Improving Indwelling Glucose Sensor Performance: Porous, Dexamethasone-Releasing Coatings that Modulate the Foreign Body Response

Inflammation and the formation of an avascular fibrous capsule have been identified as the key factors controlling the wound healing associated failure of implantable glucose sensors. Our aim is to guide advantageous tissue remodeling around implanted sensor leads by the temporal release of dexamethasone (Dex), a potent anti-inflammatory agent, in combination with the presentation of a stable textured surface.

First, Dex-releasing polyurethane porous coatings of controlled pore size and thickness were fabricated using salt-leaching/gas-foaming technique. Porosity, pore size, thickness, drug release kinetics, drug loading amount, and drug bioactivity were evaluated. In vitro sensor functionality test were performed to determine if Dex-releasing porous coatings interfered with sensor performance (increased signal attenuation and/or response times) compared to bare sensors. Drug release from coatings monitored over two weeks presented an initial fast release followed by a slower release. Total release from coatings was highly dependent on initial drug loading amount. Functional in vitro testing of glucose sensors deployed with porous coatings against glucose standards demonstrated that highly porous coatings minimally affected signal strength and response rate. Bioactivity of the released drug was determined by monitoring Dex-mediated, dose-dependent apoptosis of human peripheral blood derived monocytes in culture.

The tissue modifying effects of Dex-releasing porous coatings were accessed by fully implanting Tygon® tubing in the subcutaneous space of healthy and diabetic rats. Based on encouraging results from these studies, we deployed Dex-releasing porous coatings from the tips of functional sensors in both diabetic and healthy rats. We evaluated if the tissue modifying effects translated into accurate, maintainable and reliable sensor signals in the long-term. Sensor functionality was accessed by continuously monitoring glucose levels and performing acute glucose challenges at specified time points.

Sensors treated with porous Dex-releasing coatings showed diminished inflammation and enhanced vascularization of the tissue surrounding the implants in healthy rats. Functional sensors with Dex-releasing porous coatings showed enhanced sensor sensitivity over a 21-day period when compared to controls. Enhanced sensor sensitivity was accompanied with an increase in sensor signal lag and MARD score. These results indicated that Dex-loaded porous coatings were able to elicit a favorable tissue response, and that such tissue microenvironment could be conducive towards extending the performance window of glucose sensors in vivo.

The diabetic pilot animal study showed differences in wound healing patters between healthy and diabetic subjects. Diabetic rats showed lower levels of inflammation and vascularization of the tissue surrounding implants when compared to their healthy counterparts. Also, functional sensors treated with Dex-releasing porous coatings did not show enhanced sensor sensitivity over a 21-day period. Moreover, increased in sensor signal lag and MARD scores were present in porous coated sensors regardless of Dex-loading when compared to bare implants. These results suggest that the altered wound healing patterns presented in diabetic tissues may lead to premature sensor failure when compared to sensors implanted in healthy rats.

Hemolymph Functions In Mytilus-Californianus - Cytochemistry Of Hemocytes And Their Responses To Foreign Implants And Hemolymph Factors In Phagocytosis

The hemocytes of Mytilus californianus are of three types: small and large basophils and large granular acidophils. The basophils contain lysosomal enzymes and phagocytose colloidal carbon. Agglutinins for yeast and human A Rh+ve erythrocytes are present in plasma, but are not needed for effective phagocytosis; in vitro both acidophilic and basophilic hemocytes rapidly phagocytose these particles. Plasma proteins, analyzed electrophoretically, are under strong homeostatic control. When Mya arenaria mantle is placed orthotopically on M. californianus mantle, the implant is invaded by host hemocytes in a manner consistent with that described in other published reports on molluscan graft rejection. Steady state is achieved by 26 days postimplant. Second- and third-set implants are rejected more rapidly than are first-set implants, but this is not a specific response. Third-set implants elicit a host cellular response that is more localized than the response to first-set implants. These data do not permit conclusions with respect to memory in these molluscan immune responses, but do imply a qualitative “improvement” in this quasi-immune response of M. californianus.

The Euro as an International Currency: explaining puzzling first evidence from the foreign exchange markets

This paper presents evidence that the bid-ask spreads in euro rates increased relative to the corresponding bid-ask spreads in the German mark (DM) prior to the creation of the currency union. This comes with a decrease in transaction volume in the euro rates relative to the previous DM rates. The starkest example is the DM(euro)/yen rate in which the spread has risen by almost two-thirds while the volume decreased by more than one third. This outcome is surprising because the common currency concentrated market liquidity in fewer external euro rates and higher volume tends to be associated with lower spreads. We propose a microstructure explanation based on a change in the information environment of the FX market. The elimination of many cross currency pairs increased the market transparency for order flow imbalances in the dealership market. It is argued that higher market transparency adversely affects the inventory risk sharing efficiency of the dealership market and induces the observed euro spread increase and transaction volume shortfall.

'Foreign' Terror? London Bombings, Resistance and the Failing State

The British government's response to the London bombings sought to make the terror of that day foreign, even though it appeared largely domestic. This helped construct it as unusual, contingent, part of the uncontrollable ‘otherness’ of the ‘foreign’. However, it also drew the response into the arena of British foreign policy, where the ‘failing state’ has been the dominant conceptualisation of insecurity and terrorism, especially since September 11th. When the bombings are examined through the ‘failing state’ disturbing and important problems are uncovered. Primarily, the ‘failing state’ discourse deconstructs under the influence of the terrorism in London, revealing that Britain itself is a ‘failing state’ by its own description and producing a generalisation of state ‘failure’. It thereby reveals several possible sites for responding to and resisting the government's representation.

Textualising British Politics: Deconstructing the subject of British foreign policy

British politics has been described as a sub-discipline crying out for methodological and ideational cross-fertilisation. Where other areas of political science have benefited from new ideas, British politics has remained largely atheoretical and underdeveloped. This has changed recently with the rise of interpretivism but the study of British politics would also benefit from more serious engagement with poststructuralism. With this in mind, I examine how the thought of Jacques Derrida and deconstruction could be useful for thinking through the foundations of British politics, re-examining what appears natural or given and revealing the problematic and contradictory status of these foundations. After suggesting the need to 'textualise' British politics', I illustrate how deconstruction operates in a specific context, that of British foreign policy since 1997. This exploration reveals how certain decisions (such as the invasion of Iraq in 2003) became possible in the first place, and how their basis in an idea of an 'us' and a 'them', a coherent, autonomous subject separate from its object, is deeply problematic. Such a critical reading of British politics is impossible within the dominant interpretivist framework, and opens up new possibilities for thought which form an important supplement to existing ways of studying the field.