Comparison of Effects of Different Statins on Contrast-Induced Acute Kidney Injury in Rats: Histopathological and Biochemical Findings.

Statins are a promising new strategy to prevent contrast-induced acute kidney injury (CI-AKI). In this study we compared the ameliorative effect of different statins in a rat model of CI-AKI. Sprague-Dawley rats were divided into five groups: control group; CI-AKI group; CI-AKI + rosuvastatin group (10 mg/kg/day); CI-AKI + simvastatin group (80 mg/kg/day); and CI-AKI + atorvastatin group (20 mg/kg/day). CI-AKI was induced by dehydration for 72 hours, followed by furosemide intramuscular injection 20 minutes before low-osmolar contrast media (CM) intravenous injection. Statins were administered by oral gavage once daily for 3 consecutive days before CM injection and once 4 hours after CM injection. Rats were sacrificed 24 hours after CM injection, and renal function, kidney histopathology, nitric oxide (NO) metabolites, and markers of oxidative stress, inflammation, and apoptosis were evaluated. The results showed that atorvastatin and rosuvastatin but not simvastatin ameliorated CM-induced serum creatinine elevation and histopathological alterations. Atorvastatin and rosuvastatin showed similar effectiveness against CM-induced oxidative stress, but simvastatin was less effective. Atorvastatin was most effective against NO system dysfunction and cell apoptosis, whereas rosuvastatin was most effective against inflammation. Our findings indicate that statins exhibit differential effects in preventing CI-AKI when given at equivalent lipid-lowering doses.

Use of Both Serum Cystatin C and Creatinine as Diagnostic Criteria for Contrast-Induced Acute Kidney Injury and Its Clinical Implications.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) was traditionally defined as an increase in serum creatinine (sCr) after contrast media exposure. Recently, serum cystatin C (sCyC) has been proposed as an alternative to detect acute changes in renal function. The clinical implications of combining sCyC and sCr to diagnose CI-AKI remain unknown. METHODS AND RESULTS: One thousand seventy-one consecutive patients undergoing coronary angiography/intervention were prospectively enrolled. SCyC and sCr were assessed at baseline and 24 to 48 hours after contrast media exposure. CI-AKI determined by sCr (CI-AKIsCr) was defined as an sCr increase greater than 0.3 mg/dL or 50% from baseline. Major adverse events at 12 months were assessed. CI-AKIsCr developed in 25 patients (2.3%). Twelve-month follow-up was available for 1063 patients; major adverse events occurred in 61 patients (5.7%). By receiver operating characteristic curve analysis, an sCyC increase of greater than 15% was the optimal cutoff for CI-AKIsCr detection, which occurred in 187 patients (17.4%). To evaluate the use of both sCyC and sCr as CI-AKI diagnostic criteria, we stratified patients into 3 groups: no CI-AKI, CI-AKI detected by a single marker, and CI-AKI detected by both markers. Multivariable logistic regression revealed that the predictability of major adverse events increased in a stepwise fashion in the 3 groups (no-CI-AKI group as the reference, CI-AKI detected by a single marker: odds ratio=2.25, 95% CI: 1.24-4.10, P<0.01; CI-AKI detected by both markers: odds ratio=10.00, 95% CI: 3.13-31.91, P<0.001). CONCLUSIONS: Combining sCyC and sCr to diagnose CI-AKI would be beneficial for risk stratification and prognosis in patients after contrast media exposure.

Circulating MicroRNA-188, -30a, and -30e as Early Biomarkers for Contrast-Induced Acute Kidney Injury.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is typically defined by an increase in serum creatinine after intravascular administration of contrast medium. Because creatinine is an unreliable indicator of acute changes in kidney function, we assessed whether circulating microRNAs (miRNAs) could serve as biomarkers for early detection of CI-AKI. METHODS AND RESULTS: Using a rat model of CI-AKI, we first evaluated the miRNA profile of rat plasma and kidney. Three miRNA species with >1.5-fold increase in plasma samples of CI-AKI rats, including miRNA-188, miRNA-30a, and miRNA-30e, were selected as candidate miRNAs. Quantitative real-time polymerase chain reaction showed that these candidate miRNAs peaked in concentration around 4 hours after contrast medium exposure and were relatively renal-specific. We compared the plasma levels of these candidate miRNAs in 71 patients who underwent coronary angiography or percutaneous coronary intervention and developed CI-AKI with those of 71 matched controls. The plasma levels of the 3 candidate miRNAs were significantly elevated in the CI-AKI group as compared to the control group. Receiver operating characteristic analysis showed that these miRNAs significantly distinguished patients with CI-AKI from those without CI-AKI. MiRNA composites were highly accurate for CI-AKI prediction, as shown in maximized specificity by treble-positive miRNA composite or maximized Youden index by any-positive miRNA composite. Moreover, the selected miRNAs changes were associated with Mehran Risk Scores. CONCLUSIONS: Plasma levels of candidate miRNAs significantly distinguished patients with CI-AKI from those without CI-AKI. Thus, miRNAs are potential biomarkers for early detection of CI-AKI.

Orphan nuclear receptor Nur77 Inhibits Oxidized LDL-induced differentiation of RAW264.7 murine macrophage cell line into dendritic like cells.

BACKGROUND: Nur77 is an orphan nuclear receptor expressed in human atheroma. In vascular cells in vitro, Nur77 expression is induced by pro-inflammatory factors, such as oxidized LDL (oxLDL). METHODS: We analyze the role of Nur77 in the oxLDL-induced differentiation of macrophages into dendritic cells (DC). The murine RAW264.7 macrophage cell line was stably transfected with expression plasmids encoding either GFP or GFP fusions with either full-length Nur77 (GFP-Nur77), Nur77 lacking the DNA binding domain (GFP-Nur77-ΔDBD) or Nur77 lacking the transactivation domain (GFP-Nur77-ΔTAD). RESULTS: GFP-Nur77 overexpression significantly suppressed the effect of oxLDL treatment on DC morphologic changes, expression of DC maturation markers, endocytic activity, allogeneic activation of T cell proliferation, and the activity and secretion of pro-inflammatory cytokines. Analysis of GFP-Nur77-ΔTAD and GFP-Nur77-ΔDBD indicated that the Nur77 DNA binding and transactivation domains were both required for this effect. GFP-Nur77-ΔDBD consistently had the opposite effect to GFP-Nur77, increasing DC-type differentiation in all assays. Interestingly, GFP-Nur77-ΔDBD protein was cytosolic, whereas GFP-Nur77 and GFP-Nur77-ΔTAD were both nuclear. CONCLUSIONS: These data show that GFP-Nur77 inhibited differentiation of oxLDL-treated macrophages into DC. The effects of Nur77 on the macrophage phenotype may involve changes in its subcellular distribution.

[Seasonal variation characteristics of algae biomass in Chaohu Lake].

The biomass and distribution of algae community in Chaohu Lake were investigated in 2008. At the same time, the seasonal variations of algae translocation between the sediment and overlying water were also quantitative studied by self-made "algae up/down trap". Chaohu Lake was dominated by Cyanobacteria all the year, and dominant Cyanobacteria species changed in different seasons. In spring, Anabaena was the dominant species, and Microcystis was the subdominant species; In the whole summer and autumn, the dominant species is Microcystis. Algae biomass increased significantly from May and the maximum appeared in August, was 146.37 mg x m(-3) with Chl-a. The value of algae biomass were 9.75-16.24 mg x kg(-1) in the surface sediments, and the minimum appeared in Summer, then the algae biomass increased gradually with the maximum value in winter. Translocation process between the sediment and the overlying water occurred throughout the study period. The recruitment rates increased at first with the maximum rates in early August, was 0.036 8 mg x (m2 x d) (-1), and then had a downward tendency. However the sedimentation rates increased slowly firstly with the maximum rate in early September, then it decreased sharply, was 0.032 1 mg x (m2 x d)(-1). Multiple stepwise regression showed that temperature was the most significant factor for the algae biomass in Chaohu Lake, Total nitrogen (TN) and Total phosphorus(TP) are sub-important factors.

[Seasonal occurrence characteristics of different forms of nitrogen in the sediments of Chaohu Lake].

Seasonal characteristics of the free nitrogen (FN), the exchangeable nitrogen (EN), the acid hydrolysable nitrogen (HN) and the residual nitrogen (RN) in the surface sediment of Chaohu Lake were analyzed by sequential extraction method. The correlations among the nitrogen fractions with the total nitrogen (TN) and the mineralizable nitrogen (MN) were discussed considering the seasonal variations of the TN and MN. The results show that the concentrations of FN, EN and TN are lower in summer and higher in autumn and winter, NH4(+)-N is the main fraction of FN and EN. TN concentrations are much higher in West Chaohu Lake with the maximum concentration of 2280.47 mg/kg in the west lake center than in the East Chaohu Lake. The seasonal order of mineralizable nitrogen (MN) content is winter> spring > autumn > summer. The bio-available nitrogen fraction varies with different seasons, which is the amino acid nitrogen (AAN) in spring, EN in summer and autumn, FN in winter. The study about seasonal occurrence characteristics of nitrogen fractions in sediment provided foundational data for lake ecological security evaluation and nitrogen release evaluation.