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)

In this study, we present a case of mild PBC that had anti-p97/VCP. A 53-year-old woman had been suspected of having chronic liver disease since 1983. In 1998, she visited the clinic, complaining of struma and pruritus. Laboratory findings on the first visit showed elevated levels of alkaline phosphatase (ALP) 454 IU/l(110-360), gammaGTP 250IU/l(-45) and IgM 671mg/dl(35-220). A screening of anti-mitochondrial antibody test was positive at a 1:80 dilution. A liver biopsy specimen revealed PBC at Scheuer stage 1. Following a treatment of ursodeoxycolic acid (UDCA) 300mg/day for 6 months, AMA and IgM were reduced to 1:20 and 220mg/dl, respectively. However, she was found to have low titer of anti-p97/VCP antibodies, determined by immunoprecipitation of radiolabeled recombinant protein produced by in vitro translation and transcription of the full length p97 cDNA. She has continued to be clinically stable following administration of UDCA 300mg. A PBC patient with anti-p97/VCP antibody showed a milder clinical course, suggesting some beneficial role of this antibody.
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PMID:[Case of primary biliary cirrhosis patient with anti-p97/VCP antibodies presenting a mild clinical course]. 1572 86

A nearly 5 year-old boy presented with proximal muscle weakness, reduced muscle bulk, a positive Gower sign and Trendelenburg gait. He was known to have cholestatic liver disease. Investigations revealed markedly low serum total calcium, elevated alkaline phosphatase, very low serum 25-hydroxyvitamin D, and radiographs consistent with active rickets despite the ongoing administration of a water-soluble preparation of vitamin D. Only i.v. calcitriol acutely corrected the hypocalcemia, despite trying several oral preparations, suggesting that malabsorption secondary to chronic liver disease was the cause of his rickets. Intramuscular calciferol quickly corrected his muscle weakness and X-ray findings. Myopathy secondary to vitamin D deficiency is an uncommon diagnosis in children. Intermittent calciferol is an inexpensive and practical treatment for vitamin D deficiency, especially if associated with malabsorption.
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PMID:Treatment of malabsorption vitamin D deficiency myopathy with intramuscular vitamin D. 1612 49

Multiple factors can contribute to the development of osteodystrophy in patients with chronic liver disease (CLD). Recently, two new cytokines, osteoprotegerin (OPG) and the receptor activator of nuclear factor-kB ligand (RANKL), have been implicated in the pathogenesis of postmenopausal osteoporosis and other metabolic bone diseases. Therefore, the aim of our study was to evaluate bone metabolism, bone mineral density (BMD) and OPG/RANKL system in 65 male patients with CLD and in 65 healthy controls. Our patients showed lower BMD values than controls both at lumbar and femoral levels. Moreover, they had an unbalanced bone turnover with an increased resorption phase, as shown by high levels of urinary deoxypyridinoline and a decreased formation phase, as shown by the slightly, but significant, low levels of bone-alkaline phosphatase. Patients showed lower plasma levels of free-testosterone than controls and higher - although not significantly so - plasma levels of 17 beta-estradiol. Furthermore, patients with CLD had higher levels of sex hormone-binding globulin and OPG, and lower levels of 25-hydroxyvitamin D (25-HOD) and IGF-I than the control group, while RANKL levels were similar in the two groups. In conclusion, our data do not confirm the hypothesis that the OPG/RANKL system could exert a key role in the pathogenesis of hepatic osteodystrophy, but rather that the observed increase in OPG levels may represent either the result of the inflammatory process per se or a compensation for the observed enhanced bone resorption.
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PMID:Hepatic osteodystrophy: does the osteoprotegerin/receptor activator of nuclear factor-kB ligand system play a role? 1627 62

Reduced bone density is commonly encountered in patients with chronic liver disease. Prior studies have shown that unconjugated bilirubin inhibits osteoblast activity and function in vitro and in animal models of bone mineralization. To determine whether hyperbilirubinemia promotes the development of hepatic osteodystrophy, bone mineral density (BMD) was measured by dual energy X-ray absorptiometry in a cohort of 86 consecutive patients with chronic liver disease referred for liver transplant evaluation. The mean age of the study population was 52 years (range, 22-73), in which 52% were female and 90% were white. Average bone density values were significantly lower than expected for age, race, and sex, with Z-scores for the femoral neck and spine of -0.50 (95% confidence interval [CI] -0.63 to -0.37; p=0.0003) and -0.69 (95% CI -0.85 to -0.52; p=0.0001), respectively. Sixty-one subjects (71%) exhibited reduced BMD (T-score of femoral neck or spine<or=-1 standard deviation [SD] below the young-adult mean), and 18 subjects (21%) met criteria for osteoporosis (T-score<-2.5 SD). Stepwise logistic regression analyses identified significant associations between BMD and serum creatinine, alkaline phosphatase, age, and gender. On the other hand, neither unconjugated, nor conjugated, nor total serum bilirubin levels were found to predict diminished BMD. The lack of association between serum unconjugated bilirubin levels and bone mineralization was validated in hyperbilirubinemic Gunn rats, in which BMD and serum osteocalcin levels were no different than in wild-type rodents. In conclusion, the finding that serum bilirubin levels do not correlate with reduced BMD in patients with end-stage liver disease, and that chronic unconjugated hyperbilirubinemia does not lead to alterations in bone mineralization in Gunn rats, suggests that bilirubin is not a major contributing factor to hepatic osteodystrophy.
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PMID:Hyperbilirubinemia is not a major contributing factor to altered bone mineral density in patients with chronic liver disease. 1673 39

An increased frequency of infections has been reported in patients with chronic liver disease. The tendency of patients in this population to acquire UTI is not completely understood. We aimed at investigating the incidence of UTI in children with cirrhosis, before liver transplantation. Twenty-six children (9 girls, 17 boys; mean age, 7.66 +/- 5.73 yr) with chronic liver disease who had undergone liver transplantation between 2002 and 2004 were included. On admission for liver transplantation, patients were examined for presence of UTI. Serum biochemistry, complete blood cell count, urinalysis and culture, glomerular filtration rate, and abdominal ultrasonography were performed prior to liver transplantation. Ten of 26 patients (38.5%) were found to have symptomatic UTI. Urine cultures revealed E. coli in five (50%), Klebsiella pneumoniae in three (30%), Enterococcus faecalis in one (10%), and Enterobacter aeruginosa in one (10%) patient(s), respectively, as etiologic factors. The etiologies of chronic liver disease in our patients with UTI were BA in five, PFIC in three, Wilson's disease in one, and alpha-1 antitrypsin deficiency in one patient. We found a significantly greater number of UTIs in patients with biliary atresia than in those without biliary atresia (p < 0.05). The mean age of the patients with UTI was 2.75 +/- 3.49 yr, which was significantly lower than in those without UTI (9.75 +/- 4.86 yr, p < 0.05). Levels for white blood cells, thrombocytes, ALT, and alkaline phosphatase were significantly higher in patients with UTI than in those without UTI. There were no significant differences between the groups with regard to serum albumin, bilirubin, AST, GGT, BUN, or creatinine levels, glomerular filtration rate, duration of disease, and PELD scores. In patients with bacteriuria, renal USG revealed normal findings in all, but except one patient who had pelvicalyceal dilatation. Scintigraphic findings demonstrated acute pyelonephritis in six (60%) patients with UTI. VCUG demonstrated vesicoureteral reflux in two patients. In conclusion, symptomatic UTI is common in children with cirrhosis. It occurs more frequently in patients with biliary atresia than it does in patients with other types of chronic liver disease. In febrile children with chronic liver disease, UTI should be considered in the differential diagnosis.
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PMID:Frequency of urinary tract infection in pediatric liver transplantation candidates. 1749 20

In this study we retrospectively assessed the prevalence of impaired liver function in all 49 patients suffering from Mediterranean Spotted Fever (MSF) consecutively admitted to our department over the last four years. The main parameters of liver function and ultrasound of upper abdomen were performed at entry and at the end of treatment. At admission mean values of transaminases were above the normal limits and significantly higher when compared to mean serum levels at recovery. 55% and 51% of patients had serum values of GOT and GPT, respectively, above the normal limits versus 1% and 2% at the end of treatment. Mean serum values of alkaline phosphatase (AP) were within the normal limits at entry in hospital, but 22 of them had serum values above the normal limits. The same proportion was seen for gamma glutamiltranspeptidase values. Eighteen patients (36.7%) had both transaminases and AP above the normal limits. There were no significant differences among serum values of albumin, bilirubin and gamma globulin before and after therapy. Platelet count, on the contrary, was significantly reduced at admission (p < 0.0001). At ultrasound half of the patients showed hepatomegaly with a hepatitis-like pattern and 39% of patients had splenomegaly. In conclusion, this study confirms previous data from the literature showing a high frequency of liver impairment during the course of MSF, which is usually mild-moderate. In a few cases, however, the increase of transaminases could be serious and the recovery delayed, but never, in our experience, has there been progression toward chronic liver disease.
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PMID:[Abnormal liver function in Mediterranean spotted fever]. 1759 97

Adiponectin possesses anti-inflammatory, insulin-sensitizing and anti-atherosclerotic properties. The aim of this study was to assess the levels of serum adiponectin in patients with chronic viral hepatitis C and B and correlate them with parameters exploring insulin resistance and indices of chronic liver disease. Seventy-two patients with chronic hepatitis C virus (HCV) infection and 73 patients with chronic hepatitis B virus (HBV) infection, matched for age and sex, were studied. All individuals were examined for serum concentrations of adiponectin, insulin, C-peptide and homeostasis model assessment for insulin resistance (HOMA-IR). Viral parameters and liver histology were also evaluated. Serum adiponectin levels were significantly higher in HCV compared with HBV-infected patients. Correlation analysis in the whole group demonstrated that serum adiponectin was positively correlated with aspartate aminotransferase, alkaline phosphatase, globulins, high-density lipoprotein cholesterol and staging score, while it was negatively correlated with body mass index, insulin, C-peptide and HOMA-IR. Logistic regression analysis identified type of infection (HCV vs HBV), alcohol consumption more than 25 g daily, serum total globulin and low C-peptide as significant predictive variables associated with high adiponectin levels. Higher levels of serum adiponectin in HCV compared with HBV patients could have a role in the slower disease progression of chronic HCV infection. In addition, alcohol intake more than 25 g daily seems to be a significant predictor for hyperadiponectinaemia in patients with chronic viral hepatitis C or B. Finally, in this study, a clear positive association between adiponectin and hepatic necroinflammation or staging score was not found.
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PMID:Serum adiponectin in chronic hepatitis C and B. 1765 Feb 92

Bone loss has been shown to be associated with chronic liver disease (CLD) caused by ethanol consumption or viral infection, and trabecular bone is affected more than cortical bone. We therefore used calcaneal ultrasound to compare the bone status of 54 males and 20 females with CLD in northern Nigeria with 88 age- and gender-matched healthy controls. Serum levels of bone-specific alkaline phosphatase (BSAP) and the N-terminal telopeptide of type-1 collagen (NTx) were also measured to estimate relative rates of bone synthesis and turnover, respectively. The mean stiffness index (SI) of the males with CLD and the male controls were not different; however, the mean SI of the female subjects with CLD was lower than for the female controls (101 vs. 86, p=0.003). The levels of NTx and BSAP were markedly elevated in the males, but not in the females, with CLD. Liver function tests did not correlate with ultrasound parameters or biochemical markers of bone metabolism. These results show that Nigerian women, but not males, with CLD have decreased bone density as assessed by calcaneal ultrasound; however, the high rate of bone turnover in Nigerian males with CLD indicates that they are at risk for bone loss.
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PMID:Use of calcaneal ultrasound and biochemical markers to assess the density and metabolic state of the bones of adults with hepatic cirrhosis. 1791 12

Adefovir dipivoxyl (ADV) effectively suppresses hepatitis B virus (HBV) replication but exhibits nephrotoxicity with severe hypophosphatemia when administered at a high dosage. This is the first report of severe hypophosphatemic osteomalacia induced by ADV at 10 mg/day. A 42-year-old man with HBV-related chronic liver disease presented with generalized bone pain, especially in the left ankle. He had been taking ADV for more than 1.5 years following a clinical breakthrough due to lamivudine-resistant HBV. Aggravating severe hypophosphatemia and elevated serum alkaline phosphatase levels with high bone fraction had been noted after 6 months of ADV therapy. Bone densitometry, simple bone X-rays, and a whole-body bone scan demonstrated osteoporosis and multiple areas with hot uptake, especially in the left ankle. All the image findings and symptoms improved after correcting the hypophosphatemia.
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PMID:[A case of severe hypophosphatemia related to adefovir dipivoxil treatment in a patient with liver cirrhosis related to hepatitis B virus]. 1881 61

Estimation of liver damage is important in the pathophysiological and toxicological study of liver disease. As a novel, non-invasive marker of liver damage, we studied the efficacy of urine bile acids (UBA) in a rat model of liver disease. Thioacetamide (TAA)-treated rats were used in this study. Single intraperitoneal administration of high-dose TAA induces severe damage to the liver, and thus is used as a model of acute hepatitis. Continuous administration of low-dose TAA yields mild damage to the liver, and induces cirrhosis and hepatic tumors. In this study, it was found that both acute and chronic administration of TAA was associated with a dose-dependent elevation of UBA. The elevation of UBA content correlated with the alteration of blood biochemical indicators, and UBA screening showed a remarkable ability to distinguish liver-damaged rats from healthy rats. In particular, UBA analysis was found to have high sensitivity, specificity, and positive predictive value for the screening of rats with abnormal serum alkaline phosphatase (ALP) activity due to chronic liver damage, which was confirmed to include cholestasis and subsequent cirrhosis by liver histological analysis. In conclusion, we demonstrated that measurement of UBA is a simple, non-invasive and effective method for the screening of cholestasis in TAA-treated rats. We suggest that UBA analysis may have potent applicability for monitoring the progress of liver damage in animal models of chronic liver disease, such as cirrhosis and hepatic encephalopathy.
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PMID:Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats. 1918 33


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