Outcome of fetuses with short femur length detected at second-trimester anomaly scan: a national survey.

OBJECTIVE: To assess the relationship between the finding of fetal femur diaphysis length (FL) below the 5(th) percentile at the second-trimester scan and pregnancy outcome, in a population in which more than 90% of women attend first-trimester screening. METHODS: This was a retrospective study of all Danish singleton pregnancies with a 17-22-week anomaly scan between 1 January 2008 and 30 June 2011. Information on FL and gestational age (GA) at anomaly scan, on birth weight and GA at delivery and on chromosomal abnormalities was obtained from the Danish Fetal Medicine Database. RESULTS: Short FL was identified in 2718 (1.8%) of 147,766 fetuses and was present in 11 (16.2%) of the 68 fetuses affected by trisomy 21 (positive likelihood ratio (LR+) 8.8 (95% CI, 5.1-15.2)). Trisomy 13/18 and unbalanced autosomal structural abnormalities were also associated with a short FL in three (12.0%, LR+ 6.5 (95% CI, 2.3-18.9)) and eight (32.0%, LR+ 17.4 (95% CI, 9.8-30.9)) of the cases, respectively. The risk of a fetus having trisomy 21, trisomy 18, trisomy 13 or an unbalanced autosomal structural abnormality was 1 : 123 (95% CI, 79-192), given a short FL. Pregnancies with a fetus with short FL were more often affected by early preterm delivery (before 34 weeks) (5.6%; odds ratio (OR) = 4.2 (95% CI, 3.5-4.9)) and small-for-gestational-age (SGA) infants (13.9%; OR = 4.3 (95% CI, 3.8-4.8)). CONCLUSION: Short FL at the second-trimester anomaly scan is associated with a significantly higher relative risk of chromosomal abnormalities, and a substantially higher absolute risk for SGA and early preterm delivery.

1,2,3-triazolyl amino acids as AMPA receptor ligands.

The central nervous system glutamate receptors are an important target for drug discovery. Herein we report initial investigations into the synthesis and glutamate receptor activity of 1,2,3-triazolyl amino acids. Two compounds were found to be selective AMPA receptor ligands, which warrant further investigation.

Granulocyte-macrophage colony-stimulating factor delays neutrophil constitutive apoptosis through phosphoinositide 3-kinase and extracellular signal-regulated kinase pathways.

Activated neutrophils play an important role in the pathogenesis of sepsis, glomerulonephritis, acute renal failure, and other inflammatory processes. The resolution of neutrophil-induced inflammation relies, in large part, on removal of apoptotic neutrophils. Neutrophils are constitutively committed to apoptosis, but inflammatory mediators, such as GM-CSF, slow neutrophil apoptosis by incompletely understood mechanisms. We addressed the hypothesis that GM-CSF delays neutrophil apoptosis by activation of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI 3-kinase) pathways. GM-CSF (20 ng/ml) significantly inhibited neutrophil apoptosis (GM-CSF, 32 vs 65% of cells p < 0. 0001). GM-CSF activated the PI 3-kinase/Akt pathway as determined by phosphorylation of Akt and BAD. GM-CSF-dependent Akt and BAD phosphorylation was blocked by the PI 3-kinase inhibitor LY294002. A role for the PI 3-kinase/Akt pathway in GM-CSF-stimulated delay of apoptosis was indicated by the ability of LY294002 to attenuate apoptosis delay. GM-CSF-dependent inhibition of apoptosis was significantly attenuated by PD98059, an ERK pathway inhibitor. LY294002 and PD98059 did not produce additive inhibition of apoptosis delay. To determine whether PI 3-kinase and ERK are used by other ligands that delay neutrophil apoptosis, we examined the role of these pathways in IL-8-induced apoptosis delay. LY294002 blocked IL-8-dependent Akt phosphorylation. PD98059 and LY294002 significantly attenuated IL-8 delay of apoptosis. These results indicate IL-8 and GM-CSF act, in part, to delay neutrophil apoptosis by stimulating PI 3-kinase and ERK-dependent pathways.

Regulation of expression of type II sodium-phosphate cotransporters by protein kinases A and C.

The purpose of the present study was to determine the effect of protein kinase A and protein kinase C activation on the membrane expression of NaPi-4, the type II sodium-phosphate cotransporter in OK cells. NaPi-4 expression was measured using polyclonal antisera produced in rabbits against a peptide identical to the carboxy-terminal 12-amino acid sequence of NaPi-4. The antisera identified an apically localized protein by confocal imaging of intact OK cells and a broad band of 110-140 kDa by immunoblot analysis of OK cell membranes. Treatment of OK cells with parathyroid hormone (PTH) decreased the intensity of the 110- to 140-kDa band, which was detectable by 2 h, maximal by 4 h at 62%, and sustained for 24 h. 8-Bromo-cAMP (8-BrcAMP) inhibited NaPi-4 expression for up to 24 h by over 90%. However, phorbol 12-myristate 13-acetate inhibited NaPi-4 expression by less than 10%. PTH-(3-34), a fragment which stimulates only protein kinase C, inhibited phosphate transport but also had no effect on NaPi-4 expression. We conclude that protein kinase A but not protein kinase C inhibits sodium-phosphate uptake in OK cells by downregulation of NaPi-4 expression.