Background : Long‐term non‐steroidal anti‐inflammatory drug (NSAID) intake may induce increased intestinal permeability, eventually resulting in enteropathy. Because increased permeability might be related to cell damage resulting from energy depletion, it was hypothesized that glutamine—the major energy source of the intestinal mucosal cell—might prevent permeability changes. Methods : The 6‐h urinary excretion of 51Cr‐EDTA after an oral load of 51Cr‐EDTA was used in this study as a measure for intestinal permeability. Healthy volunteers underwent a series of permeability tests: (i) basal test; (ii) test following NSAID (indomethacin); (iii) test following NSAID in combination with glutamine and/or misoprostol. Results : The NSAID induced increased permeability in all volunteers. Pre‐treatment with glutamine (3 × 7 g daily, 1 week before NSAID‐dosing) did not prevent the NSAID‐induced increase in permeability. Multiple doses of glutamine close in time to NSAID‐dosing resulted in significantly lower permeability compared to the NSAID without glutamine. Co‐administration of misoprostol with the multiple‐dose scheme of glutamine resulted in a further reduction in the NSAID‐induced increase in permeability. Conclusions : Glutamine decreases the permeability changes caused by NSAID‐dosing when it is administered close in time, and misoprostol has a synergistic effect.

Cholecystokinin is the main hormone involved in postprandial gallbladder contraction. There is also considerable gallbladder contraction in the fasting state, associated with phase III of the gastrointestinal migrating motor complex and release of the hormone motilin. It has been proposed that intraduodenal bile salts exert a negative-feedback control on postprandial cholecystokinin release and resulting gallbladder contraction. We wanted to elucidate whether a similar control mechanism on gallbladder contraction exists in the fasting state. We therefore performed gallbladder ultrasonography and 24-h antroduodenal motility registrations and determined plasma cholecystokinin and motilin levels in six healthy subjects before and after acute (4 g) and chronic (8 days; 8 g day(-1)) oral cholestyramine. Acute cholestyramine strongly decreased gallbladder volumes and increased motilin without changed cholecystokinin levels. There was a negative relationship between gallbladder volumes and plasma motilin levels. Although there was a persistent fasting pattern of antroduodenal motility, its cycle length was increased (P < 0.03) with markedly longer phase II (P < 0. 005). Fasting gallbladder volumes 24 h later were still strongly decreased but gradually increased to pretreatment levels. Before and after 8 days cholestyramine, interdigestive and postprandial gallbladder emptying, intestinal migrating motor complex and hormone levels did not differ. We conclude that acute (but not chronic) intraduodenal bile salt depletion with cholestyramine affects gallbladder and antroduodenal motility, possibly partly related to motilin release.

With the Effort Sharing Regulation, Member States are challenged to steer their societies – particularly the agriculture, buildings, waste and transport sectors – towards lower greenhouse gas emissions. The Effort Sharing Regulation illustrates the large extent to which the European Union (EU) relies on the use of hard law for addressing climate change, including binding enforcement provisions. The approach of the Effort Sharing Regulation is, in essence, simple: it consists of individual binding emission reduction targets for Member States, which are given various options to achieve compliance in a supposedly flexible, cost‐effective way. In this sense, the effort sharing approach is a continuation of the regulatory approach put forward by the Kyoto Protocol. The Effort Sharing Regulation can also serve as an example for third countries to adopt binding emission reduction targets, and it can be considered whether it would be beneficial to link such binding targets of third countries with this EU mechanism. However, a closer look at the Regulation highlights the challenges for its implementation, and the correct use of flexibilities, together with the proper application of the monitoring and enforcement provisions will be key for a successful outcome. The reputation of the EU taking leadership for combating climate change hinges on demonstrating compliance and on taking effective enforcement action where needed.

1 I am grateful to Jelmer Procee (student-assistant, Metro) for his help when preparing this article and I would like to thank an anonymous referee for his or her useful comments. Finally, I appreciate the fruitful discussion I had with Chris Dekkers about the topic .The views and analysis expressed in this article are the full responsibility of the author. 2 See about the emerging field of 'Climate Law' and the extraordinary reliance on market-based policy instruments B.J. Richardson, 'Climate law and economic policy instruments: a new field of environmental law'

In an attempt to discriminate between tectonically induced sea‐level changes and glacio‐eustacy, the Ekklissia and Arakthos sections (Epirus, NW Greece) are examined, applying (dinocyst) palynology, sedimentology and magnetostratigraphy. The sections, located in the Pindos Foreland Basin, both comprise the transition from pelagic limestones to hemipelagic silty clays and turbidite sandstones, reflecting the onset of flysch sedimentation as a result of the Pindos thrust activity. Despite an overall tectonic overprint, relative changes of sea level can be reconstructed, using (i) continental/marine palynomorph ratios, (ii) relative abundance of inshore and offshore dinoflagellate cysts, and (iii) taxa indicative of relatively cold and warm sea‐surface temperature, that can be calibrated against the Global Polarity Time Scale (GPTS). Increased fluxes of marginal marine and continental palynomorphs coincide with colder periods on a ‘third‐order’ scale, which thus appear to be related to glacio‐eustatic trends in sea‐level. The larger scale is attributed to the increasing effect of tectonics and acts on a ‘second‐order scale’.