Toxicity of statins on rat skeletal muscle mitochondria

Abstract.: We investigated mitochondrial toxicity of four lipophilic stains (cerivastatin, fluvastatin, atorvastatin, simvastatin) and one hydrophilic statin (pravastatin). In L6 cells (rat skeletal muscle cell line), the four lipophilic statins (100μmol/l) induced death in 27-49% of the cells. Pravastatin was not toxic up to 1mmol/l. Cerivastatin, fluvastatin and atorvastatin (100μmol/l) decreased the mitochondrial membrane potential by 49-65%, whereas simvastatin and pravastatin were less toxic. In isolated rat skeletal muscle mitochondria, all statins, except pravastatin, decreased glutamate-driven state 3 respiration and respiratory control ratio. Beta-oxidation was decreased by 88-96% in the presence of 100μmol/l of the lipophilic statins, but only at higher concentrations by pravastatin. Mitochondrial swelling, cytochrome c release and DNA fragmentation was induced in L6 cells by the four lipophilic statins, but not by pravastatin. Lipophilic statins impair the function of skeletal muscle mitochondria, whereas the hydrophilic pravastatin is significantly less toxi

Surveillance for European bat lyssavirus in Swiss bats

Most countries in Western Europe are currently free of rabies in terrestrial mammals. Nevertheless, rabies remains a residual risk to public health due to the natural circulation of bat-specific viruses, such as European bat lyssaviruses (EBLVs). European bat lyssavirus types 1 and 2 (EBLV-1 and EBLV-2) are widely distributed throughout Europe, but little is known of their true prevalence and epidemiology. We report that only three out of 837 brains taken from bats submitted to the Swiss Rabies Centre between 1976 and 2009 were found by immunofluorescence (FAT) to be positive for EBLVs. All three positive cases were in Myotis daubentoni, from 1992, 1993 and 2002. In addition to this passive surveillance, we undertook a targeted survey in 2009, aimed at detecting lyssaviruses in live bats in Switzerland. A total of 237 bats of the species M. daubentoni, Myotis myotis, Eptesicus serotinus and Nyctalus noctula were captured at different sites in western Switzerland. Oropharyngeal swabs and blood from each individual were analysed by RT-PCR and rapid fluorescent focus inhibition test (RFFIT), respectively. RNA corresponding to EBLV-2 was detected from oropharyngeal swabs of a single M. daubentoni bat, but no infectious virus was found. Molecular phylogenetic analysis revealed that the corresponding sequence was closely related to the other EBLV-2 sequences identified in previous rabies isolates from Swiss bats (particularly to that found at Geneva in 2002). Three M. daubentoni bats were found to be seropositive by RFFIT. In conclusion, even though the prevalence is low in Switzerland, continuous management and surveillance are required to assess the potential risk to public healt

Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging

Detecting metabolites and parent compound within a cell type is now a priority for pharmaceutical development. In this context, three-dimensional secondary ion mass spectrometry (SIMS) imaging was used to investigate the cellular uptake of the antiarrhythmic agent amiodarone, a phospholipidosis-inducing pharmaceutical compound. The high lateral resolution and 3D imaging capabilities of SIMS combined with the multiplex capabilities of ToF mass spectrometric detection allows for the visualization of pharmaceutical compound and metabolites in single cells. The intact, unlabeled drug compound was successfully detected at therapeutic dosages in macrophages (cell line: NR8383). Chemical information from endogenous biomolecules was used to correlate drug distributions with morphological features. From this spatial analysis, amiodarone was detected throughout the cell with the majority of the compound found in the membrane and subsurface regions and absent in the nuclear regions. Similar results were obtained when the macrophages were doped with amiodarone metabolite, desethylamiodarone. The FWHM lateral resolution measured across an intracellular interface in a high lateral resolution ion images was approximately 550 nm. Overall, this approach provides the basis for studying cellular uptake of pharmaceutical compounds and their metabolites on the single cell level

Für den Erfolg entscheidend: metallfreie zirkoniumdioxidbasierte Rekonstruktionen - Bearbeitungsschritte zum Erfolg

Metallfreie Rekonstruktionen setzten sich aufgrund der guten Ästhetik, Biokompatibilität und der guten mechanischen Eigenschaften immer stärker durch. Zirkoniumdioxid als Gerüstmaterial wird mittlerweile fast in jedem Labor bearbeitet. Leider wird immer häufiger festgestellt, dass dieses Material eine „Sonderbearbeitung“ benötigt und sich nicht wie die herkömmlichen VMK-Rekonstruktionen lässt. In dem vorliegenden Beitrag werden die mechanischen Eigenschaften und die Verarbeitungsarten von Zirkoniumdioxidrekonstruktionen mit VMK-Versorgung gegenübergestellt und diskutiert

Quantifying rates of detachment faulting and erosion in the central Menderes Massif (western Turkey) by thermochronology and cosmogenic 10

Exhumation of rocks in extensional tectonic settings results from a combination of normal faulting and erosion but the relative contribution of these processes has rarely been quantified. Here we present new low-temperature thermochronological data and the first Be-10-based catchment-wide erosion rates from the Boz Dag region in the central Menderes Massif, which has experienced NNE-SSW extension since the Miocene. The slip rate of the shallow-dipping Gediz detachment fault, which defines the northern flank of the Boz Dag block, is 4.3 (+3.0/-1.2) mm a(-1), as constrained by zircon (U-Th)/He ages of c. 4-2 Ma in the footwall. Apatite and zircon (U-Th)/He and fission-track ages from the northern flank of the Boz Dag block yield exhumation rates of 0.6-2 km Ma(-1) beneath the Gediz detachment, whereas those on the southern flank are only 0.2-0.6 km Ma(-1). Erosion of catchments on the northern and southern flanks proceeds at rates of 80-180 and 330-460 mm ka(-1), respectively. This marked contrast is a combined effect of the topographic asymmetry of the Boz Dag block and differences in rock erodibility. If these erosion rates persisted in the past, rock exhumation on the northern flank occurred predominantly by tectonic denudation, whereas rocks on the southern flank were mainly exhumed by erosion

Black managers in further education: career hopes and hesitations

This article reports on an exploratory study of black managers in Further Education colleges and records their individual views and experiences. The premise of this article is that, contrary to rhetoric about equal opportunities, black managers are experiencing barriers in progressing their careers. With examples from participants on a postgraduate programme in management, the article explores their experiences and perceptions and illustrates the various forms these barriers can take. The study follows seven black managers and their career aspirations over an 18-month period. The article suggests that black managers face additional constraints to progressing their careers and this has implications for organizations, and, in particular, how they encourage and maintain a diverse workforce