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Randomized Controlled Trial
. 2014 May 13:8:519-27.
doi: 10.2147/DDDT.S61770. eCollection 2014.

The effects of sulodexide on both clinical and molecular parameters in patients with mixed arterial and venous ulcers of lower limbs

Raffaele Serra  1 , Luca Gallelli  2 , Angela Conti  3 , Giovanni De Caridi  4 , Mafalda Massara  4 , Francesco Spinelli  4 , Gianluca Buffone  3 , Francesco Giuseppe Caliò  5 , Bruno Amato  6 , Simona Ceglia  7 , Giuseppe Spaziano  8 , Luca Scaramuzzino  9 , Alessia Giovanna Ferrarese  10 , Raffaele Grande  3 , Stefano de Franciscis  1
Affiliations
Randomized Controlled Trial

The effects of sulodexide on both clinical and molecular parameters in patients with mixed arterial and venous ulcers of lower limbs

Raffaele Serra et al. Drug Des Devel Ther. .

Abstract

Background: Mixed venous and arterial ulcers account for approximately 15%-30% of all venous leg ulcerations. Several studies have shown that matrix metalloproteinases (MMPs) and neutrophil gelatinase-associated lipocalin (NGAL) play a central role in the pathophysiology of venous and arterial diseases. Some studies have shown the efficacy of glycosaminoglycans, such as sulodexide (SDX), in treating patients with leg ulcers. The aim of this study was to evaluate clinical effects of SDX and its correlation with MMPs and NGAL expression in patients with mixed arterial and venous leg ulcers.

Methods: Patients eligible for this study were of both sexes, older than 20 years, and with a clinical and instrumental diagnosis of mixed ulcer.

Results: Fifty-three patients of both sexes were enrolled and divided into two groups by means of randomization tables. Group A (treated group) comprised 18 females and ten males (median age: 68.7 years) treated with standard treatment (compression therapy and surgery) + SDX (600 lipoprotein lipase-releasing units/day intramuscularly) for 15 days followed by SDX 250 lipase-releasing units every 12 hours day orally for 6 months as adjunctive treatment. Group B (control group) comprised 17 females and eight males (median age: 64.2 years) treated with standard treatment only (compression therapy and surgery). The type of surgery was chosen according to anatomical level of vein incompetence: superficial venous open surgery and/or subfascial endoscopic perforating surgery. In all enrolled patients, blood samples were collected in order to evaluate the plasma levels of MMPs and NGAL through enzyme-linked immunosorbent assay. These results were compared to another control group (Group C) of healthy individuals. Moreover, biopsies of ulcers were taken to evaluate the tissue expression of MMPs and NGAL through Western blot analysis. Our results revealed that SDX treatment is able to reduce both plasma levels and tissue expression of MMPs improving the clinical conditions in patients with mixed ulcers.

Conclusion: Inhibition of MMPs could represent a possible therapeutic intervention to limit the progression of leg ulceration. In particular, our findings demonstrate the efficacy of SDX in patients with mixed arterial and venous chronic ulcers of the lower limbs.

Keywords: arterial ulcer; metalloproteinases; mixed ulcer; neutrophil gelatinase-associated lipocalin.

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Figures

Figure 1
Figure 1
Western blot evaluation of MMPs and NGAL expression in wound tissues taken at the time of surgery in patients with CVUs treated (Group A) or not (Group B) with sulodexide at T1 and T2 of the study. Notes: Data are expressed as arbitrary units, where the higher value has been considered equal to 100. *P<0.05; **P<0.01. Abbreviations: CVU, chronic venous ulceration; NGAL, neutrophil gelatinase-associated lipocalin; MMP, matrix metalloprotease.
Figure 2
Figure 2
Results of qualify of life questionnaire in chronic venous ulceration patients treated with sulodexide for 6 months (at the end of the study) (Group A).
Figure 3
Figure 3
Results of qualify of life questionnaire in untreated chronic venous ulceration patients (at the end of the study) (Group B).
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References

    1. Patton LR. Are community leg ulcer clinics more cost-effective than home care visits? J Wound Care. 2009;18(2):49–50. 52. - PubMed
    1. Hampton S. An introduction to various types of leg ulcers and their management. Br J Nurs. 2006;15(11):S9–S13. - PubMed
    1. Forssgren A, Fransson I, Nelzén O. Leg ulcer point prevalence can be decreased by broad-scale intervention: a follow-up cross-sectional study of a defined geographical population. Acta Derm Venereol. 2008;88(3):252–256. - PubMed
    1. Andersson E, Hansson C, Swanbeck G. Leg and foot ulcer prevalence and investigation of the peripheral arterial and venous circulation in a randomised elderly population. An epidemiological survey and clinical investigation. Acta Derm Venereol. 1993;73(1):57–61. - PubMed
    1. Apelqvist JA, Lepäntalo MJ. The ulcerated leg: when to revascularize. Diabetes Metab Res Rev. 2012;28(Suppl 1):30–35. - PubMed

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