Inhibition of human mevalonate kinase by allosteric inhibitors of farnesyl pyrophosphate synthase.

Mevalonate kinase is a key regulator of the mevalonate pathway, subject to feedback inhibition by the downstream metabolite farnesyl pyrophosphate. In this study, we validated the hypothesis that monophosphonate compounds mimicking farnesyl pyrophosphate can inhibit mevalonate kinase. Exploring compounds originally synthesized as allosteric inhibitors of farnesyl pyrophosphate synthase, we discovered mevalonate kinase inhibitors with nanomolar activity.

Lumbar spondylolysis and spondylolytic spondylolisthesis: who should be have surgery? An algorithmic approach.

Lumbar spondylolysis and spondylolisthesis are common spinal disorders that most of the times are incidental findings or respond favorably to conservative treatment. In a small percentage of the patients, surgical intervention becomes necessary. Because too much attention has been paid to novel surgical techniques and new modern spinal implants, some of fundamental concepts have been forgotten.