Jack Rudick

Influence of Glucagon on Pancreatic Exocrine Secretion

Effects of small amounts of glucagon on. pancreatic exocrine function were studied in 7 pancreatic fistula dogs in (a) the resting state, (b) during continuous intravenous infusion of secretin, and (c) during infusion of secretin with pancreozymin. Glucagon produced no significant stimulation of secretion in the resting gland but markedly depressed volume flow and enzyme concentrations in the stimulated gland. Inhibition of enzyme output was greater than was inhibition of volume and bicarbonate output.

Effects of prostaglandin E1 on pancreatic exocrine function.

Effects of prostaglandin E1 (PGE1) on pancreatic secretion were evaluated in 5 dogs with chronic duodenal fistulae. PGE1 was administered in single doses (0.5 to 50 μg per kg) or by continuous intravenous infusion (0.5 to 5.0 μg per kg per min) with the pancreas in the resting state or secreting in response to (a) secretin and (b) secretin with pancreozymin. Inhibition of volume and bicarbonate concentration occurred in the resting and stimulated gland: ED50 was 23 μg per kg by single injections and 1.8 μg per kg per min by continuous infusion. In contrast, enzyme output was stimulated, but the efficacy of PGE1 was less than that of pancreozymin. It is concluded that PGE1 has a dual effect on the pancreas—inhibition of volume and electrolytes and stimulation of enzyme elaboration—but it is not clear whether PGE1 plays a physiologic role in the regulation of pancreatic exocrine function.

Observations on the Growth and Metabolic Functions of Cultured Cells Derived from Human Adipose Tissue

Summary The growth and metabolic activity of cultured cells derived from human adipose tissue (CAT cells) were studied and compared to cultured skin fibroblasts. The morphological appearance of the CAT cells was distinctly different from that of fibroblasts. The growth rate of CAT cells as measured by 3H-thymidine incorporation was much slower than the fibroblast growth rate. Cultured CAT cells synthesized significantly more 14C-lipid from 14C-glucose, while fibroblast cultures had a higher metabolic rate as measured by CO2 production. Insulin stimulated 3H-thymidine incorporation in both CAT and fibroblast cultures. The CAT cells did not show a consistent insulin response of lipid or CO2 production, but this may be a reflection of donor age or nutritional status. Even though the CAT cell may be a type of stromal cell peculiar to adipose tissue rather than a preadipocyte or adipocyte, it may prove useful in studies of human obesity.

Mucosal Blood Flow in Canine Antral and Fundic Pouches

Aminopyrine clearance was used to compare mucosal blood flow in the resting and stimulated fundus and antrum. The intraluminal instillation of 0.16 n HCl provided a p H gradient allowing aminopyrine to move into the lumen. Resting mucosal perfusion was 0.64 ± E 0.23 (sd) ml per min per g of mucosa for the fundus and 0.34 ± E 0.10 ml per min per g of wet mucosa for the antrum. Extrapolated mucosal blood flow of the resting fundus by plotting aminopyrine clearance against acid output during secretory stimulation correlated well with mucosal blood flow during acid instillations. Graded doses of histamine by intravenous infusion stimulated mucosal blood flow in the fundus parallel to acid secretion; a maximal dose (2 μg of base per kg per min) increased mucosal perfusion of the fundus 4-fold and doubled antral mucosal perfusion. Isoproterenol (1 μg per kg per min intravenously) increased mucosal blood flow to the resting fundus by 100% and to the antrum by 110%. Vasopressin (4 mU per kg per min intravenously) decreased resting fundic mucosal blood flow by 75% and antral blood flow by 80%. The present study lends further support to the validity of aminopyrine clearance as a measure of mucosal blood flow. It is further shown that: (1) aminopyrine clearance in the fundus and antrum is not dependent on the secretion of hydrogen ions and can be measured by using exogenous acid; (2) no redistribution of mucosal blood flow from antrum to corpus occurs with histamine stimulation; (3) primary alterations in mucosal blood flow can be induced in both pouches by vasoactive drugs without affecting acid secretion.

Dysphagia and lower esophageal sphincter abnormalities after proximal gastric vagotomy

We studied 96 patients subjected to elective proximal gastric vagotomy for intractable duodenal ulceration. Dysphagia was a frequent finding and occurred in 32 percent. It appeared in the immediate postoperative period and usually lasted for 1 to 2 months without any abnormalities in lower esophageal sphincter function. In five patients, dysphagia was severe and, although transient, was associated with changes in lower esophageal function simulating those observed in achalasia. The mechanism of these motor abnormalities is probably due to a reversible neuromuscular dysfunction of the lower esophageal sphincter.

Acid absorption in the canine duodenum.

Alterations in composition of isosmotic acid solutions were studied in exteriorized segments of the proximal (Brunners gland area) and distal canine duodenum, mounted in lucite chambers. Varying concentrations of HCl (40, 80, 120, 160 mEq/l) made isotonic by the addition of NaCl were instilled into the chamber, removed in 15 minutes and analyzed for volume, electrolytes, protein content and osmolality. Both proximal and distal duodenal mucosa modified the instilled solution with a loss of H+ and a gain in Na+ and K+, which occurred at similar rates independent of the acid concentration of the instilled solution. The rate of ionic movement was twice that for the antrum, and 30-100 times that of the fundus. Calculated H+ loss across the entire duodenal mucosa at these rates could account for 17.5% of the peak acid output from the canine stomach. The loss of H+ could not be accounted for on the basis of neutralization and probably represented transmucosal insorption. In addition to the neutralization of gastric acid by pancreatic juice and bile, duodenal mucosa thus plays an important role in the maintenance of intraluminal pH. Duodenal mucosal permeability to H+ may be related to the vulnerability of the duodenal mucosa to acid-peptic ulceration.

Effects of Some Inhibitors of Sodium Transport (Adenosine Triphosphatase Inhibitors) on Pancreatic Secretion

Pancreatic electrolyte secretion has usually been considered to involve the active transport of HCO 3 - and the passive diffusion of Na + and K + . Since a (Na + , K + ) adenosine triphosphatase has been identified in the canine pancreas, we studied the effect of some adenosine triphosphatase inhibitors to determine whether the transport of Na + might be an active process. Three adenosine triphosphatase inhibitors, ouabain (0.04 mg per kg), furosemide (1 and 5 mg per kg), and ethacrynic acid (1 and 4 mg per kg), were studied in 5 secretin-stimulated pancreatic fistual dogs. All produced a significant decrease in volume flow, HCO 3 − concentration, Na + and K + output, and an increase of enzyme output. The effect began in 10 min. rose to a peak in 60 min, and was over 1 hr later. At the doses used, ouabain had the most profound effect. The data suggest that the pancreatic secretion of electrolytes may be in part dependent on an (Na + , K + ) adenosine triphosphatase system acting on a sodium pump.

Effect of Emulsions of Medium and Long Chain Triglyceride on Human Adipose Tissue Prostaglandin Production in Vitro

Preliminary in vitro studies have been performed to assess the effect of experimental lipid emulsions of varying fatty acid composition on human adipose tissue metabolism. Subcutaneous human adipose tissue was obtained during elective surgery and placed in tissue culture. Physical mixtures of long chain triglyceride (LCT) and/or medium chain triglyceride (MCT) were added to the tissue culture medium so that the final concentration was 400 mg/dl. After a 3-day incubation period the tissue was harvested, placed in buffer and used to determine in vitro production of the prostaglandins prostacyclin I2 (measured as its stable endproduct 6-keto PGF1 alpha), thromboxane A2 (measured as TXB2), and prostaglandin E2. Measurements of the fatty acid profile found in the neutral- and phospholipid fraction of the adipose tissue and fat cell size were also made. The results demonstrate that samples incubated in 100% MCT had the most significant increase in prostaglandin production whereas those incubated in 100% LCT had the most significant decrease in activity of the three prostaglandins assayed, when compared to controls. The addition of LCT to MCT caused a dose-related decrease in adipose tissue prostaglandin production. There were no significant changes in the profile of fatty acids found in the neutral- or phospholipid fraction of adipose tissue. The results indicate that the relative level of MCT/LCT incubated with human adipose tissue has a significant effect on prostaglandin production.

Pancreatic Exocrine Secretion During and After Pregnancy

Pancreatitis occurring in late pregnancy and in the puerperium has been documented as an entity unrelated to cholelithiasis or hyperlipidemia. Canine pancreatic exocrine function has been studied during pregnancy and the puerperium. Pancreatic secretion was evaluated in eight pregnant female mongrel dogs prepared with Thomas duodenal and gastric fistulae, during pregnancy (corresponding to the third trimester in humans), during the puerperium, and several months after whelping. Basal secretion (volume and HCO3) was increased during pregnancy and the puerperium. The response to exogenous secretin (submaximal and maximal) was unchanged during pregnancy but decreased in the puerperium. Resting enzyme output was increased during pregnancy and the puerperium; the responses to cholecystokinin-pancreozymin during pregnancy were even more profoundly increased. Although the mechanism is speculative, these alterations in pancreatic function might contribute to the development of pancreatitis in pregnancy and the puerperium.

Effects of commercial pancreozymin preparation (Cecekin) and gastrin pentapeptide upon acid and pepsin secretion in gastric fistula dogs

Abstract This study compared the stimulatory effects of pancreozymin-cholecystokinin (Cecekin) and gastrin pentapeptide upon gastric secretion and confirmed that small doses of pancreozymin stimulated both acid and pepsin secretion from gastric fistula dogs. Acid output with pancreozymin was about one-third of that in response to pentapeptide, but this difference was narrowed by the addition of a small dose of methacholine. Pepsin secretion was equally stimulated by both drugs. The differences between the effects of the two drugs may be due to an antral inhibitory mechanism; contaminants of the commercial pancreozymin preparation were probably insufficient to account for these differences.