Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The level of adenosine 3':5'-cyclic monophosphate (cAMP) and the activity of adenyl cyclase were studied in the pancreas under normal conditions and during acute hemorrhagic pancreatitis induced by intraductal injection of fresh trypsin-bile-blood mixture. In addition, the adenyl cyclase was localized histochemically in the pancreas. Basal cAMP concentration and adenyl cyclase activity were 0.88 +/- 0.11 pmoles/mg wet tissue and 3.39 +/- 0.21 pmoles/mg protein/min, respectively. The acute pancreatitis drastically reduced the adenyl cyclase activity at 15 minutes to 1.66 +/- 0.54 pmoles/mg protein/min, and totally suppressed adenyl cyclase activity at 30 minutes after the onset of pancreatitis without affecting cAMP levels. The presence of sodium fluoride in the incubation medium prolonged the enzyme activity up to 45 minutes. The progressive disappearance of adenyl cyclase activity presumably resulted from the destruction of cellular integrity caused by autodigestion by the active proteolytic enzymes released during pancreatitis.
 ...
PMID:Adenyl cyclase and cyclic AMP (cAMP) in acute experimental pancreatitis. 18 29

In two cases of typical small-cell bronchial carcinoma (one of them peripheral, small and clinically not diagnosed) destructive parenchylmal metastases in the pancreas, carcinomatous lymphoangiosis and infiltration of the larger excretory ducts by tumour cells were demonstrated. In both the clinical course was dominated by tryptic pancreatitis with treatment-refractory hypokalaemia. Since pancreatic metastases occur in about 10% of bronchial carcinomas, tryptic pancreatitis is, however, only rarely observed. It is, therefore, likely that autodigestion occurs only if in addition to parenchymal destruction by the metastases there are other factors. These may be blockage of lymphatic flow by carcinomatous lymphangiosis and duct stenosis by tumour infiltration of the walls. Hypercorticism due to ectopic ACTH production by the small-cell carcinoma may also be factor, but is without proof.
 ...
PMID:[Tryptic pancreatitis in small-cell bronchial carcinoma (author's transl)]. 19 62

A series of 62 operated cases of acute necroto-hemorrhagic pancreatitis is presented along with discussion of the four principle objectives of surgical treatment: exposure, evaluation and selective resection of the lesions followed by close observation. Based on peroperative determination of anatomic site and macroscopic character, a double codification for each lesion is proposed. This codification provides the surgeon an objective basis for his choice of the type of procedure to be done. The surgery itself has a dual purpose: to eradicate frank necrosis and to protect the remaining tissue from autodigestion by installing one or more drains for irrigation and lavage of the lesion site. In the case of stage 3 necrosis, the procedure must include a left pancreatectomy of varying extent.
 ...
PMID:[Acute necrotizing pancreatitis and post-operative irrigation-lavage]. 54 93

The pathophysiology of pancreatic autodigestion is poorly understood. Pancreatitis affects all age groups, and the diagnosis is sometimes missed when serum amylase and lipase activities are not measured in the child with abdominal pain. Acute pancreatitis in children has become a more commonly seen condition and the causes have varied. Laboratory and radiological studies play an important role in determining the diagnosis and prognosis. Family history is important in the diagnosis of idiopathic hereditary pancreatitis. Most acute episodes resolve with supportive care, but the mortality in acute pancreatitis is currently about 15% (Hadorn et al., 1980). Endoscopic retrograde cholangiopancreatography or an endoscopic retrograde pancreatogram may be necessary to investigate relapses of pancreatitis. Chronic pancreatitis can be a life-threatening condition requiring lifetime medical management.
 ...
PMID:Pancreatitis in children. 147 58

1989 represents the 100th anniversary of Reginald Fitz's initial characterization of acute pancreatitis. Our current understanding of this disease has advanced little beyond Fitz's early description. While survival from pancreatitis has improved largely through advancements in critical care techniques, no medical or surgical therapy exists that can limit pancreatic autodigestion and inflammation. Recent investigations have suggested that pancreatitis may result from a disruption of normal stimulus-secretion coupling within the acinar cell. Future research based on these observations may ultimately result in successful therapy for this disease.
 ...
PMID:Acute pancreatitis at its centenary. The contribution of Reginald Fitz. 219 39

In severe necrotizing pancreatitis, the retroperitoneum is the main site both of autodigestion and of the production of toxins. With the aim of removing necrotic tissues and active enzymes from the retroperitoneum, we developed a surgical approach based on a wide exposure of the pancreas and on the insertion of multiple drainages with postoperative irrigations with hypertonic solutions and antiproteases. We treated 191 patients, and our results correlated with the timing of the operation. The operative mortality rate ranges from 8.1 in patients undergoing our procedure within 48 hours from the onset of the disease to 28.4 per cent when the operation was delayed for more than 96 hours. Our technique is detailed and the indications as to the timing of surgical treatment in instances of pancreatitis are discussed.
 ...
PMID:Retroperitoneal and peritoneal drainage and lavage in the treatment of severe necrotizing pancreatitis. 230 44

The mechanism leading to exocrine pancreatic disease in children differs from those encountered in adult patients: I. In acute pancreatitis autodigestion of the gland by proteolytic enzymes may occur and two mechanisms may play a role. 1. Reflux of biliary secretions (e.g. in malformations of the duct system) facilitates activation of trypsinogen by enteropeptidase and leads to the presence of active proteolytic enzymes in the gland (exogenous activation). 2. Lysosomal enzymes may play a role in the intracellular activation of zymogens if inflammation leads to a fusion of lysosomes with zymogen granules (endogenous activation). II. In chronic relapsing and hereditary pancreatitis malformations of the pancreatico-biliary duct system must be sought because surgery may be indicated (common channel syndrome and choledochal cysts). III. Among the hereditary diseases leading to pancreatic insufficiency cystic fibrosis (CF) plays the main role. Haplotype analysis has shown that two genetically different types of CF exists (PS and PI). The pancreas shows manifest insufficiency only in the PI-types which occur in more than 70% of cases but the distribution of haplotypes is different in different ethnic groups. In spite of the recent discovery of the cystic fibrosis gene the exact mechanism leading to exocrine pancreatic dysfunction in CF is not clear, but diminished chloride and bicarbonate secretion, may be the result of a disturbance in the regulation of chloride channels, on acinar or ductular level. In the Shwachman-Diamond syndrome a very severe type of exocrine insufficiency with unknown etiology is encountered at birth.
 ...
PMID:[Physiopathology of the exocrine pancreas in children]. 269 2

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.
 ...
PMID:Role of pancreatic enzymes and their substrates in autodigestion of the pancreas. In vitro studies with isolated rat pancreatic acini. 291 45

The appearance of vacuoles inside acinar cells characterizes an early stage of development in different models of acute pancreatitis and, possibly, also in human disease. The vacuoles have been shown to contain both digestive and lysosomal enzymes. This abnormal admixture may have important implications for the pathogenesis of pancreatitis because the lysosomal enzyme cathepsin B can activate trypsinogen and may, by this way, trigger pancreatic autodigestion. For the activation process of trypsinogen by cathepsin B, however, an acidic pH is required. This study, therefore, looked for evidence of vacuole acidification in two different models of acute pancreatitis. Edematous pancreatitis was induced in rats by hyperstimulation with cerulein and hemorrhagic pancreatitis was induced in mice by feeding a choline-deficient, ethionine-supplemented diet. Pancreatic acinar cells were isolated at different times after induction of pancreatitis and incubated with 50 microM of acridine orange to identify acidic intracellular compartments. As shown in previous work, zymogen granules are the main acidic compartment of normal acinar cells; they remained acidic throughout the course of pancreatitis in both models. Vacuoles became increasingly more frequent in both models as pancreatitis progressed. Throughout development of pancreatitis, vacuoles accumulated acridine orange indicating an acidic interior. Addition of a protonophore (10 microM monensin or 5 microM carbonyl cyanide m-chlorophenylhydrazone [CCCP] or a weak base (5 mM NH4Cl) completely and rapidly abolished acridine orange fluorescence inside both zymogen granules and vacuoles providing further evidence for an acidic interior. The acidification of vacuoles seen in two different models of pancreatitis may be an important requirement for activation of trypsinogen by cathepsin B and thus for the development of acute pancreatitis.
 ...
PMID:Intracellular vacuoles in experimental acute pancreatitis in rats and mice are an acidified compartment. 333 39

To study the regulation of the successive steps along the secretory pathway in the rat exocrine pancreas the model of in vivo infusion of synthetic caerulein in conscious rats for periods up to 72 h was combined with electron microscopy and in vitro analysis of protein synthesis, intracellular protein transport and enzyme discharge using isolated pancreatic lobules. Prolonged and maximal hormonal stimulation was obtained with 0.25 microgram kg-1 h-1 caerulein and resulted in a 80-90% depletion of enzyme stores within 1 to 3 h, followed by coordinate and anticoordinate changes in individual rates of (pro-)enzyme synthesis after a lag period of 3 h. One group (two amylases) revealed a decrease in synthesis to levels about 10-fold lower than controls. A third group of proteins (one trypsinogen, lipase, proelastase) did not show changes in synthesis with hormone stimulation. The sum of such alterations led to an increase in total rate of synthesis after 6 h, which was combined with acceleration of intracellular transport, packaging, and granule discharge, thus enabling a sustained rate of secretion over the period of stimulation. In contrast, infusion of a supramaximal dose of caerulein (5.0 micrograms kg-1 h-1) induced acute edematous pancreatitis and led to an almost complete reduction of volume and protein output from the cannulated main pancreatic duct. Using freeze-fracture techniques and thin-section electron microscopy, earliest structural alterations were observed at membranes of zymogen granules and the plasma membrane. Fusion of zymogen granules among each other led to formation of large membrane-bound vacuoles within the cytoplasm. These and individual zymogen granules fused with the lateral instead of the apical plasma membrane, discharging their content into the interstitial space. Vacuole formation was associated with activation of lysosomes and with cytoplasmic destruction of acinar cells. The findings indicated severe changes in the specificity of the intracellular membrane fusion process induced by supramaximal doses of caerulein, which finally resulted in autodigestion of the pancreas.
 ...
PMID:Structural and biochemical characterization of maximal and supramaximal hormonal stimulation of rat exocrine pancreas. 385 14


1 2 3 4 5 6 7 Next >>