Old-growth Policy

Most federal legislation and policies (e.g., the Wilderness Act, Endangered Species Act, National Forest Management Act) fail to speak directly to the need for old-growth protection, recruitment, and restoration on federal lands. Various policy and attitudinal barriers must be changed to move beyond the current situation. For example, in order to achieve the goal of healthy old growth in frequent-fire forests, the public must be educated regarding the evolutionary nature of these ecosystems and persuaded that collaborative action rather than preservation and litigation is the best course for the future of these forests. Land managers and policy makers must be encouraged to look beyond the single-species management paradigm toward managing natural processes, such as fire, so that ecosystems fall within the natural range of variability. They must also see that, given their recent evidence of catastrophic fires, management must take place outside the wildland—urban interface in order to protect old-growth forest attributes and human infrastructure. This means that, in some wilderness areas, management may be required. Land managers, researchers, and policy makers will also have to agree on a definition of old growth in frequent-fire landscapes; simply adopting a definition from the mesic Pacific Northwest will not work. Moreover, the culture within the federal agencies needs revamping to allow for more innovation, especially in terms of tree thinning and wildland fire use. Funding for comprehensive restoration treatments needs to be increased, and monitoring of the Healthy Forest Initiative and Healthy Forest Restoration Act must be undertaken

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes