Haruaki Warabi

Studies of glycogen-induced inflammation of mice. Dynamics of inflammatory responses and influence of antiinflammatory drugs and protease inhibitors.

The intraperitoneal injection of glycogen in the mouse resulted, shortly thereafter, in the accumulation of 14–23 million neutrophils in the peritoneal cavity and a four-fold increase in the numbers of circulating neutrophils. Preceding the influx of leukocytes, the exudation of plasma proteins and the chemotactic activity for mouse neutrophil in vitro increased in the peritoneal fluid. Among various protease inhibitors examined, chymostatin alone suppressed the plasma protein exudation. Indomethacin and dexamethasone reduced the accumulation of white cells and protein exudation. These nonsteroidal and steroidal antiinflammatory drugs were equally effective whether given simultaneously with or 60 min before glycogen or whether administered intraperitoneally or orally. Colchicine showed a suppressive effect on the leukocyte accumulation but enhanced the protein exudation.

Investigations on the therapeutic regimen of a novel non-steroidal anti-inflammatory drug, the UHAC62 capsule.

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.