Discovery of new pharmacological agents is needed to control the progression of osteoarthritis (OA) characterized by progressive joint cartilage damage. Human OA chondrocyte cultures (OAC) were either applied to S-Allyl cysteine (SAC), a sulfur-containing amino acid derivative, or colchicine, an ancient anti-inflammatory therapeutic, for 24 hours. SAC or colchicine did not change viability at 1 nM-10 µM but inhibited p-JNK/pan-JNK. While SAC seems to be more effective, both agents inhibited reactive oxygen species (ROS), 3-nitrotyrosine (3-NT), lipid-hydroperoxides (LPO), advanced lipoxidation end-products (ALEs as 4-hydroxy-2-nonenal, HNE) and advanced glycation end-products (AGEs), and increased glutathione-peroxidase (GPx) and type-II-collagen (COL2). IL-1β, IL-6 and osteopontin (OPN) were more strongly inhibited by SAC than in colchicine. In contrast, TNF-α was inhibited only by SAC, and COX2 only by colchicine. Casp-1/ICE, GM-CSF, receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLR4) were inhibited by both agents, but bone morphogenetic protein 7 (BMP7) was partially inhibited by SAC while induced by colchicine. The nuclear factor erythroid 2-related factor 2 (Nrf2) was induced by SAC; in contrast it was inhibited by colchicine. Although exerting opposite effects on TNF-α, COX2, BMP7 and Nrf2, SAC and colchicine exhibit anti-osteoarthritic properties in OAC by modulating redox sensitive inflammatory signaling.
12, 24, and 60 months post RT. Parameters analyzed included perfusion defects, wall thickening (WT), wall motion abnormalities (WM) and dyssynchronous contractions (DS). Analyses were done using spearman R correlation analysis, Mann-Whitney U test and Dunnett's multiple comparisons test. Results: There were no significant differences seen in baseline characteristics (age, pathology, hormone status, technique, use of adjuvant chemo, or cardiac risk factors) between left-sided (n Z 102) and rightsided (n Z 79) RT patients. As expected, those receiving RT to left side had significantly greater mean cardiac dose (4.3 vs. 0.9Gy; p<0.001) and Dmax (45.4 vs. 6.3Gy; p<0.001). Radiation to the left breast did not significantly alter end diastolic volume, end systolic volume or ejection fraction at any timepoint. There was a significant increase in total perfusion defects seen post RT compared to baseline in left sided patients (4.1% vs. 2.8% p Z 0.042) which was not seen in right sided patients. The perfusion defect returned to baseline by 1-year post RT, and remains normal at 2-and 5-years post RT. The global scoring of myocardial perfusion as measured by summed rest score (SRS) also showed a significant increase by 1.35 pts (4.1 vs. 2.8; p Z 0.006) post RT for left sided patients. These changes were significantly correlated with max cardiac dose (p Z 0.03). No localized perfusion defect, DS, WT, WM changes were seen. No adverse cardiac outcomes were reported. Conclusion: Patients receiving left breast RT did not show differ in standard measures of cardiac function such as ESV, EDV, and EF at any timepoint. There were mild perfusion defects seen post-RT, evidenced by worsened global non-gated SRS and total perfusion defect post RT in left sided patients. Worsened non-gated SRS was correlated with mean cardiac dose. Perfusion deficits normalized by 1-year post RT, and remained unchanged out to 5 years, suggesting a potential for cardiac remodeling post-RT.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.