The 'knowledge politics' of democratic peace theory

How do academic ideas influence US foreign policy, under what conditions and with what consequences? This article traces the rise, ‘securitisation’ and political consequences of democratic peace theory (DPT) in the United States by exploring the work of Doyle, Diamond and Fukuyama. Ideas influence US foreign policy under different circumstances, but are most likely to do either during and after crises when the policy environment permits ‘new thinking’, or when these ideas have been developed through state-connected elite knowledge networks, or when they are (or appear paradigmatically congenial to) foreign policymakers’ mindsets, or, finally, when they become institutionally-embedded. The appropriation of DPT by foreign policymakers has categorised the world into antagonistic blocs – democratic/non-democratic zones of peace/turmoil – as the corollary to a renewed American mission to make the world ‘safer’ through ‘democracy’ promotion. The roles of networked organic intellectuals – in universities and think tanks, for instance – were particularly important in elevating DPT from the academy to national security managers

New insights into the systemic effects of oral lactoferrin: transcriptome profiling

The immunomodulatory nature of lactoferrin (LF) derives from its ability to bridge innate and adaptive immunity in obtaining physiological equilibrium. LF is an attractive molecule for treatment of diseases that compromise immune homeostasis. Oral delivery is a preferable method for LF administration; however, its bioavailability is affected by protein degradation and absorption. The aim of this study was to evaluate the systemic effects of orally and intravenously (IV) administered recombinant human LF (rhLF) on blood cell transcriptome profiling. Rats were administered a single dose of rhLF by gavage or IV. The transcriptome profiles from the control and the rhLF-treated rats after 3, 6, and 24 h were analyzed using a Clariom D microarray. The results showed differentially expressed genes in response to IV as well as oral administered rhLF including coding and noncoding RNAs. Moreover, a comparison of the differentially expressed genes between oral and IV administration of LF, after 6 h, revealed that the majority (72.8%) of the genes altered in response to oral administration of rhLF were the same as for the IV treatment. The pathway profiles showed similarities in up-regulation of specific genes involved in oxidative stress and inflammatory responses for both routes of treatments. These findings provide evidence of the systemic signal transduction effects of orally administered rhLF.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Differential effects of prophylactic, concurrent and therapeutic lactoferrin treatment on LPS-induced inflammatory responses in mice

Mice injected with endotoxin develop endotoxaemia and endotoxin-induced death, accompanied by the oxidative burst and overproduction of inflammatory mediators. Lactoferrin, an iron binding protein, provides a natural feedback mechanism to control the development of such metabolic imbalance and protects against deleterious effects of endotoxin. We investigated the effects of intraperitoneal administration of human lactoferrin on lipopolysaccharide (LPS)-induced release of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10) and nitric oxide (NO) in vivo. Lactoferrin was administered as a prophylactic, concurrent or therapeutic event relative to endotoxic shock by intravenous injection of LPS. Inflammatory mediators were measured in serum at 2, 6 and 18 h post-shock induction. Administration of lactoferrin 1 h before LPS resulted in a rather uniform inhibition of all mediators; TNF by 82%, IL-6 by 43%, IL-10 by 47% at 2 h following LPS injection,and reduction in NO (80%) at 6 h post-shock. Prophylactic administration of lactoferrin at 18 h prior to LPS injection resulted in similar decreases in TNF-α (95%) and in NO (62%), but no statistical reduction in IL-6 or IL-10. Similarly, when lactoferrin was administered as a therapeutic post-induction of endotoxic shock, significant reductions were apparent in TNF-α and NO in serum, but no significant effect was seen on IL-6 and IL-10. These results suggest that the mechanism of action for lactoferrin contains a component for differential regulation of cellular immune responses during in vivo models of sepsis

Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthma

Pollen grains contain reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidases and in contact with mucosal surfaces generate superoxide anion ([Formula: see text]). In the presence of iron, [Formula: see text] may be converted to more reactive oxygen radicals, such as to H(2)O(2) and/or (•)OH, which may augment antigen-induced airway inflammation. The aim of the study was to examine the impact of lactoferrin (LF), an iron-binding protein, on ragweed (Ambrosia artemisiifolia) pollen extract (RWE)-induced cellular oxidative stress levels in cultured bronchial epithelial cells and accumulation of inflammatory and mucin-producing cells in airways in a mouse model of allergic airway inflammation. Results show that LF lowered RWE-induced increase in cellular reactive oxygen species (ROS) levels in bronchial epithelial cells. Most importantly, LF significantly decreased accumulation of eosinophils into airways and subepithelium of intranasally challenged, sensitized mice. LF also prevented development of mucin-producing cells. Amb a 1, the major allergenic ragweed pollen antigen lacking NAD(P)H oxidase activity, induced low-grade airway inflammation. When administered along with glucose oxidase (G-ox), a superoxide-generating enzyme, Amb a 1 induced robust airway inflammation, which was significantly lowered by LF. Surprisingly, LF decreased also inflammation caused by Amb a 1 alone. Iron-saturated hololactoferrin had only a marginal effect on RWE-induced cellular ROS levels and RWE- or Amb a 1 plus G-ox-induced inflammation. We postulate that free iron in the airways chemically reduces [Formula: see text] to more reactive species which augment antigen-induced inflammation in a mouse model of asthma. Our results suggest the utility of LF in human allergic inflammatory disorders