Increased striatal VMAT2 binding in mice after chronic administration of methcathinone and manganese

Intravenous use of a psychostimulant drug containing methcathinone (ephedrone) and manganese causes an irreversible extrapyramidal syndrome in drug abusers. We aimed to reproduce the syndrome in mice to evaluate dopaminergic damage. C57/B6 mice were intraperitoneally injected once a day with the study drug or saline for a period of 27 weeks. Motor activity was recorded in an automated motility-box. After 13 and 27 weeks of treatment, ex vivo digital autoradiography was performed using [11C]dihydrotetrabenazine ([11C]DTBZ). After 27 weeks of treatment [11C]DTBZ autoradiography demonstrated a significant increase in the striatum-to-cerebellum binding ratio compared with saline treated controls. At the same time point, there was no evident change in motor activity. Increased [11C]DTBZ binding may indicate vesicular monoamine transporter type 2 (VMAT2) function is altered. The lack of extrapyramidal symptoms in animals could be attributed to low dosing regimen or high metabolic rate

EUCAST rapid antimicrobial susceptibility testing (RAST) in blood cultures: validation in 55 European laboratories

Objectives: When bloodstream infections are caused by resistant bacteria, rapid antimicrobial susceptibility testing (RAST) is important for adjustment of therapy. The EUCAST RAST method, directly from positive blood cultures, was validated in a multi-laboratory study in Europe. Methods: RAST was performed in 40 laboratories in northern Europe (NE) and 15 in southern Europe (SE) from clinical blood cultures positive for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus or Streptococcus pneumoniae. Categorical results at 4, 6 and 8 h of incubation were compared with results for EUCAST standard 16-20 h disc diffusion. The method, preliminary breakpoints and the performance of the laboratories were evaluated. Results: The total number of isolates was 833/318 in NE/SE. The number of zone diameters that could be read (88%, 96% and 99%) and interpreted (70%, 81% and 85%) increased with incubation time (4, 6 and 8 h). The categorical agreement was acceptable, with total error rates in NE/SE of 2.4%/4.9% at 4 h, 1.1%/3.5% at 6 h and 1.1%/3.3% at 8 h. False susceptibility at 4, 6 and 8 h of incubation was below 0.3% and 1.1% in NE and SE, respectively, and the corresponding percentages for false resistance were below 1.9% and 2.8%. After fine-tuning breakpoints, more zones could be interpreted (73%, 89% and 93%), with only marginally affected error rates. Conclusions: The EUCAST RAST method can be implemented in routine laboratories without major investments. It provides reliable antimicrobial susceptibility testing results for relevant bloodstream infection pathogens after 4-6 h of incubation. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.This work was supported by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) through its regular support of the development of EUCAST methodology and by the Medical Research Council of Southeast Sweden (grant number FORSS-744451).publishedVersio

Extracellular Superoxide Dismutase Is a Growth Regulatory Mediator of Tissue Injury Recovery

Extracellular superoxide dismutase (SOD3) gene therapy has been shown to attenuate tissue damages and to improve the recovery of the tissue injuries, but the cellular events delivering the therapeutic response of the enzyme are not well defined. In the current work, we overexpressed SOD3 in rat hindlimb ischemia model to study the signal transduction and injury healing following the sod3 gene transfer. The data suggest a novel sod3 gene transfer–derived signal transduction cascade through Ras-Mek-Erk mitogenic pathway leading to activation of AP1 and CRE transcription factors, increased vascular endothelial growth factor (VEGF)-A and cyclin D1 expression, increased cell proliferation, and consequently improved metabolic functionality of the injured tissue. Increased cell proliferation could explain the improved metabolic performance and the healing of the tissue damages after the sod3 gene transfer. The present data is a novel description of the molecular mechanism of SOD3-mediated recovery of tissue injury and suggests a new physiological role for SOD3 as a Ras regulatory molecule in signal transduction