Targeting Acidic Mammalian chitinase Is Effective in Animal Model of Asthma.

This article highlights our work toward the identification of a potent, selective, and efficacious acidic mammalian chitinase (AMCase) inhibitor. Rational design, guided by X-ray analysis of several inhibitors bound to human chitotriosidase (hCHIT1), led to the identification of compound 7f as a highly potent AMCase inhibitor (IC values of 14 and 19 nM against human and mouse enzyme, respectively) and selective (>150× against mCHIT1) with very good PK properties. This compound dosed once daily at 30 mg/kg po showed significant anti-inflammatory efficacy in HDM-induced allergic airway inflammation in mice, reducing inflammatory cell influx in the BALF and total IgE concentration in plasma, which correlated with decrease of chitinolytic activity.

SAR and evaluation of novel 5H-benzo[c][1,8]naphthyridin-6-one analogs as Aurora kinase inhibitors.

Several potent Aurora kinase inhibitors derived from 5H-benzo[c][1,8]naphthyridin-6-one scaffold were identified. A crystal structure of Aurora kinase A in complex with an initial hit revealed a binding mode of the inhibitor within the ATP binding site and provided insight for structure-guided compound optimization. Subsequent SAR campaign provided a potent and selective pan Aurora inhibitor, which demonstrated potent target modulation and antiproliferative effects in the pancreatic cell line, MIAPaCa-2.

Anterior shoulder forces in professional and Little League pitchers.

Background: The developing musculoskeletal system of a youth pitcher is substantially different from that of the adult professional pitcher, predisposing the younger players to a different set of injuries.

Methods: High-speed videography of 39 professional and 13 youth pitchers were obtained. High-speed motion analysis was performed to calculate average anterior forces and arm positions at maximal force generation.

When should I do rural general practice? A qualitative study of job/life satisfaction of male rural GPs of differing ages in New Zealand.

Aims: There is a shortage of rural general practitioners in New Zealand (NZ), and many are approaching retirement. This qualitative study was undertaken to investigate the perceived advantages and disadvantages of rural general practice at various stages of family life of male NZ-trained GPs.

Methods: Semi-structured interviews were conducted with 12 male NZ-trained rural GPs from the Waikato and Northland regions during December 2006.