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

Polish accomplishments in clinical and experimental pancreatology concern acute (AP) and chronic (CP) pancreatitis. Special notice was drawn in Polish studies on hemostasis disorders in acute experimental pancreatitis (AEP), and resulting clinical implications (possibility of thrombotic-embolic complications leading to hemorrhagic defects associated with coagulation factors consumption). Studies on lysosomal hydrolases role in AEP pathogenesis were discussed. In those studies notice was drawn to initiating role of zymogen activation by lysosomal hydrolases, especially beta-glucuronidase, with smaller activity of acid phosphatase and cathepsin in this process. It was stated, that also lysosomal enzymes are released from macrophages obtained from bronchoalveolar lavage fluid in AEP. It was revealed that prostacyclin (PGI(2)) shows stabilizing effect on lysosomes in liver and kidneys in AEP. Platelets activating factor antagonist inhibits pulmonary lysosomal hydrolases activity in such conditions. Polish studies concerning reactive forms of oxygen role in AEP pathogenesis are one of the first in Europe. Oxidative-antioxidative balance was disturbed in acute pancreatitis course and associated multiorgan changes both under experimental conditions and in humans. Oxidative stress as an early prognostic symptom in AP in humans was also emphasized, showing correlation of oxidative stress indicators with phospholipase A serum activity and polymorphonuclear elastase in plasma of patients with different degree of this disease. In a range of clinical studies special attention should be given to studies concerning lipid disorders as an AP etiological factor in humans. Clear decrease in lipoprotein lipase activity in AP in humans was determined. Polish studies concerning importance of sphincterectomy in acute gallstone derivative pancreatitis (AGP) were presented. Polish researchers accomplishments in chronic alcoholic pancreatitis (CAP) etiopathogenesis were discussed.
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PMID:Pancreas; pancreatitis--Polish accomplishments. 1507 70

Melatonin, produced from L-tryptophan, protects the pancreas against acute damage by improving the antioxidative status of tissue. Melatonin receptors have been detected in the brain, but the contribution of these receptors to the pancreatic protection is unknown. The aim of our study was to compare the effects of melatonin precursor; L-tryptophan given intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) on the course of acute pancreatitis. Acute pancreatitis was induced by subcutaneous infusion of caerulein (5 microg/kg-h x 5 h). L-tryptophan was given i.p. (2.5, 25 or 250 mg/kg) or administered into right cerebral ventricle (0.02, 0.2 or 2.0 mg/rat) 30 min prior to the start of caerulein infusion. Plasma amylase, lipase and TNF alpha activities were measured to determine the severity of caerulein-induced pancreatitis (CIP). The lipid peroxidation products: malonylodialdehyde and 4-hydroksynonenal (MDA + 4-HNE) and activity of superoxide dismutase (SOD) were measured in the pancreas of intact or CIP rats with or without L-tryptophan pretreatment. Melatonin blood level was measured by RIA. CIP was confirmed by histological examination and manifested as an edema and rises of plasma levels of amylase, lipase and TNF alpha (by 550%, 1000% and 600%). MDA + 4-HNE was increased by 600%, whereas SOD activity was reduced by 75% in the pancreas of CIP rats. All manifestations of CIP were significantly reduced by pretreatment of the rats with L-tryptophan given i.c.v. at doses of 0.2 or 2.0 mg/rat, or by peripheral administration of this amino acid used at dose of 250 mg/kg i.p. In control rats plasma level of melatonin averaged about 40 +/- 2 pg/ml and was not significantly affected by CIP, by central application of L-tryptophan (0.02, 0.2 or 2.0 mg/rat) or by peripheral administration of this melatonin precursor used at doses of 2.5 or 25 mg/kg i.p. Plasma melatonin level was markedly increased by pretreatment of the rats with L-tryptophan given i.p. at dose of 250 mg/kg. We conclude that central administration of melatonin precursor; L-tryptophan, as well as peripheral application of high dose of this melatonin precursor prevented the pancreatic damage produced by CIP. The favorable effect of peripherally administered L-tryptophan could be related to the rise of melatonin plasma level and to pancreatoprotective action of this indoleamine. The beneficial effect of centrally administered L-tryptophan could be mediated through activation of central receptors for locally produced melatonin.
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PMID:Melatonin precursor; L-tryptophan protects the pancreas from development of acute pancreatitis through the central site of action. 1508 81

Serine proteases are attractive targets for the design of enzyme inhibitors since they are involved in the etiology of several diseases. Within the class of serine proteases, HLE is one of the most destructive enzymes in the body. It is implicated in the promotion or exacerbation of a number of diseases including pancreatitis, acute respiratory syndrome, rheumatoid arthritis, atherosclerosis, pulmonary emphysema, and cystic fibrosis. Thrombin, a trypsin-like serine protease, plays a dual role in thrombogenesis, including fibrin formation and platelet activation. As a result, thrombin constitutes one of the most widely studied targets for antithrombotic strategy. Numerous inhibitors of serine proteases have been reported during the past three decades. Among them, coumarin-type molecules displayed a high inhibitory potency towards various serine proteases. At that time, halomethyl dihydrocoumarins have been shown to behave as the first general suicide inhibitors of serine protease. These molecules inhibit several proteases such as human leucocyte elastase, porcine pancreatic elastase, thrombin, urokinase and human plasmin. Isocoumarins are very effective as mechanism-based inhibitors of serine proteases. Pharmacomodulation on the 3-alkoxy-4-chloroisocoumarins and the 3-alkoxy-7-amino-4-chloroisocoumarins led to strong inhibitors of numerous serine proteases such as HLE, human factor XIa and XIIa, thrombin, urokinase and kallikrein. Recently, a series of coumarins characterised by an alkyl, aryl ester, amide, thioester or ketone in the position 3 and an electrophilic chloromethyl moiety in the position 6 have been developed. These compounds were found to be high inhibitors of alpha-chymotrypin, HLE and human thrombin.
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PMID:Coumarin and isocoumarin as serine protease inhibitors. 1557 71

Severity stratification is a critical issue in acute pancreatitis that strongly influences diagnostic and therapeutic decision making. According to the widely used Atlanta classification, "severe" disease comprises various local and systemic complications that are associated with an increased risk of mortality. However, results from recent clinical studies indicate that these complications vary in their effect on outcome, and many are not necessarily life threatening on their own. Therefore, "severe," as defined by Atlanta, must be distinguished from "prognostic," aiming at nonsurvival. In the first week after disease onset, pancreatitis-related organ failure is the preferred variable for predicting severity and prognosis because it outweighs morphologic complications. Contrast-enhanced CT and MRI allow for accurate stratification of local severity beyond the first week after symptom onset. Among the biochemical markers, C-reactive protein is still the parameter of choice to assess attack severity, although prognostic estimation is not possible. Other markers, including pancreatic protease activation peptides, interleukins-6 and -8, and polymorphonuclear elastase are useful early indicators of severity. Procalcitonin is one of the most promising single markers for assessment of major complications and prognosis throughout the disease course.
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PMID:Predicting severity of acute pancreatitis. 1741 55

Bacterial endotoxin (lipopolysaccharide, LPS), at high concentration is responsible for sepsis, and neonatal mortality, however low concentration of LPS protected the pancreas against acute damage. The aim of this study was to investigate the effect of exposition of suckling rats to LPS on the course of acute pancreatitis at adult age. Suckling rat (30-40g) received intraperitoneal (i.p.) injection of saline (control) or LPS from Escherichia coli or Salmonella typhi (5, 10 or 15 mg/kg-day) during 5 consecutive days. Two months later these rats have been subjected to i.p. cearulein infusion (25 microg/kg) to produce caerulein-induced pancreatitis (CIP). The following parameters were tested: pancreatic weight and morphology, plasma amylase and lipase activities, interleukin 1beta (IL-1 beta), interleukin 6 (IL-6), and interleukin 10 (IL-10) plasma concentrations. Pancreatic concentration of superoxide dismutase (SOD) and lipid peroxidation products; malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) have been also measured. Caerulein infusion produced CIP in all animals tested, that was confirmed by histological examination. In the rats, which have been subjected in the neonatal period of life to LPS at doses 10 or 15 mg/kg-day x 5 days, all manifestations of CIP have been reduced. In these animals acute inflammatory infiltration of pancreatic tissue and pancreatic cell vacuolization have been significantly diminished. Also pancreatic weight, plasma lipase and alpha-amylase activities, as well as plasma concentrations of IL-1beta and IL-6 have been markedly decreased, whereas plasma anti-inflammatory IL-10 concentration was significantly increased in these animals as compared to the control rats, subjected in the infancy to saline injection instead of LPS. Caerulein-induced fall in pancreatic SOD concentration was reversed and accompanied by significant reduction of MDA + 4 HNE in the pancreatic tissue. The effects of LPS derived from E. coli or S. typhi were similar. Pretreatment of suckling rats with LPS at dose of 10 mg/kg-day x 5 days resulted in the most prominent attenuation of acute pancreatitis at adult age, whereas LPS at dose of 5 mg/kg-day x 5 days given to the neonatal rats failed to affect significantly acute pancreatitis induced in these animals 2 months later. We conclude that: 1/ Prolonged exposition of suckling rats to bacterial endotoxin attenuated acute pancreatitis induced in these animals at adult age. 2/ This effect could be related to the increased concentration of antioxidative enzyme SO in the pancreatic tissue and to the modulation of cytokines production in these animals.
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PMID:Endotoxemia in newborn rats attenuates acute pancreatitis at adult age. 1744 Feb 32


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