These findings suggest the value of measuring health status in diabetes mellitus patients, because it is able to comprehensively evaluate the patient's health condition, and add another dimension to the subjective symptoms and laboratory data.

Infiltration of LCs is orchestrated by CCR6. Further, LCs residing in the lesional epithelia may be a mature phenotype. Moreover, infiltration of T cells in OLP could be mediated by signaling pathways through CXCR3 and CCR5.

Hyperglycemia-induced embryonic malformations may be due to an increase in radical formation and depletion of intracellular glutathione (GSH) in embryonic tissues. In the past, we have investigated the role of the glutathione-dependent antioxidant system and GSH on diabetes-related embryonic malformations. Embryos from streptozotocin-induced diabetic rats on gestational day 11 showed a significantly higher frequency of embryonic malformations (neural lesions 21.5 vs. 2.8%, P<0.001; nonneural lesions 47.4 vs. 6.4%, P<0.001) and growth retardation than those of normal mothers. The formation of intracellular reactive oxygen species (ROS), estimated by flow cytometry, was increased in isolated embryonic cells of diabetic rats on gestational day 11. The concentration of intracellular GSH in embryonic tissues of diabetic pregnant rats on day 11 was significantly lower than that of normal rats. The activity of y-glutamylcysteine synthetase (gamma-GCS), the rate-limiting GSH synthesizing enzyme, in embryos of diabetic rats was significantly low, associated with reduced expression of gamma-GCS mRNA. Administration of buthionine sulfoxamine (BSO), a specific inhibitor of gamma-GCS, to diabetic rats during the period of maximal teratogenic susceptibility (days 6-11 of gestation) reduced GSH by 46.7% and increased the frequency of neural lesions (62.1 vs. 21.5%, P<0.01) and nonneural lesions (79.3 vs. 47.4%, P<0.01). Administration of GSH ester to diabetic rats restored GSH concentration in the embryos and reduced the formation of ROS, leading to normalization of neural lesions (1.9 vs. 21.5%) and improvement in nonneural lesions (26.7 vs. 47.4%) and growth retardation. Administration of insulin in another group of pregnant rats during the same period resulted in complete normalization of neural lesions (4.3 vs. 21.5%), nonneural lesions (4.3 vs. 47.4%), and growth retardation with the restoration of GSH contents. Our results indicate that GSH depletion and impaired responsiveness of GSH-synthesizing enzyme to oxidative stress during organogenesis may have important roles in the development of embryonic malformations in diabetes.

Synovitis, which is characterized by the infiltration of inflammatory cells, often accompanies progression of temporomandibular joint disorder (TMD) symptoms. Because IL-1β is elevated in synovial fluids obtained from TMDs, we hypothesized that IL-1β-responsive genes in synoviocytes may help identify the putative genes associated with synovitis. Using microarray analysis, we found that monocyte chemoattractant protein-1 (MCP-1) mRNA levels were elevated in IL-1β-stimulated synoviocytes. MCP-1 is a member of the chemokine superfamily. The production of MCP-1 was increased in synoviocytes treated with IL-1β. When IL-1β was injected into the cavities of rat TMJs, inflammatory cells and MCP-1-positive cells were detected in the synovial tissues. Furthermore, MCP-1 levels were higher in synovial fluids from individuals with pain compared with those without pain. Inhibitors of MAP-kinases and NF-κB reduced IL-1β-induced MCP-1 production. These results suggest that MCP-1 stimulated by IL-1β is one of the factors associated with the inflammatory progression of TMDs.