These findings provide preliminary evidence that Lyprinol may be potentially useful in ameliorating symptoms of IBD. The benefit, however, is unlikely to be due to the omega-3 fatty acid content. Dose-response evaluation of Lyprinol in experimental IBD is warranted.

Cytotoxic effects of Metvan (cis-[VO(OSO)(Mephen)], where Mephen = 4,7-dimethyl-1,10-phenanthroline) and its analogues with 1,10-phenanthroline (phen) and 2,2'-bipyridine (bpy) ligands in cultured human lung cancer (A549) cells have been re-investigated in conjunction with reactivity of the V(IV) complexes in neutral aerated aqueous solutions and in cell culture medium. All the V(IV) complexes underwent rapid oxidation to the corresponding V(V) species (cis-[V(O)L]), followed by release of free ligands (shown by electrospray mass spectrometry). Decomposition of V(IV) complexes in cell culture medium within minutes at 310 K was confirmed by UV-Vis and EPR spectroscopies. High cytotoxicities (low μM or sub-μM IC range in 72 h assays) were observed for the phen and Mephen complexes, but they were not different from that of the corresponding free ligands, which confirmed that the original V(IV) complexes played no significant role in the observed biological activities. The cytotoxicities of the ligands were most likely due to their complexation of redox-active essential metal ions, such as Cu(II) and Fe(II), in the medium, and their increased cellular uptake, leading to oxidative stress-related cell death. These results emphasize the need to assess the stability of metal-based drugs under the conditions of biological assays, particularly when biologically active ligands, such as 1,10-phenanthroline and its derivatives, are used. These ligands have high systemic toxicities in vivo and their release in the GI tract and blood makes the complexes unsuitable for use as anti-cancer drugs.

In an attempt to improve postoperative pain management an intravenous infusion of pethidine was designed to provide stable therapeutic blood concentrations. Ten female patients undergoing elective abdominal hysterectomy were studied. After commencement of the infusion, blood pethidine concentrations increased rapidly and exceeded 0.46 p,g/ml after four hours. The mean steady-state concentration of 0.67 p,g/ml was reached by twenty-four hours. This infusion regimen resulted in the abolition of severe pain after three hours and analgesia continued for the duration of the two day study. Significant blood concentrations of the metabolite norpethidine were found although clinically no toxic effects were observed. Side effects of pethidine were infrequent. Controlled continuous intravenous infusion of pethidine produced stable blood concentrations and provided excellent pain control.

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Bisoprolol was the preferred betablocker and prescribed in 80%. Mineralocorticoid inhibitors and ivabradine were underutilised at 25% and 8% of patients. Cardiac Resynchronisation Therapy was used in 9%. There were very few mortalities at 3% (n=3) at the median follow-up of 403 (IQR 239-896) days. Conclusion: Most first line medications from GDMT were prescribed in our patients. Underuse of mineralocorticoid inhibitors may be explained by the concern of hyperkalaemia and renal dysfunction from ARNi use.

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