ABSTRACT
OBJECTIVE: This systematic review with network meta-analysis was performed to compare the effectiveness of oral anti-inflammatory drugs used in Brazil for osteoarthritis. PATIENTS AND METHODS: Randomized clinical trials evaluating ultramicronised diclofenac, diclofenac, celecoxib, etodolac and placebo in patients with osteoarthritis were identified. A search was conducted in May 2021 through PubMed, Scopus and Web of Science databases. A network meta-analysis was developed for efficacy outcome related to analgesia measured by the pain subscale of the Western Ontario and McMaster Universities tool. In addition, surface under the cumulative ranking was performed to rank the drugs in relation to this outcome. RESULTS: Twelve randomized clinical trials were included. Overall, ultramicronised diclofenac 105 mg/day (UD105) was better than all the others, including ultramicronised diclofenac 70 mg/day (UD70). In addition, surface under the cumulative ranking resulted in the following order: 1) ultramicronised diclofenac 105 mg/day (100%), 2) ultramicronised diclofenac 70 mg/day (80%), 3) celecoxib 200 mg/day (49%), 4) diclofenac 100 mg/day (48%), 5) placebo (19%) and 6) diclofenac 150 mg/day (6%). CONCLUSIONS: Ultramicronised diclofenac demonstrated superior efficacy compared to other conventional anti-inflammatory drugs and placebo in relieving osteoarthritis pain.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Diclofenac/administration & dosage , Osteoarthritis/drug therapy , Pain/drug therapy , Celecoxib/administration & dosage , Humans , Network Meta-Analysis , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
The mouse H-2Kd gene gives rise to several transcripts by alternative splicing. In addition to encoding the known Kd antigen, it could thus encode at least one minor hypothetical Kd-like molecule, with a distinct NH2 terminus. The existence of this "24" product can be inferred from a cDNA clone which was previously isolated. We have engineered both this cDNA and its canonical counterpart into a eukaryotic expression vector. After transfer of these constructs into mouse fibroblasts, we obtained cells expressing either one of the transcripts, but not both. In cytotoxicity tests, we found no expression of the "24" product on the cell surface, nor did we obtain any clue concerning its function. In contrast, cells which express Kd antigen, but none of the possible Kd-like molecules produced by alternative splicing, were functional in all aspects examined. We conclude that alternative splicing does not contribute to the known function of the Kd antigen.
Subject(s)
H-2 Antigens/genetics , Animals , Cloning, Molecular , Cytotoxicity, Immunologic , H-2 Antigens/immunology , Isoantibodies/immunology , Lymphocyte Cooperation , Mice , Mice, Inbred Strains , RNA Splicing , RNA, Messenger/genetics , Structure-Activity Relationship , T-Lymphocytes, Cytotoxic/immunology , TransfectionABSTRACT
A cDNA library constructed from liver mRNA of DBA/2 (H-2d) mice has been screened with H-2-specific probes. The nucleotide sequence of one clone (pH-2d-24) indicates that it derives from an H-2 gene with an unexpected exon-intron organization. Nucleotide sequence comparisons suggest that two distinct mRNAs are produced from a single H-2Kd gene by a mechanism involving the use of alternative splicing sites in its 5' region. pH-2d-24 carries an open reading frame encoding a thus-far-undescribed polypeptide product identical to an H-2Kd-molecule, except for the NH2-terminal half of the first domain.
