Oxygen sensors and energy sensors act synergistically to achieve a graded alteration in gene expression: Consequences for assessing the level of neuroprotection in response to stressors

Changes in gene expression are associated with switching to an autoprotected phenotype in response to environmental and physiological stress. Ubiquitous molecular chaperones from the heat shock protein (HSP) superfamily confer neuronal protection that can be blocked by antibodies. Recent research has focused on the interactions between the molecular sensors that affect the increased expression of neuroprotective HSPs above constitutive levels. An examination of the conditions under which the expression of heat shock protein 70 (Hsp70) was up regulated in a hypoxia and anoxia tolerant tropical species, the epaulette shark (Hemiscyllium ocellatum), revealed that up-regulation was dependent on exceeding a stimulus threshold for an oxidative stressor. While hypoxic-preconditioning confers neuroprotective changes, there was no increase in the level of Hsp70 indicating that its increased expression was not associated with achieving a neuroprotected state in response to hypoxia in the epaulette shark. Conversely, there was a significant increase in Hsp70 in response to anoxic-preconditioning, highlighting the presence of a stimulus threshold barrier and raising the possibility that, in this species, Hsp70 contributes to the neuroprotective response to extreme crises, such as oxidative stress. Interestingly, there was a synergistic effect of coincident stressors on Hsp70 expression, which was revealed when metabolic stress was superimposed upon oxidative stress. Brain energy charge was significantly lower when adenosine receptor blockade, provided by treatment with aminophylline, was present prior to the final anoxic episode, under these circumstances, the level of Hsp70 induced was significantly higher than in the pair-matched saline treated controls. An understanding of the molecular and metabolic basis for neuroprotective switches, which result in an up-regulation of neuroprotective Hsp70 expression in the brain, is needed so that intervention strategies can be devised to manage CNS pathologies and minimise damage caused by ischemia and trauma. In addition, the current findings indicate that measurements of HSP expression per se may provide a useful correlate of the level of neuroprotection achieved in the switch to an autoprotected phenotype.

Supreme Emergencies and the protection of non-combatants in war

Is it ever justifiable to target non-combatants deliberately? This article assesses Michael Walzer's claim that the deliberate targeting of non-combatants may be justifiable during 'supreme emergencies', a view that has received some support but that has elicited little debate. It argues that the supreme emergencies exception to the prohibition on targeting non-combatants is problematic for at least four reasons. First, its utilitarianism contradicts Walzer's wider ethics of war based on a conception of human rights. Second, the exception may undermine the principle of non-combatant immunity. Third, it is based on a historical fallacy. Finally, it is predicated on a strategic fallacy-the idea that killing noncombatants can win wars. The case for rejecting the exception, however, has been opposed by those who persuasively argue that it is wrong to tie leaders' hands when they confront supreme emergencies. The final part of the article addresses this question and suggests that the principle of proportionality may give political leaders room for manoeuvre in supreme emergencies without permitting them deliberately to target non-combatants.

Suntans and sun protection in Australian teen media: 1999 to 2000

In this study, the portrayal of tanned skin and sun protection in magazines, television programs, and movies popular with Australian adolescents were analyzed. Images of models in magazines (n = 1,791), regular/supporting characters in television programs (it = 867), and regular/supporting characters in cinema movies (n = 2,836) for the 12-month period August 1999 to July 2000 were coded and analyzed. Alight tan was the most predominant tan level, and protective clothing was the most common sun protection measure displayed across all forms of media. There were significant associations between gender and tan levels in the television and movie samples. Although it is important to monitor the portrayal of tan levels and sun protection measures in media targeting adolescents, overall, the authors' findings revealed a media environment generally supportive of sun protection objectives.

Arthritic disease suppression and cartilage protection with glycosaminoglycan polypeptide complexes (Peptacans) derived from the cartilage extracellular matrix: A novel approach to therapy

Molecular fragments of cartilage are antigenic and can stimulate an autoimmune response. Oral administration of type II collagen prevents disease onset in animal models of arthritis but the effects of other matrix components have not been reported. We evaluated glycosaminoglycan polypeptides (GAG-P) and matrix proteins (CaP) from cartilage for a) mitigating disease activity in rats with collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) and b) stimulating proteoglycan (PG) synthesis by chondrocytes in-vitro. CIA and AIA were established in Wistar rats using standard methods. Agents were administered orally (10–200 mg/kg), either for seven days prior to disease induction (toleragenic protocol), or continuously for 15 days after injecting the arthritigen (prophylactic protocol). Joint swelling and arthritis scores were determined on day 15. Histological sections of joint tissues were assessed post-necropsy. In chondrocyte cultures, CaP + / − interleukin-1 stimulated PG biosynthesis. CaP was also active in preventing arthritis onset at 3.3, 10 or 20 mg/kg in the rat CIA model using the toleragenic protocol. It was only active at 20 and 200 mg/kg in the CIA prophylactic protocol. GAG-P was active in the CIA toleragenic protocol at 20 mg/kg but chondroitin sulfate and glucosamine hydrochloride or glucosamine sulfate were all inactive. The efficacy of CaP in the rat AIA model was less than in the CIA model. These findings lead us to suggest that oral CaP could be used as a disease-modifying anti-arthritic drug.

Primary prevention of skin cancer: A review of sun protection in Australia and internationally

The incidence of skin cancer is increasing worldwide. Protecting the skin from the sun by wearing protective clothing, using a sunscreen with appropriate sun protection factor, wearing a hat, and avoiding the sun are recommended as primary preventive activities by cancer agencies. In this paper the recent data relating to skin cancer primary preventive behaviour in Australia and other countries is reviewed. Comparison of the studies in a table format summarizing the methods, objectives, participants, findings and implications may be obtained from the corresponding author. The sun protection knowledge, attitudes and behaviour patterns observed in Australia are similar in other countries, although Australian studies generally, report higher knowledge levels about skin cancer and higher levels of sun protection. The findings suggest that sunscreen is the most frequent method of sun protection used across all age groups, despite recommendations that it should be at? adjunct to other forms of protection. While young children's sun protective behaviour is largely influenced by their parents' behaviours, they are still tinder protected, and sun protective measures such as seeking shade, avoiding the sun and protective clothing need to be emphasized. Adolescents have the lowest skin protection rates of all age groups. Within the adult age range, women and people with sensitive skin were most likely to be using skin protection. However, women were also more likely than men to sunbath deliberately and to use sun-tanning booths. The relationship between skin protection knowledge and attitudes, attitudes towards tanning and skin protection behaviour needs further investigation. Further studies need to include detailed assessments of sunscreen use and application patterns, and future health promotion activities need to focus on sun protection by wearing clothing and seeking shade to avoid increases in the sunburn rates observed to date.

Interagency collaboration between child protection and mental health services: Practices, attitudes and barriers

Objective: The aim of this paper is to examine some of the factors that facilitate and hinder interagency collaboration between child protection services and mental health services in cases where there is a parent with a mental illness and there are protection concerns for the child(ren). The paper reports on agency practices, worker attitudes and experiences, and barriers to effective collaboration. Method: A self-administered, cross-sectional survey was developed and distributed via direct mail or via line supervisors to workers in statutory child protection services, adult mental health services, child and youth mental health services, and Suspected Child Abuse and Neglect (SCAN) Teams. There were 232 completed questionnaires returned, with an overall response rate of 21%. Thirty-eight percent of respondents were statutory child protection workers. 39% were adult mental health workers, 16% were child and youth mental health workers, and 4% were SCAN Team medical officers (with 3% missing data). Results: Analysis revealed that workers were engaging in a moderate amount of interagency contact, but that they were unhappy with the support provided by their agency. Principle components analysis and multivariate analysis of variance (MANOVA) on items assessing attitudes toward other workers identified four factors, which differed in rates of endorsement: inadequate training, positive regard for child protection workers, positive regard for mental health workers, and mutual mistrust (from highest to lowest level of endorsement). The same procedure identified the relative endorsement of five factors extracted from items about potential barriers: inadequate resources, confidentiality, gaps in interagency processes, unrealistic expectations, and professional knowledge domains and boundaries. Conclusions: Mental health and child protection professionals believe that collaborative practice is necessary; however, their efforts are hindered by a lack of supportive structures and practices at the organizational level. (c) 2005 Published by Elsevier Ltd.