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Objective: The objective of this study was to investigate the relationship between asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, oxidative-nitrosative damage, and glucoregulation in acute pancreatitis (AP)., Methods: The study evaluated serum levels of ADMA, nitrotyrosine, and urinary 8-hydroxydeoxyguanosine in 40 male patients hospitalized for AP at baseline and at 2 and 10 days of treatment, respectively. The patients were classified into a mild and a moderately severe AP group (MAP and MSAP, respectively) according to Atlanta classification criteria. Glycemic status was evaluated by a 75-g oral glucose tolerance test 1 month after AP onset. Forty age-matched healthy subjects served as control subjects., Results: Significant decrease of ADMA and increased levels of nitrotyrosine and urinary 8-hydroxydeoxyguanosine were found in MSAP, but not in MAP at baseline, with ADMA correction toward control levels at the 10th day of treatment. Fructosamine was found to significantly influence ADMA levels (r = -0.362, P = 0.002). After AP recovery, either impaired glucose tolerance or diabetes was identified with the oral glucose tolerance test in 10.5% and 92.8% of patients with MAP and MSAP, respectively., Conclusions: Insufficient inhibition of nitric oxide synthesis, through reduced bioavailability of ADMA, might be a novel significant contributory factor to the severity of AP and subsequent development of hyperglycemia.

Objectives: In reference to our earlier publication, laboratory tests that reflect severe intravascular volume depletion can be used for predicting the severity of acute pancreatitis (AP). The aim of the study was to assess whether urinary level of neutrophil gelatinase-associated lipocalin (NGAL) could represent a useful marker of AP severity., Methods: We observed a cohort of 104 prospectively enrolled patients. The patients were classified into 3 groups: mild AP, moderately severe AP, and severe AP. Urine samples were collected on admission (NGAL-as) and during the first 24 hours (NGAL-first day) for examination of urinary level of NGAL concentrations from the first day., Results: Acute pancreatitis was considered severe in 16 (15%) patients, moderately severe in 25 (24%) patients, and mild in 63 (61%) patients.There were statistically significant trends for an increase in severity (P = 0.04, P = 0.003) and mortality (P < 0.031, P = 0.01) with raising NGAL-as and NGAL-first day concentrations, respectively. The areas under the curve for severity predicted by NGAL-as and NGAL-first day were 0.75 and 0.93, respectively. The areas under the curve for mortality prediction by NGAL-as and NGAL-first day were 0.980 and 0.92, respectively., Conclusions: The urinary level of NGAL is a promising new diagnostic and prognostic factor for severe AP in an early stage of the disease.

Objectives: A simple urinary trypsinogen-2 test was evaluated for the diagnosis of acute pancreatitis., Methods: This prospective multicenter study enrolled consecutive patients with acute abdominal pain who presented to the emergency department or who were hospitalized at 1 of 21 medical institutions in Japan. Patients were tested with urinary trypsinogen-2 dipstick test and a quantitative trypsinogen-2 assay, and these values were compared with serum amylase and lipase findings., Results: A total of 412 patients were enrolled. The trypsinogen-2 dipstick test was positive in 107 of 156 patients with acute pancreatitis (sensitivity, 68.6%) and in 33 of 256 patients with nonpancreatic abdominal pain (specificity, 87.1%). The sensitivity for the diagnosis of pancreatitis caused by alcohol and gallstones by the dipstick test was 72.2% and 81.8%, respectively, which was much higher than those associated with amylase testing. There are several degrees of positivity within the urinary trypsinogen-2 dipstick test. Modification of the cutoff point such that positive (+) and most positive (++) results were interpreted as a positive result, the specificity and positive likelihood ratio increased to 92.2% and 7.63, respectively., Conclusions: This simple, rapid, easy, and noninvasive urinary trypsinogen-2 test can diagnose or rule out most cases of acute pancreatitis.

Objectives: The aim of this prospective study was to evaluate the diagnostic value of the rapid urinary trypsinogen-2 test strip in post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis., Methods: A total of 150 patients were tested with the urinary trypsinogen-2 test strip and serum levels of amylase and lipase before ERCP and 3 hours after ERCP. The diagnostic value of urinary trypsinogen-2 strip test compared with that of serum amylase and lipase was analyzed., Results: Post-ERCP pancreatitis was diagnosed in 13 (8.7%) of 150 patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of urinary trypsinogen-2 dipstick test at 3 hours after ERCP are 84.6%, 97.1%, 73.3%, 98.5%, and 96%, respectively. At the cutoff level of 3 times the upper reference limit, the negative predictive values of amylase and lipase were comparable to that urinary trypsinogen-2 strip test; however, their positive predictive values (42.9% and 36.4%, respectively) were markedly lower than that of urinary trypsinogen-2 test (73.3%)., Conclusions: The urinary trypsinogen-2 dipstick test is a useful test for early diagnosis of post-ERCP pancreatitis. A negative urinary dipstick test at 3 hours after the procedure rules out post-ERCP pancreatitis with a high probability and allows of early discharge plan.

Objectives: In acute pancreatitis (AP), rapid diagnosis and early treatment are of importance for clinical outcome. Urinary trypsinogen-2 has been suggested as a promising diagnostic marker; however, studies using the urinary trypsinogen-2 dipstick test (UTDT) have provided varying results., Methods: The study was set to evaluate the use of the UTDT (Actim Pancreatitis; Medix Biochemica, Kauniainen, Finland, Medinor, Roskilde, Denmark) in apparent first attack of AP in daily clinics. Acute pancreatitis was defined as more than a 3-fold increase in plasma amylase levels. We included 75 patients admitted with AP. Thirty-four patients with acute abdominal pain of causes other than AP served as a control group., Results: In 58 of 75 patients, the UTDT result was positive, giving a sensitivity of 77% (95% confidence interval [CI]: 66%-86%). In severe cases, the sensitivity improved to 87% (95% CI: 69%-96%). In 33 of 34 controls, the test result was negative, giving a specificity of 97% (95% CI: 84%-99.9%)., Conclusion: The UTDT had a low sensitivity but high specificity. These results do not support the UTDT to replace standard plasma amylase for the diagnosis of apparent first attack of AP. However, the test demonstrated an adequate sensitivity to be used for rapid early screening of AP in daily clinics.

Objectives: Early diagnosis of acute pancreatitis remains a challenge. A rapid dipstick screening test for acute pancreatitis has been developed. This prospective study was designed to evaluate the diagnostic value and time course of the rapid urinary trypsinogen-2 test strip in acute pancreatitis, with comparisons with serum amylase and serum lipase., Methods: A total of 165 patients with acute abdominal pain (67 with acute pancreatitis and 98 with other acute abdominal diseases) attending our emergency unit were included. All patients were tested with the urinary trypsinogen-2 test strip, and serum amylase and serum lipase concentrations were determined simultaneously. To measure the time course of the urinary trypsinogen-2 test, 32 patients with acute pancreatitis were tested with a urinary trypsinogen-2 test strip on days 1, 2, 3, and 4 after admission., Results: Using a cutoff level of 50 microg/L for urinary trypsinogen-2, the sensitivity, specificity, and accuracy of the urinary trypsinogen-2 test strip for recognition of acute pancreatitis were 89.6%, 85.7%, and 87.3%, respectively. The diagnostic accuracy rates of serum amylase and serum lipase were 88.5% and 93.3%, using cutoff values of 3 times the upper normal limits for serum amylase and serum lipase, respectively. All but one of the 17 patients with severe acute pancreatitis was detected by the test strip (sensitivity, 94.1%). The time-course study of the urinary trypsinogen-2 test strip revealed that the sensitivity on days 1, 2, 3, and 4 was 90.6%, 81.2%, 59.4%, and 50%, respectively. There was no significant difference in the sensitivity between urinary trypsinogen-2 and serum lipase; however, the sensitivity values of serum lipase were significantly higher than those of serum amylase from days 1 to 4., Conclusion: The rapid urinary trypsinogen-2 test is a reliable and simple method for the early diagnosis of acute pancreatitis. A positive test identifies patients in need of further diagnostic measures. The urinary trypsinogen-2 test can be performed in health care units where laboratory testing facilities are not immediately available.

Background: Serum and urine concentrations of the activation peptide of carboxypeptidase B (CAPAP) and urinary trypsinogen activation peptide (TAP) as prognostic markers in acute pancreatitis were compared., Method: Fifty-two patients with acute pancreatitis hospitalized within 24 hours after symptom onset were prospectively studied. Blood and urine samples were obtained during the first 3 days of the hospital stay., Results: Pancreatitis was severe in 17 patients and mild in 35 (Atlanta criteria). Median serum CAPAP levels on days 1 and 2 and of urine CAPAP and TAP on days 1, 2, and 3 were significantly higher in severe pancreatitis than in mild disease. On the first day of admission, TAP was the most accurate predictor of severity (sensitivity, 92.3%; specificity, 80%; positive and negative predictive values, 63.2% and 96.6%, respectively), with a 4.61 positive likelihood ratio for a cutoff value of 18.10 nmol/L, whereas within 24 hours after symptom onset, urinary CAPAP was superior (sensitivity, 88.9%; specificity, 81.3%; positive and negative predictive values 72.7% and 92.9%, respectively), with a 4.72 positive likelihood ratio for a cutoff value of 15.45 nmol/L., Conclusion: Serum and urine CAPAP levels and urinary TAP are accurate in the early assessment of severity in acute pancreatitis. Urine CAPAP levels was the most accurate marker 24 hours after onset of symptoms.

Introduction: Acute pancreatitis may be initiated by interference with the pancreatic outflow to the duodenum. This flow is normally regulated by reflex relaxation of the sphincter of Oddi in which nitric oxide is an important mediator., Aim: To test the hypothesis that acute pancreatitis involves a depletion in serum L-arginine resulting in impaired production of nitric oxide., Methods: We measured serum L-arginine and L-citrulline and urinary nitrite/nitrate concentrations 1 to 3 days after the onset of symptoms in 11 patients with gallstone pancreatitis, 10 patients with alcoholic pancreatitis, and 6 patients with idiopathic pancreatitis. We compared their results with those from control groups of 13 healthy blood donors, 9 patients fasting before hernia operations, 8 patients with acute cholecystitis, and 9 alcoholic subjects but no pancreatitis. Serum arginine and citrulline concentrations were measured with high performance liquid chromatography, and urinary nitrite/nitrate spectrophotometrically., Results: Patients with acute pancreatitis, of whatever cause, had lower serum L-arginine and L-citrulline concentrations than controls. Patients with gallstone and idiopathic pancreatitis also have reduced urinary concentrations of nitrite and nitrate but this was not seen in patients with alcoholic pancreatitis., Conclusions: L-arginine and L-citrulline concentrations are depleted in the serum of patients with acute pancreatitis. Reduced urinary nitrite and nitrate in gallstone pancreatitis indicate that there is a defect formation of nitric oxide. This may cause a functional obstruction of the outflow of pancreatic juice to the duodenum and so may be involved in the pathophysiology of acute pancreatitis.

Trypsinogen activation peptide (TAP) is a useful marker of severe acute pancreatitis. However, it is sometimes difficult to detect an elevation of plasma TAP in patients with acute pancreatitis because TAP is rapidly cleared from plasma. Therefore, urine TAP has been evaluated to provide an accurate prediction of the outcome of pancreatitis. In the present study, we examined the time course of plasma and urine TAP simultaneously after induction of taurocholate-induced pancreatitis in rats. Plasma TAP levels peaked at 1 hour after the induction of pancreatitis and then gradually decreased, but was still higher than prepancreatitis levels at 48 hours. Significant increases in urine TAP levels were seen at 0-6, 6-12, and 30-36 hours after induction of pancreatitis. The peak level of urine TAP output and TAP/creatinine ratio was observed at 6-12 and 30-36 hours, respectively. Urine TAP concentration showed a significant correlation with both urine TAP/creatinine ratio and TAP output in urine (p < 0.01). In conclusion, plasma TAP increased immediately after the induction of pancreatitis, but excretion of TAP into urine was delayed several hours in taurocholate-induced pancreatitis in rats. The measurement of urine TAP concentration alone sufficiently can reflect the amount of TAP liberated in the pancreas at initial stage of acute pancreatitis.

Acute pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) occurs in 3-18% of patients undergoing either diagnostic or therapeutic ERCP. We prospectively measured urinary trypsinogen activation peptides (TAP) by an automated anti-TAP enzyme-linked immunoassay among 107 patients 4 h after ERCP to determine whether this measurement helps in the early diagnosis of ERCP-induced pancreatitis. Pancreatitis was documented in 10 of 107 patients (9.3%). All episodes were graded as mild. Urinary TAP was not significantly increased. We conclude that measurement of urinary TAP 4 h after ERCP is not helpful in documenting mild ERCP-induced acute pancreatitis.

An enzyme-linked immunosorbent assay for trypsinogen activation peptide (TAP) was used to measure urinary TAP levels in standard feline models of acute oedematous pancreatitis and acute haemorrhagic pancreatitis. It has been shown that the extent of pancreatic damage as assessed histologically is significantly greater in the model of acute haemorrhagic pancreatitis. This increase in damage has been found to be associated with a significantly greater increase in the excretion of urinary TAP.

Urinary and serum zinc levels were determined in 51 patients with chronic pancreatitis. Urinary zinc excretion in patients with chronic calcified pancreatitis (832 +/- 111 micrograms/day) (mean +/- SE) but not in noncalcified pancreatitis (684 +/- 65 micrograms/day) was significantly higher than in normal controls (418 +/- 46 micrograms/day). The urinary zinc excretion increased with deterioration of exocrine pancreatic function. Serum zinc levels in advanced pancreatitis (105.9 +/- 4.5 micrograms/100 ml) were significantly higher when compared to the pancreatitis with normal exocrine pancreatic function (91.6 +/- 3.0 micrograms/100 ml), but the difference was less pronounced than for urinary zinc excretion. This may be due to complicating diabetes, which usually lowers serum zinc. Serum zinc and urinary zinc excretion were low in a patient with chronic calcified pancreatitis complicated with a pulmonary abscess and hypoalbuminemia. In conclusion, urinary and serum zinc levels in chronic pancreatitis were increased as a result of exocrine pancreatic dysfunction. Association of diabetes may lower serum zinc, and associated malnutrition depresses both urinary and serum zinc levels.

Lipase, in contrast to amylase, is completely reabsorbed by the proximal tubules after glomerular filtration. Therefore, no lipase is detectable in the unconcentrated urine according to the current opinion. The handling of lipase (detected with an enzyme-immunoassay) by the kidney was investigated in comparison with creatinine, amylase, and beta-2-microglobulin by clearance studies in acute pancreatitis (n = 10), burn injury (n = 4), glomerular proteinuria (n = 8), and controls without evidence of pancreatic or renal diseases (n = 5). In initial stages of acute pancreatitis a measurable clearance of lipase (mean: 49.6 microliters/min, range: 0.5-234) was found in association with corresponding increased clearances of beta-2-microglobulin (mean: 10.5 ml/min, range: 0.02-58.9) and of amylase (mean: 8.9 ml/min, range: 2.4-22.6) in nine of ten patients. This finding is consistent with a defect of tubular function. However, regression analysis failed to show a significant correlation between lipase and beta-2-microglobulin clearance. Repeated measurements during the course of pancreatitis in seven patients showed reversibility of tubular dysfunction. In patients with burn injury a similar elevation of clearances of beta-2-microglobulin and of amylase was found, but tubular dysfunction in this condition was not associated with lipasuria. In glomerular proteinuria a lipase clearance was found in two of five cases with moderate, and in the other three cases with severe impairment of creatinine clearance. beta-2-microglobulin clearance was normal in the former and only slightly elevated in the latter group. In conclusion lipase is measurable in the urine of most patients with acute pancreatitis as a result of a reversible tubular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)