Mechanisms of bone loss in inflammatory arthritis: diagnosis and therapeutic implications

Rheumatoid arthritis represents an excellent model in which to gain insights into the local and systemic effects of joint inflammation on skeletal tissues. Three forms of bone disease have been described in rheumatoid arthritis. These include: focal bone loss affecting the immediate subchondral bone and bone at the joint margins; periarticular osteopenia adjacent to inflamed joints; and generalized osteoporosis involving the axial and appendicular skeleton. Although these three forms of bone loss have several features in common, careful histomorphometric and histopathological analysis of bone tissues from different skeletal sites, as well as the use of urinary and serum biochemical markers of bone remodeling, provide compelling evidence that different mechanisms are involved in their pathogenesis. An understanding of these distinct pathological forms of bone loss has relevance not only with respect to gaining insights into the different pathological mechanisms, but also for developing specific and effective strategies for preventing the different forms of bone loss in rheumatoid arthritis

Bone and cartilage in osteoarthritis: is what's best for one good or bad for the other?

The interest in the relationship between articular cartilage and the structural and functional properties of peri-articular bone relates to the intimate contact that exists between these tissues in joints that are susceptible to the development of osteoarthritis (OA). The demonstration in several animal models that osteoporosis and decreased bone tissue modulus leads to an increased propensity for the development of post-traumatic OA is paradoxical in light of the extensive epidemiological literature indicating that individuals with high systemic bone mass, assessed by bone mineral density, are at increased risk for OA. These observations underscore the need for further studies to define the pathophysiological mechanisms involved in the interaction between subchondral bone and articular cartilage and for applying this information to the development of therapeutic interventions to improve the outcomes in patients with OA

Synthesis and Biological Activity of A Series of Nitrated Cyclopenta-Fused Polycyclic Aromatic Hydrocarbons

In order to test current hypotheses of nitroarene-induced mutagenesis, a series of nitrated cyclopenta-fused isomers of benzanthracene and pyrene (Fig.4) were synthesized and their mutagenic activities toward Salmonella typhimurium were evaluated in the Ames plate incorporation assay. Current theories state that endogenous enzymes present in bacterial and mammalian cells activate nitroarenes via reduction to hydroxylamines which can be converted upon protonation or conjugation to nitrenium ions which are the postulated active chemical species. Thus mutagenic activity should be correlated with both the "ease of reduction" of the compound as well as the stability of the postulated arylnitrenium ion. The theoretical "ease of reduction" of the nitrated polycyclic aromatic hydrocarbons (PAH) in this study was determined by calculating lowest unoccupied molecular orbital (LUMO) energies (Klopman et al., 1984); our results indicate that they should be readily reduced by the nitroreductase enzymes. Huckel molecular orbital calculations indicate that the nitrenium ions should also be exceptionally stable compared to other nitroPAH. Thus these compounds are anticipated to be active mutagens whose activity should parallel the stability of the nitrenium ions. However, while these compounds do produce significant numbers of revertants in the Ames assay, they are not nearly as active as some of the more potent nitroarenes. Reasons for this relative lack of activity are discussed and modifications in the above mentioned theories are proposed.Master of Science in Public Healt

567 ANTI-INFLAMMATORY ACTIVITY OF AN ETHANOLIC CAESALPINIA SAPPAN EXTRACT IN HUMAN CHONDROCYTES IN VITRO

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The role of TNF-receptor family members and other TRAF-dependent receptors in bone resorption

The contribution of osteoclasts to the process of bone loss in inflammatory arthritis has recently been demonstrated. Studies in osteoclast biology have led to the identification of factors responsible for the differentiation and activation of osteoclasts, the most important of which is the receptor activator of NF-κB ligand/osteoclast differentiation factor (RANKL/ODF), a tumor necrosis factor (TNF)-like protein. The RANKL/ODF receptor, receptor activator of NF-κB (RANK), is a TNF-receptor family member present on both osteoclast precursors and mature osteoclasts. Like other TNF-family receptors and the IL-1 receptor, RANK mediates its signal transduction via TNF receptor-associated factor (TRAF) proteins, suggesting that the signaling pathways activated by RANK and other inflammatory cytokines involved in osteoclast differentiation and activation are interconnected

Confirmation of Parity Violation in the Gamma Decay of 180Hfm^{180}Hf^{m}

This paper reports measurements using the technique of On Line Nuclear Orientation (OLNO) which reexamine the gamma decay of isomeric $^{\rm 180}$Hf$^{\rm m}$ and specifically the 501 keV 8$^{\rm -}$ -- 6$^{\rm +}$ transition. The irregular admixture of E2 to M2/E3 multipolarity in this transition, deduced from the forward-backward asymmetry of its angular distribution, has for decades stood as the prime evidence for parity mixing in nuclear states. The experiment, based on ion implantation of the newly developed mass-separated $^{\rm 180}$Hf$^{\rm m}$ beam at ISOLDE, CERN into an iron foil maintained at millikelvin temperatures, produces higher degrees of polarization than were achieved in previous studies of this system. The value found for the E2/M2 mixing ratio, $\epsilon$ = -0.0324(16)(17), is in close agreement with the previous published average value $\epsilon$ = - 0.030(2), in full confirmation of the presence of the irregular E2 admixture in the 501 keV transition. The temperature dependence of the forward-backward asymmetry has been measured over a more extended range of nuclear polarization than previously possible, giving further evidence for parity mixing of the 8$^{\rm -}$ and 8$^{\rm +}$ levels and the deduced E2/M2 mixing ratio.Comment: 28 pages, 9 figures, accepted for publication in Physical Review