The superoxide-producing NADPH oxidase consists of membrane-associated cytochrome b₅₅₈ (gp 91-phox and p 22-phox) and cytosolic components. We purified a 260 kDa cytosolic complex which was essential for the activation of NADPH oxidase. This complex was composed of p 47-phox, p 67-phox and a novel p 40-phox. We examined the translocation of p 40-phox in a cell-free system using membrane and purified p 47-phox/p 67-phox/p 40-phox complex. p 40-phox was translocated to the membrane by arachidonic acid in a dose-dependent manner. The translocation pattern of p 40-phux was similar to those of p 47-phox and p 67-phox. Immunoprecipitation assay revealed that p 40-phox was dissociated from p 47-phox and p 67-phox during activation. Furthermore, a synthetic peptide corresponding to carboxyl-terminus of p 40-phox inhibited the activation of NADPH oxidase and translocation of p 40-phox, p 47-phox and p 67-phox. These observations suggest that p 40-phox may play a role in the activation of NADPH oxidase through interacting with p 47-phox and p 67-phox via its carboxyl-terminus.

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Glucocorticoids are one of the most commonly prescribed classes of medication in treatment of various connective tissue diseases. A wide rage of biologic effects by glucocorticoids are mediated through binding of glucocorticoids to the receptors which have been characterized in detail as one of the ligand-activated trans-acting factors in eukaryotes. Despite promising benefits of glucocorticoids to suppress inflammatory processes in clinical uses, serious side effects of glucocorticoids, especially in a long term use, have been known. Development of osteoporosis, that is one of the major complications during high doses of glucocorticoid therapy, however, has possibly controlled by the use of bisphosphonates. In this review, we discussed recent advances of the glucocorticoid therapy in connective tissue diseases.

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Dipeptidyl peptidase IV (DP IV, CD26) is a serine exopeptidase which selectively cleaves the penultimate proline residue of polypeptides. This enzyme is also expressed on activated T cells. To assess the relevance of DP IV in immunological disorders, we evaluated the pharmacological effects of specific DP IV inhibitors. A competitive inhibitor of DP IV, Lys (Z (NO₂) ) -thiazolidide suppressed mitogen-induced and antigen-induced proliferation of T cells. In vivo pharmacological effects were assessed by using alkyldiamine-and collagen-induced arthritis models, which share several pathological features with rheumatoid arthritis. A competitive inhibitor of DP IV (Lys (Z (NO₂) ) -thiazolidide), an irreversible inhibitor (Ala-Pro-nitrobenzoyl hydroxylamime), and a transition state substrate analog of DP IV (Ala-boroPro) suppressed alkyldiamine-induced arthritis. Ala-boroPro also suppressed collagen-induced arthritis. These results suggest that DP IV may play a role in the pathogenesis of certain inflammatory diseases through immune regulation.

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Aly (alymphoplasia) /aly mutant (ALY) mice were established as an animal model for immunodeficiency bearing an autosomal recessive gene with lack of lymph nodes and immunoglobulin especially IgA. Recently, Tsubata reported ALY mice exhibited autoimmune multiple exocrinopathy that strikingly resembles human Sjoegren's syndrome. Since the ALY mice lack conventional B cells, they had relatively abundant CD5⁺B cells producing IL-10 constitutively in lymphoid organs. IL-10 is a soluble protein produced by helper T (Th) cells, macrophages (Mφ), and B cells, that exhibits a wide array of both immunosuppressive and immunostimulatory properites.
In order to explore the pathological significance of IL-10 in autoimmune exocrinopathy, ALY mice were administrated either anti-IL-10 or isotype control antibody continuously from 8 to 24 weeks. At 24 weeks, we sacrificed them and subjected the exocrine organs to pathological examinations.
Inflammatory changes in lacrimal and salivary glands were significantly reduced by anti-IL-10 antibody treatment in ALY mutant mice. These results suggest that IL-10 might be involve the pathophysiology in multiple autoimmune exocrinopathy in ALY mutant mice.

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The effect of Sairei-to on radiation induced stomatitis was studied in vitro using human oral epithelial cells and compared with that of Oren-to. Sairei-to (30-300 μg/ml) suppressed both the decrease in adherent cell number after irradiation at 8 Gy and the decrease in cell proliferation after irradiation at 4 Gy in a dose-dependent manner. Without irradiation, however, the drug did not affect the number of adherent cells or the ability of cell proliferation. Although Oren-to (10-100 μg/ml) also suppressed the decrease in adherent cell number after irradiation in a dose-dependent manner, cell proliferative ability was suppressed (100 μg/ml) irrespective of the presence or absence of irradiation. It is suggested that Sairei-to suppresses radiation induced injuries in oral mucosal cells without affecting normal cell function.

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Administation of non-steroidal anti-inflammatory drugs (NSAIDS) can cause adverse reactions, particularly gastric problems. Methods to ameliorate these adverse reactions have been suggested, such as use of selective cyclo-oxygenase-2 (COX-2) inhibitors, use of NSAID prodrugs, and development of agents with inflammatory tissue selectivity.
The present study of zaltoprofen, a selective COX-2, inhibitor investigated the drug level in synovial fluid as well as its efficasy and safety.
We measured the zaitoprofen concentration in the blood and synovial fluid of patients with osteoarthritis of the knee at two and four weeks after drug administration. The blood levels at and 4 weeks were 3.43 and 2.69 μg/m1, respectively, while the synovial fluid levels were 1.0 and 1.0μg/ml, respectively, The percent transfer to synovial fluid was 29.1% and 35.7% respectively.
The final general improvement rate was 40%, and neither adverse reactions nor abnormal laboratory test results were detected in any patient.

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