Vaginosis. Vaginal microbiota. / Vaginosis. Microbiota vaginal.

The latest advances in the vaginal microbiome and molecular diagnosis of bacterial vaginosis have allowed for a better knowledge of this entity, characterising aspects of its pathogenesis and the establishment of the vaginal biolayer, the models and new theories of its aetiology, how it is transmitted, with it being considered nowadays as a probable sexually transmitted infection, the separation of other entities such as aerobic vaginosis, its molecular diagnosis and treatment with new molecules to prevent frequent relapses. This entity and the study of the vaginal microbiome have made it possible to consider these infections as a polymicrobial syndrome, putting an end to the dogma: one microorganism, one disease. In addition, a lesser-known entity such as aerobic vaginosis and the methods for its detection are updated.

An overview of properties of Amphora (Acidform) contraceptive vaginal gel.

INTRODUCTION: Although only a minority of contracepting women rely solely on spermicides, they may soon be the only ongoing female method available without a prescription in the United States. Spermicides are also combined with other methods for additional pregnancy protection and/or lubrication. Nonoxynol-9 (N-9), the active ingredient in most spermicides, is cytotoxic and may increase risk of transmission of HIV and other sexually transmitted infections, especially in high-risk women. Amphora (previously called Acidform) is a noncytotoxic spermicide composed of a series of generally regarded as safe compounds, which maintains the acidity of the vagina following coitus to immobilize and kill sperm. Amphora is currently Food and Drug Administration-approved as a vaginal lubricant. Amphora is currently being tested in a multicenter Phase III contraceptive trial. AREAS COVERED: This paper describes key properties of Amphora, including its acid-buffering abilities, viscosity, stability, bioadhesiveness, and tolerability. EXPERT OPINION: Amphora is a nontoxic spermicide that maintains the pH within the vagina at levels less than 5.0 for hours, which immobilizes and kills sperm as well as many sexually transmitted pathogens. If the current clinical trial demonstrates safety, efficacy, and tolerability of Amphora as a contraceptive, it would represent a viable alternative to N-9. Its potential as a microbicide warrants further investigation.

A phase I randomized postcoital testing and safety study of the Caya diaphragm used with 3% Nonoxynol-9 gel, ContraGel or no gel.

OBJECTIVES: The Caya® Diaphragm is a newly approved single-size, nonlatex diaphragm. Contragel® is a personal lubricant containing lactic acid approved in Europe and other countries for use with vaginal barrier devices. This study assessed the effectiveness in preventing sperm from penetrating midcycle cervical mucus of Caya with Contragel, Caya with 3% nonoxynol-9 (N-9) and Caya alone. STUDY DESIGN: Phase I multicenter, single-blind, randomized, crossover, nonsignificant risk study at two sites: Eastern Virginia Medical School, Norfolk, VA, USA, and Profamilia, Santo Domingo, Dominican Republic. Healthy, sexually active women 18-45years old, not at risk for pregnancy due to tubal occlusion, were eligible. Each participant was seen in nine visits, completing a baseline cycle (without product use) followed by three test cycles (sequence determined by randomization), each consisting of a cervical mucus check visit and a postcoital test visit. To proceed to test cycles, the baseline postcoital test had to show adequate cervical mucus and >5 progressively motile sperm per high power field (PMS/HPF). RESULTS: All women had an average of <5 PMS/HPF during the test cycle of each study arm, the primary endpoint. Caya with ContraGel and Caya with N-9 reduced the average number of PMS/HPF from 22.5 to 0. Caya alone reduced the average number of PMS/HPF from 22.5 to 0.4. There were two possibly product-related mild adverse events. CONCLUSION: This study supports that Caya with ContraGel is safe and functions as well as Caya with N-9 in preventing PMS from reaching midcycle cervical mucus. IMPLICATIONS: A single-size diaphragm used with a personal lubricant gel containing lactic acid appears to be safe and to function as well as the same diaphragm used with N-9 in preventing PMS from reaching midcycle cervical mucus.

Contraceptive efficacy, safety, fit, and acceptability of a single-size diaphragm developed with end-user input.

OBJECTIVE: To estimate contraceptive efficacy, safety, acceptability, and fit of a single-size diaphragm used with contraceptive gel. METHODS: We conducted a multicenter trial in which 450 couples used the single-size diaphragm, 300 randomized to acid-buffering gel and 150 to nonoxynol-9, for at least 190 days and six menstrual cycles. Visits were at enrollment and after menstrual cycles 1, 3, and 6. Study outcomes included pregnancy probability, safety, acceptability, and fit. Pregnancy and safety were compared with an historical control group who used a standard diaphragm with these gels. RESULTS: Most (439/450 [98%]) women could be fitted with the single-size diaphragm. A total of 421 of 450 (94%) provided follow-up. The 35 study pregnancies yielded 6-month Kaplan-Meier cumulative typical use pregnancy probabilities per 100 women with 95% confidence intervals (CIs) of 10.4 (6.9-14.0) for all users and 9.6 (5.5-13.6) and 12.5 (5.4-19.5) with acid-buffering gel and nonoxynol-9, respectively. Historical control analysis yielded a propensity score-adjusted estimate of this pregnancy probability for the single-size diaphragm of 11.3 compared with 10.7 per 100 women for the standard diaphragm ([rounded] difference 0.7, 95% CI -3.6 to 4.9). Approximately half (51%) reported at least one urogenital event but compared favorably to the standard diaphragm in historical control analysis. Most (282/342 [82%]) liked the diaphragm. Results suggest that if provided by a clinician, 94% (95% CI 92-96%) could insert, correctly position, and remove the diaphragm. CONCLUSION: The single-size diaphragm was safe, as effective as a standard diaphragm, and acceptable when used with contraceptive gel. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00578877.

ACIDFORM: a review of the evidence.

OBJECTIVE: ACIDFORM is a candidate microbicide with spermicidal properties. A large Phase 3 trial is underway, and it is anticipated that this product will be approved for contraceptive use and marketed soon in the United States. The goal of this article is to critically review the evidence supporting the properties, safety profile and different uses of ACIDFORM gel. STUDY DESIGN: We searched PubMed and Medline for any published literature on ACIDFORM. RESULTS: ACIDFORM is an acidifying agent that works by lowering the vaginal pH to enhance the normal vaginal defenses. In addition to strong acid-buffering properties, ACIDFORM has high bioadhesive and viscosity-retaining properties. Several Phase 1 clinical trials have demonstrated the vaginal safety of ACIDFORM used alone or in combination with a diaphragm, although dose-dependent side effects appear to be present. Studies investigating the efficacy of ACIDFORM against sexually transmitted infections (STIs) are promising, but further trials are needed. CONCLUSIONS: The properties of ACIDFORM offer many advantages for use, either alone or in combination with another active ingredient, such as Tenofovir. Potential applications for ACIDFORM include use as a personal lubricant, a vaginal contraceptive (alone or with a barrier method) and a microbicidal product or as a formulation vehicle for an active ingredient. IMPLICATIONS: ACIDFORM is a candidate female-controlled vaginal preparation with microbicidal and spermicidal properties. A dual protection method could prevent unwanted pregnancies and reduce the risk of STI acquisition.

Effect of lubricants and a vaginal spermicide gel on the detection of prostate specific antigen, a biomarker of semen exposure, using a quantitative (Abbott ARCHITECT) assay.

OBJECTIVES: Little is known about the effects of commonly used lubricants on detection of biomarkers of semen exposure. We investigated the in vitro effect of Gynol®, K-Y Jelly®, Replens®, Astroglide®, Carbopol, and Silicorel on quantitative detection of prostate specific antigen (PSA). STUDY DESIGN: A predetermined concentration of each of the gels was added to serially diluted semen samples. Additionally, serial dilutions of each of the gels were added to three different semen dilutions (high, medium, or low). The resulting samples were tested for PSA on the Abbott ARCHITECT System. RESULTS: When using the Abbott ARCHITECT system, the only products that inhibited PSA detection were Gynol® and Replens®. The inhibition caused by Gynol® was dose-dependent, but that of Replens was dose-independent. K-Y Jelly®-spiked samples had higher PSA values than controls. CONCLUSIONS: Caution is warranted when using the Abbott quantitative assay for PSA detection as a biomarker of semen exposure in settings where Gynol®, Replens® or K-Y Jelly® might also have been used. Neither Astroglide® nor Silicorel inhibited PSA detection. Additional studies evaluating other vaginal products, including microbicides, and their effects on other assays, are needed. In vivo studies will be especially important to optimize PSA detection from clinical samples. IMPLICATIONS: Researchers should consider the potential for specific lubricants or any vaginal products to affect the particular assay used for semen biomarker detection. The Abbott ARCHITECT's total PSA assay should not be used with the product Replens. Caution is warranted when using the assay in settings where Gynol or K-Y jelly may have been used.

Quantitative assessment of altered rectal mucosal permeability due to rectally applied nonoxynol-9, biopsy, and simulated intercourse.

BACKGROUND: Microbicide toxicity may reduce the efficacy of topical preexposure prophylaxis for human immunodeficiency virus (HIV) transmission. Noninvasive quantitative measures of microbicide toxicity would usefully inform microbicide development. METHODS: Ten subjects received 3 one-time interventions: 5 mL of Normosol-R fluid alone (negative control), 5 mL of 2% nonoxynol-9 (N-9) gel, and 5 mL of Normosol-R with coital simulation and sigmoidoscopic biopsy (CS + BX). Each dose of N-9 and Normosol-R contained 500 µCi of (99m)technetium-diethylene triamine pentaacetic acid. Plasma and urine radioactivity was assessed over 24 hours. RESULTS: The plasma radioisotope concentration peaked 1 hour after N-9 dosing. The mean maximum radioisotope concentration after N-9 receipt was 12.0 times (95% confidence interval [CI], 6.8-21.0) and 8.4 times (95% CI, 5.2-13.5) the mean concentration after Normosol-R control receipt and CS + BX receipt, respectively; paired differences persisted for 24 hours. After N-9 dosing, the urine isotope level was 3.6 times (95% CI, 1.1-11.4) the level observed 8 hours after Normosol-R control receipt and 4.0 times (95% CI, 1.4-11.4) the level observed 4 hours after CS + BX receipt. Permeability after CS + BX receipt was greater than that after Normosol-R control receipt in 0-2-hour urine specimens only (mean permeability, 2.4; 95% CI, 1.0-5.8) but was not greater in blood. CONCLUSIONS: Plasma sampling after rectal radioisotope administration provided quantitative estimates of altered mucosal permeability after chemical and mechanical stresses. Permeability testing may provide a useful noninvasive adjunct to assess the mucosal effects of candidate microbicides. Clinical Trials Registration. NCT00389311.

Effectiveness of an optimized benzalkonium chloride gel as vaginal contraceptive: a randomized controlled trial among Chinese women.

BACKGROUND: This study was conducted to evaluate the efficacy, safety and acceptability of a newly developed benzalkonium chloride (BZK) contraceptive gel which was compared to nonoxynol-9 (N-9) gel. STUDY DESIGN: A Phase II, multicenter, randomized, controlled study at three Chinese centers was conducted to compare 120 women who used BZK gel with 120 women who used N-9 gel for 6 months. Contraceptive efficacy was assessed by pregnancy rate, and safety was evaluated by adverse events report, gynecologic examination, Papanicolaou smears, leukorrhea test, and blood and urine tests. The acceptability was assessed through follow-up visit forms and a questionnaire at the 6-month visit. RESULTS: Net cumulative rates in the BZK group at 6 months were as follows: follow-up 100%, terminations 5.1%, pregnancy 1.7%, medical reasons 0% and fear of failure 3.4%. At 6 months, the rates in the N-9 group were as follows: follow-up 99.2%, terminations 9.4%, pregnancy 0.9%, medical reasons 2.5%, fear of failure 3.4% and other personal reasons 2.6%. No significant difference in pregnancy rate and termination rate between the two groups was found (p>.05). Seven cases in the BZK group (5.8%) complained about leukorrhagia and vaginal irritation symptoms (itching and burning) at 6 months, while 16 cases in the N-9 group (13.3%) had similar complaints (p<.05). This significant difference continued to exist until the 6-month visit. The general satisfaction rate for BZK gel use (72.8%) is significantly higher than that for N-9 gel (42.5%). CONCLUSION: The optimized BZK gel is comparable to N-9 gel in terms of contraceptive efficacy and safety, and may be more acceptable to Chinese users.

Phase I randomized safety study of twice daily dosing of acidform vaginal gel: candidate antimicrobial contraceptive.

BACKGROUND: Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. METHODS: Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC) placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL) at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays. RESULTS: The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002). While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08). CONCLUSIONS: Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than placebo and lower levels of antimicrobial (lactoferrin) and anti-inflammatory (IL-1ra) proteins. These findings indicate the need for additional safety studies of this candidate non-hormonal contraceptive. TRIAL REGISTRATION: ClinicalTrials.gov NCT00850837.

Contraceptive efficacy and safety of HerbOshield™ vaginal gel in rats.

BACKGROUND: Spermicides represent one of the methods of contraception. The synthetic agents available as spermicides produce severe side effects. Hence, there is a need to replace these agents with safe and effective agents such as plant-based contraceptive agents. STUDY DESIGN: The objective of the present study was to develop and evaluate a stable, safe, effective and easily acceptable contraceptive delivery system containing herbal drug. Efforts were made to evaluate the contraceptive potential of the hydroalcoholic extract from the seeds of Annona squamosa Linn. and the vaginal gel HerbOshield™ containing the extract. RESULTS: Spermicidal effect was evaluated in vitro using healthy human spermatozoa and in vivo in rats. The in vitro results demonstrated that HerbOshield™ vaginal gel is an effective spermicide. At a 100-mg/mL dose, complete immobilization of human spermatozoa was observed within 20 s. None of the treated animals conceived, indicating 100% contraceptive effect as compared to Gynol II, a nonoxynol-9-containing marketed formulation, which showed only 67% contraceptive effect in vivo. HerbOshield™ vaginal gel was found to be safe in animals during a 14-day toxicity study. CONCLUSIONS: HerbOshield™ vaginal gel was found to be safe and effective in rats and could be developed as a potential vaginal contraceptive for future use in humans.

Optical coherence tomography compared with colposcopy for assessment of vaginal epithelial damage: a randomized controlled trial.

OBJECTIVE: Colposcopy has been used to detect epithelial damage with vaginal microbicides. In animal models, optical coherence tomography provided increased sensitivity over colposcopy in detecting epithelial injury. This randomized, double-blinded, clinical study compared optical coherence tomography to colposcopy for the evaluation of epithelial injury in women using placebo or nonoxynol-9. METHODS: Thirty women aged 18-45 were randomized to use hydroxyethyl cellulose placebo or nonoxynol-9 vaginal gel twice daily for 5.5 days. Imaging with colposcopy and optical coherence tomography was performed before product use, after the last dose, and 1 week later. Colposcopy was graded using standard criteria. Optical coherence tomography images were scored for epithelial integrity based on a published scoring system and were measured for epithelial thickness. RESULTS: Colposcopy findings, optical coherence tomography scores, and epithelial thicknesses were similar between treatment groups at baseline. After treatment, there were significant differences between the nonoxynol-9 (1.37) and control group (1.15) optical coherence tomography scores (P<.001), indicating epithelial injury, and there was epithelial thinning in the nonoxynol-9 group (237 micrometers) compared with the control group (292 micrometers; P=.008). There were no significant posttreatment colposcopic differences in epithelial disruption between treatment groups, with only increased erythema noted after nonoxynol-9 use (P=.02). CONCLUSION: Optical coherence tomography detected epithelial disruption and thinning not identified by colposcopy. Vaginal epithelial thickness, a measure previously available only through biopsy, decreased after nonoxynol-9 use, a finding that may contribute to increased susceptibility to human immunodeficiency virus after frequent use. Optical coherence tomography shows promise for the noninvasive clinical assessment of vaginal epithelial damage. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry, www.umin.ac.jp/ctr/index.htm, R000006186. LEVEL OF EVIDENCE: I.

Mucosal integrity and inflammatory markers in the female lower genital tract as potential screening tools for vaginal microbicides.

BACKGROUND: In the female genital tract, vaginal colposcopy, endometrial mucosal integrity and inflammatory mediators are potential in vivo biomarkers of microbicide and contraceptive safety. STUDY DESIGN: A randomized, blinded crossover trial of 18 subjects comparing effects of nonoxynol-9 vaginal gel (Gynol II; putative inflammatory gel), hydroxyethyl cellulose gel (HEC; putative inert gel) and no gel exposure on endometrial and vaginal epithelial integrity and endometrial and vaginal inflammatory markers [interleukin (IL) 1ß, IL-6, IL-8, MCP-1, MIP-1α, MIP-1ß, RANTES, tumor necrosis factor α, IL-1RA, IL-10, SLPI). RESULTS: Gynol II was associated with more vaginal lesions. No endometrial disruptions were observed across conditions. In the vagina, RANTES (p=.055) and IL-6 (p=.04) were higher after HEC exposure than at baseline. In the endometrium, IL-1ß (p=.003) and IL-8 (p=.025) were lower after Gynol II cycles than after no gel. CONCLUSIONS: Gynol II and HEC may modulate inflammatory markers in the vagina and endometrium. How these changes relate to infection susceptibility warrants further study.

Novel trichomonacidal spermicides.

Metronidazole, the U.S. Food and Drug Administration-approved drug against trichomoniasis, is nonspermicidal and thus cannot offer pregnancy protection when used vaginally. Furthermore, increasing resistance of Trichomonas vaginalis to 5-nitro-imidazoles is a cause for serious concern. On the other hand, the vaginal spermicide nonoxynol-9 (N-9) does not protect against sexually transmitted diseases and HIV in clinical situations but may in fact increase their incidence due to its nonspecific, surfactant action. We therefore designed dually active, nonsurfactant molecules that were capable of killing Trichomonas vaginalis (both metronidazole-susceptible and -resistant strains) and irreversibly inactivating 100% human sperm at doses that were noncytotoxic to human cervical epithelial (HeLa) cells and vaginal microflora (lactobacilli) in vitro. Anaerobic energy metabolism, cell motility, and defense against reactive oxygen species, which are key to survival of both sperm and Trichomonas in the host after intravaginal inoculation, depend crucially on availability of free thiols. Consequently, molecules were designed with carbodithioic acid moiety as the major pharmacophore, and chemical variations were incorporated to provide high excess of reactive thiols for interacting with accessible thiols on sperm and Trichomonas. We report here the in vitro activities, structure-activity relationships, and safety profiles of these spermicidal antitrichomonas agents, the most promising of which was more effective than N-9 (the OTC spermicide) in inactivating human sperm and more efficacious than metronidazole in killing Trichomonas vaginalis (including metronidazole-resistant strain). It also significantly reduced the available free thiols on human sperm and inhibited the cytoadherence of Trichomonas on HeLa cells. Experimentally in vitro, the new compounds appeared to be safer than N-9 for vaginal use.

Recurrent urinary tract infection.

OBJECTIVE: to provide an update of the definition, epidemiology, clinical presentation, investigation, treatment, and prevention of recurrent urinary tract infections in women. OPTIONS: continuous antibiotic prophylaxis, post-coital antibiotic prophylaxis, and acute self-treatment are all efficient alternatives to prevent recurrent urinary tract infection. Vaginal estrogen and cranberry juice can also be effective prophylaxis alternatives. EVIDENCE: a search of PubMed and The Cochrane Library for articles published in English identified the most relevant literature. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date restrictions. VALUES: this update is the consensus of the Sub-Committee on Urogynaecology of the Society of Obstetricians and Gynaecologists of Canada. Recommendations were made according to the guidelines developed by the Canadian Task Force on Preventive Health Care (Table 1). OPTIONS: recurrent urinary tract infections need careful investigation and can be efficiently treated and prevented. Different prophylaxis options can be selected according to each patient's characteristics.

Contraceptive efficacy, acceptability, and safety of C31G and nonoxynol-9 spermicidal gels: a randomized controlled trial.

OBJECTIVE: To estimate whether a gel containing the spermicide C31G was noninferior to a commercially available product containing nonoxynol-9. METHODS: Participants were healthy, sexually active women aged 18-40 years. Measured outcomes included pregnancy rates, continuation rates, adverse events, and acceptability. The primary study outcome was contraceptive efficacy. Sample size was calculated at a 2.5% significance level using a one-sided test based on assumed 6-month pregnancy probability of 15% in the nonoxynol-9 group. Sample size was sufficient to reject, with 80% power, the null hypothesis that pregnancy probability in the C31G arm would be more than 5% higher. RESULTS: Nine hundred thirty-two women were randomized in the C31G group and 633 in the nonoxynol-9 group. For randomized patients with at least one episode of coitus (modified intent-to-treat group), 6-month pregnancy probabilities were 12.0% (95% confidence interval [CI] 9.3-14.7%) and 12.0% (95% CI 8.7-15.3%) for C31G and nonoxynol-9,respectively. Twelve-month pregnancy probabilities were 13.8% (95% CI 7.6-20%) for C31G and 19.8% (95% CI 10.9-28.7%) for nonoxynol-9. Two serious adverse events were deemed possibly related to study product and neither occurred in the C31G group. Three fourths of users in either group reported that they liked their assigned study product. Approximately 40% of patients discontinued prematurely for reasons other than pregnancy with 11% lost to follow-up. CONCLUSION: C31G demonstrated noninferior contraceptive efficacy compared with nonoxynol-9. C31G may provide another marketable option for women seeking spermicidal contraception. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00274261.

The association between use of spermicides or male condoms and major structural birth defects.

BACKGROUND: Women may become pregnant while using contraceptives. Commonly used contraceptives containing spermicides may or may not be associated with an increased occurrence of structural birth defects. STUDY DESIGN: Utilizing data from the National Birth Defects Prevention Study, we assessed maternal reports of spermicide and male condom use 1 to 3 months following conception among case (n=11,050) and control (n=4723) mothers. We assessed the association between spermicide use and 27 types of birth defects and that between condom use and 32 types of birth defects. RESULTS: Maternal spermicide use during the first 3 months following conception was associated with a significant increase in the occurrence of only 1 of 27 birth defects, perimembranous ventricular septal defects (adjusted odds ratio=2.40, 95% confidence interval=1.25-4.62). There was no significant association between maternal use of male condoms during the first 3 months following conception and any of 32 types of birth defects. CONCLUSIONS: The increased occurrence of perimembranous ventricular septal defects among spermicide users may be real or may be a chance finding. Overall, the findings are consistent with those of most previous studies that observed no increased risk for birth defects among spermicide users.

Acaciaside-B-enriched fraction of Acacia auriculiformis is a prospective spermicide with no mutagenic property.

As a part of our continued venture to develop a safe and effective spermicide, we have identified a triterpene glycoside (Acaciaside-B (Ac-B))-enriched fraction (Ac-B-en) isolated from the seeds of Acacia auriculiformis and evaluated its spermicidal potential in vitro. Sperm motility was completely inhibited within 20 s at a minimum effective concentration (MEC) of 120 microg/ml. Tests for sperm viability by dual fluoroprobe staining showed the effect to be spermicidal with an EC(50) of 35.20 microg/ml. A series of investigations including tests for hypo-osmotic swelling, membrane lipid peroxidation, and electron microscopy document that the spermicidal effect of the fraction involves loss of sperm plasma membrane integrity and dissolution of the acrosomal vesicle--the two most important structural components that play diverse roles in physiological functions of sperm including fertilization. The fraction at 10 x MEC exerted no detrimental effects on in vitro growth of Lactobacillus acidophilus, which is considered the major constituent of vaginal microflora that maintains vaginal health. Ames tests performed with different strains of Salmonella typhimurium including TA 97a, 98, 100, and 102, which detect mutagens causing bp substitution or frameshifting at G-C or A-T bp, demonstrate no mutagenic potential of the fraction. Significant spermicidal potential with no possible mutagenic effect and adverse impacts on lactobacilli growth attests to the credential of Ac-B-en as a prospective future spermicide for the development of a safe and effective vaginal contraceptive formulation.

Safety studies of a recently developed microbicidal contraceptive gel (UniPron) in female baboons (Papio anubis).

To identify any toxicity on the vaginal epithelium, liver and kidney following UIniPron administration, ten healthy female olive baboons (Papio anubis) of reproductive age and of proven fertility were used. Five baboons were each treated with 15 g of UniPron intravaginally twice a week for 20-weeks and venous blood collected before and after each treatment. Venous blood was collected from five control animals as in the experimental females, but these control animals were not given any treatment. The endpoints that were evaluated included clinical chemistry profiles on kidney and liver functions and vaginal histopathology. Female baboons treated with 15 g of UniPron intravaginally showed no detectable adverse effects on clinical chemistry profiles investigated and vaginal histopathology. Repeated intravaginal exposure of female baboons to UniPron did not induce detectable vaginal irritation and there were no detectable histological changes. We conclude that administration of UniPron into baboon vagina did not cause any detectable toxicity.

Characterization of indigenous vaginal lactobacilli from healthy women as probiotic candidates

The probiotic relevant characteristics of 45 strains of vaginal Lactobacillus isolated from healthy women were analyzed. Of these, 21 strains were classified as L. crispatus, 17 as L. jensenii, six as L. gasseri, and one as L. plantarum. The rate of acidification varied significantly between the strains as did their ability to form biofilms. None used glycogen as a fermentable carbohydrate. H2O2 generation was common, especially among L. jensenii isolates (88%). No bacteriocinogenic strains were detected. Most strains harbored plasmids (from 1 to 7) of various sizes, those in excess of 50 kb being frequent. One of these plasmids was found to be promiscuous since it hybridized with extrachromosomal bands of 15 isolates. All strains were resistant to metronidazole, ciprofloxacin, gentamicin, clindamycin, trimethoprim, and sulfametoxazole and susceptible to a series of beta-lactams, erythromycin, tetracycline, and benzalkonium chloride. Almost half of the strains were highly resistant to nonoxinol 9, which is commonly used as a spermicide. Based on these analyses, strains of all three common species are proposed as new probiotic candidates (AU)

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