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Curcumin exhibits anti-inflammatory and antitumor activity and is being tested in clinical trials as a chemopreventive agent for colon cancer. Curcumin's chemopreventive activity was tested in a transgenic mouse model of lung cancer that expresses the human Ki-ras(G12C) allele in a doxycycline (DOX) inducible and lung-specific manner. The effects of curcumin were compared with the lung tumor promoter, butylated hydroxytoluene (BHT), and the lung cancer chemopreventive agent, sulindac. Treatment of DOX-induced mice with dietary curcumin increased tumor multiplicity (36.3 +/- 0.9 versus 24.3 +/- 0.2) and progression to later stage lesions, results which were similar to animals that were co-treated with DOX/BHT. Microscopic examination showed that the percentage of lung lesions that were adenomas and adenocarcinomas increased to 66% in DOX/BHT, 66% in DOX/curcumin and 49% in DOX/BHT/curcumin-treated groups relative to DOX only treated mice (19%). Immunohistochemical analysis also showed increased evidence of inflammation in DOX/BHT, DOX/curcumin and DOX/BHT/curcumin mice relative to DOX only treated mice. In contrast, co-treatment of DOX/BHT mice with 200 p.p.m. [DOSAGE ERROR CORRECTED] of sulindac inhibited the progression of lung lesions and reduced the inflammation. Lung tissue from DOX/curcumin-treated mice demonstrated a significant increase (33%; P = 0.01) in oxidative damage, as assessed by the levels of carbonyl protein formation, relative to DOX-treated control mice after 1 week on the curcumin diet. These results suggest that curcumin may exhibit organ-specific effects to enhance reactive oxygen species formation in the damaged lung epithelium of smokers and ex-smokers. Ongoing clinical trials thus may need to exclude smokers and ex-smokers in chemopreventive trials of curcumin.

Serum and synovial tissue from 26 patients with rheumatoid arthritis (RA) (according to the diagnostic criteria of the American Rheumatism Association) and 26 patients with osteoarthritis (OA) were examined. Among the RA group, the female to male ratio was 4.2:1, and the age range was 44-82 yr with a mean of 64.0 yr; joints from which synovium was sampled were hip (n = 12), knee (n = 9), ankle (n = 3) and shoulder (n = 2). The duration of rheumatoid disease ranged from 6 to 24 yr with a mean of 13.9 yr. Among the OA group, the female to male ratio was 2.25:1, and the age range was 51-88 yr with a mean of 68.2 yr; joints from which synovium was sampled were hip (n = 18) and knee (n = 8). Twenty-one patients from the RA group and 20 patients from the OA group had evidence of previous parvovirus B19 infection (serum anti-B19 IgG), and all patients from both groups were serum anti-B19 IgM negative. Synovial sections from all 52 patients were stained with mouse monoclonal antibodies, 3H8 (to B19 capsid proteins) and alpha-P (to blood group P antigen). All tissue sections examined were found to be negative for both B19 capsid proteins and blood group P antigen. Using a nested polymerase chain reaction (PCR) assay, all patients were negative for serum B19 DNA. However, B19 DNA was demonstrated in the synovium of 10 of 26 RA patients and 9 of 26 OA patients; uncorrected chi 2 value = 0.08; degrees of freedom = 1; P = 0.77. All 19 patients testing positive for synovial B19 DNA had evidence of prior exposure to B19 infection (serum anti-B19 IgG). In conclusion, although there is published evidence of chronic rheumatoid-like arthropathy following acute parvovirus B19 infection, our findings do not support the involvement of B19 in the aetiopathogenesis of RA.

There is little known about the effect of both reduced weight bearing and exposure to radiation during spaceflight on the mechanically-sensitive cartilage lining the knee joint. In this study, we characterized cartilage damage in rat knees after periods of reduced weight bearing with/without exposure to solar-flare-relevant radiation, then cartilage recovery after return to weight bearing. Male Sprague Dawley rats (n = 120) were either hindlimb unloaded (HLU) via tail suspension or remained weight bearing in cages (GROUND). On day 5, half of the HLU and GROUND rats were 1 Gy total-body X-ray irradiated during HLU, and half were sham irradiated (SHAM), yielding 4 groups: GROUND-SHAM; GROUND-IR; HLU-SHAM; and HLU-IR. Hindlimbs were collected from half of each group of rats on day 13. The remaining rats were then removed from HLU or remained weight bearing, and hindlimbs from these rats were collected on day 62. On day 13, glycosaminoglycan (GAG) content in cartilage lining the tibial plateau and femoral condyles of HLU rats was lower than that of the GROUND animals. Likewise, on day 13, immunoreactivity of the collagen type II-degrading matrix metalloproteinase-13 (MMP-13) and of a resultant metalloproteinase-generated neoepitope VDIPEN was increased in all groups versus GROUND-SHAM. Clustering of chondrocytes indicating cartilage damage was present in all HLU and IR groups versus GROUND-SHAM on day 13. On day 62, after 49 days of reloading, the loss of GAG content was attenuated in the HLU-SHAM and HLU-IR groups, and the increased VDIPEN staining in all treatment groups was attenuated. However, the increased chondrocyte clustering remained in all treatment groups on day 62. MMP-13 activity also remained elevated in the GROUND-IR and HLU-IR groups. Increased T2 relaxation times, measured on day 62 using 7T MRI, were greater in GROUND-IR and HLU-IR knees, indicating persistent cartilage damage in the irradiated groups. Both HLU and total-body irradiation resulted in acute degenerative and pre-arthritic changes in the knee articular cartilage of rats. A return to normal weight bearing resulted in some recovery from cartilage degradation. However, radiation delivered as both a single challenge and when combined with HLU resulted in chronic cartilage damage. These findings suggest that radiation exposure during spaceflight leads to and/or impairs recovery of cartilage upon return to reloading, generating long-term joint problems for astronauts.

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