The three major phases in the secretory process in the exocrine pancreas (synthesis, intracellular transport, zymogen discharge) have been tested in vitro after changing circulating insulin levels in rats in vivo. One group of rats received a continuous infusion of glucose for periods up to 72 hours, which keeps blood glucose levels above 200 mg/100 ml and immunoreactive insulin (IRI) raised to 130 muU/ml. As a result of this treatment, amylase content in the pancreas increases by 25% while chymotrypsinogen and lipase show a comparable decrease. The rate of total protein synthesis increased by 40% after 48 hours of infusion. The basal and carbamylcholine stimulated discharge of newly synthesized proteins are not altered. The baseline discharge of amylase is increased significantly, while the discharge of lipase and chymotrypsinogen decreased below control levels. Similar results are obtained, if circulating insulin levels are raised by the application of glibenblamide (HB419) for a period of 24 hours. Protein synthesis increases by 26.5% and baseline discharge of amylase by 50%. In chronic alloxan diabetic animals the alteration of the exocrine pancreatic function depends on the severity of the diabetes and relates to circulating insulin levels. Animals with highest blood glucose levels and low or undetectable insulin concentrations show a disappearance of amylase from the exocrine pancreas and a depression of the rate of protein synthesis by 30%. The results suggest a direct effect of insulin on protein biosynthesis and zymogen discharge, most pronounced for amylase.

Pancreatic secretion and plasma cholecystokinin (CCK) and secretin levels were measured in 10 healthy volunteers after application of a serine protease inhibitor (camostate) to study the mechanism of feedback regulation. Camostate produced a strong inhibition of trypsin and chymotrypsin activity in duodenal juice for 1 h. This was accompanied by an increase in duodenal aspirate volume and pancreatic enzyme secretion under both basal and secretin-stimulated conditions. Due to inhibition of tryptic activity, survival of lipase activity in duodenal juice was prolonged. In control experiments we ruled out that the volume and the pH of the solution were responsible for stimulation of pancreatic secretion. The protease inhibitor did not alter pancreatic secretion, which was stimulated by a test meal. Plasma levels of CCK and secretin were not changed after duodenal perfusion of camostate. These observations suggest that trypsin and chymotrypsin are involved in feedback regulation of pancreatic secretion in man which is, however, not mediated by CCK or secretin.

In this study, the cholesteryl octanoate breath test was used to monitor the release and activity of cholesterol esterase from different preparations of pancreatin in patients with severe pancreatic exocrine insufficiency. We compared treatment with acid resistant enteric coated microspheres (Panzytrat 20.000, Nordmark, FRG) to treatment with identical uncoated enzyme supplements with and without adjunctive cimetidine.

Rat dorsal prostate epithelium was studied in intact adult animals, in animals castrated for three days and in rats after inhibition of prolactin secretion. Thin sections, electron-microscopic autoradiographs and freeze-fracture replicas were used to analyze the process of apocrine secretion in this gland. The rough endoplasmic reticulum and the Golgi apparatus of the secretory cells are well developed, but secretory granules are absent. The only sign indicating release of secretory material is the appearance of blebs originating from the apical plasma membrane. Freeze-fracture replicas of the apical plasma membrane reveal that the blebs develop randomly from the bases of microvilli-like protrusions. In vitro pulse labeling of the proteins using 3H-leucine resulted in a labeling of the apical blebs. A post-castration period of three days was sufficient to reduce drastically the number and size of the apical blebs conhree weeks by application of lisuride, a synthetic ergot alkaloid, also induced regressive changes in the secretory cells. The apical blebs were still present, but they were shrunken and their content appeared condensed. These experimental conditions proved that the apical blebs are closely related to the functional activity of the cells and are interpreted as true apocrine secretion in the rat dorsal epithelium.

This report concerns a 17-year-old male patient with atypical mycosis fungoides (m.f.). Initial examination revealed generalized lymphoma and uncharacteristic livid skin efflorescence. The patient developed bone marrow involvement and meningeal leukaemia 6 months later. Diagnosis was confirmed by immunohistochemistry and electron microscopy. Aggressive chemotherapy yielded no response.

Zusammenfassung ! Grundlagen: Der duodeno-gastro-ösophageale Reflux (DGER) wird als unabhängiger Risikofaktor für die Entstehung einer komplizierten gastro-öso-phagealen Refluxerkrankung (GERD) angesehen. Sowohl klinische als auch epidemiologische Daten lassen vermuten, dass eine Cholezystektomie (CCE) das Ausmaß eines DGER beeinflussen könnte. Methoden: 132 Patienten (67 Frauen, 65 Männer, Altersmedian 55) mit typischen klinischen Beschwerden einer GERD wurden in die Studie eingeschlossen. Die Patienten wurden unterteilt in cholezystektomiert (CCE-Gruppe, n = 25) und nicht cholezystektomiert (nCCE-Gruppe, n = 107). Die standardisiert durchgeführte Diagnostik beinhaltete eine 24-h-pH-Metrie mit Bilitec 2000 und Ösophagusmanometrie sowie eine Ösophago-gastro-Duodenoskopie. Ergebnisse: Die statistische Analyse erbrachte keine signifikanten Unterschiede weder in Quantität noch Qualität von Refluxsymptomen zwischen den Patienten mit und ohne Cholezystektomie. Weitergehend unterschied sich die CCE-Gruppe weder in dem Ausmaß des sauren Refluxes noch in dem Auftreten oder der Schwere einer Refluxösophagitis von der nCCE-Gruppe. Jedoch wies die CCE-Gruppe einen signifikant höheren Prozentsatz von Patienten mit einem pathologisch gesteigerten DGER im Vergleich zu der nCCE-Gruppe auf (76 vs. 55%, p < 0,01). Entsprechend zeichnete sich die CCE-Gruppe durch einen signifikant höheren DGERD im Vergleich zu der nCCE-Gruppe aus (15,5% ± 14,1 vs. 8,6% ± 15,4; p < 0,05). Schlussfolgerung: In der hier vorgestellten Studie konnte erstmals der potenzielle Einfluss einer Cholezystektomie auf das Ausmaß des DGER in Patienten mit klinischen Symptomen einer Refluxerkrankung unter Verwendung des Bilitec 2000 gezeigt werden. Sowohl die Frequenz als auch das Ausmaß des DGER waren in der CCEAbstract ! Backgrounds: Duodenal-Gastro-Esophageal Reflux (DGER) represents an independent risk factor for the development of complicated Gastro-esophageal-reflux-disease (GERD) and Barrett's esophagus. Clinical and epidemiological data suggest a potential association between cholecystectomy (CCE) and augmented bile reflux. Methods: 132 patients (67 women, 65 men, median age 55) with typical symptoms of GERD were enrolled in the study and divided in cholecystectomized (CCE-group: n = 107) and noncholecystectomized (nCCE-group: n = 25) patients. Standardized clinical work-up of patients included combined esophageal 24 h pH-measurement and Bilitec 2000 esophageal manometry and upper endoscopy. Results: In the statistical analysis no differences between the cholecystectomized group (CCEgroup, n = 25) and the patients without cholecystectomy (nCCE-group, n = 107) could be observed in quantity or quality of reflux symptoms. Furthermore, neither acid reflux nor severity of inflammation and frequency of Barrett's esophagus significantly differed between the nCCE and CCEgroup. However, the percentage of patients with pathological DGER were significantly higher in the CCE-group as compared to the nCCE-group (76 vs. 55%, p < 0.01). Moreover, the CCE-group revealed ...

The guanidino acid esters (FOY, FOY-305) represent a new class of potent proteinase inhibitors and are thought to have a beneficial effect on the course of acute pancreatitis. Because of their structure and low molecular size they might enter cells and interfere with cellular processes. To test this possibility in the case of the exocrine pancreas a series of in vivo and in vitro studies was carried out to analyse intracellular transport and discharge of pancreatic enzymes in the presence of FOY-305. The infusion of FOY-305 to conscious rats led to a transient inhibition of protein and enzyme discharge from the cannulated pancreas accompanied by lower serum enzyme levels and increased enzyme content in the pancreas. An identical inhibition of discharge of newly synthesized proteins was observed in vitro in the presence of 1 microM FOY-305. The analysis of the release of individual enzymes using separation on two-dimensional gels showed a pronounced inhibition of mainly the release of acidic proteins. FOY-305 not only interfered with discharge of serine proteinases (trypsinogen, chymotrypsinogen, proelastase) but also with procarboxypeptidases and lipase. It was concluded that FOY-305 enters the acinar cell and due to an unspecific binding to acidic proteins interferes with the intracellular transport of individual enzyme proteins during their passage through the membrane-bound cellular compartments. This charge-dependent effect is independent of the inhibitory effect on enzymatic activity of serine proteinases.

Our data confirm that high-dose pantoprazole therapy effectively exerts acid suppression in GERD patients with combined pathological reflux. However, DGER could only normalised in 50 % of patients. High levels of DGER at diagnosis enhance the risk of persistent DGER under PPI therapy and are associated with a reduced clinical outcome.