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Background and objectives Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by autoimmune activation leading to local and systemic consequences. Self-reactive T cells play a decisive role in the initiation and maintenance of the disease process. This disease course has been deeply modified by disease-modifying anti-rheumatic drugs that block pro-inflammatory cytokines, but still more than 1/3 of patients do not respond adequately to treatment. To overcome this limitation, mesenchymal stromal cells (MSC) based therapies have been recently explored. MSC are a population of adult non-hematopoietic stem cells with the ability to immunomodulate different cells of the immune system. The aim of this study was to verify the immunomodulatory activity of bone marrow (BM)-derived MSC on peripheral blood helper (Th) and cytotoxic T cells (Tc), distributed among their different functional compartments (naïve, central memory, effector memory and effector) from RA patients and healthy individuals. Materials and methods To this purpose we preformed co-cultures with mononuclear cells and BM-MSC from 12 RA patients and 8 controls during 20 h in a ratio of 2:1 (MNC:BM-MSC). Then, T cells were activated with PMA and ionomycin for 4 h to induce cytokine production by T cells. The frequency of Th and Tc cells producing cytokines (IL-2, IFN-γ, TNF-α, IL-6, IL-17 and IL-9) among the different functional compartments was measured by flow cytometry. Moreover, IL-4, IL-10, TGF-β and CTLA-4 mRNA expression was assessed after cell sorting of CD4+ and CD8+ T cells. Results BM-MSC clearly induced a decrease in the frequency of CD4+ and CD8+ T cells producing pro-inflammatory cytokines (for all the cytokines analysed) in all functional compartments and in both groups under study. However, the intensity of inhibition varied with the cytokine and the T cell functional compartment. Regarding the mRNA expression, in the presence of BM-MSC, we observed an increase of IL-4, IL-10, TGF-β and CTLA-4 in purified CD4+ T cells for both groups, although in a lower extent in RA patients. Likewise, BM-MSC induced an augment of mRNA levels of the abovementioned molecules in CD8+ T cells, although a more pronounced mRNA expression was observed in RA patients, excepting for IL-4, which expression decreased in both groups. Conclusions Our data show that BM-MSC effectively inhibit pro-inflammatory cytokines production by Th and Tc in all functional compartments and increase the mRNA expression of anti-inflammatory molecules in both T cell subpopulations. These results support their potential utility in the treatment of autoimmune diseases.

fracture in the normal population. The overall prevalence of identified risk factors was low but smoking and body weight are both modifiable thus health promotion messages should aim to target these risk factors.

Characterisation and reproduction studies of Amazonian species are extremely important for the recovery and preservation of this biome. The objective of this study was to morphologically characterise the fruits and seeds of Enterolobium contortisiliquum, as well as to verify the influence of seed mass and methods for breaking dormancy. Two evaluation periods consisting of 100 fruits and 500 seeds were analysed for morphological parameters. An experimental design of a complete randomised 2 × 3 × 3 factorial scheme was used to assess the effect of time in storage, mass and breaking dormancy. The important factors consisted of two periods (one and five months after seed collection), three classes of seed mass (< 0.877 g, 0.887-1.09 g and > 1.09 g) and two methods for breaking dormancy (sulphuric acid and mechanical scarification + control group) were identified. The evaluated parameters were germination, germination speed index, stem diameter, average germination time, radicle length, seedling height and the fresh and dry weights of root, shoot and total biomass. Mechanical scarification and sulphuric acid immersion promoted breaking dormancy in seeds of E. contortisiliquum, while the medium and large seeds showed better initial development. Mechanical scarification is recommended for breaking the seed dormancy of this species.

Methods Rheumatologists from seven hospitals completed an audit form on consecutive patients in rheumatology outpatient departments over six months. Information on details of all orthopaedic procedures, waiting times, inpatient stays, complications, concurrent rheumatological drug therapies was obtained from medical records and from patients themselves (inflammatory joint disease was primary diagnosis in 81%). Results A total of 406 orthopaedic operations were performed in 293 patients, 106 total knee replacements (26%), 71 total hip replacements (17.5%), 48 wrist/hand joint operations (12%), 27 forefoot arthroplasties (6.7%), 15 shoulder replacements (3.7%), 14 elbow replacements (3.4%), 12 ankle fusions (3%) and the remainder miscellaneous.The main post operative complications which resulted in increased lenght of inpatient stay were wound sepsis (17), chest infection (4), deep vein thrombosis (4) joint dislocation/fracture (3). Main second line drugs were sulphasalzine (65) and methotrexate ( 58) and steroids were used by 39 patients. Figures will show differences between centres for waiting times (median 9 months) and inpatient stays (median 7 days). Conclusion Marked variations in waiting times could be identified to specific local difficulties which are being addressed. Cessation or changes in second line drugs were uncommon and created only short lasting problems, but need to be reviewed regularly.