ABSTRACT
OBJECTIVE AND DESIGN: 1-(Carboxymethyl)-3,5-diphenyl-2-methylbenzene (CDB), a novel arylacetic acid, was evaluated in vivo for its ability to inhibit acute and chronic inflammation as well as acute pain. MATERIALS AND METHODS: The effects of CDB were evaluated using the following assays: 1) acute inflammation induced by the injection of carrageenan, bradykinin and serotonin into the subplantar region of the hind paw of rats; 2) chronic inflammation produced by the injection of Mycobacterium butyricum into the base of the tail of rats; 3) acute pain induced by the i.p. injection of phenyl-p-quinone into mice resulting in the production of writhes; 4) cyclooxygenase (COX) activity, including COX-1 and COX-2, evaluated using whole blood; and 5) activity of peptidylglycine alpha-monooxygenase (PAM) isolated from Xenopus laevis skin. RESULTS: CDB (10 to 100mg/kg s.c.) produced a dose-dependent inhibition of carrageenan edema (ED50 of 41 mg/ kg at 3 h) which continued for up to 12 h. Using a therapeutic dosing regimen, this compound inhibited hind paw inflammation (>70%) and arthogram scores in rats with adjuvant-induced arthritis. This compound also possessed significant analgesic activity in mice (70% inhibition with 50mg/kg). CDB, however, lacked inhibitory activity on bradykinin and serotonin-induced edema. In addition, CDB significantly inhibited COX-I activity (IC50 approximately = 17 microM) while having only a weak inhibitory activity on both COX-2 and PAM activity. CONCLUSIONS: CDB is an effective anti-inflammatory/analgesic agent whose mechanism of action appears to be associated with inhibition of COX-1 activity.
Subject(s)
Acetates/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Benzene/pharmacology , Inflammation/drug therapy , Multienzyme Complexes , Animals , Arthritis, Experimental/drug therapy , Bradykinin , Carrageenan , Cyclooxygenase Inhibitors/pharmacology , Edema/chemically induced , Edema/drug therapy , Enzyme Inhibitors/pharmacology , Foot/pathology , Inflammation/chemically induced , Male , Mice , Mixed Function Oxygenases/antagonists & inhibitors , Pain Measurement/drug effects , Rats , Rats, Sprague-Dawley , Reaction Time/drug effects , SerotoninABSTRACT
A diagnosis of coenuriasis was made in a spectacled langur raised in captivity. Multiple cysts removed from the subcutaneous tissues and later from the abdominal cavity were identified as coenuri, typical of the genus Taenia. Post-surgical treatment of the remaining cysts with praziquantel was assessed with whole body computerized tomography (CT). CT at 6 weeks post-treatment revealed a reduction in size and increased calcification of abdominal cysts as compared to pretreatment CT. Cyst fluid antigens in ELISA assays showed a high titer (1:5, 120) IgG response in the langur serum, while no IgM response could be detected. No decrease in IgG titer was seen 6 weeks after treatment. Immunoblot analyses identified several parasite-specific antigens with apparent molecular weights of greater than 92.5 (3 bands), 88, 41, 37, and 34 kDa.
