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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examines the influence of ovariectomy and administration of a pharmacologic dose of estradiol on amylase release from isolated-dispersed rat pancreatic acini and cholecystokinin receptors on rat acinar cell membranes. Rats were sham ovariectomized (intact) or ovariectomized (Ovx) and 21 day timed release pellets containing either estradiol (2.5 mg) or vehicle, were implanted subcutaneously. Eighteen days later, pancreatic acini were isolated from rats by collagenase digestion and differential centrifugation. Total cellular amylase, basal and cholecystokinin octapeptide (CCK8) stimulated amylase release and CCK membrane receptors were measured. Acini isolated from estradiol treated Ovx rats had significantly greater total cellular amylase, compared to acini isolated from either intact or Ovx rats. The amplitude of both total stimulated amylase release and percent total stimulated amylase release were significantly greater for acini isolated from vehicle treated Ovx rats, than acini isolated from either intact or estradiol treated Ovx rats. The magnitude of percent total amylase release of acini isolated from estradiol treated Ovx rats was significantly lower than that of acini isolated from intact rats. Cholecystokinin receptor concentration was significantly greater on membranes prepared from vehicle treated Ovx rats, compared to membranes prepared from either intact or estradiol treated Ovx rats. These data indicate that ovariectomy is associated with increased responsiveness of pancreatic acini to CCK stimulation, while chronic estradiol treatment of ovariectomized rats is associated with increased total cellular amylase and decreased acinar cell responsiveness to CCK8. Estrogen mediated alterations in acinar cell amylase content and amylase release may play a role in estrogen related pancreatitis.
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PMID:Estrogens influence cholecystokinin stimulated pancreatic amylase release and acinar cell membrane cholecystokinin receptors in rat. 170 70

Minced pancreas or a collagenase solution alone had no effect on blood pressure when infused into experimental animals. However, collagenase digested fragments or the digested pancreatic supernatant (PSF) produces profound hypotension. Previously we have shown that aprotinin, a proteolytic enzyme inhibitor, successfully blocked PSF-induced hypotension in the pig but did not alter this hypotension in the dog or monkey. Species variability of aprotinin blockade was further investigated by infusing PSF from either the pig, dog, or monkey into five animals of the other two species ("across species"). PSF alone produced hypotension in every animal "across species" but PSF "across species" and in combination with aprotinin did not produce a hypotensive reaction in each "across species" combination. These species differences of the aprotinin blockade should be considered when seeking reasons why aprotinin has not proven effective in preventing the morbidity and mortality of human pancreatitis.
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PMID:Effectiveness of aprotinin in blocking a hypotensive factor of pancreatic origin from the pig, dog and monkey. 240 75

Intrapancreatic activation of proteases is believed to play a major role in the pathogenesis of acute necrotizing pancreatitis. Several authors have questioned, however, the central role of trypsin in autodigestion of the pancreas. To clarify the direct effects of pancreatic enzymes and other related factors on acinar cells, we used the model of isolated pancreatic acini. Acini were prepared from male Wistar rats by collagenase digestion. Protein synthesis was measured by incubation of acini with [35S]methionine. Acini were resuspended thereafter in fresh buffer and further incubated for 30-90 min under various conditions [e.g., with pancreatic homogenates, ascites (from rats with pancreatitis induced by sodium taurocholate), pure pancreatic enzymes, and other factors]. The percentage of release of newly synthesized proteins into the culture medium was regarded as a biochemical parameter of cellular integrity. A morphologic score of cellular integrity was obtained via light microscopic evaluation of acini at the end of the various incubations by measuring the degree of cell lysis, loss of cell granules, ballooning, formation of vacuoles, and karyopyknosis. When normal [35S]methionine-labeled pancreatic acini were incubated with various factors, the percentage of release of labeled proteins into the medium was as follows: incubation with HEPES/Ringer's buffer, 1.8%; hemorrhagic pancreatic ascites, 3.8%; pancreatic homogenates, 2.0%; lipase, 1.8%; phospholipase A2, 3.0%; phospholipase A2 + lecithin, 3.2%; trypsin, 2.5%; 5% olive oil, 1.8%; ascites + olive oil, 78.3%; ascites + homogenized epididymal fat, 79.9%; lipase + olive oil, 32.0%; pancreatic homogenates + olive oil, 28.0%; diolein, 2.65%; and oleic acid, 62.9%. The cellular release of radiolabeled proteins showed an inverse correlation with cellular integrity as shown by light microscopy. We postulate that interstitial release of degradation products from triglycerides by lipase causes cellular disruption. Whereas phospholipase A2 and proteases do not seem to be very harmful in the early phases of cellular damage, lipase may play a major role in acute necrotizing pancreatitis.
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PMID:Role of pancreatic enzymes and their substrates in autodigestion of the pancreas. In vitro studies with isolated rat pancreatic acini. 291 45

In order to study the changes of lipid metabolism in acute pancreatitis, the following experiments were performed in monogrel dogs. Bile-induced pancreatitis (severe type) and collagenase-induced pancreatitis (mild type) were prepared, and changes of FFA, TG, IRI and IRG were determined for one week. In addition, IVFTT and PHLA were determined at 24th hour, on the 3rd day and 7th day. A rise of FFA was observed during the first 24 hours, which was considered the lypolytic stage. On the 3rd day TG reached the maximal level, while K values in IVFTT and PHLA showed the lowest levels. The above results suggest that the elimination mechanism of TG was impaired on the 3rd day. Changes of FFA, TG, IRI and IRG showed marked differences between the two groups. Therefore it is thought that lipid metabolism in acute pancreatitis is regulated by balance of endogenous pancreatic hormones.
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PMID:[Lipid metabolism in experimental acute pancreatitis]. 329 13

The early pathogenetic steps that finally lead to acinar cell necrosis in acute pancreatitis have been characterized only scarcely as yet. Among a lot of hypotheses, one concept favors disturbances of cellular energy metabolism as a major factor that contributes to preterm cell decline. To investigate, whether an experimental acute pancreatitis alters cell respiration, the respiratory capacities of acinar cells isolated from rats with acute pancreatitis were measured. Acute pancreatitis was induced using Popper's model, i.e., a combination of duct obstruction, secretory stimulation, and mesenteric short-term ischemia with subsequent reperfusion. Acinar cells were isolated using a collagenase digestion technique. The respiratory rates of the isolated cells in suspension were measured at 37 degrees C in 100% oxygen-saturated N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-buffered Eagle's-minimal essential medium. Resting respiration of the acinar cells uniformly amounted to about 60 pmol of O2/s x 10(6) cells in both the control and the pancreatitis group. Cellular respiration could significantly be stimulated by stepwise uncoupling of oxidative phosphorylation by means of 2,4-dinitrophenol in all cell suspensions investigated. The maximum rate of stimulated respiration was diminished in the cells isolated from rats with acute pancreatitis as compared with the controls (79.3 +/- 5.0 vs. 160.2 +/- 15.5 pmol of O2/s x 10(6) cells, p < .05), however. This reduced respiratory load capacity of the acinar cells in acute pancreatitis reflects the restricted ability of the cells to increase respiration on enhanced cellular demand. Since mitochondrial respiration is coupled to oxidative phosphorylation, an altered energy-transforming potential of the acinar cells in acute pancreatitis becomes evident.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acinar cell respiration in experimental acute pancreatitis. 777 97

Some recent proposals in management of alcoholic liver disease are discussed focusing on early diagnosis and treatment of alcohol abuse itself, alcoholic hepatitis early mortality, clinical meaning of nutritional therapy, serological approach and treatment of hepatic fibrosis, and problems in liver transplantation for end stage alcoholic liver cirrhosis. CAGE or similar systematized brief questionnaires, and desialylated transferrin/total transferrin ratio as serological marker, seems to be interesting contributions to "hidden" alcohol abuse diagnosis and abstinence control while psycho-social support and voluntary incorporation to self-aid groups are the best weapons to reach persistent abstinence. Corticosteroids seems to improve survival in a selected group of patients with severe alcoholic hepatitis, specially in those presenting encephalopathy but free of GI bleeding, decompensated diabetes, active infections, pancreatitis, and other contraindications or adverse effects of these drugs. Relationship between direct toxicity and nutritional deficiencies in pathogenesis of alcoholic liver injury are not clear enough, but malnutrition is generally present in patients requiring hospitalization, and related to clinical severity; oral, enteral or parenteral nutritional supplementation in this order of preference according to patients condition, associated or not with steroid anabolics, are useful in cases with moderate to severe alcoholic hepatitis or decompensated cirrhosis to eliminate the catabolic state, reaching a better nitrogen balance and liver function tests, without special adverse effects. A special role on liver regeneration is discussed. Antioxidants and supernutrients are special "modern" aspects of nutritional therapy in alcoholic liver disease generally related to the MEOS activation in chronic alcoholism, the excessive production of free radicals, and the depletion of glutathione, membrane phospholipids (specially phosphatidycholine), and vitamin A, E, and C. Natural supplements as soybean polyunsaturated lecithin, with high concentration of phosphatidycholine, or oral supplementation with natural metabolic products depleted from the liver of chronic heavy drinkers, such SAMe, have an interesting rationale based on experimental and clinical findings besides availability and costs. Carotenoids and tocopherols supplementation seems to be an useful tool, but are limited in the case of vitamin A because its special toxicity in chronic alcoholism. Serological markers of metabolism of liver connective tissue are clearly involved in fibrogenesis process and other inflammatory connected events; standardization of laboratory methods surely will result in new possibilities of non-invasive valuation of liver injury, evolution and therapeutic response; special histological damage such as sinusoidal "cappilarization" (type i.v. collagen and laminin), endothelial sinusoidal cell function (seric hyaluronate), or collagenase activity (TIMP-1 or tissue inhibitor of metalloproteinases-1) seems to be valuable by these new technologies.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[New suggestions for the management of alcoholic liver diseases]. 852 63

Interleukin-1 beta (IL-1) is a proinflammatory cytokine which is produced within the pancreas during acute pancreatitis reaching levels which are toxic to many cell types. Since antagonism of this cytokine provides dramatic survival benefits during lethal pancreatitis, we hypothesized that IL-1 had direct secretagogue and cytolytic effects within the pancreas. The effect of IL-1 on pancreatic exocrine function and tissue viability was assessed in vivo by blockade of IL-1 with varying doses of IL-1 receptor antagonist (IL-1ra) prior to the induction of either moderate (caerulein-induced) or severe (choline deficient diet-induced) necrotizing pancreatitis. Subsequent in vitro studies were conducted to determine the direct effect of IL-1 on dispersed rat acini prepared through collagenase digestion. Amylase release was measured after a 30-min incubation with varying doses of recombinant IL-1 beta. Viability was determined in the presence of IL-1 via trypan blue exclusion at multiple time points. Blockade of the IL-1 receptor decreased pancreatic amylase release and tissue necrosis in both models of pancreatitis in a dose-dependent fashion (1.0 mg/kg, P = NS; 10 mg/kg, P < 0.05; 100 mg/kg, P < 0.05). Despite these in vivo findings, the addition of IL-1 to acini in vitro had no effect on exocrine function and failed to decrease acini viability (both, P = NS). Pancreatic amylase release and tissue necrosis are significantly attenuated during experimental pancreatitis by IL-1 antagonism. These changes do not appear to be due to the direct action of IL-1 on pancreatic acini and are likely due to more complex interactions between acini and cytokine-producing leukocytes.
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PMID:Acute pancreatitis-induced enzyme release and necrosis are attenuated by IL-1 antagonism through an indirect mechanism. 907 Jan 89

It was reported that free fatty acids degraded from triglycerides by lipase may play a major role in acute necrotizing or hyperlipidemia-induced pancreatitis. We hypothesized that this injury may be related to the peroxidation of cell membrane phospholipids and tested this hypothesis using isolated pancreatic acini. Pancreatic acini were prepared from male Sprague-Dawley rats by collagenase digestion. Linoleic acid was added (0.1-1.0 mM) to the acinar cell suspension to induce cell injury. Acinar cell damage was measured by lactate dehydrogenase release and by trypan blue exclusion. Phosphatidylcholine hydroperoxide and alpha-tocopherol in the acinar cells were measured. Protective effects of alpha-tocopherol (0.5, 5.0 mM) against this type of cell injury were also evaluated. When isolated acinar cells were treated with linoleic acid, a significant decrease in viability was observed in a time- and dose-dependent manner. In addition, the levels of phosphatidylcholine hydroperoxide after treatment of 0.5 mM of linoleic acid were increased and levels of alpha-tocopherol were decreased significantly. alpha-Tocopherol significantly ameliorated both cellular injury (p < 0.01) and increases in phosphatidylcholine hydroperoxide (p < 0.01). These data suggest that lipid peroxidation of the cellular membrane is an important component of the pancreatic cell injury mediated by free fatty acids.
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PMID:Involvement of lipid peroxidation in free fatty acid-induced isolated rat pancreatic acinar cell injury. 982 Nov 80

We investigated the time-course of changes in pancreatic fibrosis accompanied with pancreatitis in WBN/Kob rats. The areas of fibrosis and fatty replacement were analysed morphometrically, and biochemical measurements of pancreatic and plasma prolyl hydroxylase and of pancreatic collagenase were assessed. Male rats showed acute pancreatitis at 2-3 months of age, lesions that later underwent a transition to widespread fibrosis. The fibrosis then decreased, and the fibrotic tissue was replaced with adipose tissue. Morphometrically, the fibrotic area reached its maximal size when the rats were 4 months old, diminishing thereafter. The fibrosis occurred mainly in the intralobular space, and was principally attributable to type-III collagen. Type-I collagen scarcely appeared throughout the experimental period. Alpha-Smooth muscle actin appeared in and around myofibroblasts that developed in an early stage and diminished later in accordance with the progressive manner of fibrosis. The plasma prolyl hydroxylase level was higher in males than in females from 4 through 10 months of age. Pancreatic collagenase activity in the males also increased during the same period. These findings suggest that pancreatic fibrosis in male WBN/Kob rats is affected by the balance between prolyl hydroxylase and collagenase.
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PMID:Histopathological and biochemical studies on pancreatic fibrosis in WBN/Kob rats. 1007 Dec 40

Disruption or absence of hepatocyte keratins 8 and 18 is associated with chronic hepatitis, marked hepatocyte fragility, and a significant predisposition to stress-induced liver injury. In contrast, pancreatic keratin disruption in transgenic mice that express keratin 18 Arg89 --> Cys (K18C) is not associated with an obvious pancreatic pathology. We compared the effects of keratin filament disruption on pancreatic acini or acinar cell viability, and on cholecystokinin (CCK)-stimulated secretion, in transgenic mice that overexpress wild-type keratin 18 and harbor normal extended keratin filaments (TG2) and K18C mice. We also compared the response of these mice to pancreatitis induced by a choline-deficient ethionine-supplemented diet or by caerulein. Despite extensive cytoplasmic keratin filament disruption, the apicolateral keratin filament bundles appear intact in the acinar pancreas of K18C mice, as determined ultrastructurally and by light microscopy. No significant pancreatitis-associated histologic, serologic, or F-actin/keratin apicolateral redistribution differences were noted between TG2 and K18C mice. Acinar cell viability and yield after collagenase digestion were lower in K18C than in TG2 mice, but the yields of intact acini and their (125)I-CCK uptake and responses to CCK-stimulated secretion were similar. Our results indicate that keratin filament reorganization is a normal physiologic response to pancreatic cell injury, but an intact keratin cytoplasmic filament network is not as essential in protection from cell injury as in the liver. These findings raise the possibility that the abundant apicolateral acinar keratin filaments, which are not as evident in hepatocytes, may play the cytoprotective role that is seen in liver and other tissues. Alternatively, identical keratins may function differently in different tissues.
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PMID:Effects of keratin filament disruption on exocrine pancreas-stimulated secretion and susceptibility to injury. 1069 32


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