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
Summary: Spermicidal effect of Jieze No. 1 (JZ1) in combination with nonoxynol-9 (N-9) was examined in vitro. The minimum spermicidal concentration of JZ1 decoction, N-9 and their mixture solution in 20 s and 3 min w...Summary: Spermicidal effect of Jieze No. 1 (JZ1) in combination with nonoxynol-9 (N-9) was examined in vitro. The minimum spermicidal concentration of JZ1 decoction, N-9 and their mixture solution in 20 s and 3 min were examined by improved spermicidal test of Sander-cramer in vitro. The percentages of progressively moving spermatozoa, moving spermatozoa and viable spermatozoa were also observed 20 s, 3 min and 30 min after the addition of the liquid medicine. Our results showed that sperms did not recover their activities in a revival test when the minimum spermicidal concentration of either JZ1 decoction, or N-9, or the mixed solution of the two agents, was used. N-9 (JZ1 in the mixed group) showed significant differences in the percentages of progressively moving spermatozoa, moving spermatozoa, and visible spermatozoa in 20 s, 3 min, and 30 min, when compared with N-9 alone (P<0.01). We are led to conclude that JZ1 decoction can improve N-9 spermicidal action in vitro, and when used in combination with N-9, it has synergic effect.展开更多
The yaginal contraceptive sponge is made Of polyurethane containing 1g of nonoxynol-9.The gross cumulative twelve month life fable pregnancy rate of 352 cases nsf'ng yaginal contraceptive sponge was 5.7/100 women ...The yaginal contraceptive sponge is made Of polyurethane containing 1g of nonoxynol-9.The gross cumulative twelve month life fable pregnancy rate of 352 cases nsf'ng yaginal contraceptive sponge was 5.7/100 women and foe methodpregnancy rate was 2.3/100 women. The gross cumulative continuation rate per 100 women was 74.Only 2 patients(1.0/100 women)suffering from vaginitis and itching of vulva no longer wished to continue in the study.Over the course of the study no significant changes were observed in any of the laboratory parameters such as yagina & cervix smear etc.that had been monitored. This modality associated with few side effects and its effectiveness rate and also indicaled a protection from the risk ofacquring of sex-transmitted diseases.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 �
基金This project was supported by the National"10th Five Year"Key Technologies R & D (N0.2004BA709B13 02).
文摘Summary: Spermicidal effect of Jieze No. 1 (JZ1) in combination with nonoxynol-9 (N-9) was examined in vitro. The minimum spermicidal concentration of JZ1 decoction, N-9 and their mixture solution in 20 s and 3 min were examined by improved spermicidal test of Sander-cramer in vitro. The percentages of progressively moving spermatozoa, moving spermatozoa and viable spermatozoa were also observed 20 s, 3 min and 30 min after the addition of the liquid medicine. Our results showed that sperms did not recover their activities in a revival test when the minimum spermicidal concentration of either JZ1 decoction, or N-9, or the mixed solution of the two agents, was used. N-9 (JZ1 in the mixed group) showed significant differences in the percentages of progressively moving spermatozoa, moving spermatozoa, and visible spermatozoa in 20 s, 3 min, and 30 min, when compared with N-9 alone (P<0.01). We are led to conclude that JZ1 decoction can improve N-9 spermicidal action in vitro, and when used in combination with N-9, it has synergic effect.
文摘The yaginal contraceptive sponge is made Of polyurethane containing 1g of nonoxynol-9.The gross cumulative twelve month life fable pregnancy rate of 352 cases nsf'ng yaginal contraceptive sponge was 5.7/100 women and foe methodpregnancy rate was 2.3/100 women. The gross cumulative continuation rate per 100 women was 74.Only 2 patients(1.0/100 women)suffering from vaginitis and itching of vulva no longer wished to continue in the study.Over the course of the study no significant changes were observed in any of the laboratory parameters such as yagina & cervix smear etc.that had been monitored. This modality associated with few side effects and its effectiveness rate and also indicaled a protection from the risk ofacquring of sex-transmitted diseases.
