Cardiac chymase: pathophysiological role and therapeutic potential of chymase inhibitors

On release from cardiac mast cells, alpha-chymase converts angiotensin I (Ang I) to Ang II. In addition to Ang II formation, alpha-chymase is capable of activating TGF-beta 1 and IL-1 beta, forming endothelins consisting of 31 amino acids, degrading endothelin-1, altering lipid metabolism, and degrading the extracellular matrix. Under physiological conditions the role of chymase in the mast cells of the heart is uncertain. In pathological situations, chymase may be secreted and have important effects on the heart. Thus, in animal models of cardiomyopathy, pressure overload, and myocardial infarction, there are increases in both chymase mRNA levels and chymase activity in the heart. In human diseased heart homogenates, alterations in chymase activity have also been reported. These findings have raised the possibility that inhibition of chymase may have a role in the therapy of cardiac disease. The selective chymase inhibitors developed to date include TY-51076, SUN-C8257, BCEAB, NK320, and TEI-E548. These have yet to be tested in humans, but promising results have been obtained in animal models of myocardial infarction, cardiomyopathy, and tachycardia-induced heart failure. It seems likely that orally active inhibitors of chymase could have a place in the treatment of cardiac diseases where injury-induced mast cell degranulation contributes to the pathology.

The changing nature and role of the head of department

There is little doubt that devolution of responsibility to schools and the growth of school-based management have impacted upon the role and workload of school leaders. Not only Principals have been affected by these changes as Welch (1996) argues that Principals of public secondary schools have passed responsibility down to Deputy-principals and to Heads of Department. As such, the Head of Department role, like other school administration positions, has undergone significant change. Of interest to this paper is the changing role of Heads of Department in secondary schools. This study reports on the findings of semi-structured interviews with eight Heads of Department from four public secondary schools and Principals from each of these schools in South East Queensland. Four years after the first set of interviews, two heads of department were reinterviewed. Both sets of interviews focused upon the role, change, and the importance of leadership. The research generated eight specific themes each of which was considered consistent with the nature of the role in a period of significant cultural change. These were the difference in perceptions regarding the Head of Department role, held by Principals and Heads of Department; Head of Department leadership in terms of a curriculum framed department or whole school leadership; how individuals perceived leadership, and how they learned of leadership; the impact of the changing culture upon the individual Head of Department; the growing influence of situational factors upon the role; the impact of managerialism; the changing nature of a secondary school department; and a growing and more complex workload, and the need for different skills. Furthermore, the findings pointed towards the need for effective change processes and a reconceptualized head of department role. The paper concludes with some implications for the ongoing professional development needs of Heads of Department.

Teamwork in Health and Rehabilitation Sciences: Evaluation of a multiprofessional workshop

This paper outlines a multiprofessional education workshop piloted and subsequently conducted with a cohort of 81 graduate entry students of occupational therapy, physiotherapy, speech pathology and audiology. The rationale for, and format of, the workshop is outlined, followed by comparisons between students' knowledge about teamwork prior to and after the four-hour workshop. The workshop was based on a real case scenario of a child with Developmental Coordination Disorder (DCD). Students completed pre- and post-workshop questionnaires about their knowledge of DCD, teamwork and the roles of various professionals and parents; and a post-workshop questionnaire about their views regarding the utility of the workshop, its strengths, and learning outcomes. The evaluation indicated that the workshop was overwhelmingly successful from the students' perspective in: (1) enhancing their understanding about DCD and its multifaceted impact on school age children; (2) developing a deeper appreciation of the importance of teamwork itself; (3) refining their understanding of their own profession's role and (4) developing an appreciation of the role of other professions and parents in working with children with complex needs, and their families. Limitations of this study and directions for future research are discussed.

Role of oxidative stress in age-associated chronic kidney pathologies

The kidneys exhibit age-associated deterioration in function via a loss of 20% to 25% kidney mass, particularly from the renal cortex and increased fibrosis. Oxidative stress has been found to mediate age-associated renal cell injury and cell death, particularly apoptosis. Oxidative stress results from an imbalance between the levels of free radicals generated during aerobic metabolism, inflammation, and infection and the safe breakdown of these species by endogenous and exogenous scavengers. Other factors may influence these pathologies. For example, growth hormone and caloric restriction have been shown to influence life span, although neither method of prolonging life is likely to find general acceptance in humans. Some genetic knockout models offer promise; for example, knockout of the p66 isoform of the Shc gene in mice increases life span by 30%, but appetite, size, and fertility are retained. Whether the increase in life span is via increased kidney health is not yet clear, but decreasing the age-related renal pathologies will no doubt aid in increasing life span and health in general. This review looks at the role and modulation of factors that influence life span, in particular modulation of oxidative stress, with particular relevance to age-related renal pathologies. (C) 2005 by the National Kidney Foundation, Inc.

Substrate specifity of protein kinases and computational prediction of substrates

To ensure signalling fidelity, kinases must act only on a defined subset of cellular targets. Appreciating the basis for this substrate specificity is essential for understanding the role of an individual protein kinase in a particular cellular process. The specificity in the cell is determined by a combination of peptide specificity of the kinase (the molecular recognition of the sequence surrounding the phosphorylation site), substrate recruitment and phosphatase activity. Peptide specificity plays a crucial role and depends on the complementarity between the kinase and the substrate and therefore on their three-dimensional structures. Methods for experimental identification of kinase substrates and characterization of specificity are expensive and laborious, therefore, computational approaches are being developed to reduce the amount of experimental work required in substrate identification. We discuss the structural basis of substrate specificity of protein kinases and review the experimental and computational methods used to obtain specificity information. (c) 2005 Elsevier B.V. All rights reserved.

Diplomatic divergence in the antipodes: Globalisation, foreign policy and state identity in Australia and New Zealand

This article compares the constitutive relationship between foreign policy and globalisation in Australia and New Zealand. Drawing upon insights from constructivist international relations theory we argue that foreign policy instantiates a state's social identity, its self-understanding of its role and moral purpose by projecting a distinctive image onto the global stage. We explore the differences and the similarities between Australia and New Zealand by examining how each country views international order, global trade, global governance and human rights and international security. Although both countries appear to be transforming themselves into more 'globalised' states, there are significant differences in the way each seeks to balance the competing strategic and normative demands. This diplomatic divergence, we argue, stems from different conceptions of state identity.

General practice in Australia 2020: "robust and ready" or "rudderless and reeling"?

The future role and structure of Australian general practice remains uncertain, despite a decade of seemingly constant change following the release of the National Health Strategy papers. Some of the suggested change strategies (such as rural Practice Incentive Payments and practice accreditation) have been implemented; others (such as general practitioner involvement with area health authorities in delivering national goals and targets for communities) still await attention. An overarching vision for our health care system in 2020 and general practice's role within it are still to be clearly enunciated. Australia is at variance with other Western countries, such as the United Kingdom, Canada and New Zealand, which have spent significant time refocusing their health systems to deal with an ageing population with an increased burden of chronic disease. Health bureaucrats and governments need to invest strategically in operational primary care now. This will require the active commitment of general practice's national bodies to articulate and actively promote a shared vision for Australian general practice.