摘要:

This conference marked the end of an era of uncertainty about mechanisms initiating acute pancreatitis in humans, the validity of various animal models, and the relationship between acute and chronic pancreatitis. It is now clear that active trypsin plays a central role in the initiation of one or more types of acute pancreatitis. It is now possible to identify certain individuals at risk for pancreatitis before the first attack through genetic testing and to distinguish hereditary pancreatitis from other forms of pancreatitis. The importance of identifying the site and mechanism of trypsinogen activation in animal models of acute pancreatitis has also been realized. Furthermore, it is now clear that human chronic pancreatitis can arise from recurrent attacks of acute pancreatitis through the necrosis-fibrosis sequence. The initial presentation of the strikingly high incidence of cystic fibrosis mutations in idiopathic chronic pancreatitis and relapsing acute pancreatitis was unveiled, suggesting another strong genetic predisposition to pancreatitis. Finally, the strong influence of prolonged chronic pancreatitis in the development of pancreatic cancer is now clear. Thus, this conference marked the beginning of an new era of pancreatic research based on molecular mechanisms in humans and it opened the possibility of developing new therapies designed to limit or prevent human suffering from many diseases of the pancreas.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

This study evaluated the new criteria for the diagnosis of chronic pancreatitis (CP) with endoscopic retrograde pancreatography (ERP) proposed by the Japan Pancreas Society in 1995 by comparing it with the older criteria of the Japanese Society of Gastroenterology proposed in 1983. No significant differences were noted between the two when the diagnostic sensitivity of ERP was considered in calcifying CP. Among 54 patients of noncalcifying CP (group I) with ERP diagnosis of moderate or advanced pancreatitis by the previous criteria, only one of 22 with the localized type was definite CP. The remaining 21 were ruled out as either definite or probable CP, and six were classified as having chronic obstructive pancreatitis based on the new criteria. In contrast, a diagnosis of definite CP was made not only for all the 32 patients with CP (group I) of diffuse type but also in 11 cases of CP (group II) with diffuse minimal pancreatitis showing irregular dilatation of the side branches with scattered distribution throughout the gland. In a series of 15 follow-up patients with CP (group II) having initial ERP diagnosis of minimal pancreatitis, CP group I developed in three of five cases of diffuse minimal pancreatitis, which is consistent with definite CP by the new criteria, whereas progression to this group of CP was found in none of the 10 patients with localized minimal pancreatitis. These results indicate that although localized CP is excluded from CP, the incidence of diffuse noncalcifying CP diagnosed by ERCP was increased with the new criteria, and detecting radiologic features with diffuse irregular dilatation of the branch ducts based on these criteria may lead to early diagnosis of CP.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Activated endogenous mediators of inflammation have important roles in the pathogenesis and complications of acute pancreatitis (AP). These mediators include bactericidal/permeability-increasing protein (BPI) and phospholipase A2(PLA2). The time course of their activation during human AP is not known. The aim of this study was to evaluate the kinetics of BPI, group I (pancreatic) and group II (synovial type) PLA, during human AP with temporally defined onset, as being induced by endoscopic retrograde cholangiopancreatography (ERCP). Serum samples of 273 consecutive patients undergoing ERCP were collected before and at 3, 6, and 24 h after ERCP. Twenty-four (8.7%) patients developed ERCP-induced pancreatitis. Seven of them were graded to have a severe disease. Forty randomly selected patients undergoing ERCP without evidence of pancreatitis served as controls. The serum concentrations of BPI and groups I and II PLA, were measured by specific immunoassays. The mean concentration of BPI increased from 14 to 26 μg/L at 24 h after ERCP in patients with AP. In the control group, BPI values remained unchanged, and the difference was statistically significant (p <0.001). The increase of BPI was seen in 22 of 28 patients with AP at 3 h after the onset of the disease. BPI values were higher in severe post-ERCP pancreatitis than in mild disease (p = 0.07; NS). The serum concentrations of group II PLA2before ERCP were consistently higher in the control patients than in the patients with pancreatitis, 65.8 and 14.2 μ/L, respectively. High baseline values in the control group were associated with preexisting infectious diseases. Thereafter, the mean concentration decreased in the control group to 44 μ/L and increased in the pancreatitis group up to 27.5 μ/L. The difference was statistically significant (p = 0.007). Increased group II PLA, values were seen in 10 of 17 patients with mild AP and in five of seven patients with severe disease. There were no significant differences in group I or II PLA, values in patients with mild or severe AP. The serum concentration of group I PLA, increased in the patients with post-ERCP pancreatitis from 5.4 to 37.5 μ/L at 24 h. The difference was statistically significant, (p <0.001) as compared with controls. In conclusion, in acute pancreatitis, the increase of BPI in serum starts at 3 h after the onset of the disease, and the concentration seems to correlate with the severity of the disease. Increased group II PLA, concentrations also were seen in patients with mild AP. The kinetics of group I PLA, resembles that of other pancreatic enzymes.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The regenerative process after acute inflammation of the pancreas is characterized by cell proliferation as well as synthesis and transient deposition of extracellular matrix. Although the regulation of these processes is still unknown, there is growing evidence that the coordinated activity of various growth factors plays an important role in regeneration. Cerulein-induced pancreatitis in the rat was used to analyze whether growth factors and their receptor concentrations are changed in the acute pancreatitis. Messenger RNA hybridization revealed an individual expression pattern for each analyzed growth factor. The mRNA levels of platelet-derived growth factor B (PDGF B), epidermal growth factor (EGF), and insulin-like growth factor 2 (IGF-2) were not altered, whereas fibroblast growth factor-1 (FGF-1) and 2, IGF-1, transforming growth factor-α(TGFα), and hepatocyte growth factor (HGF) showed markedly increased concentrations with different expression maxima and duration compared with mRNA levels in healthy pancreata. The FGF-2 and IGF-1 expressions were increased between 1 and 3 days after induction of pancreatitis with maxima at day 2. HGF and FGF-I mRNAs were upregulated between days 3 and 5. In contrast, TGFα exhibited the most prolonged overexpression. In the corresponding receptors, only c-met, the HGF-binding protein, showed higher mRNA and protein levels, whereas the expression of the other receptors did not change. Furthermore, in cultured pancreatic epithelial cells, HGF stimulated the expression of its own receptor in an autocrine manner. These results point out that the highly coordinated process of regeneration after pancreatitis may be influenced by a sequential induction and expression of peptide growth factors and their receptors.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The mechanism of fibrogenesis in the pancreas is not well known. We analyzed the role of prolylhydroxylase and collagenase activities in the development of fibrosis in chronic alcoholic pancreatitis (CAP). Nineteen patients with CAP and 11 controls (organ donors) with normal pancreatic histology were included in the study. Pancreatic tissue was obtained from all subjects to measure (a) area of fibrosis (histomorphometric method); (b) prolylhydroxylase activity (PHase), which reflects the intracellular synthesis of collagen (Hutton's method); and (c) collagenase activity, which reflects the degradation of ollagen (collagenase assay system,3H). The percentage of the fibrosis area in relation to the total area of pancreatic tissue was significantly higher in CAP than in the control group (70.6 ± 20.2% vs. 4.6 ± 1.8%; p <0.001). Mean pancreatic Phase activity was also significantly higher in CAP than in the control group (775 ± 258 cpm/mg/protein/h vs. 405 ± 151 cpm/mg/protein/h; p <0.001). The collagenase activity was significantly lower in CAP than in the control group (8.7 ± 3.5 cpm/cpmadded/mg protein vs. 18.0 ± 3.9 cpm/cpmadded/mg protein; p <0.001). A significant correlation was observed between percentage fibrosis evaluated histomorphometrically and Phase activity in all patients (r = 0.72; p <0.001), and between PHase and collagenase activities in controls (r = 0.70; p = 0.024), but not in CAP. Pancreatic tissue in CAP has an increased fibrogenic activity and an impaired collagendegradation capacity. These findings might explain the excessive development of fibrosis in CAP.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Bacterial translocation leading to subsequent infectious complications is a significant determinant of outcome in acute hemorrhagic pancreatitis (AHP). The colonic ileus and impaired intestinal barrier function that often accompany AHP may predispose to translocation. Sennoside is a naturally occurring cathartic and choleretic agent that stimulates intestinal mucous secretion and has potent promotility effects. The impact of sennoside-induced intestinal motility and secretory function on bacterial translocation and survival was studied in a rat model of AHP. Severe acute pancreatitis was induced in rats by the intraductal infusion of 2% sodium deoxycholate (DCA, 0.4 ml/kg). A group of sham-operated rats (group A) received intraductal saline, whereas experimental animals were subsequently administered distilled water (group B) or sennoside solution (group C) by gavage every 8 h. After 48 h, intestinal transit of fluorescein isothiocyanate-labeled dextran, serum endotoxin, and amylase levels, and bacterial translocation to mesenteric lymph nodes (MLNs) and pancreatic tissue were determined. The pancreas and intestine were sampled for histologic study. All group A animals survived and did not develop pancreatitis or endotoxemia, whereas groups B and C all demonstrated severe hemorrhagic pancreatitis with evidence of necrosis. Mortality at 48 h was 55% in group B versus 12.5% in group C. Inhibition of intestinal motility was noted in 40% versus 20%, and endotoxin levels were 61.36 ±8.26 pgL versus 5.41 ±3.58 pg/L in group B versus group C rats, respectively (p <0.001). Pancreatic tissue and MLN cultures were positive in 100% of group B survivors versus 14% of group C survivors (p <0.05). Histologic examination of the intestine in group C animals showed increased mucous secretion, proliferation of goblet cells, and evidence of rapid turnover/renewal of enterocytes. Treatment with the cathartic agent, sennoside, reduced translocation of endotoxin and bacteria, restored intestinal motility, increased mucous secretion, and reduced mortality in a model of acute hemorrhagic pancreatitis in the rat. Other cathartics may have similar properties and may be useful in preventing infectious complications in acute pancreatitis.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

We diverted bile and pancreatic juice from jejunal blind loops of different lengths in conscious rats to see if the pancreatic secretory response was dependent on the length of the jejunal blind loop. Short-term bile and pancreatic juice diversion from a short jejunal blind loop, representing only 8-10% of the total length of the small intestine, stimulated a significant increase in pancreatic exocrine secretion. Short-term bile and pancreatic juice diversion from jejunal blind loops of increasing length resulted in a progressive decrease in the pancreatic secretory response to diversion (i.e., there appears to be a length-dependent inhibition of the pancreatic secretory response to short-term bile and pancreatic juice diversion from the jejunum). Cholinergic receptor blockade with atropine eliminated this length-dependent inhibition of pancreatic exocrine secretion during short-term bile and pancreatic juice diversion. In contrast to what was observed with short-term bile and pancreatic juice diversion, there was a length-dependent increase in pancreatic secretion during long-term bile and pancreatic juice diversion. The jejunal-bypass rat model can facilitate the investigation of the intestinal mechanisms mediating feedback regulation of pancreatic exocrine secretion.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Stimulation of extrinsic nerves markedly alters pancreatic endocrine and exocrine secretion, yet little is known of the neurochemical organization and physiologic roles of specific neural pathways within the pancreas. Here we report histochemical staining for acetylcholinesterase (AChE), NADPHdiaphorase (NADPH-d), nitric oxide synthase (NOS), and several neuropeptides to identify the neurotransmitter content of rabbit pancreatic nerves. An extensive network of AChEpositive nerve fibers was found throughout the islets, acini, ducts, ganglia, and blood vessels. All pancreatic neurons were AChE positive, two thirds were NADPH-d positive, and many were NOS positive. Ganglia in the headneck region were connected to the duodenal myenteric plexus by AChE- and NADPH-d-positive fibers, and NADPH-d-positive pancreatic neurons appeared to send processes toward both the duodenum and pancreas. Many pancreatic neurons were vasoactive intestinal peptide (VIP) positive, and VIP nerve terminals were abundant in ganglia, acini, islets, and ducts. Pituitary adenylate cyclase-activating peptide (PACAP-38)-positive fibers also were observed within acini and passing through ganglia. Substance P (SP)-, calcitonin gene-related peptide (CGRP)-, and dopamine P-hydroxylase (DBH)-positive fibers were abundant along blood vessels and ducts, and varicose fibers were observed in pancreatic ganglia. Fine galanin-positive fibers were also occasionally observed running with blood vessels and through ganglia. Thus the rabbit pancreas receives a dense, diverse innervation by cholinergic, adrenergic, and peptidergic nerves and cholinergic pancreatic neurons, most also containing VIP or NOS or both, appear to innervate both endocrine and exocrine tissue, and may mediate local communication between the duodenum and pancreas.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Pancreatic neurons receive and integrate synaptic input from a wide variety of extrinsic nerves while providing the predominant innervation of pancreatic acini, ducts, and islets of Langerhans. Here we report the first primary cultures of adult rabbit pancreatic neurons, isolated from extrinsic nerves and secretory cells, and evaluate the neurochemical and electrical properties of these neurons. Pancreatic cultures consisted of single and clustered neurons, extended varicose processes after 3 4 days in culture, and formed interconnecting networks of neurons after 7-10 days. Isolated pancreatic islet cells, added to established neuron cultures, remained attached and viable for several weeks and received innervation by varicose nerve fibers. Histochemical staining revealed populations of neurons positive for acetylcholinesterase (75%), NADPH-diaphorase (62%), nitric oxide synthase (73%), and/or vasoactive intestinal peptide (VIP) (65%). Intracellular recordings revealed active and passive electrical properties comparable to those of neurons from intact ganglia. Several distinct populations of neurons were identified by their firing patterns (phasic vs. tonic) in response to prolonged depolarizing currents or the amplitude and duration of their after-spike hyperpolarizations. Low-amplitude, pacemaker-like potentials were observed in 25% of the neurons and, in older cultures with extensive networks of fibers, spontaneous fast excitatory postsynaptic potentials (EPSPs) also occurred. Thus these cultures retained the salient neurochemical and electrophysiologic properties observed in pancreatic neurons from intact ganglia and offer a good model for studies of the intrinsic innervation of the pancreas.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The islet response to a high-fat diet, which induces insulin resistance, was investigated in Sprague-Dawley rats. It was found that the insulin response to glucose (15 or 25 mg/min, i.v.) was not different between rats given a high-fat diet and control rats after 2 weeks but was significantly reduced in rats fed high-fat diets after 4 (by 46 ± 9%; p <0.001) and 8 weeks (by 68 ± 12%; p <0.001). However, after 2 weeks of a high-fat diet, stimulated insulin secretion from isolated islets incubated for 60 min in 5.6, 8.3, and 11.1 mM glucose was impaired. When islets isolated from rats given a high-fat diet for 2 weeks were perifused, it was evident that the first-phase insulin secretion was impaired (seen during the first 6 min after increase of glucose from 3.3 to 8.3 mM). Insulin gene expression, examined by quantitative in situ hybridization, was impaired after 2 weeks of high-fat diet (52% decrease in mRNAlabeling; p <0.001). Islet hypertrophy was not evident in rats given high-fat diet, as determined by areas of either islet profiles in dark-field images or isolated islets. Islet innervation, as revealed by immunostaining for vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), was increased after 2,4, and 8 weeks of high-fat diet. Thus induction of insulin resistance by high-fat diet in Sprague-Dawley rats results after 2 weeks in impaired glucose-stimulated insulin secretion in vitro, impaired insulin gene expression, and hyperinnervation of the islets without any sign of islet hypertrophy, whereas the in vivo insulin response to glucose, although normal after 2 weeks, is impaired after 4 weeks.

ISSN:0885-3177    

出版商:OVID    

年代:1999

数据来源: OVID