ISSN:0885-3177    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Chronic ethanol ingestion is a primary factor in the development of pancreatitis in humans. Alterations in both enzyme secretion and protein synthesis have been implicated as causative factors. We determined the effect of chronic ethanol feeding on the content and synthesis rates of digestive enzymes in dispersed acini from rats that were pair-fed isocaloric diets with or without ethanol for 3–6 months. Total protein content and synthesis were unchanged. The relative synthetic rates of individual digestive enzymes were analyzed using scanning laser den-sitometry of 1-D sodium dodecylsulfate (SDS) gels. The content of all measurable digestive enzymes except amylase increased in acini from ethanol-fed rats. Relative synthetic rates were examined in pancreatic acini labeled in vitro with [35S]methionine. Liquid scintillation counting of radiolabeled digestive enzymes extracted from gelslices revealed that amylase synthesis in ethanol-fed rats decreased 2.8-fold compared with controls whereas the synthetic rates of proelastase 1 and 2, chymotrypsinogen, and trypsinogen increased by 1.5-, 1.4-, 1.8-, and 1.6-fold, respectively. Total cellular RNA was extracted from control and ethanol-fed rats and subjected to Northern and dot blot analysis. Amylase mRNA decreased in ethanol-fed rats whereas chymotrypsinogen and trypsinogen mRNA content increased, indicating that the effect of ethanol on expression of these genes was regulated at a step prior to translation. Elastase mRNA content was not altered, suggesting that the increased synthesis of proelastase may be regulated posttranscriptionally.

ISSN:0885-3177    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

A ruptured pseudoaneurysm is the most rapidly fatal complication encountered in patients with chronic pancreatitis, with a reported mortality rate of 12.5% in treated patients to >90% in those untreated. Although reportedly a rare complication of chronic pancreatitis, a pseudoaneurysm is encountered in 6–9.5% of patients with chronic pancreatitis and as many as 17% of all patients operated on for chronic pancreatitis. Timely diagnosis and treatment seems to result in markedly reduced mortality. Four patients with bleeding pseudoaneurysms associated with chronic pancreatitis and pseudocysts were encountered recently at Virginia Mason Medical Center. These patients' charts, as well as the English literature, were reviewed in detail. All of our cases occurred in alcoholic males. Pseudocysts with pancreatic ductal or pseudocyst rupture were seen in three cases. All had a history of crescendo-decrescendo pain episodes and had evidence of bleeding or were bleeding at presentation. Splenic vein occlusion was identified in 50% of the cases. A pseudoaneurysm was documented by angiography in all patients. Embolization was success fully attempted without complication in two patients. Three patients were ultimately treated with a pylorussparing (2) or standard (1) pancreaticoduodenectomy. These three are alive and doing well at 16, 26, and 52 months from the time of their procedure. A fourth patient was treated nonoperatively, because of severe comorbid disease and aberrant anatomy, with successful embolization of the pseudoaneurysm and biliary and pancreatic stenting. The pseudocyst resolved and he is asymptomatic 12 months after therapy. We advocate preoperative arteriography in all patients with suspected or known arterial pseudoaneurysm. Transcatheter embolization should be attempted in all symptomatic patients with pseudoaneurysms to prevent or treat bleeding episodes. Resection of the pseudocyst and pseudoaneurysm is optimal treatment, but interventional radiologic or gastroenterologic methods may allow for successful nonoperative management in selected patients.

ISSN:0885-3177    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The effect of pancreatic ductal and parenchymal changes on exocrine pancreatic function was analyzed prospectively in 75 patients with chronic pancreatitis (CP). Endoscopic retrograde pancreatography (ERP), computed tomography (CT), and serum pancreolauryl test (PLT) were performed to evaluate the degree of ductal, parenchymal, and functional changes, respectively. Results were evaluated by stepwise multivariate logistic regression and are expressed as the odds ratio (OR). A strong association was found between the degree of ductal changes in ERP and the degree of exocrine functional impairment (OR = 5.8). However, the association between the degree of parenchymal changes in CT and the degree of pancreatic dysfunction was weaker and was clearly confounded by the degree of ductal changes. On the basis of these findings, we suggest that the development of exocrine pancreatic functional impairment in patients with CP depends primarily on the degree of ductal changes, while parenchymal abnormalities play a less important role.

ISSN:0885-3177    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

In experimental models of pancreatitis lipid peroxidation products are increased possibly because of an enhanced generation of oxygen radicals. The purpose of this study was to determine whether lipid peroxidation products are increased in pancreatic tissue and serum of patients suffering from chronic or acute pancreatitis. In 20 patients undergoing operative treatment for chronic (n= 11) and acute pancreatitis (n= 9) the levels of malondialdehyde, conjugated dienes, and reduced and oxidized glutathione were determined in resected tissue samples. The excised tissue was examined and evaluated by light microscopy. Shortly before operation the serum concentrations of malondialdehyde, α-amylase, and lipase were measured. Pancreatic tissue from eight organ donors who had no abdominal trauma or pancreatic disease served as control. In chronic pancreatitis, conjugated dienes as well as malondialdehyde concentrations in the tissue were significantly elevated. Reduced glutathione was significantly decreased, suggesting glutathione depletion due to oxida-tive stress. In acute pancreatitis only the tissue and serum malondialdehyde levels were significantly high, whereas conjugated dienes remained within the normal range. Serum malondialdehyde levels correlated significantly with tissue concentrations (r= 0.76;p< 0.05) but not with the clinical course or the enzyme levels. In chronic pancreatitis, the increased tissue levels of lipid peroxidation products and the changes in glutathione metabolism suggest ongoing peroxidation of lipids due to an enhanced generation of oxygen radicals. In hemorrhagic necrotizing pancreatitis, however, oxygen radical-induced lipid peroxidation cannot be proven. Apparently, other patho-mechanisms are involved in the development of the severe tissue damage.

ISSN:0885-3177    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The present study was designed to investigate the effects of the carcinogenic agent azaserine on the induction of pancreatic and hepatic polyamine metabolism in rats. One single injection of 30 mg azaserine/kg body weight i.p. is known to induce adenoma and subsequently carcinoma, predominantly in the pancreas, after several months. Male Lewis rats were treated with either azaserine (30 mg/kg body weight i.p.) or saline and 5–10 animals per group were sacrificed 2, 6, 9, 12, 18, 24, and 48 h later. Furthermore, animals were simultaneously treated with the ornithine decarboxylase (ODC) inhibitor a-difluoromethylornithine (DFMO) or the polyamine oxidase inhibitor MDL 72527 and killed 6 and 12 h after azaserine injection. The azaserine-induced significant increase in pancreatic putrescine concentrations was accompanied by an increase in spermidine/spermineN1-acetyltransferase but unchanged ODC and was significantly inhibited byN, N′-bis(2,3-butadienyl)putrescine MDL 72527) but not by DFMO.S-Adenosylmethionine decarboxylase (SAM-DC) activity was significantly decreased in the pancreata of azaserine-treated animals compared to controls. In contrast, the azaserine-induced significant increase in hepatic putrescine was lower and transient, was accompanied by an increase in ODC and SAM-DC, and was completely inhibited by simultaneous DFMO treatment but not by MDL 72527. These data show completely different patterns of activation of polyamine metabolism in the pancreas and in the liver: Azaserine treatment forms putrescine in the liver by de novo synthesis via ODC only, while azaserine-induced pancreatic putrescine is exclusively produced by the intercon-version pathway via oxidation ofN1-acetylspermidine.

ISSN:0885-3177    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Free radicals have been implicated in β-cell destruction. Pancreatic antioxidant enzymatic defenses provide significant endogenous protection from these highly cytotoxic effector molecules. In our colony of BB rats, the reliability of peripheral blood lymphocyte count (PBLC) as a predictor of diabetes onset was assessed in 99 male and 110 female BB rats. In rats with a PBLC <4,200 mm3, 90% of males and 86% of females developed diabetes by 120 days of age and are designated “lymphopenic” or BBL. Rats with a PBLC >4,200 mm3have a much lower incidence of insulin-dependent diabetes mellitus (IDDM) and are designated “nonlymphopenic” or BBNL. In separate cohorts of normoglycemic (prediabetic) BBL rats (high risk for developing diabetes) and BBNL rats (low risk for developing diabetes), the activities of pancreatic cytosolic antioxidant enzymes, copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), and glutathione peroxidase (GPX) were determined. Alterations in CuZnSOD and CAT were noted in BBL males only as compared to BBNL males and BBL and BBNL females. CuZnSOD and CAT activities were significantly lower in BBL males. GPX showed a similar trend. The changes in pancreatic antioxidant enzymes precede overt hyperglycemia in male rats at risk for development of diabetes and may result in increased β-cell vulnerability to oxygen-derived free radical destruction.

ISSN:0885-3177    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The involvement of phospholipase D (PLD) in phosphatidylcholine hydrolysis by epidermal (EGF), insulin-like (IGF-I), and basic fibroblast (bFGF) growth factors was investigated in rat pancreatic acini. Acini were prelabeled with [3H]myristic acid which is mostly incorporated into phosphatidylcholine. EGF, IGF-I, and bFGF caused significant and dose-dependent increases in [3H]phosphatidic acid (PA) accumulation in the presence of propranolol, a phosphatidic acid phosphohydrolase inhibitor. The effects of EGF and IGF-I were significant after 5, 15, and 30 min of stimulation, whereas that of bFGF was evident only at 30 min. PA production in response to all three factors was dose dependent with maximal responses to EGF at 25 nM, to IGF-I at 16.5 nM, and to bFGF at 50 pM. Preincubation of acini with staurosporine, a protein kinase C and tyrosine kinase inhibitor, totally inhibited PA production by the three factors. Similarly, acini preincubation with genistein, a specific tyrosine kinase inhibitor, also neutralized the influence of the three factors on PA accumulation. In the presence of 1% ethanol, EGF, IGF-I, and bFGF caused significant phosphatidylethanol production after 20 min of incubation, thus confirming the involvement of PLD in PA production. These data present for the first time the description of a new signaling pathway through which EGF, IGF-I, and bFGF may operate to induce some of their specific effects on the pancreas in association with these growth factor receptors' tyrosine kinase activity.

ISSN:0885-3177    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Male athymic “nude” mice (ANM) of the USC colony manifest spontaneous fasting hyperglycemia and reduced glucose tolerance; it has been proposed that they may represent a model of nonobese non-insulindependent diabetes. Following the recent demonstration that insulin secretion from the isolated, perfused pancreas of the male ANM appears to be hypersensitive to glucose, the function of individual pancreatic islet β cells was investigated by measuring the membrane potential electrical activity. Initial studies demonstrated that the cyclic pattern of electrical activity in isolated female ANM islets is indistinguishable from that in control mouse islets. In contrast to control and female ANM β cells, in which 11.1 mMglucose evoked approximately 50% maximal electrical activity, this concentration evoked almost 80% maximal activity in male ANM β cells (p< 0.01). Investigating electrical responses at different glucose concentrations demonstrated that this increased sensitivity to glucose extends across the concentration range 2.8 to 22 mM. Assuming that in these islets, as in normal islets, electrical activity is associated with insulin release, these data indicate that the glucose-versus-insulin secretion dose-response is shifted to lower glucose concentrations at the level of the individual β cell. Although this study demonstrates that altered β-cell function occurs in the isolated islet of the male ANM, further investigation is under way to determine how the observed β-cell glucose hypersensitivity is related to the hyperglycemia and impaired glucose tolerance that develop in these animals in vivo.

ISSN:0885-3177    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

To elucidate the pathophysiology of diabetes mellitus in male WBN/Kob rats, we performed pancreatic perfusion experiments and histopathological studies. Intraperitoneal glucose tolerance tests showed a diabetic pattern in 12-month-old WBN/Kob rats. In perfused pancreata of WBN/Kob rats, both the first and the second phases of insulin secretion in response to a 16.7 mMglucose challenge were markedly reduced compared with those in age-matched Wistar rats (p< 0.01, respectively). Furthermore, the insulin secretion rate in response to glucopenia (1.4 mM) was significantly higher (p< 0.05) and the decrement in insulin secretion was significantly lower (p< 0.05) in WBN/Kob rats. The decrement in glucagon secretion with 16.7 mMglucose was significantly blunted (p< 0.001), and the glucagon secretion rate in response to glucopenia was also significantly lower in WBN/Kob rats than in controls (p< 0.01). Although insulin secretion in response to 10 mMarginine was also moderately reduced in WBN/Kob rats (p< 0.05), the glucagon secretion rates in response to 10 mMarginine were similar in the two groups. Histopathological examination revealed widespread disappearance of acinar cells and islets, inflammatory changes, and marked fibrosis in the pancreata of WBN/Kob rats. Irnrnunohistochemical studies showed decreased numbers of B cells in the islets of WBN/Kob rats. These findings suggest that this WBN/Kob rat strain is a useful model for studying not only pathogenesis, but also pathophysiology, i.e., defective hormonal secretion, in some types of human diabetes mellitus.

ISSN:0885-3177    

出版商:OVID    

年代:1995

数据来源: OVID