In order to specifically examine the expression of the spinal glutamate transporters, a novel line of double transgenic GLT-1-enhanced green fluorescent protein
(eGFP)/GLAST-Discosoma Red (DsRed) promoter mice was used. Adult mice received propentofylline (10 mg/kg) or saline via i.p. injection starting 1 h prior to L5-spinal nerve transection and then daily for 12 days. Mice receiving saline exhibited punctate expression of both eGFP (GLT-1 promoter activation) and DsRed GSK126 research buy (GLAST promoter activation) in the dorsal horn of the spinal cord, which was decreased ipsilateral to nerve injury on day 12. Propentofylline administration reinstated promoter activation on the injured side as evidenced by an equal number of eGFP (GLT-1) and DsRed (GLAST) puncta in both dorsal horns. As demonstrated in previous studies, propentofylline induced a concomitant reversal of L5 spinal nerve transection-induced expression of glial fibrillary acidic protein (GFAP). The ability of propentofylline to alter glial glutamate transporters highlights the importance of controlling aberrant glial activation in neuropathic pain and suggests one possible mechanism for the anti-allodynic action of this drug. (c) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Purpose:
A significant proportion of patients with prostate cancer with
Gleason score 6 disease at biopsy is LCL161 upgraded to Gleason score 7 or higher after radical prostatectomy, all increasing the risk of adverse outcome. We identified clinical and pathological parameters that predict pathological upgrading in this population.
Materials and Methods: A total of 268 patients with biopsy Gleason score 6 prostate cancer who underwent biopsy and radical prostatectomy between October 1999 and January 2007 were included in the study. Pretreatment characteristics were used to identify predictors of pathological upgrading. Upgrading significance was established by comparing radical prostatectomy pathology between cases that were and were not upgraded.
Results: A total of 134 patients (50%) were upgraded postoperatively to Gleason score 7 or higher. Preoperative prostate specific antigen greater than 5.0 ng/ml (p = 0.036), prostate weight 60 gm or less (p = 0.004) and more cancer volume at biopsy, defined by cancer involving greater than 5% of the biopsy tissue (p = 0.002), greater than 1 biopsy core (p <0.001) or greater than 10% of any core (p = 0.014), were associated with pathological upgrading. Upgraded patients were more likely to have extraprostatic extension and positive surgical margins at radical prostatectomy (p <0.001 and 0.001, respectively).