Dynamic flow synthesis of porous organic cages

The dynamic covalent synthesis of two imine-based porous organic cages was successfully transferred from batch to continuous flow. The same flow reactor was then used to scramble the constituents of these two cages in differing ratios to form cage mixtures. Preparative HPLC purification of one of these mixtures allowed rapid access to a desymmetrised cage molecule.We thank the Engineering and Physical Sciences Research Council (EPSRC) for financial support under the Grants EP/H000925/1 (AIC), EP/K009494/1 (SVL) and EP/M004120/1 (SVL), and Pfizer Worldwide Research & Development (CB). The authors would like to thank EPSRC Dial-a-Molecule Grand Challenge Network (EP/K004840/1) for funding a placement with SVL via the Interdisciplinary Mobility Funding scheme (AGS).This is the author accepted manuscript. The final version is available from RSC via http://dx.doi.org/10.1039/C5CC07447

The role of levosimendan in acute heart failure complicating acute coronary syndrome: A review and expert consensus opinion

Peer reviewe

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Caveolin-1 limits the contribution of BK(Ca) channel to EDHF-mediated arteriolar dilation: implications in diet-induced obesity

AIMS: Caveolin-1 (Cav-1) interacts with large conductance Ca(2+)-activated potassium channels (BKCa) and likely exerts a negative regulatory effect on the channel activity. We investigated the role of Cav-1 in modulating BK(Ca) channel-mediated, endothelium-derived hyperpolarizing factor (EDHF)-dependent arteriolar dilation in normal condition and in an experimental model of obesity. METHODS AND RESULTS: In isolated, pressurized (80 mmHg) gracilis muscle arterioles (approximately 100 microm) of Cav-1 knockout mice, acetylcholine (ACh)-induced, EDHF-mediated dilations were enhanced and were significantly reduced by the BK(Ca) channel inhibitor, iberiotoxin (IBTX), whereas IBTX had no effect on EDHF-mediated dilations in the wild-type mice. Dilations to the selective BK(Ca) channel opener, NS-1619 were augmented in the Cav-1 knockout mice. In high-fat diet-treated, obese rats ACh-induced coronary arteriolar dilations were preserved, whereas IBTX-sensitive, ACh-induced and also NS-1619-evoked vasodilations were augmented when compared with lean animals. In coronary arterioles of obese rats a reduced protein expression of Cav-1 was detected by western immunoblotting and immunohistochemistry. Moreover, in coronary arterioles of lean rats, disruption of caveolae with methyl-beta-cyclodextrin augmented IBTX-sensitive, ACh-induced, and also NS-1619-evoked dilations. CONCLUSION: Thus, under normal conditions, Cav-1 limits the contribution of the BK(Ca) channel to EDHF-mediated arteriolar dilation. In obesity, a reduced expression of Cav-1 leads to greater contribution of the BK(Ca) channel to EDHF-mediated response, which seems essential for maintained coronary dilation

Impact of periprocedural morphine use on mortality in STEMI patients treated with primary PCI.

BackgroundIntravenous morphine (MO) decreases the effect of all oral platelet P2Y12 receptor inhibitors in vitro and observational reports suggest that its use may be associated with larger infarct size. Yet, there are limited data available about the impact of this interaction on clinical outcomes. We studied the effect of MO on mortality in ST-segment elevation myocardial infarction (STEMI) patients treated with primary PCI using a prospective registry.MethodsOf the 1255 patients who underwent primary PCI, 397 received MO based on physician's judgment. Clopidogrel was used as P2Y12 receptor antagonist in all cases. Median follow-up time was 7.5 years with 457 deaths. To adjust for confounding, two propensity score-based procedures were performed: 1 to 1 matching (PSM, 728 cases), and inverse probability of treatment weighting (IPTW) retaining data from all patients. Primary outcome measure was time to all-cause death, whereas predischarge left ventricular ejection fraction (LVEF) was used as secondary end point.ResultsAn adequate balance on baseline covariates was achieved by both methods. We found no difference in survival as the HR (MO/no MO) was 0.98 (95% confidence interval [CI]: 0.76-1.26), p = 0.86 using PSM and 1.01 (95% CI: 0.84-1.23), p = 0.88 with IPTW. Likewise, distributions of LVEFs were similar using either methods: with PSM, median LVEFs were 50.0% (interquartile range [IQR]: 43.0%-55.3%) vs 50.0% (IQR: 42.0%-55.0%) in the no MO and MO groups, respectively (p = 0.76), whereas using IPTW, they were 50.0% (IQR: 42.5%-55.0%) vs 50.0% (IQR: 41.0%-55.0%), respectively (p = 0.86).ConclusionsOur data suggest that morphine use may have no impact on long-term mortality and on predischarge ejection fraction in STEMI patients treated with primary PCI