Pharmacological modulation of the endocannabinoid system in a viral model of multiple sclerosis

Theiler’s virus infection of the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis (MS). Cannabinoids have been shown to exert beneficial effects on animal models of MS and evidence suggests that the endocannabinoid system plays a role in the tonic control of spasticity. In this study we show that OMDM1 [(R)-N-oleoyl-(1¢-hydroxybenzyl)-2¢-ethanolamine] and OMDM2 [(S)-N-oleoyl-(1¢-hydroxybenzyl)-2¢- ethanolamine], two selective inhibitors of the putative endocannabinoid transporter and hence of endocannabinoid inactivation, provide an effective therapy for Theiler murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Treatment of TMEV-infected mice with OMDM1 and OMDM2 enhanced anandamide levels in the spinal cord and ameliorated motor symptoms. This was associated with a down-regulation of inflammatory responses in the spinal cord. In addition we show that OMDM1 and OMDM2 down-regulate macrophage function by (i) decreasing the surface expression of major histocompatibility complex (MHC) class II molecules, (ii) inhibiting nitric oxide synthase-2 (NOS-2) expression and (iii) reducing the production of the pro-inflammatory cytokines interleukin-1beta (IL-1b) and interleukin-12 (IL-12p40). Taken together, these results point to the manipulation of the endocannabinoid system as a possible strategy to develop futureMS therapeutic drugs

Clinical studies and anti-inflammatory mechanisms of treatments

In this exciting era, we are coming closer and closer to bringing an anti‐inflammatory therapy to the clinic for the purpose of seizure prevention, modification, and/or suppression. At present, it is unclear what this approach might entail, and what form it will take. Irrespective of the therapy that ultimately reaches the clinic, there will be some commonalities with regard to clinical trials. A number of animal models have now been used to identify inflammation as a major underlying mechanism of both chronic seizures and the epileptogenic process. These models have demonstrated that specific anti‐inflammatory treatments can be effective at both suppressing chronic seizures and interfering with the process of epileptogenesis. Some of these have already been evaluated in early phase clinical trials. It can be expected that there will soon be more clinical trials of both “conventional, broad spectrum” anti‐inflammatory agents and novel new approaches to utilizing specific anti‐inflammatory therapies with drugs or other therapeutic interventions. A summary of some of those approaches appears below, as well as a discussion of the issues facing clinical trials in this new domain

Bridging the Valley: Recruiting and Retaining STEM Majors

In the face of declining STEM enrollments, four neighboring institutions in Virginia’s Shenandoah Valley came together to address the issue of STEM retention on their campuses with support from the National Science Foundation. James Madison University (JMU), Blue Ridge Community College (BRCC), Eastern Mennonite University (EMU), and Bridgewater College (BC) undertook a six-year project, with funding from National Science Foundation’s STEM Talent Expansion Program (STEP) grant (DUE-0756838), to enhance student retention in STEM on each campus. The partnership, dubbed Bridging the Valley (BTV), developed a set of interventions designed to actively improve student outcomes. A summer bridge workshop (SBW) and collaborative learning communities (CLC), implemented during the academic year, were two of the most substantive interventions included in the BTV program

Bordetella avium antibiotic resistance, novel enrichment culture, and antigenic characterization

Bordetella avium continues to be an economic issue in the turkey industry as the causative agent of bordetellosis, which often leads to serious secondary infections. This study presents a broad characterization of the antibiotic resistance patterns in this diverse collection of B. avium strains collected over the past thirty years. In addition, the plasmid basis for the antibiotic resistance was characterized. The antibiotic resistance pattern allowed the development of a novel enrichment culture method that was subsequently employed to gather new isolates from diseased turkeys and a healthy sawhet owl. While a healthy turkey flock was shown to seroconvert by four weeks-of-age, attempts to culture B. avium from healthy turkey poults were unsuccessful. Western blot of B. avium strains using pooled serum from diseased and healthy commercial turkey flocks revealed both antigenic similarities and differences between strains. In sum, the work documents the continued exposure of commercial turkey flocks to B. avium and the need for development of an effective, inexpensive vaccine to control spread of the disease. © 2012 Elsevier B.V.NIH R-15-AI057382-03Peer Reviewe