Objective. Angiotensin II (Ang II) is known to have proinflammatory actions, and Ang II type 1 (AT 1 ) receptors are up-regulated in the rheumatoid synovium, suggesting that this receptor could be a therapeutic target. The purpose of this study was to investigate the antiinflammatory potential of the selective AT 1 receptor antagonist losartan, which is currently used for the treatment of cardiovascular disease.Methods. Dose-ranging studies of losartan (1-50 mg/kg) were initially conducted in a rat model of acute (carrageenan/kaolin) arthritis, with subsequent evaluation in a rat model of adjuvant-induced arthritis (Freund's complete adjuvant). Losartan (10 -10 to 10 -6 M) was further tested ex vivo in human inflammatory synovitis, using collagenase-digested synovium.Results. Western blot and immunohistochemical analyses both revealed a substantial increase in AT 1 receptor protein content in synovium from acutely and chronically inflamed rat knee joints. Similarly, synovial Ang I/II protein content was elevated during inflammation. Losartan inhibited acute joint inflammation in a dose-dependent manner, with 15 mg/kg being the optimal dose (and used in subsequent studies). Both prophylactic and therapeutic administration of 15 mg/kg of losartan substantially reduced knee joint swelling in rats with adjuvant monarthritis (>50%; P < 0.0001). Losartan also suppressed tumor necrosis factor ␣ generation from inflamed human synovium in a dosedependent manner (P < 0.05).Conclusion. Targeting the angiotensin pathway, particularly AT 1 receptors, could have significant therapeutic potential. Randomized placebo-controlled trials are now warranted to establish the extent to which angiotensin receptor blockers may provide antiinflammatory benefits.

Aim: To compare the incidence of various integrin subunits in human cataract anterior lens epithelial cells (A-LEC) and in two mammalian LEC lines. Methods: Circular sections of anterior capsules with attached LEC were obtained during cataract surgery. Integrin subunits were immunolocalised in these anterior LEC and in a human and rabbit LEC line, using four monoclonal antibodies specific for subunits a2, a3, and a5, and b subunit 2. Results: All of these subunits were found in at least a proportion A-LEC samples as follows: a2 71%, a3 92%, a5 62%, and b2 24%. The human LEC line was immunoreactive for a2 and a3 only. The rabbit lens epithelial cell line was immunoreactive for a5 but there was no staining for a2, a3, or b2. Conclusion: The A-LEC and mammalian LEC lines showed a similarity in their pattern of integrin expression. As these integrins are receptors for extracellular matrix (ECM) components, they are likely to be associated with the attachment and migration of LECs that precedes capsular opacification. Therefore these cell lines may be useful in the elucidation of mechanisms involved the pathogenesis of capsule opacification.

Purpose To examine the lens epithelial cells obtained from the anterior lens capsules removed during cataract surgery and detect various subclasses of the cell surface adhesion molecules known as integrins. Methods The circular sections of anterior capsules with attached lens epithelial cells (LECs) were obtained during cataract surgery from 28 patients. The lens capsules were immunohistochemically stained. Results CD49b CD49c, CD49e, and CD18 were detected in varying degrees in specimens obtained from human cataractous lenses. The positive percentages were 33, 75, 33, and 20%, respectively. The most striking feature was the increasing staining profiles towards the edges of the capsules (away from the central part of the lens capsules) for CD49c, suggesting that the LECs showed higher immunoreactivity for this antibody. The immunoreactivity for CD49b and CD49e was weaker. This was absent for CD18 in the central part of the lens capsules. Conclusion The positive expression of antibodies suggests that specific integrin subunits were expressed in LECs of human cataracts. These results suggest that lens epithelial cells expressing CD49b, CD49c, CD49e, and CD18 might be precursors in the process of anterior lens epithelial cell (A cell) adhesion, and hence play a role in anterior capsule opacification or in subsequent migration and a possible role in posterior capsule opacification.

We are six nursing students who recognised that people with learning disabilities, and their carers, can sometimes receive care which does not meet their needs. They also have some of the poorest health in the country.