Comparisons in the present data examined CHD outcomes limited to those requiring hospitalization

We also found similar associations for hard CHD events. What are the potential clinical and research implications of these findings? Clinicians should use the FRS with caution in older adults, as it underestimates the absolute CHD risk by 51% in women and 8% in men and does not discriminate effectively between those who will have CHD events and those who will not. Mandating VTE prophylaxis increases the risk of prolonged wound drainage, extended hospital stay, and surgical site infection.In the first phase, which developed up to 6h, edema is of low intensity, while in the second phase, edema is more pronounced and peaks at 72h after l-carrageenan injection. Another important feature of this model is that, as the inflammation progresses, an increasing number of T cells infiltrate the draining lymph nodes of the l-carrageenan-injected paws thereby this model is also reminiscent of a typical type III immune reaction. In this reaction regional lymph nodes are the source of effector T cells that are postulated to extravasate at the site of antigen challenge and in turn, recruit and activate a variety of nonspecific inflammatory cells. Perthamide C significantly inhibited the myeloperoxidase activity, a marker of neutrophil infiltration in tissue, in the early phase of the inflammatory reaction. This effect was coupled to a reduced expression of the endothelial nitric oxide synthase while COX-1, iNOS and COX-2 expression were unaffected. Thus, perthamide C inhibitory effect in vivo is fast on onset and its action is possibly linked to modulation of eNOSderived NO. This feature well fit with the finding that, in this model, the increase in vascular permeability in the early phase is dependent upon eNOS-derived NO. Most likely the modulation of perthamide C operated on eNOS is linked to its ability to bind hsp90. Indeed, hsp90 is instrumental for eNOS activation as elegantly demonstrated in the paper. Perthamide C reduced up to 96 h the expression of both NOS isoforms i.e. eNOS and iNOS without affecting COXs expression i.e. COX-1 and COX-2. This peculiar selectivity toward the two enzymes deputed to produce NO lead us to investigate on a possible action of perthamide C on lymphocytes infiltration and activation that is typical of the second phase of this animal model. Indeed, it is widely accepted that NO plays an important role in immunomodulation and neutrophil trafficking. In order to be consistent, we approached this issue by studying the proliferation of PLN lymphocytes harvested from mice receiving in vivo perthamide C. Lymphocytes challenged in vitro with Con A displayed a reduced proliferation demonstrating that the effect of perthamide C in vivo involves also these cellular population. This result suggested a potential immuno-suppressor activity for perthamide C. In order to further investigate this effect a study was carried out in vitro on lymphocytes recovered from naive mice.