Metabolic effects of carnitine and carnitine analogs.

Metabolic effects of carnitine and carnitine analogs.
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肉碱和肉碱类似物的代谢作用。

DOI:
10.1007/978-1-4684-5826-8_10
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发表时间:
1990
影响因子:
--
通讯作者:
Griffith,OW
Griffith,OW
中科院分区:
医学4区
文献类型:
--
作者:
Ohtsuka,Y;Clark,DJ;Griffith,OW

文献摘要

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肝硬化是一种常见且严重的疾病,预后不良(1)。肝脏灌注和功能丧失会损害肝脏解毒反应,并使中枢神经系统(CNS)暴露于氨基酸失衡和多种毒素,包括氨、硫醇、短链脂肪酸和“中等”分子量分子(2)。尽管所有这些分子都单独或协同地导致肝性脑病,但有大量证据表明中枢神经系统氨水平升高是一个主要因素。肝病患者的血液和脑脊液中氨浓度通常很高,向门腔静脉分流明显的患者输注氨引起的反应在临床上与即将发生的肝昏迷难以区分。在实验动物中,急性施用铵盐会导致惊厥、昏迷和死亡。虽然已经设计了几种针对肝性脑病相关氨中毒的治疗方法,但没有一种在逆转该疾病的发病率和死亡率方面完全有效。显然需要更好的控制氨代谢和毒性的方法。
Cirrhosis of the liver is a common and serious disease with a poor prognosis (1). Loss of liver perfusion and function compromises hepatic detoxification reactions and exposes the central nervous system (CNS) to amino acid imbalances and to multiple toxins including ammonia, mercaptans, short-chain fatty acids, and “middle” molecular weight molecules (2). Although all of these molecules contribute individually and perhaps synergistically to hepatic encephalopathy, there is abundant evidence that elevated CNS ammonia levels are a major factor. Ammonia concentrations are often high in the blood and cerebrospinal fluid of patients with liver disease, and ammonia infusion into patients with significant portacaval shunting evokes a reaction clinically indistinguishable from impending hepatic coma. In experimental animals, acute administration of ammonium salts causes convulsions, coma and death. Although several therapies directed at hepatic encephalopathy-associated ammonia intoxication have been devised, none is completely effective in reversing the morbidity and mortality of the disorder. Better methods for controlling ammonia metabolism and toxicity are clearly needed.
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