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 effect of methylcarbonylmethyl 2(S)-14-(4-guanidino-benzoyloxy) phenyl] propionate methanesulfonate (TT-S24) on experimental pancreatitis in rats was examined in comparison with that of camostat. TT-S24 showed a preventive effect on increases in plasma amylase activity and pancreatic weight induced by cerulein injection. TT-S24 also reduced an increase in plasma amylase activity induced by taurocholate. TT-S24 effectively prevented the mortality induced by an injection of a mixture of trypsin and taurocholate. TT-S24 showed no effect on an increase in amylase activity 6 h after duodenum ligation (closed duodenal loop pancreatitis), indicating that the drug had no effect on the initiation and propagation step of closed duodenal loop pancreatitis. On the other hand, TT-S24 reduced an increase in amylase activity 6 h after release of the duodenum ligation. TT-S24 showed anti-trypsin, anti-kallikrein, anti-thrombin and anti-plasmin activities. The effect of TT-S24 on some experimental pancreatitis models was nearly equal to or somewhat more potent in most instances to that of camostat. Therefore, TT-S24 should be useful in the clinical treatment of pancreatitis.
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PMID:Effect of methylcarbonylmethyl 2(S)-[4-(4-guanidino-benzoyloxy)phenyl] propionate methanesulfonate (TT-S24) on experimental pancreatitis in rats. 955 50

We attempted to administer PEG-L-asparaginase (PEG-L-A) following hematologic recovery to 38 patients undergoing autologous or allogeneic marrow transplantation for acute lymphoblastic leukemia (ALL). Twenty-four patients (12 of 22 receiving allogeneic and 12 of 16 receiving autologous transplants) received between one and 12 doses of PEG-L-A, including nine who completed the planned 12 doses of therapy. The toxicities encountered were similar to those observed in non-transplanted patients undergoing therapy with PEG-L-A and included allergic reactions, pancreatitis, weight loss, hypoalbuminemia, and low levels of anti-thrombin III. Of the 24 who received the drug, eight remain in remission. Of 12 patients in second remission at the time of transplantation who received PEG-L-A, five of seven who received allogeneic and two of five who received autologous transplants remain in remission, 16+ to 46+ months from transplant. While PEG-L-A could be administered to most of the patients undergoing marrow transplantation for ALL, most patients either relapsed while receiving the drug or developed toxicities which resulted in abbreviated courses. At this time, we cannot recommend PEG-L-A as single agent, post-BMT chemotherapy.
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PMID:Toxicity, pharmacology and feasibility of administration of PEG-L-asparaginase as consolidation therapy in patients undergoing bone marrow transplantation for acute lymphoblastic leukemia. 961 79

Proteinase-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved by trypsin within the NH2-terminus, exposing a tethered ligand that binds and activates the receptor. We examined the secretory effects of trypsin, mediated through PAR-2, on well-differentiated nontransformed dog pancreatic duct epithelial cells (PDEC). Trypsin and activating peptide (AP or SLIGRL-NH2, corresponding to the PAR-2 tethered ligand) stimulated both an 125I- efflux inhibited by Ca2+-activated Cl- channel inhibitors and a 86Rb+ efflux inhibited by a Ca2+-activated K+ channel inhibitor. The reverse peptide (LRGILS-NH2) and inhibited trypsin were inactive. Thrombin had no effect, suggesting absence of PAR-1, PAR-3, or PAR-4. In Ussing chambers, trypsin and AP stimulated a short-circuit current from the basolateral, but not apical, surface of PDEC monolayers. In monolayers permeabilized basolaterally or apically with nystatin, AP activated apical Cl- and basolateral K+ conductances. PAR-2 agonists increased [Ca2+]i in PDEC, and the calcium chelator BAPTA inhibited the secretory effects of AP. PAR-2 expression on dog pancreatic ducts and PDEC was verified by immunofluorescence. Thus, trypsin interacts with basolateral PAR-2 to increase [Ca2+]i and activate ion channels in PDEC. In pancreatitis, when trypsinogen is prematurely activated, PAR-2-mediated ductal secretion may promote clearance of toxins and debris.
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PMID:Trypsin activates pancreatic duct epithelial cell ion channels through proteinase-activated receptor-2. 991 38

Pancreatic pseudoaneurysm is a relatively uncommon complication of chronic pancreatitis, with an associated high mortality if rupture or hemorrhage occurs. We present a case of pancreatic pseudoaneurysm complicating pancreatitis which was successfully treated by direct percutaneous injection of thrombin into the aneurysmal sac. Follow-up at 8 weeks did not demonstrate recurrence. This case indicates that percutaneous thrombin injection offers effective treatment of visceral arterial pseudoaneurysms.
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PMID:Ultrasonic-guided percutaneous injection of pancreatic pseudoaneurysm with thrombin. 1456 87

The impact of alcohol intake on mortality from all causes has been described in a large number of prospective population studies from many countries. Most have shown a J-shaped relation between alcohol intake and subsequent mortality, indicating that there are both beneficial and harmful effects of ethanol on health. The risk of death from ischemic heart disease is seen to be significantly increased, and highest among abstainers, but not significantly increased among heavy drinkers. Some studies have found plausible mechanisms for the beneficial effect of light to moderate drinking. Subjects with a moderate alcohol intake have a higher level of high density lipoprotein than abstainers. Further, moderate drinkers are seen to have a lower low density lipoprotein. Also, alcohol has a beneficial effect on platelet aggregation, and thrombin level in blood is higher among drinkers than among non-drinkers. In the other end of the range of intake, the ascending leg of the U-shaped curve has been explained by the increased risk of cirrhosis, pancreatitis, and development oropharynx, oesophagus, and breast cancer. In exploring the French paradox, it has been suggested that wine may have beneficial effects additional to that of ethanol. Recently, several prospective population studies have supported this idea. It is, however, also likely that the apparent additional beneficial effect of wine on health in addition to the effect of ethanol itself is a consequence of confounding.
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PMID:Epidemiologic evidence for the cardioprotective effects associated with consumption of alcoholic beverages. 1500 14

For a long time fibrinopeptide A(FPA), fibrinopeptide B(FPB), D-dimer, FM test, serum FDP, and thrombin anti-thrombin complex(TAT) are being used as molecular markers to for sure diagnose hypercoagulable state and thrombus formation. Indeed these molecular markers are very useful for diagnosing thrombus formation, disseminated intravascular coagulation(DIC), and the indicator of treatment of DIC. But these molecular parameters are not enough and difficult for prognosis of the disease or predicting the complication of patients as the most important subject for clinicians. The soluble fibrin monomer-fibrinogen complex (SF) is a complex coupling fibrin monomer and fibrinogen molecules to be formed in the early-activated state of blood coagulation. Thus such a molecular complex is expected to serve as a parameter for the diagnosis of thrombus formation and DIC, in particular its early stage. The aim of the present study is to evaluate a potential usefulness of a newly developed SF test utilizing an SF specific monoclonal antibody (IF-43). We measured SF together with established other parameters in 195 patients with DIC, subclinical DIC/hypercoagulable state, and non-DIC. The diagnosis of DIC was made based on a modified version of the criteria established by the Ministry of Health, Labor and Welfare of Japan. Underlying disease includes leukemia, malignant lymphoma, myelodysplastic syndrome (MDS), multiple injury, giant ovarian tumor, prostatic cancer with multiple bone metastasis, lung cancer, breast cancer with multiple lung and bone metastasis, severe pneumoniae, sepsis, hemophagocytic syndrome (HPS), and rheumatoid arthritis. The SF levels in DIC patients were significantly higher than those in the subclinical DIC/hypercoagulable state, and the non-DIC patients. Receiver operating characteristic (ROC) analysis shows that the specificity and sensitivity of the SF assay appears to be satisfactory. As the level of SF reflects the thrombin generation activity in plasma, it would serve as a strong tool to selectively kick up the state of thrombin generation. These results indicate that the SF could be a specific and reliable parameter for the diagnosis of DIC and contribute to legitimate managements of patients with DIC. The excessive life response to serious clinical insults, such as sepsis, severe pancreatitis, trauma and shock, is called systemic inflammatory response syndrome (SIRS). Once SIRS occurs, people may often die from serious complications such as adult respiratory distress syndrome (ARDS), acute lung injury (ALI), disseminated intravascular coagulation (DIC) and multiple organ failure (MOF). Especially, ALI followed by pneumoniae associated with SIRS could depend on patient's prognosis and life. That is to say, it seems to be urgent for clinicians to make differential diagnosis between Pneumoniae associated with SIRS and Coagulopathy (PASC) and Simple Pneumoniae (SP). Soluble fibrin monomer-fibrinogen complex(SF) is formed in the early-activated state of blood coagulation. Thus such a molecular complex is expected to serve as a parameter for the diagnosis of coagulopathy, in particular its early stage. The aim of the present study is to make differential diagnosis between Pneumoniae associated with SIRS and Coagulopathy (PASC) and Simple Pneumoniae(SP) by using a newly developed SF test utilizing an SF specific monoclonal antibody (IF-43). We measured SF together with established other parameters, hemogram, blood laboratory items in 7 patients with PASC and 17 patients with SP. The diagnosis of Pneumoniae was defined according to the criteria: clinical symptoms abnormal shadow in both Chest X-p and Chest CT, increased level of CRP, number of WBC. The diagnosis of SIRS was based on the criteria established by American College of Chest Physicians (ACCP)/Society of Critical Care Medicine (SCCM) Consensus Conference held in August of 1991 in Northbrook, IL (USA). Underlying disease includes leukemias, malignant lymphoma, myelodysplastic syndrome (MDS), multiple myeloma, idiopathic thrombocytopenia purpura(ITP), multiple injury (bone fracture), cerebral hemorrhage, enterocolitis, Appendicitis, lung cancer, larynx cancer, bronchiolitis obliterans organizing pneumonia(BOOP), chronic obstructive pulmonary disease(COPD), sepsis. The SF levels in PASC patients are significantly higher than those in SP patients (p < 0.001). Otherwise, there is no significant difference of the CRP levels between in PASC group and SP group (p < ns). There is no co-relationship between SF level and D-dimer level. Receiver operating characteristic (ROC) analysis shows that the specificity and sensitivity of the SF assay appears to be quite satisfactory. As the level of SF reflects the thrombin generation activity in plasma, it would serve as a strong tool to selectively kick up the state of thrombin generation. These results indicate that the SF could be a specific and reliable parameter for the diagnosis of PASC and contribute to legitimate managements of patients with PASC.
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PMID:[A novel molecular marker for thrombus formation and life prognosis--clinical usefulness of measurement of soluble fibrin monomer-fibrinogen complex (SF)]. 1516 5

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

Aprotinin (Trasylol) is a serine protease inhibitor, isolated from bovine lung that initially was marketed for the treatment of pancreatitis. In the mid 1980s, reports of its ability to decrease hemorrhaging after cardiopulmonary bypass surgery introduced the drug to the realm of cardiac surgery. Unfortunately, its introduction into this arena was followed by the publication of multiple studies and case reports that blamed aprotinin for poor outcomes in the form of early graft closure. More than 17 years have passed since the initial article describing the use of aprotinin during cardiopulmonary bypass, and with time there has been a significant increase in scientific knowledge and clinical experience. Interestingly, modern literature does not support the dogma that aprotinin is a procoagulant. Aprotinin increases the activated partial thromboplastin time (aPTT), as well as the kaolin- and celite-activated clotting time (ACT), regardless of heparin. Aprotinin, because of its ability to inhibit kallikrein, has been found to decrease thrombin antithrombin III complexes, fibrin-split products, fibrinopeptide 1+2, prothrombin fragments, and all markers of thrombin formation. Some authors have suggested that it may have a synergistic effect with heparin to ensure graft patency. Anticoagulation monitoring during the use of aprotinin also has been developed based on early studies. Aprotinin administration does influence the results of various ACT tests, and consequently different methods of testing anticoagulation have been developed. Researchers have demonstrated that the celite ACT is not "artificially" prolonged in the presence of heparin and aprotinin, rather the kaolin ACT is "artificially" shortened. This article will review the scientific literature with regard to aprotinin's anticoagulatory effects and review the current recommendations for hemostasis monitoring during the use of aprotinin.
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PMID:Aprotinin and hemostasis monitoring concerns during cardiac surgery. 1567 83

Metastasis is one of the major causes of mortality in cancer. It is well known that the activities of cell surface serine proteases are especially enhanced in malignant tumors. Proteolytic degradation of the extracellular matrix and basal membrane is a crucial event for tumor cell invasion and metastasis formation. FOY-305 (Foypan), a remedy for tumor pancreatitis, is a broad spectrum synthetic serine protease inhibitor which inhibits enzymatic activities including trypsin, thrombin, kallikrein and plasmin. Using Lewis lung carcinoma cell, we found that FOY-305 inhibited both spontaneous and experimental pulmonary metastasis. Furthermore, the combined treatment of FOY-305 and a traditional anti-cancer drug, 5-FU or bleomycin, resulted in marked enhancement of anti-pulmonary metastatic activity.
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PMID:Antimetastatic activity of a synthetic serine protease inhibitor, FOY-305 (Foypan). 1579 65

Pseudoaneurysms in the visceral arteries are rare complications of pancreatitis. In the reported case, a 42-year-old man with a splenic pseudoaneurysm was successfully treated by computed tomography (CT)-guided direct thrombin injection into the pseudoaneurysm lumen. Selective catheterization of the splenic artery had proven technically impossible. During the procedure, contrast medium was injected via a pigtail catheter into the aorta for planning, correct positioning of the needle tip, and control imaging after injection. CT examinations 1 day, 3 weeks, and 6 months after treatment demonstrated complete occlusion shrinkage of the pseudoaneurysm, and the patient was symptom-free.
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PMID:Percutaneous treatment of a splenic artery pseudoaneurysm by thrombin injection. 1600 12


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