EVALUATION OF C31G VS NONOXYNOL-9 AS TOPICAL MICROBICIDES

生殖道沙眼衣原体血清型D-K是导致流行的原因 性传播感染在美国，影响超过400万男性， 妇女和婴儿每年。在女性中，如果不进行治疗，衣原体可能 从子宫颈管向子宫内膜呈管状扩散 （输卵管炎）和输卵管（输卵管炎）-星座 被定义为盆腔炎。由于输卵管 疤痕和/或卵子运输受损，异位妊娠和 可能发生不孕症。很明显，衣原体疾病 初级、二级和三级卫生保健问题，其中妇女承担 特别负担，因为她们不良生殖健康风险增加， 后果迫切需要有效的局部杀微生物剂来帮助 预防和控制性传播感染。 该补助金的目的是评估主题的作用 杀微生物剂C316（及其衍生物B58 A和B64 D）与壬苯醇醚-9在 pH5.7和7.0对沙眼衣原体血清型E及其靶宿主细胞的作用。 将对杀微生物剂的浓度进行定量， 与极化人生殖器上皮细胞的相容性和细胞毒性 细胞（鳞状柱状，柱状），使用荧光素二乙酸酯和丙啶 在特定目标1中使用碘化物，在特定目标2中使用分离的衣原体。 放射性标记的感染性单质（EB）和代谢 通过SDS-PAGE分析活性网状体的抗原损失， 免疫印迹、放射自显影和免疫电镜， 活力：还将测定暴露于杀微生物剂的EB是否附着于 宿主上皮细胞和包涵体发育。具体目标3中， 杀菌剂暴露对人生殖器上皮细胞极化影响 (a)正常感染和（B）持续感染衣原体， 通过荧光和透射电子显微镜检查， 雌激素和雌激素加孕激素的调节作用将是 具体目标4。未接触和接触杀微生物剂的感染者 将比较极化的人上皮细胞的过早分化的增加。 衣原体抗原从包涵体中释放并分泌到宿主体内 细胞表面-包埋后免疫标记电子显微镜 在Lowicryl中处理的样本（特定目标5）。最后，我们将 确定炎症反应细胞是否迁移到衣原体- 受感染的极化上皮细胞受到杀微生物剂暴露的调节。

Genital Chlamydia trachomatis serovars D-K are responsible for epidemic sexually transmitted infections in the USA, affecting over 4 million men, women and infants per year. In women, without treatment, chlamydiae may spread canalicularly from the endocervical canal to the endometrium (endometritis), and the fallopian tubes (salpingitis)- the constellation of which is defined as pelvic inflammatory disease. As a result of tubal scarring and/or impaired ovum transportation, ectopic pregnancy and infertility can occur. Clearly, chlamydial diseases constitute significant primary, secondary and tertiary health care concerns in which women bear a special burden because of their increased risk of adverse reproductive consequences. Effective topical microbicides are urgently needed to help prevent and control sexually transmitted infections. The purpose of this grant is to evaluate the action of the topical microbicide C316 (and its derivatives B58A and B64D) versus nonoxynol-9 at pH 5.7 and 7.0 on Chlamydia trachomatis serovar E and its target host cell. The concentrations of the microbicides will be quantitated for compatibility and cytotoxicity with polarized human genital epithelial cells (squamocolumnar, columnar) using fluorescein diacetate and propidium iodide in Specific Aim 1 and with isolated chlamydiae in Specific Aim 2. Both radiolabeled infectious elementary bodies (EB) and metabolically active reticulate bodies will be analyzed for loss of antigens by SDS-PAGE, Western blots, autoradiography, and immunoelectron microscopy and for viability: microbicide-exposed EB will also be assayed for attachment to host epithelial cells and inclusion development. In Specific Aim 3, the effect of microbicide exposure on polarized human genital epithelial cells (a) normally infected and (b) persistently infected with chlamydiae will be examined by fluorescence and transmission electron microscopy, and modulation of the effect by estrogen and estrogen plus progesterone will be assessed in Specific Aim 4. Unexposed and microbicide-exposed infected polarized human epithelial cells will be compared for increased premature chlamydial antigen release from inclusions and antigen secretion to host cell surface - by post-embedding immunolabeling of electron microscopy samples processed in Lowicryl (Specific Aim 5). Finally, we shall determine wether or not inflammatory response cell migration to chlamydiae- infected polarized epithelial cells is modulated by microbicide exposure.