摘要:

Little is known about the influence of cutting the extrinsic pancreatic nerves on the morphology and function of the intrapancreatic nerves in dogs. For this reason, intrapancreatic nerves of mongrel dogs were studied, using electron microscopy and immunohistochemistry, after truncal vagotomy, after celiac and superior mesenteric ganglionectomy, and after a combination of both operations, i.e., removing all extrinsic nerves of the pancreas. Dogs with intact extrinsic and intrinsic pancreatic nerves served as controls. Studies were performed 1–2 weeks and up to 5 months after one or both denervation procedures. For immunohistochemical and electron microscopic studies the animals were perfused with glutaraldehyde-formaldehyde-picric acid solution and the tissue was embedded in Epon or paraffin. Both immunohistochemical and electron microscopic studies revealed that signs of degenerating intrapancreatic nerves occurred only in the early phase (up to 30 days) after operation. After 60 days, hypertrophy of pancreatic nerve fibers was observed. The most striking finding was that the integrity of the intrapancreatic ganglia and nerves was almost preserved after complete extrinsic denervation. In controls there was a strong intrapancreatic innervation with vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI), substance P (SP), and neuropeptide Y (NPY) nerves. SP and NPY-nerves significantly decreased after the different denervation procedures, but the other peptidergic nerves were not altered by truncal vagotomy, ganglionectomy, or the combination of both procedures. We conclude that the dog pancreas contains extensive intrinsic peptidergic nerves, which, with the exception of SP and NPY-nerves, are greatly independent of the integrity of the extrinsic nerves.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Pancreatic polypeptide (PP) and peptide YY (PYY) are inhibitors of pancreatic exocrine secretion in vivo but not in vitro, which suggests intermediate mechanisms of action. To examine the role of pancreatic blood flow in these inhibitory effects, xenon-133 gas clearance was used to measure pancreatic blood flow while simultaneously measuring pancreatic exocrine secretion. PP or PYY (400 pmol/kg/h) was administered during the intermediate hour of a 3-h secretin (125 ng/kg/h)/cholecystokinin octapeptide (CCK-8) (50 ng/kg/h) infusion. Exocrine secretion and pancreatic blood flow during the PP or PYY hours were compared with that observed in the first and third hours of the secretin/CCK-8 infusion. PP and PYY significantly inhibited secretin/ CCK-8-induced pancreatic exocrine secretion. In addition, PYY (but not PP) significantly reduced pancreatic blood flow during secretin/CCK-8 stimulation. Nevertheless, there was no correlation between pancreatic blood flow and bicarbonate or protein outputs. It is concluded that changes in pancreatic blood flow do not mediate the inhibitory effects of PP or PYY on the exocrine pancreas.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Five cases of localized ectasiae of pancreatic ducts associated with epithelial mucinous metaplasia have been previously reported by Itai et al. (Radiology1986;161:697–700). During a 1-year period, we collected four new observations of patients presenting with recurrent attacks of pancreatic pain due to similar clusters of cystlike dilated ducts communicating with the main pancreatic duct and lined by a columnar epithelium interspersed with numerous goblet cells. Duct lumina were filled with mucous. Carcinoembryonic antigen levels were high in the pure pancreatic juice, but normal in the blood. Sonography and CT scan showed cystlike, intrapancreatic defects localized three times in the head of the pancreas and once in the body. Endoscopic retrograde cholangiopancreatography (ERCP) showed a huge dilation of some collateral ducts filled by radiolucent defects. The main pancreatic duct was dilated proximally to pathological ducts in three cases. Neither pancreatic stones nor exocrine insufficiency could be demonstrated 7 years after the clinical onset; one case presented with an in situ carcinoma. Since mucinous ductal ectasia is a precancerous state, surgery is mandatory. ERCP is probably the best method of diagnosis.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We studied the effect of a synthetic octapeptide somatostatin analog, SMS 201–995 (sandostatin), on pancreatic exocrine secretion and on plasma secretin and cholecystokinin (CCK) levels in vivo in anesthetized rats. The exocrine pancreas was stimulated by either intravenous infusion of both secretin (0.06 CU/kg/h) and cholecystokinin octapeptide (CCK-8) (0.03 u-g/kg/h) or intraduodenal infusion of oleic acid (pH 6.5) in a dose of 0.25 mmol/h. Intravenous administration of SMS 201–995 in three different doses of 100, 200, and 400 ng/kg/h resulted in dose-related inhibition of pancreatic secretion in terms of volume, bicarbonate, and amylase stimulated by exogenous secretin and CCK. Intraduodenal oleic acid stimulated pancreatic secretion, including volume, bicarbonate, and amylase, and this was accompanied by a significant elevation in the plasma concentrations of secretin and CCK. Intravenous administration of SMS 201–995 in the three different doses described above caused dose-dependent suppression of the increase in pancreatic exocrine secretion as well as the plasma concentration of secretin and CCK induced by intraduodenal infusion of oleic acid. It is concluded that SMS 201–995 inhibits pancreatic exocrine secretion and the release of endogenous hormones, such as secretin and CCK, in rats.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Human pancreatic elastase 1 (El) is a novel pancreas-specific proteinase that has not yet been investigated after pancreatic transplantation (PTx). Using a recently developed El ELISA, we studied the El serum curves in 36 type I diabetic patients subjected to PTx with enteric exocrine diversion from the pretransplant value up to 8 years after transplantation (w = 731 samples). A characteristical pattern was observed: following PTx, El rose above the normal range to a peak within 6 days and then gradually fell to stabilize after 4–6 weeks at an elevated level (10 ng/ml) for approximately 1 year. Two to 8 years after PTx, El levels were still slightly elevated (1–6 ng/ml) in 14/20 patients. During 24 acute rejection episodes, El was found not to be a sensitive rejection marker during the early postoperative period because of its slow decline from the peak level. However, increasing El levels in seven patients more than 2 months after PTx were associated with a variety of lesions to the pancreatic graft, thus suggesting a useful marker indicating exocrine graft damage late after PTx. The slightly elevated levels even years after PTx are most probably due to the non-portal venous drainage of the pancreatic graft.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Fetoacinar pancreatic (FAP) protein is a specific component of the human exocrine pancreas that may have a role in the differentiation and transformation of this organ. In order to set out a model for studies on the regulation of FAP, 47 established cell lines from human cancer of different origins were tested for FAP expression using the monoclonal antibody J28 (Mab J28). Only two, both pancreatic, were positive. This finding supports the already reported pancreatic specificity of this antigen. Strongest expression was shown by the BxPC-3 cell line, derived from a moderately well-differentiated adenocarcinoma in the body of the pancreas. In BxPC-3 cells grown in Roswell Park Memorial Institute (RPMI) 1640–10% fetal bovine serum (FBS), Mab J28 immunostaining was localized in the cytoplasm of the cells. In serum-free medium, cells quickly died. Growth and FAP expression were maintained when this medium was supplemented with insulin. FAP is not released to the culture medium, as evidenced by absence of reaction with the monoclonal antibody on nitrocellulose dot-blots. On the contrary, a positive reaction was observed in cell homogenates made by sonication or by extraction with 0.1% Triton. A competitive enzyme-linked immunosorbent assay (ELISA), using biotinylated FAP, was developed to quantify the protein in cell homogenates. Concentrations of FAP in homogenates from cells cultured in standard conditions or serum-free supplemented with insulin were in the range of 0.28–0.40 μg FAP/ mg total protein. The electrophoretic pattern of FAP from cultured cells was similar to that of the protein present in fetal pancreas, amniotic fluids, or pathological pancreatic juices, consisting of a main 110 kDa protein and lower Mr glycosilation variants.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Chronic treatment with bovine pancreatic polypeptide (bPP) is reported to decrease body weight and reduce fasting glucose and insulin concentrations in congenitally obese mice. The present study examines the effects of acute and chronic bPP treatment on insulin release and glucose clearance in lean and obese rodents. After single injections of 0, 5, 50, or 500 μg of bPP/kg of body weight, the insulin response to an intragastric glucose meal (5 g/kg of body weight) was substantially inhibited by the two higher doses of bPP. The change in glucose concentration over time was similar among all animals except those receiving the highest dose of bPP (500 μg/kg of body weight); in this group, glucose rose to higher levels and was slower to return to basal levels. Chronic treatment of rats with 200 μg of bPP/day/kg of body weight for 5 days did not modify glucose or insulin responses to the glucose meal, but did increase the activity of hepatic glycogen synthase. In contrast, basal glucose levels were lower in obese mice (ob/ob) treated with bPP and glucose clearance was improved in the treated group after injection of exogenous insulin. Islet hormone concentrations in pancreatic extracts were compared in lean and obese mice treated with and without 200 u-g of bPP/day/kg of body weight for 5 days. The pancreases of obese mice had higher concentrations of insulin and PP, and treatment with exogenous bPP increased endogenous PP in the pancreases of both phenotypes. Treatment with exogenous bPP also increased the insulin content of obese pancreases, but was without effect in pancreases of lean mice. Somatostatin content did not differ between lean and obese mice, and treatment with bPP produced no change in pancreatic somatostatin in either phenotype. The present results suggest that acute administration of PP inhibits insulin release. Chronic PP treatment of congenitally obese rodents but not lean animals produces a selective beneficial effect on basal glucose levels and improves peripheral sensitivity to insulin.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Neonatal rats treated with streptozotocin on day 5 after birth (n5-STZ model) exhibited, when fully grown, a frank basal hyperglycemia (17.4 ± 0.7 vs. 6.6 ± 0.2 mmol/L in nondiabetic rats), a specific failure of glucose-induced insulin release, and hyperresponse to arginine. To investigate whether or not chronic correction of the hyperglycemia can improve the defects on insulin secretion, we tested diverse maneuvers, all of which aimed to lower chronically the hyperglycemia. Insulin secretion was studied with the isolated perfused pancreas preparation. A 16-day subcutaneous insulin therapy (=10 U/kg/day) unevenly correcting the plasma glucose levels (10.8 ± 1.6 mmol/L) did not improve the lack of insulin response to glucose while the arginine-induced insulin release returned to values close to normal. A 28-day intraperitoneal phlorizin infusion (50 mg/kg/day) or a 20-day oral vanadate administration (40 mg/kg/day) caused near normalization of the basal plasma glucose level in the treated n5-STZ rats (7.8 ± 0.5 and 8.2 ± 0.5 mmol/L, respectively). Nevertheless, these treatments did not correct the insulin secretion in response to glucose nor the hyperresponsiveness to arginine. Furthermore, we investigated whether or not glucopenia in vitro could restore the glucose-induced insulin release in this diabetic model. After a 50 min glucose-free period, the insulin response to a subsequent glucose stimulation still did not materialize. These observations suggest that in the present n5-STZ diabetic model, (a) hyperresponsiveness to arginine cannot be solely regarded as a residual effect of hyperglycemia; (b) the return to normal values of insulin release in response to arginine after insulin therapy, despite a still prevailing mild hyperglycemia, suggests that exogenous insulin per se may regulate to some extent the diabetic B cells; and (c) near normalization of the basal glucose levels is not a sufficient condition to obtain improvement of the B-cell response to glucose, such a finding being consistent with the concept that stringent normalization of glycemia is a prerequisite.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

A noncompetitive enzyme-linked immunosorbent assay (ELISA) has been developed for the quantitative determination of porcine pancreatic colipase. Calibration curves were established by coating polystyrene immuno-plates with pure procolipase or its trypsin-activated derivative. Bound antigen was detected with antiporcine procolipase polyclonal antibodies. Under optimizing conditions, the minimal detectable amount of porcine colipase was 0.1 ng, which is about 1,000 times less than the minimal amount that can be assayed titrimetrically. The useful range of the immunoassay was between 0.1 to 1 ng (2–20 μg/L). Under standard assay conditions, no distinction can be made between the precursor and activated forms of the cofactor. Results of immunochemical determinations of colipase in porcine pancreatic juice and tissue extract were in good agreement with those obtained with the potentio-metric method. The specific determination of activated colipase in pancreatic juice was performed by coating the immunoplates with antigen in solution in PBS with 0.5 g/L of Tween 20. The detergent selectively impaired the binding of procolipase to the plate. Determination of colipase in human pancreatic juice carried out under the same experimental conditions showed that the minimal amount of human cofactor detectable with ELISA was 1 ng due to partial immunological crossreactivity of the human and porcine proteins. Immunoassay performed with antiporcine procolipase monoclonal antibodies (Mab) showed lower sensitivity than that performed with polyclonal antibodies. However, Mab 72.11, a monoclonal antibody that reacted only with porcine procolipase, allowed specific detection and differential determination of the precursor form of porcine colipase in pancreatic juice. ELISA performed with pure human colipase indicated that no antiporcine procolipase monoclonal antibodies cross-reacted with the human cofactor.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Fecal isoamylase activity was studied in 93 consecutive patients (26 in the recovery stage of acute pancreatitis, 24 with chronic pancreatitis, 13 with pancreatic cancer, and 30 with other gastrointestinal diseases) and compared with fecal chymotrypsin activity and the results of the secretin test. Seventy-six healthy subjects were studied as controls. Both pancreatic (p)-type and salivary (s)-type isoamylase activities in stool were determined by inhibitor assay as well as cellulose acetate electrophoresis. The mean fecal amylase activity in healthy subjects was 757 ± 88 IU/g (p-type isoamylase: 77 ± 2%; s-type isoamylase: 23 ± 2%). There was a good correlation between fecal p-type isoamylase and chymotrypsin activities (r = 0.625,p< 0.001). Fecal p-type isoamylase activity in patients with chronic pancreatitis and pancreatic cancer was significantly lower than in healthy subjects (p< 0.001). Patients with moderate and severe exocrine pancreatic insufficiency as determined by the secretin test had significantly lower fecal p-type isoamylase activity. Daily fat intake did not affect fecal amylase or isoamylase activities. Fecal s-type isoamylase activity in patients with hypoacidity was significantly higher than in patients with hyperacidity, but no difference in fecal p-type isoamylase activity was observed. It is concluded that analysis of fecal isoamylase activity is useful in the assessment of pancreatic function.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID