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Covering: 2008 and 2009. Previous review: Nat. Prod. Rep., 2008, 25, 919 [ABSTRACT FROM AUTHOR]

To investigate the roles of CD59a in the protection of joint tissue in the context of murine antigen?induced arthritis (AIA).AIA was triggered in CD59a?deficient (CD59a?/?) mice and in CD59a?sufficient (CD59a+/+) controls; the course and severity of disease were compared between groups. The effects on arthritis of restoring CD59 to the joint in CD59a?/? mice by use of a membrane?targeted recombinant CD59 were also explored.Disease, as assessed clinically by measurement of joint swelling on day 1 (P < 0.0001), day 2 (P < 0.01), and day 7 (P < 0.02) and histologically from indicators of joint damage on day 21 (P < 0.02), was significantly enhanced in CD59a?/? mice compared with CD59a+/+ wild?type controls. Membrane attack complex (MAC) deposition in the arthritic joints of CD59a?/? mice was also increased compared with that in the joints of CD59a+/+ controls. Restitution of CD59 activity in joints of CD59a?/? mice was attempted with soluble recombinant rat CD59 (sCD59) or with a novel membrane?targeted rat CD59 derivative (sCD59?APT542). Strong immunohistochemical staining of the synovial membrane and subsynovial tissue was apparent in sCD59?APT542–injected joints, but not in joints injected with untargeted sCD59. Intraarticular administration of sCD59?APT542 markedly ameliorated disease severity in CD59a?/? mice, knee swelling was significantly reduced over the time course of the disease, and joint damage, assessed histologically, was significantly milder on day 21 (P < 0.05).These data firmly implicate the MAC of complement as a major effector of joint damage in the murine AIA model of rheumatoid arthritis (RA), and they provide a rationale for the inhibition of MAC assembly as a therapeutic strategy for RA. [ABSTRACT FROM AUTHOR]

Background: Treatment of gastroesophageal reflux (GER) with proton-pump inhibitors (PPI) improves symptoms of asthma in some patients. However, the effects of a PPI on ventilatory function are still controversial. In this study, we measured ventilatory function in asthma patients treated with a PPI in order to identify those in whom a therapeutic effect on asthma can be expected from the acid suppression. Methods: From a cohort of 114 consecutive patients with bronchial asthma, 53 patients agreed to participate in the study and were treated with rabeprazole 20 mg daily for 8 weeks during an asymptomatic, stable period with no exacerbations of their asthma. Of the 53 patients, 22 were diagnosed as GER on the basis of the QUEST questionnaire and endoscopic examination. The patients were monitored for improvement in ventilatory function. Results: Four patients dropped out because of adverse drug reactions. All the patients with GER noted an improvement in reflux symptoms with PPI treatment. An improvement of more than 20% in peak expiratory flow (PEF) was observed in 8 of 21 GER patients but in none of the non-GER patients. Factors predictive of improvement in PEF with rabeprazole therapy were the QUEST score (odds ratio: 1.47, 95% CI: 1.06-2.04, P = 0.022) and steroid-dependency of asthma (odds ratio: 0.01, 95% CI: 0.001-0.31, P = 0.008). Conclusions: Treatment with rabeprazole is expected to ameliorate asthma in non-steroid-dependent patients who have symptomatic GER defined by the QUEST score. [ABSTRACT FROM AUTHOR]