1.Delineation of the Functional Properties and the Mechanism of Action of TMPPAA, an Allosteric Agonist and Positive Allosteric Modulator of 5-HT3 Receptors.
Gasiorek A1, Trattnig SM1, Ahring PK2, Kristiansen U1, Frølund B1, Frederiksen K3, Jensen AA4. Biochem Pharmacol. 2016 Apr 13. pii: S0006-2952(16)30026-0. doi: 10.1016/j.bcp.2016.04.004. [Epub ahead of print]
We have previously identified a novel class of 5-hydroxytryptamine type 3 receptor (5-HT3R) agonists sharing little structural similarity with orthosteric 5-HT3R ligands (Jørgensen et al., 2011). In the present study we have elucidated the functional characteristics and the mechanism of action of one of these compounds, trans-3-(4-methoxyphenyl)-N-(pentan-3-yl)acrylamide (TMPPAA). In electrophysiological recordings TMPPAA was found to be a highly-efficacious partial agonist equipotent with 5-HT at the 5-HT3A receptor (5-HT3AR) expressed in COS-7 cells and somewhat less potent at the receptor expressed in Xenopus oocytes. The desensitization kinetics of TMPPAA-evoked currents were very different from those mediated by 5-HT. Moreover, repeated TMPPAA applications resulted in progressive current run-down and persistent non-responsiveness of the receptor to TMPPAA, but not to 5-HT. In addition to its direct activation, TMPPAA potentiated 5-HT-mediated 5-HT3AR signalling, and the allosteric link between the two binding sites was corroborated by the analogous ability of 5-HT to potentiate TMPPAA-evoked responses.
2.EMG changes during continuous intraoperative neuromonitoring with sustained recurrent laryngeal nerve traction in a porcine model.
Brauckhoff K1,2, Aas T3, Biermann M4, Husby P4,5. Langenbecks Arch Surg. 2016 Apr 16. [Epub ahead of print]
PURPOSE: Traction is the most common cause of injury to the recurrent laryngeal nerve (RLN) in endocrine neck surgery. The purpose of this study was to evaluate specific alterations to the electromyogram (EMG) and verify safe alarm limits in a porcine model of sustained traction of the RLN using continuous intraoperative neuromonitoring (C-IONM).
3.Risk factors for current and future unmet supportive care needs of people with pancreatic cancer. A longitudinal study.
Beesley VL1, Wockner LF2, O'Rourke P2, Janda M3, Goldstein D4,5, Gooden H6, Merrett ND7,8, O'Connell DL9, Rowlands IJ10, Wyld DK11,12, Neale RE2. Support Care Cancer. 2016 Apr 16. [Epub ahead of print]
PURPOSE: This study aims to determine if the supportive care needs of people with pancreatic cancer change over time and identify the factors associated with current and future unmet needs.
4.Long-term risk of venous thrombosis after stopping anticoagulants for a first unprovoked event: A multi-national cohort.
Rodger MA1, Scarvelis D2, Kahn SR3, Wells PS2, Anderson DA4, Chagnon I5, Le Gal G2, Gandara E2, Solymoss S6, Sabri E2, Kovacs MJ7. Thromb Res. 2016 Mar 29. pii: S0049-3848(16)30087-1. doi: 10.1016/j.thromres.2016.03.028. [Epub ahead of print]
BACKGROUND: Choosing short-term (3-6 months) or indefinite anticoagulation after a first unprovoked venous thromboembolic event (VTE) is a common and difficult clinical decision. The long-term absolute risk of recurrent VTE after a first unprovoked VTE, in all patients and sub-groups, is not well established, hindering decision making.