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

A specific ELISA has been developed for the determination of alpha 1-proteinase inhibitor-bound leukocyte elastase in canine plasma and tissue fluids. Comparison of the sequence of the first 16 N-terminal amino acids of the isolated canine leukocyte elastase to other elastases indicated moderate homology with porcine pancreatic elastase and pronounced identity with human leukocyte elastase. Normal canine plasma contains about 66 micrograms/l leukocyte elastase measured as elastase alpha 1-proteinases inhibitor complexes. This represents about 70% of the total amount of leukocyte elastase released in plasma. The remaining 30% is bound by alpha 1 alpha 2-macroglobulin. Blood coagulation leads to a rapid release of elastase from the leukocytes. Slow intravenous infusion of a lethal dose of endotoxin into dogs is followed by a marked drop in leukocyte count and a simultaneous rapid increase in plasma leukocyte elastase concentration reaching a plateau level of 2-3 mg/l plasma. Bile-induced pancreatitis in dogs is accompanied by successive increases in leukocyte elastase levels in plasma as well as in peritoneal exudates, reaching a level of about 15 mg/l in the exudates during the late stages of disease.
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PMID:Release of immunoreactive canine leukocyte elastase normally and in endotoxin and pancreatitic shock. 169 Apr 43

Complexes of alpha 1-proteinase inhibitor and leukocyte elastase could be demonstrated by crossed immunoelectrophoresis of the peritoneal fluid from four patients who developed a pancreatic abscess during an attack of pancreatitis. No such complexes were seen in 69 patients with acute pancreatitis without an abscess. The complexes were demonstrable 2-3 days before the abscess was clinically evident. They may thus be diagnostically and therapeutically important. The appearance of these complexes denotes the liberation of large amounts of leukocyte elastase. This may help explain the pathophysiology and high mortality of the pancreatic abscess, since leukocyte elastase is known to cause degradation of all components of connective tissue and also degradation and activation of many components within the different cascade systems.
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PMID:Leukocyte elastase alpha 1-proteinase inhibitor complexes may diagnose pancreatic abscesses early. 348 7

Proteases have a wide range of functions: digestion (pancreatic proteases), protein catabolism (lysosomal proteases), blood coagulation, immune defences (complement), cellular division and proliferation, generation of biologically active oligopeptides (kinins, hormones) from inactive polypeptide precursors, inactivation of these oligopeptides, etc. The body protects itself against its own proteases, either by confining them to a given compartment (lysosome), by synthesising them in the form of inactive precursors (trypsinogen, prothrombin, etc.), or by synthesising proteins with an antiprotease activity. Any disturbance in one of the elements of this protective system may lead to severe pathological consequences: acute hemorrhagic pancreatitis with shock, coagulation disturbances (deficient hepatic synthesis of coagulation factors, congenital antithrombin III deficiency), angioneurotic oedema (congenital deficiency of C'l esterase inhibitor) pulmonary emphysema (local secretion of leukocyte elastase, congenital deficiency of alpha a-antitrypsin).
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PMID:[Problems in intensive care posed by imbalance in the protease--protease inhibitor system]. 611 Dec 72

The role of the inflammatory response in acute pancreatitis and its relation with the clinical course was examined. This study examined if the serial measurement of polymorphonuclear granulocyte (PMN) elastase/A1PI complex, phospholipase A catalytic activity, C reactive protein, and other acute phase proteins, and the protease inhibitor alpha 2-macroglobulin, provides meaningful information for prognosis. Eighty non-consecutive patients with acute pancreatitis, classified according to their clinical outcome into mild (n = 40) and severe pancreatitis (n = 40), were followed up daily. Between 48 hours, median values of PMN-elastase, C reactive protein--and most of the acute phase proteins--and phospholipase A activity, were significantly higher in the severe pancreatitis group. PMN elastase shows a dynamic course and it reaches an early peak value at days 1-2, followed by C reactive protein (days 2-4) phospholipase A (day 3), and a negative peak for alpha 2-macroglobulin (days 4-5). PMN elastase (day 1) and C reactive protein (day 2) were selected by discriminant analysis as the most useful variables studied to allow the early accurate prediction of severity (sensitivity 100%, specificity 95%). Little or no predictive additional value was found for all other variables studied. These results strongly suggest a close relation between inflammatory parameters and clinical course in acute pancreatitis, and discriminant analysis of these variables provides a useful method to classify severity.
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PMID:Inflammatory response in the early prediction of severity in human acute pancreatitis. 751 79

Levels of leukocyte elastase and neutrophil protease 4 (NP4(3)) in plasma and peritoneal exudate were studied in 25 patients with severe, acute pancreatitis. Pancreatitis was diagnosed from the clinical picture and an increased serum amylase level. The diagnosis was verified by computerized tomography, ultrasound, and findings at operation or autopsy. Peritoneal exudate on admission contained high concentrations of leukocyte elastase (6100 +/- 2000 micrograms/l) and NP4(3) (2310 +/- 900 micrograms/l). High initial levels were found also in plasma, which contained 659 +/- 110 micrograms/l of leukocyte elastase and 254 +/- 33 micrograms/l of NP4(3). The levels in plasma were still increased 3 weeks after the acute attack, also in the absence of complications, indicating that the resolution of acute pancreatitis is a protracted process. Plasma levels of both leukocyte proteases were persistently increased in patients with pancreatic abscess, in contrast to the gradual decrease seen in patients with a pseudocyst or uncomplicated recovery. The levels were increased already before the abscess was diagnosed clinically, which indicates that determinations of leukocyte elastase and NP4(3) may be helpful in detecting this complication. A pathophysiologic role for leukocyte proteases in the development of severe, acute pancreatitis should be considered.
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PMID:Levels of leukocyte proteases in plasma and peritoneal exudate in severe, acute pancreatitis. 804 15

In acute pancreatitis, particularly in severe cases, polymorphonuclear neutrophil (PMN) elastase induces tissue damage in remote organs such as the lung, as well in the pancreas itself. Therefore, we examined the therapeutic effect of a specific synthetic inhibitor of PMN elastase (ONO-5046: Ono Pharmaceuticals, Osaka, Japan) on the lung, liver, and kidney, as well as pancreas, in severe hemorrhagic pancreatitis in dogs. Acute hemorrhagic pancreatitis was induced by the injection of a mixture of autologous bile and porcine trypsin into the main pancreatic duct. Lipopolysaccharide (LPS) was administered intravenously as a septic challenge. Two animal groups were used. In one group, continuous infusion of ONO-5046 was started prior to the injection of LPS (ONO group). In the other group (control), saline was infused instead. At the end of the experiment (330 min after the injection of bile and trypsin), the pancreas revealed severe hemorrhagic pancreatitis, and a large amount of bloody ascites had accumulated in the peritoneal cavity. The white blood cell count was markedly reduced in response to the induction of pancreatitis, and was decreased further by the septic attack, irrespective of the administration of ONO-5046, although the count increased again in the ONO group. Serum levels of amylase and alpha2-macroglobulin-trypsin complex increased similarly in both groups following administration of bile and trypsin. Serum Ca levels decreased in both groups. At the end of the experiment, the wet weight of the lung was slightly higher in the control group (without ONO-5046). Microscopically, the pancreas showed severe hemorrhage accompanied by extensive interstitial edema in both groups. The lung and liver demonstrated mild infiltration of inflammatory cells in the interstitium in both groups, although the inflammatory change in the liver was slightly milder in the ONO group. These findings indicate that severe hemorrhagic pancreatitis cannot be alleviated by the administration of a specific inhibitor of PMN elastase alone, although this may lessen damage to remote organs such as the liver and lung. The white blood cell count decreased markedly after the induction of acute pancreatitis, and much more after a septic challenge. This seems to be closely related to the accumulation of bloody ascites in the peritoneal cavity.
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PMID:Effect of a specific synthetic inhibitor of neutrophil elastase (ONO-5046) on the course of acute hemorrhagic pancreatitis in dogs. 993 92

Central nervous system affects pancreatic secretion of enzymes however, the neural modulation of acute pancreatitis has not been investigated. Leptin and melatonin have been recently reported to affect the inflammatory response of various tissues. The identification of specific receptors for both peptides in the pancreas suggests that leptin and melatonin could contribute to the pancreatic protection against inflammation. The aim of this study was: 1/ to compare the effect of intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) administration of leptin or melatonin on the course of caerulein-induced pancreatitis (CIP) in the rat, 2/ to examine the involvement of sensory nerves (SN) and calcitonin gene-related peptide (CGRP) in pancreatic protection afforded by leptin or melatonin, 3/ to assess the effect of tested peptides on lipid peroxidation products (MDA + 4-HNE) in the pancreas of CIP rats, 4/ to investigate the influence of leptin or melatonin on nitric oxide (NO) release from isolated pancreatic acini and 5/ to determine the effects of caerulein and leptin on leptin receptor gene expression in these acini by RT-PCR. CIP was induced by subcutaneous (s.c.) infusion of caerulein (25 microg/kg) to the conscious rats, confirmed by the significant increases of pancreatic weight and plasma amylase and by histological examination. This was accompanied in marked reduction of pancreatic blood flow and significant rise of MDA + 4-HNE in the pancreas. Leptin or melatonin were administered i.p. or i.c.v. 30 min prior to the start of CIP. Deactivation of SN was produced by s.c. capsaicin (100 mg/kg). An antagonist of CGRP, CGRP 8-37 (100 microg/kg i.p.), was given together with leptin or melatonin to the CIP rats. MDA + 4-HNE was measured using LPO commercial kit. NO was determined using the Griess reaction. Pretreatment of CIP rats with i.p. leptin (2 or 10 microg/kg) or melatonin (10 or 50 mg/kg) significantly attenuated the severity of CIP. Similar protective effects were observed following i.c.v. application of leptin (0.4 or 2 microg/rat) but not melatonin (10 or 40 microg/rat) to the CIP rats. Capsaicin deactivation of SN oradministration of CGRP 8-37 abolished above beneficial effects of leptin on CIP, whereas melatonin-induced protection of pancreas was unaffected. Pretreatment with i.p. melatonin (10 or 50 mg/kg), but not leptin, significantly reduced MDA + 4-HNE in the pancreas of CIP rats. Leptin (10(-10) - 10(-6) M) but not melatonin (10(-8) - 10(-5) M) significantly stimulated NO release from isolated pancreatic acini. Leptin receptor gene expression in these acini was significantly increased by caerulein and leptin. We conclude that 1/ central or peripheral pretreatment with leptin protects the pancreas against its damage induced by CIP, whereas melatonin exerts its protective effect only when given i.p., but not following its i.c.v. adminstration, 2/ activation of leptin receptor in the pancreatic acini appears to be involved in the beneficial effects of leptin on acute pancreatitis, 3/ the protective effects of leptin involve sensory nerves, CGRP and increased generation of NO whereas melatonin-induced protection of the pancreas depends mainly on the antioxidant local effect of this indole, and scavenging of the radical oxygen species in the pancreatic tissue.
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PMID:Sensory nerves in central and peripheral control of pancreatic integrity by leptin and melatonin. 1193 19

Melatonin, a pineal secretory product, synthesized from l-tryptophan, has received increased attention because of its antioxidative and immunomodulatory properties. It has been detected in the gut and shown to protect the gastric mucosa, and liver from acute damage, but the role of melatonin in the protection of the pancreas against acute inflammation is not clear. The aim of this study was to investigate the effects of melatonin and its precursor, l-tryptophan, on caerulein-induced pancreatitis (CIP) and on ischemia/reperfusion (I/R)-provoked pancreatitis in rats. CIP was induced by subcutaneous infusion of caerulein to the rats (25 microg/kg). I/R was induced by clamping of the inferior splenic artery for 30 min followed by 2 hr of reperfusion. Melatonin (10, 25 or 50 mg/hr) or l-tryptophan (50, 100 or 250 mg/kg) was given as a bolus intraperitoneal (i.p.) injection 30 min prior to the onset of pancreatitis. CIP and I/R were confirmed by histologic examination and manifested by typical pancreatic edema, by an increase of plasma levels of amylase (by 500% in CIP and by 40% in I/R) and the pro-inflammatory tumor necrosis factor alpha (TNFalpha) (by 500%). Lipid peroxidation products such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), were increased several fold in the pancreas CIP and I/R, whereas pancreatic blood flow (PBF) was significantly reduced in these animals. Pretreatment of rats subjected to CIP or to I/R with melatonin (25 or 50 mg/kg i.p.) or l-tryptophan (100 or 250 mg/kg i.p.) significantly reduced pancreatic edema, plasma levels of amylase and TNFalpha and diminished pancreatic MDA + 4-HNE contents, while enhancing PBF, pancreatic integrity and plasma levels of the anti-inflammatory interleukin 10 (IL-10). This was accompanied by a marked and dose-dependent rise of plasma melatonin immunoreactivity. Gene expression of N-acetyl transferase, an enzyme involved in melatonin biosynthesis, was detected in the pancreas of normal rats and was significantly enhanced in the rats with CIP. We conclude that exogenous melatonin, and that produced from l-tryptophan, attenuates pancreatic damage induced by CIP or by I/R and this effect may be attributable to the reduction in lipid peroxidation and TNFalpha release combined with an increase of plasma anti-inflammatory IL-10 in rats with acute pancreatitis.
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PMID:Protective effect of melatonin and its precursor L-tryptophan on acute pancreatitis induced by caerulein overstimulation or ischemia/reperfusion. 1248 71

The present study investigated the involvement of endogenous melatonin in the prevention of pancreatic damage provoked by caerulein-induced pancreatitis (CIP) by using the luzindole, the antagonist of melatonin MT2 receptors. CIP was produced by subcutaneous infusion of caerulein to conscious rats (25 microg/kg). Luzindole (1, 2 or 4 mg/kg) was given as an intraperitoneal bolus injection 30 min prior to the start of CIP. Lipid peroxidation products, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were measured in the pancreas by LPO-584 commercial kit. CIP was confirmed by histological examination and manifested by significant increases of plasma activities of amylase, lipase and tumor necrosis factor alpha (TNFalpha) (by 500%, 1000% and 600%, respectively) comparing to the control values. This was accompanied by a 40% limitation in pancreatic blood flow (PBF) and by 200% increase of MDA+4-HNE in the pancreas of CIP rats. Administration of luzindole to the CIP rats reduced PBF, aggravated the histological manifestations of pancreatitis, resulted in the significant augmentation of pancreatic MDA + 4-HNE content, and produced the marked increases of plasma levels of lipase, amylase and TNFalpha, comparing to the values observes in the rats with CIP alone. These results suggest that endogenous melatonin through its receptor MT2 plays an important role in the attenuation of pancreatic damage produced by overstimulation with caerulein.
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PMID:Role of endogenous melatonin and its MT2 receptor in the modulation of caerulein-induced pancreatitis in the rat. 1251 Aug 64

In a patient with an undiagnosed pleural effusion, the first question to answer is whether the fluid is an exudate or a transudate. This is usually determined by means of Light's criteria, which differentiate transudative effusions from exudative effusions by measuring the levels of total protein and lactate dehydrogenase in the pleural fluid (PF) and serum. In patients under diuretic treatment, Light's criteria misclassify transudates as exudates, but the serum to pleural fluid albumin gradient usually remains above 12 g/L. When tests are done only in PF, protein concentration >30 g/L performs at least as well as the other individual markers. To diagnose tuberculous pleuritis among exudates, PF adenosine deaminase and PF interferon-g exhibit high diagnostic accuracy. When malignancy is suspected the addition of tumour markers to the results of cytologic analysis increases the rate of detection. Other biochemical markers are useful in specific circumstances involving pleural effusion, such as amylase in effusions due to pancreatitis, or oesophageal rupture, and triglycerides in chylothorax. Several PF markers are associated with complicated parapneumonic effusion - e.g. low PF pH and glucose, and high PF LDH activity -- although PF pH appears to be the best biochemical aid in decisions regarding chest tube drainage. Recent reports suggest that neutrophil-derived enzymes (polymorphonuclear elastase and myeloperoxidase) can be useful as early indicators of the need of chest tube insertion; however these findings must be confirmed in large series. This review discusses the clinical usefulness of biochemical markers in the diagnosis and management of pleural effusions. The vast majority of prospective studies in this field have been conducted in adults and, although the mechanisms of pleural effusion production do not differ in children and adults, the prevalence of each etiologic cause does. Therefore it seems advisable to confirm or recalculate the predictive values of each marker in the paediatric population.
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PMID:Useful clinical biological markers in diagnosis of pleural effusions in children. 1498 Feb 72


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