpretation These findings, in patients whose acute abdominal pain was known to be pancreatic in origin or not, are encouraging but need to be confirmed in a consecutive series of patients in whom the diagnosis of pancreatitis is in doubt.

Cholecystokinin-8 induces edematous pancreatitis in dogs associated with short burst of trypsinogen activation

To study the early pathogenesis of acute edematous pancreatitis in dogs, we examined the relationship of pancreatic hyperstimulation with cholecystokinin-8 (10 micrograms/kg/hr intravenously for 6 hr) to alterations in circulating pancreatic enzymes and pancreatic morphology with special reference to trypsinogen activation. Cholecystokinin-8 infusion was associated with increases in plasma amylase, lipase, trypsin-like immunoreactivity, and plasma and urine trypsinogen activation peptide. Pancreatic parenchymal swelling and interlobular and subcapsular fluid accumulations were detected ultrasonographically within 2 hr of cholecystokinin-8. Circulating trypsin-like immunoreactivity and trypsinogen activation peptide in urine reached a peak at 2 and 4 hr, respectively, then declined despite progressive increases in circulating amylase and lipase and intrapancreatic fluid. No significant changes were observed in dogs receiving a saline infusion. This study illustrates that cholecystokinin-8 induces edematous pancreatitis in dogs that is associated with a short-lived burst of trypsinogen activation.

The Relationship Between Pancreatic Enzyme Release and Activation and the Acute-Phase Protein Response in Patients with Acute Pancreatitis

It has been suggested that the severity of an attack of acute pancreatitis is related to the presence of intraglandular trypsinogen activation and that disease severity is also reflected by the degree of the acute-phase protein response. In this study we examine the relationships among amylase release, the degree of trypsinogen and prophospholipase A2 activation [as measured by urinary trypsinogen activation peptide (TAP) and prophospholipase A2 activation peptide (PLAP) concentrations], and the serum concentrations of the acute phase-protein C-reactive protein (CRP) and the principal mediator of the acute-phase protein response, interleukin-6 (IL-6). Twenty-four patients (14 mild and 10 severe attacks) were studied. Peak serum amylase concentrations were seen within 12 h and peak urinary TAP/creatinine (Cr) and PLAP/Cr ratios between 12 and 24 h after the onset of symptoms, preceding those of IL-6 and CRP. The integrated TAP/Cr and PLAP/Cr responses were significantly greater in those with severe disease [95% confidence internal (CI) = 106-259.6 pmol/mmol/h, p < 0.0008; and 95.1% CI = 462.2-3887 pmol/mmol/h, p < 0.003, respectively]. The integrated amylase response was not significantly greater in those with severe disease (95.6% CI = -415 to 832 IU/L/h, p < 0.14). There was a strong correlation among the integrated IL-6, TAP/Cr (r = 0.63, p < 0.01), and PLAP/Cr (r = 0.64, p < 0.01) responses but a poor correlation with the integrated amylase response (r = 0.19, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary trypsinogen activation peptide (TAP) predicts severity in acute pancreatitis: [formula omitted], C Fernandez del Castillo, AL Warshaw, W Steinberg, J Hermon-Taylor, JE Valenzuela, M Hariri, PA Banks. Brigham and Women's Hospital, Massachusetts General Hosptial, Boston, George Washington University Medical Center, Washington D.C., University of Southern California, Los Angeles, and St. Georges Hospital, London

Urinary trypsinogen activation peptide (TAP) predicts severity in acute pancreatitis: [formula omitted], C Fernandez del Castillo, AL Warshaw, W Steinberg, J Hermon-Taylor, JE Valenzuela, M Hariri, PA Banks. Brigham and Women's Hospital, Massachusetts General Hosptial, Boston, George Washington University Medical Center, Washington D.C., University of Southern California, Los Angeles, and St. Georges Hospital, London

Dopamine in models of alcoholic acute pancreatitis.

Acute oedematous pancreatitis and acute haemorrhagic pancreatitis were studied using the low pressure duct perfusion models of alcoholic pancreatitis in cats. After creating either form over 24 hours, each pancreas was histologically graded and assigned an inflammatory score (0-16; absent-severe). Urinary trypsinogen activation peptide concentrations were also used as a measure of severity. Using the model of acute haemorrhagic pancreatitis, it was previously shown that low dose dopamine (5 micrograms/kg.m) reduced the inflammatory score at 24 hours and that this effect was mediated by a reduction in pancreatic microvascular permeability acting via dopaminergic and beta adrenergic receptors. Further studies were conducted and are reported here. In experiment 1 different doses of dopamine in established alcoholic acute haemorrhagic pancreatitis were studied. In group 1 control cats (no dopamine), the inflammatory score was 10.5 (interquartile range (IQR)4). In groups 2, 3, and 4, haemorrhagic pancreatitis was induced. Twelve hours later dopamine was infused for six hours, in the doses of 2 micrograms/kg.min, 5 micrograms/kg.min, and 50 micrograms/kg.min respectively. The inflammatory score in group 2 was 7 (IQR 0.5, p < 0.05 v group 1), in group 3 it was 7 (IQR 2, p < 0.05 v group 1), and in group 4 it was 7 (IQR 4, p < 0.05 v group 1). This was matched by significantly lower levels of urinary tripsinogen activation peptide at 24 hours. In experiment 2 (group 5) we tried to reduce microvascular permeability further by combining dopamine with antihistamines, but there was no improvement in the inflammatory score. As oedematous pancreatitis is the commoner and milder form of acute pancreatitis in clinical practice, in experiment 3 we looked at the effect of dopamine in this model. In group 6 control cats (no treatment), the inflammatory score was 7 (IQR 3, p < 0.05 v group 1). In group 7 cats given dopamine (5 micrograms/kg.min for six hours) from 12 hours after the onset of actue oedematous pancreatitis, the inflammatory score was reduced to 4(IQR 2, p < 0.05 v group 6). This was matched by a significant reduction in the 24 hour urinary tripsin activation peptide concentration.

URINARY LEVELS OF ACTIVATED TRYPSIN IN WHOLE -ORGAN PANCREAS TRANSPLANT PATIENTS WITH DUODENOCYSTOSTOMIES

Urinary levels of trypsinogen and active trypsin were measured in 34 urine samples from 14 patients an average of 23 months following whole organ pancreas transplantation and duodenocystostomy. Timed urine specimens obtained 30 min and 90 min following a time zero void were collected from 5 patients in an effort to define the kinetics of trypsinogen secretion and activation. Total urinary protein and urinary pH were correlated with urinary levels of trypsin and trypsinogen. Twenty-one specimens from 8 normal volunteers and a single specimen from a pancreas transplant patient with a duodenoenterostomy served as controls. Activated trypsin was present in 33 of 34 specimens from 13 of the 14 transplant patients. The average total trypsin activity in all samples was 84.4 micrograms/ml urine (+/- SE 9.6). Trypsinogen was present in 13 of 34 samples, from 7 of 14 patients. The average trypsinogen concentration of all 34 samples was 9.6 +/- 6.2 micrograms/ml. No trypsin or trypsinogen activity was identified in any control sample. In the 5 patients undergoing timed urine collections total trypsin increased an average of 1.3-fold at 30 min and 1.1-fold at 90 min relative to time zero. Urinary trypsinogen increased an average of 7.1-fold at 30 min and 3.1-fold at 90 min following the initial void. Urinary pH and total urinary protein failed to show a significant correlation with urinary levels of total trypsin or trypsinogen. These data suggest that trypsinogen is rapidly converted to active trypsin following secretion into the bladder, resulting in the high urinary trypsin levels that were detected in the majority of patients.