MICROBICIDES IN MODEL SYSTEMS

在这一竞争更新中描述的研究集中在我们当前研究的三个主要领域：a.)继续开发和表征作为包括单纯疱疹病毒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)在内的性传播疾病的靶标的体外和体内模型系统，包括人类异种移植。B.)扩大对配方C31G制剂的研究，以优化递送和杀菌活性，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微生物剂，可应用于阴道，并提供保护，除其他药物外，防止HPV。还将对包括N-9或C31G与烷基硫酸盐组合的配方进行评估。申请将有四个主要项目，包括：第一个项目将重点放在异种移植模型和烷基硫酸盐化合物功效的演示上。将编制异种移植物的细胞和酶学图谱。第二个项目将侧重于继续研究C31G、单独和IR与烷基硫酸盐杀菌剂的联合使用。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选定的三种病毒性性病。将在阴道异种移植模型中进行这些感染的自然病史，以及使用选定的杀菌剂进行干预研究。其他模型病毒系统(例如，兔口腔乳头状瘤病毒)也将被用作替代系统。这四个项目将侧重于沙眼衣原体感染和确定有效的杀菌干预措施，以及其对已经感染沙眼衣原体的细胞内衣原体的后果。将在猪模型中建立沙眼衣原体感染的模型，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.