Histamine and tryptase modulate asthmatic airway smooth muscle GM-CSF and RANTES release.

Degranulating mast cells are increased in the airway smooth muscle (ASM) of asthmatics, where they may influence ASM function. The aim of the present study was to determine whether histamine and tryptase modulate ASM cell granulocyte-macrophage colony-stimulating factor (GM-CSF) and RANTES (regulated on activation, normal T-cell expressed and secreted) release and also to examine which receptors are involved in this release. Confluent, quiescent ASM cells from asthmatic and nonasthmatic donors were treated with histamine (1 microM-100 microM) with and without histamine receptor antagonist pre-treatment, or the protease-activated receptor (PAR)-2 agonists tryptase (0.5-5 nM) and SLIGKV (100 and 400 microM). The cells were then stimulated with interleukin (IL)-1beta and/or tumour necrosis factor (TNF)-alpha (10 ng.mL(-1)) or left unstimulated for 24 h. Release of GM-CSF and RANTES was determined by ELISA and prostaglandin (PG)E(2) measured by enzyme immunoassay. Neither histamine nor tryptase induced ASM GM-CSF or RANTES secretion. However, histamine increased IL-1beta-induced GM-CSF release and markedly reduced TNF-alpha-induced RANTES release by both asthmatic and nonasthmatic cells to a similar extent, but did not modulate PGE(2) release. All changes involved activation of the histamine H1 receptor as they were partially or fully blocked by chlorpheniramine, but not ranitidine. Tryptase, via its proteolytic activity, also potentiated GM-CSF, but not RANTES, release from asthmatic and nonasthmatic ASM cells induced by both cytokines. PAR-2 involvement in the tryptase potentiation was unlikely because SLIGKV had no effect. In conclusion, mast cells, through histamine and tryptase, may locally modulate airway smooth muscle-induced inflammation in asthma.     

The αvβ6 integrin plays a role in compromised epidermal wound healing

The alphavbeta6 integrin is an exclusively epithelial integrin that is highly expressed during fetal development. In adult tissue, alphavbeta6 integrin is expressed during inflammation, carcinogenesis, and in wound healing. We previously reported that alphavbeta6 integrin is highly expressed in poorly healing human wounds and its over-expression is associated with chronic wounds in a mouse model. The objective of this study was to investigate the role of alphavbeta6 integrin in compromised wound healing induced by hydrocortisone treatment or aging by using young and old mice deficient in or overexpressing the beta6 integrin subunit in the epidermis. Untreated aged beta6 integrin-deficient (beta6-/-) animals showed a significant delay in wound healing when compared to their age-matched controls or younger beta6-/- mice. The most significant delay was observed at the stages where granulation tissue deposition was occurring. Hydrocortisone treatment significantly delayed wound healing in wild-type and beta6 integrin-deficient mice in comparison with the untreated controls. However, hydrocortisone treatment in beta6 integrin overexpressing animals did not cause a significant delay in wound healing. The results of this study suggest that alphavbeta6 integrin plays an important role in wound healing in animals compromised by either age or stress mimicked by hydrocortisone.     

Integrating Nursing Care into Systems of Care for Children with Emotional and Behavioral Disorders

PROBLEM: Recent developments in providing care to children with emotional and behavioral disorders, especially those with serious emotional disturbance, have included the establishment of systems of care. Guided by a set of principles and values, these systems of care have organized and delivered services to children and families with complex needs. To date, nurses have not had a salient role in systems of care. RESULTS: It is estimated that 20% of American children and adolescents have an emotional or mental disorder. As many as two thirds of these children are not receiving services. Systems of care have been funded to provide services for these children, particularly for the most severely affected. To date, nursing has not had a prominent role in these systems of care. CONCLUSIONS: Based on their knowledge, skills, and holistic approach to care, nurses could better integrate nursing care into systems of care. Possible roles as case managers, primary therapists, in-home interventionists, and in educational programs are suggested.     

Autonomy and modernisation: the management of change in an English primary care trust

Recent New Labour policy for the ‘modernisation’ of Government places a good deal of emphasis on decentralisation. This emphasis is particularly marked in relation to the organisation of primary care. However, like hospitals and other National Health Service institutions, primary care trusts (PCTs) are subject to a substantial raft of centrally established performance targets and indicators, including those which contribute to the public award of between zero and three performance ‘stars’. This raises questions about the extent to which employees can exercise autonomy in the context of rigid top‐down directives. This paper presents findings from a study using participant observation and interviews to examine the impact of a training course aimed ostensibly at increasing employee autonomy in an English PCT. The suggestion is that attempts to make employees more autonomous can be seen as a strategy for increasing central control based upon the internalisation by the employees of centrally promulgated values. The attraction of such strategies is that they may be potentially more effective and less costly than alternative strategies of direct control. However, the study suggests that the outcome of attempts by such methods as programmes to increase employee autonomy may be very different from those intended.