BACKGROUND AND PURPOSENF-kB has been implicated as a therapeutic target for the treatment of rheumatoid arthritis. We previously synthesized a thiourea analogue, SPA0355, which suppressed NF-kB activity. Here we have assessed the anti-inflammatory and anti-arthritic effects of SPA0355. EXPERIMENTAL APPROACHWe evaluated the effects of SPA0355 on human rheumatoid fibroblast-like synoviocytes in vitro and on collagen-induced arthritis (CIA) in mice in vivo. KEY RESULTSIn vitro experiments demonstrated that SPA0355 suppressed chemokine production, matrix metalloproteinase secretion and cell proliferation induced by TNF-a in rheumatoid fibroblast-like synoviocytes. In addition, SPA0355 inhibited osteoclast differentiation induced by macrophage colony-stimulating factor and the receptor activator of NF-kB ligand, in bone marrow macrophages. Mice with CIA that were pretreated with SPA0355 had a lower cumulative disease incidence and severity of arthritis, based on hind paw thickness, radiological and histopathological findings, and inflammatory cytokine levels, than mice treated with vehicle. Mice treated with SPA0355, after the onset of CIA, also showed significantly decreased disease incidence and joint oedema. The in vitro and in vivo protective effects of SPA0355 were mediated by inhibition of the NF-kB signalling pathway. CONCLUSION AND IMPLICATIONSTaken together, these results suggested that using SPA0355 to block the NF-kB pathway in rheumatoid joints reduced both the inflammatory responses and tissue destruction. Therefore, SPA0355 may have therapeutic value in preventing or delaying joint destruction in patients with rheumatoid arthritis.

Background: Cerebrospinal fluid (CSF) leakage is a complication that any surgeon working in the field of skull base surgery does not wish to encounter. The surgical approach to the skull base often varies, and the various sizes and locations of skull base lesions make it difficult to determine the cause of CSF leakage. However, it is useful to investigate which factors contribute to postoperative CSF leakage. Methods: Related studies were identified by searching the following databases: PubMed/Medline, Embase, and Web of Sciences through December 2019. Random-effects models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The Newcastle-Ottawa scale was used to evaluate the quality of observational studies. Results: Our search yielded 56 retrospective cohort studies involving a total of 11,826 skull base surgical procedures. The overall rate of postoperative CSF leakage was 7.2%. The effect of obesity on postoperative CSF leakage had an OR of 1.88, and the effect of perioperative radiotherapy on postoperative CSF leakage yielded an OR of 1.87. High intraoperative CSF flow rate also had a significant OR of 2.98. On the other hand, a pedicled vascularized flap efficiently reduced the risk of postoperative CSF leakage. Defect size and the presence or absence of a lumbar drain had no effect on postoperative CSF leakage. Conclusions: This comprehensive quantitative assessment of postoperative CSF leakage showed that obesity, perioperative radiotherapy, and high intraoperative CSF flow rate raised the risk of CSF leakage; however, a pedicled vascularized flap can effectively reduce the risk of postoperative CSF leakage.

A 5 year old boy with serological and clinical evidence of Mycoplasma pneumoniae infection, which was complicated by popliteal artery thrombosis, is described. Intra-arterial urokinase, in conjunction with medical treatment, resulted in clinical recovery and angiographic resolution of the thrombus. The variety of extrapulmonary complications associated with the M pneumoniae infections continues to broaden. Thrombolytic therapies should be considered when similar clinical circumstances arise. (Postgrad Med J 2001;77:723-724)

Growth failure appears to be a major problem for nephrotic children who fail to respond to steroid therapy. Recently altered serum insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) profiles are reported in renal failure and glomerulonephritis. In this study, the serum IGFBP profile was evaluated by Western ligand blot and RIA in 22 patients with the nephrotic syndrome. Serum IGFBP-3 was decreased, whereas IGFBP-2 was increased in most patients with the nephrotic syndrome. The mean serum IGFBP-3 level was 2123 +/- 531 ng/mL in active states and was increased to a normal level (3593 +/- 407 ng/mL) in remission states. We also measured serum IGF-I by RIA. The serum concentration of IGF-I (mean +/- SD) was 67.4 +/- 23.2 ng/mL in active states and was increased to 127.1 +/- 21.8 ng/mL in remission states, but was still lower than that in control subjects (180.4 +/- 15.8 ng/mL). IGF-I and IGFBP-3 levels were not correlated with primary renal diseases or the amount of proteinuria. For serum IGF-IGFBP complexes, 150-kDa complexes were significantly decreased in patients with the nephrotic syndrome compared with those in control subjects. In urine from nephrotic syndrome patients, 150- and 50-kDa complexes were found, whereas these complexes did not exist in the urine of control subjects. We speculate that low serum IGF-I and IGFBP-3 levels would be partially due to the increased urinary losses of serum IGF-IGFBP complexes, especially that of 150 kDa, and these changes may contribute to growth failure in persistent nephrotic syndrome.