Influence of selected factors on serum AFP levels in pregnant women in terms of prenatal screening accuracy — literature review

Alpha-fetoprotein (AFP) is one of the biochemical components of the triple (T-3) and quadruple (T-4) test used so far in prenatal screening mainly for trisomy 21 (T21) and neural tube defects (NTDs). Based on many years of experience and data collected during these studies, a variety of factors have been identified that can affect a pregnant woman's serum AFP level, and thus the risk assessment of trisomy 21 (T21) and neural tube defects. These include both unaccounted for purely medical data (e.g., from baseline information about the patient, assisted reproduction methods used, comorbidities and emerging pregnancy pathologies) and errors made during statistical analysis. Since the triple or quadruple test is usually performed between 15 and 20 weeks of pregnancy, most scientific studies are based solely on results from this period of pregnancy — limited data are available for the first and third trimesters of pregnancy. In the era of new improved screening tests, AFP has the potential to become an independent marker for pregnancy well-being evaluation

RNF168-mediated H2AX ubiquitination recruits 53BP1 to DNA double-strand breaks

53BP1 protein is critical for repair of DNA double-strand breaks (DSBs) by non-homologous end-joining repair pathway. 53BP1 binds to dimethylated histones, however, its recruitment to sites of DNA DSBs in addition requires E3 ubiquitin ligases RNF8 and RNF168. The upstream events involve H2AX phosphorylation, RNF8 and RNF168 recruitment, ubiquitination of chromatin proteins, notably histones H2A and H2AX, and, subsequently, recruitment of 53BP1. How protein ubiquitination stimulates 53BP1 recruitment is unclear. Here, we compared the roles of RNF8 and RNF168 and explored the role of H2A/H2AX ubiquitination on 53BP1 recruitment to DNA DSBs. Mild ectopic expression of RNF168 in RNF8-deficient cells rescued 53BP1 recruitment 53BP1 to DNA DSBs. In addition, we show that RNF8 with D443R substitution in RING-domain that mimics RNF168 activity rescued 53BP1 recruitment to DNA DSBs in RNF168-deficient cells. We found that expressing an ubiquitin-H2AX fusion protein rescued 53BP1 recruitment in RNF8 and RNF168-deficient cells. Similar effects were observed when other bulky moieties, including green fluorescent protein, were fused to H2AX N-terminus. Our results suggest that RNF168-mediated H2A/H2AX ubiquitination facilitates 53BP1 recruitment by opening up chromatin

Hepatic aminotransferases of normal and IUGR fetuses in cord blood at birth

Background: The accepted standard for assessing the wellbeing of the newborn is the Apgar score and blood gas analysis. However, the prediction of neonatal morbidity or mortality is limited. In small-for-gestation (SGA) fetuses at 18-38 weeks of gestation, pO(2) is <5th centile both in the umbilical artery and vein in 30%. In a previous study in singleton term neonates cardiac specific enzymes (B-type natriuretic peptide, BNP and cardiac troponin T, cTnT) are increased in growth-restricted fetuses compared with normals. Aims: To test the hypothesis, that fetuses with intra uterine growth restriction (IUGR) have elevated AST (GOT) and ALT (GPT) aminotransferases as a result of hypoxic liver cell injury, and to establish references ranges. Study design: Prospective cohort study, serum of umbilical artery (n = 156) and vein (n = 180), 599 normal singletons at 37(+0)-42(+0) weeks, neonates with IUGR (n = 41). analysis for pH, birthweight and maternal weight, spontaneous vs cesarean section, vein vs artery and for the sex. Outcome measures: Aspartate aminotransferase (AST. GOT) and Alanine aminotransferase (ALT, GPT) were measured in normals and IUGR neonates. Results: Neonates with IUGR (n = 41) had AST values that were not different from the reference group, but had significantly lower ALT (-1.49, 95% CI - 1.98 to - 1.00 vs 0.14, 95% CI - 0.42-0.13), (p<0.001), (Fig. 3). Conclusions: In neonates with IUGR, hypoxic hepatic injury markers in cord blood were not elevated. Rather, a substantially reduced ALT suggests a down-regulated hepatic activity. (C) 2011 Elsevier Ireland Ltd. All rights reserved

Alpha-fetoprotein (AFP) — new aspects of a well-known marker in perinatology

Alpha-fetoprotein (AFP) is a serum protein, which is characteristic of the fetal development period and a well-known oncological marker. The predominance of AFP among serum proteins is common in fetal life, whereas after birthing its functions are gradually taken over by albumins. An understanding of the mechanism of AFP transfer between fetus and mother has led to the development of screening tests for identifying neural tube defects and Down’s syndrome. Currently, the knowledge on patophysiology and the possible importance of AFP in perinatology and fetal medicine extends far beyond those 2 disease states. Throughout the 50 years of research on AFP, there has been dynamic progress of diagnostic techniques, from the qualitative ones that are used solely for scientific studies to the widely used radioimmunoassays and immunoenzymatic assays (enzyme-linked immunosorbent assay, chemiluminescence immunoassay, time-resolved fluorescence immunoassay). Some genetic mutations cause complete inhibition of AFP production by the fetus. This affects the results of screening tests during pregnancy, and also leads to constantly high levels of AFP in adults, which are not linked to oncogenesis.

Biochemical tissue-specific injury markers of the heart and brain in postpartum cord blood

OBJECTIVE: We sought to establish references ranges and to test the hypothesis that biochemical tissue-specific markers for the heart in umbilical cord blood of newborns with cardiac defects and intrauterine growth restriction (IUGR) are abnormal. STUDY DESIGN: A prospective study was conducted. Serum samples of the umbilical vein (n = 280) and artery (n = 156) from 599 healthy newborns at 37(+0)-42(+0) weeks of gestation were collected. Total creatine kinase (CK), CK-MB heart type (CK-MB), cardiac troponin T (cTnT), myoglobin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and S100 were measured. Reference ranges for each marker were constructed. Concentrations of tissue-specific markers from umbilical cord blood of neonates with cardiac defects (n = 10) and IUGR (n = 41) were plotted against the established reference ranges. RESULTS: Reference ranges for each studied marker were established for both umbilical artery and vein. In fetuses with cardiac defects, both NT-proBNP (4/6 [66%] in the artery, 7/10 [70%] in the vein) and cTnT (2/10 [20%] in the vein) were increased. In fetuses with IUGR in the vein, NT-proBNP (10/41 [24%]) and cTnT (5/41 [12%]) were increased, whereas S100 (9/41 [21%]) was decreased. CONCLUSION: In a subset of neonates with cardiac defects or growth restriction, irrespective of the pH at birth, tissue-specific injury markers for the heart in umbilical cord blood are abnormal