Glycodelin is internalized by peripheral monocytes.

Glycodelin is produced by the endometrial cells during the luteal phase and first trimester of pregnancy and plays a role in the regulation of the endometrial immunology. However, the molecular connection between glycodelin and the maternal immune system is not clear. To better understand the possible physiological interaction between the endometrium and the maternal immune system, we investigated (1) whether glycodelin binds to mainly peripheral monocytes, and in case (2) whether the binding to the membrane only depends on the protein backbone or a carbohydrate structure is needed, and in case (3) whether glycodelin is internalized after binding to the membrane. We demonstrated that glycodelin - with or without the carbohydrate structure - was preferentially bound and internalized to peripheral monocytes. Surprisingly, we found signals in the nucleus of the monocytes indicating a potential regulating effect of glycodelin may be exerted through the nucleus. However, further studies should be performed to confirm this finding.

Recommendations on Measurement Units - Why and How.

Globally, laboratories are producing, communicating, and exchanging millions of laboratory examination values to multiple parties every day. For most values, 'measurement units' are required to make the numerical values comparable and meaningful. However, a non-systematic use of 'measurement units' can create errors in communication between health care providers and become a risk to patient safety. Therefore, the Committee of Nomenclature for Properties and Units (C-NPU) recommends using an unambiguous terminology of 'measurement units', for daily patient care and scientific publications. In this work, C-NPU summarizes the recommendations on 'measurement units', explaining the reasons and the principles of the 'measurement units' used in laboratory medicine.

Part II: Biochemical changes after pituitary adenylate cyclase-activating polypeptide-38 infusion in migraine patients.

Background Intravenous infusion of pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) provokes migraine attacks in 65-70% of migraine without aura (MO) patients. We investigated whether PACAP38 infusion causes changes in the endogenous production of PACAP38, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), tumour necrosis factor alpha (TNFα), S100 calcium binding protein B (S100B), neuron-specific enolase and pituitary hormones in migraine patients. Methods We allocated 32 previously genotyped MO patients to receive intravenous infusion PACAP38 (10 pmol/kg/minute) for 20 minutes and recorded migraine-like attacks. Sixteen of the patients were carriers of the risk allele rs2274316 ( MEF2D), which confers increased risk of MO and may regulate PACAP38 expression, and 16 were non-carriers. We collected blood samples at baseline and 20, 30, 40, 60 and 90 minutes after the start of the infusion. A control group of six healthy volunteers received intravenous saline. Results PACAP38 infusion caused significant changes in plasma concentrations of VIP ( p = 0.026), prolactin ( p = 0.011), S100B ( p < 0.001) and thyroid-stimulating hormone (TSH; p = 0.015), but not CGRP ( p = 0.642) and TNFα ( p = 0.535). We found no difference in measured biochemical variables after PACAP38 infusion in patients who later developed migraine-like attacks compared to those who did not ( p > 0.05). There was no difference in the changes of biochemical variables between patients with and without the MEF2D-associated gene variant ( p > 0.05). Conclusion PACAP38 infusion elevated the plasma levels of VIP, prolactin, S100B and TSH, but not CGRP and TNFα. Development of delayed migraine-like attacks or the presence of the MEF2D gene variant was not associated with pre-ictal changes in plasma levels of neuropeptides, TNFα and pituitary hormones.

Affinity purification of native glycodelin from amniotic fluid for biological investigations and development of a glycodelin ELISA for clinical studies.

INTRODUCTION: Glycodelin is a glycoprotein with different oligosaccharides that are responsible for its diverse biological functions in contraception and immunosuppression. Therefore, it is necessary to have access to adequate amounts of glycodelin with retained carbohydrate structure for functional studies because the carbohydrate part can be lacking or be insufficient in recombinant glycodelin from prokaryotic and eukaryotic cell systems. METHODS AND RESULTS: Native glycodelin was purified from amniotic fluid by a series of affinity chromatography steps and had many glycosylated forms verified by mass spectrometry. About 7.5 mg glycodelin was obtained from 1.5 L amniotic fluid. No high molecular mass forms of glycodelin were found in amniotic fluid. Aliquots of the purified glycodelin were used as an immunogen in rabbits for antibody production against glycodelin and a calibrator in a highly sensitive glycodelin enzyme-linked immunosorbent assay (ELISA) with a detection limit of about 1 µg/L. CONCLUSIONS: Native glycodelin was purified from amniotic fluid and used as an immunogen for raising a rabbit antibody against glycodelin and a calibrator in a highly sensitive glycodelin ELISA. We found no high molecular mass forms of glycodelin in amniotic fluid. Aliquots of the purified glycodelin were set aside for functional studies which are in progress.

Investigation on the ability of first trimester glycodelin and angiopoietin-2 to predict small-for-gestational age pregnancies at delivery.

BACKGROUND: The aim was to investigate whether first trimester glycodelin and angiopoietin-2 can predict small-for-gestational age (SGA) at delivery, individually or in combination. METHODS: In this case-control study we measured glycodelin and angiopoietin-2 on serum from 170 singleton pregnant women delivering SGA neonates and 985 singleton pregnant women delivering normal-weighted neonates. All values were converted to multiples of the medians (MoM). RESULTS: Pregnant women delivering SGA neonates had lower first trimester glycodelin and angiopoietin-2 MoM values [median (interquartile range)] compared with pregnant women delivering normal-weighted neonates for glycodelin: 0.86 (0.58-1.24) vs. 1.03 (0.74-1.45), p<0.001, and for angiopoietin-2: 0.89 (0.69-1.19) vs. 1.01 (0.78-1.31), p<0.001. The prediction performances of the biomarkers showed that the areas under the curve (AUC) were 0.59 (glycodelin), 0.58 (angiopoietin-2), and 0.60 (glycodelin and angiopoietin-2). CONCLUSIONS: We demonstrated that first trimester glycodelin and angiopoietin-2 were associated with SGA, but they were, individually and in combination, poor predictors of SGA at delivery. The AUCs were low which indicate low detection rates and high false positive rates.

First trimester PAPP-A2, PAPP-A and hCGß in small-for-gestational-age pregnancies.

BACKGROUND: Pregnancy-associated plasma protein-A2 (PAPP-A2) is a recently discovered protease that cleaves a subset of insulin-like growth factor binding proteins (IGFBP). The molecular function suggests its involvement in the IGF system that is vital for fetal growth and development. Our objectives were to establish first trimester median curves of PAPP-A2, PAPP-A and hCGß for singleton normal pregnancies and to investigate whether an altered level of one or more of the biomarkers is associated with small-for-gestational-age (SGA) neonates before and after stratification according to maternal hypertension and/or proteinuria. METHODS: This was a case-control study based on 985 pregnant women delivering normal-weighted neonates and 170 pregnant women delivering SGA neonates. PAPP-A2 was measured by ELISA. PAPP-A and hCGß were measured by an automatic analyzer. Median curves from 8+1 to 14+0 were established and all concentration values were converted to multiples of the median (MoM) values. RESULTS: Before stratification the SGA cases had unaffected PAPP-A2 MoM and hCGß MoM levels but lower PAPP-A MoM compared with normal controls. After stratification the SGA normotensive subgroup had lower PAPP-A2 MoM and PAPP-A MoM levels than the normal normotensive subgroup. Severe preeclamptic women delivering SGA neonates had higher PAPP-A2 MoM compared to the normotensive women delivering SGA neonates. CONCLUSIONS: Pregnant women delivering SGA neonates did not have altered levels of PAPP-A2 or hCGß but had lower PAPP-A level in the first trimester compared with pregnant women delivering normal-weighted neonates. Pregnancies complicated with severe preeclampsia and SGA may be associated with high PAPP-A2 level.