Mechanism of canine gastric hypersecretion after complete pancreatic ductal obstruction

1963 ◽  
Vol 205 (1) ◽  
pp. 89-93 ◽  
Author(s):  
Michael F. Hein ◽  
William Silen ◽  
Harold A. Harper

The effect of pancreatic enzymes (Viokase) on the gastric hypersecretion induced by pancreatic ductal ligation was studied in seven dogs with Heidenhain pouches. The pancreatic ducts were completely ligated after base-line determinations of the daily output of acid and secretory response of the pouches to histamine and tests of hepatic function. The influence on these tests of the preligation control diet and the following experimental diets was studied after the pancreatic duct ligation in varying sequence for 5–47 days: 1) control diet incubated with Viokase; 2) control diet mixed but not incubated with Viokase; 3) control diet incubated with heat-inactivated Viokase. Complete ligation of the pancreatic ducts was followed by marked gastric hypersecretion while the dogs were fed the control diet. Both the diet incubated with Viokase and the diet mixed with Viokase and then allowed to stand for 1–3 hr before feeding caused significant reduction of such hypersecretion. Evidence of hepatocellular damage was found after pancreatic ductal obstruction when active pancreatic enzymes were not added to the control diet.

1988 ◽  
Vol 254 (6) ◽  
pp. G837-G842 ◽  
Author(s):  
S. Watanabe ◽  
K. Y. Lee ◽  
T. M. Chang ◽  
L. Berger-Ornstein ◽  
W. Y. Chey

In dogs prepared with either pancreatic duct ligation (PDL) or chronic pancreatic fistula (PF), we investigated the effect of pancreatic enzymes on release of cholecystokinin (CCK) in response to corn oil in the upper small intestine. In control dogs without PDL, intraduodenal administration of corn oil (Lipomul containing 15 mmol of triglyceride) resulted in a marked and sharp increase in plasma CCK concentration during the 1st h, which then decreased during the following 1.5 h. In PDL dogs, on the other hand, no immediate increase occurred during the 1st 45 min after which a modest but gradual increase occurred in plasma CCK concentration during the following 2 h. Likewise, plasma CCK concentration increased significantly when Lipomul predigested with pancreatic enzymes or oleic acid was administered to PDL dogs. The increase was comparable to the response to Lipomul alone in control dogs. The infusion of Lipomul resulted in similar responses of plasma CCK in PF dogs as were found in PDL dogs when pancreatic juice was diverted to the exterior from the duodenum. The increases in plasma CCK paralleled the pancreatic protein secretion, and a significant correlation was found between plasma CCK concentration and the protein output. The present observations indicate that release of endogenous CCK by fat from the upper small intestine depends on an adequate digestion of neutral fat by pancreatic enzymes. Thus pancreatic enzymes play an important role on release of CCK in response to a neutral fat.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Andreas Minh Luu ◽  
Alexander Brock ◽  
Sabrina Ritz ◽  
Sandra Junghänel ◽  
Ingo Aldag ◽  
...  

Abstract Background Pancreatic duct ligation in a minipig model leads to exocrine pancreatic insufficiency (EPI). This allows the study of digestive processes and pancreatic enzyme replacement therapies. However, detailed descriptions of the surgical procedure, perioperative management, a determination of exocrine pancreatic insufficiency are scarce in the literature. Data of the long-term health status of minipigs upon EPI induction are still not available. Therefore, the present study describes in detail an experimental approach to the induction of exocrine pancreatic insufficiency via pancreatic duct ligation in minipigs and the long term follow up of the animal’s health state. Methods 14 Goettingen minipigs underwent pancreatic duct ligation via midline laparotomy for the induction of exocrine pancreatic insufficiency. Fecal fat content, fat absorption, chymotrypsin levels, body weight and blood vitamin and glucose levels were determined. Results Exocrine pancreatic insufficiency was successfully induced in 12 Goettingen minipigs. Two minipigs failed to develop exocrine insufficiency most likely due to undetected accessory pancreatic ducts. All animals tolerated the procedure very well and gained weight within 8 weeks after surgery without requiring pancreatic enzyme replacement therapy. The follow up for approx. 180 weeks showed a stable body weight and health state of the animals with normal blood glucose levels (Table 1). From approx. 130 weeks post pancreatic duct ligation, all animals were supplemented with pancreatic enzymes and vitamins resulting in blood concentrations almost within the reference range. Conclusions Pancreatic duct ligation in minipigs is an excellent method of inducing exocrine pancreatic insufficiency. It is important to identify and ligate accessory pancreatic ducts since persistence of accessory ducts will lead to maintenance of exocrine pancreatic function. The EPI model caused no persistent side effects in the animals and has the potential to be used in long-term EPI studies with up to 100 weeks post-OP without supplementation with enzymes and vitamins.


2020 ◽  
Author(s):  
Andreas Minh Luu ◽  
Alexander Brock ◽  
Sabrina Ritz ◽  
Sandra Junghänel ◽  
Ingo Aldag ◽  
...  

Abstract BackgroundPancreatic duct ligation in a minipig model leads to exocrine pancreatic insufficiency (EPI). This allows studies of digestive processes and pancreatic enzyme replacement therapies (PERT). However, detailed descriptions of the surgical procedure, perioperative management, and determination of exocrine pancreatic insufficiency are scarce in literature. To date, data of long-term health status of minipigs after induction of EPI are not available. This study describes in detail the experimental approach of EPI-induction via pancreatic duct ligation in minipigs and long-term results of the animal’s health state.Methods14 Goettingen minipigs underwent pancreatic duct ligation via midline laparotomy for the induction of exocrine pancreatic insufficiency. Fecal fat content, fat absorption, body weight, chymotrypsin levels, blood vitamin levels and glucose levels were determined. Follow-up data was gathered for a period of 180 weeks postoperatively.ResultsExocrine pancreatic insufficiency was successfully induced in 12 Goettingen minipigs. Fecal fat content increased from 9.0% to 30.9% (p < 0.001). Mean coefficient of fat absorption decreased from 90% (± 2.8) to 24.2% (± 8.3). PERT led to a significant increase of fat absorption. Two minipigs failed to develop exocrine insufficiency most likely due to undetected accessory pancreatic ducts. All animals tolerated the procedure very well and gained weight within 6 weeks past surgery. Follow up for 180 weeks showed a stable body weight and health state of the animals with normal blood glucose levels. Vitamin E and B12 levels dropped significantly between post-op week 125 and 134 requiring vitamin supplementation. ConclusionsPancreatic duct ligation in minipigs is an excellent method to induce exocrine pancreatic insufficiency. It is important to identify and ligate accessory pancreatic ducts since persistence of accessory ducts will lead to maintenance of exocrine pancreatic function. The EPI model caused no persistent side effects in the animals and can be applied in long-term EPI studies. However, it is important to substitute Vitamin B12 and E as their concentration drops in the long-term period.


Author(s):  
J. Metz ◽  
M. Merlo ◽  
W. G. Forssmann

Structure and function of intercellular junctions were studied under the electronmicroscope using conventional thin sectioning and freeze-etch replicas. Alterations of tight and gap junctions were analyzed 1. of exocrine pancreatic cells under cell isolation conditions and pancreatic duct ligation and 2. of hepatocytes during extrahepatic cholestasis.During the different steps of cell isolation of exocrine pancreatic cells, gradual changes of tight and gap junctions were observed. Tight junctions, which formed belt-like structures around the apex of control acinar cells in situ, subsequently diminished, became interrupted and were concentrated into macular areas (Fig. 1). Aggregations of membrane associated particles, which looked similar to gap junctions, were intermixed within tight junctional areas (Fig. 1). These structures continously disappeared in the last stages of the isolation procedure. The intercellular junctions were finally separated without destroying the integrity of the cell membrane, which was confirmed with porcion yellow, lanthanum chloride and horse radish peroxidase.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marta Cáceres ◽  
Rita Quesada ◽  
Mar Iglesias ◽  
Francisco X. Real ◽  
Maria Villamonte ◽  
...  

An amendment to this paper has been published and can be accessed via a link at the top of the paper.


1986 ◽  
Vol 237 (2) ◽  
pp. 455-461 ◽  
Author(s):  
G M Cowell ◽  
J Tranum-Jensen ◽  
H Sjöström ◽  
O Norén

Pig sucrase/isomaltase (EC 3.2.1.48/10) was purified from intestinal microvillar vesicles prepared from animals with and without pancreatic-duct ligation to obtain the single-chain pro form and the proteolytically cleaved final form respectively. The purified enzymes were re-incorporated into phosphatidylcholine vesicles and analysed by electron microscopy after negative staining. The two forms of the enzyme were observed as identical series of characteristic projected views that could be unified in a single dimeric model, containing two sucrase and two isomaltase units. This shows a homodimeric functional organization similar to that of other microvillar hydrolases. The bulk of the dimer was separated from the membrane by a maximal gap of 3.5 nm, representing a junctional segment connecting the intramembrane section of the anchor to the catalytically active domain of sucrase/isomaltase. The enzyme complex protrudes from the membrane for a distance of up to 17 nm. From charge-shift immunoelectrophoresic studies of hydrophilic prosucrase/isomaltase and from electron microscopy of reconstituted pro-sucrase/isomaltase, there was no evidence to suggest the presence of anchoring sequences between the sucrase and isomaltase subunits.


1988 ◽  
Vol 118 (2) ◽  
pp. 227-232 ◽  
Author(s):  
L. G. Guijarro ◽  
E. Arilla

ABSTRACT Atrophy of the exocrine pancreas was induced in rabbits by pancreatic duct ligation. Somatostatin concentration and binding in cytosol from rabbit duodenal mucosa were studied after 6 and 14 weeks of pancreatic duct ligation. Somatostatin-like immunoreactivity was significantly increased in the duodenal mucosa in both periods. Scatchard analysis showed a parallel increase in the number of binding sites rather than a change in their affinity. The physiological significance of these findings remains to be clarified. J. Endocr. (1988) 118, 227–232


2003 ◽  
Vol 285 (5) ◽  
pp. G1004-G1013 ◽  
Author(s):  
Zhi Zhong ◽  
Matthias Froh ◽  
Mark Lehnert ◽  
Robert Schoonhoven ◽  
Liu Yang ◽  
...  

Accumulation of hydrophobic bile acids during cholestasis leads to generation of oxygen free radicals in the liver. Accordingly, this study investigated whether polyphenols from green tea Camellia sinenesis, which are potent free radical scavengers, decrease hepatic injury caused by experimental cholestasis. Rats were fed a standard chow or a diet containing 0.1% polyphenolic extracts from C. sinenesis starting 3 days before bile duct ligation. After bile duct ligation, serum alanine transaminase increased to 760 U/l after 1 day in rats fed a control diet. Focal necrosis and bile duct proliferation were also observed after 1–2 days, and fibrosis developed 2–3 wk after bile duct ligation. Additionally, procollagen-α1(I) mRNA increased 30-fold 3 wk after bile duct ligation, accompanied by increased expression of α-smooth muscle actin and transforming growth factor-β and the accumulation of 4-hydroxynenonal, an end product of lipid peroxidation. Polyphenol feeding blocked or blunted all of these bile duct ligation-dependent changes by 45–73%. Together, the results indicate that cholestasis due to bile duct ligation causes liver injury by mechanisms involving oxidative stress. Polyphenols from C. sinenesis scavenge oxygen radicals and prevent activation of stellate cells, thereby minimizing liver fibrosis.


Sign in / Sign up

Export Citation Format

Share Document