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I Ihse

Publications and source records attributed to I Ihse.

At least 37 records · Page 2Linked to original sources
PubMed1998

The effect of intermittent injections of CCK-8S and the CCK-A receptor antagonist devazepide on cell proliferation in exocrine rat pancreas.

CONCLUSION: Intermittent injections of sulfated cholecystokinin-8 (CCK-8S) or devazepide caused long-lasting effects on cell proliferation in exocrine pancreas in contrast to continuous infusion. The acinar cells responded to both treatments with changes in the labeling index (LI) during the whole study period. When studying the influence of stimulation and inhibition of the CCK-A receptor on cell proliferation in the exocrine pancreas, not only are the drugs and doses of importance but also the mode of administration. BACKGROUND: Continuous infusion of CCK-8S or the CCK-A receptor antagonist devazepide induces transient changes in acinar cell proliferation in rat pancreas. The aim of the present experiments was to study whether intermittent administration of CCK-8S or devazepide prevents receptor desensitization and thereby affects exocrine pancreatic cell proliferation persistently. METHODS: Male Sprague-Dawley rats were injected subcutaneously twice daily with CCK-8S (6 micrograms), devazepide (240 micrograms) or bovine serum albumin (BSA). The rats were sacrificed after 18 and 36 h and 3 and 7 d. One hour before sacrifice, the rats were injected intraperitoneally with 1 mCi/kg of tritiated thymidine. The pancreatic weight and the contents of water, protein, and DNA were determined. The LI (number of labeled cells/100 cells) of exocrine pancreatic cells was determined microscopically after autoradiography. RESULTS: The concentration of plasma CCK was slightly increased by devazepide, but the increase was more pronounced by CCK-8S. The pancreatic wet weight was transiently increased 18 h after the start of CCK-8S injections (+14%), whereas devazepide caused a reduction after 7 d (-22%). The protein content was uninfluenced and the DNA content was decreased at 36 h with either treatment. CCK-8S increased the LI in acinar and centroacinar cells throughout the study period, but the ductal cell LI was increased only after 18 and 36 h. Injection of devazepide was followed by decreased LI of acinar cells throughout the study period. Also, the centroacinar and ductal cell LI decreased initially but returned to control values after 7 d.

Animals↗
PubMed1998

The inhibitory effect of an EGF receptor-specific tyrosine kinase inhibitor on pancreatic cancer cell lines was more potent than inhibitory antibodies against the receptors for EGF and IGF I.

CONCLUSION: Epidermal growth factor (EGF) increased the cell number of the two pancreatic cancer cell lines, MiaPaCa-2 and LN-36, in vitro. A blockade of the EGF-R tyrosine kinase with tyrphostin was more efficient in reducing the cell number than inhibiting receptor antibodies. IGF-1 increased the cell number, and blockade of the IGF-1-R initially decreased the cell number that later was followed by an increase in LN-36. BACKGROUND/AIM: The receptors and ligands of EGF and insulin-like growth factor-1 (IGF-1) are overexpressed in pancreatic cancer tissue. The aim of the present experiments was to study the effects of EGF and IGF-1 on the cell number in two pancreatic cancer cell lines. MATERIAL AND METHODS: MiaPaCa-2 cells were grown in 0.2% fetal calf serum (FCS) and the newly established LN-36 cells in serum-free medium (SFM). The cell number was measured with the XTT method. The effects of EGF and IGF-1 were studied in combination with inhibiting receptor antibodies and an EGF-R-specific tyrosine kinase inhibitor, tyrphostin B56. RESULTS: MiaPaCa-2 responded with increased cell number to stimulation with EGF, and at 10(-8) M or higher concentrations a dose-response pattern was seen. Administration of B56 to MiaPaCa-2 decreased the cell number by 87%. The inhibiting EGF-R-Ab only inhibited EGF-induced increase in cell number. IGF-1 doubled the cell number of MiaPaCa-2 and increased the cell growth induced by EGF. The inhibiting IGF-1-R-Ab reduced the cell number by 10%. The LN-36 cell line responded to EGF with an increased cell number with a maximum at 5 x 10(-9) M after 96 h. B56 reduced the cell number by 90% at 10(-5) M, with less effect during stimulation with EGF. In contrast to B56, the inhibiting EGF-R-Ab in the same experiment did not reduce the cell number. LN-36 responded to IGF-1 with an increased cell number, but EGF-stimulated growth was not influenced. The inhibiting IGF-1-R-Ab reduced the cell number and suppressed the IGF-1 stimulated increase after 24 h and later it induced an increased cell number.

Antibodies↗
PubMed1998

[Combination therapy in oncology (multimodal treatment) in pancreatic tumors].

The majority of patients with pancreatic cancer have systemic disease already at diagnosis, and nearly all patients will develop recurrence following radical resection. Thus, surgical treatment alone is insufficient. The paper focuses on adjuvant multimodal treatment and reviews the current status of pre- and postoperative chemoradiation, intraoperative radiotherapy (IORT), adjuvant chemotherapy, and regional infusion therapy. Studies in this area are hampered by often being non-randomized and with too few patients included. Overall there presently is no adjuvant multimodal treatment which can be suggested for routine use. However, two ongoing prospective randomized studies (ESPAC-1 and an EORTC study) will have enough statistical power to give reliable information on the topic. It is hoped that these and other studies will form the basis for further proper clinical trials on multimodal treatment in pancreatic cancer with the aim at long last to improve the extremely poor survival in these patients.

Adenocarcinoma↗
PubMed1998

Computed tomography and laparoscopy in the assessment of the patient with pancreatic cancer.

BACKGROUND: In most patients with pancreatic cancer, the tumor is unresectable. Nonoperative methods for palliation of jaundice, duodenal obstruction, and pain currently are being developed. Preoperative assessment of resectability of the tumor is becoming more and more important to avoid unnecessary operations. The aim of this study was to compare computed tomography (CT) and laparoscopy with special reference to the additive role of the latter technique in predicting unresectability of pancreatic cancers. STUDY DESIGN: Sixty patients with exocrine pancreatic cancer were assessed prospectively with both CT and laparoscopy. On the basis of metastatic spread or signs of vascular involvement, the radiologist and the laparoscopist independently reported the tumors as probably unresectable or resectable. RESULTS: The predictive value for unresectability was 100% for both CT and laparoscopy. Sensitivity in predicting unresectability was 69% for both techniques, and the corresponding figure for specificity was 100%. When CT and laparoscopy were evaluated together, an improvement in sensitivity to 87% was observed (p < 0.05). Separately, CT and laparoscopy correctly predicted resectability in only 30% and 38% of the patients, respectively. The presence of liver metastases was overlooked by CT in 13 of 32 patients (40%). Every fourth patient who was found to have unresectable tumor at CT was falsely classified as resectable by the laparoscopist, leading to unnecessary laparotomies. On the other hand, 9 of 24 patients (38%) with resectable disease at CT were deemed unresectable at the subsequent laparoscopy. CONCLUSIONS: Laparoscopy and CT independently and reliably predicted unresectability of pancreatic cancer, but the methods were inaccurate in forecasting resectability. The results suggest that CT examination should be done in patients who are candidates for attempted curative surgical procedures, whereas laparoscopy should be restricted to Those Judged resectable at CT.

Humans↗
PubMed1998

Effect of endoscopic sphincterotomy and interval cholecystectomy on late outcome after gallstone pancreatitis.

BACKGROUND: Endoscopic sphincterotomy alone, or followed by cholecystectomy, are options in patients with gallstone pancreatitis. METHODS: Ninety-six patients of median age 74 (range 30-93) years with gallstone pancreatitis had endoscopic retrograde cholangiography and were followed for a median of 84 (range 33-168) months. Forty-eight of 49 patients with, and nine of 47 without, common bile duct (CBD) stones had urgent endoscopic sphincterotomy. One patient with, and six without, CBD stones had delayed endoscopic sphincterotomy a median of 35 (range 12-111) days after acute pancreatitis. Thus, 64 patients had endoscopic sphincterotomy (group 1) and 32 did not (group 2). Fifteen and 16 patients in each group respectively had interval cholecystectomy after a median of 3 months and 1 month. RESULTS: Patients in groups 1 and 2 had similar rates of interval cholecystectomy (15 of 64 versus 16 of 32 patients respectively) or required cholecystectomy (15 of 49 versus five of 16 patients), recurrent CBD calculi (three of 64 versus three of 32 patients) or total length of hospitalization after interval cholecystectomy (median 15.5 and 15 days) or required (median 22 and 24 days) cholecystectomy. The overall incidence of recurrent pancreatitis was one of 64 patients in group 1 and five of 32 in group 2 (P = 0.02), but after interval cholecystectomy the recurrence rate of biliopancreatic symptoms was similar (one of 15 patients versus three of 16 patients respectively). CONCLUSION: Endoscopic sphincterotomy, but not interval cholecystectomy, reduced the overall incidence of recurrent pancreatitis, but not of late biliary complications. Some 31 per cent of the patients required cholecystectomy, suggesting that routine cholecystectomy should be considered in fit patients following acute pancreatitis.

Adult↗
PubMed1998

Effect of a platelet-activating factor antagonist on pancreatitis-associated gut barrier dysfunction in rats.

Platelet-activating factor (PAF) may play a critical and primary role in the pathogenesis of acute pancreatitis and pancreatitis-associated distant organ injury. The present study evaluated the effect of a PAF antagonist, lexipafant (an (S)-4-methyl-2[methyl-imidazo[4,5-c]pyridin-1-ylmethyl)-benzene sulphonyl]-amino]pentanoic acid ethyl ester, BB-882; British Biotech Ltd.), on the potential prevention of gut barrier dysfunction, by measuring gut origin sepsis, bidirectional permeability of the intestinal barrier, and pancreatic capillary endothelial barrier integrity, in acute pancreatitis induced by intraductal infusion of 5% sodium taurodeoxycholate. Pancreatic endothelial permeability significantly increased in animals with acute pancreatitis, whereas pretreatment with lexipafant had a preventive effect (p < 0.05 vs. pancreatitis with saline). Similarly, alterations noted in hematocrit and plasma levels of lipase and calcium were counteracted by the PAF antagonist. It also prevented the increase in albumin leakage from blood to the mucosal interstitium and from blood to the intestinal lumen in acute pancreatitis. Albumin passage from the gut lumen to blood in animals with pancreatitis pretreated with saline increased from 3 h and on, and lexipafant prevented alterations in mucosal epithelial permeability. Bacterial translocation was commonly seen in pancreatitis, whereas only a few positive cultures were observed in pancreatitis animals given lexipafant. Microthrombosis in intestinal villi seemed less frequent after lexipafant pretreatment. We conclude that (a) PAF may play a role in the pathogenesis of pancreatitis-associated intestinal dysfunction, (b) PAF may be involved in the development of distant organ dysfunction by triggering endothelial barrier dysfunction, and (c) PAF antagonists may provide potential agents for preventing pancreatitis-associated gut barrier dysfunction.

Acute Disease↗
PubMed1997

Intravascular ultrasound for evaluation of portal venous involvement in pancreatic cancer.

The aim of this study was to evaluate the accuracy of intravascular ultrasound (IVUS) in diagnosing tumour involvement of the portal vein in patients with exocrine cancer of the head of the pancreas. Seven consecutive patients with a preoperative diagnosis of carcinoma, preoperatively deemed to be resectable, were examined with IVUS of the portal vein during surgery. The IVUS catheters were 6.2 F (2.0 mm) in diameter with a 20-MHz transducer and were introduced into the portal vasculature through the mesenteric superior vein. All patients had tumour extending to the portal vein as demonstrated at histopathological examinations in six cases and at surgical dissection in one case. The IVUS technique correctly identified all these patients, whereas five patients were incorrectly deemed at surgery not to have tumour involvement of the portal vein. These results indicate that IVUS is a very sensitive method for the evaluation of tumour involvement of the portal vein.

Aged↗
PubMed1997

The effect of selective sympathetic denervation on pancreatic exocrine secretion.

The purpose of this study was to investigate the influence of selective sympathetic denervation of the rat pancreas on exocrine secretion and to study whether the observed effects were due to pancreatic trophism. Sprague-Dawley rats were divided into two groups. One group underwent selective sympathetic denervation by skeletonizing the superior and inferior pancreaticoduodenal and splenic arteries. The other group underwent simple laparotomy and served as controls. One week after the operation a catheter was introduced into the bile-pancreatic duct and pancreatic juice was collected at 30-min intervals for 4 h. The output of bicarbonate, total protein, amylase, trypsin, chymotrypsin, lipase, colipase and carboxyesterlipase were determined. Following denervation secretion of pancreatic enzymes was significantly enhanced compared with sham-operated animals. We did not find any signs of pancreatic trophism 1 week after denervation.

Amylases↗
PubMed1997

Epidermal growth factor induces cell proliferation in mouse pancreas and salivary glands.

Epidermal growth factor (EGF) is a mitogenic stimulus in many tissues and occurs in large amounts in the pancreas and salivary glands. Whether EGF is mitogenic in the pancreas is controversial, and the EGF effect has not been studied in the salivary glands. Therefore, the aim of the present study was to investigate the possible effects on the pancreas and parotid and submandibular glands at different time intervals after exogenous EGF administration. Human recombinant EGF was infused subcutaneously by osmotic minipumps in three groups of mice (for 1, 3, and 7 days, respectively) at a dosage of 10 micrograms/kg/h (1.6 mumol/kg/h). Tritiated thymidine was infused intraperitoneally by osmotic minipumps for the same time periods, but only for the last 3 days in the 7-day group. After 1 day the pancreas increased in weight and the increase persisted throughout the study. No effect was seen on the parotid or submandibular gland wet weight. A slight transient increase in pancreas protein content was observed, whereas amylase content was unaffected. The labeling index of serous and ductal cells in the parotid gland increased from the third day. After 7 days, all cell types studied in the pancreas and parotid and submandibular glands were in a hyperproliferative state. The results show that EGF evoked a strong proliferative response on all cell types studied in the pancreas and parotid and submandibular glands.

Animals↗
PubMed1997

Biliodigestive shunt evokes hyperCCKemia and trophic effects in the rat pancreas, but not in the liver or gastrointestinal tract.

The influence of bile on the release of cholecystokinin (CCK) and, thereby, on the regulation of exocrine pancreatic function and growth is unsettled. The aim of this study was to elucidate the effect of long-term diversion of bile from the upper small intestine of CCK release and on the pancreas, liver, and gastrointestinal tract. A surgical biliodigestive shunt was performed in rats, diverting the bile flow directly to the middle of the small intestine. The animals were killed after 4 or 12 weeks. Plasma CCK and trophic effects on the pancreas, liver, and gastrointestinal tract were determined, as were the trypsin and chymotrypsin contents in the intestine. The CCK concentration in plasma increased 10-fold at both time points studied. The pancreas doubled its weight from 4 weeks onward. Also, pancreatic protein, DNA, and amylase contents were increased throughout the study. The liver and gastrointestinal tract were unaffected. Intraluminal bile plays a role in the feedback regulation of CCK release and is involved in this way in the control of pancreatic growth but has no similar effects on the liver or gastrointestinal tract.

Amylases↗
PubMed1997

Epidermal growth factor induces increased mucosal thickness of the small intestine in mouse.

Epidermal growth factor (EGF) is known to exert a mitogenic effect in different tissues, including the digestive tract. The aim of the present study was to evaluate whether long-term infusion of EGF causes trophic effects in the gastrointestinal tract of female mice. The animals were infused subcutaneously in the neck with human recombinant EGF in a dose of 10 micrograms/kg/h (1.6 nmol/kg/h) using an osmotic minipump for 1, 3 and 7 days, respectively. Tritiated thymidine was continuously infused intraperitoneally during the same period, except in the 7-day group, where it was infused during the last 3 days. The mucosal thickness was measured microscopically. As a measurement of DNA synthesis, the amount of thymidine retained in the mucosa was registered using a scintillation counter. After 1 day of EGF infusion, the mucosal thickness was increased in the antrum and, after 3 days, in the fundus. In the proximal duodenum, an increased depth of the crypts was seen after 1 day, followed by increased villi height after 3 and 7 days; in the distal duodenum, EGF evoked increased villi height after 3 and 7 days. The height of villi was increased after 7 days in the jejunum and ileum in the EGF-treated animals. The tritium incorporation was increased in the fundus of the stomach and the proximal duodenum in the EGF-treated animals after 3 days, whereas no significant increase in tritiated thymidine incorporation could be detected in the EGF-treated animals after 1 and 7 days compared to the controls. In conclusion, continuous infusion of EGF evoked increased mucosal thickness in the small intestine, while the trophic effects were only of a short duration in the stomach and absent in the colon.

Animals↗
PubMed1997

Total parenteral nutrition affects the tropic effect of cholecystokinin on the exocrine pancreas.

BACKGROUND: Cholecystokinin (CCK) exerts trophic effects on the exocrine pancreas. Total parenteral nutrition (TPN) results in hypotrophy of the pancreas. The present study aimed to examine the effect of exogenous and endogenous CCK during TPN. METHODS: Seventy-two Sprague-Dawley rats were orally fed or given TPN after pancreaticobiliary diversion (PBD) and were infused with CCK-8S or the CCK-receptor antagonist devazepide for 7 days. RESULTS: Infusion of CCK and PBD caused hyperCCKemia, whereas TPN did not influence the concentration of plasma CCK. The reduced pancreatic contents during TPN could be reversed by CCK but not by PBD. The hyperplastic response to CCK in orally fed rats was abolished during TPN. Devazepide did not influence the pancreatic variables in orally fed and TPN-treated rats. CONCLUSION: TPN reduces the hyperplastic response of the exocrine pancreas to CCK, and CCK reverses the hypotrophy seen during TPN. The effects of CCK on the exocrine pancreas seems to need enteral nutrition for the full expression.

Animals↗