The enzyme toilet rim block 'pCure' does not efficiently remove drug residues in a hospital setting - exemplifying the importance of on-site implementation testing.

Introduction: Negative environmental effects of active pharmaceutical ingredients (APIs) are increasingly recognized, especially concerning antibiotics, and hospitals are important point sources. "pCure" is a toilet rim block containing API-degrading enzymes; the producing company claims positive in vitro results but no implementation studies have been performed. Materials and methods: In a university hospital setting, 16 weeks were randomized to installation or no installation of pCure in all 261 toilets connected to the same cesspit where sewage water was sampled daily. Ninety-six samples were analyzed for 102 APIs using liquid chromatography/tandem mass spectrometry. Results and Discussion: Fifty-one APIs were detected with a large variation in levels but no significant differences in the initial statistical analysis. More statistical testing of API level ratios (pCure installed/not installed) yielded some cases of significant decrease. Differences were small and not consistent when comparing means and medians. We cannot exclude a small pCure effect but clearly pCure has no effect of biological importance. Conclusion: pCure is not useful to reduce drug residue discharge in a hospital setting. In a bigger perspective, our study exemplifies that products claiming to reduce an environmental problem need to be tested in on-site implementation studies by independent researchers before reaching the market.

Possible role of an ischemic preconditioning-like response mechanism in K(ATP) channel opener-mediated protection against streptozotocin-induced suppression of rat pancreatic islet function.

Potassium channel openers (KCOs) decrease insulin secretion from beta-cells. Some KCOs also protect against damage to beta-cell function and type 1 diabetes in animal models. Previously we have found that the KCO NNC 55-0118 counteracted islet cell dysfunction, and this was associated with a lowering of the mitochondrial membrane potential (Deltapsi). Presently we aimed to explore whether inhibition of insulin secretion per se or rather inhibition of mitochondrial function correlates to counteraction of beta-cell suppression. For this we used two novel KCOs (NNC 55-0321 and NNC 55-0462), which at certain concentrations have different actions regarding insulin secretion and the Deltapsi, with NNC 55-0321 being a potent inhibitor of Deltapsi and NNC 55-0462 being a potent inhibitor of insulin secretion. At 10 microM NNC 55-0321, but not with NNC 55-0462, the islet ATP content and ATP/ADP ratio was acutely decreased. This was accompanied by a complete protection against streptozotocin-induced suppression of islet insulin secretion using the former KCO. In cardiac research KCOs have been used to induce an ischemic preconditioning (IPC) response. In line with an IPC-like mechanism we found that NNC 55-0321 induced an initial free oxygen radical formation, PKC-epsilon isoform activation and a subsequent phosphorylation of the survival promoting factor Akt. Thus, KCOs may elicit mitochondrial events that resemble classical IPC seen in cardiomyocytes, and this could explain the enhanced islet cell function observed. KCOs with this property may be particularly interesting compounds to study as a rescue therapy during acute episodes of beta-cell suppression/destruction.