Offspring of parents with Balkan Endemic Nephropathy have higher C-reactive protein levels suggestive of inflammatory processes: a longitudinal study

<p>Abstract</p> <p>Background</p> <p>Despite the characteristic extensive tubulointerstitial fibrosis, Balkan Endemic Nephropathy (BEN) is usually considered a non-inflammatory disease.</p> <p>Methods</p> <p>We examined a marker of inflammation, C-reactive protein (CRP), in the offspring of patients with BEN, a population at risk for BEN, prior to development of established disease to determine if an inflammatory process could be identified in the early stages of the disease. In 2003/04, 102 adult offspring whose parents had BEN and a control group of 99 adult offspring of non-BEN patients were enrolled in this prospective study. This cohort was re-examined yearly for four consecutive years. Levels of serum CRP were measured in years 3 and 4 and compared between groups. The data were analyzed with mixed models.</p> <p>Results</p> <p>Compared to controls, offspring of BEN parents had statistically higher CRP levels in two consecutive years, suggestive of early inflammatory reactivity. Whenever the mother was affected by BEN (both parents, or mother only), serum CRP was significantly increased, but not if only the father had BEN. CRP was inversely related to kidney cortex width but not to markers or renal function.</p> <p>Conclusion</p> <p>Early stages of BEN may involve inflammatory processes. The observation of a maternal involvement supports the concept of fetal programming, which has been implicated in the pathogenesis of other chronic kidney diseases.</p

RNA-interference in rice against Rice tungro bacilliform virus results in its decreased accumulation in inoculated rice plants

Rice tungro is a viral disease seriously affecting rice production in South and Southeast Asia. Tungro is caused by the simultaneous infection in rice of Rice tungro bacilliform virus (RTBV), a double-stranded DNA virus and Rice tungro spherical virus (RTSV), a single-stranded RNA virus. To apply the concept of RNA-interference (RNAi) for the control of RTBV infection, transgenic rice plants expressing DNA encoding ORF IV of RTBV, both in sense as well as in anti-sense orientation, resulting in the formation of double-stranded (ds) RNA, were raised. RNA blot analysis of two representative lines indicated specific degradation of the transgene transcripts and the accumulation of small molecular weight RNA, a hallmark for RNA-interference. In the two transgenic lines expressing ds-RNA, different resistance responses were observed against RTBV. In one of the above lines (RTBV-O-Ds1), there was an initial rapid buildup of RTBV levels following inoculation, comparable to that of untransformed controls, followed by a sharp reduction, resulting in approximately 50-fold lower viral titers, whereas the untransformed controls maintained high levels of the virus till 40 days post-inoculation (dpi). In RTBV-O-Ds2, RTBV DNA levels gradually rose from an initial low to almost 60% levels of the control by 40 dpi. Line RTBV-O-Ds1 showed symptoms of tungro similar to the untransformed control lines, whereas line RTBV-O-Ds2 showed extremely mild symptoms

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

Tetrathiomolybdate (choline salt; ATN-224), a specific, high-affinity copper binder, is currently being evaluated in several phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase 1 (SOD1) leading to antiangiogenic and antitumour effects. The pharmacodynamics of tetrathiomolybdate has been followed by tracking ceruloplasmin (Cp), a biomarker for systemic copper. However, at least in mice, the inhibition of angiogenesis occurs before a measurable decrease in systemic copper is observed. Thus, the identification and characterisation of other biomarkers to follow the activity of ATN-224 in the clinic is of great interest. Here, we present the preclinical evaluation of two potential biomarkers for the activity of ATN-224: (i) SOD activity measurements in blood cells in mice and (ii) levels of endothelial progenitor cells (EPCs) in bonnet macaques treated with ATN-224. The superoxide dismutase activity in blood cells in mice is rapidly inhibited by ATN-224 treatment at doses at which angiogenesis is maximally inhibited. Furthermore, ATN-224 dosing in bonnet macaques causes a profound and reversible decrease in EPCs without significant toxicity. Thus, both SOD activity measurements and levels of EPCs may be useful biomarkers of the antiangiogenic activity of ATN-224 to be used in its clinical development