Known risk factors for the development of TB were assessed over a 12-year period; Cox regression was used to estimate the hazard ratios (HRs) of TB, adjusting for the other factors.
RESULTS: Among 33 146 TB contacts, 228 developed TB during the study period (TB rate 668 per 100 000 population, 95%CI 604-783). The main risk factors for TB development were malnutrition (HR 37.5), no treatment of latent
TB infection (HR 25) or <6 months of treatment (HR 5.38), age 0-10 years (HR 7.87), being a household contact (HR 8.47) and having a tuberculin AZD0156 in vivo skin test induration of >= 5 mm (HR >= 4.99). Bacille Calmette-Guerin vaccination significantly reduced the risk of TB development (HR 0.32, 95%CI 0.20-0.50).
CONCLUSIONS: Among contacts of TB cases, we have identified the few factors that carry a very high risk for developing TB. These factors identify populations
at highest risk and permit more effective TB control.”
“Objective: Fibrosis is a major contributor to joint stiffness in osteoarthritis (OA). We investigated several factors associated with the persistence of transforming growth factor beta (TGF-beta)-induced fibrosis and whether these factors also play a role in OA-related fibrosis.
Design: Mice were injected intra-articularly (i.a.) with an adenovirus encoding either TGF-beta or connective tissue growth factor (CTGF). In addition, we induced OA by i.a. injection of bacterial collagenase into the right knee joint of C57BL/6 mice. mRNA was isolated from the synovium for Q-PCR analysis of the gene expression of various extracellular matrix (ECM) components, ECM degraders, growth Ulixertinib purchase factors and collagen cross-linking-related enzymes. Sections of murine knee joints injected with Ad-TGF-beta or Ad-CTGF or from experimental OA were stained for lysyl hydroxylase 2 (LH2). The number of pyridinoline cross-links per triple helix collagen in synovium biopsies was determined with high-performance liquid chromatography (HPLC).
Results: Expression of collagen alpha-1(I) chain precursor (Colla1), tissue inhibitor of metalloproteinases 1 (TIMP1) and especially procollagen-lysine, 2-oxoglutarate
5-dioxygenase 2b (Plod2b) were highly upregulated by Kinase inhibitor Library ���� TGF-beta but not by CTGF. Elevated expression of Plod2b mRNA was associated with high lysyl hydroxylase 2 (LH2) protein staining after TGF-beta overexpression and in experimental OA. Furthermore, in experimental OA the number of hydroxypyridinoline cross-links was significant increased compared to control knee joints.
Conclusions: Our data show that elevated LH2b expression is associated with the persistent nature of TGF-beta-induced fibrosis. Also in experimental OA, LH2b expression as well as the number of hydroxypyridinoline cross-link were significantly upregulated. We propose that LH2b, and the subsequent increase in pyridinoline cross-links, is responsible for the persistent fibrosis in experimental OA. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd.