Search

Eur J Clin Invest 2010; 40 (10): 893–902 Abstract Background Clusterin (Apolipoprotein J), a plasma protein with cytoprotective and complement-inhibiting activities, localizes in the infarcted heart during myocardial infarction (MI). Recently, we have shown a protective effect of exogenous clusterin in vitro on ischaemically challenged cardiomyocytes independent of complement. We therefore hypothesized that intravenous clusterin administration would reduce myocardial infarction damage. Methods Wistar rats undergoing experimental MI, induced by 40 min ligation of a coronary vessel, were treated with either clusterin (n = 15) or vehicle (n = 13) intravenously, for 3 days post-MI. After 4 weeks, hearts were analysed. The putative role of megalin, a clusterin receptor, was also studied. Results Administration of human clusterin significantly reduced both infarct size (with 75 ± 5%) and death of animals (23% vehicle group vs. 0% clusterin group). Importantly, histochemical analysis showed no signs of impaired wound healing in the clusterin group. In addition, significantly increased numbers of macrophages were found in the clusterin group. We also found that the clusterin receptor megalin was present on cardiomyocytes in vitro which, however, was not influenced by ischaemia. Human clusterin co-localized with this receptor in vitro, but not in the human heart. In addition, using a megalin inhibitor, we found that clusterin did not exert its protective effect on cardiomyocytes through megalin. Conclusions Our results thus show that clusterin has a protective effect on cardiomyocytes after acute myocardial infarction in vivo, independent of its receptor megalin. This indicates that clusterin, or a clusterin derivate, is a potential therapeutic agent in the treatment of MI.

Background In the Netherlands, prenatal screening for trisomy 21 in the first trimester of pregnancy for singletons is conducted through a combined test based on maternal age, nuchal translucency measurement and maternal serum free β-hCG and PAPP-A. In our clinic risk calculations in twins are currently based on the NT of both fetuses instead of the combined test. In this study we looked at differences in early first-trimester free β-hCG and PAPP-A between mono- and dichorionic twins. Methods A total of 202 twin pregnant women participated in the study and agreed to donate first-trimester serum for research. Results The data of 200 twins with normal outcome were used for setting up reference values for free β-hCG and PAPP-A. Trisomy 21 was identified in the two remaining pregnancies. The overall median weight-corrected MoM was 1.99 for free β-hCG, and 2.14 for PAPP-A in all twins. Monochorionic twins have a significantly lower free β-hCG weight-corrected MoM (1.53 vs 2.11; Mann-Whitney U, p = 0.002) and a significantly lower PAPP-A weight-corrected MoM (1.59 vs 2.40; Mann-Whitney U, p = 0.003) compared to dichorionic. Conclusion This study strengthened the need to make a distinction between mono- and dichorionic twins for the risk calculation in Down syndrome screening as biochemical markers are significantly lower in monochorionic than in dichorionic twins.

Objective To construct reference ranges for spiral artery (SA) flow velocities and examine the possibility to predict intra uterine growth restricted (IUGR) fetuses, pregnancy-induced hypertension (PIH) and/or preeclampsia. Methods Spiral artery flow velocity measurements were performed using Color Doppler between 11 to 13 + 6, between 14 to 17 + 6 and between 18 to 24 weeks of gestation, each measurement was performed twice. Spiral artery flow velocities were analyzed with multilevel modeling: individual regression curves were estimated and combined to obtain the reference intervals for SA flow velocities in normal pregnancies. Mann–Whitney U tests was used to compare the deviation from expected flow velocity between normal and complicated pregnancies. Results One hundred and eight pregnancies were included; 4 pregnancies were complicated with preeclampsia, 10 pregnancies with IUGR fetuses (

Purpose. Determine the reproducibility of 3D ultrasound (3DUS) measurements of fetal and placental volumes. Methods. We included 34 pregnant women between gestational weeks (GW) 11–18. Two operators independently acquired fetal and placental volumes using 3DUS. Each volume was acquired twice and stored on disk for off-line analysis. Intra- and interobserver reproducibility was expressed in the intra- and interclass correlation coefficient (intra-CC and inter-CC). In addition, the 3DUS volumes acquired by the first operator were calculated by the second and vice-versa to evaluate the effect of volume acquisition and caliper placement. A value >0.75 was considered a good agreement. Results. Fetal and placental volume measurements were successful in 97% of all cases. Between GW 11–14 and 14–18 the median fetal volume was 20.8 (5.0–35.1) and 51.7 (37.9–132.8) ml, the median placental volume was 71.3 (40.9–111.9) and 120.7 (94.2– 273.7) ml. Bland-Altman plots were used for statistical analysis. The intraobserver reproducibility was good for fetus (intra-CC: 0.99; 0.99) and placenta (intra-CC: 0.99; 0.98). Also, interobserver reproducibility was good for fetus (inter-CC 0.98) and placenta (inter-CC 0.98). In addition, regardless of the operator who acquired the volumes, the inter-CC remained good for both fetus (inter-CC: 0.99; 0.99) and placenta (inter-CC: 0.97; 0.99). Conclusion. The reproducibility of fetal and placental volume measurements by 3DUS between GW 11–18 is good. In addition, individually chosen caliper placement and volume acquisition has no effect on the calculation of either volumes. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2007