Tryptase mediates hyperresponsiveness in isolated guinea pig bronchi

Hyperresponsiveness of airway smooth muscle to allergens and environmental factors has long been associated with the pathophysiology of asthma. Tryptase, a serine protease of lung mast cells, has been implicated as one of the mediators involved in the induction of hyperresponsiveness. As a consequence, tryptase inhibitors have become the subject of study as potential novel therapeutic agents for asthma. Secretory leukocyte protease inhibitor (SLPI) is a naturally occurring protein of human airways which exhibits anti-tryptase activity. To assess the potential therapeutic utility of SLPI in asthma, its effects were evaluated using in vitro and ex vivo models of airway hyperresponsiveness and compared with the effects of the small molecule tryptase inhibitor APC-366. Our results demonstrate that SLPI inhibits tryptase-mediated hyperresponsiveness in vitro and attenuates the hyperresponsiveness observed in airway smooth muscle from antigen-sensitized animals subjected to antigen exposure. The small molecule tryptase inhibitor APC-366 has a similar inhibitory effect. Thus, tryptase appears to be a significant contributor to the development of hyperresponsiveness in these models. To the extent that tryptase contributes to the development and progression of asthma, SLPI may possess therapeutic potential in this disease setting.     

3D-FEA of osseointegration percentages and patterns on implant-bone interfacial stresses

The aim of this study was to investigate the expression and distribution patterns of the inducible isoform of nitric oxide synthase (iNOS) in rat placenta during gestation and term labour. The expression of iNOS isoform was assessed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting with monoclonal antibodies. Two specific bands were detected corresponding to 135 and 124 kDa in all placenta samples. The upper band (135 kDa) was identified as iNOS due to its correspondence with the band obtained with mouse macrophages (positive control). Compared with its concentrations on day 16, iNOS decreased steadily toward the end of gestation to approximately 37% on day 20, 20% on day 22 before labour and 12% during labour (p < 0.01). The lower band (124 kDa) drastically increased (to almost double) from day 16 to day 18 but returned to initial values on day 22, during delivery. Immunohistochemical staining of placentae at day 16 and 22 using rabbit polyclonal anti-iNOS antibody revealed labelling specifically concentrated in the trophospongial cell layer, at the fetal-maternal interface. The most conspicuous iNOS staining was associated with islands of cells referred to as vacuolated 'glycogen cells'. Staining was greatly decreased during labour. The changes in placental iNOS expression suggest a 'paracrine' role for NO in regulating uterine contractility, blood flow and immunosuppression required for pregnancy maintenance. NO withdrawal at term may also be involved in the initiation of labour.