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首页> 外文期刊>Translational research: the journal of laboratory and clinical medicine >Inflammatory targets of therapy in sickle cell disease
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Inflammatory targets of therapy in sickle cell disease

机译:镰状细胞病的炎性治疗靶标

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摘要

Sickle cell disease (SCD) is a monogenic globin disorder characterized by the production of a structurally abnormal hemoglobin (Hb) variant Hb S, which causes severe hemolytic anemia, episodic painful vaso-occlusion, and ultimately end-organ damage. The primary disease pathophysiology is intracellular Hb S polymerization and consequent sickling of erythrocytes. It has become evident for more than several decades that a more complex disease process contributes to the myriad of clinical complications seen in patients with SCD with inflammation playing a central role. Drugs targeting specific inflammatory pathways therefore offer an attractive therapeutic strategy to ameliorate many of the clinical events in SCD. In addition, they are useful tools to dissect the molecular and cellular mechanisms that promote individual clinical events and for developing improved therapeutics to address more challenging clinical dilemmas such as refractoriness to opioids or hyperalgesia. Here, we discuss the prospect of targeting multiple inflammatory pathways implicated in the pathogenesis of SCD with a focus on new therapeutics, striving to link the actions of the anti-inflammatory agents to a defined pathobiology, and specific clinical manifestations of SCD. We also review the anti-inflammatory attributes and the cognate inflammatory targets of hydroxyurea, the only Food and Drug Administration-approved drug for SCD.
机译:镰状细胞病(SCD)是一种单基因球蛋白疾病,其特征是结构异常的血红蛋白(Hb)变异Hb S的产生,导致严重的溶血性贫血,发作性疼痛性血管闭塞和最终导致终末器官损害。主要的疾病病理生理学是细胞内Hb S聚合和随之而来的红细胞镰状化。几十年来,越来越明显的是,更复杂的疾病过程导致了SCD患者中无数的临床并发症,其中炎症起着核心作用。因此,靶向特定炎症途径的药物提供了一种有吸引力的治疗策略,以改善SCD中的许多临床事件。此外,它们是剖析促进个体临床事件的分子和细胞机制,以及开发改进的疗法以解决更具挑战性的临床难题(如阿片类药物的难治性或痛觉过敏)的有用工具。在这里,我们讨论靶向于SCD发病机制中涉及的多种炎症途径的前景,重点是新疗法,力图将抗炎药的作用与确定的病理生物学和SCD的特定临床表现联系起来。我们还审查了羟基脲的抗炎特性和相关的炎性靶标,羟基脲是美国食品和药物管理局批准的唯一SCD药物。

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