摘要:

Pancreatic enzyme extracts have been used for several decades to decrease maldigestion of macro-and micronutrients due to pancreatic insufficiency and to alleviate various abdominal symptoms, including the pain of alcohol-induced chronic pancreatitis and distal intestinal obstruction. Decreasing nutrient maldigestion and malabsorption in pancreatic insufficiency is of additional critical importance because improvement in nutritional status reduces morbidity and mortality. For example, pancreatic sufficient patients with cystic fibrosis (CF) demonstrate a slower decline in pulmonary function. In spite of the recognized importance of pancreatic enzymes, several problems exist with current preparations, and as newer enzyme preparations are marketed, proper evaluation becomes critical. There is a clear need to optimize the constituents of enzyme preparations, improve manufacturing processes, and find better sources of enzymes. Other issues that need addressing include standardization of the ratios of enzymes (lipase, amylase, protease) in these products; the stability of the enzymes at room temperature; the shelf life of the finished product; whether there are significant batch-to-batch differences; and the need for a USP reference standard.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

In previous studies we found that duodenectomy abolished the interdigestive cycles of plasma motilin and pancreatic polypeptide (PP). In the current studies, we tested the hypothesis that an intact duodenopancreatic axis is necessary for normal postprandial release of pancreatic (PP, insulin) and gut peptides (gastric inhibitory peptide, GIP; cholecystokinin octapeptides, CCK-8; neurotensin; and gastrin). Consequently, we measured plasma concentration of pancreatic and gut hormones in normal and duodenectomized dogs after gavage feeding of a 250-ml liquid formula diet in conscious animals. After completing the experiments, pancreatic tissue concentrations of PP and insulin were measured. Removal of the duodenum was associated with decreases in postprandial plasma concentrations of PP (p < 0.05) and insulin (p< 0.05) and in pancreatic tissue concentrations of insulin (p= 0.01). Duodenectomy, however, did not alter postprandial plasma concentrations of GIP, CCK-8, neurotensin, or gastrin nor pancreatic tissue concentrations of PP. These effects of duodenectomy may be due to disruption of duodenopancreatic neural connections or loss of vagus sensitive (non-GIP) humoral factors. Decreased postprandial insulin concentrations may be due to lack of a neural or humoral insulinotropic factor arising from the duodenum.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The objective of this work was to devise methods for the isolation and culture of duct epithelium from rhesus monkey pancreas with the expectation that such methods would be applicable to the human pancreas. This objective is important because of the role duct epithelium appears to play in human diseases such as pancreatic cancer and cystic fibrosis. Pieces of freshly procured pancreas were minced and enzymatically dissociated, resulting in a digest that contained a few isolated ductules (intralobular ducts) as well as numerous small tissue fragments consisting of roughly equal proportions of ductular and acinar cells. These fragments were suspended in a rat tail collagen gel and cultured for up to 2 weeks in a medium supplemented with cholera toxin, epidermal growth factor, and other additives. A few cystic ductular fragments were initially observed among a large number of predominantly solid fragments. Later, most of the solid fragments also became cystic and eventually resembled the ductules except for being spherical. Autoradiographic analysis of DNA synthesis showed that the cysts possessed a proliferative potential. The cysts consisted almost entirely of ductule-like epithelium with no recognizable acinar cells, and exhibited greatly reduced concentrations of the acinar marker enzymes amylase, chymotrypsin, and y-glutamyl transferase. In contrast, the specific activity of the duct marker enzyme carbonic anhydrase was elevated in freshly isolated digests compared with the whole pancreas and this elevated activity was maintained for 4–5 days of culture, after which it declined. Other evidence for the ductular nature of the cysts was their low density relative to freshly isolated acinar tissue, their ability to distend (suggestive of fluid/ electrolyte secretion), and the accumulation of mucins at the apical borders of the cells. The results show that fragments of rhesus monkey pancreas that are enriched in ductular epithelium assume some of the properties of ductular cells when cultured in a collagen gel. These epithelial preparations should facilitate biochemical and physiological studies of this important pancreatic cell type.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To measure the synthesis of pancreatic enzymes requires the separation of pancreatic juice proteins. The aim of the present study was to separate amylase, lipase, and trypsinogen present in dog pancreatic juice by using a hydrophobic interaction high-performance liquid chromatography (HPLC). During a 40-min, four-stage gradient of decreasing sodium sulfate concentration, dog pancreatic juice proteins were separated into 10 peaks based on hydrophobicity. Amylase, lipase, and trypsinogen were identified in HPLC fractions by measuring enzyme activity and molecular weight. Amylase and lipase were present in separate peaks. By sodium dodecyl sulfate (SDS) gel electrophoresis, peak 10, the only peak with amylase activity had a single protein, but peak 3, containing lipase, and peak 9, containing trypsinogen, had two or more proteins. Trypsinogen activity was also detected as a main protein in peak 5 and the molecular weight of this protein, 26 kDa corresponds to that of dog trypsinogen. Trypsinogen was not identified in peak 9 by SDS gel electrophoresis because other proteins were close to this location on the gel. In summary, the proteins and activities of amylase, lipase, and two trypsinogens secreted by the dog pancreas can be separated rapidly by hydrophobic interaction liquid chromatography. Also, this one step procedure recovers 87% of amylase from dog pancreatic juice as a single protein.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To investigate the effects of phospholipase A, (PLA,) on leukotriene (LT) generation, we evaluated LTB, and LTC4production by human leukocytes after incubation with porcine pancreatic and snake venom PLA2The pancreatic and venom PLA2did not induce LTB4and LTC4generation by human leukocytes alone. However, both types of PLA, promoted opsonized zymosan-induced LTB4production in a dose-dependent manner (from 10−10to 10−8M), whereas they had no effect on opsonized zymosan-induced LTC, generation. This promoting effect of pancreatic and venom PLA, required Ca2+in the incubation medium and was inhibited by mepacrine (10−5M). These findings suggest that increased production of PLA2in combination with inflammatory stimuli such as endotoxin enhance LTB4biosynthesis in acute pancreatitis.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The aim of the study was to establish whether correlations were discernible between calcification, smoking, and other variables—including alcohol intake—in chronic pancreatitis. A total of 637 patients with chronic pancreatitis diagnosed over the period of 1973—1989 were reviewed. Only patients who had had one or more instrumental tests (ultrasonography, endoscopic retrograde cholangiopancreatography, computed tomography, plain film of the abdomen) every 3 years were included in the study. Onset of calcification was taken as the end point of the follow-up. No statistically significant correlation was found between alcohol intake and calcification. As regards smoking habits, patients were divided into two groups: nonsmokers and medium-to-heavy smokers (210 cigarettedday). Of 637 patients, only 570 fulfilled our criteria. Three hundred seventy-six patients (66%) developed calcifications, whereas 64 (10%) already presented calcifications at the time of diagnosis. Smoking correlated with formation of calcifications (p < 0.004). The mean time to onset of calcification in smokers was 8 years as against 12 years in nonsmokers. The relative risk of calcification in smokers versus nonsmokers was 1.21 (95% confidence limits: 1.10-1.32). By the end of follow-up (17 years), 277 smokers (69%) with chronic pancreatitis had developed calcifications compared with only 93 nonsmokers (55%). The results show that, in this sample of chronic pancreatitis sufferers, smokers present a significantly increased risk of developing calcifications.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

In a prospective clinical-experimental study, 15 consecutive patients with chronic pancreatitis, operated on because of severe pain, were examined for the effects of a duodenum-preserving resection of the pancreas head on endocrine pancreas function. This was done by means of oral and intravenous glucose tolerance testing before the operation, on the 10th or 11th day postoperatively, and 3 months after the operation. In addition to glucose levels in the peripheral venous blood, levels of insulin, C-peptide, glucagon, and pancreatic polypeptide were determined. As indicated by the k value, glucose tolerance improved postoperatively in 10 patients (66.6%); three patients (19.9%) showed no change, and one patient (6.6%) was worse. Only one patient (6.6%) developed evident diabetes mellitus immediately postoperatively. Pre- and postoperative levels of insulin and C-peptide showed no significant differences. The fasting levels of glucagon were significantly lower postoperatively than before the operation (p< 0.01). The stimulation of pancreatic polypeptide after oral glucose was significantly lower postoperatively (p< 0.01). Duodenum-preserving pancreas head resection does not lead to an impairment of glucose tolerance in the majority of patients; a deterioration was observed only in few cases (13.3%).

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The pancreatic lesions in 6- to 36-week-oldspontaneously hypertensive rats (SHR), stroke prone SHR (SHRSP) and Wistar-Kyoto rats (WKY) were examined histopathologically. Inflammatory cell infiltration with hemorrhage and stromal fibrosis became evident in 12-week-old SHR and SHRSP together with acinar atrophy and/or degeneration and ductular proliferation. These changes in SHR and SHRSP were even more prominent at the age of 24 weeks and extremely severe at 36 weeks. In addition, in SHR and SHRSP over 12 weeks of age, small necrosis of acinar cells was found occasionally together with fibrosis and arteriosclerosis. Pancreatic arteriosclerosis was marked in SHR and SHRSP over 24 weeks of age at the level of arterioles <200 p,m in diameter. Adrenergic nerve fibers stained by fluorescence his-tochemistry were present around the pancreatic arteries and ducts and within the parenchyma, and they were denser in SHR and SHRSP than in WKY, indicating hy-perinnervation of the sympathetic nervous system in SHR and SHRSP. It is suggested that the pancreatic ischemia caused by arteriosclerosis due to facilitation of the sympathetic nervous system is an important factor in the pathogenesis of the spontaneous pancreatitis of SHR and SHRSP.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To assess the risk of pancreatic cancer in subjects with tropical calcifying pancreatitis (TCP), we have followed 185 patients with TCP from the Diabetes Research Center in Madras, India for an average of 4.5 years. The diagnosis of TCP was based upon longstanding epigastric pain, laboratory tests, presence of pancreatic calculi, endoscopic retrograde cholangiopan-creatography (ERCP) findings, and ultrasonography. During the follow-up period, 24 patients died from all causes, with 6 deaths (25%) from cancer of the pancreas. Three pancreatic cancers were biopsy positive. Average age at onset of pancreatic cancer was 45.6 * 7.3 years—considerably younger than for Western populations. When compared with the background pancreatic cancer rate, subjects with TCP appear to have a significantly increased risk of pancreatic cancer: relative risk = 100, 95% CI = 37–218. Even under the most stringent assumptions (restricting the analysis to biopsy-proven cases, assuming that the true background rate of pancreatic cancer in Madras resembles high-risk Western populations, assuming that tropical pancreatitis begins at birth) the risk is still elevated: relative risk = 5, 95% CI = 1.03-3-14.6. The exact mechanism linking various forms of pancreatitis to pancreatic cancer remains to be elucidated.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The role of oxygen-derived free radicals in the pathogenesis of acute pancreatitis was studied in a new model of acute hemorrhagic pancreatitis and cerulein-induced edematous pancreatitis in rats. Hemorrhagic pancreatitis was produced by administering two intraper-itoneal doses of cerulein [40 μg/kg body weight (BW)] at 1-h intervals following water immersion stress applied for 5 h. Edematous pancreatitis was induced by injecting cerulein as described but without water immersion. Five hours after the first injection of cerulein, pancreatic edema and elevation of serum amylase level were more marked in the animals with hemorrhagic than with edematous pancreatitis. Five hours after the first injection of cerulein, marked hemorrhage and venous dilatation were observed only in those with hemorrhagic pancreatitis. Local pancreatic blood flow decreased to ∼60% of control values in the animals with edematous pancreatitis, and to ∼30% of control values in those with hemorrhagic pancreatitis. To evaluate the involvement of oxygen radicals, some rats received three intraperitoneal injections of superoxide dismutase (SOD 10,700 Ulkg BW) and cat-alase (132,000 U/kg BW) beginning 15 min before the first injection of cerulein and repeated at 1-h intervals. No significant effect of free radical scavengers was observed on the edematous pancreatitis. However, in hemorrhagic pancreatitis, treatment with SOD and catalase completely suppressed the hemorrhage and venous dilatation of the pancreas, significantly reduced the pancreatic wet weight and the serum amylase level, and reduced the histologic alterations. However, after treatment with SOD and catalase, no differences were observed in local pancreatic blood flow. These findings indicate that stress produced microvascular damage such as pancreatic hemorrhage following the generation of oxygen radicals, and that these radicals produced severe damage to the pancreas.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID