ABSTRACT
BACKGROUND: Cyclooxygenase-2 selective inhibitors were developed in order to reduce the incidence of life-threatening gastrointestinal ulcer complications compared with non-selective non-steroidal anti-inflammatory drugs. Previous outcomes studies have, variously, lacked power to investigate this endpoint, focused on broader outcomes, or been too small to quantify the influence of aspirin. AIM: To evaluate lumiracoxib, a novel cyclooxygenase-2 selective inhibitor, vs. non-selective non-steroidal anti-inflammatory drugs in an outcomes study of considerably increased size. This paper describes the study's methodology. METHODS AND PATIENTS: The Therapeutic Arthritis Research and Gastrointestinal Event Trial was a randomized, double-blind, 52-week study of lumiracoxib 400 mg once daily (two to four times the recommended dose for osteoarthritis) versus naproxen 500 mg twice daily or ibuprofen 800 mg three-times daily in patients with osteoarthritis. Randomization was stratified for low-dose aspirin use and age (< or = 64, 65-74, > or= 75 years). The study was powered to investigate upper gastrointestinal ulcer complications (primary endpoint) in patients not taking aspirin and in the overall study population; other endpoints included cardiovascular, renal and hepatic measures. CONCLUSIONS: Therapeutic Arthritis Research and Gastrointestinal Event Trial was designed to provide definitive answers concerning the gastrointestinal safety of lumiracoxib, addressing the controversial issues arising from outcomes studies with other cyclooxygenase-2 selective inhibitors.
Subject(s)
Cyclooxygenase Inhibitors/adverse effects , Isoenzymes/antagonists & inhibitors , Organic Chemicals/adverse effects , Osteoarthritis/drug therapy , Peptic Ulcer/chemically induced , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Aspirin/administration & dosage , Aspirin/adverse effects , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/administration & dosage , Diclofenac/analogs & derivatives , Dose-Response Relationship, Drug , Double-Blind Method , Health Status , Humans , Ibuprofen/administration & dosage , Ibuprofen/adverse effects , Membrane Proteins , Middle Aged , Naproxen/administration & dosage , Naproxen/adverse effects , Organic Chemicals/administration & dosage , Prognosis , Prostaglandin-Endoperoxide Synthases , Risk FactorsABSTRACT
Seven strains of Leptospira interrogans belonging to seven different serogroups, and one strain of Leptospira biflexa were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with gradient gels and immunoblotting with hyperimmune rabbit sera raised against each strain. The molecular masses of the proteins were calculated with a polynomial regression model. The SDS-PAGE patterns of the L. interrogans strains were similar and characterized by 24 common bands. This profile was not found for L. biflexa. The immunoblots obtained either with the seven anti-L. interrogans sera or the anti-L. biflexa serum allowed a clear distinction between the two species. Taken as a whole, the L. interrogans strain patterns revealed by the seven anti-L. interrogans sera were similar, sharing eight common major bands. A serovar- or serogroup-specific antigenic zone, ranging from 21 to 26 kDa, was also identified.
Subject(s)
Antigens, Bacterial/analysis , Leptospira interrogans/immunology , Leptospira/immunology , Animals , Antigens, Bacterial/chemistry , Cattle , Dogs , Electrophoresis, Polyacrylamide Gel , Immunoblotting , Leptospira/classification , Leptospira interrogans/classification , Molecular WeightABSTRACT
Antigenic recognition of leptospiral antigens by vaccinated or infected dogs was studied by microagglutination test (MAT) and by western blots. In western blots, serovar specific antigens detected by MAT migrated in the 18-31 kDa zone. The 25-31 zone seemed to be linked to antigens indicating virulence of the strain. These antigens are LPS. The first antibodies made after infection are produced against LPS migrating in the 14 kDa zone. Many protein antigens are common in leptospires belonging to different serogroups. Virulent strains exhibited specific antigens in the 45 and 32-34 kDa zones.