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During the last decade, growing evidence has shown that serum gamma-glutamyl transpeptidase (GGT) is an independent prognostic marker for cardiac death and reinfarction, both in unselected populations and in patients with coronary artery disease. Clinical and epidemiological evidence indicates that the prognostic value of GGT is largely independent of other risk factors for cardiovascular disease and alcohol consumption. The catalytic activity of GGT, which is present on the surface of cell membranes and in serum, is responsible for the extracellular catabolism of the antioxidant glutathione. Cysteinyl glycine deriving from the hydrolysis of glutathione performed by GGT has been found to trigger iron-dependent production of reactive oxygen species as well as low-density lipoprotein oxidation in vitro. The localization of GGT within the coronary plaque ( Figure) provides a pathological basis for the hypothesis of a direct participation of GGT in low-density lipoprotein oxidation within the plaque and in atherogenesis and coronary artery disease progression.From the Department of Experimental Pathology, University of Pisa, Pisa (A. Paolicchi, A. Pompella); the Institute of Clinical Physiology, National Research Council, Pisa (M.E., C.P.); Azienda Ospedaliera Pisana, Pisa (E.C.); and Clinica Villa Maria Beatrice, Firenze (E.G., G.P.), Italy.Correspondence Histochemical and immunohistochemical demonstration of GGT enzyme activity within a frozen section of coronary atheroma from endoarteriectomy in vivo. Histochemical reaction for GGT enzyme activity was performed by using the specific substrate gamma-glutamyl-4-methoxy-2-naphtylamide and the diazonium salt Fast Garnet GBC as a chromogen. A strong GGT activity (the red stain) is selectively present in correspondence of the core of the atheroma, while the fibrous cap stains negative (A, magnification 20ϫ). The identification of the enzyme was confirmed immunohistochemically using a polyclonal antibody directed against the heavy chain of human GGT, which marked the same part of the atheroma (B and C, magnification 40ϫ and 10ϫ, respectively). The homogeneous immunostaining of oxidized lipid-containing foam cells by the antibody is evident at higher magnification (B). For the sake of confirming the localization of GGT activity, another section of the same specimen was immunostained with an antibody directed against CD 68ϩ cells (ie, macrophages), selectively identifying foam cells (D and E, magnification 10ϫ and 40ϫ, respectively).

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Ex situ normothermic machine perfusion (NMP) might minimize ischemia/reperfusion injury (IRI) of liver grafts. In this study, 20 primary liver transplantation recipients of older grafts (≥70 years) were randomized 1:1 to NMP or cold storage (CS) groups. The primary study endpoint was to evaluate graft and patient survival at 6 months posttransplantation. The secondary endpoint was to evaluate liver and bile duct biopsies; IRI by means of peak transaminases within 7 days after surgery; and incidence of biliary complications at month 6. Liver and bile duct biopsies were collected at bench surgery, end of ex situ NMP, and end of transplant surgery. Interleukin (IL) 6, IL10, and tumor necrosis factor α (TNF-α) perfusate concentrations were tested during NMP. All grafts were successfully transplanted. Median (interquartile range) posttransplant aspartate aminotransferase peak was 709 (371-1575) IU/L for NMP and 574 (377-1162) IU/L for CS (P = 0.597). There was 1 hepatic artery thrombosis in the NMP group and 1 death in the CS group. In NMP, we observed high TNF-α perfusate levels, and these were inversely correlated with lactate (P < 0.001). Electron microscopy showed decreased mitochondrial volume density and steatosis and an increased volume density of autophagic vacuoles at the end of transplantation in NMP versus CS patients (P < 0.001). Use of NMP with older liver grafts is associated with histological evidence of reduced IRI, although the clinical benefit remains to be demonstrated. The use of very old donors in liver transplantation (LT)is showing favorable results, (1) but this practice is not universally implemented (2) because of concerns about a higher risk for primary nonfunction (PNF), delayed graft function (DGF), (3) and worse longterm graft survival. (4) In our recent series of octogenarian donors, we reported favorable overall longterm results, and we found that hepatitis C virus (HCV) recurrence and ischemic-type biliary lesions (ITBLs) were 2 independent causes of graft loss in this population. (5) Although availability of direct antiviral agents is reducing the impact of donor age on HCV recurrence, (6) prevention of ischemia/reperfusion injury (IRI) is pivotal to the practice of elderly donor LT and for donation after circulatory death (DCD) donors. (7,8) Even though the concept of the ideal donor is well defined, (4,9) the definition of extended criteria donors remains controversial. Increased donor age contributes to a higher risk ghinOlfi et al.

The results obtained suggest the presence in plaques of a serum-like GGT protein, indicating that a direct contribution of serum GGT to enzyme activity found within atherosclerotic lesions is possible. Data also indicate the occurrence of GGT-mediated redox reactions within plaque environment, which might influence plaque progression.

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