Expansion of the Structure-Activity Relationship Profile of Triaminopyrimidines as Inhibitors of Caspase-1.

Caspase-1 is a sought-after therapeutic target for inflammatory conditions due to its role in activation and release of pro-inflammatory cytokines, but there has been little success getting drugs into the clinic. We have previously shown triaminopyrimidines such as CK-1-41 are potent, reversible small molecule inhibitors of caspase-1, likely binding in an allosteric site within the enzyme. A series of analogs of CK-1-41 were synthesized and tested against caspase-1 to develop a more robust structure-activity relationship profile.

Factors associated with keel bone damage - a longitudinal study of commercial layer flocks during the laying period.

1. Keel bone damage, such as deformations and fractures, is a severe problem regarding animal welfare in layers. To identify risk factors under commercial conditions, 33 layer flocks (22 barn, 11 free range) with white ( = 18), brown ( = 11) and mixed ( = 4) genotypes were examined.

Use of invasive cardiopulmonary exercise testing to diagnose preload reserve failure in patients with liver disease.

In this case series, we describe the use of invasive cardiopulmonary exercise testing (iCPET) to diagnose heart failure due to preload reserve failure in two patients with progressive dyspnoea. We demonstrate that underlying liver disease contributes to preload reserve failure as a cause of exertional dysfunction. In liver diseases such as non-alcoholic fatty liver disease (NAFLD), fibrotic changes to the sinusoidal liver architecture occur leading to an increased transhepatic sinusoidal pressure gradient.