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)

Elevated LDL (low density lipoprotein) cholesterol is considered an established risk factor for the development of atherosclerotic sequelae. In this context, low HDL cholesterol and/or raised triglyceride levels are now also receiving increasing attention as independent risk factors for atherosclerosis. The protective HDL cholesterol should be as high as possible (> 40 mg/dl or 1.0 mmol/l). Low HDL cholesterol levels are associated with an increased coronary risk that cannot be eliminated by lowering LDL cholesterol concentrations. Measures to elevate HDL are primarily dietary adjustments, cessation of smoking, weight reduction and increased physical activity. Triglyceride levels above 1000 mg/dL are also associated with an increased risk for the development of pancreatitis, and therefore also need to be treated.
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PMID:[Increased triglycerides and/or low HDL cholesterol. A risk factor needing treatment?]. 1242 24

In the 1359 published patients with multiorgan cholesterol crystal embolism (CCE), the digestive system seems to be the third most frequently affected system. Yet, this system received hitherto only little attention in the medical literature. Therefore, the aim of the present study was to clinically characterize the subset of patients with CCE involving the digestive system, based on our institutional experience and a review of the literature. Cases with CCE in a 7-yr period (1995-2001) were sought in the computerized records of our medical center. Of the CCE patients, those with digestive system involvement that could be related to CCE were included in this study. The clinical features of CCE were determined and compared with those found in published series. Fourteen cases with CCE were identified, giving an annual incidence of 0.8 per 10(5). Digestive system involvement was found in five (36%) of the 14 patients. All five patients had established atherosclerosis. Precipitating factors were vascular manipulations or anticoagulation treatment in four of these five patients. Two patterns of disease appeared: acute catastrophic multiorgan disorder with poor prognosis and chronic and more indolent GI disease. Abdominal pain, GI bleeding, fever, and diarrhea were the most common manifestations, resulting from bowel infarction, mucosal ulcerations, hepatocellular liver disorder, and/or pancreatitis. CCE is a systemic disorder with a frequent involvement of the digestive system and protean clinical manifestations. It should, therefore, be considered in any gastroenterological patient with atherosclerosis and recent vascular manipulations or systemic anticoagulation.
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PMID:Cholesterol crystal embolization to the digestive system: characterization of a common, yet overlooked presentation of atheroembolism. 1287 65

Acute acalculous cholecystitis is characterized by acute inflammation of the gallbladder in the absence of stones, usually occurring in elderly and critically ill patients with atherosclerosis, recent surgery or trauma, or hemodynamic instability. Patients may present with only unexplained fever, leukocytosis, and hyperamylasemia without right upper quadrant tenderness. If untreated, rapid progression to gangrene and perforation occurs. Surgical cholecystectomy and cholecystostomy provide the most definitive treatment although recent studies indicate success with percutaneous or endoscopic cholecystostomy. Cholesterolosis and adenomyomatosis of the gallbladder are usually clinically silent and incidental findings at the time of cholecystectomy. Cholesterolosis is characterized by mucosal villous hyperplasia with excessive accumulation of cholesterol esters within epithelial macrophages. Usually clinically silent, the condition rarely is associated with biliary symptoms or idiopathic pancreatitis and cannot reliably be detected by ultrasonography. Adenomyomatosis describes an acquired, hyperplastic lesion of the gallbladder characterized by excessive proliferation of surface epithelium with invaginations into a thickened muscularis propria. Ultrasonography may reveal a thickened gallbladder wall with intramural diverticula. Adenomyomatosis may portend a higher risk of gallbladder malignancy. Most cases of cholesterolosis and adenomyomatosis identified by imaging require no specific treatment. Gallbladder polyps include all mucosal projections into the gallbladder lumen and include cholesterol polyps, adenomyomas, inflammatory polyps, adenomas, and other miscellaneous polyps. Most polyps are nonneoplastic and rarely cause symptoms. Cholecystectomy is advocated for polyps greater than 10 mm in size because of increased risk of adenomatous or carcinomatous features.
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PMID:Gallbladder polyps, cholesterolosis, adenomyomatosis, and acute acalculous cholecystitis. 1471 68

Dyslipidemia, characterized by elevated serum levels of triglycerides and reduced levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol, has been recognized in patients with human immunodeficiency virus (HIV) infection. It is thought that elevated levels of circulating cytokines, such as tumor necrosis factor-alpha and interferon-alpha, may alter lipid metabolism in patients with HIV infection. Protease inhibitors, such as saquinavir, indinavir and ritonavir, have been found to decrease mortality and improve quality of life in patients with HIV infection. However, these drugs have been associated with a syndrome of fat redistribution, insulin resistance, and hyperlipidemia. Elevations in serum total cholesterol and triglyceride levels, along with dyslipidemia that typically occurs in patients with HIV infection, may predispose patients to complications such as premature atherosclerosis and pancreatitis. It has been estimated that hypercholesterolemia and hypertriglyceridemia occur in greater than 50% of protease inhibitor recipients after 2 years of therapy, and that the risk of developing hyperlipidemia increases with the duration of treatment with protease inhibitors. In general, treatment of hyperlipidemia should follow National Cholesterol Education Program guidelines; efforts should be made to modify/control coronary heart disease risk factors (i.e. smoking; hypertension; diabetes mellitus) and maximize lifestyle modifications, primarily dietary intervention and exercise, in these patients. Where indicated, treatment usually consists of either pravastatin or atorvastatin for patients with elevated serum levels of LDL-C and/or total cholesterol. Atorvastatin is more potent in lowering serum total cholesterol and triglycerides compared with other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, but it is also associated with more drug interactions compared with pravastatin. Simvastatin and lovastatin are significantly metabolized by cytochrome P450 enzymes (CYP3A4) and are therefore not recommended for coadministration with protease inhibitors. A fibric acid derivative (gemfibrozil or fenofibrate) should be used in patients with primary hypertriglyceridemia. However, it must be kept in mind that protease inhibitors, such as nelfinavir and ritonavir, induce enzymes involved in the metabolism of the fibric acid derivatives and may, therefore, reduce the lipid-lowering activity of coadministered gemfibrozil or fenofibrate. In certain patients HMG-CoA reductase inhibitors may be used in combination with fibric acid derivatives but patients should be carefully monitored for liver and skeletal muscle toxicity. Select patients may experience improvements in serum lipid levels when their offending protease inhibitor(s) is/are exchanged for efavirenz, nevirapine, or abacavir; however each patient's virologic and immunologic status must be taken closely into consideration.
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PMID:Management of protease inhibitor-associated hyperlipidemia. 1472 85

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

Functional deficiency of lipoprotein lipase (LPL) was found in a patient with severe hypertriglyceridemia. The patient was 39-year-old man with a plasma triglyceride level of 2032 mg/dl, and suffered from recurrent pancreatitis. His post heparin plasma LPL mass was almost normal, but the LPL activity was remarkably decreased. Gene analysis showed that homozygote missense mutation (204 Asp (GAC)-Glu (GAG)) exists in exon 5 of LPL gene. The patient LPL purified from post heparin plasma scarcely hydrolyzed VLDL-triglyceride and also triolein emulsified with Triton X-100 or phosphatidylcholine. When phosphatidylethenolamine, phosphatidylserine and cardiolipin were used as an emulsifier for triolein, triolein-hydrolyzing activity of the patient's LPL was observed and was much higher than that of wild-type LPL. Mutant LPL gene (Asp204-Glu) was made by site-direct mutagenesis and was transfected to COS-1 cell. The expressed LPL (Asp204-Glu) also showed the same properties. These results suggested that the LPL (Asp204-Glu) is a functional deficiency, and the activity could be recovered by using acidic phospholipids as an emulsifier.
Atherosclerosis 2005 Nov
PMID:The recovery of dysfunctional lipoprotein lipase (Asp204-Glu) activity by modification of substrate. 1587 72

Visceral artery aneurysms (VAA) are uncommon pathologies. We report a case of the first CAPD patient with obstructive jaundice directly related to VAA. A 25-year-old man with a four-year history of hemodialysis followed by two years of CAPD was admitted due to jaundice. He had two episodes of peritonitis. An abdominal ultrasonogram and a selective common hepatic arteriogram confirmed the presence of a 5 cm saccular aneurysm supplied from the gastroduodenal artery and a 4 cm fusiform aneurysm supplied from the proximal part of the common hepatic artery. The gastroduodenal artery was responsible for the impression of the common bile duct. In the operation, the gastroduodenal artery aneurysm was completely excised after its proximal and distal ends were ligated. The proximal and distal ends of the hepatic artery were also ligated. A prosthetic graft (PTFE), which extended from the splenic artery to the distal portion of the hepatic artery, was placed. In this way, the arterial blood flow of the liver was re-established. Patients with VAAs present with a constellation of symptoms including abdominal pain, jaundice and shock (due to rupture of aneurysm). Pancreatitis, and atherosclerosis have been reported to be the most common causes of VAAs. In conclusion, when CAPD patients present with jaundice or hemorrhagic shock with abdominal pain, VAA should be considered in differential diagnosis, especially if patients have a history of frequent pancreatitis episodes, and severe risk factors for atherosclerosis.
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PMID:Obstructive icterus directly related to visceral artery aneurysm in a CAPD patient. 1596 Jan 53

Severe hypertriglyceridemia (HTG) is a metabolic disturbance often seen in clinical practice. It is known to induce life-threatening acute pancreatitis, but its role in atherogenesis remains elusive. Hemorheological abnormality was thought to play an important role in pathogenesis of both pancreatitis and atherosclerosis. However, hemorheology in severe HTG was not well investigated. Recently, we established a severe HTG mouse model deficient in lipoprotein lipase (LPL) in which severe HTG was observed to cause a significant increase in plasma viscosity. Disturbances of erythrocytes were also documented, including decreased deformability, electrophoresis rate, and membrane fluidity, and increased osmotic fragility. Scanning electron microscopy demonstrated that most erythrocytes of LPL deficient mice deformed with protrusions, irregular appearances or indistinct concaves. Analysis of erythrocyte membrane lipids showed decreased cholesterol (Ch) and phospholipid (PL) contents but unaltered Ch/PL ratio. The changes of membrane lipids may be partially responsible for the hemorheological and morphologic abnormalities of erythrocytes. This study indicated that severe HTG could lead to significant impairment of hemorheology and this model may be useful in delineating the role of severe HTG in the pathogenesis of hyperlipidemic pancreatitis and atherosclerosis.
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PMID:Hemorheological abnormalities in lipoprotein lipase deficient mice with severe hypertriglyceridemia. 1646 Jun 82

Superior mesenteric artery and pancreaticoduodenal artery aneurysms are rare. Agenesis of the celiac axis has only been reported four times. The reported etiologies of superior mesenteric artery and branch artery aneurysms include infection, atherosclerosis, inflammatory processes such as pancreatitis, dissection, collagen vascular disorders, polyarteritis nodosa, and trauma. We report an aneurysm of the superior mesenteric artery (SMA) branch, the inferior pancreaticoduodenal artery, arising in a patient with congenital absence of the celiac trunk. The patient presented with intermittent left upper quadrant pain without weight loss or change in bowel habits. The aneurysm was identified on abdominal computed tomography scan with angiographic confirmation of the aberrant anatomy. The patient was treated by aneurysmectomy and pancreaticoduodenal artery reconstruction with an interposition vein graft from the SMA. The patient recovered without complications and is asymptomatic with a patent vein graft 2 years after operation.
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PMID:Superior mesenteric artery branch aneurysm with absence of the celiac trunk. 1695 80

With current dietary therapy, life expectancy in glycogen storage disease (GSD) has improved considerably and more children reach adulthood. Notwithstanding intensive dietary therapy, moderate to severe hyperlipidaemia is still observed frequently. There is limited information about the type and extent of hyperlipidaemia. We studied the lipid profile in 20 patients, aged 8-54 years, of the three (types I, III and IX) most common forms of adult GSD. Hyperlipidaemia was shown to be type-specific, affecting predominantly patients with GSD type Ia, who showed marked combined hypercholesterolaemia and hypertriglyceridaemia. By contrast, a heterogeneous distribution of HDL was found in patients with GSD I and III. There was no significant difference in Apo Al and Apo B concentrations between groups. In addition, mass measurements of the fractions of VLDL1, VLDL2 and IDL were raised in all patients with GSD Ia by comparison with all other patients with GSD. Patients with GSD type Ia have lipid concentrations and individual mass measurements that are consistent with ranges found in patients who have a significant risk of atherosclerosis. Accumulated evidence, however, suggest GSD type Ia patients do not have an increased risk of atherosclerotic cardiovascular disease (CVD) but the reason remains unknown. Intervention to reduce their lipid levels could therefore be on the basis of seeking to prevent the risk of pancreatitis rather than that of CVD.
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PMID:Serum lipid and lipoprotein profile of patients with glycogen storage disease types I, III and IX. 1740 2


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