In persons at high risk for diabetes, insulin at the dosage used in this study does not delay or prevent type 1 diabetes.

Prostaglandins (PGs) are lipid molecules that profoundly affect cellular processes including inflammation and immune response. Pathways contributing to PG output are highly regulated in antigen-presenting cells such as macrophages and monocytes, which produce large quantities of these molecules upon activation. In this report, we demonstrate aberrant constitutive expression of the normally inducible cyclooxygenase PG synthase 2 (PGS 2 / COX-2) in nonactivated monocytes of humans with insulin-dependent diabetes mellitus (IDDM) and those with islet autoantibodies at increased risk of developing this disease. Constitutive PGS 2 appears to characterize a high risk for diabetes as it correlates with and predicts a low first-phase insulin response in autoantibody-positive subjects. Abnormal PGS 2 expression in at-risk subjects affected immune response in vitro, as the presence of a specific PGS 2 inhibitor, NS398, significantly increased IL-2 receptor α-chain (CD25) expression on phytohemagglutinin-stimulated T cells. The effect of PGS 2 on CD25 expression was most profound in subjects expressing both DR04 and DQβ0302 high-risk alleles, suggesting that this cyclooxygenase interacts with diabetes-associated MHC class II antigens to limit T-cell activation. These results indicate that constitutive PGS 2 expression in monocytes defines an antigen-presenting cell defect affecting immune response, and that this expression is a novel cell-associated risk marker for IDDM.

Flavor and color concentrates were prepared by a vacuum distillation process from cold pressed Valencia and midseason orange oils and were analyzed quantitatively by gas chromatography. Twentyfive major and minor constituents were identified by mass spectrometry. The influence of the concentration process on oxygenated flavor compounds, primarily aldehydes and alcohols, was evaluated. Aldehydes and color values were determined by chemical and spectrophotometric methods. When compared with midseason orange oils, 25-35s higher concentration of oxygenated flavor compounds and of total aldehydes were found in Valencia orange oils. Midseason oils had 20-30s higher color values when compared with Valencia oils. Cold pressed oils concentrated to 25-fold had an increase in color value of 20-fold, while the concentration of oxygenated flavor compounds increased about 10 times.

These findings suggest that high level monocyte PGS2 expression, although subject to fluctuation, is present in at-risk subjects at an early age and is maintained during progression to and after type 1 diabetes onset.