RESUMO
In this effort, we report the development of a portable inspiratory-expiratory training device for use in rehabilitation of participants with cardiovascular and respiratory motor deficits. The device uses existing airway restriction components to establish a manually adjustable respiratory training apparatus and includes an integrated pressure sensor with custom software to direct and track therapy sessions. The battery-powered system promotes proven rehabilitation methodologies performed at the clinic in a platform to be translated to the home for participants with spinal cord injuries.
Assuntos
Exercícios Respiratórios/instrumentação , Traumatismos da Medula Espinal/reabilitação , Expiração , Humanos , Inalação , Músculos Respiratórios , Traumatismos da Medula Espinal/complicaçõesRESUMO
The transformation of an aryloxybutanoic acid ultra high-throughput screening (uHTS) hit into a potent and selective series of G-protein coupled receptor 120 (GPR120) agonists is reported. uHTS hit 1 demonstrated an excellent rodent pharmacokinetic profile and selectivity over the related fatty acid receptor GPR40, but only modest GPR120 potency. Optimization of the "left-hand" aryl group led to compound 6, which demonstrated a GPR120 mechanism-based pharmacodynamic effect in a mouse oral glucose tolerance test (oGTT). Further optimization gave rise to the benzofuran propanoic acid series (exemplified by compound 37), which demonstrated acute mechanism-based pharmacodynamic effects. The combination of in vivo efficacy and attractive rodent pharmacodynamic profiles suggests compounds generated from this series may afford attractive candidates for the treatment of Type 2 diabetes.