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Presence of nucleosomes in plasma and increased thrombin generation in dogs with acute and chronic gastroenteropathies
Research in Veterinary Science ( IF 2.4 ) Pub Date : 2020-11-20 , DOI: 10.1016/j.rvsc.2020.11.012
A.K.H. Krogh , J.G. Lyngby , C.R. Bjørnvad , L.N. Nielsen

Neutrophil extracellular traps (NETs) which contain nucleosomes protect the host by eliminating extracellular pathogens. However, any inflammatory stimuli can activate NETs and eventually lead to an immune overreaction leading to autoimmune diseases and thrombosis. Acute/chronic gastroenteropathies(aGE/cGE) are prevalent in dogs, and are associated with a strong inflammatory component. The aim of this study was to investigate if dogs with aGE and cGE have increased concentrations of nucleosomes indicative of NETs formation, and whether increased concentrations of nucleosomes are associated with hypercoagulability determined by increased thrombin generation.

Twenty-six dogs were enrolled. The dogs were healthy (n = 11), or presented with aGE(n = 7) or cGE(n = 8). Minimum database including CRP, APTT, PT and fibrinogen, was obtained from all dogs. Citrated plasma was batched and used for subsequent analyses. Nucleosome concentration was analysed using a Cell-Death Detection ELISA-kit and thrombin generation by a calibrated automated thrombogram assay.

No statistical differences in nucleosome concentrations were present between the groups. Although a numerically increased concentration of nucleosomes where seen in dogs with aGE(median;range) (0.019 AU;0.003–0.088) and cGE(0.023 AU;0.011–0.256) compared to controls(0.007 AU;0.003–0.042). One dog with GI-lymphoma demonstrated a markedly increased concentration of nucleosomes(0.256 AU). Dogs with aGE showed increased thrombin generation by increased peak (p = 0.03) and endogenous thrombin potential(p = 0.03); and increased CRP(p = 0.001), fibrinogen (p = 0.0002) and prolonged APTT(p = 0.03) compared to controls.

This proof of concept study demonstrates that dogs with aGE and cGE have presence of nucleosomes with marked increase in one dog with GI-lymphoma. Nucleosomes might be linked to haemostatic alterations in dogs with inflammatory and neoplastic diseases.



中文翻译:

急性和慢性肠胃病犬血浆中核小体的存在和凝血酶生成的增加

Neutrophil extracellular traps (NETs) which contain nucleosomes protect the host by eliminating extracellular pathogens. However, any inflammatory stimuli can activate NETs and eventually lead to an immune overreaction leading to autoimmune diseases and thrombosis. Acute/chronic gastroenteropathies(aGE/cGE) are prevalent in dogs, and are associated with a strong inflammatory component. The aim of this study was to investigate if dogs with aGE and cGE have increased concentrations of nucleosomes indicative of NETs formation, and whether increased concentrations of nucleosomes are associated with hypercoagulability determined by increased thrombin generation.

招募了26只狗。这些狗是健康的(n  = 11),或出现aGE(n  = 7)或cGE(n  = 8)。从所有犬获得包括CRP,APTT,PT和纤维蛋白原的最低数据库。分批处理柠檬化血浆,并用于后续分析。使用细胞死亡检测ELISA试剂盒分析核小体浓度,并通过校准的自动血栓图测定法生成凝血酶。

两组之间的核小体浓度无统计学差异。尽管与对照组(0.007 AU; 0.003-0.042)相比,aGE(中位数;范围)(0.019 AU; 0.003-0.088)和cGE(0.023 AU; 0.011-0.256)的狗中核小体的浓度有所增加。一只患有胃肠道淋巴瘤的狗表现出明显增加的核小体浓度(0.256 AU)。患有aGE的狗表现出通过增加峰值(p  = 0.03)和内源性凝血酶电位(p = 0.03)来增加凝血酶的产生。与 对照组相比,CRP(p  = 0.001),纤维蛋白原(p  = 0.0002)和APTT延长(p = 0.03)增加。

这项概念验证研究表明,患有aGE和cGE的狗中存在核小体,其中有GI淋巴瘤的狗明显增加。核小体可能与患有炎性和肿瘤性疾病的犬的止血变化有关。

更新日期:2020-11-21
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