Ex vivo immunomodulatory effect of all-trans-retinoic acid during Behçet’s disease: a study in Algerian patients

Uveitis, recurrent oral and genital ulcerations associated with skin lesions are the major symptoms of a chronic multisystemic inflammatory disorder known as Behçet’s disease (BD). High prevalence of this dreaded disease has been observed in the Mediterranean basin, including Algeria and along the Silk Road. Although the etiologic agent of this disease remains uncertain, many hypotheses have been advanced in its pathogenesis. Our team has previously reported high levels of nitric oxide (NO) in sera of BD patients, suggesting its deleterious effect during chronic inflammation. In our current study, the aim is to investigate the ex vivo immunomodulatory effect of all-trans-retinoic acid (ATRA) on NO pathway in Algerian BD patients. First, peripheral blood mononuclear cells isolated from active and inactive BD patients and healthy controls were cultured with different concentrations of ATRA. NO production was estimated with the Griess method. To elucidate the underlying mechanisms of ATRA effect on NO production, we analyze inducible nitric oxide synthase expression and nuclear factor-κB (NF-κB) activity by immunofluorescence test. Our results revealed a higher production of NO in active BD compared with the inactive stage and healthy controls. We observed that ATRA inhibits NO production in BD both in active and inactive stages and inhibits NF-κB translocation. In conclusion, we report a relationship between NO production and the disease activity. ATRA down-regulates NO production in BD patients. This immunomodulatory effect seems to be mediated through NF-κB pathway. All these findings suggest that ATRA could be considered as a promising therapy for BD.     

Iron metabolism imbalance at the time of listing increases overall and infectious mortality after liver transplantation

BACKGROUND Liver transplantation(LT) is the best treatment for patients with liver cancer or end stage cirrhosis, but it is still associated with a significant mortality. Therefore identifying factors associated with mortality could help improve patient management. The impact of iron metabolism, which could be a relevant therapeutic target, yield discrepant results in this setting. Previous studies suggest that increased serum ferritin is associated with higher mortality.Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered.AIM To assess the impact of pre-transplant iron metabolism parameters on posttransplant survival.METHODS From 2001 to 2011, 553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included. Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient. Serum ferritin(SF) and transferrin saturation(TS) were studied as continuous and categorical variable. Cox regression analysis was used to determine mortality risks factors. Follow-up data were obtained from the local and national database regarding causes of death.RESULTS At the end of a 95-mo median follow-up, 196 patients were dead, 38 of them because of infections. In multivariate analysis, overall mortality was significantly associated with TS 75% [HR: 1.73(1.14; 2.63)], SF 100 μg/L [HR: 1.62(1.12;2.35)], hepatocellular carcinoma [HR: 1.58(1.15; 2.26)], estimated glomerular filtration rate(CKD EPI Cystatin C) [HR: 0.99(0.98; 0.99)], and packed red blood cell transfusion [HR: 1.05(1.03; 1.08)]. Kaplan Meier curves show that patients with low SF( 100 μg/L) or high SF( 400 μg/L) have lower survival rates at 36 mo than patients with normal SF(P = 0.008 and P = 0.016 respectively). Patients with TS higher than 75% had higher mortality at 12 mo(91.4% ± 1.4% vs 84.6% ±3.1%, P = 0.039). TS 75% was significantly associated with infection related death [HR: 3.06(1.13; 8.23)].CONCLUSION Our results show that iron metabolism imbalance(either deficiency or overload)is associated with post-transplant overall and infectious mortality. Impact of iron supplementation or depletion should be assessed in prospective study.     

Comorbidities,Treatment and Ensuing Survival in Men with Prostate Cancer

Background  

Comorbidity is poorly integrated into prostate cancer decision making.