The lactate conundrum in wound healing: Clinical and experimental findings indicate the requirement for a rapid point-of-care diagnostic

The lactate conundrum in wound healing: Clinical and experimental findings indicate the requirement for a rapid point-of-care diagnostic
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DOI:
10.1002/btpr.1561
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发表时间:
2012-07-01
影响因子:
2.9
通讯作者:
Vowden, Peter
Vowden, Peter
中科院分区:
工程技术4区
文献类型:
--
作者:
Britland, Stephen;Ross-Smith, Oliver;Vowden, Peter

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慢性伤口的日益流行对拥有先进医疗保健服务的国家具有重大的财政影响。尽管人们认识到容易导致难以愈合的伤口的疾病,但对其病因了解较少,部分原因是伤口管理从业者缺乏专门的诊断支持。愈合的预后指标可能是伤口生物化学固有的,但在常规临床研究中仍然不可见;乳酸就是一个例子。在这项研究中,20名在医院接受伤口处理的患者渗出液中的乳酸浓度是不同的,但在某些情况下接近或超过20 mM。体外活性研究表明,成纤维细胞和内皮细胞耐受低浓度乳酸(110 MM),但细胞活性受到高浓度乳酸(=20 mM)的严重影响。划痕单层实验表明,随着乳酸剂量的增加,细胞迁移早于活性受到影响,免疫细胞化学表明这与细胞骨架破坏有关。开发了一种基于酶的乳酸盐比色分析原型,可在临床实践中快速产生颜色变化,并能够在凝胶载体中发挥作用,同时考虑到了护理点试纸的应用。一项涉及30名志愿者的随机单盲试验,使用色谱图校准测定结果表明,乳酸浓度可以可靠地估计,精确度为5 mm;这表明生理和病理乳酸浓度可以区分开来。目前的数据表明,试纸片式比色分析可能包含一种可行的诊断工具,用于识别高创伤乳酸风险患者。(C)2012年美国化学工程师协会生物技术。计划,28:917924,2012年
The increasing prevalence of chronic wounds has significant financial implications for nations with advanced healthcare provision. Although the diseases that predispose to hard-to-heal wounds are recognized, their etiology is less well understood, partly because practitioners in wound management lack specialized diagnostic support. Prognostic indicators for healing may be inherent to wound biochemistry but remain invisible under routine clinical investigation; lactate is an example of this. In this study, lactate concentration in exudate obtained from 20 patients undergoing wound management in hospital was variable but in some cases approached or exceeded 20 mM. In vitro viability studies indicated that fibroblasts and endothelial cells tolerated low levels of lactate (110 mM), but cell viability was severely compromised by high lactate concentrations (=20 mM). Scratched monolayer experiments revealed that cell migration was affected earlier than viability in response to increasing lactate dose, and this was shown by immunocytochemistry to be associated with cytoskeletal disruption. A prototype enzyme-based colorimetric assay for lactate generating a color change that was rapid in the context of clinical practise, and capable of functioning within a gel vehicle, was developed with point-of-care dipstick applications in mind. A randomized single-blinded trial involving 30 volunteers and using a color chart to calibrate the assay demonstrated that lactate concentration could be reliably estimated with 5 mM precision; this suggesting that physiological and pathological lactate concentration could be distinguished. The present data suggest that a dipstick-type colorimetric assay could comprise a viable diagnostic tool for identifying patients at-risk from high-wound lactate.(c) 2012 American Institute of Chemical Engineers Biotechnol. Prog., 28: 917924, 2012