A functional human IgM response to HIV-1 Env after immunization with NYVAC HIV C

Env-specific IgG and IgM were detected in 25 and 60%, respectively, of volunteers immunized with NYVAC expressing clade C gp120. The serum sample with the highest IgM titre but undetectable IgG neutralized the homologous isolate with a reciprocal IC90 titre of 7.8 in the absence of complement, and 24.4 in the presence of complement (P = 0.0003). These results suggest that vaccine-induced, Env-specific IgM may have antiviral activity and should be subjected to further investigation.     

Role of the AheABC efflux pump in Aeromonas hydrophila intrinsic multidrug resistance

Gene inactivation and complementation experiments showed that the tripartite AheABC efflux pump of Aeromonas hydrophila extruded at least 13 substrates, including nine antibiotics. The use of phenylalanine-arginine-beta-naphthylamide (PAbetaN) revealed an additional system(s) contributing to intrinsic resistance. This is the first analysis of the role of multidrug efflux systems in Aeromonas spp.     

Antioxidants in central nervous system diseases: preclinical promise and translational challenges

Oxidative damage is strongly implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and stroke (brain ischemia/reperfusion injury). The availability of transgenic and toxin-inducible models of these conditions has facilitated the preclinical evaluation of putative antioxidant agents ranging from prototypic natural antioxidants such as vitamin E (alpha-tocopherol) to sophisticated synthetic free radical traps and catalytic oxidants. Literature review shows that antioxidant therapies have enjoyed general success in preclinical studies across disparate animal models, but little benefit in human intervention studies or clinical trials. Recent high-profile failures of vitamin E trials in Parkinson's disease, and nitrone therapies in stroke, have diminished enthusiasm to pursue antioxidant neuroprotectants in the clinic. The translational disappointment of antioxidants likely arises from a combination of factors including failure to understand the drug candidate's mechanism of action in relationship to human disease, and failure to conduct preclinical studies using concentration and time parameters relevant to the clinical setting. This review discusses the rationale for using antioxidants in the prophylaxis or mitigation of human neurodiseases, with a critical discussion regarding ways in which future preclinical studies may be adjusted to offer more predictive value in selecting agents for translation into human trials.