Skin Autofluorescence Predicts Cardiovascular Mortality in Patients on Chronic Hemodialysis

Tissue accumulation of advanced glycation end products (AGE) is thought to contribute to the progression of cardiovascular disease (CVD). Skin autofluorescence, a non‐invasive measure of AGE accumulation using autofluorescence of the skin under ultraviolet light, has been reported to be an independent predictor of mortality associated with CVD in Caucasian patients on chronic hemodialysis. The aim of this study was to assess the predictive value of skin autofluorescence on all‐cause and cardiovascular mortality in non‐Caucasian (Japanese) patients on chronic hemodialysis. Baseline skin autofluorescence was measured with an autofluorescence reader in 128 non‐Caucasian (Japanese) patients on chronic hemodialysis. All‐cause and cardiovascular mortality was monitored prospectively during a period of 6 years. During the follow‐up period, 42 of the 128 patients died; 19 of those patients died of CVD. Skin autofluorescence did not have a significant effect on all‐cause mortality. However, age, carotid artery intima‐media thickness (IMT), serum albumin, high‐sensitivity C‐reactive protein (hsCRP), skin autofluorescence and pre‐existing CVD were significantly correlated with cardiovascular mortality. Multivariate Cox regression analysis showed skin autofluorescence (adjusted hazard ratio [HR] 3.97; 95% confidence interval [CI]1.67–9.43), serum albumin (adjusted HR 0.05; 95% CI 0.01–0.32), and hsCRP (adjusted HR 1.55; 95% CI 1.18–2.05) to be independent predictors of cardiovascular mortality. The present study suggests that skin autofluorescence is an independent predictor of cardiovascular mortality in non‐Caucasian (Japanese) patients on chronic hemodialysis.     

Dihydrotestosterone inhibits lectin-like oxidized-LDL receptor-1 expression in aortic endothelial cells via a NF-κB/AP-1-mediated mechanism

The mechanisms involved in the antiatherosclerotic effects of androgens are unclear. Although lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in endothelial cells plays critical roles in atherosclerosis, the effects of androgens on endothelial LOX-1 expression has not been examined. Therefore, to investigate the effects of dihydrotestosterone (DHT) on LOX-1 expression in rabbit aortic endothelial cells and cultured human aortic endothelial cells (HAEC), pellets containing DHT or placebo were s.c. implanted into 26 male New Zealand white rabbits at the time of castration or sham operation. The rabbits were then fed a high-cholesterol diet (HCD) for 2 wk. Microscopic examination of the aortic arch revealed that DHT significantly reduced HCD-induced LOX-1 expression in endothelial cells compared with placebo. In cultured HAEC, DHT at concentrations above 10(-9) to 10(-7) mol/liter inhibited TNFα-induced LOX-1 mRNA and protein expression. Deletion and mutation analysis of human LOX-1 promoter-luciferase constructs transfected into HAEC with an androgen receptor (AR) expression plasmid revealed that the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element (TRE; nucleotides -60/-53) contributed to the inhibitory effects of DHT on TNFα-induced LOX-1 expression. Chromatin immunoprecipitation (ChIP) and re-ChIP assays revealed that TNFα- and TPA-dependent enrichment of p65 and phosphorylated c-Jun in the TRE chromatin region was inhibited by DHT-AR. Consistent with these results, DHT also suppressed TPA-induced expression of LOX-1. In conclusion, DHT exerts antiatherosclerotic effects by suppressing endothelial LOX-1 expression. This effect is partly mediated by the suppression of nuclear factor-κB- and activator protein 1-dependent activation of the LOX-1 promoter.     

A Prospective Analysis of Efficacy and Long-Term Outcome of Radiation Therapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Background/Aims: Few studies exist on the efficacy and long-term outcome of radiation therapy (RT) for gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: Twenty-two patients with stage I or stage II(1) disease were prospectively evaluated, including 14 patients without Helicobacter pylori(H. pylori) infection and 8 patients with persistent lymphoma after H. pylori eradication. RT dose was 30 Gy in daily fractions of 1.5 Gy. All patients underwent endoscopic and histological follow-up regularly. Results: The study included 22 patients with a mean age of 63 years. The t(11;18)(q21;q21) translocation occurred in 8 of the 22 cases. All patients showed complete remission without any serious toxicity. At a median follow-up evaluation 74 months (range 27-159) after completion of RT, the overall and relapse-free survival rates after 5 years were 91 and 84%, respectively. Although no patient showed local recurrence of lymphoma, distant recurrence was detected in 3 patients, all of whom were H. pylori negative; MALT lymphoma relapsed in two patients with the t(11;18)(q21;q21) translocation, and diffuse large-cell lymphoma developed in one patient without the translocation. Conclusion: RT provides excellent local control of the gastric MALT lymphoma. However, continuous follow-up is mandatory as relapse may occur in other sites.