Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes

Cytokines;Chemokines;Toxicology;过表达;细胞因子;趋化因子;MSD;Cytokines;Chemokines;Toxicology
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Brouwers O, Niessen PM, Miyata T, Ostergaard JA, Flyvbjerg A, Peutz-Kootstra CJ, Sieber J, Mundel PH, Brownlee M, Janssen BJ, De Mey JG, Stehouwer CD, Schalkwijk CG.

  • Diabetologia
  • 2014
  • 10.46
  • 17(5):R253.
  • Human,Mouse,Non-Human Primate,Rat
  • MSD
  • Cell culture supernatants, urine
  • 免疫/内分泌
  • 糖尿病
  • Albumin, HAVCR1 KIM-1, MCP-1, Osteopontin

相关货号

LXMH07-6LXMH10-9LXMH11-1LXMH111-1LXMH13-1LXMH30-1LXMH37-1LXMH40-1LXMH44-1LXMH46-1LXMH54-1LXMH71-1LXMH87-1LXMM08-1LXMM08-2LXMM09-1LXMM10-3LXMM50-1LXMM58-1LXMN10-1LXMN10-2LXMN24-2LXMN61-1LXMR04-1

Abstract

Introduction: Despite recent modifications, the clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment. This study was designed to test the hypothesis that a biomarker panel would be useful for biologic confirmation of the clinical diagnosis of ARDS in patients at risk of developing ARDS due to severe sepsis.

Methods: This was a retrospective case control study of 100 patients with severe sepsis and no evidence of ARDS compared to 100 patients with severe sepsis and evidence of ARDS on at least two of their first four ICU days. A panel that included 11 biomarkers of inflammation, fibroblast activation, proteolytic injury, endothelial injury, and lung epithelial injury was measured in plasma from the morning of ICU day two. A backward elimination model building strategy on 1,000 bootstrapped data was used to select the best performing biomarkers for further consideration in a logistic regression model for diagnosis of ARDS.

Results: Using the five best-performing biomarkers (surfactant protein-D (SP-D), receptor for advanced glycation end-products (RAGE), interleukin-8 (IL-8), club cell secretory protein (CC-16), and interleukin-6 (IL-6)) the area under the receiver operator characteristic curve (AUC) was 0.75 (95% CI: 0.7 to 0.84) for the diagnosis of ARDS. The AUC improved to 0.82 (95% CI: 0.77 to 0.90) for diagnosis of severe ARDS, defined as ARDS present on all four of the first four ICU days.

Conclusions: Abnormal levels of five plasma biomarkers including three biomarkers generated by lung epithelium (SP-D, RAGE, CC-16) provided excellent discrimination for diagnosis of ARDS in patients with severe sepsis. Altered levels of plasma biomarkers may be useful biologic confirmation of the diagnosis of ARDS in patients with sepsis, and also potentially for selecting patients for clinical trials that are designed to reduce lung epithelial injury.
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