Local delivery of RA may circumvent
adverse side effects, but may simultaneously reduce the therapeutic benefits of the therapy. Here, we investigated whether local or systemic RA treatment differentially affected pro-inflammatory cytokine expression early after rat SO. Pro-inflammatory cytokines GSK621 in vitro IL-1 beta, IL-6 and TNF alpha were investigated at 6 h after moderate contusion injury of the thoracic (T9) spinal cord, when mRNA levels are known to peak. Rats were either treated with intrathecal RA (0, 2.5, 10, or 100 ng) or received an intraperitoneal injection of RA (15 mg/kg bodyweight). Surprisingly intrathecal RA up to amounts of 100 ng did not attenuate SCI-induced increases in gene-expression of pro-inflammatory cytokines. In contrast, intraperitoneal RA rendered a 60%, 35% and 58% reduction of IL-1 beta, IL-6 and TNF alpha mRNA levels, respectively. Although local doses higher than 100 ng RA may reduce pro-inflammatory cytokine gene-expression, such doses precipitate and possibly increase risks of adverse side effects. We conclude that in contrast to systemic delivery, intrathecal administration of RA up to doses of 100 ng is ineffective in reducing early pro-inflammatory cytokine gene-expression.
Selleck BMS202 Future studies are required to investigate the effects of single intraperitoneal RA treatment on long-term SCI outcome. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Critical limb ischemia (CLI) continues to form a substantial burden on Western healthcare. Many patients still face amputation as a last treatment option. Autologous bone marrow (BM)-derived cell administration has emerged
as a potential new treatment, but proof for sustainable clinical effects of BM-derived cell therapy in CLI is still lacking. The JUVENTAS (reJUVenating www.selleck.cn/products/jib-04.html ENdothelial progenitor cells via Transcutaneous intra-Arterial Supplementation) trial is the first randomized, placebo-controlled, double-blinded clinical trial on repeated intra-arterial BM mononuclear cell (MNC) infusion in 110 to 160 CLI patients, designed to provide definite proof for the efficacy of stem cell therapy. Primary outcome is the incidence of major amputation at 6 months. Inclusion of patients is well underway. If BM-MNC cells therapy is beneficial, it could become a novel treatment to prevent amputation in patients with CM. (J Vasc Surg 2010;51:1564-8.)”
“Recent brain functional magnetic resonance imaging (fMRI) studies have shown that chronic back pain (CBP) alters brain dynamics beyond the feeling of pain. In particular, the response of the brain default mode network (DMN) during an attention task was found abnormal. In the present work similar alterations are demonstrated for spontaneous resting patterns of fMRI brain activity over a population of CBP patients (n = 12, 29-67 years old, mean = 51.2).