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In order to objectively compare the efficacy and the safety of Bredinin for longterm treatment of rheumatoid arthritis, a multicenter, randomized, post-marketing surveillance study was conducted using two different daily doses of 150 and 300 mg per day. One hundred and thirty-three patients participated in this study which lasted 48 weeks or longer. Efficacy was assessed with a total of 104 cases (63 cases: 150 mg/day, 41 cases: 300 mg/day) . Safety was assessed with a total of 133 cases (77 cases: 150 mg/day, 50 cases: 300 mg/day) . The following are a summary of the study.1. In the assessment of efficacy, there were no significant differences in the clinical parameters between the 150 and 300 mg/day patient groups.2. The combined percentages of patients with a final grobal assessment of “improved” and better in the 150 and 300 mg groups were 33.1 % and 53.7 % respectively. The percentages of patients with a final grobal assessment of “slightly improved” and better in the 150 and 300 mg groups were 00.7 % and 80.5 % respectively. Althougt the differences were not statistically significant, the percentage of patients showing improvements was higher in the 300 mg group than in the 150 mg group.3. The overall safety rating showed the incidence of adverse reactions in the 150 and 300 mg groups to have been 1.3 % and 7.1 %, respectively, which were not statistically different.4. As for rheumatoid arthritis activity measures which include swollen and painful joint counts, grip strength, morning stiffness, Lansbury's activity index and ADL scores, similar degrees of improvements were observed both in the 150 and 300 mg groups. However, improvement in swollen joint count was more marked in the 300 mg group than in the 150 mg group.5. The results of the present study indicate than mizoribine (150 or 300 mg/day) is useful drug for the long-term treatment of rheumatoid arthritis.

A double-blind comparative study among 9 medical centers was conducted in order to investigate the optimal daily administration schedule of UHAC62 (Generic name: Meloxicam), a kind of non-steroidal anti-inflammatory oxycam agent. The daily 10 mg of UHAC62, which had been considered as an optimal dose, was administered either once daily, immediately after supper (Group O), or given twice a day divided into 5 mg immediately after breakfast and supper (Group T), both for weeks to patients with rheumatoid arthritis.Out of the total 52 patients, 1 patient was excluded from the analyses; and 41 patients (Group O: 23 cases, Group T: 18 cases), 51 patients (Group O: 27 cases, Group T: 24 cases) and 44 patients (Group O: 24 cases, Group T: 20 cases) were subjected to the ratings of Final Global Improvement, Overall Safety, and Usefulness, respectively. The results showed the following:(1) The ratio of the patients who showed a better than “Moderate Improvement” in the Final Global Improvement Rating was 30.4 % and 27.8 % in the Group O and Group T, respectively.(2) The ratio of the patients on whom the test drug was shown to be “Completely Safe” in the Overall Safety Rating was 88.9% and 91.7% in the Group O and Group T, respectively. All of the adverse drug reactions which were seen in the patients of Group O and the 2 patients of the Group T were assessed as “mild”.(3) The ratio of the patients on whom the test drug was rated as better than “Useful” was 29.2% and 25.0 % in the Group O and Group T, respectively.There was no significant difference in the overall evaluations and the improvement rating of the symptoms between the groups.According to these results, it was considered that the once daily administration of UHAC62 might be more promising for materializing a higher compliance in the patients who need long-term administration, although both regimens, the once and the twice daily administrations are applicable.

In order to confirm efficacy, safety and utility of mizoribine (MZR) for treatment of rheumatoid arthritis, we conducted a 24 weeks double-blind controlled study using lobenzarit disodium (CCA) as a control drug and obtained the following results.(1) The study involved 72 cases for MZR group and 77 cases for CCA group. There were no significant differences in patients' backgrounds between the two groups.(2) Final global improvement rate was evaluated as “improvement” or more in 26.8% (15/56) for MZR group vs. 12.3% (8/65) for CCA group, “slight improvement” or more in 55.4% (31/56) for MZR group VS. 36.9% (24/65) for CCA group. There was no significance for any of these differences.(3) The incidence of side effects of MZR group was 31.9% and that of CCA group was 48.7%. No serious side effect was observed in both groups.(4) Radiographic films of 41 patients participating in this study were evaluated in a random order by two readers. Only in the CCA group (21 patients) was a statistically significant increase in the mean value of erosion score as well as damage score. These results show that MZR do retarded radiographic progression of joint destruction in the treatment of rheumatoid arthritis.(5) The utility of MZR group was superior to CCA group. These results indicate that mizoribine is a useful drug for treatment of rheumatoid arthritis.

Kinetics of inflammatory cell accumulation in mice in response to glycogen and influence of protease inhibitors and anti-inflammatory drugs were studied. Leukocytes in blood maximally increased at 2 hr after glycogen injection. The maximum cell accumulation in the peritoneal cavity was observed at 8 hr, whereas the protein content in the peritoneal exudate reached the maximum level at 1-2 hr and then decreased. Among drugs examined, indomethacin and dexamethasone suppressed markedly the accumulation of white cells and protein exudation.

The presence of cryoglobulins which are usually mixed type, such as IgG-IgM, IgG-IgG has been reported in the serum of patients with collagen diseases and suggested as one of the evidence of circulating immune complex.In this paper, we report the effect of D-Pc treatmen for 2 cases of RA and Sjogren syndrome with hyper-cryoglobulinemia.Case 1, 54 years old woman, diagnosed as Sjogren syndrome, had mixed IgG-IgM cryoglobulinemia and microscopic hematuria with moderate proteinuria.After 6 months of D-Pc therapy, the cryoprotein diminished and significant reduction of proteinuria was observed.Her clinical symptomes and findings also were improved.Case 2, 49 years old woman with odefinite RA had been treated with low dose (5 mg/ day) of prednisolone for long time. But many abnormal symptoms such as skin bleeding, erythema nodosum and muscle pain was seen and also high concentration of IgG-IgM mixed type cryoglobulin was detected in her serum.After treatment with D-Pc, dramatic immunological changes and clinical improvement was also observed.We consider that D-Pc therapy will be effective to some case of collagen diseases with cryoglobulinemia.

Chemotaxis of neutrophils or macrophages is a complex behavioral response to chemoattractant and one of the more important processes by which cells move from the blood vessels to an inflammatory site in the tissues. In this review, I will discuss about recent progresses in the field of research for mechanisms of chemotaxis first. The discovery of formyl peptides as chemoattractant by Dr. E. Schiffmann has given us many new knowledge about the mechanisms of chemotaxis. Highly radioactive peptides were used to demonstrate and study the peptide receptors on the human and the animal neutrophils or macrophages. The receptors on the cell membrane mediated both chemotaxis and release of lysosomal enzymes. Post receptor events which occur subsequent to the interaction of attractant with receptor are not clear yet. But the internalization of receptor-attractant complex into the cell, the involvement of methylation reaction and transglutaminase appear to be important way of regulating chemotaxis. Secondary, agents that are not chemoattractants themselves but that regulate cell movement are termed modulators. I am interested in the phenomenon that tumors show depressed immunity and susceptibility to infection. Many studies indicate that tumors produce substances that depress accumulation of cells to the site of tumors for the protection of themselves. To demonstrate such modulator is also essential for the study of inflammatory process.