RESUMEN
BACKGROUND: Changes in clinical practice are brought about by the weight of clinical evidence for and against an intervention. Clinical evidence of efficacy relies on the dissemination of research results, usually by publication in medical journals which is often seen as a pre-requisite for progression of an intervention through further clinical trials or implementation studies. HOW FAR HAS RESEARCH PROGRESSED ALONG THE TRANSLATIONAL PATHWAY?: We undertook an exploratory exercise to determine where basic and translational medical research is currently published. Original research articles (329 in total) published in high impact general and specialist medical journals were classified into different stages of research within the translational medicine pathway. WHERE IS TRANSLATIONAL RESEARCH PUBLISHED?: The general medical journals had the broadest spread of published research over the translational pathway. The specialist journals tended to be positioned to disseminate the research findings of early stage translational research from basic science results through to early stages of clinical testing. CONCLUSION: It is not possible for one journal to satisfy all the needs of the reader and the author along the translational medicine pathway. For an intervention to progress along the translational pathway background information should be readily accessible in the article. This pathway is currently being actively managed by the funding agencies but the next challenge is to ensure the pathway operates efficiently and does not allow promising innovations to languish and to provide a smoother transition for interventions to reach the clinic in a quicker timescale. It is clear that the dissemination of results in the right place at the right time is crucial to the transition of an intervention from the laboratory to clinical practice.
Asunto(s)
Publicaciones Periódicas como Asunto , Edición , Investigación Biomédica TraslacionalRESUMEN
There is increasing evidence that modified phospholipid products of low density lipoprotein (LDL) oxidation mediate inflammatory processes within vulnerable atherosclerotic lesions. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is present in vulnerable plaque regions where it acts on phospholipid oxidation products to generate the pro-inflammatory lysophsopholipids and oxidized non-esterified fatty acids. This association together with identification of circulating Lp-PLA(2) levels as an independent predictor of cardiovascular disease provides a rationale for development of Lp-PLA(2) inhibitors as therapy for atherosclerosis. Here we report a systematic analysis of the effects of in vitro oxidation in the absence and presence of an Lp-PLA(2) inhibitor on the phosphatidylcholine (PC) composition of human LDL. Mass spectrometry identifies three classes of PC whose concentration is significantly enhanced during LDL oxidation. Of these, a series of molecules, represented by peaks in the m/z range 594-666 and identified as truncated PC oxidation products by accurate mass measurements using an LTQ Orbitrap mass spectrometer, are the predominant substrates for Lp-PLA(2). A second series of oxidation products, represented by peaks in the m/z range 746-830 and identified by LTQ Orbitrap analysis as non-truncated oxidized PCs, are quantitatively more abundant but are less efficient Lp-PLA(2) substrates. The major PC products of Lp-PLA(2), saturated and mono-unsaturated lyso-PC, constitute the third class. Mass spectrometric analysis confirms the presence of many of these PCs within human atherosclerotic lesions, suggesting that they could potentially be used as in vivo markers of atherosclerotic disease progression and response to Lp-PLA(2) inhibitor therapy.