[Pancreatic secretion in domestic sprue]. / Pankreassekretion bei einheimischer Sprue.

Pancreatic function was determined (using the secretin-pancreozymin test) before the use of gluten-free diet in 22 patients with endemic (celiac) sprue. Water and bicarbonate secretion were within normal limits, if anything there was a trend to high-normal values. Remarkable and apparently characteristic for celiac sprue was the only slight contraction of the gallbladder after intravenous injection of submaximal doses of cholecystokinin-pancreozymin (CCK). Secretion of the 3 enzymes amylase, lipase and trypsin was decreased in about one third of cases, the difference relating both to the concentrations and the amount secreted, compared with normal control values was significant (P greater than 0.01). But in no case was the reduced enzyme secretion so marked that one would expect maldigestion. Multivariate non-linear discriminance analysis demonstrated that pancreatic secretion in sprue is quite distinct from that in healthy subjects and those with chronic pancreatitis. It is assumed that there is a pattern of exocrine pancreatic secretion typical for sprue.

[The influence of exogenous cyclic nucleotides and theophylline on the hydrokinetic and ecbolic function of the isolated perfused canine pancreas (author's transl)]. / Die Wirkung von exogenen zyklischen Nucleotiden und Theophyllin auf die hydrokinetische und ekbolische Funktion des isoliert perfundierten Hundepankreas.

The influence of exogenous cyclic nucleotides or theophylline either on basal or stimulated volume and protein secretion is studied on the isolated perfused canine pancreas in dependence on varied extracellular calcium concentrations. Bt2cAMP or theophylline do not influence basal secretory rates of pancreatic juice but potentiate secretin-stimulated volume output. They additionally increase basal protein secretion under exclusive secretin stimulation and potentiate dose-dependently CCK- or acetylcholine-induced protein output. The hydrokinetic and ecbolic effects of Bt2cAMP and theophylline persist in a calcium-free medium but fail in normalizing inhibited protein secretion during calcium deprivation. Bt2cGMP neither increases basal nor stimulated volume and protein secretion. The demonstrated influence of Bt2cAMP and theophylline on ductal volume and acinar protein secretion accomplishes two criteria, as suggested by Sutherland, for cAMP as second messenger for secretin and CCK or acetylcholine as well.

[Behavior of cellular cyclic nucleotides after hydrokinetic or ecbolic stimulation of the canine pancreas]. / Das Verhalten zellulärer zyklischer Nucleotide nach hydrokinetischer und ekbolischer Stimulierung des Hundepankreas.

The studies deal with the influence of secretin and various ecbolic secretagogues on tissue levels of cAMP and cGMP in vivo and in the isolated perfused canine pancreas. The mutual behaviour of cellular cAMP and cGMP is observed and compared with the time course of the respective secretory events. Synthetic secretin as well as CCK, acetylcholine or Caerulein likewise elevate tissue cAMP and cGMP simultaneously. There exists no difference in the magnitude of increase and in the time course of changes in tissue cyclic nucleotide levels between hydrokinetic and ecbolic stimulation. The rise in cAMP and cGMP coincides with the onset of the respective secretory events and reaches peak values contemporarily to the excretory maxima. The following decrease in tissue cyclic nucleotides approximatively parallels juice or enzyme secretion in the isolated perfused pancreas but differs widely in vivo. Under this condition cAMP and cGMP rapidly fall to basal levels during undiminished excretory function and show a second rise after cessation of the latter. Secretin and various ecbolic secretagogues do not increase tissue content of cyclic nucleotides in the same dose-dependent manner as can be observed with pancreatic secretion. The behaviour of cAMP and cGMP after addition of secretin and CCK or acetylcholine remains widely unchanged during calcium-free perfusion in spite of an extensive excretory inhibition. The corresponding rise in cellular cAMP and cGMP in the sequence of hydrokinetic as well as of ecbolic stimulation points to an analogous intracellular mediation of various secretagogues in different target cells of the exocrine canine pancreas.

Hydrokinetic activity of secretion and secretin analogues, modified in the N-terminal sequence, and of vasoactive intestinal peptide in the dog pancreas.

In the dog pancreas in vivo, the biological activity of secretin and vasoactive intestinal peptide was compared to that of secretin analogues modified in their N-terminal hexapeptide and to X-secretion (alpha, beta-Asp3-secretin) and Y-secretin (a conversion product of X-secretin consisting of about 15% secretin and 85% beta-Asp3-secretin). Replacement of Asp3 by glutamic acid reduced secretin activity markedly. Replacement by neutral amino acids abolished the activity nearly completely. alpha, beta-Asp3-secretin and beta-Asp3-secretin appeared to be ineffective. The results indicate that the free beta-carboxy group of the side chain of the Asp3 residue of the secretin molecule is of decisive importance for hydrokinetic action.

Calcium secretion in the isolated perfused canine pancreas.

The quantitative relation of calcium and protein secretion was studied on the isolated perfused canine pancreas at different secretory states of hydrokinetic and ecbolic stimulation and various extracellular Ca++-concentrations. 1. Calcium and protein secretion are correlated at both ecbolic and hydrokinetic stimulation as well as by biological or synthetic secretion. 2. Enzyme-associated calcium was estimated at 35 nmol/mg protein and did not vary under differing stimulatory and secretory conditions. 3. During variable concentrations of synthetic secretin basal protein and calcium concentrations in the pancreatic juice show a hyperbolic relationship to the respective rates of fluid secretion. At flow rates beyond 3 ml/5 min the calcium concentrations asymptotically tend to 0.46 mEq/l while protein concentrations nearly decrease to zero. Moreover, the y-intercept of the regressionline correlating the calcium and protein concentrations gives with 0.48 mEq/l Ca++ additional evidence of the existence and magnitude of an enzyme-independent calcium fraction, which seems to remain constant over the whole range of secretory rates. 4. The omission of perfusate calcium does not abolish the calcium-protein correlation either at hydrokinetic or at ecbolic stimulation, but diminishes the enzyme-independent calcium fraction. 5. Enhancing perfusate Ca++-concentrations augments calcium output byt fails in stimulating enzyme secretion. It is concluded that at exclusively hydrokinetic stimulation basal secreted protein with a definite amount of chelated calcium is diluted by variable rates of pancreatic juice containing enzyme independent Ca++ at a constant concentration. During different secretory states of hydrokinetic or ecbolic stimulation the respective proportions of enzyme associated and independent calcium vary, and thus determine changes in the calcium-protein ratios. Extracellular calcium can only influence the non-protein-bound calcium fraction of the pancreatic juice presumably by diffusion from the extracellular fluid through the ductal epithelium rather than by an active secretory mechanism.

[Effect of caerulein on the exocrine pancreas function in man; examinations of dose effects and comparisons with the effect of cholecystokinin/pankreozymin (author's transl)]. / Wirkung von Caerulein auf die exokrine Pankreasfunktion des Menschen; Dosiswirkungsuntersuchungen und Vergleiche mit dem Effekt von Cholecystokinin/Pankreozymin.

The purpose of the study was to examine the secretory response of the exocrine pancreas in man to various doses of the synthesised decapeptide Caerulein (Takus), 5, 10 and 20 ng/kg Caerulein injected intravenously during an infusion of 0,5 CU/kg/h Secretin (GIH) produced a linear increase of enzyme secretion (amylase, lipase, trypsin and chymotrypsin) and also an increase in the water and bicarbonate secretion of the pancreas which is induced by Secretin. The injection of 40 ng/kg Caerulein led to no further increase of the ecbolic function. The intravenous injection of 1 Ivy dog unit (IDU/kg and 20 and 40 ng/kg Caerulein have an identical effect on the exocrine pancreas, there were no statistic differences.

Fecal chymotroypsin: a study on its diagnostic value by comparison with the secretin-cholecystokinin test.

Fecal chymotrypsin (CT) activities were determined in 149 randomly collected fecal specimens of 80 patients in whom the pancreatic function had been tested by a secretin-cholecystokinin test. There was a significant correlation between fecal CT activities and outputs of trypsin (r = 0.3451, p less than 0.01) and amylase (r = 0.3285, p less than 0.01) in duodenal juice. Fecal CT activities were normal in all patients who--based upon enzyme outputs in duodenal juice after stimulation with secretin and CCK/PZ--were classified as 'borderline cases', in most patients with 'low-normal' pancreatic function, and in a significant number of patients with established insufficiency of exocrine pancreas. On the other hand, fecal CT activities were abnormal in patients with severely impaired output of trypsin in duodenal juice, and only 7% of the fecal specimens from patients with established normal function of exocrine pancreas had abnormal low CT activities. It is concluded that the sensitivity of the fecal enzyme method is rather low as compared to the secretin-cholecystokinin test, but that fecal CT determinations give valuable diagnostic information in patients with more pronounced insufficiency of the exocrine pancreas.

[The influence of extracellular calcium on volume, enzyme and calcium secretion in the isolated perfused canine pancreas (author's transl)]. / Der Einfluss des extrazellulären Calciums auf die Saft-, Enzym- und Calciumsekretion des isoliert perfundierten Hundepankreas

1. The kinetics of Ca++ and enzyme secretion are of corresponding pattern as well at hydrokinetic as at ecbolic stimulation. 2. Physiological respectively pathophysiologically relevant changes of perfusate Ca++ concentrations do not influence pancreatic Ca++ secretion. Extracellular Ca++ concentrations beyond 12 mEq/1 initiate an enzyme independent Ca++ secretion. 3. Hydrokinetic or ecbolic stimulated pancreatic secretion do not distinguish in calcium/protein ratio. 4. Basal and stimulated enzyme secretion of isolated perfused canine pancreas remain unaffected by increments of extracellular Ca++ concentrations even at pharmacological values. 5. The stimulated enzyme- and Ca++ secretion remain constant during hypocalcemic perfusate conditions but decrease to basal values in Ca++ free media, rapidly and completely reversible by recalcification of the perfusate. 6. The secretin stimulated volume secretion remains unchanged either by extremely hypercalcemic or Ca++ depleted perfusate conditions.

[Computer-oriented documentation of quantitative and qualitative data in gastroenterology (author's transl)]. / Computergerechte Dokumentation quantitativer und qualitativer Daten in der Gastroenterologie

Computer-oriented documentation of quantitative and qualitative data obtained from patients with gastroenterological diseases is described as an example of a method when considering a relatively small number of patients. All qualitative and quantitative features are entered uncoded in a data booklet and subsequently on port-a-punch cards. After extensive computerized error check - and correction, as need arises, - the data are transferred to a data base and stored on magnetic disk. The ISIS information system, in conjunction with special routines provides access to the data in any combination desired. Analysis of the data, both on an individual and a statistical basis is thus facilitated.

[The effect of natural and synthetic secretin on insulin secretion (author's transl)]. / Die Wirkung von natürlichem und synthetischem Secretin auf die Insulinsekretion.

The effect of natural secretin (G.I.H.) and synthetic secretin (Wünsch) on the secretion of insulin was investigated. Natural as well as synthetic secretin causes a short uniphasic release of insulin without influence on the concentration of glucose in the serum. Since the insulin releasing effect on synthetic secretin was demonstrated, it is clear, that the release of insulin by preparations of natural secretin mentioned in medical literature is not due to contamination by other peptides.

[Pancreatic secretion of patients with chronic renal insufficiency (author's transl)]. / Exokrine Pankreasfunktion bei chronischer Niereninsuffizienz

Pancreatic function tests were performed in 15 patients with advanced renal insufficiency. Pancreatic secretion was stimulated with CCK/PZ and secretin and 60 minutes later with bile given intraduodenally and CCK/PZ and secretin intravenously. The Wilcoxon-test showed that there were significantly higher lipase levels in serum and lower amylase amounts in duodenal juice compared to normal volunteers. No differences could be demonstratd for volume, maximal bicarbonate concentration, lipase and trypsin outputs. It could be shown by nonlinear discriminant analysis that pancreatic secretion might specifically be changed in patients with chronic renal failure. These patients can be definitely differentiated according to the secretion pattern from normal controls and patients with chronic pancreatitis, pancreatic carcinoma, chronic and acute duodenal ulcer.