title: Use of a non-specific immunomodulation therapy as a therapeutic vasculogenesis strategy in no-option critical limb ischemia patients.
abstract: OBJECTIVE
  Inflammatory mediators contribute to the impairment of vasculogenesis by reducing endothelial progenitor cells (EPCs) mobilization in atherosclerotic vasculopathy. We tested the hypothesis that administration of an oxygen/ozone mixture (IMT) might counteract this pathophysiological mechanism and enhance limb tissue perfusion in patients with critical limb ischemia (CLI).
  
  
  METHODS
  Randomized patients with rest pain or ischemic ulcers and transcutaneous oxygen tension (TcPO(2)) <40 mmHg and/or toe pressure <50 mmHg received placebo (n=74) or a non-specific immunomodulation therapy (IMT) (n=77), autologous blood exposed to oxygen/ozone gas mixture by intragluteal injection, on day 1, 2, 7, and once a week thereafter for at least 22 weeks. Patients were evaluated for changes in TcPO(2), levels of circulating EPCs (CD34/KDR-positive cells) and inflammation (tumor necrosis factor-alpha-TNF-alpha).
  
  
  RESULTS
  TcPO(2) and CD34/CD133-positive cells increased at 22 weeks in IMT group (P<0.01) whereas no changes were observed in placebo group. TNF-alpha levels decreased at 6 months in IMT group (P<0.001) whereas no changes were observed in placebo group. There was a strong positive correlation between CD34/KDR-positive cells and TcPO(2) (r=0.56, P<0.01). Moreover, there was an inverse correlation between CD34/KDR-positive cells and TNF-alpha (r=-0.51, P<0.01).
  
  
  CONCLUSIONS
  Intramuscular injection of IMT may improve wound healing and limb salvage in patients with CLI.
authors.affiliation: Department of Geriatrics and Metabolic Diseases, Second University of Naples, Piazza Miraglia, 2. 80138 Napoli, Italy. raffaele.marfella@unina2.it
authors.forename: Raffaele
authors.initials: R
authors.lastname: Marfella
authors.forename: Carlo
authors.initials: C
authors.lastname: Luongo
authors.forename: Antonino
authors.initials: A
authors.lastname: Coppola
authors.forename: Margherita
authors.initials: M
authors.lastname: Luongo
authors.forename: Paola
authors.initials: P
authors.lastname: Capodanno
authors.forename: Roberto
authors.initials: R
authors.lastname: Ruggiero
authors.forename: Luigi
authors.initials: L
authors.lastname: Mascolo
authors.forename: Immacolata
authors.initials: I
authors.lastname: Ambrosino
authors.forename: Celestino
authors.initials: C
authors.lastname: Sardu
authors.forename: Virginia
authors.initials: V
authors.lastname: Boccardi
authors.forename: Biagio
authors.initials: B
authors.lastname: Lettieri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paolisso
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000096:biosynthesis; D042783:Endothelial Cells; D005121:Extremities / Q000098:blood supply / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006439:Hemodynamics; D006801:Humans; D056747:Immunomodulation; D007249:Inflammation; D007511:Ischemia / Q000473:pathology* / Q000628:therapy*; D008875:Middle Aged; D010100:Oxygen / Q000737:chemistry*; D010126:Ozone; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014456:Ulcer / Q000473:pathology* / Q000628:therapy; D014945:Wound Healing
chemical_list: D018952:Antigens, CD34; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; D010126:Ozone; D010100:Oxygen