MICROBICIDES IN MODEL SYSTEMS

在这个竞争性更新中描述的研究集中在我们当前研究的三个主要领域：继续开发和鉴定体外和体内模型系统，包括人类异种移植物，作为性传播疾病的靶点，包括单纯疱疹病毒2型（HS-2）、人乳头瘤病毒（hpv）、沙眼衣原体和人类免疫缺陷病毒（HIV）。b。)扩展配方C31G制剂的研究，以优化递送和杀微生物活性，包括递送产品的药效学。c。)建立配方烷基硫酸盐作为局部杀菌剂，可以应用于阴道和提供保护，从hpv除了其他药剂。包括N-9或C31G与烷基硫酸盐组合的配方也将进行评估。第一个项目将侧重于异种移植模型和烷基硫酸盐化合物的功效论证。将编制异种移植物的细胞和酶谱。第二个项目将重点继续研究C31G，单独使用和与烷基硫酸酯杀菌剂联合使用。将研究其在人体和体外模型中的药效学。第三个项目将重点关注三种选定的病毒性传播疾病。这些感染的自然历史在阴道异种移植模型将进行，以及选择杀菌剂的干预研究。其他模型病毒系统（例如，兔口腔乳头瘤病毒）也将用作替代系统。这四个项目将重点关注沙眼衣原体感染，确定有效的杀微生物干预措施，以及在已经感染沙眼衣原体的猪模型中对细胞内衣原体的影响，并在该系统中测试杀微生物剂。

The research described in this competing renewal focuses on three main areas of our current research: a.) Continued development and characterization of model in vitro and in vivo systems, including human xenografts, as targets for STDs including herpes simplex virus type 2 (HS-2), human papillomaviruses (HPVs), Chlamydia trachomatis and human immunodeficiency virus (HIV). b.) Expansion of studies with formulated C31G preparations to optimize delivery and microbicidal activity, including pharmacodynamics of the delivered product. c.) Establishment of formulated alkyl sulfates as topical microbicides that can be applied to the vagina and provide protection from HPVs in addition to the other agents. Formulations that include N-9 or C31G in combination with alkyl sulfates will also be evaluated. The application will have four main projects including: The first Project will focus on the xenograft model and the demonstration of the efficacy of the alkyl sulfate compounds. Cellular and enzymatic profiles of the xenografts will be compiled. The second Project will focus on continued studies with C31G, alone and ir combination with alkyl sulfate microbicides. The pharmacodynamics in humans and in vitro models will be studied. The third Project will focus on the three selected viral STDs. Natural history of these infections in the vaginal xenograft model will be carried out as well as intervention studies with selected microbicides. Other model virus systems (for example, the rabbit oral papillomavirus) will also be used as surrogate systems. The four Project will focus on C. trachomatis infection and identification of effective microbicidal interventions as well as the consequences thereof for intracellular chlamydiae in already infected natural infections of C. trachomatis in a porcine model will be established and microbicides tested in this system.