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Sergio Coccheri,1 Ferdinando Mannello2 1Cardiovascular Medicine, University of Bologna, Bologna, 2Department of Biomolecular Sciences (Section Clinical Biochemistry and Cell Biology), University 'Carlo Bo', Urbino, Italy Abstract: Sulodexide (SDX), a sulfated polysaccharide complex extracted from porcine intestinal mucosa, is a blend of two glycosaminoglycan (GAG) entities, namely a fast-moving heparin (HP) fraction and a dermatan sulfate (DS; 20%) component. The compound is unique among HP-like substances in that it is biologically active by both the parenteral and oral routes. A main feature of the agent is to undergo extensive absorption by the vascular endothelium. For this reason, in preclinical studies, SDX administered parenterally displays an antithrombotic action similar to that of HPs but associated with fewer alterations of the blood clotting mechanisms and tests, thus being much less conducive to bleeding risk than HPs. When given orally, SDX is associated with minimal changes in classic coagulation tests, but maintains a number of important effects on the structure and function of endothelial cells (EC), and the intercellular matrix. These activities include prevention or restoration of the integrity and permeability of EC, counteraction versus chemical, toxic or metabolic EC injury, regulation of EC–blood cell interactions, inhibition of microvascular inflammatory and proliferative changes, and other similar effects, thus allowing oral SDX to be considered as an endothelial-protecting agent. The best available clinical evidence of the efficacy of SDX administered orally with or without an initial parenteral phase is the following: alleviation of symptoms in chronic venous disease and especially acceleration of healing of venous leg ulcers; prevention of cardiovascular events in survivors after acute myocardial infarction; marked improvement of intermittent claudication in patients with peripheral occlusive arterial disease; and abatement of proteinuria in patients with diabetic nephropathy that may contribute to the amelioration or stabilization of kidney function. Although further clinical trials are warranted, SDX is presently widely accepted in many countries as an effective and safe long-term, endothelial-protecting drug. Keywords: sulodexide, glycosaminoglycans, chronic venous disease, cardiovascular disease, diabetic nephropathy

Aims Patients with peripheral arterial obstructive disease require treatment to prevent major cardiovascular events and to relieve intermittent claudication. The walking performance of peripheral arterial obstructive disease patients was used to evaluate the usefulness of sulodexide, a glycosaminoglycan containing fast moving heparin and dermatan sulphate.Methods and Results A randomized, multicentre, double-blind, placebo-controlled study was performed in 286 patients with Leriche-Fontaine stage II peripheral arterial obstructive disease. Patients received placebo (n=143) or sulodexide (n=143) for 27 weeks. The primary end-point was the doubling of the pain-free walking distance at the end of treatment, and this was achieved by 23·8% of patients treated with sulodexide and 9·1% of those on placebo (P=0·001). The pain-free walking distance increased on average (±SE) by 83·2±8·6m (+64·7% from baseline) with sulodexide and 36·7±6·2m (+29·9% from baseline) with placebo (P=0·001). The maximum walking distance increased by 142·3±15·8m (+76·0% from baseline) and 54·5±8·4m (+27·9% from baseline) (P<0·001), respectively. Results for patients with type II diabetes were similar to those for non-diabetic patients. Plasma fibrinogen decreased with sulodexide, but increased with placebo.Conclusion Sulodexide improved the walking ability of peripheral arterial obstructive disease patients to a significantly greater extent than placebo, with a concurrent significant decrease in fibrinogen. The treatment was well tolerated. Copyright 2001 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved. [ABSTRACT FROM PUBLISHER]

Aims The interaction between the R506Q mutation of factor V and the G20210A mutation of prothrombin with oral contraceptives on venous thromboembolism was evaluated.Methods and Results Three hundred and one women of reproductive age who had venous thromboembolism (140 while using oral contraceptives) and 650 healthy women (173 on oral contraceptives at presentation) were examined. Of the patients, 19·3% were carriers of R506Q (two homozygotes) and 9·6% were heterozygous carriers of G20210A; eight patients (2·7%) were heterozygous for both mutations. Among controls, 2·9% were carriers of R506Q, 3·1% of G20210A, while one case was a heterozygous carrier of both mutations. The relative risk (odds ratio) associated with carriership of R506Q or G20210A mutations was 10·3 and 4·7, respectively; it was 45·6 in carriers of both mutations. The odds ratio of using oral contraceptives in the absence of both mutations was 2·4. The odds ratios according to oral contraceptives use and the presence of R506Q or G20210A or both mutations were 41·0, 58·6 and 86·5, respectively. While the odds ratio for R506Q remains elevated (8·9) in non-oral contraceptive users, the odds ratio for G20210A was 2·0 and did not reach statistical significance.Conclusions Our data showed a strong interaction between oral contraceptive use and the presence of either R506Q or G20210A mutations. In non-oral contraceptive users the risk of venous thromboembolism was significantly increased in carriers of R506Q but not in those with the G20210A mutation. [ABSTRACT FROM PUBLISHER]