Inhibitory effect of calcitonin on pure human pancreatic secretion.

The inhibitory effect of calcitonin on human pancreatic secretion was evaluated to examine whether the different results reported earlier between humans, cats and dogs can be ascribed to the different sensitivity of these species to calcitonin, as suggested by some investigators. Pancreatic juice was obtained by endoscopic cannulation of the pancreatic duct from 11 patients with relapsing pancreatitis during intravenous infusion of secretin (1 U/kg/h) plus caerulein (0.04 microgram/kg/h). After steady secretion was attained 20 min after the beginning of collection, five 2-min fractions were obtained before, and ten 2-min fractions were obtained after intravenous infusion of calcitonin (1 IU/kg/h). The pre- and post-calcitonin fractions from each patient were compared by Student's t-test. Calcitonin inhibited the secretory volume (26.8 to 65.6%) and bicarbonate secretion (21.4 to 62.0%) in 8 patients, and amylase (48.4 to 89.5%) and lipase secretion (47.4 to 90.5%) in all patients. The present studies reconfirmed that prominent inhibition of enzyme secretion occurs in humans. A new finding was that significant inhibition of the secretory volume and bicarbonate secretion occurs in humans. The inhibitory effects of calcitonin in humans did not appear to differ from those in cats and dogs, when evaluated similarly with the use of pure pancreatic juice.

Studies on the effect of glucagon on human pancreatic secretion by analysis of endoscopically obtained pure pancreatic juice.

The effect of glucagon on human exocrine pancreatic secretion was evaluated in ten patients by analysis of pure pancreatic juice. Pancreatic juice was obtained by endoscopic cannulation of the pancreatic duct at 2-min intervals during constant intravenous infusion of secretin (1 U per kg of body weight per hr) plus caerulein (0.04 micrograms per kg of body weight per hr). Since steady secretion was established 20 minutes after the start of juice collection, a further five 2-min fractions were collected as controls, then constant intravenous infusion of glucagon (15 micrograms per kg of body weight per hr) was commenced. Pancreatic juice was collected for a further 20 minutes. The control fractions and post-glucagon fractions were compared in each patient using Student's test. Glucagon depressed secretin-caerulein-stimulated pancreatic secretions. More uniform reductions were observed in the concentration and output of protein and enzymes. Individual variations were observed in the secretory volume and bicarbonate concentration and output. Amylase and lipase were depressed in a parallel fashion in seven patients and in the remaining three, amylase was more depressed than lipase. The post-glucagon reduction in pancreatic secretion was not proportional to the rise in plasma glucagon and blood glucose.

Histochemical studies on protein plugs obtained by endoscopic retrograde catheterization of the papilla.

In order to elucidate mechanisms of protein plug formation, histochemical studies were performed on aggregates and protein plugs present in pancreatic juice. Pancreatic juice was obtained from three control subjects and five patients with chronic pancreatitis through endoscopic retrograde catheterization of the papilla. Specimens for staining were prepared in two ways: (1) fixed with 10 per cent formaldehyde, embedded in paraffin and sectioned, and (2) placed on slide glass and fixed with isopropylalcohol. Staining included hematoxylin-eosin, periodic-acid Schiff, von Kossa, alcian blue, toluidine blue and double staining with PAS and AB. The process of protein plug formation can be as follows: (1) a prerequisite for aggregate formation, consisting of clusters of desquamated epithelial cells, highly concentrated sulfated acidic mucopolysaccharide and neutral mucopolysaccharide, (2) formation of aggregates in which epithelial cells and amorphous substance are interlaced with developing fine reticular substance, (3) enlargement of aggregates by fusion with adjacent aggregates through bridging action of the reticular substance sprouting, like prickles, from their surface, and (4) "maturity" of aggregates, taking a three-dimensional form which result in a spherical, spheroidal or cylindrical protein plug.

Comparative studies on viscosity and concentration of protein and hexosamine in pure pancreatic juice.

In order to investigate the cause of an increase in viscosity of pancreatic juice in patients with chronic pancreatitis, we performed comparative studies on voscosity and concentration of protein, hexosamine, three hydrolytic enzymes (amylase, chymotrypsinogen and lipase), calcium and gamma-Glutamyltranspeptidase in pure pancreatic juice. Pure pancreatic juice (PPJ) was obtained from seven control subjects, 10 patients with probable chronic pancreatitis and six patients with definite chronic pancreatitis by means of endoscopic retrograde catheterization of the papilla. Specimens were collected in ice-cooled tubes during the initial four-minute period and thereafter at two-minute intervals for 20 minutes after a rapid intravenous injection of secretin (Eisai Secrepan, 1 U/kg of body weight) and then at one-minute intervals for 10 minutes after a rapid intravenous injection of pancreozymin (Boots, 1 U/kg of body weight). It was demonstrated that the viscosity of PPJ was closely related to the concentration of hydrolytic enzyme protein, hexosamine and the presence of mucous substance and protein plugs.

The calcium concentration in human pure pancreatic juice in chronic pancreatitis.

Calcium concentration in human pure pancreatic juice was determined during wash-out period, secretin stimulation and pancreozymin stimulation. Specimens were collected by endoscopic retrograde catheterization of the papilla at one minute intervals for 20 minutes after intravenous injection of secretin (Eisai, 1 U/kg) and for 10 minutes after pancreozymin injection (Boots, 1 U/kg). The determination was also made in duodenal juice obtained during the ordinary pancreozymin-secretin test. Calcium concentration in duodenal juice was significantly raised in patients with chronic pancreatitis (suspected, definite or calcifying), confirming the results of previous investigators. Calcium concentration and calcium per mg of protein in human pure pancreatic juice were significantly raised in patients with chronic pancreatitis (suspected, definite or calcifying). Calcium per mg of protein in normal human pure pancreatic juice was quite similar to that reported in zymogen granules of the guinea-pig pancreas. Calcium output in human pure pancreatic juice was also significantly raised in patients with suspected chronic pancreatitis; it was within normal limits in patients with definite or calcifying chronic pancreatitis due to decreased volume output. Significance of these findings were discussed in relation to pathogenesis and early detection of chronic pancreatitis.

The hexosamine concentration and output in human pure pancreatic juice in chronic pancreatitis.

Hexosamine concentration in human pure pancreatic juice was determined during wash-out phase and secretin stimulation phase. Specimens were collected by endoscopic retrograde catheterization of the papilla at one minute intervals for 20 minutes after intravenous injection of secretin (Eisai, 1 U/kg) and for 10 minutes after pancreozymin injection (Boots, 1 U/kg). In suspected and established chronic pancreatitis (calcifying or non-calcifying), hexosamine concentration was significantly raised during both wash-out phase and secretin phase. Hexosamine output was significantly raised in suspected chronic pancreatitis and non-calcifying chronic pancreatitis during both wash-out phase and secretin phase; in calcifying chronic pancreatitis, no significant increase in hexosamine output was noted during both phases because of decreased secretory volume. Significance of these findings was discussed in relation to the pathogenesis of chronic pancreatitis.