摘要:

We reported previously that dietary proteins stimulate pancreatic secretion by a mechanism not involved in masking trypsin activity in rats that have bile-pancreatic juice (BPJ) diverted from the proximal small intestine for 7 days. However, BPJ in the distal small intestine is possibly responsible for the stimulation of pancreatic secretion in chronic BPJ- diverted rats. To examine whether the BPJ-dependent mechanism operates in the distal small intestine of chronic BPJ- diverted rats, we investigated pancreatic responses after inhibition or removal of pancreatic trypsin activity in the distal small intestine of conscious rats. Duodenal instillation of soybean trypsin inhibitor (SBTI), which is a proteinaceous trypsin inhibitor, stimulated pancreatic secretion in the chronic BPJ-diverted rats, whereas a nonpeptidic trypsin inhibitor, FOY 305, did not. Heal administration of both trypsin inhibitors did not enhance pancreatic secretion in the diverted rats. Exclusion of luminal BPJ from the distal small intestine was also ineffective in causing pancreatic exocrine secretion in the chronic BPJ-diverted rats. These observations reveal that ileal BPJ does not contribute to the stimulation of pancreatic secretion in rats that have BPJ chronically diverted into the ileum, as in intact rats, and that a duodenal instillation of SBTI stimulates pancreatic secretion as a protein, and not as a trypsin inhibitor.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Bacterial infectious complications are the most common cause of morbidity and mortality associated with acute pancreatitis. Most pathogens are common gastrointestinal flora, indicating that the gut is the source of pancreatitis-related infections. However, the route whereby the microorganisms reach distant organs remains speculative. We tested the hypothesis that spread of bacteria occurs via a transperitoneal pathway. Acute interstitial pancreatitis (AIP) was induced in antibiotic (gentamicin, bacithracin, neomycin)-decontaminated rats by intravenous infusion of cerulein. Effects of pancreatic necrosis (PN) were studied in rats that received additional injections into the peritoneal cavity of pancreatic tissue obtained from donor rats. The rats were inoculated withEscherichia coli(O2:KN:H18) resistant to the antibiotics used for decontamination either orally (1012microorganisms; experiment I) or intraperitoneally (108microorganisms; experiment II). Moreover, the rat peritoneal cavity wash was inoculated with 108E. coli in vitro (experiment. III). In rats with AIP and PN, recovery of the bacteria from liver, spleen, pancreas, lung, and blood following oral inoculation demonstrated that acute pancreatitis promotes bacterial translocation from the gut. The absence ofE. coliin these organs following intraperitoneal inoculation showed that the bacteria do not spread from the peritoneal cavity. Rats with PN clearedE. colifrom the peritoneal cavity in a shorter period than rats with AIP and controls (5 vs. 7 and 8 days;p< 0.05). The multiplication rate ofE. coliin peritoneal cavity wash was lower in rats with PN than in rats with AIP and controls(p< 0.01). We conclude that (1) translocation ofE. colifrom the gut during cerulein-induced acute pancreatitis occurs via nonperitoneal pathways, (2) the peritoneal cavity acts as a trap for the bacteria rather than a source of bacterial seeding, and (3) PN impairs survival ofE. coliin the peritonealcavityvia inhibition of the bacterial multiplication in this model.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The capacity for intercellular communication (IC) via gap junctions is found in normal pancreatic acinar cells. The major role of IC is considered to be the maintenance of tissue homeostasis and the regulation of signal transmissions. Up to now, the participation of IC via gap junctions in acute pancreatitis has not been reported. We investigated the role of IC in cerulein (Cn)-induced acute pancreatitis in rats using irsogladine, an enhancer of IC via gap junction. Acute edematous pancreatitis was induced in rats by two intraperitoneal injections of 40 μg/kg Cn. Rats received various doses (25, 50, or 100 mg/kg body weight) of irsogladine orally, 15 and 2 h before the first Cn injection. The normal control group received only vehicle. The severity of pancreatitis was evaluated enzymatically and histologically 5 h after the first Cn injection. In Cn-induced acute pancreatitis, irsogladine significantly lowered the serum amylase level, the pancreatic wet weight, and the pancreatic amylase and DNA contents, in a dose-dependent manner. Particularly, the amylase content improved to the level of the normal controls. Histologically, the severity of pancreatitis was reduced significantly by treatment with irsogladine and no discernible vacuolization was seen in the group with 100 mg/kg irsogladine treatment. By immunofluorostaining pancreata with anti-connexin 32 (Cx32; a gap junction protein) antibody, we found that pancreatic acini were diffusely positive for Cx32 in the control group, but the number of Cx32-positive grains decreased markedly, to 19%, in the pancreatitis group. With 100 mg/kg irsogladine treatment, the number of Cx32 grains recovered to 70% of the normal control value. These findings indicate that IC via gap junction is disturbed in Cn-induced pancreatitis, which may result in the breakdown of tissue homeostasis and the progression of acute pancreatitis.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The behavior of neutrophils in a rat acute pancreatitis model was observed in the pancreas and liver using fluorescence microscopy with an image analyzing system after labeling with a specific fluorescent reagent. Nonviable cells of both organs were also labeled and quantified. The role of nitric oxide in neutrophil accumulation and organ damage was estimated by administering a relatively selective inhibitor of constitutive nitric oxide synthase,N-nitro-L-arginine (L-NNA). The animal model of acute pancreatitis was induced by cerulein injection (80 mg/kg). Two groups were created, one given and the other not given L-NNA (2.5 mg/kg) prior to the induction of pancreatitis. The number of accumulated neutrophils in the pancreas and liver increased in a time-dependent manner. There was a close relation between the distribution of the neutrophils and inviable acinar cells or hepatocytes. When pretreated with L-NNA, the numbers of accumulated neutrophils and nonviable cells increased significantly in the pancreas. In the liver, a more pronounced accumulation of neutrophils was observed after treatment with L-NNA. Although hepatocyte injury was mild despite the neutrophil accumulation in the control, such injury was marked in the group treated with L-NNA. This suggests that neutrophils serve an important role in exacerbating acute pancreatitis and that nitric oxide provides a defense mechanism against neutrophil accumulation in pancreas and liver.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The effects of a synthetic putative luminal cholecystokinin (CCK) releasing factor (LCRF) fragment (1–35) on pancreatic exocrine secretion were examined in conscious Wistar rats and a mutant strain of rats lacking the CCK-A receptor. Intraduodenal injection of graded doses of the LCRF fragment induced biphasic responses in Wistar rats. The injection of 0.1 μg of the LCRF fragment produced a maximal response, while 1 μg produced a lower response. No significant effect was observed in rats lacking the CCK-A receptor. The synthetic LCRF fragment stimulated pancreatic secretion via CCK-A receptors in conscious rats.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

To determine the effect of long-term blockade of cholecystokinin (CCK) on both pancreatic storage and secretion processes, L 364,718 (a CCK receptor antagonist) was administered to rats at 0.1 mg/kg/day for 3, 7, and 15 days. Zymogen granules were analyzed by flow cytometry to determine their light scattering properties—forward scatter and side scatter—as well as their amylase content measured by a specific antiserum. The mean number of zymogen granules per cell was counted on pancreatic sections using electron microscopy. DNA content, pancreatic weight, and enzyme secretion were also studied under both basal conditions and CCK infusion at a dose of 1.25 μg/kg/h, which is able to displace the CCK receptor antagonist. Two subpopulations of zymogen granules (Z1and Z2) were identified on the basis of their light scattering parameters, in both control and L 364,718-treated rats. L 364,718 administered for 3, 7, and 15 days induced a significant reduction in the amylase content of individual zymogen granules, for both Z1and Z2zymogen granule subsets. In contrast, the number of zymogen granules per cell increased from day +3 of treatment onward, the highest values being detected at day +7. Hyperplasia was observed only at day +15. Basal enzyme secretion decreased significantly in rats treated with L 364,718 for 3 and 7 days but recovered to control values after 15 days of treatment. No significant differences in CCK- stimulated amylase secretion were observed between control and L 364,718-treated rats. At day +15 of L 364,718 treatment a significant increase in enzyme secretion was observed with respect to shorter treatment periods; this was associated with a significant increase in both the number of cells and the number of zymogen granules per cell. Our results indicate that chronic administration of L 364,718 induces a biphasic effect on pancreatic function. Interestingly, although enzyme secretion reached recovery after long-term treatment (15 days), the storage process is altered since the mean enzyme content in each individual zymogen granule remains significantly reduced.

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0885-3177    

出版商:OVID    

年代:1997

数据来源: OVID