Introduction and aim: General transplant outcome of HCV kidney transplant recipients (KTRs) is worse than that of non-infected one. Direct acting antivirals (DAAs) resulted efficacious also in KTRs. Drug interactions between Calcineurin inhibitors (CNI) and DAAs had been described. Immunological rejection is the Achilles heel of kidney transplantation. Thus, the impact of DAAs on CNI levels and the effect on renal function need to be evaluated.

Rossini, M.; Fiorentino, M.; Schena, A.; Lucarelli, G.; Selvaggi, F. P.; Schena, F. P.; Ditonno, P.; Grandaliano, G. Author Information

ABSTRACT A study on lipolysis of Southern Italy short‐ripened dry‐cured sausages manufactured without and with starters was carried out. Samples were submitted to microbiological and chemical analysis during drying and ripening, whereas sensory analysis was performed at the end of the ripening. The starters, addition caused the inhibition of the Enterobacteriaceae. An increase of free fatty acids (FFAs) and diacylglycerols (DAGs) during the ripening was observed. The addition of starter did not affect FFA and DAG release. The DAG profile including 1,2‐ and 1,3‐isomers was analyzed for the first time in dry‐cured sausages. Oleic, linoleic and palmitic acids, and 1,2‐, 1,3‐palmitinolein, 1,2‐ and 1,3‐diolein were the most abundant compounds in FFA and DAG, respectively. A decrease in the concentration of some 1,2‐DAG and an increase of 1,3‐OO and 1,3‐OP species during the process was observed. Finally, the addition of starter cultures slightly influenced the sensory properties of sausages.PRACTICAL APPLICATIONSIn this work the development and application of an analytical method for the determination of free fatty acids (FFAs) and diacylglycerols (DAGs) in sausages was achieved. DAGs are intermediate products of hydrolysis and also constitute a substrate for hydrolysis reactions leading to FFA release. These latter compounds undergo a series of reactions leading to the formation of low‐molecular‐weight products responsible for sensory properties of dry‐cured sausages. Therefore, the assessment of these lipolysis products is a useful tool for evaluating the ripening process of dry‐cured sausages.

The Id-proteins are a family of four related proteins implicated in the control of differentiation and cell-cycle progression. Down-regulation of Id-gene expression is essential for the differentiation of several cell types. In addition, deregulated Id2 activity inhibits the Rb tumor suppressor pathway and promotes the expression of vascular endothelial growth factor (VEGF). Several members of VEGF family could be involved in Kaposi's sarcoma (KS) development and progression. Lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) is the first marker of lymphatic endothelial competence during development in the mature vasculature, and is also expressed on KS spindle cells. Rapamycin (RAPA), an immunosuppressive drug, has been shown to reverse KS growth and to reduce tumor angiogenesis. We evaluate, in transplantation-associated KS and in cultured KS-cells the RAPA effect on Id2 and on de novo lymphangiogenesis. Markers of lymphatic-endothelial-cells (VEGFR-3, LYVE-1) and Id2, expressed at low levels within the normal skin, were up-regulated in KS and returned to normal levels after RAPA introduction. The association between Id2 and lymphangiogenesis is suggested by co-localization of Id2, VEGFR-3 and LYVE-1. RAPA inhibition on Id2 expression was confirmed in vitro in KS-cells, both in basal conditions and upon stimulation with VEGF. In conclusion, our data would suggest a novel molecular mechanism for the antineoplastic effects of RAPA in posttransplant KS.

Introduction. There is some debate as to whether patients (pts) with chronic hepatitis C on haemodialysis should receive treatment for hepatitis C virus (HCV). However, not treating pts who will undergo renal transplantation (RT) may lead to an increased risk of HCV allograft nephropathy and progression of liver disease. The issue of anti-HCV therapy in haemodialysis pts listed for RT is now under active review.

The lipolysis evolution have been studied in Ciauscolo, a typical sausage from the Italian region of Marche and Umbria whose characteristic is the ability to be spread. Samples have been collected at production and after 1, 3, 10, 20, 30, and 45 days. Microbiological (lactic bacteria, coagulase-negative cocci, yeasts) and chemical analyses (total and free fatty acids and diglycerides determinations) have been performed at each time. As shown by viable counts, the lactic acid bacteria content was much larger than coagulase-negative cocci and yeast content. Concerning the total fatty acid (TFA) composition, monounsaturated fatty acids (MUFA) were the most abundant followed by saturated (SFA) and polyunsaturated ones (MUFA). This peculiarity gives to Ciauscolo some nutritional advantages with respect to other sausage product. A high lipolytic activity was demonstrated by the increase in free fatty acids (FFA) and diglycerides (DC), which reached the maximum value after 30 days of maturation. FFA composition showed a distribution different from that of TFA: SFA were the most abundant followed by MUFA and PUFA. Diglycerides containing 34, 36 and 32 atoms of carbon were found in a decreasing order of concentrations. During maturation, FFA and DG contents showed an exponential correlation caused by the major production of FFA. The high production of FFA, precursors of the aroma compounds as a consequence of the oxidation processes, could contribute to the development of the sensory characteristics of Ciauscolo.

Delayed graft function (DGF) in kidney transplantation is associated with an increased risk of acute rejection. Myeloid dendritic cells (DCs) are involved in graft rejection, whereas plasmacytoid DCs may play a role in inducing tolerance. We evaluated the presence and phenotype of the DCs in renal graft biopsies of 15 patients with DGF collected before and 7-15 days after transplantation. Biopsies taken from normal patients and from transplant recipients with acute calcineurin inhibitors (CNIs) nephrotoxicity served as a control group. Specific markers of myeloid, plasmacytoid, and mature DCs were imaged by confocal microscopy and immunohistochemistry. In normal kidneys and pre-transplant biopsies, sparse niches of myeloid and plasmacytoid cells were found but these were significantly increased with few mature cells during DGF. This same pattern was seen in acute rejection but with overall higher cell numbers. In CNI nephrotoxicity, myeloid cells were slightly increased but plasmacytoid cells were significantly higher than in DGF. Using a pig model, we found that a short period of warm ischemia followed by reperfusion led to myeloid cell infiltration of the kidney. Our data suggest that ischemia-reperfusion injury may cause an imbalance between intragraft myeloid and plasmacytoid DCs, which might be related to DGF and acute rejection.

Amantadine may augment virological response rates to interferon-based therapy in chronic hepatitis C patients. Using a novel design, amantadine was studied in naïve genotype 1 patients treated in combination with peginterferon alfa-2a (40KD)/ribavirin.Patients enrolled in this randomized, placebo-controlled multicenter trial were stratified by single-dose interferon sensitivity (stratum I, 24-h HCV-RNA decline >1.4-log10; II, 0.8–1.39-log10; III, <0.8-log10; a reliable means of identifying nonresponders to interferon/ribavirin) and fibrosis grade (F0/1/2 vs. F3/4) at baseline. All patients received peginterferon alfa-2a (40KD) 180 μg/week plus ribavirin 1000–1200 mg/day and were randomized to receive amantadine 100 mg twice daily (N=114) or placebo (N=95) for 48 weeks.Week-24 virological response rates in strata II and III, the primary outcome, were similar in patients treated with amantadine (63.7%) or placebo (65.7%), as were sustained virological response rates at week 72 (46.5 and 51.6%, respectively). Adverse event profiles were similar and amantadine did not improve health-related quality of life compared with placebo. Interferon sensitivity was the only significant predictor of treatment outcome.Adding amantadine to peginterferon alfa-2a (40KD)/ribavirin combination therapy does not augment virological response rates in genotype 1 patients. Virological response was almost exclusively determined by interferon sensitivity at baseline.

The increased efficiency of immunosuppressive drugs obtained in the last few years has significantly reduced the incidence of acute rejection, prolonging transplant survival rates. The inevitable trade-off was however an increased rate of post-transplant infections and malignancies. Furthermore, this problem might get more and more serious in the next future due to the increasing incidence of cancer in immunosuppressed transplant recipients; the introduction of new immunosuppressive strategies is expected to extend significantly allograft survival. The inclusion of older recipients in transplant programs will also likely increase this problem. Thus, cancer may represent a serious cause of morbidity and mortality in patients otherwise successfully treated by organ transplantation. Nevertheless, effective approaches to deal with malignancies in immunosuppressed patients are still far from the clinical arena. Therefore, once cancer occurs in a transplant recipient, clinicians only have two options: to reduce or withdraw the immunosuppression eventually causing acute or chronic allograft rejection, or to continue the standard immunosuppressive therapy while beginning specific therapy for the malignancy. Several clinical studies suggest that the use of immunosuppressive drugs may result in increased cancer incidence, in transplant as well as autoimmune disease patients. This clinical observation is supported by experimental data showing that these drugs enhance cancer cell growth characteristics and inhibit DNA repair mechanisms, clearly suggesting that the increased incidence of neoplastic disease in patients treated with several immunosuppressive drugs is at least partially independent of their immunosuppressive action. In this scenario it is of particular interest the fact that some immunosuppressive drugs have both an anti-rejection and anti-neoplastic activity. In this review we focus our attention on this potential dual role of immunosuppressive therapy in the development of neoplasia in transplanted patients.