Heart failure biomarker levels correlate with invasive haemodynamics in pulmonary valve replacement.

BACKGROUND: Although widely used in cardiology, relation of heart failure biomarkers to cardiac haemodynamics in patients with CHD (and in particular with pulmonary insufficiency undergoing pulmonary valve replacement) remains unclear. We hypothesised that the cardiac function biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble suppressor of tumorigenicity 2, and galectin-3 would have significant associations to right ventricular haemodynamic derangements. METHODS: Consecutive patients ( n = 16) undergoing cardiac catheterisation for transcatheter pulmonary valve replacement were studied. NT-proBNP, soluble suppressor of tumorigenicity 2, and galectin-3 levels were measured using a multiplex enzyme-linked immunosorbent assay from a pre-intervention blood sample obtained after sheath placement. Spearman correlation was used to identify significant correlations (p ≤ 0.05) of biomarkers with baseline cardiac haemodynamics. Cardiac MRI data (indexed right ventricular and left ventricular end-diastolic volumes and ejection fraction) prior to device placement were also compared to biomarker levels. RESULTS: NT-proBNP and soluble suppressor of tumorigenicity 2 were significantly correlated (p < 0.01) with baseline mean right atrial pressure and right ventricular end-diastolic pressure. Only NT-proBNP was significantly correlated with age. Galectin-3 did not have significant associations in this cohort. Cardiac MRI measures of right ventricular function and volume were not correlated to biomarker levels or right heart haemodynamics. CONCLUSIONS: NT-proBNP and soluble suppressor of tumorigenicity 2, biomarkers of myocardial strain, significantly correlated to invasive pressure haemodynamics in transcatheter pulmonary valve replacement patients. Serial determination of soluble suppressor of tumorigenicity 2, as it was not associated with age, may be superior to serial measurement of NT-proBNP as an indicator for timing of pulmonary valve replacement.

Other mechanical methods for pre-induction cervical ripening.

Pre-induction cervical ripening is an important part of the labor induction process in women with an unfavorable cervix. This can be achieved either by pharmacologic or mechanical methods of cervical ripening. While the Foley catheter is the most commonly used mechanical method for labor induction, other mechanical methods are also available. This article reviews the safety profiles of osmotic dilators, extra-amniotic saline infusion, double-balloon catheters, and also compares their efficacy to that of other mechanical and pharmacologic cervical ripening methods. While mechanical methods have been shown to be safe and effective for cervical ripening, none of these alternatives has been shown to be superior to the Foley catheter.

Directed evolution of a probe ligase with activity in the secretory pathway and application to imaging intercellular protein-protein interactions.

Previously, we reported a new method for intracellular protein labeling in living cells called PRIME (probe incorporation mediated by enzymes). PRIME uses a mutant of Escherichia coli lipoic acid ligase (LplA) to catalyze covalent probe ligation onto a 13-amino acid peptide recognition sequence. While our first demonstration labeled proteins with a coumarin fluorophore, subsequent engineering produced alkyl azide and trans-cyclooctene ligases as well as an interaction-dependent form of the coumarin PRIME method (ID-PRIME). One major limitation of the PRIME methodologies is that LplA mutants have very low activity in the secretory pathway. Here, we extend PRIME labeling to oxidizing compartments such as the endoplasmic reticulum and the cell surface. We used yeast-display evolution and four rounds of selection to isolate LplA mutants with improved picolyl azide ligation activity. Then we compared the ligation activities of the evolved mutants both in vitro and on the mammalian cell surface. We characterized the picolyl azide ligation activity of the most active LplA variant in vitro, in the endoplasmic reticulum, and at the mammalian cell surface. Finally, we used the optimized LplA variant to label neurexin and neuroligin interactions at the mammalian cell surface in just 5 min. Compared to another method for imaging these protein-protein interactions (GFP recomplementation across synapses), our optimized ID-PRIME ligase is faster, more sensitive, and does not trap interacting proteins in a complex (nontrapping).