The activity of nonsteroidal antiinflammatory drugs (NSAIDs) in rheumatoid arthritis is not only due to the inhibition of the production of prostaglandins, which can even have beneficial immunosuppressive effects in chronic inflammatory processes. Since we speculated that these drugs could also act by protecting endogenous proteins against denaturation, we evaluated their effect on heat-induced denaturation human serum albumin (HSA) in comparison with several fatty acids which are known to be potent stabilizers of this protein. By the Mizushimas assay and a recently developed HPLC assay, we observed that NSAIDs were slightly less active [EC50 to approximately 10(-5)-10(-4) M] than FA and that the HPLC method was less sensitive but more selective than the turbidimetric assay, i.e. it was capable of distinguishing true antiaggregant agents like FA and NSAIDs from substances capable of inhibiting the precipitation of denatured protein aggregates. In conclusion, this survey could be useful for the development of more effective agents in protein condensation diseases like rheumatic disorders, cataract and Alzheimers disease.

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Prostaglandin D synthetase (PGD‐S; prostaglandin‐H2 D‐isomerase, EC 5,3,99,2), a 30 kDa glycoprotein also known as β‐trace protein that catalyzes the formation of prostaglandin D2 (PGD2) from PGH2, was purified to apparent homogeneity from human cerebrospinal fluid (CSF) using a two‐step procedure involving HPLC on a Vydac C8 reversed‐phase column and high performance electrophoresis chromatography (HPEC) using a 10% T SDS‐polyacrylamide gel. The purity of PGD‐S isolated from CSF was confirmed by silver stained SDS‐polyacrylamide gel and direct protein microsequencing (NH2‐APEAQVSVQPNFQ). A highly specific polyclonal antibody was prepared against this protein for immunoassay development. Using an ELISA, it was found that the concentration of PGD‐S in CSF did not alter significantly in different pathological conditions of the central nervous system (CNS). These include dementia (n=9), hydrocephalus (n=4), neuropathy (n=11), optic neuritis (n=4), multiple sclerosis (n=11), and demyelinating syndrome (n=11), when compared to normal individuals (n=12); however, the level of PGD‐S in the CSF obtained from patients with brain tumor (n=11), was reduced by as much as 2‐fold when compared to control samples (n=12) illustrating PGD‐S is a potentially useful marker for brain tumor.

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