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Alcohol metabolites and lipopolysaccharide: Roles in the development and/or progression of alcoholic liver disease 被引量:20
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作者 Courtney S Schaffert michael J Duryee +5 位作者 Carlos D Hunter Bartlett C Hamilton 3rd Amy L DeVeney mary m Huerter Lynell W Klassen geoffrey m thiele 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第10期1209-1218,共10页
The onset of alcoholic liver disease (ALD) is initiated by different cell types in the liver and a number of different factors including: products derived from ethanol-induced inflammation, ethanol metabolites, and th... The onset of alcoholic liver disease (ALD) is initiated by different cell types in the liver and a number of different factors including: products derived from ethanol-induced inflammation, ethanol metabolites, and the indirect reactions from those metabolites. Ethanol oxidation results in the production of metabolites that have been shown to bind and form protein adducts, and to increase inflammatory, fibrotic and cirrhotic responses. Lipopolysaccharide (LPS) has many deleterious effects and plays a significant role in a number of disease processes by increasing inflammatory cytokine release. In ALD, LPS is thought to be derived from a breakdown in the intestinal wall enabling LPS from resident gut bacterial cell walls to leak into the blood stream. The ability of adducts and LPS to independently stimulate the various cells of the liver provides for a two-hit mechanism by which various biological responses are induced and result in liver injury. Therefore, the purpose of this article is to evaluate the effects of a two-hit combination of ethanol metabolites and LPS on the cells of the liver to increase inflamma-tion and fi brosis, and play a role in the development and/or progression of ALD. 展开更多
关键词 Alcoholic liver disease Inflammation FIBROSIS Sinusoidal liver endothelial cells Kupffer cells HEPATOCYTE Stellate cells Precision cut liver slices
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Immunological response in alcoholic liver disease 被引量:9
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作者 michael J Duryee Lynell W Klassen geoffrey m thiele 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第37期4938-4946,共9页
The development of alcoholic liver disease (ALD) can be attributed to many factors that cause damage to the liver and alter its functions. Data collected over the last 30 years strongly suggests that an immune compone... The development of alcoholic liver disease (ALD) can be attributed to many factors that cause damage to the liver and alter its functions. Data collected over the last 30 years strongly suggests that an immune component may be involved in the onset of this disease. This is best evidenced by the detection of circulating autoantibodies, infiltration of immune cells in the liver, and the detection of hepatic aldehyde modified proteins in patients with ALD. Experimentally, there are numerous immune responses that occur when proteins are modified with the metabolites of ethanol. These products are formed in response to the high oxidative state of the liver during ethanol metabolism, causing the release of many inflammatory processes and potential of necrosis or apoptosis of liver cells. Should cellular proteins become modified with these reactive alcohol metabolites and be recognized by the immune system, then immune responses may be initiated. Therefore, it was the purpose of this article to shed some insight into how the immune system is involved in the development and/or progression of ALD. 展开更多
关键词 Alcoholic liver disease Liver endothelial cells Aldehyde adducts Oxidative stress Immune system CYTOKINES METABOLISM
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类风湿关节炎中心血管风险增加:机制和意义
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作者 Bryant R England geoffrey m thiele +3 位作者 Daniel R Anderson Ted R mikuls 赵震(译) 刘田(审校) 《英国医学杂志中文版》 2019年第2期94-107,共14页
类风湿关节炎是一种系统性自身免疫病,其特点之一为心血管疾病的高发病率和高病死率。类风湿关节炎和心血管疾病相关联的机制包括共有的炎症介质、肽/蛋白质的翻译后修饰,以及随后的免疫应答、脂蛋白组成和功能的改变、氧化应激增加和... 类风湿关节炎是一种系统性自身免疫病,其特点之一为心血管疾病的高发病率和高病死率。类风湿关节炎和心血管疾病相关联的机制包括共有的炎症介质、肽/蛋白质的翻译后修饰,以及随后的免疫应答、脂蛋白组成和功能的改变、氧化应激增加和内皮细胞功能障碍。尽管人们对这些机制及其与传统心血管危险因素的复杂相互作用有了越来越多的了解,但对于在类风湿关节炎背景下进行最佳的危险分层、预防和治疗方法仍然未知。减少心血管疾病所致负担的综合性措施,除需对传统危险因素把控外,还要对类风湿关节炎固有的危险因素(如疾病活动度增加)进行优化管理。对类风湿关节炎的治疗似乎对心血管风险以及关联这些疾病的机制产生了不同的影响。需要更多的研究来确定是否存在优先的类风湿关节炎治疗方法可以预防心血管疾病。最终,对于在类风湿关节炎中心血管疾病的独特机制的了解将有助于危险分层,以及在该患者群体中确定有效降低心血管风险的新靶点。 展开更多
关键词 类风湿关节炎 心血管风险 心血管危险因素 心血管疾病 系统性自身免疫病 内皮细胞功能障碍 治疗方法 危险分层
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