CHARACTERIZATION OF MOLECULARLY CLONED SIMIAN HUMAN IMMUNODEFICIENCY VIRUSES

我们这项研究的目标是开发一种安全、可逆的方法 抑制月经的一类化合物 抗孕激素。此前我们曾表示，短期系统性 先灵抗孕激素ZK 137 316(ZK316)治疗将 抑制月经。我们现在进行了一项长期的研究 ZK316对骑行恒河猴的影响。在这项研究中，所有的 动物表现出正常的治疗前月经周期(Mean_SE； 28.3~1.4天)。注射用ZK316 0.05 mg/kg和0.1 mg/kg 100 天数阻碍了月经，并显著延长了 所有猴子的月经间歇期。月经间期 对照组、0.0 5组和0.1组的时间间隔分别为28.1~0.83、131.1~ 10.1d和134.7d(P&lt；0.001)。在过去30年中 经过几天的治疗，对照组的猴子表现正常 雌激素(E_2)和孕酮(P)的月经周期模式。在……里面 另外，ZK316 0.05 mg/kg组(n=4) 卵泡期E2水平正常(包括E2激增)和 在本组中，ZK316抑制了正常黄体期的P。 月经，尽管黄体P期末正常下降 这个循环。然而，0.1 mg/kg组的所有猴子都失败了 出现正常的雌二醇峰(雌二醇水平高于200 pg/ml)或 黄体期P(&gt；1 ng/ml)在黄体期最后30天的正常水平 治疗。尽管这组人阻止了排卵，但所有的 猴子表现出正常的非高峰水平(~30-100 pg/ml)。 所有ZK316治疗的猴子在40天内恢复正常的周期性 治疗后周期长度在所有组均正常(29.8 _3.0天)。未检测到治疗的不良反应。 研究中的猴子。总而言之，我们现在已经表明 长期的抗孕激素治疗将可逆地抑制月经 在恒河猴身上。国防部资金分包合同 出版物：Slayden OD，Chwalisz K，Vidgoff J，Brenner RM。剂量 新一代抗孕激素ZK-137-316的相关效应 去势和骑行的恒河猴。生物报告(附录1)58：186,1998 (摘要365)。Slayden OD，Zelinski-Wooten MB，Chwalisz K，Stouffer RL、Brenner Rm.低氧对循环恒河猴的慢性治疗 抗孕激素ZK 137 316剂量的形态计量学评价 子宫和输卵管。《哼唱报告》13：269-277,1998。泽林斯基-伍腾MB， 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容 Brenner Rm，Stouffer RL.一种慢性、低剂量的治疗方案 抗孕激素ZK 137 316可防止恒河猴怀孕。哼哼声 报告13：2132-2138,1998。Zelinski-Wooten MB，Slayden OD，Chwalisz 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--文摘内容自行车运动的慢性治疗 恒河猴服用低剂量抗孕激素ZK 137 316 建立允许正常月经周期的养生法。 《哼唱》13：259-267,1998。

Our goal in this research is to develop a safe, reversible method of menstrual suppression with a class of compounds called antiprogestins. Previously we showed that short-term systemic treatment with the Schering antiprogestin ZK 137 316 (ZK316) will suppress menstruation. We have now conducted a long-term study of cycling rhesus monkeys treated with ZK316. In this study, all of the animals exhibited normal pretreatment menstrual cycles (mean _ SE; 28.3 _ 1.4 days). Injection with ZK316 at 0.05 and 0.1 mg/kg for 100 days blocked menstruation and significantly extended the intermenstrual interval in all of the monkeys. Intermenstrual interval in the control, 0.05 and 0.1 groups were 28.1 _ 0.83, 131.1 _ 10.1 and 134 _ 8.7 days, respectively (P < 0.001). During the last 30 days of treatment, the monkeys in the control group expressed normal menstrual cycle patterns of estradiol (E2) and progesterone (P). In addition, all of the monkeys in the 0.05 mg/kg ZK316 grou p (n = 4) had normal follicular phase levels of E2 (including an E2 surge) and normal luteal phase levels of P. In this group, ZK316 suppressed menstruation despite a normal decline in luteal phase P at the end of the cycle. However, all of the monkeys in the 0.1 mg/kg group failed to develop a normal E2 surge (E2 levels rising above 200 pg/ml) or normal luteal phase levels of P (>1 ng/ml) during the last 30 days of treatment. Despite blockade of ovulation in this group, all of the monkeys showed normal nonsurge levels of E2 levels (~30-100 pg/ml). All ZK316-treated monkeys returned to normal cyclicity within 40 days and posttreatment cycle lengths were normal in all of the groups (29.8 _ 3.0 days). No untoward effects of treatment were detected in the monkeys during the study. In summary, we have now shown that long-term antiprogestin treatment will reversibly inhibit menstruation in rhesus monkeys. FUNDING Department of Defense Subcontract PUBLICATIONS Slayden OD, Chwalisz K, Vidgoff J, Brenner RM. Dose related effects of the new generation antiprogestin ZK 137 316 in spayed and cycling rhesus macaques. Biol Reprod (Suppl 1) 58:186,1998 (abstract 365). Slayden OD, Zelinski-Wooten MB, Chwalisz K, Stouffer RL, Brenner RM. Chronic treatment of cycling rhesus monkeys with low doses of the antiprogestin ZK 137 316 Morphometric assessment of the uterus and oviduct. Hum Reprod 13:269-277, 1998. Zelinski-Wooten MB, Chwalisz K, Illiff SA, Niemeyer CL, Eaton GG, Loriaux DL, Slayden OD, Brenner RM, Stouffer RL. A chronic, low dose regimen of the antiprogestin ZK 137 316 prevents pregnancy in rhesus monkeys. Hum Reprod 13:2132-2138, 1998. Zelinski-Wooten MB, Slayden OD, Chwalisz K, Hess DL, Brenner RM, Stouffer RL. Chronic treatment of cycling rhesus monkeys with low doses of the antiprogestin ZK 137 316 Establishment of a regimen that permits normal menstrual cyclicity. Hum Reprod 13:259-267, 1998.