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Biomedical subjects

H Printz

Publications and source records attributed to H Printz.

32 records · Page 2Linked to original sources

Secretion of lysosomal and digestive enzymes into pancreatic juice under physiological and pathological conditions in rabbits.

To investigate the possible secretion of lysosomal enzymes into pancreatic juice during stimulation with a pancreatic secretagogue under both physiological and pathological conditions, we measured the amount of cathepsin B, a lysosomal enzyme, in the pancreatic juice during the infusion of 6 different concentrations of caerulein (0.02, 0.05, 0.2, 0.5, 1.0, and 2.0 micrograms/kg. hr). In one group of rabbits the pancreatic duct was only cannulated (free-flow group); in others the pancreatic duct was obstructed for 7 hours and secretin was infused at 0.2 CU/kg. hr (obstructed group). In addition, we evaluated the effect of the intraduodenal instillation of a liquid meal (2 g/kg) on the secretion of lysosomal enzymes into pancreatic juice. Caerulein stimulated the secretion of cathepsin B into pancreatic juice in a dose-dependent manner, as it did that of amylase, and at higher concentrations of caerulein (1.0 and 2.0 micrograms/kg. hr), both cathepsin B output and amylase output were decreased. There was a significant positive correlation between cathepsin B output and amylase output into pancreatic juice during stimulation with caerulein. Blockage of the pancreatic duct for 7 hours caused a significant rise in serum amylase levels and a redistribution of cathepsin B activity in the pancreatic subcellular fractions, as a result of which an increased amount of cathepsin B was recovered in the pellet obtained by 1000 x g centrifugation for 15 min, which contained many zymogen granules. These changes noted after short-term pancreatic duct obstruction are very similar to those previously noted in the early stage of diet-and caerulein-induced experimental pancreatitis, suggesting the colocalization of lysosomal enzyme and digestive enzymes. In the duct-obstructed animals, the secretion of cathepsin B stimulated by caerulein was significantly greater than in the free-flow group. Furthermore, the intraduodenal instillation of a liquid meal caused the secretion of cathepsin B into the pancreatic juice along with amylase. These results indicate that under physiological conditions, such as food intake, lysosomal enzymes are secreted into the pancreatic juice in response to stimulation by gut hormones in the same manner as classical pancreatic digestive enzymes. Moreover, zymogen colocalized with lysosomal enzymes in duct-obstructed animals is secreted into pancreatic juice in increased amounts together with digestive enzymes; this finding suggests that lysosomal enzymes play important pathophysiological roles in pancreatic juice and that acinar cells are altered to maintain cellular organization by secreting the potentially dangerous lysosomal enzymes. This pancreatic duct-obstructed rabbit model should be useful in clarifying the early events of acute pancreatitis.

Amylases↗

Intraoperative ultrasonography in surgery for chronic pancreatitis.

We report our experience with intraoperative ultrasonography in 49 patients undergoing surgery for chronic pancreatitis. Among drainage procedures, there were 14 laterolateral pancreaticojejunostomies, 15 pseudocystojejunostomies, and 2 pseudocystoduodenostomies. Under the guidance of intraoperative ultrasonography, left sided partial resection of the pancreas was performed in 7 patients, whereas a Whipple-type procedure was necessary in 6 cases. All preoperatively diagnosed pseudocysts, abscess formations, and dilated pancreatic ductal systems could be easily localized with the assistance of intraoperative ultrasound. Additionally to diagnoses already made preoperatively, intraoperative ultrasonography revealed a second, smaller pseudocyst in one patient and pancreaticolithiasis in another case. However, significant assistance and comfort to the operating surgeon was provided in all cases by intraoperative ultrasound imaging. This technique, which is cost effective and minimally invasive, proved to be extremely helpful in localizing pancreatic fluid collections and the course of the pancreatic duct. It facilitates the operation by reducing tissue traumatization and operative time. In experienced hands, intraoperative ultrasonography is a reliable method and a useful adjunct to the surgeon.

Adult↗

Cytotoxic effects of cyclosporin A on the exocrine pancreas in rats.

The current study was done to evaluate the subacute toxic effects of cyclosporin A (CS) on the exocrine pancreas and the protective effect of potent protease inhibitor camostate (FOY-305). CS administration (15 milligrams, twice a day) for 14 days caused a significant increase in serum amylase levels, pancreatic amylase and cathepsin B content and mild acinar cell vacuolization and interstitial edema. CS also caused the redistribution of cathepsin B activity from the lysosomal fraction to the zymogen fraction, indicating colocalization of lysosomal enzyme with pancreatic digestive enzymes. The administration of camostate (150 milligrams per kilogram, twice a day for 14 days) almost completely prevented the toxic changes induced by CS. These results indicate that CS induces exocrine pancreatic injury and that lysosomal enzymes play important roles in the pathogenesis of the injury. The results also suggest the usefulness of camostate in protecting the exocrine pancreas in patients treated with CS after organ transplantation, because it can inhibit some proteases that are closely involved in the fragility of the subcellular organelles.

Amylases↗

[Chronic purulent, draining, indolent pancreatic head pancreatitis with extrahepatic cholestasis].

Over the period of two weeks a 19-year-old man developed gradually increasing painless jaundice with dark urine and light-coloured soft stools (6-7 times daily), as well as loss of appetite, nausea and nagging itch. Biochemical tests indicated marked cholestasis (alkaline phosphatase 800 U/l, gamma-GT 206 U/l). Abdominal ultrasound examination revealed high-grade stenosis of the distal choledochal duct caused by an enlargement of the head of the pancreas and computed tomography confirmed a tumour in this location. Endoscopic retrograde cholangiopancreatography demonstrated filiform stenosis of the major pancreatic duct and prepapillary stenosis of the choledochal duct. Several needle biopsies failed to establish a definitive diagnosis. A Whipple operation was performed: the stomach was preserved but about 40% of pancreatic tissue resected. Histologically there was chronic suppurative pancreatitis of the head of the pancreas. The patient was symptom-free 6 months after the operation. The case illustrates that it is not always possible in a painless pancreatic tumour to distinguish between pancreatitis and malignant tumour.

Adult↗

[Comparative microstructural studies on collagen and elastic fiber systems of the cruciate ligaments].

The aim of the present study was to compare the collagenous fibre systems of the anterior (ACL) with the posterior cruciate ligament (PCL). 22 cruciate ligaments were examined by the combined use of light-, transmission- and scanning electron microscopy. Characteristic interligamental differences were established. ACL: more anchoring type VI collagen, thinner but more branched fibrils, complex collagen networks, much more elastic elements. PCL: more type IV collagen, many intrinsic vessels, thicker fibrils, parallel fibre arrangement. The results indicate that the ACL is exposed at the first line to rotational forces, the PCL probably more to tensional forces. The collagen fibre arrangement of the cruciate ligaments is to take into consideration by the surgeon.

Adult↗

A network model of catecholamine effects: gain, signal-to-noise ratio, and behavior.

At the level of individual neurons, catecholamine release increases the responsivity of cells to excitatory and inhibitory inputs. A model of catecholamine effects in a network of neural-like elements is presented, which shows that (i) changes in the responsivity of individual elements do not affect their ability to detect a signal and ignore noise but (ii) the same changes in cell responsivity in a network of such elements do improve the signal detection performance of the network as a whole. The second result is used in a computer simulation based on principles of parallel distributed processing to account for the effect of central nervous system stimulants on the signal detection performance of human subjects.

Behavior↗

Effects of hemorrhagic shock, aspirin, and ethanol on secretagogue-induced experimental pancreatitis.

The effects of hemorrhagic shock, aspirin, and ethanol on the biochemical and morphologic changes of experimental pancreatitis were evaluated. Pancreatitis was induced by infusing rats with a supramaximally stimulating dose (5 micrograms/kg/h) of caerulein. Hemorrhagic shock was established by removing sufficient blood to reduce mean arterial pressure by 30%, where it was maintained for 30 min. Aspirin (25 mg/kg) and ethanol (2 g/kg) were administered through an orogastric tube at 8-h intervals for 48 h. Hemorrhagic shock did not alter the degree of hyperamylasemia, pancreatic edema, cathepsin B subcellular redistribution, or in vitro LDH leakage that characterize this model of pancreatitis. Hemorrhagic shock did, however, worsen the morphologic evidence of pancreatic injury. Administration of aspirin with ethanol did not alter the degree of hyperamylasemia, pancreatic edema, or subcellular cathepsin B redistribution. Aspirin-ethanol pretreatment also did not alter the morphologic severity of pancreatitis. These observations indicate that hemorrhagic shock worsens the microscopic evidence of pancreatitis induced by supramaximal secretagogue stimulation. In contrast, aspirin-ethanol pretreatment, which might have been expected to increase pancreatic ductal permeability, did not alter the severity of this model of experimental pancreatitis.

Amylases↗

Protein profiles in rabbit pancreatic juice analyzed by HPLC after stimulation of secretion by secretin and cerulein.

This study analyzed the secretory pattern of pancreatic proteins released from the rabbit pancreas after acute stimulation of secretion by the cholecystokinin analog cerulein. To facilitate this, a new analytical approach utilizing high performance liquid chromatography (HPLC) was considered. Secretin (0.1 CU/kg x h) was intravenously infused in anaesthetized rabbits in combination with cerulein (0.05, 0.2 or 0.05 followed by 0.2 ug/kg x h) over 3 hours. Pancreatic juice was collected from the main pancreatic duct. The release of protein, amylase, trypsin and chymotrypsin was measured by conventional photometric methods, and the protein profiles were analyzed by reversed phase HPLC. Separation of pancreatic juice proteins by HPLC (Nucleosil 300-7 RP column; injection of 50 ul aliquots of samples normalized to 10 mg/ml protein concentration) resulted in a resolution of up to 16 peaks. Peaks representing amylase, prolipase, prophospholipase A2, procarboxypeptidases, chymotrypsinogen, trypsinogen, and glycoproteins were identified with some certainty by SDS-gel electrophoresis. Secretin infusion produced a small and short lasting rise in total protein secretion but lead to a persistent increase of fluid flow. The release of enzymes followed a mainly parallel pattern according to the photometric measurements. The resolution of the whole profile of pancreatic juice proteins by HPLC demonstrated only minor variations without a consistent or increasing tendency towards a preferential release of individual enzymes. Since even microheterogenities in the samples became apparent after HPLC, this approach would be sensitive enough to mirror effects like nonparallel release of enzymes.

Animals↗

Effect of atropine on feedback regulation of pancreatic secretion in rats.

In the present study the effect of atropine on feedback regulation of pancreatic function was investigated in male rats. Orogastric tube feeding of a single dose of the protease inhibitor camostate (100 mg) caused a 6-fold increase in plasma CCK. This was accompanied by a 50% decrease in pancreatic enzyme content for up to 6 h. The effect of i.v. infusion of atropine (100 micrograms.kg-1.h-1) was studied 60 and 180 min after camostate feeding. Atropine completely abolished the decrease in enzyme content 180 min after camostate feeding. The stimulated CCK plasma levels were significantly lowered by the infusion of atropine 60 min, but not 180 min, after feeding of camostate. It is discussed that a cholinergic pathway mediates CCK release in the early phase of feedback regulation of pancreatic function.

Amylases↗

Experimental pancreatitis is mediated by low-affinity cholecystokinin receptors that inhibit digestive enzyme secretion.

Rats infused with a supramaximally stimulating dose of the cholecystokinin (CCK) analog caerulein develop acute edematous pancreatitis. Using CCK-JMV-180, a recently developed CCK analog that acts as an agonist at high-affinity CCK receptors but antagonizes the effect of CCK at low-affinity receptors, we have determined that caerulein induces pancreatitis by interacting with low-affinity CCK receptors. Those low-affinity receptors mediate CCK-induced inhibition of digestive enzyme secretion from the pancreas. Our observations, therefore, suggest that this form of experimental pancreatitis results from the inhibition of pancreatic digestive enzyme secretion.

Acute Disease↗

Influence of experimental hyperthyroidism on the adult rat pancreas, small intestine, and blood gastrin levels.

Thyroxine modulates the ontogenic changes of animal tissues. In this study, the effects of experimental hyperthyroidism on the adult rat pancreas, small intestine, and serum gastrin were evaluated. Hyperthyroidism was induced by oral feeding of thyroxine (T4) in increasing dosages (150-450 micrograms/kg body weight; 3 weeks) and controlled by measurements of the circulating hormones. The increase of thyroid hormones in blood (T4 ng/dl: thyroxine-treated rats 10.8 vs. controls 3.3; p less than 0.01; given are means) was accompanied by hypergastrinemia (IR-gastrin pg/ml: T4-treated rats 169 vs. controls 25; p less than 0.05). The T4-treated animals consumed more food but lost about 20 g of their initial body weight. Pancreatic wet weight (g: T4-treatment 1.72 vs. controls 1.42; p less than 0.05), DNA (micrograms/g body weight: T4-treatment 2.42 vs. controls 1.5; p less than 0.05), and protein (micrograms/g body weight: T4-treatment 131.7 vs. controls 63.5; p less than 0.05) were increased, whereas no pronounced influence on pancreatic amylase, trypsin, and chymotrypsin was found. The gut wet weight after thyroxine administration (18.1 g vs. 15.4 g of controls; p less than 0.05) was elevated, but length, DNA, protein, and brush border enzyme activities remained unaltered. Our data demonstrate in adult rats a small but significant trophic response of pancreas and gut to repeated oral thyroxine administration.

Animals↗

Endogenous CCK release and pancreatic growth in rats after feeding a proteinase inhibitor (camostate).

The serine proteinase inhibitor camostate was fed to rats in single, daily doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg for 5, 10, or 15 days. Within 5 days, pancreatic size and protein, DNA, and enzyme content increased significantly. After prolonged administration, this trophic effect was more pronounced, and anticoordinate regulation of the synthetic rate of individual secretory proteins was observed. While enzyme content and protein synthesis of trypsinogen and chymotrypsinogen were increased, respective values for amylase were drastically reduced. Plasma levels of cholecystokinin (CCK) did not differ from controls when measured 24 h after administration of camostate. Immediately after oral feeding of camostate, CCK levels increased 10-fold above controls, reached a maximum after 90 min, and remained elevated for more than 6 h. Proglumide, a CCK-receptor antagonist, only slightly reduced the trophic action of the proteinase inhibitor. The data indicate that endogenous CCK release by a proteinase inhibitor is as potent in the modulation of pancreatic growth and individual enzyme synthesis as exogenous hormone application.

Animals↗

GLP-1 release in man after lower large bowel resection or intrarectal glucose administration.

BACKGROUND: This study addresses the question whether the insulinotropic gut hormone, glucagon-like peptide-1 (GLP-1), is released from the lower large bowel upon oral or rectal glucose uptake. METHODS: It was evaluated whether rectum or sigmoid colon resection alters glucose homeostasis or the plasma levels of the insulinotropic gut hormone, gastric inhibitory polypeptide (GIP), or GLP-1. Six men and 3 women (age 63 +/- 8 years, BMI 25.4 +/- 4.0 kg/m2) with normal preoperative fasting glucose values were treated before and after resection of large bowel segments. Fasting oral glucose tolerance (OGT, 75 g glucose/300 ml) tests were performed both before and 10 days postoperatively. Another approach aimed to clarify whether luminal glucose stimulation in the rectum/sigmoid colon increases GLP-1 plasma levels. Ten healthy volunteers (4 males, 6 females, age 25 +/- 2 years, BMI 22.1 +/- 2.4 kg/m2) received enemas with both saline and, 7 days later, 1 g/kg body weight glucose (70% glucose solution) intrarectally. RESULTS: Neither rectum nor sigmoid colon resection led to significant changes in the pre- and postoperative glucose responses to OGT testing, or insulin, GIP and GLP-1 release. Intrarectal glucose instillation increased blood glucose by about 10 mg/dl with parallel small elevations in immunoreactive insulin and immunoreactive C peptide. However, plasma GLP-1 levels remained unaltered. CONCLUSION: Our data make it unlikely that GLP-1 derived from the lower large bowel contributes significantly to maintain normal glucose tolerance.

Administration, Rectal↗