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:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin is used as standard anticoagulant in the extracorporeal circuit of hemodialysis. Widespread use of this drug revealed several potentially adverse effects, such as release of lipoprotein lipase and hepatic lipase from the endothelial surface. Recently it was found that anticoagulatory potency and provocation of adverse effects are linked to different subfractions of heparin. A heparin subfraction of 4000 to 6000 Daltons rather specifically inhibits factor Xa and therefore has a very high antithrombotic potency. Its effects on release of lipases are minor. During a four year period five patients on maintenance hemodialysis were treated with this low molecular weight heparin (LMWH) subfraction. Additionally, another five patients successively received standard heparin, LMWH and again standard heparin. At all circumstances during treatment with LMWH there was a significant (0.001 less than P less than 0.05) reduction both of cholesterol and triglyceride blood concentrations. LMWH is efficient in avoiding clotting in extracorporeal circuit during hemodialysis in doses of 17 to 95 U/kg (initial dose) and 7 to 20 U/kg/hr (continuous dose).
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PMID:Reduced lipid concentrations during four years of dialysis with low molecular weight heparin. 166 3

Two different preparations of hepatic triglyceride lipase (HTGL) with comparable lipolytic activities, purified from post-heparin human plasma, were assessed for their anti-Xa activities by two clotting and one chromogenic method. Preparation 1, prepared by heparin affinity followed by ion exchange chromatography, did not contain antithrombin III and exhibited no anti-Xa activity in any of the assay systems. Preparation 2, prepared by two consecutive heparin affinity chromatography steps, was active in all three assay systems, and was shown to contain antithrombin III (AT III). Addition of purified AT III to preparation 1 did not result in the anti-factor Xa activity of preparation 2, and monoclonal antibodies to AT III did not antagonize the activity of preparation 2. These results show that the anti-Xa activity of some HTGL preparations is neither due to the lipase itself nor to the content of AT III, but suggest, that it could be due to contamination with another protein, which binds to heparin sepharose columns but is removed during ion exchange chromatography. Most likely the effect is due to the extrinsic pathway inhibitor (EPI), also called lipoprotein-associated coagulation inhibitor (LACI), which has recently been shown to be released by heparin.
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PMID:Anti-Xa clotting activities in different hepatic-triglyceride lipase preparations from post-heparin plasma. 175 3

Three human volunteers were injected with a range of doses of pentosan polysulphate, SP54, i.v. or s.c. A competitive binding assay (CBA) for sulphated polysaccharides was used to detect circulating SP54 after doses as low as 1 mg i.v. and a linear relationship was observed between the peak plasma concentration of SP54 measured by CBA and the administered dose. A comparison was made between the clearance of SP54 measured by CBA and its anticoagulant and lipolytic activities. SP54 was detectable by CBA after doses which caused no alteration in activated partial thromboplastin time (APTT) or anti-factor Xa activity but after which a small increase of lipase activity was measurable. After SP54 at 10 mg i.v. or 100 mg s.c. anti-factor Xa activity was 4-6 times greater than would be expected from the in vitro activity of the concentrations of SP54 measured by CBA. Like heparin and other heparin analogues, SP54 caused an increase in plasma concentrations of platelet factor 4 (PF4) without a concomitant rise in beta-thromboglobulin (beta-TG). It is concluded that the newly developed CBA will provide a more sensitive means than conventional bioassays for the determination of plasma concentrations of SP54.
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PMID:Metabolism of sodium pentosan polysulphate in man measured by a new competitive binding assay for sulphated polysaccharides--comparison with effects upon anticoagulant activity, lipolysis and platelet alpha-granule proteins. 241 64

Lipoprotein lipases from human, bovine or guinea-pig milk were purified, judged for domain relationships by characterization of sites sensitive to proteases, and structurally compared. The subunit of human lipoprotein lipase migrated slightly slower than those of bovine or guinea-pig lipoprotein lipases on sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Bovine lipoprotein lipase is known to be a dimer of two non-covalently linked subunits of equal size, and the lipases from all three sources now yielded homogeneous N-terminal amino acid sequences (followed for 15-27 residues). The results indicate that the two subunits are identical. Bovine lipoprotein lipase had two additional N-terminal residues, Asp-Arg, compared to the human and guinea-pig enzymes, and the next two positions revealed residue differences, but further on homologies were extensive between all three enzymes as far as presently traced. Exposure of bovine lipoprotein lipase to trypsin led to production of three fragments (T1, T2a, and T2b), suggesting cleavage at exposed segments delineating domain borders. Time studies gave no evidence for precursor-product relationships between the fragments, and prolonged digestion did not lead to further cleavage. Fragments T2a and T2b had the same N-terminal sequence as intact lipase. Fragment T1 revealed a new sequence, and represents the C-terminal half of the molecule. Plasmin caused a similar cleavage as trypsin, whereas thrombin, factor Xa, and tissue plasminogen activator did not cleave the enzyme. Chymotrypsin cleaved off a relatively small fragment from the C-terminal of the molecule, after which exposure to trypsin still resulted in cleavage at the same sites as in intact lipase. Tryptic cleavage of guinea-pig lipoprotein lipase yielded two fragments. One had a similar size as bovine fragment T2b; the other had a similar size as bovine fragment T1 and an N-terminal sequence homologous with that of T1. Thus, trypsin recognizes the same unique site in guinea-pig lipoprotein lipase as in the bovine enzyme. This confirms the conclusion that this segment is the border between two domains in the subunit. The binding site for heparin was retained after both tryptic and chymotryptic cleavages and was identified as localized in the C-terminal part of the molecule.
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PMID:Lipoprotein lipases from cow, guinea-pig and man. Structural characterization and identification of protease-sensitive internal regions. 353 11

Human hepatic triglyceride lipase (HTGL), purified from plasma obtained after heparin injection, markedly enhanced the anti-Xa clotting activity of normal plasma. This was shown to be caused by direct inhibition of factor Xa clotting activity by HTGL, although the amidolytic activity of factor Xa was unaffected. Preincubation of factor Xa with CaCl2 and phospholipid reduced the rate of inhibition of HTGL, indicating that phospholipid-binding sites may be involved. Heparin, and low-affinity heparin, reduced the anti-Xa activity of HTGL, suggesting that heparin and factor Xa compete for the same binding sites on the lipase molecule. These results suggest that at least part of the enhanced anti-Xa clotting activity observed after injection of heparin and heparin analogues is caused by the release of HTGL. This release could contribute toward the anticoagulant and antithrombotic actions of these drugs.
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PMID:Anti-Xa activity of human hepatic triglyceride lipase. 358 39

Drug monitoring for valproic acid (Convulex) was performed in 200 children with a newly developed HPLC procedure and in part with an enzyme immunoassay (EMIT). In addition the activities of the transaminases and the lipase were determined as well as platelet count, prothrombin time, thrombin time, partial thromboplastin time, fibrinogen concentration and in some cases the coagulation factors II, V and X. There is not a higher frequency for pathological laboratory findings with higher serum levels. 81 children exhibited pathological findings, however only in one case therapy had to be stopped. Recommendations when to stop therapy are given.
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PMID:[Drug monitoring for valproic acid with HPLC or EMIT and concomitant measurements of clinical-chemical parameters (author's transl)]. 680 13

Heparin was absorbed through the rectal mucosa of rodents and primates only when administered in solutions containing sodium cholate or sodium deoxycholate (DOC). The absorption of heparin was monitored by following the increase in plasma radioactivity after administration of [35S]heparin, and by measurement of its biological effects: plasma lipase activity and prolongation of partial thromboplastin time (PTT). Following administration of the same concn of heparin in solutions lacking bile salts, there was almost no radioactivity in the blood, no prolongation of PTT and no release of plasma lipase activity. The PTT effect was found to be a less sensitive test of heparin absorption than the plasma lipase activity.
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PMID:Bile salts facilitate the absorption of heparin from the intestine. 683 25

Some or most of the turnover of lipoprotein lipase (LPL) occurs by dissociation from vascular endothelial sites in extrahepatic tissues and further degradation in the liver. Heparin greatly enhances this dissociation and delays but does not abolish uptake in the liver, raising the possibility that heparin could lead to accelerated catabolism of functional LPL. To investigate this, we determined time curves for heparin (anti-factor Xa activity) and for LPL and hepatic lipase after injection in rats of two doses of conventional unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). The high dose (250 U/kg) of both heparins resulted in similar initial levels of LPL activity in plasma, but at 30 minutes the activity with LMWH had declined by more than 80%, whereas with UFH it remained essentially unchanged during this time. In contrast, time curves for heparin activity in blood were similar for the two heparins. The low dose (50 U/kg) led to lower initial levels of LPL activity with LMWH in spite of slower elimination of heparin activity from the blood. These results agree with previous studies that indicate that LMWH has a similar ability as UFH to release LPL, but a lesser ability to delay its removal by the liver. Only slight differences were noted in the time curves for hepatic lipase with the two heparins. To assess the possible depletion of the lipases, we administered a second large dose of conventional heparin. One hour after the first injection, the second injection resulted in lower plasma LPL activities in all four groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Depletion of lipoprotein lipase after heparin administration. 839 74

Warfarin overdose leads to hypoprothrombinemia and bleeding diathesis. We report here the case of a 47 year old woman who ingested an overdose of a non-steroidal anti-inflammatory drug, sold in Mexico under the name of Wobenzym (R), and containing, according to the manufacturer: pancreatin, bromelin, papain, lipase, amylase, trypsin, alpha chymotrypsin and rutin. She developed skin, urinary and gastrointestinal bleeding and was found to be apparently under the effect of a coumadin overdose, i.e. prolonged prothrombin time, prolonged activated thromboplastin time, and low functional and antigenic levels of prothrombin. A platelet count, and the thrombin, reptilase and bleeding times were normal. All laboratory and clinical abnormalities reverted to normal by using fresh frozen plasma and parenteral vitamin K. In addition, we were able to show that the commercial preparation could prolong the prothrombin time in rabbits and, by high-performance liquid chromatography, a pike consonant with purified coumadin was found in the drug. It is concluded that this drug is probably contaminated by coumadin, and that physicians must be aware of its potential side effects.
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PMID:[Probable coumarin poisoning upon ingestion of an anti-inflammatory agent]. 896 87

The aim of the study was to develop a model for the pre-exercise elevation of plasma free fatty acids in the horse, with a view to its future use in investigations of fat metabolism during exercise. A comparison of the lipase releasing and anticoagulative effects of heparin and a related substance pentosan polysulphate was investigated. Furthermore, the ability of heparin and pentosan polysulphate to affect an increase in plasma free fatty acid concentration, when co-administered with-a triglyceride emulsion, was quantified. Doses of 0.39 and 1.3 mg kg-1 body wt of heparin and pentosan polysulphate respectively, administered intravenously, resulted in a significant increase in plasma total lipase activity (P < 0.001). There was, however, no significant difference in plasma lipase activity between treatments. Heparin resulted in a mean 14 +/- 6.5-fold increase in activated partial thromboplastin time compared with a mean 1.6 +/- 0.1-fold increase with pentosan polysulphate. Both heparin and pentosan polysulphate when coadministered with a triglyceride emulsion (lverlip 20) resulted in a significant increase in plasma free fatty acid concentration (P < 0.001), although there was no significant difference between treatments. Thus, whereas a higher dose of pentosan polysulphate elicited a comparable lipolytic effect to heparin, including significant elevation of plasma free fatty acids, this was associated with a much reduced effect upon clotting function. Pentosan polysulphate, therefore, represents a suitable alternative to heparin for the elevation of plasma free fatty acids before exercise when used in conjunction with a triglyceride emulsion.
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PMID:A comparison of the lipolytic and anticoagulative properties of heparin and pentosan polysulphate in the thoroughbred horse. 905 47


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