PLASMA HOMOCYST (E) INE CONCENTRAT IS ASSOCIAT W/ VARIATION IN CAROTID PLAQUE ARE

血浆同型半胱氨酸 (E) 浓缩物与颈动脉斑块的变化有关

• 批准号: 6312910
• 负责人: JOHN Charles SPENCE
• 金额: $ 10.1万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6312910
• 关键词: Mammalia; clinical research; hormones; model design /development; reproductive system; women's health

In primates, treatment with antiprogestins including RU 486 and ZK 137 316 will both block progesterone (P) action, and also inhibit estrogen stimulated proliferation in the endometrium. This action of antiprogestins would be of benefit to women treated with estrogen replacement therapy as a method of blocking untoward effects of estrogen on the endometrium. ZK 230 211 (ZK211) is a potent new generation antiprogestin produced by Schering AG, that can be administered both orally and systemically. The goal of this research was to determine if ZK211 will inhibit the proliferative actions of estrogen delivered continuously for 5 months. Six groups of rhesus macaques (n = 5 each) were treated with estradiol (E2)-filled implants for 5 months. Three of the groups were also injected daily with 3 different doses of ZK211 (0. 01, 0.05 and 0.25 mg/kg). P is known to oppose the proliferative action of E2 in the endometrium. Therefore, for comparison, 1 group received E2 plus a low dose of P (2 cm P implants) and one group received E2 plus a high dose of P (6 cm P implants). Control animals (group 6) received estrogen alone. Treatment with ZK211 resulted in a severe reduction of endometrial mass, which was associated with a dose dependent inhibition of epithelial cell proliferation. At higher doses of ZK211, this effect resulted in the upper portions of the glands degenerating and trapping secretory material. These higher doses led to formation of moderate size endometrial cysts, which appeared to contain trapped secretory material. There was no evidence of endometrial hyperplasia or metaplasia. As anticipated, long-term E2 + P treatment resulted in a dose-dependent decidualization response that was marked by extensive spiral artery hypertrophy. This effect on the spiral arteries was opposite to the reaction to that seen with ZK 211 which inhibited vascular development. We conclude that inhibition of vascular development by ZK 211 may be the key factor underlying the degenerative inhibition and blockade of estrogen-dependent endometrial proliferation induced by this antiprogestin. FUNDING Contract with Schering AG, Berlin, Germany PUBLICATIONS None

在灵长类动物中，使用包括RU 486和ZK在内的抗孕激素治疗 137 316既能阻断孕酮（P）的作用，也能抑制 雌激素刺激子宫内膜增殖。 的这个动作 抗孕激素对接受雌激素治疗的妇女有益 替代疗法作为一种阻断 子宫内膜上的雌激素 ZK 230 211（ZK 211）是一种强大的新型 由Schering AG生产的第二代抗胰蛋白酶素，其可以是 口服和全身给药。 本研究的目的 是为了确定ZK 211是否会抑制 雌激素连续给药5个月。 六组恒河猴 用雌二醇（E2）填充的植入物处理猕猴（每种n = 5 五个月 其中三组也每天注射3 ZK211（0. 01、0.05和0.25 mg/kg）。 P已知 对抗E2在子宫内膜中的增殖作用。 因此，我们认为， 作为对照，1组接受E2加低剂量P（2cm P 一组接受E2加高剂量P（6 cm P 植入物）。 对照动物（第6组）仅接受雌激素。 ZK 211治疗导致子宫内膜严重减少， 质量，这与剂量依赖性抑制有关， 上皮细胞增殖 在较高剂量的ZK 211下，这种效应 导致腺体的上部退化并陷入 分泌物质 这些较高的剂量导致形成中度 大小的子宫内膜囊肿，其中似乎包含被困分泌 材料 没有子宫内膜增生的证据， 化生 正如预期的那样，长期E2 + P治疗导致了 剂量依赖性蜕膜化反应，其特征是广泛的 螺旋动脉肥大 这种对螺旋动脉的影响是 与ZK 211所见的反应相反，ZK 211抑制了 血管发育 我们的结论是，抑制血管 ZK 211的发展可能是潜在的关键因素 雌激素依赖性子宫内膜的退行性抑制和阻断 由这种抗胰蛋白酶素诱导的增殖。 融资合同 Schering AG，柏林，德国出版物无