Cyclooxygenase-2 mediates the cardioprotective effects of the late phase of ischemic preconditioning in conscious rabbits

We examined the role of cyclooxygenase-2 (COX-2) in the late phase of ischemic preconditioning (PC). A total of 176 conscious rabbits were used. Ischemic PC (six cycles of 4-min coronary occlusions/4-min reperfusions) resulted in a rapid increase in myocardial COX-2 mRNA levels (+231 ± 64% at 1 h; RNase protection assay) followed 24 h later by an increase in COX-2 protein expression (+216 ± 79%; Western blotting) and in the myocardial content of prostaglandin (PG)E2 and 6-keto-PGF1α (+250 ± 85% and +259 ± 107%, respectively; enzyme immunoassay). Administration of two unrelated COX-2 selective inhibitors (NS-398 and celecoxib) 24 h after ischemic PC abolished the ischemic PC-induced increase in tissue levels of PGE2 and 6-keto-PGF1α. The same doses of NS-398 and celecoxib, given 24 h after ischemic PC, completely blocked the cardioprotective effects of late PC against both myocardial stunning and myocardial infarction, indicating that COX-2 activity is necessary for this phenomenon to occur. Neither NS-398 nor celecoxib lowered PGE2 or 6-keto-PGF1α levels in the nonischemic region of preconditioned rabbits, indicating that constitutive COX-1 activity was unaffected. Taken together, these results demonstrate that, in conscious rabbits, up-regulation of COX-2 plays an essential role in the cardioprotection afforded by the late phase of ischemic PC. Therefore, this study identifies COX-2 as a cardioprotective protein. The analysis of arachidonic acid metabolites strongly points to PGE2 and/or PGI2 as the likely effectors of COX-2-dependent protection. The recognition that COX-2 mediates the antistunning and antiinfarct effects of late PC impels a reassessment of current views regarding this enzyme, which is generally regarded as detrimental.

Enantioselective alkylation of β-keto esters promoted by dimeric Cinchona-derived ammonium salts as recoverable organocatalysts

Dimeric anthracenyldimethyl-derived Cinchona ammonium salts are used as chiral organocatalysts in 5 mol% for the phase-transfer enantioselective alkylation reaction of 2-alkoxycarbonyl-1-indanones with activated bromides. The corresponding adducts bearing a new all-carbon quaternary center are obtained usually in high yield and with moderate and opposite enantioselectivity (up to 55%) when using ammonium salts derived from quinidine and its pseudoenantiomer quinine as organocatalysts. These catalysts can be almost quantitatively recovered by precipitation in ether and reused.

Copper-Catalyzed Asymmetric Alkylation of β-Keto Esters with Xanthydrols

The copper(II) triflate-tert-butyl-bisoxazoline [Cu(OTf)2-t-Bu-BOX]-catalyzed asymmetric alkylation of β-keto esters using free benzylic alcohols such as xanthydrols, as alkylating agents, is herein described for the first time. This green protocol renders in general the corresponding products with good results in terms of both yields and enantioselectivities using different keto esters, even when quaternary stereocenters were created. The scope, limitations and mechanistic aspects of the process are also discussed.

Cameron’s reality check on Europe. EPIN [Working] Paper No. 38, 15 April 2014

Ever since Prime Minister David Cameron made his major speech on Europe on 23 January 2013, in which he argued for some kind of new deal between the UK and the EU, the rest of the EU as well as the British public have been wondering what he would actually propose in operational terms. On 15 March 2014, the Prime Minister offered at least an interim reply to these questions in an article in the Daily Telegraph newspaper. This paper extracts from the Daily Telegraph article the main ideas that the Prime Minister advances. In all, 10 propositions are identified, presented in the precise language used, followed by an appraisal. The article has not attracted so much attention, mainly because its content is not particularly sensational, but that is its real importance and quality. It points the way towards resolving what otherwise would mean a huge political crisis for the UK and the EU. The Prime Minister gave the overall impression that he is not now heading towards making an impossibly difficult list of demands. On the contrary, an informed and moderate realism seems to be in the making. The package outlined in this paper could be sold in Brussels. There would then have to be a robust communications campaign to sell it to the British public. This paper is part of a series for a CEPS-EPIN project on “The British Question and the Search for a Fresh European Narrative”, which is pegged to an ambitious ongoing exercise by the British government to review all the competences of the European Union. The intention is that this should provide a basis for informed debate before the referendum on the UK remaining in the EU or not, which is scheduled for 2017.

Antitrust on the ‘G string’: What’s behind the Commission’s investigations of Google and Gazprom? CEPS Commentary, 15 June 2015

The past few weeks have marked a shift of gear in EU antitrust enforcement. First, the new European Commissioner for Competition Margarethe Vestager announced on April 15th that the Commission had sent a Statement of Objections to Google, arguing that the giant IT company abused its dominant position in the “general Internet search” market and also in the market for mobile operating systems, apps and services. Exactly one week later, she also sent a Statement of Objections to Gazprom for having created artificial barriers to trade between certain EU countries, preventing gas flows and competition across national borders and charging unfair prices in five Central and Eastern European countries. It is indeed hard to recall any other time in which two investigations of this size – both potentially leading to billions of euros of fines – have been launched almost simultaneously.

Balancing Priorities and Emergency Measures: Luxembourg’s Council Presidency. EPIN Commentary No. 30/15 January 2016

The Grand Duchy of Luxembourg held the reins of the EU Council presidency between 1 July and 31 December 2015. This was the 12th time that the second-smallest and the richest EU member state1 held the rotating Council presidency. As one of the founding members of the EU, Luxembourg has sound experience to bring to this role. It was, however, their first presidency since the entry into force of the Lisbon Treaty and its introduction of the trio presidency format, this time including Italy and Latvia. Under the slogan ‘A Union for the Citizens’, Luxembourg had the task of concluding certain major dossiers before the end of the trio’s term and was able to contribute to its overarching agenda, especially regarding the priorities of financial stability, growth stimulation and the digital agenda.

Regulation on ‘cross-border portability’ of online content services: Roaming for Netflix or the end of copyright territoriality? CEPS Commentary, 15 February 2016

In a communication to the Parliament and the Council entitled “Towards a modern, more European copyright framework” and dated 9 December 2015,1 the European Commission confirmed its intention to progressively remove the main obstacles to the functioning of the Digital Single Market for copyrighted works. The first step of this long-term plan, which was first announced in Juncker’s Political Guidelines2 and the Communication on “A Digital Single Market strategy for Europe”,3 is a proposal for a regulation aimed at ensuring the so-called ‘cross-border portability’ of online services giving access to content such as music, games, films and sporting events.4 In a nutshell, the proposed regulation seeks to enable consumers with legal access to such online content services in their country of residence to use the same services also when they are in another member state for a limited period of time. On the one hand, this legislative proposal has the full potential to resolve the (limited) issue of portability, which stems from the national dimension of copyright and the persisting territorial licensing and distribution of copyright content.5 On the other hand, as this commentary shows, the ambiguity of certain important provisions in the proposed regulation might affect its scope and effectiveness and contribute to the erosion of the principle of copyright territoriality.

The Impact of Brexit on the EU’s International Agreements. CEPS Commentary, 15 July 2016

The prospect of Brexit has kicked up a lot of dust around the now famous Article 50 TEU withdrawal procedure, and the form, scope and sequence of the ‘divorce’ and future framework agreements between the EU and the UK.[1] One issue that has received far less attention is whether the international agreements concluded by the EU will continue to apply to the UK after Brexit, and if so, how.

Sátira contra los vicios introducidos en la poesía castellana premiada por la Real Academia Española, en junta que celebró el dia 15 de octubre de 1782 /

Mode of access: Internet.

Towards the total synthesis of vibsanin E, 15-O-methylcyclovibsanin B, 3-hydroxyvibsanin E, furanovibsanin A, and 3-O-methylfuranovibsanin A

Studies detailing synthetic approaches to a variety of biosynthetically related vibsanin-type diterpenes (i.e. vibsanin E, 15-O-methylcyclovibsanin B, 3-hydroxy-vibsanin E, furano-vibsanin A, and 3-O-methylfuranovibsanin A) are discussed. Biogenetically modelled approaches are coupled with an in-vestigation of classical and modern six- to seven-membered ring-expansion protocols, which gain access to the central core of these natural products. (c) Wiley-VCH Verlag GmbH & Co.

Ameliorative effect and potential mechanism of Ermiao san on adjuvant-induced arthritis in rats

Purpose: To investigate the effect and mechanism of action of Ermiao san (EMS), a traditional Chinese herbal formula, on inflammation development and production of inflammatory mediators in adjuvantinduced arthritis (AIA). Methods: AIA was induced by injection of 0.1 ml Freund’s complete adjuvant (FCA, 10 mg/ml) in the left hind footpad of the rats. AIA rats were intragastricly treated with 0.5, 1, 2 g/kg EMS or 0.1 g/kg methotrexate from day 7 to 28 after FCA challenge. Foot volume and histological score were measured. Osteoclast number was calculated by tartrate-resistant acid phosphatase (TRAP) staining assay. Levels of prostaglandin (PG) E2, tumor necrosis factor (TNF) -α and interleukin (IL)-1β in serum were determined by enzyme-linked immunosorbent assay (ELISA) while the level of nitric oxide (NO) in serum was analyzed by Griess reaction method. Results: Foot volume, histological score, osteoclast number and serum levels of TNF-α, IL-1β, PGE2 and NO were all increased in AIA group rats on day 28 after FCA challenge (all p < 0.01) compared with control. EMS (1 and 2 g/kg) significantly decreased the foot volume of AIA rats by 10 % (p < 0.05) and 19 % (p < 0.01), respectively, compared with AIA group. Furthermore, 1 and 2 g/kg EMS significantly reduced histological score by about 28 % (p < 0.05) and 46 % (p < 0.01), respectively, as well as osteoclast number by 12 % (p < 0.05) and 15 % (p < 0.05), respectively, compared with AIA group. In addition, 1 and 2 g/kg EMS significantly decreased the serum levels of TNF-α about 23 % (p < 0.05) and 43 % (p < 0.01), IL-1β by15 % (p < 0.05) and 26 % (p < 0.01), NO 13 % (p < 0.05) and 26 % (p < 0.01) as well as PGE2 by 11 % (p < 0.05) and 15 % (p < 0.01), respectively, compared with AIA group. Conclusion: These results suggest that EMS probably alleviates arthritis development and joint destruction by decreasing the production of inflammatory mediators in AIA rats.

The Applicability Of Ordered Mesoporous Sba-15 And Its Hydrophobic Glutaraldehyde-bridge Derivative To Improve Ibuprofen-loading In Releasing System.

The mesoporous SBA-15 silica with uniform hexagonal pore, narrow pore size distribution and tuneable pore diameter was organofunctionalized with glutaraldehyde-bridged silylating agent. The precursor and its derivative silicas were ibuprofen-loaded for controlled delivery in simulated biological fluids. The synthesized silicas were characterized by elemental analysis, infrared spectroscopy, (13)C and (29)Si solid state NMR spectroscopy, nitrogen adsorption, X-ray diffractometry, thermogravimetry and scanning electron microscopy. Surface functionalization with amine containing bridged hydrophobic structure resulted in significantly decreased surface area from 802.4 to 63.0 m(2) g(-1) and pore diameter 8.0-6.0 nm, which ultimately increased the drug-loading capacity from 18.0% up to 28.3% and a very slow release rate of ibuprofen over the period of 72.5h. The in vitro drug release demonstrated that SBA-15 presented the fastest release from 25% to 27% and SBA-15GA gave near 10% of drug release in all fluids during 72.5 h. The Korsmeyer-Peppas model better fits the release data with the Fickian diffusion mechanism and zero order kinetics for synthesized mesoporous silicas. Both pore sizes and hydrophobicity influenced the rate of the release process, indicating that the chemically modified silica can be suggested to design formulation of slow and constant release over a defined period, to avoid repeated administration.

Utilization Of (15)no3 (-) By Nodulated Soybean Plants Under Conditions Of Root Hypoxia.

Waterlogging of soils is common in nature. The low availability of oxygen under these conditions leads to hypoxia of the root system impairing the development and productivity of the plant. The presence of nitrate under flooding conditions is regarded as being beneficial towards tolerance to this stress. However, it is not known how nodulated soybean plants, cultivated in the absence of nitrate and therefore not metabolically adapted to this compound, would respond to nitrate under root hypoxia in comparison with non-nodulated plants grown on nitrate. A study was conducted with (15)N labelled nitrate supplied on waterlogging for a period of 48 h using both nodulated and non-nodulated plants of different physiological ages. Enrichment of N was found in roots and leaves with incorporation of the isotope in amino acids, although to a much smaller degree under hypoxia than normoxia. This demonstrates that nitrate is taken up under hypoxic conditions and assimilated into amino acids, although to a much lesser extent than for normoxia. The similar response obtained with nodulated and non-nodulated plants indicates the rapid metabolic adaptation of nodulated plants to the presence of nitrate under hypoxia. Enrichment of N in nodules was very much weaker with a distinct enrichment pattern of amino acids (especially asparagine) suggesting that labelling arose from a tissue source external to the nodule rather than through assimilation in the nodule itself.