Interventional Laser-assisted Extraction of an Infected Trapped Ventriculoatrial Shunt Based on Techniques for Pacemaker Lead Explantation.

We present a case of successful interventional laser-assisted extraction of an endovascularly trapped long-term implanted ventriculoatrial shunt in a patient with shunt-associated septicemia. This approach is based on modified techniques for explantation of pacemaker leads and might be considered an additional option for extraction of otherwise nonremovable trapped endovascular catheters in experienced centers.

Positive modulation of synaptic and extrasynaptic GABAA receptors by an antagonist of the high affinity benzodiazepine binding site.

GABAA receptors are the major inhibitory neurotransmitter receptors in the brain and are the target for many clinically important drugs such as the benzodiazepines. Benzodiazepines act at the high-affinity binding site at the α+/γ- subunit interface. Previously, an additional low affinity binding site for diazepam located in the transmembrane (TM) domain has been described. The compound SJM-3 was recently identified in a prospective screening of ligands for the benzodiazepine binding site and investigated for its site of action. We determined the binding properties of SJM-3 at GABAA receptors recombinantly expressed in HEK-cells using radioactive ligand binding assays. Impact on function was assessed in Xenopus laevis oocytes with electrophysiological experiments using the two-electrode voltage clamp method. SJM-3 was shown to act as an antagonist at the α+/γ- site. At the same time it strongly potentiated GABA currents via the binding site for diazepam in the transmembrane domain. Mutation of a residue in M2 of the α subunit strongly reduced receptor modulation by SJM-3 and a homologous mutation in the β subunit abolished potentiation. SJM-3 acts as a more efficient modulator than diazepam at the site in the trans-membrane domain. In contrast to low concentrations of benzodiazepines, SJM-3 modulates both synaptic and extrasynaptic receptors. A detailed exploration of the membrane site may provide the basis for the design and identification of subtype-selective modulatory drugs.

An Avron rule for fragments of R-mingle

Axiomatic bases of admissible rules are obtained for fragments of the substructural logic R-mingle. In particular, it is shown that a ‘modus-ponens-like’ rule introduced by Arnon Avron forms a basis for the admissible rules of its implication and implication–fusion fragments, while a basis for the admissible rules of the full multiplicative fragment requires an additional countably infinite set of rules. Indeed, this latter case provides an example of a three-valued logic with a finitely axiomatizable consequence relation that has no finite basis for its admissible rules.