A study comparing centralized CD-ROM and decentralized intranet access to MEDLINE

Objective: The purpose of this study was to evaluate the efficacy of a decentralized intranet access in each medical department as opposed to centralized unique MEDLINE access in the medical library.

Molecular determinants of drug access to the receptor site for antiarrhythmic drugs in the cardiac Na+ channel.

The clinical efficacy of local anesthetic and antiarrhythmic drugs is due to their voltage- and frequency-dependent block of Na+ channels. Quaternary local anesthetic analogs such as QX-314, which are permanently charged and membrane-impermeant, effectively block cardiac Na+ channels when applied from either side of the membrane but block neuronal Na+ channels only from the intracellular side. This difference in extracellular access to QX-314 is retained when rat brain rIIA Na+ channel alpha subunits and rat heart rH1 Na+ channel alpha subunits are expressed transiently in tsA-201 cells. Amino acid residues in transmembrane segment S6 of homologous domain IV (IVS6) of Na+ channel alpha subunits have important effects on block by local anesthetic drugs. Although five amino acid residues in IVS6 differ between brain rIIA and cardiac rH1, exchange of these amino acid residues by site-directed mutagenesis showed that only conversion of Thr-1755 in rH1 to Val as in rIIA was sufficient to reduce the rate and extent of block by extracellular QX-314 and slow the escape of drug from closed channels after use-dependent block. Tetrodotoxin also reduced the rate of block by extracellular QX-314 and slowed escape of bound QX-314 via the extracellular pathway in rH1, indicating that QX-314 must move through the pore to escape. QX-314 binding was inhibited by mutation of Phe-1762 in the local anesthetic receptor site of rH1 to Ala whether the drug was applied extracellularly or intracellularly. Thus, QX-314 binds to a single site in the rH1 Na+ channel alpha subunit that contains Phe-1762, whether it is applied from the extracellular or intracellular side of the membrane. Access to that site from the extracellular side of the pore is determined by the amino acid at position 1755 in the rH1 cardiac Na+ channel.

Domino 1,3-Dipolar Cycloadditions of N-Alkyl-α-Amino Esters with Paraformaldehyde: A Direct Access to α-Hydroxymethyl α-Amino Acids

N-Alkyl-α-amino esters undergo a domino reaction, based on the iminium cation generation, with paraformaldehyde, followed by a 1,3-dipolar cycloaddition of the stabilized azometh­ine ylide with another equivalent of formaldehyde. The resulting products are oxazolidines, which can be transformed after hydrolysis into α-hydroxymethyl α-amino acid or its derivatives. The diastereoselective 1,3-dipolar cycloaddition was performed using sarcosine (–)-menthyl or (–)-8-phenylmenthyl esters affording the cyclic product with moderate enantiomeric ratio.

Talking with the “pouvoir constituant” in times of constitutional reform: The European Court of Justice on Private Applicants’ Access to Justice. Research Paper in Law 3/2003

[From the Introduction]. European lawyers, at least those dealing predominantly with institutional matters, are living particularly interesting times since the setting-up of the “European Convention on the Future of Europe” in December 2001.1 As the Convention’s mandate, spelled out in rather broad terms in the European Council’s declaration of Laeken,2 is potentially unlimited, and as the future constitution of the European Union (EU) will be ultimately adopted by the subsequent Intergovernmental Conference (IGC), there appears to be a great possibility to clarify, to simplify and also to reform many of the more controversial elements in the European legal construction. The present debate on the future of the European constitution also highlights the relationship between the pouvoir constituant3 and the European Courts, the Court of Justice (ECJ) and its Court of First Instance (CFI), who have to interpret the basic rules and principles of the EU.4 In that light, the present article will focus on a classic theme of the Court’s case law: the relationship between judges and pouvoir constituant. In the EU, this relationship has traditionally been marked by the ECJ’s role as driving force in the “constitutionalisation” of the EC Treaties – which has, to a large extent, been accepted and even codified by the Member States in subsequent treaty revisions. However, since 1994, the ECJ appears to be more reluctant to act as a “law-maker.”5 The recent judgment in Unión de Pequeños Agricultores (UPA)6 – an important decision by which the ECJ refused to liberalize individuals’ access to the Community Courts – is also interesting in this context. UPA may be seen as another proof of judicial restraint - or even as indicator of the beginning of a new phase in the “constitutional dialogue” between the ECJ and the “Masters of the Treaties.”