2 resultados para i.p.-injection

em Duke University


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Radiculopathy, a painful neuroinflammation that can accompany intervertebral disc herniation, is associated with locally increased levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). Systemic administration of TNF antagonists for radiculopathy in the clinic has shown mixed results, and there is growing interest in the local delivery of anti-inflammatory drugs to treat this pathology as well as similar inflammatory events of peripheral nerve injury. Curcumin, a known antagonist of TNFα in multiple cell types and tissues, was chemically modified and conjugated to a thermally responsive elastin-like polypeptide (ELP) to create an injectable depot for sustained, local delivery of curcumin to treat neuroinflammation. ELPs are biopolymers capable of thermally-triggered in situ depot formation that have been successfully employed as drug carriers and biomaterials in several applications. ELP-curcumin conjugates were shown to display high drug loading, rapidly release curcumin in vitro via degradable carbamate bonds, and retain in vitro bioactivity against TNFα-induced cytotoxicity and monocyte activation with IC50 only two-fold higher than curcumin. When injected proximal to the sciatic nerve in mice via intramuscular (i.m.) injection, ELP-curcumin conjugates underwent a thermally triggered soluble-insoluble phase transition, leading to in situ formation of a depot that released curcumin over 4days post-injection and decreased plasma AUC 7-fold.

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*Designated as an exemplary master's project for 2015-16*

This paper examines how contemporary literature contributes to the discussion of punitory justice. It uses close analysis of three contemporary novels, Margaret Atwood’s The Heart Goes Last, Hillary Jordan’s When She Woke, and Joyce Carol Oates’s Carthage, to deconstruct different conceptions of punitory justice. This analysis is framed and supported by relevant social science research on the concept of punitivity within criminal justice. Each section examines punitory justice at three levels: macro, where media messages and the predominant social conversation reside; meso, which involves penal policy and judicial process; and micro, which encompasses personal attitudes towards criminal justice. The first two chapters evaluate works by Atwood and Jordan, examining how their dystopian schemas of justice shed light on top-down and bottom-up processes of punitory justice in the real world. The third chapter uses a more realistic novel, Oates’s Carthage, to examine the ontological nature of punitory justice. It explores a variety of factors that give rise to and legitimize punitory justice, both at the personal level and within a broader cultural consensus. This chapter also discusses how both victim and perpetrator can come to stand in as metaphors to both represent and distract from broader social issues. As a whole, analysis of these three novels illuminate how current and common conceptualizations of justice have little to do with the actual act of transgression itself. Instead, justice emerges as a set of specific, conditioned responses to perceived threats, mediated by complex social, cultural, and emotive forces.