Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An autopsy case with a widespread mucosal carcinoma of the biliary tree was reported. A biochemical profile of the bile duct damage was noticed in a woman in her seventies during a gastric examination. Imaging procedures depicted irregular dilatations of intrahepatic bile ducts with a bead-like appearance. Elevated levels of serum alkaline phosphatase and gamma-glutamyltransferase with a negative antimitochondrial antibody persisted. The patient was diagnosed as primary sclerosing cholangitis, she was followed up for 4 years under preservative therapies, and died of anasarca and heart failure. Post-mortem examination showed a diffuse mucosal carcinoma of both intrahepatic and extrahepatic biliary passages including the gallbladder with a minimal invasion and scattered foci of adenoma-like area in part. There was no evidence of gallstones or pre-existing sclerosing cholangitis. The striking features of the tumor were extensive papillary growth, mucus secretion and irregular dilatation of bile ducts. The tumor may bear biological and morphological homology with intraductal papillary mucinous tumor of the pancreas.
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PMID:Diffuse mucosal carcinoma of intrahepatic and extrahepatic bile ducts including gallbladder. 1258 48

Primary sclerosing cholangitis (PSC) is increasingly diagnosed in children and adolescents, but its long-term prognosis remains uncertain. The aim of this longitudinal, cohort study was to determine the long-term outcome of children with PSC. Fifty-two children with cholangiography-proven PSC (34 boys and 18 girls; mean age 13.8 +/- 4.2 years; range, 1.5-19.6 years) who were seen at our institution over a 20-year period were followed-up for up to 16.7 years. Two thirds presented with symptoms and/or signs of PSC and 81% had concomitant inflammatory bowel disease (IBD). Twenty-five percent had total alkaline phosphatase activity within the normal range for the age group, but all of them had elevated gamma-glutamyl transpeptidase levels. Autoimmune hepatitis overlapping with PSC was present in 35% of children. A positive but transient clinical and/or biochemical response occurred under therapy with ursodeoxycholic acid, alone or in combination with immunosuppressive medications. During follow-up, 11 children underwent liver transplantation for end-stage PSC and 1 child died. The median (50%) survival free of liver transplantation was 12.7 years. Compared with an age- and gender-matched U.S. population, survival was significantly shorter in children with PSC (P <.001). In a Cox regression model, lower platelet count, splenomegaly, and older age were associated with shorter survival. Presence of autoimmune hepatitis overlapping with PSC (P =.2) or medical therapy (P =.2) did not affect survival. In conclusion, PSC significantly decreases survival in this child population. Although pharmacologic therapy may improve symptoms and liver test results initially, it does not seem to impact the long-term outcome.
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PMID:Primary sclerosing cholangitis in children: a long-term follow-up study. 1283 4

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown origin, characterized by inflammation, fibrosis, and obliteration of bile ducts, which ultimately results in biliary cirrhosis. The condition most commonly affects intrahepatic and extrahepatic bile ducts together, but sometimes only intrahepatic or extrahepatic ducts are involved. PSC is often associated with inflammatory bowel disease, especially ulcerative colitis. The majority of patients are initially asymptomatic, and identified on the basis of elevated serum levels of alkaline phosphatase or gamma-glutamyl transpeptidase, especially while screening patients with ulcerative colitis. Diagnosis is based on characteristic cholangiographic appearance with focal bile duct dilatations proximal to areas of stricturing that produce a beaded appearance. Ursodeoxycholic acid is most effective medical therapy, with other symptomatic measures, while liver transplantation is the treatment of choice for patients with advanced liver disease.
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PMID:[Primary sclerosing cholangitis--diagnosis and therapy]. 1458 67

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are chronic cholestatic liver diseases, biochemically characterized by an elevated serum bilirubin, alkaline phosphatase and gamma-glutamyl transferase. Although PBC and PSC have their own distinctive clinical, immunological, radiological and histological features, both diseases show a necro-inflammatory process, predominantly confined to the bile ducts within the portal tracts. In most patients the disease gradually progress and may lead to cirrhosis and liver failure. Transplantation may than be the only therapeutic option left.
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PMID:[Treatment of cholestatic liver disease]. 1475 10

There is no effective medical treatment for primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease that usually progresses to cirrhosis and liver failure. The aim of this study was to determine the safety and efficacy of etanercept, an inhibitor of tumor necrosis factor, in the treatment of PSC. Ten patients with clinically active PSC were studied. All had elevated serum alkaline phosphatase levels, cholangiograms that were diagnostic of PSC, and liver histology consistent with PSC. Five patients had elevated serum bilirubin levels, five had pruritus, eight had failed to respond to ursodiol and/or methotrexate, and six had rapidly recurring dominant bile duct strictures. Patients were to receive etanercept, 25 mg subcutaneously twice weekly, for 6 months if there were no side effects and for 1 year if there was evidence of efficacy after 6 months. Biochemical tests of liver function did not improve in any patient. Mean serum bilirubin levels increased significantly, from 2.0 to 3.6 mg/dl (P = 0.026). Two of the five patients with pruritus had resolution of pruritus during treatment with etanercept, recurrence when etanercept was stopped, and resolution when it was restarted, although there was little change in liver enzymes or bilirubin levels. There was no decrease in the rate of stricture formation and there were no side effects. Etanercept, at the dosage used, was well tolerated but not effective in the treatment of PSC. It may be helpful in treating pruritus due to cholestasis.
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PMID:A pilot study of etanercept in the treatment of primary sclerosing cholangitis. 1499 26

It is unknown why some patients with inflammatory bowel disease develop primary sclerosing cholangitis. We have recently shown that patients with primary sclerosing cholangitis have an increased prevalence of mutations in the gene responsible for cystic fibrosis (CFTR) compared with individuals with inflammatory bowel disease alone. Our aim was to examine whether induction of colitis by oral dextran leads to bile duct injury in mice heterozygous or homozygous for mutations in CFTR. The effect of oral administration of docosahexaenoic acid to correct a fatty acid imbalance associated with cystic fibrosis was also examined to determine whether this would prevent bile duct inflammation. Wild-type mice and mice heterozygous and homozygous for CFTR mutations were given dextran orally for 14 days to induce colitis. Bile duct injury was quantitated by blinded histological scoring and measurement of serum alkaline phosphatase activity. The effect of pretreatment with docosahexaenoic acid for 7 days was examined. Treatment of mice with 100 mg dextran/day for 9 days followed by 85 mg/day for 5 days resulted in a significant increase in bile duct injury as determined by histological scoring in homozygous cystic fibrosis mice compared with wild-type mice (P = 0.005). The bile duct injury seen in cystic fibrosis mice was reflected in a threefold increase in serum alkaline phosphatase (P = 0.0006). Pretreatment with oral docosahexaenoic acid decreased both histological evidence of bile duct injury and serum alkaline phosphatase levels. In the setting of colitis, loss of CFTR function leads to bile duct injury.
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PMID:Induction of colitis in cftr-/- mice results in bile duct injury. 1506 32

We analyzed 388 cases of primary sclerosing cholangitis (PSC) in Japan, according to a questionnaire sent to gastroenterologists. There was male predominance (59%), and interestingly there were two peaks in the age distribution as seen in the previous study. Jaundice and itching, major symptoms in PSC patients included in the diagnostic criteria, were observed only 28 and 16%, respectively. Alkaline phosphatase level was less than twofold of the upper limit of the normal range in 35%. In this regard, the diagnostic criteria in 2003 from Mayo Clinic, including cholestatic symptoms and two to three-fold increases in serum alkaline phosphatase, should be modified in Japan. Inflammatory bowel diseases were complicated in 37%, and autoimmune pancreatitis (AIP) in 7.2%. PSC cases with inflammatory bowel diseases were younger than the average, creating the first peak in the age distribution, and have similar characteristics compared to patients with PSC in foreign countries. By contrast, those with AIP, who were more than 50 years old, responded well to corticosteroid therapy. In addition, even after the exclusion of cases of sclerosing cholangitis complicated with AIP, the second peak in the age distribution was clearly evident. Therefore, we conclude that PSC patients without apparent involvement of the pancreas are present in the older patients and seem to be specific in Japan.
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PMID:Analysis of 388 cases of primary sclerosing cholangitis in Japan; Presence of a subgroup without pancreatic involvement in older patients. 1520 79

Primary biliary cirrhosis (PBC), autoimmune cholangitis (AIC = AMA-negative PBC) and primary sclerosing cholangitis (PSC) are autoimmune cholestatic liver diseases. Overlap syndromes combine characteristics of cholestatic liver diseases and autoimmune hepatitis. In PBC, alkaline phosphatase and gamma-glutamyl transferase are elevated, to a lesser degree aminotransferases. Histology shows bile duct lesions. Anti-mitochondrial antibodies are typical. Ursodeoxycholic acid (UDC) is established therapy that slows or even stops the disease progression, at least in early stages of the disease. In non-responders immunosuppression is recommended. PSC is mostly associated with chronic inflammatory bowel diseases. P-ANCA are frequent. Bile duct lesions revealed by retrograde cholangiography are characteristic. UDC is given as therapy. Bile duct strictures or bacterial cholangitis may be late sequelae and should be treated by antibiotics or bile-duct dilatation. Cirrhosis may ultimately develop in PBC and PCS. In progressed PBC or PSC liver transplantation is indicated.
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PMID:[Cholestatic liver diseases]. 1545 69

No effective medical therapy is currently available for primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA) improves liver enzymes, but its effect on liver histology is controversial. Metronidazole (MTZ) prevents PSC-like liver damage in animal models and reduces intestinal permeability. We recruited 80 patients with PSC into a randomized placebo-controlled study to evaluate the effect of UDCA and MTZ (UDCA/MTZ) compared with UDCA/placebo on the progression of PSC. Patients (41 UDCA/placebo and 39 UDCA/MTZ) were followed every third month. Assessment of liver function test, histological stage and grade, and cholangiography (via ERCP) at baseline showed no differences between the groups. After 36 months, serum aminotransferases gamma-glutamyltransferase, and alkaline phosphatase (ALP) decreased markedly in both groups, serum ALP more significantly in the UDCA/MTZ group (-337 +/- 54 U/L, P < .05) compared with the UDCA/placebo group. The New Mayo Risk Score decreased markedly only in the UDCA/MTZ group (-0.50 +/- 0.13, P < .01). The number of patients with improvement of stage (P < .05) and grade (P < .05) was higher in the combination group. ERCP findings showed no progression or improvement in 77% and 68% of patients on UDCA/MTZ and UDCA/placebo, respectively. In conclusion, combining MTZ with UDCA in PSC improved serum ALP levels and New Mayo Risk Score, but no statistically significant effect on disease progression as assessed via liver histology or ERCP was seen. Long-term studies using a higher dose of UDCA combined with MTZ in larger patient populations are indicated.
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PMID:Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: a randomized placebo-controlled trial. 1556 69

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology. Despite advances in understanding the pathophysiology underlying this disorder, no effective medical therapy has been identified for halting disease progression. The aim of this investigation was to determine the safety and estimated efficacy of mycophenolate mofetil (MMF) for the treatment of PSC. Thirty patients with PSC received MMF 1 g daily to a maximum of 3 g daily for 1 yr. Liver tests were determined at 3-month intervals with the Mayo risk score calculated at baseline and at the end of therapy. Twenty-three (77%) patients completed 1 yr of therapy. Significant but clinically marginal improvement in serum alkaline phosphatase level after 1 yr of therapy was observed (1135 +/- 581 U/L vs 912 +/- 463 U/L, p= 0.02). No other significant changes in liver biochemistries or Mayo risk score was observed. Seven patients (23%) discontinued MMF due to adverse events possibly related to therapy. Adverse reactions resolved spontaneously or with dose reduction in 10 (33%) patients. One patient developed pancreatitis, bacterial cholangitis, and sepsis during the eighth month of MMF therapy. No patient developed cytopenia on therapy. In conclusion, MMF does not appear to have clinically important benefits for PSC despite being tolerated by most patients. The results of this pilot study do not support further study of MMF as a single agent in the treatment of PSC.
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PMID:Mycophenolate mofetil for the treatment of primary sclerosing cholangitis. 1566 87


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