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胺碘酮对体外淋巴母细胞及体内外周血淋巴细胞磷脂和板层小体含量的影响。

Effect of amiodarone on the phospholipid and lamellar body content of lymphoblasts in vitro and peripheral blood lymphocytes in vivo.

作者信息

Hostetler K Y, Vande Berg J, Aldern K A, Brophy G T

机构信息

Department of Medicine, University of California, San Diego 92093.

出版信息

Biochem Pharmacol. 1991;41(6-7):1007-13. doi: 10.1016/0006-2952(91)90208-m.

Abstract

Amiodarone is useful for the treatment of ventricular arrhythmias but has been associated with a significant degree of toxicity especially to lung and liver. The drug produces phospholipid accumulation in multilamella lysosomal inclusions in many tissues due to the ability of amiodarone and desethylamiodarone to inhibit phospholipase A. The adverse effects do not correlate with the plasma levels of amiodarone but relate more closely to the cumulative dose. No clear way of predicting amiodarone toxicity has yet emerged. In this report, normal human lymphoblasts in tissue culture were shown by electron microscopy to have dose-dependent increases in multilamellar inclusions when grown with amiodarone at concentrations which are routinely observed in patients receiving the drug. The content of phospholipid also increased but this parameter was not as sensitive as the number of multilamellar inclusions. Finally, lymphocytes from patients treated with amiodarone were examined by electron microscopy and shown to have increased numbers of multilamellar bodies.

摘要

胺碘酮对室性心律失常的治疗有效,但已被证实具有显著的毒性,尤其是对肺和肝脏。由于胺碘酮和去乙基胺碘酮能够抑制磷脂酶A,该药物会在许多组织的多层溶酶体包涵体中产生磷脂蓄积。不良反应与胺碘酮的血浆水平无关,而与累积剂量关系更为密切。目前尚未出现预测胺碘酮毒性的明确方法。在本报告中,通过电子显微镜观察发现,在组织培养中,正常人类淋巴母细胞在与胺碘酮一起培养时,当胺碘酮浓度处于接受该药物治疗的患者中常规观察到的浓度时,会出现剂量依赖性的多层包涵体增加。磷脂含量也增加了,但该参数不如多层包涵体的数量敏感。最后,对接受胺碘酮治疗的患者的淋巴细胞进行电子显微镜检查,结果显示多层小体数量增加。

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