Anti-HPD monoclonal antibody, clone FQS6308

Objectives To evaluate the accuracy and reliability of a new ultrasound technique for the automatic assessment of the head-perineum distance (HPD) during childbirth. Methods HPD was measured on a total of 40 acquisition sessions in 30 laboring women both automatically by an innovative algorithm and manually by trained sonographers, assumed as gold standard. Results A significant correlation was found between manual and automatic measurements (Intra-CC = 0.994). High values of the coefficient of determination (r(2)=0.98) and low residual errors: RMSE = 2.01 mm (4.9%) were found. Conclusion The automatic algorithm for the assessment of the HPD represents a reliable technique.

Hereditary tyrosinemia type 1 (HT1) and alkaptonuria (AKU) are inherited metabolic disorders caused by defective enzymes involved in tyrosine catabolism. Nitisinone, an ex-herbicide and member of the beta-triketone family, is therapeutically applied to prevent accumulation of toxic metabolites in patients by inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD). Here, we developed a colorimetric bacterial whole-cell screening system that allows quantifying the inhibitory effects of human HPD inhibitors in a high-throughput and a robust fashion. The principle of our screening system is based on the degradation of tyrosine through 4-hydroxyphenylpyruvate into homogentisate by human HPD expressed in E. coli and subsequent production of a soluble melanin-like pigment. With the aim to optimise the assay, we tested different E. coli strains, expression and reaction temperatures, and time-points for supplementing the substrate. We found that in our assay the addition of prototypical beta-triketone HPD inhibitors decreases pigment production in a dose-dependent manner with increasing inhibitor concentrations. In addition, plate uniformity, signal variability and spatial uniformity assessment showed that we have developed a robust high-throughput screening assay that is simple to use, cost-effective and enables identification and evaluation of novel therapeutic human HPD inhibitors for the treatment of tyrosine-related metabolic disorders.