Discovery of a Novel Highly Selective Histamine H4 Receptor Antagonist for the Treatment of Atopic Dermatitis.

The histamine H4 receptor (H4R), a member of the G-protein coupled receptor family, has been considered as a potential therapeutic target for treating atopic dermatitis (AD). A large number of H4R antagonists have been disclosed, but no efficient agents controlling both pruritus and inflammation in AD have been developed yet. Here, we have discovered a novel class of orally available H4R antagonists showing strong anti-itching and anti-inflammation activity as well as excellent selectivity against off-targets. A pharmacophore-based virtual screening system constructed in-house successfully identified initial hit compound 9, and the subsequent homology model-guided optimization efficiently led us to discover pyrido[2,3- e]tetrazolo[1,5- a]pyrazine analogue 48 as a novel chemotype of a potent and highly selective H4R antagonist. Importantly, orally administered compound 48 exhibits remarkable efficacy on antipruritus and anti-inflammation with a favorable pharmacokinetic (PK) profile in several mouse models of AD. Thus, these data strongly suggest that our compound 48 is a promising clinical candidate for treatment of AD.

Imaging characteristics of persistent left cranial vena cava incidentally diagnosed with computed tomography in dogs.

Persistent left cranial vena cava (PLCVC) is an uncommon congenital thoracic venous anomaly in dogs. This study examines the clinical and CT findings of dogs diagnosed with PLCVC incidentally. In this study, complete type of PLCVC was diagnosed in 26 dogs with CT angiography. Shih tzu (17 cases) and Pekingese dogs (3 cases) were overrepresented. There was no gender predisposition, and the average age at presentation was 10.3 years. Of 26 dogs, one dog had a bridging vein connecting right and left cranial vena cavae, and another dog showed azygos vein terminating PLCVC. On the thoracic CT images in the third dog, the right cranial vena cava was absent so that right brachiocephalic vein ended to PLCVC. However, the right costocervical vein drained another vein coursing caudally to the right atrium with azygos vein. In conclusion, CT angiography is a very useful method to diagnose PLCVC and variations of related thoracic vein anomalies in dogs.

[Study on the fluorescence spectra of LaL3 with DNA].

A fluorescence method is presented for the determination of DNA. The method is based on the interaction of LaL3 [L = morin (2', 3, 4', 5, 7-Pentahydroxyflavone), 2'-OH group deprotonated] with DNA in NH3 x H2O-NH4Cl buffer of pH = 8.0, with lambdaex at 387 nm, and lambdaem at 535 nm. Enhanced fluorescence was observed for LaL3 in the presence of DNA and in the presence of buffer solution of 10%(psi) and ethanol of 10%(psi). The linear range of determination was between 0 and 15 microg x mL(-1) 1 for DNA. The method proved to be simple, easy and sensitive for the determination of DNA. The mechanism of enhancing and the reasons for the effects of acid were also discussed.