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Pancreatic acinar-like metaplasia has previously been described in the gastric mucosa and in the distal part of the oesophagus. The resemblance to pancreatic acinar cells prompted us to study the possible occurrence of secretory pancreatic proteins in these cells.Seven specimens obtained from the distal oesophagus at gastroscopy where routine microscopy showed pancreatic acinar-like metaplasia were selected for this study. Sections were subjected to immunohistochemical detection of trypsinogen, pancreatic elastase, procarboxypeptidase B and pancreatic secretory trypsin inhibitor using specific antisera. An alkaline-phosphatase-conjugated oligodeoxynucleotide probe, complementary to the transcript for trypsinogen 2 (anionic) was used for in situ hybridization.Cells with pancreatic acinar-like metaplasia were immunoreactive to all pancreatic secretory proteins studied. In situ hybridization showed the presence of trypsinogen 2 mRNA in pancreatic acinar-like metaplasia. The pancreatic proteins were not seen in other cells in the distal oesophagus.Pancreatic acinar- like metaplasia is common in the distal oesophagus and pancreatic secretory proteins, including trypsininogen 2, are produced in the oesophageal metaplastic acinar cells. The biological significance of this finding has yet not been thoroughly studied.

Infected pancreatic necrosis is the main cause of death in patients with acute pancreatitis, and therefore its early prediction is of utmost importance. Endogenous cortisol metabolism plays a basic role both in the course of acute pancreatitis and in the process of infection. The purpose of this study was to analyze corticosteroid-binding globulin (CBG), total cortisol, calculated free cortisol and adrenocorticotropic hormone as potential early predictors in order to differentiate between infected pancreatic necrosis and sterile pancreatic necrosis in patients with acute pancreatitis.Serum levels of CBG, total cortisol, calculated free cortisol, and plasma levels of adrenocorticotropic hormone were determined in 109 consecutive patients with acute pancreatitis. C-reactive protein was measured as the control parameter. Thirty-five patients developed necrotizing pancreatitis and 10 developed infection of the necrosis. Blood was monitored for 6 days after the onset of pain; 30 healthy individuals served as controls.Of all parameters only CBG showed a significant difference (p = 0.0318) in its peak levels measured in the first 48 h in patients with sterile (26.5 microg/ml, range 21.3-34.7) and infected (16.0 microg/ml, range 15.2-25.0) necrosis at a cut-off level of 16.8 microg/ml. That difference was further preserved for the first 6 days after onset of pain.In our group of patients, a decreased CBG level below 16.8 g/ml within the initial 48 h of acute pancreatitis was an early predictor of later infected pancreatic necrosis, with a positive predictive value of 100% and a negative predictive value of 87.5%.

Background Pancreatic acinar-like metaplasia has previously been described in the gastric mucosa and in the distal part of the oesophagus. The resemblance to pancreatic acinar cells prompted us to study the possible occurrence of secretory pancreatic proteins in these cells. Methods Seven specimens obtained from the distal oesophagus at gastroscopy where routine microscopy showed pancreatic acinar-like metaplasia were selected for this study. Sections were subjected to immunohistochemical detection of trypsinogen, pancreatic elastase, procarboxypeptidase B and pancreatic secretory trypsin inhibitor using specific antisera. An alkaline-phosphatase-conjugated oligodeoxynucleotide probe, complementary to the transcript for trypsinogen 2 (anionic) was used for in situ hybridization. Results Cells with pancreatic acinar-like metaplasia were immunoreactive to all pancreatic secretory proteins studied. In situ hybridization showed the presence of trypsinogen 2 mRNA in pancreatic acinar-like metaplasia. The pancreatic proteins were not seen in other cells in the distal oesophagus. Conclusion Pancreatic acinar-like metaplasia is common in the distal oesophagus and pancreatic secretory proteins, including trypsininogen 2, are produced in the oesophageal metaplastic acinar cells. The biological significance of this finding has yet not been thoroughly studied.

The rates of activation of procolipase, prophospholipase (proPLA2), chymotrypsinogen, and trypsinogen were studied after incubation of human pancreatic juice with porcine enterokinase in vitro. Under the conditions chosen procolipase was fully activated within 10 min of incubation. Full activation of phospholipase (PLA2) was seen within 15 min, whereas complete activation of chymotrypsin and trypsin was not seen until after 30 to 60 min, respectively. The different proenzymes probably differ in their suitability as substrates for trypsin. A physiologic consequence of a differentiated activation of the pancreatic proenzymes in vivo could be a delayed proteolytic degradation of the lipolytic enzymes in the intestine.

Pancreatic acinar-like metaplasia has previously been described in the gastric mucosa and in the distal part of the oesophagus. The resemblance to pancreatic acinar cells prompted us to study the possible occurrence of secretory pancreatic proteins in these cells.Seven specimens obtained from the distal oesophagus at gastroscopy where routine microscopy showed pancreatic acinar-like metaplasia were selected for this study. Sections were subjected to immunohistochemical detection of trypsinogen, pancreatic elastase, procarboxypeptidase B and pancreatic secretory trypsin inhibitor using specific antisera. An alkaline-phosphatase-conjugated oligodeoxynucleotide probe, complementary to the transcript for trypsinogen 2 (anionic) was used for in situ hybridization.Cells with pancreatic acinar-like metaplasia were immunoreactive to all pancreatic secretory proteins studied. In situ hybridization showed the presence of trypsinogen 2 mRNA in pancreatic acinar-like metaplasia. The pancreatic proteins were not seen in other cells in the distal oesophagus.Pancreatic acinar-like metaplasia is common in the distal oesophagus and pancreatic secretory proteins, including trypsininogen 2, are produced in the oesophageal metaplastic acinar cells. The biological significance of this finding has yet not been thoroughly studied.

The total pancreatic lipolytic capacity was determined in duodenal contents in healthy humans 10-120 min after a liquid test meal, by estimating the amount of pancreatic lipase, colipase, carboxyl ester lipase, and phospholipase A2 by means of radioimmunoassays and enzymatic assays. The molar concentrations of the different proteins were of the same order of magnitude. The relative specific activity (enzyme activity/milligram immunoreactive protein expressed as a percentage of the specific activity of the respective pure protein) amounted to 75-120% for lipase, 45-80% for colipase, 30-70% for carboxyl ester lipase, and 45-120% for phospholipase A2. These varied, and sometimes low values can be explained by the fact that the enzymes are inhibited or partly inactivated in the duodenal contents by surface denaturation, in which cases the products are still immunoreactive. Also, the proforms of colipase and phospholipase A2 may not always be completely activated. Furthermore, the specific activities of the pure enzymes (and thus the relative specific activities) are related to the methods used, which are not specific enough to distinguish completely the three enzymes and the cofactor in duodenal contents.

The concentrations of pancreatic amylase, immunoreactive trypsin, and immunoreactive pancreatic specific trypsin inhibitor have been studied in serum drawn from 258 patients before an endoscopic retrograde cholangiopancreatography (ERCP) examination, in which both ducts were successfully filled. The results are correlated to the morphology of the ducts and the diagnosis given at the ERCP examination. One third of the patients with normal morphology of both ducts showed an abnormal concentration of at least one of the measured specific pancreatic proteins. Sixteen out of 38 patients with changes suggestive of chronic pancreatitis and 6 out of 23 patients with changes suggestive of pancreatic cancer showed normal levels of all variables measured. The sensitivity and specificity for pancreatic disease evident by ERCP were around 0.40 and 0.80, respectively, for all three proteins.

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.

After intravenous injection of autologous purified and radiolabeled anionic and cationic trypsinogens in the dog, there is a multiexponential elimination from serum of the trypsinogens without activation to active trypsins. The results are in agreement with an elimination of the trypsinogens iva glomerular filtration, a variable tubular uptake of anionic trypsinogen, and a complete tubular uptake of cationic trypsinogen. Fractional catabolic rates for anionic trypsinogen were 0.35-0.92 h-1 and for cationic trypsinogen 0.38-1.05 h-1. The total amount of anionic trypsinogen turned over in the circulation is estimated at approximately 0.55 mg every 24 h, and the corresponding figure for cationic trypsinogen is 0.35 mg/24 h.

Elevated levels of immunoreactive pancreatic secretory trypsin inhibitor (PSTI) were found in serum from patients with perforated duodenal ulcer, bacterial peritonitis, urosepticemia, pneumonia, acute renal failure, and also after different surgical procedures. The extent of the trauma seemed to determine the maximal level of PSTI. The increase found paralleled the changes seen in the acute-phase protein antichymotrypsin. There was, however, almost no increase in trypsinogen, thought to be produced together with PSTI in the acinar cells of the pancreas. In conclusion, there is evidence that PSTI is probably also produced somewhere outside the pancreas, in agreement with recent immunohistochemical data. This production may be part of a general acute-phase reaction. Thus, PSTI may have a more general inhibitory function against trypsin-like protease release in tissue injury, instead of being a purely local trypsin inhibitor in the pancreatic gland.

Feces from normal and antibiotic-treated persons were analyzed for the content of immunoreactive trypsin and elastase. In the control group the mean concentration of immunoreactive trypsin was 13 microgram per g feces as compared to 147 in the antibiotic-treated group. Elastase was demonstrable in only 3 of 30 samples in the control group but in 20 of 26 in the antibiotic-treated group. The decreased inactivation of pancreatic proteases must depend on an altered intestinal microflora. The results suggest that reestablishment of a normal enteric flora may take months after the short time oral administration of antibiotics.

The motility in the first part of the duodenum has been studied by a method combining roentgen fluorography and multiple pressure recordings in 7 normal volunteers, in 7 patients having gastric, and in 7 having duodenal, ulcer. A significantly lower number of retrograde motor sequences was found in cases with duodenal ulcer than in normals, while patients with gastric ulcers showed no such difference. This abnormality in subjects with duodenal ulcer was interpreted as a deficiency in the transport of neutralized duodenal contents from more distal parts of the duodenum up into the bulb. The abnormality can explain the earlier known lower pH in the duodenal bulb in subjects with duodenal ulcer and contribute to the pathogenesis of the disease.

An increased sensitivity of different brain stem centers in patients with dumping symptoms following gastric resection, measured as emetic and carbon dioxide chemoreceptor sensitivity, has previously been demonstrated by the authors.A method for determination of the standard threshold of the ventilatory response to carbon dioxide (sTCO2) was applied in 55 patients with peptic ulcer prior to gastric resection. The material comprised 21 males operated upon according to B II, 20 males according to B I, and 14 females according to B I. The patients were examined one year postoperatively for dumping complaints. An sTCO2 of 38.5 mm Hg was found to be a critical level. Cases with higher threshold values preoperatively did not get dumping symptoms of clinical significance. In 20 such cases there was only one exception. The severity of the dumping symptoms in the cases with a threshold value lower than 38.5 mm Hg, seemed to depend not only on the magnitude of the threshold value but also on the type of operation.

Twenty-seven patients with dumping complaints after partial gastrectomy for peptic ulcer were examined before and during dumping provocation with hypertonic glucose solution.A continuous and simultaneous registration of EEG and respiration, including spirography and capnography, was performed. The stage of wakefulness, the breathing pattern, and the sensitivity to carbon dioxide were studied and related to the symptoms experienced by the individuals examined.The dumping cases showed a lower mean standard threshold of ventilatory response to carbon dioxide than that found in a group of normals.Following glucose a two-phasic change in respiration as well as in level of wakefulness was found. During the first twenty minutes after dumping provocation with hypertonic glucose a disturbed irregular ventilatory pattern was usually present, in severe cases even marked hyperventilation. At the same time there were signs of increased wakefulness resembling that during tense alertness. It was followed by a successive...

Cholesterol and lecithin absorption in man was studied by intestinal intubation. β-3H-sitosterol lipid-soluble marker. Cholesterol absorption was limited and progressed over the length of the small intestine; most extensive in the upper part. Lecithin was hydrolyzed to L-α-lysolecithin and free fatty acids, which were absorbed in parallel in the upper small intestine. 3.5–6.5 g lecithin and 0.2–0.4 g cholesterol were delivered via the bile during passage of a test meal. Phospholipids partitioned in a glyceride bile salt mixture in favour of the bile salt micellar phase.

The duodenal transport mechanism has been studied by a method combining roentgen-fluorography and multiple pressure recordings. Three main types of motility were distinguished: propulsive, retrograde, and static. The motor pattern in the first part of the duodenum was studied in 15 individuals under basal condition and after application in the duodenal lumen of sodium myristate. The resulting inhibition of gastric emptying was found to be correlated to a significant inhibition of the propulsive movements in the duodenum. The two others types of motor activity did not change significantly.

Ozonization has been used for decolorization of the neutral steroid fraction of fecal lipids in order to eliminate color quench in liquid scintillation counting. Decolorization is rapid and effective and no loss of radioactivity was found with choIesterol-4-14C and sitosterol-22-23-3H.

The levels of amylase, trypsinogen, and trypsin-alpha 1-protease inhibitor complexes, both in serum and in peritoneal fluid, were correlated to the severity and clinical course in 27 attacks of acute pancreatitis. Serum levels of trypsin-alpha 1-protease inhibitor complexes on admission correlated well with the severity and clinical course of the disease, whereas serum levels of amylase and trypsinogen did not. This may be of clinical importance in differentiating severe acute pancreatitis from milder and self-limiting forms of the disease.

In 1962, Hofman & BorgstroUm (1, 2) applied the then available knowledge of detergent chemistry to the problem of the physicochemical status of intestinal content during digestion of fat. In vitro studies indicated that the products of pancreatic lipolysis of triglyceride fat–mainly 2-mono-glyceride and fatty acid–form mixed micelles with bile salts in an isotropic (optically clear) solution. Ultracentrifugation of intestinal content after a fatty meal fed to man yielded an oil phase and a clear aqueous phase. The former contained mostly unchanged triglyceride and some diglyceride, the latter mainly fatty acid and mono-glyceride. It was concluded that intestinal content during digestion is a detergent solution above its critical micellar concentration (CMC). The results were consistent with the hypothesis that intestinal lipids, during fat digestion, are partitioned between a micellar and an oil phase and that absorption of dietary lipid takes place from a micellar solution containing chiefly fatty acid a...

The concentrations of pancreatic amylase, immunoreactive trypsin, and immunoreactive pancreatic specific trypsin inhibitor have been studied in serum drawn from 258 patients before an endoscopic retrograde cholangiopancreatography (ERCP) examination, in which both ducts were successfully filled. The results are correlated to the morphology of the ducts and the diagnosis given at the ERCP examination. One third of the patients with normal morphology of both ducts showed an abnormal concentration of at least one of the measured specific pancreatic proteins. Sixteen out of 38 patients with changes suggestive of chronic pancreatitis and 6 out of 23 patients with changes suggestive of pancreatic cancer showed normal levels of all variables measured. The sensitivity and specificity for pancreatic disease evident by ERCP were around 0.40 and 0.80, respectively, for all three proteins.

Erlanson, Charlotte & Borgstrom, B. 1970. Carboxyl Ester Hydrolase and Lipase of Human Pancreatic Juice and Intestinal Content. Behaviour in Gel Filtration. Scand. J. Gastroent. 5, 395-400.Human pa...