Development and use of sulodexide in vascular diseases: Implications for treatment

Drug Design, Development and Therapy

Volumn 8, Issue , 2013, Pages 49-65

  Coccheri, Sergio ^a   Mannello, Ferdinando ^b  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b UNIVERSITY OF URBINO   (Italy)

Author keywords

Cardiovascular disease; Chronic venous disease; Diabetic nephropathy; Glycosaminoglycans; Sulodexide

Indexed keywords

ACETYLSALICYLIC ACID; CATHEPSIN G; CHONDROITIN SULFATE; CYTOKINE; DERMATAN SULFATE; FIBRINOGEN; GLYCOSAMINOGLYCAN; HEPARAN SULFATE; HEPARIN; HEPARIN FRACTION; HYALURONIC ACID; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 6; KERATAN SULFATE; LIPID; PLACEBO; SULODEXIDE; TICLOPIDINE; TUMOR NECROSIS FACTOR;

ANTIATHEROSCLEROTIC ACTIVITY; ANTICOAGULATION; ANTIINFLAMMATORY ACTIVITY; ANTIPROTEINURIC ACTIVITY; BLEEDING TIME; BLOOD CLOT LYSIS; BLOOD RHEOLOGY; BLOOD VISCOSITY; CAROTID ARTERY THROMBOSIS; CHOLESTEROL BLOOD LEVEL; CHRONIC VEIN INSUFFICIENCY; CHRONIC VENOUS DISEASE; CLINICAL TRIAL (TOPIC); COMPARATIVE STUDY; COMPRESSION THERAPY; DIABETIC FOOT; DIABETIC NEPHROPATHY; DIABETIC RETINOPATHY; DOSE RESPONSE; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG EFFICACY; DYSLIPIDEMIA; END STAGE RENAL DISEASE; ENDOTHELIUM CELL; FIBRINOLYSIS; HUMAN; INTRAVENOUS ADMINISTRATION; KIDNEY FIBROSIS; LEUKOCYTE ACTIVATION; MICROCIRCULATION; NONHUMAN; ORAL DRUG ADMINISTRATION; PERIPHERAL OCCLUSIVE ARTERY DISEASE; POSTTHROMBOSIS SYNDROME; PROTEINURIA; RENAL PROTECTION; RETINA MACULA EDEMA; RETINA VEIN OCCLUSION; REVIEW; THROMBOCYTE ADHESION; THROMBOSIS; TRIACYLGLYCEROL BLOOD LEVEL; ULCER; VASCULAR DISEASE; VEIN DISEASE; VEIN THROMBOSIS; ANIMAL; CEREBROVASCULAR DISORDERS; CHEMISTRY; DIABETIC NEPHROPATHIES; DRUG EFFECTS; PERIPHERAL ARTERIAL DISEASE; PHYSIOLOGY; VASCULAR DISEASES; VENOUS THROMBOSIS;

ANIMALS; CEREBROVASCULAR DISORDERS; CLINICAL TRIALS AS TOPIC; DIABETIC NEPHROPATHIES; ENDOTHELIAL CELLS; GLYCOSAMINOGLYCANS; HUMANS; PERIPHERAL ARTERIAL DISEASE; VASCULAR DISEASES; VENOUS THROMBOSIS;

EID: 84891394278     PISSN: 11778881     EISSN: None     Source Type: Journal    
DOI: 10.2147/DDDT.S6762     Document Type: Review

References (119)

1. Afratis N, Gialeli C, Nikitovic D, et al. Glycosaminoglycans: key players in cancer cell biology and treatment. FEBS J. 2012;279:1177-1197.
2. Gandhi NS, Mancera RL. The structure of glycosaminoglycans and their interactions with proteins. Chem Biol Drug Des. 2008;72(6): 455-482.
3. Rudd TR, Skidmore MA, Guimond SE, et al. Glycosamino-glycan origin and structure revealed by multivariate analysis of NMR and CD spectra. Glycobiology. 2009;19(1):52-67.
4. Asimakopoulou A P, Theocharis AD, Tzanakakis GN, Karamanos NK. The biological role of chondroitin sulfate in cancer and chondroitin-based anticancer agents. In Vivo. 2008;22(3):385-389.
5. Lauder RM. Chondroitin sulphate: a complex molecule with potential impacts on a wide range of biological systems. Complement Ther Med. 2009;17:56-62.
6. Tollefsen DM. Vascular dermatan sulphate and heparin cofactor II. Prog Mol Biol Transl Sci. 2010;93:351-372.
7. Malavaki CJ, Theocharis AD, Lamari FN, et al. Heparan sulfate: biological signifcance, tools for biochemical analysis and structural characterization. Biomed Chromatogr. 2011;25(1-2):11-20.
8. Mulloy B. Structure and physicochemical characterisation of heparin. Handb Exp Pharmacol. 2012;(207):77-98.
9. Dreyfuss JL, Regatieri C V, Jarrouge TR, Cavalheiro R P, Sampaio LO, Nader HB. Heparan sulfate proteoglycans: structure, protein interactions and cell signaling. An Acad Bras Cienc. 2009;81(3):409-429.
10. Bick RL, Frenkel E P, Walenga J, Fareed J, Hoppensteadt DA. Unfractionated heparin, low molecular weight heparins, and pentasac-charide: basic mechanism of actions, pharmacology and clinical use. Hematol Oncol Clin North Am. 2005;19(1):1-51.
11. Bianchini P, Inventor; Opocrin SRL, Assignee. Method for preparing glucoronyl-glucosamino-glycan sulphates exhibiting antilipasaemic activity. United States patent US 3936351. February 3, 1976.
12. Silvestro L, Lanzarotti E, Marchi E, et al. Human pharmacokinetics of glycosaminoglycans using deuterium-labeled and unlabeled substances: evidence for oral absorption. Semin Thromb Hemost. 1994;20: 281-292.
13. Cosmi B, Cini M, Legnani C, Pancani C, Calanni F, Coccheri S. Additive thrombin inhibition by fast moving heparin and dermatan sulfate explains the anticoagulant effect of sulodexide, a natural mixture of glycosaminoglycans. Thromb Res. 2003;109(5-6):333-339.
14. Iacoviello L, D'Adamo MC, Pawlak K, et al. Antithrombotic activity of dermatan sulphates, heparins and their combination in an animal model of arterial thrombosis. Thromb Haemost. 1996;76(6): 1102-1107.
15. Di Carlo V, Agnelli G, Prandoni P, et al. Dermatan sulphate for the prevention of postoperative venous thromboembolism in patients with cancer. DOS (Dermatan sulphate Oncolologic Surgery) Study Group. Thromb Haemost. 1999;82(1):30-34.
16. Mannello F, Raffetto JD. Matrix metalloproteinase activity and glycosaminoglycans in chronic venous disease: the linkage among cell biology, pathology and translational research. Am J Transl Res. 2011;3(2):149-158.
17. Mattana P, Mannello F, Ferrari P, Agus GB. Vascular pathologies and infammation: the antinfammatory properties of sulodexide. J Vasc Endovasc Surg. 2012;19:1-7.
18. Plichta JK, Radek KA. Sugar coating wound repair: a review of FGF10 and DS in wound healing and their potential application in burn wounds. J Burn Care Res. 2012;33:299-310.
19. Milani MR, Busutti L, Breccia A, et al. Pharmacokinetics of sulodexide evaluation from 131-labelled fast-moving heparin after single intravenous and oral administration on man at different doses. Brit J Clin Res. 1992;3:161-178.
20. Marchi E, Barbanti M, Milani R, et al. Organ glycosaminoglycan distribution after intravenous and oral administration in rats. Semin Thromb Hemost. 1994;20:297-300.
21. Ofosu FA. Pharmacological actions of sulodexide. Semin Thromb Hemost. 1998;24:127-137.
22. Adiguzel C, Iqbal O, Hoppensteadt D, et al. Comparative anticoagulant and platelet modulatory effects of enoxaparin and Sulodexide. Clin Appl Thromb Hemost. 2009;15(5):501-511.
23. Harenberg J. Review of pharmacodynamics, pharmacokinetics, and therapeutic properties of sulodexide. Med Res Rev. 1998;18:1-20.
24. Borawski J, Dubowski M, Rydzewska-Rosolowska A, Mysliwiec M. Intravenous and oral Sulodexide versus coagulation activation markers in humans. Clin Appl Thromb Hemost. 2009;15(5):596-598.
25. Borawski J, Naumnik B, Dubowski M, Mysliwiec M. Full-length TFPI release by heparinoid Sulodexide. Clin Appl Thromb Hemost. 2010;16(4):485-487.
26. Coccheri S, Scondotto G, Agnelli G, Palazzini E, Zamboni V. Sulodexide in the treatment of intermittent claudication. Results of a randomized, double blind, multicentre, placebo-controlled study. Eur Heart J. 2002;23(13):1057-1065.
27. Callas DD, Hoppensteadt DA, Jeske W, et al. Comparative pharma-cologic profle of a glycosaminoglycan mixture, Sulodexide, and a chemically modifed heparin derivative, Suleparoid. Semin Thromb Hemost. 1993;19 Suppl 1:49-57.
28. Ceriello A, Quatrano A, Marchi E, Barbanti M, Giugliano D. Impaired fbrinolytic response to increased thrombin activation in type 1 diabetes mellitus: effects of the glycosaminoglycan sulodexide. Diabetes Metab. 1993;19(2):225-229.
29. Buchanan MR, Liao P, Smith LJ, et al. Prevention of thrombus formation and growth by antithrombin III and heparin cofactor II-dependent thrombin inhibitors:: importance of heparin cofactor II. Thromb Res. 1994;74:463-475.
30. Hornstra G, Vendelmans-Starrenburg A. Induction of experimental arterial occlusive thrombi in rats. Atherosclerosis. 1973;17(3): 369-382.
31. Andriuoli G, Mastacchi R, Barbanti M. Antithrombotic activity of a gly-cosaminoglycan (sulodexide) in rats. Thromb Res. 1984;34(1):81-86.
32. Tarugi P, Tiozzo Costa, Barbanti M, et al. Effect of sulodexide, a heparin-like compound, on experimental atherosclerosis in the rabbit. Med Sci Res. 1987;15:1071-1072.
33. Barbanti M, Guizzardi S, Calanni F, Marchi E, Babbini M. Antithrombotic and thrombolytic activity of Sulodexide in rats. Int J Clin Lab Res. 1992;22(3):179-184.
34. Agrati AM, Mauro M, Savasta C, et al. A double-blind, cross-over, placebo-controlled study of the profbrinolytic and antithrombotic effects of oral sulodexide. Adv Ther. 1992;9:147-155.
35. Mauro M, Ferraro G, Palmieri GC. Profbrinolytic and antithrombotic effects of sulodexide oral administration: a double-blind, cross-over, placebo-controlled study. Curr Ther Res. 1992;51:342-350.
36. Mannarino E, Pasqualini L, Ciuffetti G, et al. Effect of oral administration of sulodexide on fbrinolysis and plasma viscosity: a pilot study. Drug Invest. 1992;4:346-350.
37. Cerletti C, Rajtar G, Marchi E, et al. Interaction between glycosamino-glycans, platelets and leukocytes. Semin Thromb Hemost. 1994;20: 245-253.
38. Mannello F, Medda V, Ligi D, Raffetto JD. Glycosaminoglycan Sulo-dexide inhibition of MMP-9 gelatinase secretion and activity: possible pharmacological role against collagen degradation in vascular chronic diseases. Curr Vasc Pharmacol. 2013;11(3):354-365.
39. Borawski J, Dubowski M, Pawlak K, et al. Effect of Sulodexide on plasma transforming growth factor ß1 in healthy volunteers. Clin Appl Thromb Hemost. 2010;16:60-65.
40. Tiozzo R, Cingi MR, Pietrangelo A, et al. Effect of heparin-like compounds on the in vitro proliferation and protein synthesis of various cell types. Arzneimittelforschung. 1989;39(1):15-20.
41. Borawski J, Dubowski M, Pawlak K, Mysliwiec M. Sulodexide induces hepatocyte growth factor release in humans. Eur J Pharmacol. 2007;558(1-3):167-171.
42. Broekhuizen LN, Lemkes BA, Mooij HL, et al. Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus. Diabetologia. 2010;53:2646-2655.
43. Kristova V, Liskova S, Sotnikova R, et al. Sulodexide improves endothe-lial dysfunction in streptozotocin-induced diabetes in rats. Physiol Res. 2008;57:491-494.
44. Vasquez J, Mathison Y, Romero-Vecchione E, et al. Effect of sulodexide on aortic vasodilation capacity and associated morphological changes in rats with streptozotocin-induced diabetes. Invest Clin. 2010;51(4): 467-477. Spanish.
45. Crepaldi G, Fellin R, Calabrò A, et al. Double-blind multicenter trial on a new medium molecular weight glycosaminoglycan. Current therapeutic effects and perspectives for clinical use. Atherosclerosis. 1990;8(13):233-243.
46. Lunetta M, Salanitri T. Lowering of plasma viscosity by the oral administration of the glycosaminoglycan sulodexide in patients with peripheral vascular disease. J Int Med Res. 1992;20(1):45-53.
47. Cospite M, Ferrara F, Cospite V, et al. Sulodexide and the microcircu-latory component in microphlebopathies. Curr Med Res. 1992;13(1): 56-60.
48. Park HY, Kang S, Kim GY, et al. Inhibition of neointimal proliferation of rat carotid artery by sulodexide. J Korean Med Sci. 1997;12(3): 210-214.
49. Bergan JJ, Schmid-Schonbein G W, Smith PD, et al. Chronic venous disease. N Engl J Med. 2006;355(5):488-498.
50. Andreozzi GM. Sulodexide in the treatment of chronic venous disease. Am J Cardiovasc Drugs. 2012;12(2):73-81.
51. Evans CJ, Fowkes FG, Ruckley C V, et al. Prevalence of varicose veins and chronic venous insuffciency in men and women in the general population: Edinburgh Vein Study. J Epidemiol Community Health. 1999;53(3):149-153.
52. Maurins U, Hoffman BH, Losch C, et al. Distribution and prevalence of refux in the superfcial and deep venous system in the general population: results from the Bonn Vein Study, Germany. J Vasc Surg. 2008;48(3):680-687.
53. Eklof B, Rutherford RB, Bergan JJ, et al. Revision of the CEAP clas-sifcation for chronic venous disorders: consensus statement. J Vasc Surg. 2004;40(6):1248-1252.
54. Bergan JJ, Pascarella L, Schmid-Schoenbein G W. Pathogenesis of primary chronic venous disease: Insights from animal models of venous hypertension. J Vasc Surg. 2008;47(1):183-192.
55. Cohen JM, Akl EA, Khan SR. Pharmacologic and compression therapies for post thrombotic syndrome. Chest. 2012;141(2):308-320.
56. Marinović Kulišić S., Lupi D. Pharmacological treatment in patients with chronic venous disease. Acta Dermatovenerol Croat. 2012;20(3): 197-200.
57. Lauver AD, Lucchesi BR. Sulodexide: a renewed interest in this gly-cosaminoglycan. Cardiovasc Drug Rev. 2006;24(3-4):214-226.
58. Lei Y, Zheng Z, Wang Y, et al. Sulodexide may alleviate neointimal hyperplasia by inhibiting angiopoietin-2 in an arteriovenous fstula model. Mol Med Rep. 2013;7(3):831-835.
59. Saviano M, Maleti O, Liguori L. Double-blind, double-dummy, randomized, multicentre clinical assessment of the effcacy, tolerability and dose-effect relationship of Sulodexide in chronic venous insuffciency. Curr Med Res Opin. 1993;13(2):76-108.
60. Gloviczki P, Camerota AJ, Dalsing MC, et al. The care of patients with varicose veins and associated chronic venous diseases: clinical practice guidelines of the American Society for Vascular Surgery and the American Venous Forum. J Vasc Surg. 2011;53(5S):2S-28S.
61. Kahn SR. The post-thrombotic syndrome: prognosis and pitfalls. Br J Haematol. 2006;134(4):357-365.
62. Palareti G, Legnani C, Cosmi B, et al. Predictive value of D-dimer test for recurrent venous thromboembolism after anticoagulation withdrawal in subjects with a previous idiopathic event and carriers of congenital thrombophilia. Circulation. 2003;108(39):313-318.
63. Palareti G, Leali N, Coccheri S, et al. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy. Lancet. 1996;348:423-428.
64. Connors JM. Extended treatment of venous thromboembolism. N Engl J Med. 2013;368(8):767-769.
65. Becattini C, Agnelli G, Schenone A, et al. WARFASA Investigators. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med. 2012;366(1):1959-1967.
66. Brighton TA, Eikelboom J W, Mann K, et al. ASPIRE Investigators. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012;367(21):1979-1987.
67. Garcia Rodriguez LA, Lin KJ, Hernandez-Diaz S, Johansson S. Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation. 2011;123:1108-1115.
68. Cirujeda JL, Granado PC. A study on the safety, effcacy, and effciency of sulodexide compared with acenocoumarol in secondary prophylaxis in patients with deep vein thrombosis. Angiology. 2010;57(1): 53-64.
69. Errichi BM, Cesarone MR, Belcaro G, et al. Prevention of recurrent deep venous thrombosis with sulodexide: the SanVal registry. Angiology. 2004;55(3):243-249.
70. Andreozzi GM, Palareti G. Rationale and study design of the SURVET trial (Sulodexide in Secondary Prevention of Recurrent Deep Vein Thrombosis). Proceedings of the 21st International Congress on Thrombosis; July 6-9, 2010; Milan, Italy. Abstract; p 302.
71. Nicolaides AN. Chronic venous disease and the leukocyte-endothe-lium interaction: from symptoms to ulceration. Angiology. 2005;56: S11-9.
72. Falanga V, Saap LJ, Ozonoff A. Wound bed score and its correlation with healing of chronic wounds. Dermatol Ther. 2006;19(6):383-390.
73. Kurz X, Kahn SR, Abenhaim L, et al. Chronic venous disorders of the leg: epidemiology, outcomes, diagnosis and management. Summary of an evidence-based report of the VEINES task force. Venous Insuf-fciency Epidemiologic and Economic Studies. Int Angiol. 1999;18(2): 83-102.
74. Scondotto G, Aloisi D, Ferrari P, et al. Treatment of venous leg ulcers with Sulodexide. Angiology. 1999;50(1):883-889.
75. Coccheri S, Scondotto G, Agnelli G, Aloisi D, Palazzini E, Zamboni V. (SUAVIS group). Randomised, double blind, multicentre, placebo controlled study of sulodexide in the treatment of venous leg ulcers. Thromb Haemost. 2002;87(6):947-952.
76. Kucharzewski M, Franek A, Koziolek H. Treatment of venous leg ulcers with Sulodexide. Phlebologie. 2003;32:115-120.
77. Arosio E, Ferrari G, Santoro L, Gianese F, Coccheri S; Mesoglycan Venous Insuffciency Group. A placebo-controlled, double blind study of mesoglycan in the treatment of chronic venous ulcers. Eur J Vasc Endovasc Surg. 2001;22(4):365-372.
78. Nelson EA. Venous leg ulcers. Clin Evid. 2011;12:1902.
79. Kearon C, Kahan SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th ed). Chest. 2008;133: 454S-545S.
80. Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373: 1849-1860.
81. Condorelli M, Chiariello M, Dagianti A, et al. IPO-V2: a prospective, multicenter, randomized, comparative clinical investigation of the effects of sulodexide in preventing cardiovascular accidents in the frst year after acute myocardial infarction. J Am Coll Cardiol. 1994;23(1): 27-34.
82. Coccheri S, Palareti G. The cardiovascular risk burden of intermittent claudication. Eur Heart J. 2002;4(Suppl B):B46-B49.
83. Criqui MH, Denenberg JO, Langer RD, Fronek A. The epidemiology of peripheral arterial disease: importance of identifying the population at risk. Vasc Med. 1997;2:221-226.
84. Cicco G, Stingi GD, Vicenti P, Tarallo MS, Pirrelli A. Hemorheology and tissue oxygenation in hypertensives with lipoidoproteinosis and peripheral occlusive arterial disease (POAD) treated with sulo-dexide and pravastatine and evaluated with laser assisted optical rotational red cell analyzer (LORCA) and transcutaneous oxymetry. Min Cardioangiol. 1999;47:351-359.
85. Gaddi A, Galletti C, Illuminati B, et al. Meta-analysis of some results of clinical trials on sulodexide therapy in peripheral occlusive arterial disease. J Int Med Res. 1996;24:389-406.
86. Shustov SB. Controlled clinical trial on the effcacy and safety of oral sulodexide in patients with peripheral occlusive arterial disease. Curr Med Res Opin. 1997;13(19):573-582.
87. Lasierra-Cirujeda J, Coronel P, Aza MJ, Gimeno M. Use of sulodexide in patients with peripheral vascular disease. J Blood Med. 2010;1: 105-115.
88. Stella A, Tarantini G, Palareti G, et al. Pharmacological therapy after carotid endoarterectomy: heparin, sulodexide, ticlopidine. G Ital Chir Vasc. 1999;6:161-179.
89. Parnetti L, Mari D, Abate G, et al. Vascular dementia Italian sulodex-ide study (VA.D.I.S.S.). Clinical and biological results. Thromb Res. 1997;87(2):225-233.
90. Coccheri S. Approaches to prevention of cardiovascular complications and events in diabetes mellitus. Drugs. 2007;67(7):997-1026.
91. Weiss R, Niecestro R, Raz I. The role of Sulodexide in the treatment of diabetic nephropathy. Drugs. 2007;67(18):2681-2696.
92. Masola V, Onisto M, Zaza G, Lupo A, Gambaro G. A new mechanism of action of Sulodexide in diabetic nephropathy: inhibits heparanase-1 and prevents FGF-2 induced renal epithelial mesenchymal transition. J Transl Med. 2012;10:213.
93. Ciszewicz M, Polubinska A, Antoniewicz A, Suminska-Janinska K, Bre-borowicz A. Sulodexide suppresses infammation in human endothelial cells and prevents glucose cytoxicity. Transl Res. 2009;153(3): 118-123.
94. Shu J, Zeng LY, Lin KY, et al. Renal protective effects of Sulodexide in diabetic rats and its antioxidative mechanism. Nan Fang Yi Ke Da Xue Xue Bao. 2009;29(4):778-780. Chinese.
95. Yung S, Chau MK, Zhang CZ, Chan TM. Sulodexide decreases albu-minuria and regulates matrix protein accumulation in C57BL/6 mice with streptozotocin-induced type I diabetic nephropathy. PLoS One. 2013;8(1):e54501.
96. Cha JJ, Kang YS, Hyun Y Y, et al. Sulodexide improves renal function through reduction of vascular endothelial growth factor in type 2 diabetic rats. Life Sci. 2013;92(23):118-124.
97. Chen S, Fang Z, Zhu Z, Deng A, Liu J, Zhang C. Protective effect of sulodexide on podocyte injury in adriamycin nephropaty rats. J Huazhong Univ Sci Technolog Med Sci. 2009;29(6): 715-719.
98. Rossini M, Naito T, Yang H, et al. Sulodexide ameliorates early but not late kidney disease in models of radiation nephropaty and diabetic nephropaty. Nephrol Dial Transplant. 2010;25(6):1803-1810.
99. Gaddi AV, Cicero A F, Gambaro G. Nephroprotective action of glycosaminoglycans: why the pharmacological properties of sulo-dexide might be reconsidered. Int J Nephrol Renovasc Dis. 2010;3: 99-105.
100. Li P, Ma LL, Xie RJ, et al. Treatment of 5/6 nephrectomy rats with sulodexide: a novel therapy for chronic renal failure. Acta Pharmacol Sin. 2012;33(5):644-651.
101. Gambaro G, Kinalska I, Oksa A, et al. Oral sulodexide reduces albu-minuria in microalbuminuric and macroalbuminuric type 1 and type 2 diabetic patients: the Di.N.A.s: randomized trial. J Am Soc Nephrol. 2002;13(6):1615-1625.
102. Blouza S, Dakhii S, Abid H, Aissaoui M, et al; DAVET (Diabetic Albuminuria Vessel Tunisia) Study Investigators. Effcacy of low-dose oral Sulodexide in the management of diabetic nephropathy. J Nephrol. 2010;23(4):415-424.
103. Bang K, Chin HJ, Chae DW, et al. Anti-proteinuric effect of sulo-dexide in immunoglobulin a nephropathy. Yonsei Med J. 2011;52(4): 588-594.
104. Heersprink HL, Greene T, Lewis JB, et al. Collaborative Study Group. Effect of Sulodexide in patients with type 2 diabetes and persistent albuminuria. Nephrol Dial Transplant. 2008;23:1946-1954.
105. Lewis EJ, Lewis JB, Greene T, et al; Collaborative Study Group. Sulodexide for kidney protection in type 2 diabetes patients with macroalbuminuria: a randomized controlled trial. Am J Kidney Dis. 2011;58(5):729-736.
106. Packham DK, Wolfe R, Reutens AT, et al; Collaborative Study Group. Sulodexide fails to demonstrate renoprotection in overt type 2 diabetic nephropathy. J Am Soc Nephrol. 2012;23:123-130.
107. House AA, Weir MA. Sulodexide for diabetic nephropathy: another one bites the dust. Am J Kidney Dis. 2011;58(5):692-694.
108. Coccheri S. Game not over for sulodexide. Am J Kidney Dis. 2012; 59(3):467.
109. Gaddi AV, Benedetto D. Surrogate versus clinical end points and venture capital companies: the doubts of a clinician. Am J Kidney Dis. 2012;60(1):168-171.
110. Gambaro G. Discounting the effcacy of sulodexide in diabetic neph-ropathy is premature. Am J Kidney Dis. 2012;69(1):169-170.
111. Rubbi F, Caramazza R, Boccia S, et al. The effects of sulodexide on diabetic retinopathy. Minerva Cardioangiol. 2000;48(Suppl 1): 81-82.
112. Karimov KT, Shakhmaliyeva AM. Effect of sulodexide on non-proliferative diabetic retinopathy. Azerbaijan Med J. 2002;1:72-76.
113. Chin HS, Kang S W, Kawak H W, et al. Effect of sulodexide in diabetic patients with mild to moderate nonproliferative retinopathy. AAO 2011 - Annual Meeting of the American Academy of Ophtalmology. Abstract 498; p221.
114. Jin HY, Lee KE, Song SK, et al. Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats. Eur J Pharmacol. 2012;674(2-3):217-226.
115. Koblik T, Sieradzki J, Sendur R, et al. The effect of insulin and sulo-dexide (Vessel Due F) on diabetic foot syndrome. Pilot study in elderly patients. J Diabetes Complications. 2001;15(2):69-74.
116. Anfossi DG, Bella GM, Chiriotti S. Comparative study of two different protocols in the treatment of retinal vein occlusion. Minerva Opthalmol. 1992;34:29-36.
117. Szaflk J, Kaminska A. Usefulness of Vessel Due F (sulodexide) in treatment of patients with diabetic retinopathy, senile macular degeneration and retinal vein occlusion. Okulistyka. 2000;3:1-4.
118. Guidetti G. Treatment of vascular vertigo in outpatients: multicentre experience (VascVert study). Otorinolaringol. 2005;55:237-246.
119. Neri G, Baffa C, De Stefano A, et al. Management of tinnitus: oral treatment with melatonin and sulodexide. J Biol Regul Homeost Agents. 2009;23(2):103-110.