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

在灵长类动物中，抗孕激素治疗包括RU 486和ZK 137316既能阻断孕酮(P)的作用，又能抑制 雌激素刺激子宫内膜的增殖。这一行动 抗孕激素对接受雌激素治疗的女性是有益的。 替代疗法作为一种阻断不适反应的方法 子宫内膜上的雌激素。ZK 230 211(ZK211)是一种强有力的新材料 先灵股份公司生产的一代抗孕激素，可以 口服和全身给药。这项研究的目的是 是为了确定ZK211是否会抑制细胞的增殖作用 雌激素连续给药5个月。六组恒河猴 猕猴(n=5)接受雌二醇(E2)填充的植入物治疗 已经5个月了。其中三组也每天注射3 不同剂量的ZK211(0。01、0.05和0.25 mg/kg)。P是已知的 反对雌二醇在子宫内膜的增殖作用。因此， 作为对照，1组接受E2加小剂量P(2 cm P 植入物)，一组接受E2加大剂量P(6 cm P 植入物)。对照组(第6组)仅给予雌激素。 ZK211治疗后子宫内膜严重减少 质量，这与剂量依赖的抑制有关 上皮细胞增殖。在较高剂量的ZK211中，这种效应 导致腺体上部退化并被困住 分泌性材料。这些较高的剂量导致形成中等剂量的 大小的子宫内膜囊肿，似乎含有滞留的分泌物 材料。没有证据表明子宫内膜增生症或 化生。正如预期的那样，长期的E2+P治疗导致了 剂量依赖的蜕膜化反应，以广泛的 螺旋动脉肥大。这种对螺旋动脉的影响是 与ZK 211的反应相反，ZK 211抑制了 血管发育。我们得出结论，抑制血管 ZK 211的开发可能是导致 雌激素依赖性子宫内膜的退行性抑制和阻断 由这种抗孕激素引起的增殖。与以下公司签订融资合同 德国柏林先灵股份公司无出版物

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