Biomedical subjects

A Brunati

Publications and source records attributed to A Brunati.

5 recordsLinked to original sources

PubMed2004

Sequential liver-kidney transplantation.

The indications for sequential liver and kidney transplantation have not been well defined. Two categories of patients may benefit from this procedure: patients with primary renal disease associated with hepatic disorders (glomerulonephritis, tubulointerstitial nephritis, metabolic diseases, and structural diseases) and patients who develop renal failure after liver transplantation. Chronic renal failure is a frequent long-term complication after liver transplantation. End-stage renal disease develops in 2% to 10% of cases by 10 years after transplantation. Kidney transplantation appears to be a better option than dialysis for the treatment of end-stage renal disease after liver transplantation. In contrast, survival rates, after kidney transplantation are significantly lower among liver transplant patients than primary-only kidney transplant recipients. Considering the donor shortage, kidney transplantation should be cautiously considered in liver transplantation patients. New immunosuppressive drugs and protocols are needed to reduce chronic renal failure after liver transplantation.

Humans↗

PubMed2001

Antennapedia/HS1 chimeric phosphotyrosyl peptide: conformational properties, binding capability to c-Fgr SH2 domain and cell permeability.

With the aim of interfering with the signaling pathways mediated by the SH2 domains of Src-like tyrosine kinases, we synthesized a tyrosyl-phospho decapeptide, corresponding to the sequence 392-401 of HS1 protein, which inhibits the secondary phosphorylation of HS1 protein catalyzed by the Src-like kinases c-Fgr or Lyn. This phospho-peptide was modified to enter cells by coupling to the third helix of Antennapedia homeodomain, which is able to translocate across cell membranes. Here we present CD and fluorescence studies on the conformational behavior in membrane-mimicking environments and on lipid interactions of Antennapedia fragment and its chimeric phosphorylated and unphosphorylated derivatives. These studies evidenced that electrostatic rather than amphiphilic interactions determine the peptide adsorption on lipids. Experiments performed with recombinant protein containing the SH2 domain of c-Fgr fused with GST and with isolated erythrocyte membranes demonstrated that the presence of the N-terminal Antennapedia fragment only slightly affects the binding of the phospho-HS1 peptide to the SH2 domain. In fact, it has been shown that in isolated erythrocyte membranes, both phospho-HS1 peptide and its chimeric derivative greatly affect either the SH2-mediated recruitment of the c-Fgr to the transmembrane protein band 3 and the following phosphorylation of the protein catalyzed by the Src-like kinase c-Fgr. The ability of the chimeric phospho-peptide to enter cells has been demonstrated by confocal microscopy analysis.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

Use of hepatitis C virus-positive grafts in liver transplantation: a single-centre experience.

AIM: Our goal was to evaluate the outcome of HCV(+) recipients after liver transplantation (LT) using HCV(+) donors and the interaction between donor and recipient viral strain. METHODS: We performed a retrospective analysis of 21 LT performed between 1998 and 2004 using livers from HCV(+) donors in HCV(+) recipients. Two hundred thirty-seven patients with HCV cirrhosis who underwent LT with livers from HCV(-) donors were the control group. Ishak score (IS) was evaluated for all HCV(+) grafts. The considered variables included donor age, hepatic enzymes, intensive care unit stay, HCV genotype, ischemia time, recipient age, UNOS status, Child score, HCV genotype (before and 6 months after LT) and IS (after LT). We analyzed patient, graft, and disease-free survival. RESULTS: HCV(+) donors were significantly older than HCV(-) donors. The cumulative 5-year patient and graft survivals and disease free intervals were not different between groups. IS grading was more than 2/18 in two cases; the only graft with a staging score over 2/6 was retransplanted for early nonfunction. In two cases, different HCV genotypes were matched and donor strain took over the recipient strain. In one patient, donor genotyping 2a-2c took over recipient genotyping 1b and 9 months after LT recurrent hepatitis was documented, but antiviral therapy cleared HCV. CONCLUSIONS: Livers from HCV(+) donors can safely be used in HCV(+) recipients. Hepatic biopsy must always be performed; livers with bridging fibrosis should not be used. The takeover of one strain by another may change the prognosis of the patient if the predominant strain is more sensitive to antiviral therapy.

Disease-Free Survival↗

PubMedDate not supplied

Mycophenolate mofetil monotherapy in liver transplantation.

AIM: Calcineurin inhibitors (CI) are associated with significant morbidity in transplant recipients. The aim of this study was to evaluate the effectiveness and safety of mycophenolate mofetil (MMF) monotherapy in liver transplantation (LT). METHODS: We analysed 32 patients (24 males, 8 female, of mean age 55.7 years) who underwent LT between 1994 and 2003. In 29 patients immunosuppressive therapy was cyclosporine; in three patients it was tacrolimus. Eleven patients were submitted for LT due to hepatitis B cirrhosis; eight for hepatitis C cirrhosis, six for alcoholic cirrhosis, and seven for other diseases. In these patients, MMF was added gradually, simultaneously reducing the dosage of CI up to complete withdrawal. We considered the efficacy (decrease in serum creatinine) and the incidence of complications (acute and chronic rejection, leukopenia, diarrhea). RESULTS: Patients were converted to MMF after a median of 50 months after LT. MMF monotherapy was started after a median of 9 months in association with CI. Indications for switch to MMF monotherapy were adverse effects of CI (renal disfunction in 30 patients) and de novo tumoral evidence after LT in two patients. Median dosage of MMF was 750 mg twice daily (500-1500 mg). There was a statistically significant decrease in serum creatinine levels (2.02-1.7 mg/dL; P = .0001). Side effects were: leukopenia in five of 32 patients (15.6%), diarrhea in four of 32 patients (12.5%), and one acute rejection. CONCLUSION: MMF monotherapy improved renal function and was not associated with a significant risk of allograft rejection. Side effects were mild with dose regimens up to 750 mg twice daily.

Adult↗

PubMedDate not supplied

New-onset diabetes after liver transplantation.

AIM: The impact of new-onset diabetes (NOD) posttransplantation has been underestimated in the past. The aim of this study was to evaluate the incidence of diabetes after liver transplantation. METHODS: We retrospectively analyzed the incidence of NOD in 899 patients transplanted in our center. According to International Consensus 2003 Guidelines, criteria for diagnosis of diabetes were: fasting plasma glucose > or =126 mg/dL, symptoms of diabetes plus casual plasma glucose concentrations > or =200 mg/dL, and 2-hour plasma glucose levels > or =200 mg/dL during an oral glucose tolerance test. We considered only patients with follow-up over 10 months. We evaluated the risk factors correlated with NOD (age, hepatitis C virus [HCV] positivity, tacrolimus vs cyclosporine, steatosic graft), and the outcomes of diabetic patient and their grafts. RESULTS: The incidence of NOD was 10.8% (90/830 patients). Sixty nine patients were diabetic before transplantation. Recipient age >45 years (14.7% vs 6.8%, P = .002, OR = 2.4) and HCV positivity (15.5% vs 7.8%, P = .001, OR = 2.2) significantly correlated with NOD. Multivariate analysis confirmed these variables to be independently associated with diabetic risk. Tacrolimus was associated with an increased risk of NOD (16.2% in HCV-negative patients, 25% in HCV-positive patients), but this difference was not statistically significant. Steatotic grafts (>10%) were associated with an increased risk of NOD (28.6% vs 10%, P = .001, OR = 3.6). The outcome of patients and grafts in the group of diabetic patients was not significantly different from all other patients. CONCLUSIONS: The incidence of NOD was more relevant in patients older than 45 years and/or HCV-positive. A steatotic graft was an important risk factor, and the match with high-risk patients should be avoided.

Age Factors↗