4 research outputs found
Le syndrome hémolytique urémique familial récidivant lié à un déficit en protéase clivant le facteur von Willebrand (à propos de deux cas)
LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
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Apolipoprotein A5 is an inflammatory responsive gene down-regulated by tumor necrosis factor alpha and interleukin-1
Several epidemiological studies have established that elevated plasma triglyceride concentrations constitute an independent risk factor for cardiovascular diseases. In addition, systemic inflammation is associated with severe hypertriglyceridemia and previous studies have demonstrated that cytokines such as tumor necrosis factor alpha (TNFalpha;) and interleukin-1 (IL-1) can elevate plasma triglyceride levels. Recently, we identified a new apolipoprotein, APOA5, selectively expressed in the liver and showed that this gene is a crucial determinant of plasma triglyceride levels. In this study, we sought to determine whether inflammatory cytokines regulate APOA5 and consequently influence plasma triglyceride levels. We found initially that treatment of human hepatocytes with TNFalpha; or IL-1 reduced the expression of APOA5 mRNA. Subsequent, we demonstrated through transient transfection experiments that both TNFalpha; and IL-1 down-regulate human APOA5 at the transcriptional level. Further deletion analyses of the APOA5 promoter and binding assays revealed the presence of a promoter sequence, containing a PPARalpha; Response Element, responsive to cytokine stimulation. In vivo, treatment of hAPOA5 transgenic mice with TNFalpha; down-regulated the hAPOA5 gene expression in hepatocytes. In patients displaying systemic inflammation, plasma concentrations of triglycerides and ApoAV were inversely correlated. These findings demonstrate that APOA5 is an inflammatory responsive gene and constitutes a link between inflammation and triglyceride-associated cardiovascular risk
Efficacy and safety of basiliximab in pediatric renal transplant patients receiving cyclosporine, mycophenolate mofetil, and steroids
BACKGROUND: Basiliximab, a monoclonal CD25 antibody has proofed effective in reducing acute rejection episodes in adults in various immunosuppressive regimens. The effect of basiliximab in the pediatric population is controversial. METHODS: In a 12-month, double-blind, placebo-controlled trial, renal transplant patients aged 1 to 18 years were randomized to basiliximab or placebo with cyclosporine microemulsion, mycophenolate mofetil, and corticosteroids. The intent-to-treat population comprised 192 patients (100 basiliximab and 92 placebo). RESULTS: The primary efficacy endpoint, time to first biopsy-proven acute rejection episode, or treatment failure by month 6, occurred in 16.7% of basiliximab-treated patients and 21.7% of placebo-treated patients (Kaplan-Meier estimates; hazard ratio 0.72, two-sided 90% confidence interval 0.416-1.26, n.s.). The rate and severity of subclinical rejections in protocol biopsies performed at 6 months posttransplant was higher in the basiliximab group (25.0%) than in the placebo group (11.7%). Patient and death-censored graft survival at 12 months was 97% and 99%, respectively, in the basiliximab cohort, and 100% and 99% among placebo-treated patients (n.s.). Renal function was similar in both treatment groups, and there were no significant between-treatment differences in the incidence of adverse events or infections. CONCLUSIONS: Addition of basiliximab induction to a regimen of cyclosporine microemulsion, mycophenolate mofetil, and steroids resulted in a numerically lower but not significant incidence of biopsy-proven acute rejection versus placebo and excellent graft and patient survival at 1 year in pediatric renal transplant recipients. Whether this numerical difference is a true therapeutic benefit in view of the higher rate and severity of subclinical rejections in the basiliximab group in the protocol biopsy will be investigated in a long-term follow-up study