Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis.
Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis.
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DOI：
10.1038/srep33951
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发表时间：
2016-09-27
影响因子：
4.6
通讯作者：
Mole DJ
中科院分区：
文献类型：
--
作者：
Skouras C;Zheng X;Binnie M;Homer NZ;Murray TB;Robertson D;Briody L;Paterson F;Spence H;Derr L;Hayes AJ;Tsoumanis A;Lyster D;Parks RW;Garden OJ;Iredale JP;Uings IJ;Liddle J;Wright WL;Dukes G;Webster SP;Mole DJ
抑制犬尿氨酸3-单加氧酶（KMO）对实验性急性胰腺炎（AP）多器官功能障碍（MODS）的保护作用。我们旨在通过对所有可能诊断为AP的患者进行为期90天的前瞻性观察研究，精确定义与人类AP和AP- mods相关的犬尿氨酸途径激活。我们在招募后0、3、6、12、24、48、72和168小时采集外周静脉血。我们测量了色氨酸代谢物浓度，并在临床数据和疾病严重程度指数、细胞因子谱和c反应蛋白（CRP）浓度的背景下分析了这些浓度。共招募79人（年龄中位数：59.6岁；男性47人，占59.5%）。57例符合修订后的亚特兰大AP定义：25例为轻度AP， 23例为中度AP， 9例为重度AP。血浆3-羟基犬尿氨酸浓度与同期APACHE II评分相关（R2 = 0.273; Spearman rho = 0.581; P < 0.001）和CRP （R2 = 0.132; Spearman rho = 0.455, P < 0.001）。时间谱显示早期色氨酸缺失和同期3-羟基犬尿氨酸升高。此外，血浆3-羟基犬尿氨酸浓度与全身炎症和AP严重程度相关。这些发现支持了研究KMO抑制剂早期干预的基本原理，目的是降低ap相关器官功能障碍的发生率和严重程度。
Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R2 = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R2 = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction.
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影响因子：
105.7
作者：
MATTHEWS, JNS;ALTMAN, DG;ROYSTON, P
通讯作者：
ROYSTON, P
影响因子：
82.9
作者：
Mole DJ;Webster SP;Uings I;Zheng X;Binnie M;Wilson K;Hutchinson JP;Mirguet O;Walker A;Beaufils B;Ancellin N;Trottet L;Bénéton V;Mowat CG;Wilkinson M;Rowland P;Haslam C;McBride A;Homer NZ;Baily JE;Sharp MG;Garden OJ;Hughes J;Howie SE;Holmes DS;Liddle J;Iredale JP
通讯作者：
Iredale JP
影响因子：
30.5
作者：
Grohmann, U;Orabona, C;Puccetti, P
通讯作者：
Puccetti, P
影响因子：
3.7
作者：
Poesen R;Mutsaers HA;Windey K;van den Broek PH;Verweij V;Augustijns P;Kuypers D;Jansen J;Evenepoel P;Verbeke K;Meijers B;Masereeuw R
通讯作者：
Masereeuw R
影响因子：
3.1
作者：
Loegters, Tim T.;Laryea, Maurice D.;Wild, Michael
通讯作者：
Wild, Michael