Aaron S. Fink

Effect of size and density on canine gastric emptying of nondigestible solids

Previous studies suggested that the food-containing canine stomach retains large, nondigestible spheres until all food has emptied; but it is not known whether there is a threshold size or a gradation of sizes that will empty along with food. Further, nothing is known of the effects of such parameters as density, shape, and surface energy on the emptying of nondigestible particles of any given size. To answer these questions 6 dogs with chronic duodenal fistulas were studied. Radiolabeled food and spheres were collected from the fistulas to compare the rate of gastric emptying of the spheres with that of the food. After a standard test meal of 99mTc-labeled liver, steak, and water, diverted chyme was collected over a stack of sieves in 30-min fractions over 5 postcibal hours. The percent of fed spheres and fed 99mTc-labeled liver in each collection was counted, and liquid chyme was returned to the distal duodenum. Spheres with a density of 1 emptied progressively faster as sphere diameters were decreased from 5 to 1 mm; but 0.015-mm spheres emptied at about the same rate as those with diameters of 1 mm. Emptying of the spheres became similar to emptying of the 99mTc-labeled liver at about 1.6 mm. Spheres with densities less than 1 or greater than 1 emptied more slowly than spheres of the same size with a density of 1, whereas paper squares emptied the same way as spheres of comparable size and density. Surface energy did not affect emptying. The findings indicated that both sphere size and density affect their emptying in the presence of food.

A New Syndrome of Symptomatic Cutaneous Mastocytoma Producing Vasoactive Intestinal Polypeptide

An 8-mo-old male child presented with generalized flushing and apnea which followed irritation of a 1.5 x 0.5 cm cutaneous mastocytoma on the left upper arm. Peripheral venous blood samples were drawn before and after manipulation of the tumor, immediately after excision, and again 30 days later. The plasma vasoactive intestinal polypeptide level before excision was high (345 pg/ml) and was accompanied by low acid secretion (15.4 mEq/L) and hypergastrinemia (209 pg/ml), all of which returned to normal after excision of the tumor (50 pg/ml, 35.7 mEq/L, and 131 pg/ml, respectively). Serum histamine levels were undetectable. Histology of the tumor showed only mast cells and no enterochromaffin tissue. The immunoreactive vasoactive intestinal polypeptide content of the tumor was 28 ng/g wet wt and the extracted vasoactive intestinal polypeptide was immunologically indistinguishable from natural porcine vasoactive intestinal polypeptide. The child has remained asymptomatic postoperatively. We conclude that the symptoms associated with this mastocytoma may have been produced by oversecretion of vasoactive intestinal polypeptide and not histamine.

Growth and function of isolated canine pancreatic ductal cells

These studies investigated the growth characteristics and functional properties of isolated canine pancreatic ductal epithelial cells. Cells were isolated from the accessory pancreatic duct and cultured by using three conditions: on vitrogen-coated petri dishes with fibroblast conditioned medium (nonpolarized); in vitrogen-coated Transwells above a fibroblast feeder layer (polarized); or as organotypic rafts above a fibroblast-embedded collagen layer (polarized). Growth characteristics, transepithelial resistances, and carbonic anhydrase and cyclic adenosine monophosphate (AMP) responses were evaluated. Under polarized conditions, the cells grew as monolayers with columnar epithelial characteristics. The monolayers developed high transepithelial resistance and became impervious to the passage of horseradish peroxidase. Epithelial growth factor (EGF) (2 ng/ml) stimulated ductal cell growth and accelerated the formation of a high-resistance monolayer. Forskolin (10 microM) rapidly decreased transepithelial resistance. Carbonic anhydrase activity, which was lower in nonpolarized compared with polarized conditions, was stimulated by carbachol (175 microM). Secretin, however, did not stimulate carbonic anhydrase activity in these cells. Although secretin stimulated adenylyl cyclase activity in early-passage cells, this response was lost in later-passage cells. Both vasoactive intestinal polypeptide (VIP; 1 microM) and forskolin (10 microM) consistently increased adenylyl cyclase activity. Isolated canine pancreatic ductal epithelial cells proliferate in vitro, develop high-resistance epithelial monolayers, and respond to stimuli that activate adenylyl cyclase. These cells should provide a useful model for regulatory studies of ductal cell functions.

Release of Human Pancreatic Polypeptide and Gastrin in Response to Intraduodenal Stimuli: A Case Report

A recent clinical case afforded an opportunity to study the effects of duodenal stimulation on plasma human pancreatic polypeptide and gastrin concentrations, independent of gastric stimulation. A distension stimulus was provided by rapid injection of 100 ml of water and saline via a T-tube into an isolated duodenal afferent limb. In a third experiment, the saline contained 200 pg/ml of heptadecapeptide human gastrin. Within 2 min after each injection, a rapid rise in circulating human pancreatic polypeptide levels appeared that fell promptly towards basal thereafter. Injections of 100 ml of Flexical, a supplemental tube feeding, resulted in a biphasic human pancreatic polypeptide response, the initial peak comparable to that seen following distension with water, saline, or saline containing gastrin, and a second peak of much greater magnitude and duration followed the initial peak. Plasma gastrin concentrations were not influenced following any of the stimuli. Duodenal distension alone may induce an early transient increase in plasma human pancreatic polypeptide concentrations, while intraduodenal nutrients per se may induce a later increment of greater magnitude and duration.

Insulin inhibits secretin-induced pancreatic bicarbonate output via cholinergic mechanisms

Introduction Exogenous insulin inhibits secretin-stimulated pancreatic bicarbonate output via a dose-dependent mechanism; this effect is prevented by pancreatic denervation. Aims To investigate possible cholinergic mediation, we examined the effect of bethanechol on secretin-stimulated pancreatic secretion during euglycemic, hyperinsulinemic clamp. Methodology In four dogs with chronic pancreatic fistulas, euglycemic, hyperinsulinemic clamp (1.25 mU/kg/min) was begun after a 30-minute basal period; computer-assisted glucose administration maintained euglycemia. Control studies were performed with volume-matched and rate-matched vehicle infusion. After 1 hour, secretin infusion was begun at a dosage of 16 ng/kg/h; the dose was doubled every 30 minutes. The studies were then repeated during background bethanechol infusion (90 &mgr;g/kg/h) begun 30 minutes after clamp initiation. Pancreatic juice was analyzed for bicarbonate and protein; serum samples were analyzed for glucose and insulin. Results Exocrine outputs and serum glucose and insulin levels did not differ in the basal period. Insulin levels were significantly elevated during the euglycemic, hyperinsulinemic clamp (62 &mgr;U/mL versus 12 &mgr;U/mL;p < 0.01); glucose levels did not differ. As before, secretin-induced bicarbonate output was inhibited by euglycemic, hyperinsulinemic clamp. The inhibitory effect of insulin was reversed by bethanechol. Despite the euglycemic, hyperinsulinemic clamp, secretin-induced bicarbonate output was potentiated by bethanechol at higher secretin doses (p < 0.05). Conclusion These data confirm that cholinergic mechanisms mediate insulins inhibition of secretin-induced pancreatic bicarbonate output.