Nitrite directly vasodilates hypoxic vasculature via nitric oxide-dependent and -independent pathways.

BACKGROUND AND PURPOSE: It is postulated that nitrite requires reduction to nitric oxide in order to exert its relaxant effect upon isolated hypoxic vessels. Herein, we evaluate the relative contribution of nitric oxide and characterize the downstream mechanisms of nitrite-induced vasorelaxation. EXPERIMENTAL APPROACH: Aortic rings were treated with pharmacological agents and exposed to hypoxia (<1% O(2)). Following pre-constriction, nitrite (10 microM final) was added to appropriate baths; isometric tension was recorded throughout. KEY RESULTS: Nitrite (under hypoxic conditions at physiological pH) is capable of exerting physiological effects that cannot be completely inhibited by the inhibitor of soluble guanylate cyclase (sGC), 1H [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one or a nitric oxide scavenger (carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide). Simultaneous blockade of both sGC and cyclooxygenase (COX) completely inhibited the response to nitrite. With regard to the nitric oxide-dependent component, we confirm that aldehyde oxidase, but not xanthine oxidase or endothelial nitric oxide synthase, was important for the actions of nitrite in our model. CONCLUSIONS AND IMPLICATIONS: Nitric oxide generated from nitrite is not exclusively responsible for the physiological actions observed in isolated hypoxic vessels. Nitrite operates via different pathways dependent on the presence or absence of endothelium to produce vasorelaxation. In intact vessels, both sGC and COX enzymes appear to be important. Irrespective of this difference in relaxation mechanism, nitrite is capable of producing the same maximum relaxation, regardless of the presence of endothelium. Having investigated possible nitrite reduction sites, we confirm that aldehyde oxidase is important for the actions of nitrite.

Neglected issues and voices.

The 2004 Tsunami highlighted the silence which surrounds gender issues, in particular the incidence of rape and sexual abuse of women and girls displaced by natural disasters and conflict. They include lack of recognition of women's sanitation needs, the need for safe, private places to bathe, secure spaces for single women and girls, lack of contraception, accessible sexual and reproductive health care, and legal measures to be taken against men who rape and abuse women. Reports of violence against women and increased domestic violence have been documented in all tsunami affected countries. Women from across the affected region came together in New York, March 2005 at the meeting of the UN Commission for the Status of Women to review the implementation of the Beijing Platform for Action. Through their efforts at that meeting, a United Nations Resolution was passed in which Governments made commitments to address gender issues and sexual abuse in disaster situations.

Placing ethics in the centre: negotiating new spaces for ethical research in conflict situations.

Issues of power and consent, confidentiality, trust, and benefit, risks to researchers, and potential harm to participants, are all contested when working with different cultures and within environments marked by violence and insecurity. Difficulty resolving these dilemmas may paralyse ethics committees, may fail to give the guidance sought by researchers, and will not help populations who are among the world's most vulnerable. Even where efforts are made to respond to ethical guidelines and to improve practice, considerable impediments are present in many developing countries, including lack of formal ethical review structures in unstable settings, lack of required skills, limited political and institutional recognition of ethical issues, competing interests, and limitations in clinical and research practice (Elsayed 2004, Macklin 2004). In conflict settings, these limitations are more marked, and the responsibilities of the researcher for ethical practice are greater, but the mechanisms for oversight are weaker. Moreover, the constant focus on vulnerabilities and problems, and the often almost total lack of recognition of strengths and resilience, can further disempower already exploited groups and individuals. The capacity of refugees and communities in conflict to take an active role in the research process is seldom acknowledged, and undermines the potential for more innovative research which can help generate the evidence for better policy and practice.