Rheumatoid arthritis (RA) is associated with an excess cardiovascular morbidity and mortality, related to systemic inflammation with endothelial dysfunction (ED) and impaired flow-mediated vasodilation (FMD). We assessed the FMD response to anti-TNF-a treatments in 28 RA patients, aged 49.8±15.3 years: an unpaired FMD was found in 66.7% of our cases and was restored after 6 weeks of anti-TNF-a treatment (13.5±5.3% vs 4.6±4.1 %, p < 0.05). Twenty-five percent of the infliximab patients demonstrated a long term response, compared with 60% of etanercept and 100% of adalimumab patients, after 2 years (p

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Objective The gold standard for bladder regeneration in end‐stage bladder disease is the use of intestinal tissue, which is however associated with significant long‐term complications. Our study aims to bioengineer functional detrusor muscle combining bladder smooth muscle cells (SMC) and SMC‐like adipose‐derived stem cells (pADSC) in compressed collagen (CC) hydrogels and to investigate biocompatibility and tissue regeneration of such detrusor‐equivalents in a rat detrusorectomy model. Methods Compressed collagen hydrogels seeded with 1 × 106 or 4 × 106 SMC alone or in combination with pADSC in a 1:1 ratio were investigated. Morphology, phenotype, and viability as well as proteomic secretome analysis were assessed in the 1:1 co‐cultures and the respective monocultures. The hydrogels were implanted into rat bladders after partial detrusorectomy. Bladders were harvested 8 weeks after transplantation, and assessed for tissue morphology, detrusor regeneration, neo‐vascularization and ‐innervation. Results Co‐cultured cells exhibited native SMC morphology, high viability and proliferated to form microtissues in vitro. The pro‐angiogenic factors angiogenin, vascular endothelial growth factor (VEGF)‐A and ‐D were increased in the secretome of the pADSC samples. After 8 weeks of in vivo, the regenerated bladder wall showed a multilayered structure containing all bladder wall components. The overall performance of the bladder wall regeneration of CC seeded with 4 × 106cells was significantly better than with 1 × 106 cells and the combination SMC:pADCS performed slightly better than SMC alone. Conclusion Compressed collagen possesses an adequate regenerative potential to promote regeneration of bladder wall tissue in vivo. Seeded with a combination of pADSC and SMC this may well be the first step towards a functional bladder reconstruction especially in patients suffering of end‐stage bladder diseases.

BackgroundRenin Angiotensin System plays a complex role in regulating physiopathologic functional and morphological modifications at vascular level. While large information exist about Angiotensin (AT) II roles, namely in the development of vascular damage under early inflammatory conditions, little is known about AT 1-7 functions, supposed to play counteracting actions vs AT IIObjectivesTo evaluate if, in the early phases of an experimental inflammatory systemic condition namely the one induced by streptozotocin (SZ), the treatment with AT 1-7 could prevent inflammatory, pro-oxidative and structural vascular modifications, and further prevent the in vivo leukocyte trafficking activation, induced by local stimulation of well known arthritis-related proinflammatory mediators, such as thrombin (THR) or activated terminal complement complex (aTCC).MethodsIn compliance with European (86/609/EEC) and the Italian (D.L.116/92) rules for animal experiments, 4 groups each of 10-12 male Wistar rats were randomly grouped and treated respectively with sterile saline, or AT 1-7 (576 μg/kg/day), either in the presence or absence (healthy control group) of a preliminary standardized bolus intra vein infusion of 50mg/kg SZ. Saline and AT 1-7 were daily infused by osmotic sc minipump. After 3 weeks, in 4 anesthesized rats from each group, the occurrence of either basal, or THR or aTCC-induced local inflammatory inflammatory stimulation, stable adherence to the endothelial layer and extravasation of circulating fluorescently-labelled leukocytes were assessed at microvascular level by using an in vivo videomicroscopy technique. In the other rats, the immunohistochemical staining (IHS) and gene expression ex vivo analysis of mesentery vascular content of IL-6, MCP-1, Nitrotyrosine, connective tissue growth factor (CTGF), proliferative cell nuclear antigen (PCNA), together with structural changes, assessed by median wall:total vessel area ratio (W/TV) and extracellular matrix content, were also assessed.ResultsAT 1-7 did not induce any significant modification in control, healthy animals, differently AT 1-7 partly reduced the overall increase of leukocyte trafficking and extravasation in a time ranging from 15 to 60 minutes after topical exposure to THR and aTCC, while significantly inhibiting these effects (p<0.01) in rats previously treated with SZ. AT 1-7 also reduced the SZ induced percent increase of W/TV ratio (61±5 vs 87±6 of saline treated, p<0.001), local vascular content (ng/μg prot.) of IL-6 (7±1,2 vs 3±0.8, p<0.01) and MCP-1 (12±4 vs 7±2.5, p<0.05), and the percent IHS of Nitrotyrosine (25.5±6.7 vs 9.5±4, p<001), CTGF (21±4 vs 14.5±2.5, p<0.01) and PCNA (medial layer=8±3.2 vs 2.5±0.15, p<0.01). Gene expression assessments are still under evaluationConclusionsThese data suggest that AT 1-7 could play an immune modulating role even in the earlier phases of inflammatory conditions, with prevention of secondary structural tissue alterations. This could be of relevance in the development of arthritis disease, therefore our grou...