DANAZOL IN IMMUNE THROMBOCYTOPENIA AND HEMOLYTIC ANEMIA

达那唑治疗免疫性血小板减少症和溶血性贫血

• 批准号: 3152960
• 负责人: Yeon S. Ahn
• 金额: $ 13.38万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-05 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3152960
• 关键词: androgens; complement inhibitors; complement pathway; glucocorticoids; hemolytic anemia; human subject; human therapy evaluation; immunofluorescence technique; immunohematology; immunologic techniques; leukocyte activation /transformation; membrane activity; monoclonal antibody; monocyte; phagocytes; prednisone; radiotracer; remission /regression; splenectomy; suppressor T lymphocyte; thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) are ideal models to study the efficacy and mechanism of immunosuppressive therapy in autoimmune diseases. We have reported the value of danazol, an attenuated androgen, in ITP and more recently its benefit in AIHA. Our long-range objectives are to delineate the mechanism(s) of action of danazol and thereby develop an effective and safe treatment for ITP and AIHA, based on the use of sex hormones. Hormonal manipulation of autoimmunity in humans has not been studied in depth. Therefore the knowledge gained from this study can be applicable to other autoimmune diseases of man. Specific aims are (1) to estimate response rates and side effects of danazol compared to glucocorticoids, (2) to assess its value as an alternative to long-term glucocorticoid therapy and splenectomy, and (3) to study its mechanism of action based on the hypothesis that danazol induces remission by either restoring the imbalance in T cell subsets or by inhibiting complement activation. The prospective randomized protocol of ITP is designed to achieve these goals. Patients will be randomized initially to either danazol or prednisone therapy. If they fail in one, they will receive the other in the next phase and both if neither of them induces remission. Specimens before and during danazol therapy will be collected from patients to monitor antibody levels, T cell subsets, lymphocyte functions and complement components. Data will be analyzed to determine whether danazol inhibits antibody production, MPS function, T cell function or the complement system. Such immune alterations will be correlated with clinical responses. Laboratory investigations will examine the action of danazol on the immune system focusing on three major areas: the effects of danazol on (1) lymphocyte function -a) in vitro action of danazol on normal lymphocyte function (blastogenesis, suppressor cell activity-spontaneous and inducible)-b) in vivo effects on patient's lymphocytes collected before and during therapy; (2) complement system-a) in vitro effects on the complement system in normal sera b) in vivo effects on sera drawn from patients before and during danazol therapy; and (3) modulation of Fc and C3b receptors of monocyte.

特发性血小板减少性紫癜与自身免疫性溶血性贫血 AIHA是研究其疗效和机制的理想模型 自身免疫性疾病的免疫抑制治疗。 我们已经报道了 达那唑（一种减弱的雄激素）在ITP中的价值，最近， 在AIHA中受益。 我们的长远目标是界定 达那唑的作用机制，从而开发一种有效和安全的 治疗ITP和AIHA，基于性激素的使用。 激素 对人类自身免疫的操纵尚未进行深入研究。 因此，从这项研究中获得的知识可以适用于其他 人类自身免疫性疾病 具体目标是：（1）估计缓解率和副作用 达那唑与糖皮质激素相比，（2）评估其作为 替代长期糖皮质激素治疗和脾切除术，和（3）， 研究其作用机制的基础上假设达那唑诱导 通过恢复T细胞亚群的不平衡或 抑制补体激活。 ITP的前瞻性随机化方案旨在实现这些目标 目标. 患者最初将随机接受达那唑或 强的松治疗 如果他们在一个失败，他们将收到另一个， 下一个阶段，如果两者都没有诱导缓解。 标本 在达那唑治疗之前和期间将从患者中收集， 监测抗体水平、T细胞亚群、淋巴细胞功能， 互补成分 将分析数据以确定达那唑是否 抑制抗体产生、MPS功能、T细胞功能或 补体系统 这种免疫改变将与 临床反应。 实验室研究将检查达那唑对免疫系统的作用。 系统侧重于三个主要领域：达那唑的影响（1） 淋巴细胞功能-a）达那唑对正常淋巴细胞的体外作用 功能（胚细胞生成，抑制细胞活性-自发和 诱导型）-B）对之前和之后收集患者淋巴细胞的体内作用 （2）补体系统-a）对补体的体外作用 B）对取自患者之前的血清的体内影响 和达那唑治疗期间;和（3）调节Fc和C3 b受体， 单核细胞。

项目成果

Calcium-channel blockers in thrombotic diseases.

血栓性疾病中的钙通道阻滞剂。

• 发表时间: 1987
• 期刊: Advances in internal medicine
• 作者: Ahn,YS;Harrington,WJ
• 通讯作者: Harrington,WJ

Increased platelet calcium in thrombosis and related disorders and its correction by nifedipine.

血栓形成和相关疾病中血小板钙的增加及其硝苯地平的纠正。

• DOI: 10.1016/0049-3848(87)90167-8
• 发表时间: 1987
• 期刊: Thrombosis research
• 影响因子: 7.5
• 作者: Ahn,YS;Jy,W;Harrington,WJ;Shanbaky,N;Fernandez,LF;Haynes,DH
• 通讯作者: Haynes,DH

Low-dose danazol therapy in idiopathic thrombocytopenic purpura.

• DOI: 10.7326/0003-4819-107-2-177
• 发表时间: 1987-08
• 期刊: Annals of internal medicine
• 影响因子: 39.2
• 作者: Y. Ahn;R. Mylvaganam;R. Garcia;C. Kim;D. Palow;W. Harrington

Use of platelets as drug carriers for the treatment of hematologic diseases.

使用血小板作为药物载体治疗血液系统疾病。

• DOI: 10.1016/0076-6879(87)49069-1
• 发表时间: 1987
• 期刊: Methods in enzymology
• 作者: Ahn,YS;Harrington,WJ;Mylvaganam,R
• 通讯作者: Mylvaganam,R