Background To effectively block the invasion of human immunodeficiency virus (HIV)-1 on mucosal surface, vaginal anti-HIV-1 microbicides should avoid inflammatory responses and disruption of mucosa integrity because...Background To effectively block the invasion of human immunodeficiency virus (HIV)-1 on mucosal surface, vaginal anti-HIV-1 microbicides should avoid inflammatory responses and disruption of mucosa integrity because these will facilitate transepithelial viral penetration and replication. However, existing models fail to predict and evaluate vaginal mucosal toxicity induced by microbicides, and most importantly, they are unable to identify subtle or subclinical inflammatory reactions. This study was designed to develop a cost-effective in vivo model to evaluate microbicide safety in a preclinical study which can recapitulate the mucosal topical reaction.Methods A murine model was employed with nonoxynol-9 (N-9) as the topical stimulant within the vagina. Different concentrations of N-9 (1%, 3%, and 4%) were topically applied to the vagina for five consecutive days. A panel of inflammatory cytokines including interleukine-2 (IL-2), IL-4, IL-6, IL-17A, interferon-Y (IFN-Y), tumor necrosis factor-α (TNF-α), and immuno-regulatory IL-10 were assayed in vaginal lavage. Cytokines were quantified by using cytometric bead array (CBA) and reverse transcript (RT) real-time PCR. Histopathological evaluation of vaginal tissues was conducted on hematoxylin-eosin stained slides and scored with a semi-quantitative system according to the severity of epithelial disruption, leucocyte infiltration, edema, and vascular injection. The association between the cytokines and histopathological scores was assessed by linear regression analysis.Results All three concentrations of N-9 induced inflammatory cytokine production. The 4% N-9 application resulted in a consistent production of cytokines in a time-dependent manner. The cytokines reached peak expression on day three with the exception of IL-4 which reached its peak on day one. Histopathological examination of 4% N-9 treated cervicovaginal tissues on day three showed intensive damage in four mice (sores: 10-13) and moderate damage in one mouse �展开更多
Carcinoma cervix is a major cancer of women killing 510,000 women every year worldwide. Human papilloma virus (HPV) infection of cervical cells initiates the transformation of the cervical cells to malignant stage. HP...Carcinoma cervix is a major cancer of women killing 510,000 women every year worldwide. Human papilloma virus (HPV) infection of cervical cells initiates the transformation of the cervical cells to malignant stage. HPV-16 is the most frequent type of HPV causing these changes. We report here the elimination of HPV-16 from the infected cells of all (11/11) women positive for HPV-16 by 30 intra-vaginal intakes of BASANT.展开更多
According to Joint United Nations Program on HIV/AIDS (UNAIDS) report in 2009, the estimated number of people living with HIV-1 is 33.4 million, and half of the infected adults (aged 15-49 years) are women, who ac...According to Joint United Nations Program on HIV/AIDS (UNAIDS) report in 2009, the estimated number of people living with HIV-1 is 33.4 million, and half of the infected adults (aged 15-49 years) are women, who acqluired HIV-1 mainly through heterosexual exposure. In China, HIV-1 transmission through sexual contact has also increased rapidly, and has reached over 70% in overall cases; heterosexual transmission accounted for 40% and men who had sex with man (MSM) for 32.0%.展开更多
Objectives: (A) HIV prevention, using a mechanical cervical barrier in combination with microbicide. (B) Prevention of pregnancy. (C) Shield the cervix to prevent sperm penetration and Gonorrhea, Chlamydia and HIV vir...Objectives: (A) HIV prevention, using a mechanical cervical barrier in combination with microbicide. (B) Prevention of pregnancy. (C) Shield the cervix to prevent sperm penetration and Gonorrhea, Chlamydia and HIV virus invasion. Methods: We investigated a new FDA approved cervical barrier FemCap (Figure 1). The FemCap is a contraceptive device that is designed with a unique delivery system for microbicides on its cervical and vaginal sides (Figure 4) to ensure better coverage, and retention of gel on the cervix and vagina. We also compared the acceptability and adherence with the FemCap, and retention of a stained vaginal lubricant when delivered with the FemCap versus the vaginal lubricant when delivered using a traditional vaginal applicator (Figure 2). We used the same vaginal applicator utilized in the CAPRISA 0041 study, to deliver Tenofovir microbicide. Thirty women compared the use of a vaginal applicator to deliver a high viscosity stained vaginal lubricant before and after intercourse, versus the FemCap to deliver the same lubricant once before intercourse. The acceptability and efficacy of this delivery system was evaluated. Results: Forty percent (12) women missed the application of the lubricant with the vaginal applicator before intercourse and 10% missed it after intercourse. Amongst FemCap users (3) women (10%) missed application of the vaginal lubricant before intercourse and all of them inserted it after intercourse. The stained gel was better retained over the cervix (Figure 5) by single application with the FemCap versus two applications with the traditional applicator (Figure 2). Conclusions: Women in this study preferred the FemCap due to elimination of leakage and the single application, method versus two applications with the traditional vaginal applicator. The use of the FemCap, can prevent pregnancy, HIV mother-to-child transmission, enhance compliance and retention of gel over the cervix and vagina that may potentially prevent STIs and increase the efficacy of Tenofovir.展开更多
文摘Background To effectively block the invasion of human immunodeficiency virus (HIV)-1 on mucosal surface, vaginal anti-HIV-1 microbicides should avoid inflammatory responses and disruption of mucosa integrity because these will facilitate transepithelial viral penetration and replication. However, existing models fail to predict and evaluate vaginal mucosal toxicity induced by microbicides, and most importantly, they are unable to identify subtle or subclinical inflammatory reactions. This study was designed to develop a cost-effective in vivo model to evaluate microbicide safety in a preclinical study which can recapitulate the mucosal topical reaction.Methods A murine model was employed with nonoxynol-9 (N-9) as the topical stimulant within the vagina. Different concentrations of N-9 (1%, 3%, and 4%) were topically applied to the vagina for five consecutive days. A panel of inflammatory cytokines including interleukine-2 (IL-2), IL-4, IL-6, IL-17A, interferon-Y (IFN-Y), tumor necrosis factor-α (TNF-α), and immuno-regulatory IL-10 were assayed in vaginal lavage. Cytokines were quantified by using cytometric bead array (CBA) and reverse transcript (RT) real-time PCR. Histopathological evaluation of vaginal tissues was conducted on hematoxylin-eosin stained slides and scored with a semi-quantitative system according to the severity of epithelial disruption, leucocyte infiltration, edema, and vascular injection. The association between the cytokines and histopathological scores was assessed by linear regression analysis.Results All three concentrations of N-9 induced inflammatory cytokine production. The 4% N-9 application resulted in a consistent production of cytokines in a time-dependent manner. The cytokines reached peak expression on day three with the exception of IL-4 which reached its peak on day one. Histopathological examination of 4% N-9 treated cervicovaginal tissues on day three showed intensive damage in four mice (sores: 10-13) and moderate damage in one mouse �
文摘Carcinoma cervix is a major cancer of women killing 510,000 women every year worldwide. Human papilloma virus (HPV) infection of cervical cells initiates the transformation of the cervical cells to malignant stage. HPV-16 is the most frequent type of HPV causing these changes. We report here the elimination of HPV-16 from the infected cells of all (11/11) women positive for HPV-16 by 30 intra-vaginal intakes of BASANT.
文摘According to Joint United Nations Program on HIV/AIDS (UNAIDS) report in 2009, the estimated number of people living with HIV-1 is 33.4 million, and half of the infected adults (aged 15-49 years) are women, who acqluired HIV-1 mainly through heterosexual exposure. In China, HIV-1 transmission through sexual contact has also increased rapidly, and has reached over 70% in overall cases; heterosexual transmission accounted for 40% and men who had sex with man (MSM) for 32.0%.
文摘Objectives: (A) HIV prevention, using a mechanical cervical barrier in combination with microbicide. (B) Prevention of pregnancy. (C) Shield the cervix to prevent sperm penetration and Gonorrhea, Chlamydia and HIV virus invasion. Methods: We investigated a new FDA approved cervical barrier FemCap (Figure 1). The FemCap is a contraceptive device that is designed with a unique delivery system for microbicides on its cervical and vaginal sides (Figure 4) to ensure better coverage, and retention of gel on the cervix and vagina. We also compared the acceptability and adherence with the FemCap, and retention of a stained vaginal lubricant when delivered with the FemCap versus the vaginal lubricant when delivered using a traditional vaginal applicator (Figure 2). We used the same vaginal applicator utilized in the CAPRISA 0041 study, to deliver Tenofovir microbicide. Thirty women compared the use of a vaginal applicator to deliver a high viscosity stained vaginal lubricant before and after intercourse, versus the FemCap to deliver the same lubricant once before intercourse. The acceptability and efficacy of this delivery system was evaluated. Results: Forty percent (12) women missed the application of the lubricant with the vaginal applicator before intercourse and 10% missed it after intercourse. Amongst FemCap users (3) women (10%) missed application of the vaginal lubricant before intercourse and all of them inserted it after intercourse. The stained gel was better retained over the cervix (Figure 5) by single application with the FemCap versus two applications with the traditional applicator (Figure 2). Conclusions: Women in this study preferred the FemCap due to elimination of leakage and the single application, method versus two applications with the traditional vaginal applicator. The use of the FemCap, can prevent pregnancy, HIV mother-to-child transmission, enhance compliance and retention of gel over the cervix and vagina that may potentially prevent STIs and increase the efficacy of Tenofovir.