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Although the introduction of tumor necrosis factor (TNF) inhibitors represented a significant advance in the treatment of rheumatoid arthritis (RA), traditional anti-TNFα antibodies are somewhat immunogenic, and their use results in the formation of anti-drug antibodies (ADAs) and loss of efficacy (secondary failure). Ozoralizumab is a trivalent, bispecific NANOBODY® compound that differs structurally from IgGs. In this study we investigated the suppressant effect of ozoralizumab and adalimumab, an anti-TNFα IgG, on arthritis and induction of ADAs in human TNF transgenic mice. Ozoralizumab markedly suppressed arthritis progression and did not induce ADAs during long-term administration. We also developed an animal model of secondary failure by repeatedly administering adalimumab and found that switching from adalimumab to ozoralizumab was followed by superior anti-arthritis efficacy in the secondary-failure animal model. Moreover, ozoralizumab did not form large immune complexes that might lead to ADA formation. The results of our studies suggest that ozoralizumab, which exhibited low immunogenicity in the animal model used and has a different antibody structure from that of IgGs, is a promising candidate for the treatment of RA patients not only at the onset of RA but also during secondary failure of anti-TNFα treatment. [ABSTRACT FROM AUTHOR]

Examines the transition of gobiid fish Mugilogobius abei to ureogenesis. Rate of urea excretion in tissues and excreta by fish immersed in isotope-labelled ammonia solution; Glutamine content and glutamine synthase activities in liver and muscle following exposure to ammonia; Sequence of carbamoyl phosphate synthetase III activity.

Although the introduction of tumor necrosis factor (TNF) inhibitors represented a significant advance in the treatment of rheumatoid arthritis (RA), traditional anti-TNFα antibodies are somewhat immunogenic, and their use results in the formation of anti-drug antibodies (ADAs) and loss of efficacy (secondary failure). Ozoralizumab is a trivalent, bispecific NANOBODY ® compound that differs structurally from IgGs. In this study we investigated the suppressant effect of ozoralizumab and adalimumab, an anti-TNFα IgG, on arthritis and induction of ADAs in human TNF transgenic mice. Ozoralizumab markedly suppressed arthritis progression and did not induce ADAs during long-term administration. We also developed an animal model of secondary failure by repeatedly administering adalimumab and found that switching from adalimumab to ozoralizumab was followed by superior anti-arthritis efficacy in the secondary-failure animal model. Moreover, ozoralizumab did not form large immune complexes that might lead to ADA formation. The results of our studies suggest that ozoralizumab, which exhibited low immunogenicity in the animal model used and has a different antibody structure from that of IgGs, is a promising candidate for the treatment of RA patients not only at the onset of RA but also during secondary failure of anti-TNFα treatment., Competing Interests: Author CI-O, MK, HO, MY, KI, MO, MH, NM, and YF are employed by Taisho Pharmaceutical Co., Ltd. This study received funding from Taisho Pharmaceutical Co., Ltd. The funder had the following involvement with the study: the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication., (Copyright © 2022 Ishiwatari-Ogata, Kyuuma, Ogata, Yamakawa, Iwata, Ochi, Hori, Miyata and Fujii.)

Aim: To evaluate the usefulness of cytology of the pancreatic juice obtained via the endoscopic naso-pancreatic drainage tube (ENPD-C)., Methods: ENPD was performed in cases where a diagnosis could not be made other than by using endoscopic retrograde cholangiopancreatography and in cases of pancreatic neoplasms or cystic tumors, including intraductal papillary mucinous neoplasm (IPMN) suspected to have malignant potential. 35 patients (21 males and 14 females) underwent ENPD between January 2007 and June 2013. The pancreatic duct was imaged and the procedure continued in one of ENPD-C or ENPD-C plus brush cytology (ENPD-BC). We checked the cytology result and the final diagnosis., Results: The mean patient age was 69 years (range, 48-86 years). ENPD-C was performed in 24 cases and ENPD-C plus brush cytology (ENPD-BC) in 11 cases. The ENPD tube was inserted for an average of 3.5 d. The final diagnosis was confirmed on the basis of the resected specimen in 18 cases and of follow-up findings at least 6 mo after ENPD in the 18 inoperable cases. Malignancy was diagnosed in 21 cases and 14 patients were diagnosed as having a benign condition. The ratios of class V/IV:III:II/I findings were 7:7:7 in malignant cases and 0:3:11 in benign cases. The sensitivity and specificity for all patients were 33.3% and 100%, respectively. The cytology-positive rate was 37.5% (6/16) for pancreatic cancer. For IPMN cases, the sensitivity and specificity were 33% and 100%, respectively., Conclusion: Sensitivity may be further increased by adding brush cytology. Although we can diagnosis cancer in cases of a positive result, the accuracy of ENPD-C remains unsatisfactory.