Potencies of human immunodeficiency virus protease inhibitors in vitro against Plasmodium falciparum and in vivo against murine malaria

Parasite resistance to antimalarial drugs is a serious threat to human health, and novel agents that act on enzymes essential for parasite metabolism, such as proteases, are attractive targets for drug development. Recent studies have shown that clinically utilized human immunodeficiency virus (HIV) protease inhibitors can inhibit the in vitro growth of Plasmodium falciparum at or below concentrations found in human plasma after oral drug administration. The most potent in vitro antimalarial effects have been obtained for parasites treated with saquinavir, ritonavir, or lopinavir, findings confirmed in this study for a genetically distinct P. falciparum line (3D7). To investigate the potential in vivo activity of antiretroviral protease inhibitors (ARPIs) against malaria, we examined the effect of ARPI combinations in a murine model of malaria. In mice infected with Plasmodium chabaudi AS and treated orally with ritonavir-saquinavir or ritonavir-lopinavir, a delay in patency and a significant attenuation of parasitemia were observed. Using modeling and ligand docking studies we examined putative ligand binding sites of ARPIs in aspartyl proteases of P. falciparum (plasmepsins II and IV) and P. chabaudi (plasmepsin) and found that these in silico analyses support the antimalarial activity hypothesized to be mediated through inhibition of these enzymes. In addition, in vitro enzyme assays demonstrated that P. falciparum plasmepsins II and IV are both inhibited by the ARPIs saquinavir, ritonavir, and lopinavir. The combined results suggest that ARPIs have useful antimalarial activity that may be especially relevant in geographical regions where HIV and P. falciparum infections are both endemic.

In the most high and palmy state of Queensland

Peter Beattie's efforts to improve the lives of Indigenous Australians needs support.

Between safety and vulnerability:the exiled other of international relations

Inspired by the idea of safe citizenship this article queries the possibilities of safety in an age of securitization. It challenges the cosmopolitan worldview and its iteration of a global cosmopolitan citizen. It champions an account of affective citizenship, narration and attends to the trauma of exile. It offers an account of exile before suggesting an institutional design premised on politicization. This design, it is argued, facilitates moments of storytelling fostering individual empowerment. This unorthodox rendering of agency allows the traumatized exile to negotiate the world as it is, not as it could be, as a potential ‘safe’ citizen.

Justice and morality:human suffering, natural law and international politics

Bridging the contending theories of natural law and international relations, this book proposes a 'relational ontology' as the basis for rethinking our approach to international politics. The book contains a number of challenging and controversial ideas on the study of international political thought which should provoke constructive debate within international relations theory, political theory, and philosophical ethics. © Amanda Russell Beattie 2010. All rights reserved.

'Only in the leap from the lion's head will he prove his worth':natural law and international relations

This article argues the benefits of including a theological interpretation of natural law morality within the normative discourses of international politics. It challenges the assumption of a Grotian secular natural law arguing that practical reason, in a Thomist interpretation, is better suited to the demands of international political theory. It engages with themes of agency, practical reason, and community in order to enhance the content of the post-territorial community evidenced in ethical cosmopolitan debates. Likewise, it envisions a simultaneously enhancing a rapprochement among cosmopolitan and communitarian discourses of international politics facilitated through an institutional design guided by the morality of natural law.

The vulnerable subject:beyond rationalism in international relations

International Relations remains faithful to its rationalist roots focusing on instrumental forms of power and authority to address global problems and, in the process, fail to acknowledge a sense of vulnerability permeating the global community. This book challenges such assumptions establishing an account of international politics that draws on the ethical assumptions of agonism. it highlights the inherent struggle associated with individual and community based engagement to address this struggle. While it does not offer one single mode of engagement to overcome vulnerability per se, it hopes to elicit a series of reactions, on the part of the reader, provoking grater reflection on the nature of such shared vulnerabilities thereby challenging the dominance of rationalist assumptions.

Engaging autobiography:mobility trauma and international relations

This article outlines the possibilities of autobiographical stories to criticize status quo iterations of International Relations (IR). The article draws on the personal experiences of the author’s deportation order issued by the United Kingdom’s Home Office and its associated Border Agency (UKBA) to challenge the accepted assumptions of a cosmopolitan worldview as it relates to orderly international institutional design. It highlights the possibilities of trauma when border management and personal mobility collide. It suggests that mobility trauma ensues when the expectations of human mobility, outlined in Article 13 of the Universal Declaration of Human Rights, infringe the state’s role as security provider. It begins in part one with a challenge to the traditional role and understanding of international borders that sustain order within the international. It examines the unacknowledged role that human vulnerability plays within IR and institutional design while frankly engaging with human vulnerability and trauma in the second section. This section details the experiences of the author when her mobility rights were curtailed and the ensuing identity crisis prompted by such events. The final section investigates the ideas of critical cosmopolitan scholarship demanding that such discourses acknowledge and work through the possibility of failed agency when the demands of state security supersede individual mobility rights. It turns to the possibility of traumatic iterations of IR in order to probe such possibilities. The article suggests, in its conclusion, the possibility of storytelling and psychoanalysis to endorse unorthodox agency, and the possibility of a dynamic international institutional design, that challenges the status quo iterations of IR.

Seeking out the untold stories of mobility

Postedonteh blog RelationsInternational by Laura Sjoberg, an Associate Professor of Political Science at the University of Florida.