The Volatile Anesthetic Isoflurane Increases Endothelial Adenosine Generation via Microparticle Ecto-5′-Nucleotidase (CD73) Release

Endothelial dysfunction is common in acute and chronic organ injury. Isoflurane is a widely used halogenated volatile anesthetic during the perioperative period and protects against endothelial cell death and inflammation. In this study, we tested whether isoflurane induces endothelial ecto-5′-nucleotidase (CD73) and cytoprotective adenosine generation to protect against endothelial cell injury. Clinically relevant concentrations of isoflurane induced CD73 activity and increased adenosine generation in cultured human umbilical vein or mouse glomerular endothelial cells. Surprisingly, isoflurane-mediated induction of endothelial CD73 activity occurred within 1 hr and without synthesizing new CD73. We determined that isoflurane rapidly increased CD73 containing endothelial microparticles into the cell culture media. Indeed, microparticles isolated from isoflurane-treated endothelial cells had significantly higher CD73 activity as well as increased CD73 protein. In vivo, plasma from mice anesthetized with isoflurane had significantly higher endothelial cell-derived CD144+ CD73+ microparticles and had increased microparticle CD73 activity compared to plasma from pentobarbital-anesthetized mice. Supporting a critical role of CD73 in isoflurane-mediated endothelial protection, a selective CD73 inhibitor (APCP) prevented isoflurane-induced protection against human endothelial cell inflammation and apoptosis. In addition, isoflurane activated endothelial cells Rho kinase evidenced by myosin phosphatase target subunit-1 and myosin light chain phosphorylation. Furthermore, isoflurane-induced release of CD73 containing microparticles was significantly attenuated by a selective Rho kinase inhibitor (Y27632). Taken together, we conclude that the volatile anesthetic isoflurane causes Rho kinase-mediated release of endothelial microparticles containing preformed CD73 and increase adenosine generation to protect against endothelial apoptosis and inflammation

A search for hadronic events with low thrust and an isolated lepton

Using the CELLO detector at the PETRA e$^+$e$^-$ storage ring a search for hadronic events with low thrust and an isolated lepton has been carried out. The rate of such events and the thrust distribution of inclusive lepton events show no evidence for a threshold of new sources of inclusive lepton events at the highest PETRA energies. For 46.3 GeV we observe any electron event of this above type, compared to an expectation of 0.8±0.2 events from lower energy data. We do not observe any electron event of this class at the highest PETRA energies. The CELLO data thus do not support the observations of the MARK-J and JADE collaborations of an excess of muon events of the above type at s > 46.3 Ge

Searches for supersymmetric particles with the CELLO detector at PETRA

Mass limits are presented for various supersymmetric particles: scalar partners of electrons, muons, taus and quarks; photinos, winos and zinos. They were obtained from the analysis of an exposure of 48.6 pb $^{−1}$ of the CELLO detector at the PETRAe $^+$e$^−$ storage ring up to a center of mass energy of 46.8 GeV. Special attention has been given to the case where the photino is assumed to be the lightest supersymmetric particle, but other possibilities have also been considered