A fluorescent analogue of tauroursodeoxycholic acid reduces ER stress and is cytoprotective.

Tauroursodeoxycholic acid (TUDCA) is a cytoprotective ER stress inhibitor and chemical chaperone. It has therapeutic potential in a wide array of diseases but a specific macromolecular target or molecular mechanism of action remains obscure. This Letter describes an effective new synthetic approach to taurine conjugation of bile acids which we used to prepare 3α-dansyl TUDCA (4) as a probe for TUDCA actions. As a model of ER stress we used the hepatocarcinoma cell line HUH7 and stimulation with either deoxycholic acid (DCA, 200µM) or tunicamycin (5µg/ml) and measured levels of Bip/GRP78, ATF4, CHOP and XBP1s/XBP1u. Compound 4 was more effective than UDCA at inhibiting ER stress markers and had similar effects to TUDCA. In a model of cholestasis using the cytotoxic DCA to induce apoptosis, pretreatment with 4 prevented cell death similarly to TUDCA whereas the unconjugated clinically used UDCA had no effect. 3α-Dansyl TUDCA (4) appears to be a suitable reporter for TUDCA effects on ER stress and related cytoprotective activity.

Pharmacist-led medicines optimisation service in an inpatient mental health setting.

Medicines optimisation ensures that people get the best possible outcomes from their medicines. As those with severe mental illness (SMI) are frequently prescribed psychotropic medicines with potentially significant side-effects, poor adherence to treatment and physical morbidity are common. This results in suboptimal symptom control, physical health problems and negative health outcomes. The specialist mental health pharmacist (SMHP) is best placed to provide leadership for medicines optimisation in the inpatient mental health setting. By adopting a patient-centred approach to providing information, improving adherence, screening, initiating and maintaining medicines, and supporting self-advocacy, the SMHP can ensure the patients' experience of taking medicines is optimised. As there is currently limited understanding of what a baseline clinical pharmacy service in a mental health setting looks like, we aim to outline a framework for pharmacist-led medicines optimisation for those with SMI. This framework is suitable to be scaled and adapted to other settings.