title: The effects of sulodexide on both clinical and molecular parameters in patients with mixed arterial and venous ulcers of lower limbs.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, Italy ; Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Serra
authors.affiliation: Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Gallelli
authors.affiliation: Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Conti
authors.affiliation: Cardiovascular and Thoracic Department, University of Messina, Messina, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: De Caridi
authors.affiliation: Cardiovascular and Thoracic Department, University of Messina, Messina, Italy.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Massara
authors.affiliation: Cardiovascular and Thoracic Department, University of Messina, Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Spinelli
authors.affiliation: Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Buffone
authors.affiliation: Unit of Vascular Surgery, S Anna Hospital, Catanzaro, Italy.
authors.forename: Francesco Giuseppe
authors.initials: FG
authors.lastname: Caliò
authors.affiliation: Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Amato
authors.affiliation: Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Ceglia
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Spaziano
authors.affiliation: University Campus BioMedico of Rome, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Scaramuzzino
authors.affiliation: Department of General Surgery, University of Turin, Turin, Italy.
authors.forename: Alessia Giovanna
authors.initials: AG
authors.lastname: Ferrarese
authors.affiliation: Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Grande
authors.affiliation: Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, Italy ; Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: de Franciscis
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006025:Glycosaminoglycans / Q000627:therapeutic use*; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000032:analysis; D008297:Male; D020782:Matrix Metalloproteinases / Q000032:analysis; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000032:analysis; D011788:Quality of Life; D014647:Varicose Ulcer / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000209:Acute-Phase Proteins; D006025:Glycosaminoglycans; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; C007858:glucuronyl glucosamine glycan sulfate; D020782:Matrix Metalloproteinases
keywords: arterial ulcer; metalloproteinases; mixed ulcer; neutrophil gelatinase-associated lipocalin