Concurrent expression of procoagulant and plasminogen activator activities by rabbit alveolar macrophages in vitro: Opposite modulating effects of prostaglandin E2

We examined the effects of arachidonic acid metabolites on the simultaneous expression of procoagulant (PC) and plasminogen activator (PA) activities by rabbit alveolar macrophages. Incubation with lymphocyte-conditioned medium (LCM) caused a significant increase in cell-associated PC activity. Co-treatment with indomethacin (1 [mu]M) reduced this augmentation in PC activity by 33% (p 2 in concentrations as low as 1 nM. Addition of 100 nM PGE2 to these cells caused an increase in PC activity 2.7-fold greater than that achieved by LCM alone, while PGE2 suppressed released PA activity by 62%. PGE2 and indomethacin had similar but less pronounced effects on phorbol myristate acetate-treated cells. These effects of PGE2 could be duplicated by PGE1, but not by any other arachidonic acid metabolite (PGF2[alpha], PGI2, PGD2, ddPGF2[alpha], LTB4, or LTC4). While PGE2 increases intracellular levels of cAMP, the observed effects on PC and PA activities could not be reproduced fully by treatment with dibutyryl cAMP. We conclude that PGE2 amplifies the augmentation of PC activity by stimulated alveolar macrophages while concurrently inhibiting expression of plasminogen activator. This suggests that PGE2 may be a significant mediator in regulating the highly interactive processes of inflammation and coagulation/fibrinolysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27166/1/0000161.pd

Rethinking Radical Democracy

Over the course of three decades, vocabularies of radical democracy have pressed their stamp on democratic thought. Trading on the intuition that there is more to democracy than elections, they have generated critical insights into the important role that practices of pluralisation and critique play in bettering institutional politics. As a result, few would today deny the radical democratic contribution to democratic thought. What many might question, however, is its continuing traction. The paper probes this question, focusing on the nuanced place of democracy in contemporary radical work. It grapples with the difficulties that this poses for radical democrats and it suggests that a way of overcoming these difficulties – that threaten to undermine the coherence of radical democracy – is to rethink and reconstruct the distinctiveness of its vocabulary. The paper attempts such a reconstruction. It develops the idea of the promissory rule of the many and it discusses the ways it rejuvenates broader democratic thought

Revolution from above in English schools: neoliberalism, the democratic commons and education

The ideas of the New Left and the recently emerged alter-globalisation movements are marginal within current policy debates concerning the English education system. Here I seek to demonstrate the interconnections between the New Left and the alter-globalisation movement and suggest that these ideas contain a powerful corrective to the increasingly authoritarian present. The next part of the article considers the development of neoliberalism both in a theoretical context and since the arrival of the new Conservative–Liberal government in the UK. Here I outline the rapid transformation of English schools under the academies programme and look at how it has been explicitly linked to ideas of ‘moral collapse’ evident in the popular discourse of ‘Broken Britain’. Especially significant in this respect has been the labelling of comprehensive schools as ‘failures’ and the explicit imposition of more authoritarian understandings of pedagogy. I seek to explore both the rapidity of this transformation in the context of the dissatisfaction with the idea of comprehensive schools shown by the political Right and the Third Way’s reworking of socialism. Finally I briefly consider more progressive alternatives for schools and education by returning to the idea of the democratic commons. In this respect, the cultural Left needs to explore more radical alternatives beyond the defence of comprehensive schooling which sounds both nostalgic and misplaced within our global times

Are social innovation paradigms incommensurable?

This paper calls attention to the problematic use of the concept of social innovation which remains undefined despite its proliferation throughout academic and policy discourses. Extant research has thus far failed to capture the socio-political contentions which surround social innovation. This paper therefore draws upon the work of Thomas Kuhn and conducts a paradigmatic analysis of the field of social innovation which identifies two emerging schools: one technocratic, the other democratic. The paper identifies some of the key thinkers in each paradigm and explains how the struggle between these two paradigms reveals itself to be part of a broader conflict between neoliberalism and it opponents and concludes by arguing that future research focused upon local contextualised struggles will reveal which paradigm is in the ascendancy

Cuidados prestados à mulher na visita domiciliar da “Primeira Semana de Saúde Integral”

Objetivo: Avaliar o cuidado prestado à mulher na visita domiciliar da “Primeira Semana de Saúde Integral”.Método: Estudo transversal realizado em serviço especializado do Recife, Pernambuco. Entre setembro e dezembro de 2013, 190 puérperas cadastradas na Estratégia Saúde da Família responderam a um questionário para verificar a existência de associação entre a visita domiciliar e as variáveis investigadas, utilizando o teste Qui-quadrado, com nível de confiança de 95%.Resultados: Predominou idade de até 29 anos (68,5%) e risco gestacional alto (59,5%), sendo 46,9% primíparas. Na primeira semana pós-alta, 42,1% receberam visita. Constatou-se associação entre atenção pré-natal em nível local e visita na primeira semana (p=0,049). A participação do enfermeiro na visita estava associada à maior realização de exame de mama (p=0,000), abdômen (p=0,000) e investigação de condições emocionais (p=0,029).Conclusões: Evidencia-se a necessidade de instituir um planejamento rotineiro para efetuar a visita domiciliar programática, priorizando as puérperas de risco.Palavras-chave: Período pós-parto. Visita domiciliar. Estratégia Saúde da Família. Saúde da mulher. Avaliação em saúde

Disassembly and reassembly of human papillomavirus virus-like particles produces more virion-like antibody reactivity

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) vaccines based on major capsid protein L1 are licensed in over 100 countries to prevent HPV infections. The yeast-derived recombinant quadrivalent HPV L1 vaccine, GARDASIL(R), has played an important role in reducing cancer and genital warts since its introduction in 2006. The L1 proteins self-assemble into virus-like particles (VLPs).</p> <p>Results</p> <p>VLPs were subjected to post-purification disassembly and reassembly (D/R) treatment during bioprocessing to improve VLP immunoreactivity and stability. The post-D/R HPV16 VLPs and their complex with H16.V5 neutralizing antibody Fab fragments were visualized by cryo electron microscopy, showing VLPs densely decorated with antibody. Along with structural improvements, post-D/R VLPs showed markedly higher antigenicity to conformational and neutralizing monoclonal antibodies (mAbs) H16.V5, H16.E70 and H263.A2, whereas binding to mAbs recognizing linear epitopes (H16.J4, H16.O7, and H16.H5) was greatly reduced.</p> <p>Strikingly, post-D/R VLPs showed no detectable binding to H16.H5, indicating that the H16.H5 epitope is not accessible in fully assembled VLPs. An atomic homology model of the entire</p> <p>HPV16 VLP was generated based on previously determined high-resolution structures of bovine papillomavirus and HPV16 L1 pentameric capsomeres.</p> <p>Conclusions</p> <p>D/R treatment of HPV16 L1 VLPs produces more homogeneous VLPs with more virion-like antibody reactivity. These effects can be attributed to a combination of more complete and regular assembly of the VLPs, better folding of L1, reduced non-specific disulfide-mediated aggregation and increased stability of the VLPs. Markedly different antigenicity of HPV16 VLPs was observed upon D/R treatment with a panel of monoclonal antibodies targeting neutralization sensitive epitopes. Multiple epitope-specific assays with a panel of mAbs with different properties and epitopes are required to gain a better understanding of the immunochemical properties of VLPs and to correlate the observed changes at the molecular level. Mapping of known antibody epitopes to the homology model explains the changes in antibody reactivity upon D/R. In particular, the H16.H5 epitope is partially occluded by intercapsomeric interactions involving the L1 C-terminal arm. The homology model allows a more precise mapping of antibody epitopes. This work provides a better understanding of VLPs in current vaccines and could guide the design of improved vaccines or therapeutics.</p