Hydroxyfasudil-Mediated Inhibition of ROCK1 and ROCK2 Improves Kidney Function in Rat Renal Acute Ischemia-Reperfusion Injury

Renal ischemia-reperfusion (IR) injury (IRI) is a common and important trigger of acute renal injury (AKI). It is inevitably linked to transplantation. Involving both, the innate and the adaptive immune response, IRI causes subsequent sterile inflammation. Attraction to and transmigration of immune cells into the interstitium is associated with increased vascular permeability and loss of endothelial and tubular epithelial cell integrity. Considering the important role of cytoskeletal reorganization, mainly regulated by RhoGTPases, in the development of IRI we hypothesized that a preventive, selective inhibition of the Rho effector Rho-associated coiled coil containing protein kinase (ROCK) by hydroxyfasudil may improve renal IRI outcome. Using an IRI-based animal model of AKI in male Sprague Dawley rats, animals treated with hydroxyfasudil showed reduced proteinuria and polyuria as well as increased urine osmolarity when compared with sham-treated animals. In addition, renal perfusion (as assessed by 18F-fluoride Positron Emission Tomography (PET)), creatinine- and urea-clearances improved significantly. Moreover, endothelial leakage and renal inflammation was significantly reduced as determined by histology, 18F-fluordesoxyglucose-microautoradiography, Evans Blue, and real-time PCR analysis. We conclude from our study that ROCK-inhibition by hydroxyfasudil significantly improves kidney function in a rat model of acute renal IRI and is therefore a potential new therapeutic option in humans

LABOCA observations of nearby, active galaxies

We present large scale 870 micron maps of the nearby starburst galaxies NGC253, NGC4945 and the nearest giant elliptical radio galaxy Centaurus A (NGC 5128) obtained with the newly commissioned Large Apex Bolometer Camera (LABOCA) operated at the APEX telescope. Our continuum images reveal for the first time the distribution of cold dust at a angular resolution of 20" across the entire optical disks of NGC253 and NGC4945 out to a radial distance of 10' (7.5 kpc). In NGC5128 our LABOCA image also shows, for the first time at submillimeter wavelengths, the synchrotron emission associated with the radio jet and the inner radio lobes. From an analysis of the 870 micron emission in conjunction with ISO-LWS, IRAS and long wavelengths radio data we find temperatures for the cold dust in the disks of all three galaxies of 17-20 K, comparable to the dust temperatures in the disk of the Milky Way. The total gas mass in the three galaxies is determined to be 2.1, 4.2 and 2.8 x 10^9 solar masses for NGC253, NGC4945 and NGC5128, respectively. A detailed comparison between the gas masses derived from the dust continuum and the integrated CO(1-0) intensity in NGC253 suggests that changes of the CO luminosity to molecular mass conversion factor are mainly driven by a metallicity gradient and only to a lesser degree by variations of the CO excitation. An analysis of the synchrotron spectrum in the northern radio lobe of NGC5128 shows that the synchrotron emission from radio to the ultraviolet wavelengths is well described by a broken power law and that the break frequency is a function of the distance from the radio core as expected for aging electrons. We derive an outflow speed of ~0.5c at a distance of 2.6kpc from the center, consistent with the speed derived in the vicinity of the nucleus.Comment: 12 pages, 11 figures. Accepted for publication in A&

Testing QCD factorisation and charming penguins in charmless B→PV{\boldsymbol{B\to PV}}

We try a global fit of the experimental branching ratios and CP-asymmetries of the charmless $B\to PV$ decays according to QCD factorisation. We find it impossible to reach a satisfactory agreement, the confidence level (CL) of the best fit is smaller than .1 %. The main reason for this failure is the difficulty to accomodate several large experimental branching ratios of the strange channels. Furthermore, experiment was not able to exclude a large direct CP asymmetry in $\bar {B^0}\to\rho^+ \pi^-$, which is predicted very small by QCD factorisation. Trying a fit with QCD factorisation complemented by a charming-penguin inspired model we reach a best fit which is not excluded by experiment (CL of about 8 %) but is not fully convincing. These negative results must be tempered by the remark that some of the experimental data used are recent and might still evolve significantly.Comment: 21 pages, 4 figures; several typos corrected, added one footnote and two references, comments added about PQCD. To appear in Phys.Rev.

Study of B meson decays to three-body charmless hadronic final states

We report results of a study of charmless B meson decays to three-body KPiPi, KKPi and KKK final states. Measurements of branching fractions for B decays to K+0Pi+Pi-, K+K+K-, K0K+K-, KsKsK+ and KsKsKs final states are presented. The decays B0=>K0K+K-, B+=>KsKsK+ and B0=>KsKsKs are observed for the first time. We also report evidence for B+=>K+K-Pi+ decay. For the three-body final states K0K+K-, KsKsPi+, K+K+Pi- and K-Pi+Pi+ 90% confidence level upper limits are reported. Finally, we discuss the possibility of using the three-body B0=>KsK+K- decay for CP violation studies. The results are obtained with a 78 fb^-1 data sample collected at the Y(4S) resonance by the Belle detector operating at the KEKB asymmetric energy e+e- collider.Comment: 15 pages, 6 figures. To be submitted to PR

Branching Fractions of tau Leptons to Three Charged Hadrons

From electron-positron collision data collected with the CLEO detector operating at CESR near \sqrt{s}=10.6 GeV, improved measurements of the branching fractions for tau decays into three explicitly identified hadrons and a neutrino are presented as {\cal B}(\tau^-\to\pi^-\pi^+\pi^-\nu_\tau)=(9.13\pm0.05\pm0.46)%, {\cal B}(\tau^-\to K^-\pi^+\pi^-\nu_\tau)=(3.84\pm0.14\pm0.38)\times10^{-3}, {\cal B}(\tau^-\to K^-K^+\pi^-\nu_\tau)=(1.55\pm0.06\pm0.09)\times10^{-3}, and {\cal B}(\tau^-\to K^-K^+K^-\nu_\tau)<3.7\times10^{-5} at 90% C.L., where the uncertainties are statistical and systematic, respectively.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, to appear in Phys. Rev. Let

Observation of the Hadronic Transitions Chi_{b 1,2}(2P) -> omega Upsilon(1S)

The CLEO Collaboration has observed the first hadronic transition among bottomonium (b bbar) states other than the dipion transitions among vector states, Upsilon(nS) -> pi pi Upsilon(mS). In our study of Upsilon(3S) decays, we find a significant signal for Upsilon(3S) -> gamma omega Upsilon(1S) that is consistent with radiative decays Upsilon(3S) -> gamma chi_{b 1,2}(2P), followed by chi_{b 1,2} -> omega Upsilon(1S). The branching ratios we obtain are Br(chi_{b1} -> omega Upsilon(1S) = 1.63 (+0.35 -0.31) (+0.16 -0.15) % and Br(chi_{b2} -> omega Upsilon(1S) = 1.10 (+0.32 -0.28) (+0.11 - 0.10)%, in which the first error is statistical and the second is systematic.Comment: submitted to XXI Intern'l Symp on Lepton and Photon Interact'ns at High Energies, August 2003, Fermila