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)

The inhibitory effect of gabexate mesylate, which is used therapeutically in the treatment of pancreatitis and disseminated intravascular coagulation, and as a regional anticoagulant agent for hemodialysis, has been measured on bovine factor Xa, bovine alpha-thrombin, human Lys77-plasmin, human urinary kallikrein, human urokinase, porcine pancreatic beta-kallikrein-B, and bovine beta-trypsin catalyzed hydrolysis of p-nitrophenyl esters of N-alpha-carbobenzoxy-L-arginine and N-alpha-carbobenzoxy-L-lysine. On the basis of enzyme:gabexate mesylate affinities, the serine proteases can be arranged as follows: human urinary kallikrein approximately porcine pancreatic beta-kallikrein-B much less than bovine beta-trypsin approximately bovine factor Xa approximately human Lys77-plasmin approximately human urokinase approximately bovine alpha-thrombin. The mode of binding of gabexate mesylate to the serine proteases conforms to the active-reactive site geometries observed in their complexes with natural and synthetic inhibitors. Differences in gabexate mesylate affinities for these proteases reflect structural differences at their primary specificity subsite, which have been investigated by comparative analysis of amino acid sequences and by computer-graphics techniques.
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PMID:Gabexate mesylate inhibition of serine proteases: thermodynamic and computer-graphics analysis. 310 78

The influence of diazepam, droperidol, fentanyl and central transcutaneous electrical stimulation (ES) on hepatocytes was studied in experiments on healthy rats (group I). Organospecific enzymes (histidase and urokinase) were chosen for the evaluation of side effects of drugs and their combination with ES on physiological functions of the liver. Drugs and their combinations with ES used in the clinical practice caused no marked damage of hepatocytes in healthy animals. A pronounced decrease in the above enzyme activity (3-fold, as compared to the control group) was revealed in rats with acute cholestasis and pancreatitis 72 h after ES. This fact shows hepatoprotective effects of ES. The most marked unfavourable effect on hepatocytes was registered in group II, where fentanyl was used.
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PMID:[Effect of the components of electro-drug anesthesia and ataralgesia on the appearance of hepato-specific enzymes in the blood]. 349 74

Plasminogen activators (PAs) play an important role in tumor cell invasion. We have analysed the expression of tissue-type PA (t-PA), urokinase-type PA (u-PA), and their respective receptors, annexin II and u-PAR, in normal and neoplastic cultures of pancreatic cells, as well as in pancreatic tissues, and have examined their role in tumor invasiveness in vitro. Using Northern blotting, Western blotting, and ELISA, t-PA is detected in cultured pancreas cancer cells displaying a well differentiated phenotype but it is undetectable in less differentiated cells and in normal pancreatic cultures. In contrast, u-PA transcripts, protein, and enzymatic activity are detected both in cancer cells and in normal cultures. Higher levels of u-PAR and annexin II are present in cancer cells than in normal cultures and, in SK-PC-1 cells, both receptors are localized in the basolateral membrane. In vitro invasion assays indicate that both t-PA and u-PA contribute to the invasiveness of SK-PC-1 cells through reconstituted extracellular matrix. To determine the relevance of these studies to pancreas cancer, immunohistochemical assays have been used to examine the expression of t-PA, u-PA, and their receptors in normal and neoplastic tissues. t-PA is absent from normal pancreas and from tumor associated pancreatitis, whereas it is detected in the majority of pancreas cancer tissues (16/17). Annexin II is also overexpressed in some tumors (5/13). u-PAR is overexpressed in most tumor samples examined (14/15), while u-PA is weakly detected in a low number of cases (3/14); both u-PAR and u-PA are overexpressed in areas of tumor associated pancreatitis. Indirect evidences indicate that K-ras and p53 mutated proteins can regulate the expression of PAs. In pancreatic cancer we have found an association between codon 12 K-ras mutations and t-PA expression (P=0.04). These results support the contention that, in the exocrine pancreas, activation of t-PA is more specifically associated to neoplastic transformation and to the invasive phenotype, whereas the induction of u-PA/u-PAR system might be more relevant to inflammatory or non-neoplastic events.
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PMID:The plasminogen activator system in pancreas cancer: role of t-PA in the invasive potential in vitro. 948 8

A case of portal vein thrombosis (PVT) secondary to pancreatitis is presented. Patient was treated with catheter-directed thrombolysis using urokinase solution. Because the percutaneous transhepatic approach is associated with higher risk of hemorrhage we used the catheter-directed thrombolysis via the transjugular intrahepatic access to restore the patency of the thrombosed portal vein. This case shows that catheter-directed thrombolysis with transjugular approach can be effectively used in the treatment of PVT.
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PMID:Catheter-directed thrombolysis with transjugular access in portal vein thrombosis secondary to pancreatitis. 1152 14

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

Portal vein thrombosis is a rare complication accompanied with acute pancreatitis or cholangitis/cholecystitis. The main pathogenesis of portal vein thrombosis in pancreatitis or cholangitis/cholecystitis are suggested to be venous compression by pseudocyst and an imbalance between the blood coagulation and fibrinolysis. In this case report, we experienced a 63 year old male who developed portal vein thrombosis later in the course of the treatment of acute gallstone pancreatitis with cholangitis/cholecystitis without any symptom or sign. The diagnosis of portal vein thrombosis was given on follow up CT scan and serum protein S activity was decreased to 27% in laboratory study. Immediate anticoagulation therapy with heparin and thrombolytic therapy with urokinase and balloon dilatation were performed. Despite the aggressive treatment, complete reperfusion could not be obtained. With oral warfarin anticoagulation, the patient showed no disease progression and was discharged. We report a case of portal vein thrombosis as a complication of acute pancreatitis and cholangitis/cholecystitis with a review of literatures.
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PMID:[A case of portal vein thrombosis associated with acute pancreatitis and cholangitis]. 1603 Apr 6

Proteases play a key role in a variety of pathologies, including cancer, pancreatitis and thrombosis. Low molecular inhibitors can act as drugs to combat these pathologies. Twelve natural phenolic compounds and one alkaloid were evaluated. Quercetin was used as a standard in the in vitro tests on serine proteases (trypsin, thrombin and urokinase). Salicin showed a highly selective effect with a value of IC50 = 11.4 microm for thrombin, suggesting it may be a suitable lead structure for developing thrombin inhibitors and thus for perspective thrombolytics. Interesting results were also observed for hyperoside with IC50 = 8.3 microm for urokinase. The flavonoid skeleton seems to be a suitable structure for investigating urokinase inhibitors as prospective drugs for cancer therapy. A very high inhibitory activity on trypsin was observed for the flavonoid silybin (IC50 = 3.7 microm), indicating a prospective structure on which to base possible polyphenolic trypsin inhibitors.
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PMID:Inhibition activities of natural products on serine proteases. 1652 Nov 12

Proteases play a regulatory role in a variety of pathologies including cancer, pancreatitis, thromboembolic disorders, viral infections and many others. One of the possible strategies how to combat with these pathologies seems to be the use of low molecular inhibitors. Natural products were evaluated in the in vitro antiprotease assay on serine proteases (trypsin, thrombin and urokinase) and on the cysteine protease cathepsin B. We found interesting results for beta-ursolic acid isolated from Salvia officinalis, which significantly inhibited all tested proteases in vitro in the micromolar range. beta-Ursolic acid showed the strongest inhibition activity to urokinase (IC50 = 12 microM) and cathepsin B (IC50 = 10 microM) as proteases included in tumour invasion and metastasis indicated possible anticancer effectivity. Therefore, we tested the ability of beta-ursolic acid at doses of 50, 75 and 100 mg/kg given i.p. to inhibit lung colonization of beta16 mouse melanoma cells in vivo. We found, that beta-ursolic acid significantly decreased the number of B16 colonies in the lungs of mice at the dose 50 mg/kg (p < 0.05).
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PMID:Antiprotease and antimetastatic activity of ursolic acid isolated from Salvia officinalis. 1729 86

Hepatic artery thrombosis (HAT) remains one of the major causes of graft failure and mortality in liver transplant recipients. But it is a very rare in non-transplantation patient with the complication of HAT. We reported herein a case of successful urokinase intra-arterial thrombolytic treatment for HAT in an essential polycythemia vera patient following pancreato-biliary surgery. This patient underwent debridement and T-tube drainage in common bile duct for severe pancreatitis and acute suppurative obstructive cholangitis. Significant elevation of liver transaminases and white blood cell counts was noted 30 days after operation and HAT was confirmed by CT-angiography and digital subtracted angiography. Apart from malena and malaise, this patient had scarcity of evident symptoms. The only obvious risk factor relating to HAT is thrombocytosis. This patient was continuously characterized by an excess of platelets from its admission to the onset of HAT. This patient was treated successfully with continuous transcatheter arterial thrombolysis using urokinase. The symptom including malena and malaise disappeared 3 days after thrombolysis. And the patient was treated with hydroxyurea for polycythemia vera thereafter. In conclusion, physicians should be alerted that HAT can be happened in non-transplantation patients especially in those of having hypercoagulability.
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PMID:Right hepatic artery thrombosis in an essential polycythemia vera patient following pancreato-biliary surgery for severe pancreatitis. 2235 Jun 25

Portal vein thrombosis (PVT) is a relatively common complication in patients with liver cirrhosis, but several other causes might play an important role in PVT pathogenesis. We present a case of alcoholic chronic pancreatitis complicated by acute extensive PVT. The patient was managed conservatively with danaparoid sodium at first, but the thrombosis gradually extended. We then tried radiological intervention using the direct transhepatic and transjugular intrahepatic postsystemic shunt approaches. Although we were able to successfully catheterize the percutaneous transhepatic portal vein (PTP), we could not achieve recanalization of the portal vein. Therefore, PTP catheterization and systemic intravenous infusion of urokinase and heparin was performed to prevent further progression of the thrombosis and cavernous transformation was finally achieved. Computed tomography (CT) and magnetic resonance cholangiopancreatography revealed a pancreatic stone which had possibly induced dilatation of the tail duct and formation of a pancreatic pseudocyst and caused intractable pancreatitis. We performed endoscopic retrograde cholangiopancreatography and placed a stent in the pancreatic duct, which completely cured the pancreatitis. Retrospectively, the previous CT with curved multi-planar reconstruction was reviewed and a fistula was detected between the pancreatic pseudocyst and splenic vein. We concluded that the etiology of the PVT was not only inflammatory extension from pancreatitis but also a fistula between the pancreatic duct and the splenic vein.
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PMID:Acute portal vein thrombosis due to chronic relapsing pancreatitis: a fistula between a pancreatic pseudocyst and the splenic vein. 2618 9


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