Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy and safety of 20 mg simvastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) and of 16 g cholestyramine daily in the treatment of 34 hypercholesterolaemic patients have been compared after dietary treatment and stratified randomization. The effect of combined treatment with the two drugs was studied in 5 patients with severe hypercholesterolaemia. After 6 weeks of treatment the simvastatin group showed a significantly greater (p less than 0.05) decrease in the mean total plasma cholesterol concentration from 7.88 to 5.48 mmol/l than in the cholestyramine group in whom there was a fall from 7.82 to 6.73 mmol/l. Simvastatin decreased the mean plasma LDL cholesterol concentration from 6.07 to 3.76 mml/l and cholestyramine decreased it from 6.16 to 4.46 mmol/l. Simvastatin also reduced the mean plasma total triglycerides by 24%, VLDL triglycerides by 20% and VLDL cholesterol by 36%, while cholestyramine led to increases in these parameters by 64%, 85% and 63%, respectively. Mean plasma HDL cholesterol concentration and the subfractions HDL2 and HDL3 cholesterol were significantly increased by simvastatin. Simvastatin and cholestyramine reduced the mean plasma apolipoprotein B concentration by 28% and 13%, respectively. The mean plasma apolipoprotein A-I concentration was significantly higher only on simvastatin treatment. Simvastatin did not cause any subjective or objective side effects, while cholestyramine caused gastrointestinal problems in 31% of patients. Small increases in serum alanine aminotransferase (S-ALT) activity were seen with both drugs. Cholestyramine significantly raised the serum alkaline phosphatase (S-ALP) although to a level still within the normal range. It is concluded that 20 mg simvastatin was more effective than 16 g cholestyramine in the treatment of hypercholesterolaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative effects of simvastatin and cholestyramine in treatment of patients with hypercholesterolaemia. 250 17

Serum concentrations of lipids and apolipoprotein A-I, A-II and B were determined in patients with hepatic metastases of colorectal cancer, with primary liver cancer and with cirrhosis. In all three liver diseases, the HDL fraction and apolipoproteins A-I and A-II showed significantly low values, while apolipoprotein B was only increased in hepatic metastases. The decrease of apolipoprotein A-II levels was more prominent in cirrhosis, thereby enhancing the A-I/A-II ratio. This ratio is decreased in metastasis and normal in hepatomas. In patients with hepatic metastases a correlation was observed between alkaline phosphatase and apolipoprotein A-II (p less than 0.05), and between gamma-glutamyltransferase and the A-I/A-II ratio (p less than 0.05). The present work suggests that determination of apolipoproteins and lipids of the HDL fraction offers a new approach to the study of liver diseases.
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PMID:Serum apolipoproteins A-I, A-II and B in hepatic metastases. Comparison with other liver diseases: hepatomas and cirrhosis. 287 62

Effects of CS-514, a new competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on serum lipoprotein lipid and apolipoprotein levels were studied in 13 heterozygous patients with familial hypercholesterolemia. Treatment with 10 mg of CS-514 twice daily reduced total serum cholesterol, low-density lipoprotein (LDL), and intermediate-density lipoprotein (IDL) cholesterol levels by 25%, 33%, and 33%, respectively, and increased high-density lipoprotein (HDL) cholesterol levels by 15%. Apolipoprotein B, E, and C-II levels decreased by 24%, 20%, and 19%, and apolipoproteins A-I and A-II levels increased by 10% and 7%, respectively. One patient showed abnormally high levels of SGOT, SGPT, and serum alkaline phosphatase, which returned to normal levels immediately after the cessation of CS-514. No other adverse effects were observed. Thus, CS-514 reduces atherogenic lipoproteins and apolipoprotein B, and increases HDL and apolipoprotein A-I and A-II, and appears to be a useful drug for heterozygous familial hypercholesterolemia.
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PMID:Effects of CS-514 on serum lipoprotein lipid and apolipoprotein levels in patients with familial hypercholesterolemia. 310 56

A semi-automated competitive enzyme-linked immunosorbent assay for human plasma apolipoprotein (Apo) A-I has been developed which utilizes nondelipidated samples, microtiter plates, commercially available monoclonal antibodies and alkaline phosphatase conjugated second antibody. The working range of the assay is 5-100 ng of Apo A-I. The range of plasma concentrations for plasma Apo A-I was 1.21 +/- 0.34 g/l for a random sample of 40 healthy adults. Intra- and inter-assay coefficients of variation (CV) were 4 and 7%, respectively. There was a good correlation between this assay and a radial immunodiffusion assay (r = 0.96). The assay is suitable for measurement of apolipoprotein A-I in either normal or pathological plasma, lipoprotein density classes, and for cell biological and molecular biological investigations.
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PMID:Competitive enzyme-linked immunosorbent assay (ELISA) for the quantitation of apolipoprotein A-I using a monoclonal antibody. 314 56

Pig duodeno-jejunal mucosa was maintained in organ culture for up to 24 h in Eagle's minimum essential medium containing 10% foal serum. Viability was controlled by determination of alkaline phosphatase and sucrase activity in the tissue. [14C]Leucine incorporation into proteins decreased 3-fold between 2 and 24 h. Newly synthesized secreted proteins were analyzed by SDS-polyacrylamide gel electrophoresis of the whole culture medium. Apolipoprotein A-I specifically measured by immunoelectrophoresis represented 10-20% of newly secreted proteins. Only 10% of apolipoprotein A-I secreted was recovered with the lipoprotein fraction (d less than 1.21). Recombination of the medium with porcine lipoproteins or DMPC vesicles prior to ultracentrifugation allowed, respectively, the recovery of 40 and 80% of apolipoprotein A-I secreted. The lipoprotein fractions also contained some apolipoproteins B and C and, after DMPC recombination, an apolipoprotein of Mr 45 000, most likely apolipoprotein A-IV, representing about 3.5% of newly secreted proteins. The d greater than 1.21 fractions all contained a high Mr protein, identified as IgA, and an unidentified protein of Mr approximately 45 000. The addition of colchicine (125 microM) to the culture medium did not significantly modify either tissue enzyme activities or [14C]leucine incorporation. It reduced total secretion by about 40% between 2 and 8 h of incubation, without interfering with apolipoprotein A-I secretion, which then represented up to 35% of secretion products. This raises the question of the mode of secretion of apolipoprotein A-I, which may be related to the high proportion of its which is secreted free.
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PMID:Synthesis and secretion of apolipoproteins by pig intestinal mucosa in organ culture. Lack of inhibition of apolipoprotein A-I secretion by colchicine. 641 11

Abnormalities in circulating lipoprotein concentrations are a characteristic finding in patients undergoing dialytic therapy. A substantial number of these patients display type IV hyperlipoproteinemia. Certain data suggest that secondary hyperparathyroidism may induce disturbances in lipid metabolism. To evaluate the effects of pulse calcitriol therapy on the lipid profile in these patients, we undertook a prospective study in 12 patients on stable bicarbonate hemodialysis. Lipid parameters comprising cholesterol and the low- as well as the high-density lipoprotein subfractions, triglycerides, apolipoproteins A and B, serum parathyroid hormones (iPTH), alkaline phosphatase, calcium, phosphorus, hematocrit, and blood urea were obtained prior to commencement of pulse calcitriol therapy and again 8-10 weeks later. Calcitriol therapy was associated with a decrease in serum iPTH levels (701 +/- 103.9 vs. 220.3 +/- 50.5 pmol/l; p < 0.001). Significant increases in high-density lipoprotein cholesterol (32.8 +/- 2.7 vs. 38.8 +/- 2.3 mmol/l; p < 0.05) and apolipoprotein A-I (107.8 +/- 6.1 vs. 121.8 +/- 5.8 g/l; p < 0.05) were noted during the course of the study. Moreover, serum iPTH correlated inversely with high-density lipoprotein cholesterol and apolipoprotein A-I. There were no changes in other lipid parameters except for low-density lipoprotein cholesterol which showed a tendency to increase. We conclude that in short-term study, pulse oral calcitriol therapy is associated with an improvement in the lipid profile in patients with secondary hyperparathyroidism. However, it remains to be established whether ameliorating the uremic dyslipidemia results in any long-term clinical benefits.
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PMID:Effects of treatment of secondary hyperparathyroidism on the lipid profile in patients on hemodialysis. 951 59

Nowadays, bisphosphonates are considered the drugs of choice for the treatment of several bone disorders. Their exact mechanism of action is not clear but recently it has been reported that the aminobisphosphonates inhibit cholesterol biosynthesis and that this might be relevant for their actions on bone osteoclasts. The study includes 87 postmenopausal women with moderate to severe osteoporosis. The patients were randomly assigned to intravenous (iv) infusion of 50 mg of the aminobisphosphonate Neridronate dissolved in 100 ml of saline solution every 2 months for a year (44 patients). The remaining 43 served as controls. At the time of each infusion blood samples were obtained for the evaluation of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), and total and bone alkaline phosphatase (AP). Free deoxypyridinoline (f-DPD) was measured in fasting urine specimens. In the control group no significant changes were observed throughout the study period for any of the biochemical variables. In the Neridronate-treated patients both bone AP and f-DPD excretion fell significantly by 15-20%. In these patients serum total cholesterol and serum triglycerides showed marginal decreases, which were occasionally significant. LDL-C and Apo B fell by 5-6% and these changes were statistically significant at most time points. Apo A-I and HDL-C rose progressively with time. At the 12th month, HDL-C rose 17-18% (p < 0.0001) above the baseline values. Similar findings were obtained in four postmenopausal women given high iv doses of Pamidronate or Alendronate. In conclusion aminobisphophonates, at least when given iv, induce remarkable and unexpected effects on lipid metabolism with a final profile that might be clinically relevant.
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PMID:Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol. 1075 May 76

Surfactant-like particle (SLP) is a phosphatidylcholine (PC)-rich membrane produced in the small intestine, and its secretion is increased by fat feeding. In Caco-2 cells known to produce SLP, preincubation with [(3)H]palmitate labelled the SLP and was used as a marker for newly secreted membrane. SLP-associated PC and protein (d=1.07-1.08 g/ml in a linear non-equilibrium NaBr gradient) were secreted in parallel with triacylglycerols (TG) and at a rate about twice the control rate in response to feeding cells with an oleate/egg PC mixture. Cholesterol and apolipoprotein A-I identified only a small peak corresponding to high-density lipoprotein (HDL), but the largest peak corresponded with SLP (d=1.07-1.08). Palmitate incorporation into PC showed a similar small peak migrating at the density of HDL, but most labelled PC secreted from the cells was due to SLP. PC secretion, alkaline phosphatase activity, and newly synthesized immunoprecipitated SLP proteins from conditioned serum-free media migrated together at a density of >/=1.21 g/ml in a lipoprotein NaBr step gradient, and represented SLP. Glycerol incorporated into TG migrated at a peak density of 1.12 g/ml, consistent with HDL secretion from cells incubated in serum-free media. These data confirm that the secreted PC in SLP is distinct from lipoprotein particles. Incorporation of [(3)H]palmitate into the PC fraction of either whole cell homogenate or isolated brush border membranes was not affected by oleate/egg PC feeding. Both Pluronic L-81, an inhibitor of chylomicron secretion, and BMS-197636-02, a microsomal triglyceride transfer protein inhibitor, blocked the secretion of both TG and PC. Elevation of intracellular cAMP levels that stimulate surfactant secretion from type II pneumocytes caused a 50% reduction in SLP and TG secretion from Caco-2 cells. These results confirm the SLP response to fat feeding found in vivo, further supporting a role for SLP in TG secretion from the enterocyte, and show that the regulation of SLP secretion differs from that of pulmonary surfactant.
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PMID:Regulation of surfactant-like particle secretion by Caco-2 cells. 1128 80

Based on titration microcalorimetry and Caco-2 cell line transfection studies, it has been suggested that the A54T of the FABP2 gene plays a significant role in the assimilation of dietary fatty acids. However, reports were divergent with regard to the in vivo interaction between this polymorphism and postprandial lipemia. We therefore determined the influence of this intestinal fatty acid-binding protein polymorphism on intestinal fat transport using the human jejunal organ culture model, thus avoiding the interference of various circulating factors capable of metabolizing in vivo postprandial lipids. Analysis of DNA samples from 32 fetal intestines revealed 22 homozygotes for the wild-type Ala-54/Ala-54 genotype (0.83) and 10 heterozygotes for the polymorphic Thr-54/Ala-54 genotype (0.17). The Thr-encoding allele was associated with increased secretion of newly esterified triglycerides, augmented de novo apolipoprotein B synthesis, and elevated chylomicron output. On the other hand, no alterations were found in very low density lipoprotein and high density lipoprotein production, apolipoprotein A-I biogenesis, or microsomal triglyceride transfer protein mass and activity. Similarly, the alanine to threonine substitution at residue 54 did not result in changes in brush border hydrolytic activities (sucrase, glucoamylase, lactase, and alkaline phosphatase) or in glucose uptake or oxidation. Our data clearly document that the A54T polymorphism of FABP2 specifically influences small intestinal lipid absorption without modifying glucose uptake or metabolism. It is proposed that, in the absence of confounding factors such as environmental and genetic variables, the FABP2 polymorphism has an important effect on postprandial lipids in vivo, potentially influencing plasma levels of lipids and atherogenesis.
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PMID:The polymorphism at codon 54 of the FABP2 gene increases fat absorption in human intestinal explants. 1148 82

In the present study we used patient data to calculate laboratory-specific indirect reference intervals. These values were compared with reference intervals obtained for a healthy group according to recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine and manufacturer suggestions. Laboratory results (422,919 records) from all subjects of 18-45 years of age over a 1-year period were retrieved from our laboratory information system and indirect reference intervals for 40 common analytes were estimated using a modified Bhattacharya procedure. Indirect reference intervals for most of the biochemical analytes were comparable, with small differences in lower [alkaline phosphatase (ALP) (male), alanine aminotransferase (ALT), creatine kinase, iron (male), total iron-binding capacity, folic acid, calcium (female), lactate dehydrogenase (LDH), lipoprotein (a) [Lp(a)], thyroid-stimulating hormone (TSH), total triiodothyronine (T(3)), direct bilirubin, apolipoprotein A-I (apoA-I), glucose, homocysteine, total cholesterol, ferritin, total protein, ceruloplasmin, sodium, blood urea nitrogen (BUN) and uric acid (female)] and/or upper limits [albumin, ALP (male), amylase, apoA-I, creatine kinase-MB (CK-MB), total iron-binding capacity, phosphorus, glucose, total cholesterol, gamma-glutamyltransferase (gamma-GT), magnesium, total protein, high-density lipoprotein cholesterol (HDL-C), total T(3), ALP (male), ALT, aspartate aminotransferase (AST) (male), direct bilirubin (male), creatine kinase, iron, folic acid (female), Lp(a), uric acid and triglycerides], to the reference intervals determined for healthy subjects in our laboratory. The indirect reference intervals, with the exception of a few parameters (creatinine, direct total bilirubin, calcium, BUN and potassium), were not similar to the reference intervals suggested by the manufacturers. We conclude that laboratory-specific reference intervals can be determined from stored data with a relatively easy and inexpensive method. Indirect reference intervals derived from stored data may be particularly suitable for the evaluation of results for the presenting population.
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PMID:Use of total patient data for indirect estimation of reference intervals for 40 clinical chemical analytes in Turkey. 1677 35


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