Inflammation in Alzheimer's disease - in vivo quantification

Scheltens, P. [Promotor]Lammertsma, A.A. [Promotor]Berckel, B.N.M. van [Copromotor]Boellaard, R. [Copromotor

Early pregnancy biomarker discovery study for spontaneous preterm birth

(1) Objective: discover new candidate biomarkers for spontaneous preterm birth in early pregnancy samples. When fully clinically validated, early pregnancy biomarkers for sPTB give the possibility to intervene or monitor high-risk pregnancies more intensively through, as example, pelvic exams, ultrasound or sonographic cervical length surveillance. (2) Study design: Early pregnancy serum samples of eight spontaneous extreme and very preterm birth cases (&lt;32 weeks of gestational age) without any symptoms of preeclampsia and fetal growth restriction and eight uncomplicated pregnancies were analyzed by liquid chromatography mass spectrometry (LC-MS). Thirteen proteins, which were differentially expressed according to the LC-MS data, were subsequently selected for confirmation by enzyme-linked immunosorbent assay (ELISA). (3) Results: Differential expression of four candidate biomarkers was confirmed by ELISA with decreased early pregnancy levels of gelsolin and fibulin-1 and increased levels of c-reactive protein and complement C5 in the preterm birth group. (4) Conclusions: The confirmed candidate biomarkers are all to some extent related to inflammatory pathways and/or the complement system. This supports the hypothesis that both play a role in extreme and very preterm birth without any symptoms of preeclampsia and fetal growth restriction. The predictive value of complement C5, c-reactive protein, fibulin-1 and gelsolin should, therefore, be validated in another cohort with early pregnancy samples.</p

27. New echocardiogram index alternatives to MAPSE and TAPSE z-scores in children

BackgroundMitral annular plane systolic excursion (MAPSE), and tricuspid annular plane systolic excursion (TAPSE) are relatively load independent longitudinal left ventricle (LV) and right ventricle (RV) measurement in both adults and children. Normal paediatric values of MAPSE and TAPSE unlike adults are based on inconvenient z-scores. We hypothesize novel indexes of (LSI) LV longitudinal systolic index and (RSI) RV longitudinal systolic index are BSA, age, gender independent and nullifies the need for MAPSE and TAPSE z-scores.MethodsNormal echocardiograms were retrospectively reviewed from 2009 to 2011. Ejection fraction, LV dimensions, MAPSE, and TAPSE were determined. LSI and RSI were calculated using MAPSE and TAPSE divided by LV length. Echocardiogram indices were correlated. Regression analysis was done for BSA, age, and gender.ResultsTwo hundred and one patients had normal ejection fractions (67.3;±5.1%). Mean MAPSE 10.4;±3.3mm, z-score −0.07;±1.2, and LSI 0.20;±0.03; Mean TAPSE 17.4;±5.4mm, z-score 0.74;±1.7, and RSI 0.34;±0.06. LSI and MAPSE z-scores correlated, r=0.73, p<0.001. Age, gender, and BSA did not correlate with LSI. RSI and TAPSE z-scores correlated with r=0.76, p<0.001. Age influences RSI, R2=0.58, p value <0.001, BSA and gender does not. RSI, with age stratification, is significantly decreased less than 2months.ConclusionLSI obviates need for-MAPSE z scores. RSI offers an additional non TAPSE z-score method to evaluate RV function, but does not nullify age effect. RSI, especially in the first two months is decreased

Healthy and preeclamptic pregnancies show differences in Guanylate-Binding Protein-1 plasma levels

The large interferon-inducible anti-angiogenic pro-inflammatory GTPase Guanylate Binding Protein-1 (GBP-1) is produced and secreted by activated endothelial cells and is highly induced by inflammatory cytokines and inhibited by angiogenic growth factors. During pregnancy a generalized mild inflammatory response is observed. During preeclampsia this generalized inflammatory response is even further activated and activation of the endothelium occurs. We hypothesized that GBP-1 is increased in healthy pregnancy and will be even further increased during preeclampsia. In the first experiment, plasma and placentas were collected from healthy and preeclamptic pregnancies. Plasma was also collected from non-pregnant women. For the second experiment longitudinal blood samples from women with a healthy or preeclamptic pregnancy were collected from the end of the first trimester until birth and one sample postpartum. The plasma GBP-1 levels were measured by ELISA and GBP-1 mRNA and protein levels in the placenta were tested by qPCR and immunohistochemistry. During pregnancy higher plasma concentrations of GBP-1 compared with non-pregnant women were observed. Surprisingly, during preeclampsia, plasma GBP-1 levels were lower than in control pregnancies and similar to the level of non-pregnant controls. Placental GBP-1 mRNA levels were not different between healthy and preeclamptic pregnancies and GBP-1 protein was virtually undetectable in the trophoblast by immunohistochemistry in placental tissue. Evaluation of longitudinal samples showed that plasma GBP-1 concentrations increased towards the end of pregnancy in healthy pregnancies, but not in preeclampsia. In line with our hypothesis, we found higher GBP-1 plasma levels during healthy pregnancy. However, plasma GBP-1 did not further increase during preeclampsia, but was stable. Further studies are needed to evaluate why GBP-1 does not increase during preeclampsia

Kinetics of Plasma- and Erythrocyte-Astaxanthin in Healthy Subjects Following a Single and Maintenance Oral Dose

Aim & background: Astaxanthin is a unique carotenoid of predominantly marine origin providing the pink-red color to certain microalgae and accumulating in various animals higher in the food chain. It is an antioxidant without pro-oxidant properties or known side-effects following oral intake. Methods: We investigated astaxanthin kinetics in plasma and erythrocytes (RBC) of four healthy adults after a single oral 40 mg dose. Plasma- and RBC-astaxanthin were measured during 72h. Subsequently, an 8 mg/day dose was given during 17 days. Plasma- and RBC-astaxanthin were measured each morning. Results: Plasmaastaxanthin reached a peak (from 79 to 315 nmol/L) after 8h and then declined (half-life, 18h). Within 72h, plasma-astaxanthin had returned to baseline. RBC-astaxanthin reached a peak (from 63 to 137 nmol/L packed cells) at 12h and subsequently disappeared (half-life, 28h). During the daily dose, plasmaastaxanthin increased until day 10 (187 nmol/L) and then decreased to a steady concentration similar to that reached after 2 days. RBC-astaxanthin appeared to be highly variable (group median concentration, 86 nmol/L packed cells). Conclusion: We found high intra- and inter-individual variations, especially in RBC, possibly due to non-standardized time difference between astaxanthin intake and sampling, fl uctuating background intake from the diet, variable bioavailability, large distribution volume, degradation or others. Oral astaxanthin is rapidly absorbed and incorporated into RBC. The subsequent rapid decline suggests that, for a higher-than-baseline status, astaxanthin should be taken daily, at least in an early phase when total body equilibrium, if any, has not been reached yet