ceruletide and Hyperplasia

Ornithine decarboxylase (ODC) is the rate-limiting enzyme in polyamine biosynthesis. We examined circadian variations in pancreatic ODC activity and time-course effects of caerulein in fed and fasted rats. Significant circadian variations in amount of ODC activity were observed. The highest values were obtained during the dark period (1855 +/- 406 pmoles CO2/h), and the lowest during the light period (359 +/- 84 pmoles CO2/h). Caerulein treatment induced hypertrophy and hyperplasia of the pancreas in fed rats; increases in pancreatic ODC activity preceded the rise in protein and DNA contents (447 +/- 44 pmoles CO2/h and 5573 +/- 893 pmoles CO2/h, 6 and 12 h after the first injection of caerulein, respectively). In fasted rats, pancreatic ODC activity was very low (149 +/- 37 pmoles CO2/h) and caerulein treatment induced a transient increase in this activity 12 h after the first injection; hypertrophy but not hyperplasia of the pancreas was observed. In caerulein-treated fasted rats, refeeding during the night following a 48 h fasting period was not enough to increase either ODC activity or DNA content. These findings demonstrate that nutritional status is an important factor in the regulation of ODC activity and, thereby, in caerulein-induced pancreatic growth.

Topics: Animals; Cell Division; Ceruletide; Circadian Rhythm; DNA; Eating; Fasting; Hyperplasia; Hypertrophy; Male; Ornithine Decarboxylase; Pancreas; Rats; Rats, Inbred Strains; Time Factors

The present study was performed to determine the effect of the duration of chronic caerulein administration given at different doses, on the rat pancreas. Four groups of rats, one treated with 0.9% NaCl (control) and the others with caerulein 2, 5 and 10 micrograms/Kg twice a day i.p. were used. After a treatment period of 15, 30 and 60 days, 6 rats from each group were anesthetized, the pancreas was removed, and growth and composition of pancreatic tissue were determined. Small samples were taken for histological examination. Caerulein induced pancreatic hyperplasia and hypertrophy. The dose of caerulein used and the length of the treatment did not significantly modify the trophic effect. Focal perivascular and periductular lymphomonocytic infiltrates associated with cellular abnormalities were seen at 30 and 60 days. The results suggest that 1) the trophic effect of caerulein is not dose-and-time dependent and 2) morphological abnormalities can appear during long term treatment with CCK analogous.

Topics: Amylases; Analysis of Variance; Animals; Cell Nucleus; Ceruletide; Cytoplasm; DNA; Dose-Response Relationship, Drug; Hyperplasia; Injections, Intraperitoneal; Male; Organ Size; Pancreas; Proteins; Rats; Rats, Inbred Strains; Time Factors; Trypsin

The in vivo effects of epidermal growth factor (EGF) on pancreatic growth and digestive enzyme concentrations were compared with the actions of the pancreatic secretagogue caerulein in the adult rat. EGF (10 micrograms/kg BW) did not alter pancreatic weight or protein content. However, this concentration of EGF inhibited [3H]thymidine incorporation into DNA by 44%, decreased DNA content by 20%, and increased the concentrations of amylase, chymotrypsinogen, and protein by 106%, 232%, and 42%, respectively. Pancreatic acini prepared from EGF-treated rats exhibited a characteristic secretory response to caerulein that was superimposable to that obtained in acini from saline-treated rats. In both groups of acini half-maximal and maximal stimulation of amylase release occurred at approximately 5 pM and 50 pM caerulein, respectively. In contrast to EGF, caerulein (1 microgram/kg BW) increased pancreatic weight by 29% and protein content by 59%, and enhanced [3H]thymidine incorporation into DNA by 70%. Although caerulein increased the concentrations of pancreatic amylase and chymotrypsinogen by 38% and 297%, respectively, pancreatic acini prepared from caerulein-treated rats were less sensitive to the actions of caerulein in vitro when compared with acini from control rats. Indeed, the EC50 was shift from 4.8 pM to 9.8 pM after 4 days of treatment. EGF potentiated the actions of caerulein on pancreatic weight, protein content, and chymotrypsinogen concentration, and prevented the caerulein-induced alteration in the secretory responsiveness of the acinar cell. Conversely, caerulein reversed the inhibitory effect of EGF on thymidine incorporation. These findings suggest that EGF may modulate the trophic effects of certain gastrointestinal hormones, and may participate in the regulation of pancreatic exocrine function in vivo.

Topics: Amylases; Animals; Cell Division; Ceruletide; Chymotrypsin; DNA Replication; Epidermal Growth Factor; Hyperplasia; Hypertrophy; Male; Organ Size; Pancreas; Rats; Rats, Inbred Strains; Reference Values

The cerulein-stimulated pancreatic growth response was evaluated in 4- and 11-day-old female suckling CFY rats and compared with the pancreatic response of cerulein-treated 24-day-old weaned rats. Cerulein was given subcutaneously in saline in 1-, 10- and 100-micrograms/kg doses t.i.d. The increase in pancreatic DNA content was regarded as an index for hyperplasia, and the increase in pancreatic weight, protein content and enzyme activity related to milligrams of DNA as an index for hypertrophy. Three-day administration of 1- and 10-micrograms/kg doses of cerulein increased the pancreatic trypsin/DNA ratio, and doses of 100 micrograms/kg cerulein evoked pancreatic hypertrophy and hyperplasia in 4-day-old rats. Ten-day administration of 1- and 10-micrograms/kg doses induced pancreatic hypertrophy and hyperplasia, while the 100-micrograms/kg doses induced pancreatic hypertrophy in 11-day-old rats. In 24-day-old weaned rats, the 3-day administration of 1-microgram/kg doses resulted in hypertrophy of the gland, while the 100-micrograms/kg doses of cerulein evoked pancreatic aplasia and atrophy. It is concluded that the growth-promoting effect of cerulein on the newborn rat pancreas is age- and dose-dependent.

Topics: Amylases; Animals; Animals, Suckling; Ceruletide; DNA; Dose-Response Relationship, Drug; Female; Hyperplasia; Pancreas; Protein Biosynthesis; Rats; Stimulation, Chemical; Trypsin; Weaning

Chronic pancreatic insufficiency (CPI) was induced in male Wistar rats by the injection of a zein-oleic acid-linoleic acid solution into their pancreaticobiliary ducts. Animals injected developed severe pancreatic atrophy with fibrosis and greater than 90% loss of pancreatic enzyme content. The animals also developed malabsorption of fat and bentiromide. Three weeks after the CPI lesion was induced, animals were randomized to receive cerulein 2 micrograms/kg twice daily subcutaneously or saline twice daily subcutaneously for 2 weeks. Cerulein significantly increased pancreatic trypsinogen (p less than 0.03), amylase (p less than 0.01), lipase (p less than 0.02), DNA (p less than 0.02), and RNA (p less than 0.01) content and improved fat and bentiromide malabsorption as compared to saline (p less than 0.05). We conclude that cerulein therapy can cause significant hyperplasia of pancreatic acinar parenchyma in an animal model of CPI and that this therapy can partially reverse malabsorption.

Topics: Animals; Ceruletide; Chronic Disease; Disease Models, Animal; Drug Combinations; Exocrine Pancreatic Insufficiency; Hyperplasia; Linoleic Acid; Linoleic Acids; Male; Oleic Acid; Oleic Acids; Pancreas; Rats; Rats, Inbred Strains; Zein

Pancreatic hypertrophy and hyperplasia following chronic joint (CA + SE), or separate, caerulein (CA: 1 microgram . kg-1) and secretin (SE: 75 micrograms . kg-1) administration were studied in parallel with pancreatic somatostatin (SRIF) contents following 2, 4, 7 and 10 days of treatment. Parameters indicative of pancreatic growth (tissue weight, DNA and protein contents, cellular protein concentrations) increased significantly after 2 days of CA or CA + SE and reached a plateau between days 4 and 10. SE merely induced a mild hypertrophy after 4 days. Endogenous pancreatic SRIF contents varied upon treatment, differently so with each peptide regimen. Indeed, CA and CA + SE treatments decreased total SRIF contents after 2 days with no effect thereafter. SE also decreased the latter after 2 days while significant increases were observed after 7 and 10 days. The inverse relationship seemingly existing between SRIF contents and the amplitude of hormonally-induced pancreatic growth supports the hypothesis that endogenous pancreatic SRIF, operating as an 'antigrowth' factor, may participate in the exogenous CA, SE and CA + SE stimulated pancreatic growth phenomena.

Topics: Animals; Ceruletide; DNA; Drug Interactions; Hyperplasia; Hypertrophy; Male; Organ Size; Pancreas; Rats; Rats, Inbred Strains; Secretin; Somatostatin

Five hundred and two patients with good opacification of the gallbladder were studied by means of ceruletide-assisted cholecystography. A high percentage (15.7; 79 patients) was found to have hyperplastic cholecystoses. So far 26 of these patients have been operated upon because of gallstones or painful symptoms. The x-ray diagnosis was confirmed in all cases. Compared with routine cholecystography, the powerful contraction induced by ceruletide appears to lead to a more frequent recognition of hyperplastic cholecystoses.

Topics: Adolescent; Adult; Aged; Ceruletide; Female; Gallbladder Diseases; Humans; Hyperplasia; Male; Middle Aged; Radiography

Topics: Adolescent; Adult; Ceruletide; Cholangiography; Cholecystography; Female; Gallbladder; Gallbladder Diseases; Humans; Hyperplasia; Male; Middle Aged

Rats were given injections of caerulein, secretin, or a combination of these two peptides subcutaneously 3 times daily for 5, 10, or 15 days. Caerulein produced significant dose- and time-dependent increases in pancreatic weight and content of DNA, RNA, protein, amylase, and trypsinogen. Secretin produced significant increases in pancreatic weight and content of RNA and lipase after 15 days of treatment. After only 5 days of treatment with a combination of secretin plus caerulein, pancreatic weight and content of RNA and protein more than doubled, and trypsinogen content increased more than fivefold. Comparing the averages across the 5-, 10-, and 15-day values, increases in weight, protein, and trypsinogen with the combination of secretin plus caerulein were significantly greater than the sum of the effects of the peptides given singly. Using increase in DNA content as an index of hyperplasia and increases in the ratios of pancreatic weight, RNA content, and protein content to DNA content as indices of hypertrophy, we concluded that caerulein produced both hyperplasia and hypertrophy of rat pancreatic acinar cells. Secretin markedly augmented the hypertrophic action of caerulein but did not alter its hyperplastic action.

Topics: Amylases; Animals; Cell Division; Ceruletide; Dose-Response Relationship, Drug; Drug Therapy, Combination; Hyperplasia; Hypertrophy; Lipase; Male; Pancreas; Rats; Secretin; Trypsinogen