Salbutamol up-regulates matrix metalloproteinase-9 in the alveolar space in the acute respiratory distress syndrome.

Objectives: Acute respiratory distress syndrome (ARDS) is characterized by alveolar-capillary barrier damage. Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of ARDS. In the Beta Agonists in Acute Lung Injury Trial, intravenous salbutamol reduced extravascular lung water (EVLW) in patients with ARDS at day 4 but not inflammatory cytokines or neutrophil recruitment. We hypothesized that salbutamol reduces MMP activity in ARDS.

Methods: MMP-1/-2/-3/-7/-8/-9/-12/-13 was measured in supernatants of distal lung epithelial cells, type II alveolar cells, and bronchoalveolar lavage (BAL) fluid from patients in the Beta Agonists in Acute Lung Injury study by multiplex bead array and tissue inhibitors of metalloproteinases (TIMPs)-1/-2 by enzyme-linked immunosorbent assay. MMP-9 protein and activity levels were further measured by gelatin zymography and fluorokine assay.

Measurements and Main Results: BAL fluid MMP-1/-2/-3 declined by day 4, whereas total MMP-9 tended to increase. Unexpectedly, salbutamol augmented MMP-9 activity. Salbutamol induced 33.7- and 13.2-fold upregulation in total and lipocalin-associated MMP-9, respectively at day 4, compared with 2.0- and 1.3-fold increase in the placebo group, p < 0.03. Salbutamol did not affect BAL fluid TIMP-1/-2. Net active MMP-9 was higher in the salbutamol group (4222 pg/mL, interquartile range: 513-7551) at day 4 compared with placebo (151 pg/mL, 124-2108), p = 0.012. Subjects with an increase in BAL fluid MMP-9 during the 4-day period had lower EVLW measurements than those in whom MMP-9 fell (10 vs. 17 mL/kg, p = 0.004): change in lung water correlated inversely with change in MMP-9, r = -.54, p = 0.0296. Salbutamol up-regulated MMP-9 and down-regulated TIMP-1/-2 secretion in vitro by distal lung epithelial cells. Inhibition of MMP-9 activity in cultures of type II alveolar epithelial cells reduced wound healing.

Conclusions: Salbutamol specifically up-regulates MMP-9 in vitro and in vivo in patients with ARDS. Up-regulated MMP-9 is associated with a reduction in EVLW. MMP-9 activity is required for alveolar epithelial wound healing in vitro. Data suggest MMP-9 may have a previously unrecognized beneficial role in reducing pulmonary edema in ARDS by improving alveolar epithelial healing.

The Skills Agenda and the Competencies for Managing Diversity and Space

This paper evaluates skills for managing ethno-religious diversity in the context of regeneration, spatial planning and the pursuit of sustainable communities. It draws on experiences in Northern Ireland to explore the type and range of skills required in a society emerging from prolonged conflict and residential segregation. The paper concludes by highlighting the need for a more direct political engagement with agnostic practice that challenges the technical reductionism implied in generic skills frameworks. Here, the implications for practice outside the region are identified.

Negotiating Civic Space in Belfast or The Tricolour: Here Today, Gone Tomorrow’

What role does public civic space in Belfast city centre play in the negotiation of different political identities within the city? Focusing on key public events in this space the paper traces shifts in identity practices and focuses on negotiations over the uses of public space associated with Irish nationalism and British unionism. This, it is argued, gives a more sophisticated understanding of different types of ‘shared space’. The events probed are seen as precursors and possibly drivers of political change. It is concluded that the increased sharing of civic space has probably contributed to improved political relations within the city, though there remains the challenge of
understanding how public space might more effectively be used to influence
relationships between the city’s political identities in the longer term.

Beyond the shadow space: architecture as a professional and creative process; during and post-conflict.

Introduction

Much has been written about the impact of conflict on the physical nature of cities; most obviously perhaps the damage, destruction, defensive construction and spatial reconfigurations that evolve in times of conflict. Set within the context of Belfast, Northern Ireland, this paper will focus on three areas. First, a closer reading of the long-term physical impact of conflict, in particular, the spatial forms and practices that persist conceptually and culturally, and/or resist re-conceptualisation. Secondly, the effect of conflict on the nature of architectural practice itself, considering whether issues such as appointment and procurement impacted on architectural expectation and the context of operation. Thirdly, the effect of conflict on people, in particular in relation to creativity and hence the psyche of practice itself. This section will also identify the conditions that undermine or support design quality and creativity not only within times of conflict but also as society evolves out of the shadow space. 1
Twelve years on from the Peace Agreement,2 it may seem remarkable from an external perspective that Northern Ireland still needs to be reflecting on its troubled past. But the immediate post-conflict phase offered the communities of Northern Ireland place and time to experience ‘normal life’, begin to reconcile themselves to the hurt they experienced and start to reconfigure their relationships to one another. Indeed, it has often been expressed that probing the issues too much, at too early a phase, might in fact ‘Open old wounds without resolving anything’ and/or ‘Destabilise the already fragile political system.’3 This tendency not to deliberate or be too probing is therefore understandable and might be the reason why, for example, Northern Ireland's first Architecture and Built Environment policy, published in June, 2006, contains only one routine reference to ‘the Troubles’.

Clearly, however, there is a time in the development of a healthy, functioning society, when in order effectively to plan its future, it must also carry out a closer reading and deeper understanding of its past. As Maya Angelou puts it, ‘History, despite its wrenching pain/ Cannot be unlived, and if faced/ With courage, need not be lived again.’4

Increasingly, those within the creative arts sector and the built environment professions are showing interest in carrying out that closer reading, teasing out issues around conflict. This was led in part by the recent publication of the Troubles Archive by the Arts Council of Northern Ireland.5 Those involved in the academic or professional development of future generations of architects are also concerned about the relevance of a post-conflict condition. As a profession, if architects purport to be concerned with context, then the almost tangible socio-political circumstances and legacy of Northern Ireland does inevitably require direct eye contact. This paper therefore aims to bring the relationship between conflict and architectural practice in Northern Ireland into sharp focus, not to constrain or dull creative practice but to heighten its potential.