Ritonavir impairs lipoprotein lipase-mediated lipolysis and decreases uptake of fatty acids in adipose tissue

Objective - The use of the HIV protease inhibitor ritonavir (RTV) is frequently associated with hypertriglyceridemia and lipodystrophy. The aim of our study was to determine the mechanism underlying the observed hypertriglyceridemia. Methods and Results - Feeding female APOE*3-Leiden transgenic mice a Western-type diet supplemented with RTV (35...

Generation of neoheparin from E. coli K5 capsular polysaccharide

Heparin remains a major drug in prevention of thromboembolic disease. Concerns related to its animal source have prompted search for heparin analogues. The anticoagulant activity of heparin depends on a specific pentasaccharide sequence that binds antithrombin. We report the generation of a product with antithrombin-binding, anticoagulant, and...

Disagreement between bedside and laboratory activated partial thromboplastin time and international normalized ratio for various novel anticoagulants

During studies on warfarin, heparin and various anticoagulants with novel mechanisms of action, the activated partial thromboplastin time (aPTT) and the (apparent) international normalized ratio (INR) from a bedside monitor (Coagucheck Plus®) were compared with laboratory assay results. Data were compared using the Bland and Altman method of...

Apolipoprotein E*3-Leiden transgenic mice mode for hypolipidaemic drugs

Apolipoprotein (APO) E*3-Leiden mice with impaired chylomicron and VLDL (very low density lipoprotein) remnant metabolism display hyperlipidaemia and atherosclerosis. In the present study, these mice were used for testing the hypolipidaemic effect of two marketed agents, lovastatin (CAS 75330-75-5) and gemfibrozil (CAS 25812-30-0) as well as a...

Inhibition of mannose receptor-mediated-clearance of tissue-type plasminogen activator (t-PA) by dextran: A new explanation for its antithrombotic effect

Dextran is used during surgery as a prophylactic agent to prevent deep venous thrombosis. Recently it has been shown that dextran increases t-PA plasma concentrations in patients. As dextran is a potential ligand for the mannose receptor, we studied whether this glucose-polymer would be able to inhibit mannose receptor-mediated clearance of t-PA...

Reduced Response to Activated Protein C Is Associated with Increased Risk for Cerebrovascular Disease

Background: Resistance to activated protein C (APC), which results from various factors, including a mutation in the gene for coagulant factor V, has been associated with increased risk for venous thrombosis. However, its relation to arterial disease is still not well defined. Objective: To investigate the association of both response to APC and...

Familial dysfibrinogenemia and thrombophilia - Report on a study of the SSC subcommittee on fibrinogen

Approximately 250 cases of dysfibrinogenemia have been reported; 55% were asymptomatic (detected by chance), 25% had a tendency to bleeding, and 20% were reported to have a tendency to thrombosis. To establish a possible association between familial dysfibrinogenemia and thrombophilia, data on cases with both affections were collected in a study...

A bio-immuno assay to determine free tissue-type plasminogen activator (t-PA) in Stabilyte® plasma

This article describes a two-step bio-immuno assay (BIA), which determines active (free) tissue-type plasminogen activator (t-PA) in (acidified) plasma. Plasma samples, diluted in buffer of pH 6.0, are added to the wells of a microtiter plate containing an immobilised monoclonal antibody which binds t-PA without affecting t-PA activity. After an...

Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen (plasmin fragments Y)

The present study was undertaken as a step to delineate further the localization of the calcium-binding sites in fibrinogen and to assess the anticlotting properties of fibrinogen degradation products. To this purpose, fragments Y were prepared by plasmin digestion of human fibrinogen in the presence of added Ca2+, and purified. We found that,...