Inflammatory bone diseases, including rheumatoid arthritis, periodontitis and peri-implantitis, are associated not only with the production of inflammatory cytokines but also with local oxidative status, which is defined by intracellular reactive oxygen species (ROS). Osteoclast differentiation has been reported to be related to increased intracellular ROS levels in osteoclast lineage cells. Sudachitin, which is a polymethoxyflavone derived from Citrus sudachi, possesses antioxidant properties and regulates various functions in mammalian cells. However, the effects of sudachitin on inflammatory bone destruction and osteoclastogenesis remain unknown. In calvaria inflamed by a local lipopolysaccharide (LPS) injection, inflammation-induced bone destruction and the accompanying elevated expression of osteoclastogenesis-related genes were reduced by the co-administration of sudachitin and LPS. Moreover, sudachitin inhibited osteoclast formation in cultures of isolated osteoblasts and osteoclast precursors. However, sudachitin rather increased the expression of receptor activator of NF-κB ligand (RANKL), which is an important molecule triggering osteoclast differentiation, and the mRNA ratio of RANKL/osteoprotegerin that is a decoy receptor for RANKL, in the isolated osteoblasts, suggesting the presence of additional target cells. When osteoclast formation was induced from osteoclast precursors derived from bone marrow cells in the presence of soluble RANKL and macrophage colony-stimulating factor, sudachitin inhibited osteoclastogenesis without influencing cell viability. Consistently, the expression of osteoclast differentiation-related molecules including c-fos, NFATc1, cathepsin K and osteoclast fusion proteins such as DC-STAMP and Atp6v0d2 was reduced by sudachitin. In addition, sudachitin decreased activation of MAPKs such as Erk and JNK and the ROS production evoked by RANKL in osteoclast lineage cells. Our findings suggest that sudachitin is a useful agent for the treatment of anti-inflammatory bone destruction.

Background: Global interferon-␤ deficiency causes osteoporosis. Lack of interferon-␤ production by osteoclast precursors is considered to induce excess osteoclastogenesis. Results: Isolated osteocytes express higher amount of interferon-␤ mRNA than osteoclast precursors and inhibit osteoclastogenesis partially in interferon-␤-dependent manner. Conclusion: Osteocytes produce interferon-␤ as an inhibitor of osteoclastogenesis. Significance: Osteocytic interferon-␤ might be involved in the regulation of bone homeostasis.

Anomalous position of the gallbladder is relatively rare and has been reported only in isolated case reports. We tried to determine its ultrasound (US) findings on the basis of 18 such patients. In the left-side gallbladder group (nine patients), the gallbladder was imaged as an oval cystic mass in front of the pancreas. In all patients, the narrow neck of the gallbladder was clearly detected by US in the usual location before the main portal vein. Four of nine patients had small gallbladder stones. The retrohepatic gallbladder group (four patients) showed marked atrophy of the right lobe of the liver. Two patients had multiple gallstones in the bile ducts of the right lobe. All patients in the suprahepatic retrohepatic gallbladder group (four patients) were cirrhotic, and the anterior segment of the right lobe was markedly atrophied. In the intercostal scan, the gallbladder mimicked a perihepatic fluid. In the floating gallbladder group (one patient), the gallbladder was imaged as a cystic mass in the anterior abdominal wall. Surgical intervention showed a severely inflamed gallbladder, with small stones adhered into the anterior abdominal wall and partially ruptured. Knowledge of the wide range of US findings of malposition of the gallbladder helps in avoiding misdiagnosis.

No abstract

Our data indicate that FNH occurs slightly more frequently in men than in women in Japan. It occurs also at any age in both sexes, but the mean lesion size was smaller in our series than in the previous reports. Metabolic disease was seen only in male FNH patients. A direct communication between the FNH lesion and the hepatic vein is diagnostically worth noting.