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PubMed2005

AIDS vaccine: Intranasal immunization using inactivated HIV-1-capturing core-corona type polymeric nanospheres.

Polymeric nanospheres have been widely used in biomedical applications, such as drug, gene and vaccine delivery systems. Nanospheres with entrapped antigens have recently been shown to possess significant potential as vaccine delivery systems and adjuvants. We previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and intranasal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody responses in mice. In addition, vaginal washes from intranasally immunized mice were capable of neutralizing HIV-1. Moreover, simian/human immunodeficiency virus KU-2-capturing nanospheres (SHIV-NS) immunized macaques exhibited partial protection when vaginally and systemically challenged with pathogenic viruses. HIV-NS is suggested to be particularly suitable to enhance antigen delivery to dendritic cells (DCs). In this study, we investigated the mucosal antibody response in mice after the intravaginal or intranasal immunization in detail with using different sized (360, 660, 940 and 1230 nm) HIV-NS. The amount of immobilized Con A to NS was dependent on the surface area of the particle. Moreover, Con A-NS with different sizes could equally capture inactivated HIV-1. Intravaginal or intranasal immunization by HIV-NS with diameters ranging 360 to 1230 nm significantly induced vaginal antibody responses. However, significant differences on vaginal anti-HIV-1 gp120 IgA and IgG antibodies were not found after intravaginal or intranasal immunization with different sized HIV-NS. These results suggest that HIV-NS provides an efficient vaccine delivery system for the induction of a mucosal immune response and the development of a mucosal vaccine.

AIDS Vaccines↗
PubMed1991

Estrogen regulates the gonadotropin-releasing hormone-stimulated secretion of biologically active luteinizing hormone.

Estrogen produces time-dependent bidirectional effects on the GnRH-stimulated release of immunoactive LH in various species. To examine estrogen's regulation of biologically active LH secretion in response to pulsatile stimulation by GnRH, we studied estrogen-deficient postmenopausal women basally and during treatment with diethlystilbesterol (DES; 1 mg, orally, daily). Basal and GnRH-stimulated plasma concentrations of bioactive LH were assayed by the in vitro rat interstitial cell testosterone bioassay. GnRH-promoted LH secretory bursts in response to two consecutive stimuli were quantitated by multiple parameter deconvolution analysis. Basal half-lives of LH averaged 171 +/- 17 min (immunoactive) and 223 +/- 10 min (bioactive). Analysis of variance revealed a significant decrease in mean basal plasma bioactive LH concentrations on days 10 and 30 of DES treatment. Mean serum immunoactive LH concentrations fell similarly. DES significantly increased the half-life of immunoactive LH (days 5 and 10), but did not change that of bioactive LH. GnRH self-priming of bioactive LH secretion (increased LH secretory peak 2 compared to peak 1) was demonstrated, with a maximal value on day 10 of DES treatment. In addition, the ratio of the mass of bioactive to immunoactive LH secreted in response to the first GnRH pulse was significantly enhanced by estrogen on day 5, whereas that after the second pulse of GnRH was significantly suppressed on day 30 of DES. The self-priming action of GnRH on bioactive LH release evident in the presence of oral DES was corroborated in a separate group of six women, who were treated for 30 days with 17 beta-estradiol via an intravaginally placed Silastic ring. In conclusion, we infer that estrogen exerts a highly selective effect on the gonadotroph secretory process, such that successive GnRH stimuli result in an increase in the maximal rate and mass of secretion of biologically active LH.

Administration, Intravaginal↗
PubMed2003

Action of 25 microg 17beta-oestradiol vaginal tablets in the treatment of vaginal atrophy in Greek postmenopausal women; clinical study.

PURPOSE: To evaluate the clinical efficacy and safety of intravaginal application of 25 microg micronized oestradiol in postmenopausal women from the Greek population suffering from symptoms related to vaginal atrophy. MATERIALS AND METHODS: 91 women suffering from vaginal dryness, vaginal itching and dyspareunea were treated with 25 microg 17beta-oestradiol vaginal tablets. The duration of treatment was 12 weeks. During the first two weeks the women inserted one vaginal tablet intravaginally once daily. Thereafter, the women inserted one tablet twice per week with at least a 3-day interval between treatments to maintain therapeutic response for ten weeks. Efficacy was evaluated by the relief of vaginal symptoms and safety by the concentrations of serum oestradiol (E2) and follicular-stimulating hormone (FSH). Pretreatment and post-treatment findings were compared and each patient served as her own control. RESULTS: The rates of symptoms of vaginal dryness, vaginal itching and dyspareunea showed statistically significant differences over the course of the trial (Cochran Q test, p < 0.001). No one complained of vaginal dryness and vaginal itching after four and six weeks of treatment respectively, while in one patient the sensation of dyspareunea remained constant after the fourth week of treatment. Despite the statistically significant increase in blood oestradiol levels in relation to baseline values (ANOVA model of repeated measures, p < 0.001), these levels were within the normal range for postmenopausal women. Also, serum FSH levels were statistically significantly reduced from 47.4 mIU/ml at entry into the study to 45.5 mIU/ml after two weeks of treatment (dependent samples t-test, p < 0.003), but were clearly within the postmenopausal range. CONCLUSIONS: The twice-weekly local single treatment with vaginal tablets containing 25 microg of 17beta-oestradiol was effective and safe for the relief of symptoms related to atrophic vaginitis in postmenopausal women from the Greek population.

Administration, Intravaginal↗
PubMed1990

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. I. Contraceptive efficacy and side effects. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

A multicentre clinical trial, including 19 centres in 13 countries, assessed the contraceptive efficacy and clinical acceptability of a Silastic 382 vaginal ring releasing 20 micrograms of levonorgestrel for at least 90 days. A total of 1005 women entered the study and 8176.74 woman-months of experience was gathered. The rate of intrauterine pregnancy at one year of use was 3.6 per 100 women (95% confidence interval 2.2-5.0), and of ectopic pregnancy, 0.2% (one case). The principal reasons for discontinuation were menstrual disturbances (17.2% at one year), vaginal symptoms (6.0%) and repeated expulsion of the ring (7.1%). The pregnancy rate with this 20 micrograms levonorgestrel-releasing vaginal ring compares favourably with that of a low estrogen combination oral contraceptive tested by WHO and is less than half that of a progestogen-only oral contraceptive in a WHO randomized study. It is concluded that the WHO intravaginal ring releasing an average of 20 micrograms of levonorgestrel per 24 hours is an effective method of contraception for at least one year of use.

Administration, Intravaginal↗
PubMed2005

PRO 2000 gel inhibits HIV and herpes simplex virus infection following vaginal application: a double-blind placebo-controlled trial.

BACKGROUND: Microbicides used to prevent the transmission of human immunodeficiency virus (HIV) are advancing to clinical trials on the basis of activity observed in vitro and in animal models. However, no data demonstrate activity of microbicides after application in humans. This study was designed to determine the antiviral activity in cervicovaginal lavage (CVL) samples collected after intravaginal application of 0.5% PRO 2000 gel (Indevus). METHODS: A randomized, double-blind study was conducted to assess the anti-HIV and anti-herpes simplex virus (HSV) activity of PRO 2000 in CVL samples obtained at screening (48 hours before) and 1 hour after application of study or placebo gel. HeLa cells or human macrophages were inoculated with CVL samples spiked with replication-defective HIV containing a luciferase indicator gene and pseudotyped with an R5 envelope. Human cervical epithelial cells were inoculated with CVL samples and challenged with HSV-2(G), and the virus titer was then determined. RESULTS: CVL samples obtained after application of PRO 2000 gel significantly inhibited HIV and HSV infection by at least 1000-fold, compared with CVL samples obtained at screening (P < .001). There were no differences in cytokine levels between the drug and placebo groups. CONCLUSIONS: PRO 2000 gel (0.5%) is sufficiently bioavailable and retains substantial antiviral activity after intravaginal application. This strategy provides a mechanism for testing the efficacy of a microbicide before embarking on large-scale clinical trials.

Administration, Intravaginal↗
PubMed1980

Ovum transport in the rhesus monkey following postovulatory intravaginal 15(S)-15-methyl prostaglandin F2 alpha-methyl ester administration.

The effects of postovulatory intravaginal 15(S)-15-methyl prostaglandin F2 alpha-methyl ester (Me PGF2 alpha) on ovum transport was assessed in the spontaneously ovulatory rhesus monkey. A single suppository containing 3.0 mg of Me PGF2 alpha in lipid base was inserted intravaginally in adult female monkeys 14 to 36 hours following laparoscopically timed ovulation. The reproductive tract was flushed 2, 4, or 24 hours later to recover ova. Four of five ova were recovered at 2 hours, one of five at 4 hours, and none of five at 24 hours after insertion. All ova recovered were in the oviduct. Since ova are normally found in the oviduct until 72 hours after ovulation, these results are interpreted to indicate acceleration and expulsion of ova from the tract following exposure to intravaginal Me PGF2 alpha in excess of 4 hours.

Animals↗
PubMed1993

Efficacy of intravaginal 0.75% metronidazole gel for the treatment of bacterial vaginosis.

OBJECTIVE: To assess the efficacy of 0.75% metronidazole vaginal gel, formulated at pH 4.0, for the treatment of bacterial vaginosis in a double-blind, placebo-controlled crossover trial. METHODS: Fifty-three women with bacterial vaginosis (clue cells of at least 20% plus vaginal pH of at least 4.7, amine odor, or homogeneous discharge) were enrolled. Women with concomitant infection by Candida, Trichomonas, Chlamydia trachomatis, or Neisseria gonorrhoeae were excluded. Five grams of metronidazole gel or placebo was inserted intravaginally twice daily for 5 days. Response to therapy was evaluated at 4-16 days and 1 month after treatment. RESULTS: Twenty-six of the 30 women (87%) who received metronidazole were free of bacterial vaginosis 9-21 days after enrollment, compared with only four (17%) of 23 placebo-treated women (P < .001). Women who were cured were followed prospectively. Those who had persistent bacterial vaginosis were crossed over to metronidazole gel in an open trial; bacterial vaginosis was eradicated in 21 of 23 (91%) of these women at the 2-week follow-up. Recurrent bacterial vaginosis developed within 1 month in four (15%) of 26 women who were initially cured after receiving metronidazole gel. Response to therapy was accompanied by a decrease in vaginal Bacteroides, Gardnerella vaginalis, and Mycoplasma hominis. CONCLUSIONS: Treatment with intravaginal metronidazole gel resulted in a clinical cure in 87% (placebo-controlled trial) to 91% (crossover trial) of women with bacterial vaginosis. The recurrence rate of 15% at 1 month after treatment is similar to that reported with oral metronidazole.

Administration, Intravaginal↗
PubMed2004

Intravaginal metronidazole gel versus metronidazole plus nystatin ovules for bacterial vaginosis: a randomized controlled trial.

OBJECTIVE: We compared metronidazole 0.75% gel (containing 37.5 mg metronidazole per dose) with ovules containing metronidazole 500 mg and nystatin 100,000 U, for intravaginal treatment of bacterial vaginosis (BV). STUDY DESIGN: In a single-blinded trial, symptomatic women with BV by both Amsel and Nugent criteria were randomly assigned to gel or ovules, once nightly for 5 nights, and asked to return 3 times after treatment. Analyses were intent-to-treat. RESULTS: Of 151 women with BV by both criteria at enrollment, 138 (91%) returned at least once. Product limit estimates for persistence or recurrence of BV at 14, 42, and 104 days were 20% (95% CI 10%-29%), 38% (95% CI 25%-48%), and 52% (95% CI 37%-63%) after gel treatment, and 4% (95% CI 0%-9%), 17% (95% CI 7%-26%), and 33% (95% CI 21%-46%) after ovule treatment ( P = .01). Among women without BV at first follow-up, subsequent intercourse without condoms independently predicted subsequent recurrence ( P </= .01). CONCLUSION: Metronidazole/nystatin ovules were significantly more effective than metronidazole gel. Unprotected sex predicted recurrence after initial improvement.

Administration, Intravaginal↗
PubMed2004

The effect of intravaginal applied GnRH-agonist on the time of ovulation and subsequent reproductive performance of weaned multiparous sows.

In order to prove the effect of 'fixed time insemination' and insemination at standing oestrus after post-weaning application of GnRH, in a Croatian large breeding unit, 502 sows were assigned to three groups and were artificially inseminated (AI) at their first post-weaning oestrus as many times as they stand, in 24-h intervals. The groups were treated as follows: group 1 (control, n = 160) were AI during their standing reflex; group 2 ['GnRH-fixed time insemination' (GnRH-FT-AI), n = 175] were AI, independent of detection of oestrus and following administration of GnRH-agonist at 96 h post-weaning; group 3 [GnRH insemination at standing oestrus (GnRH-OE-AI), n = 167] the animals were GnRH-agonist treated as group 2 and were AI at their standing reflex. Pre-trial daily average lactational feed intake, average daily feed intake from weaning to oestrus, oestrus within 6 days post-weaning (%), ovulation within 6 days post-weaning (%), weaning-to-oestrus interval (h), duration of oestrus (h), follicle size (mm), interval from oestrus to ovulation (h), subsequent day 24 pregnancy rate (%), farrowing rate (%) and total pigs born were evaluated. Pre-trial average daily lactational voluntary feed intake was 7.1 +/- 0.08 kg in group 1, 7.0 +/- 0.07 kg in group 2 and 7.1 +/- 0.17 kg in group 3 (p > 0.05). Average voluntary daily feed intake from weaning to oestrus was 5.1 +/- 0.3 kg in group 1, 5.2 +/- 0.5 kg in group 2 and 5.2 +/- 0.19 kg in group 3 (p > 0.05). Oestrus was detected within 6 days post-weaning in 134 (83.8%) in control, 164 (93.7%) in GnRH-FT-AI and 155 (92.8%) animals in GnRH-OE-AI groups (p = 0.05). Follicle size did not differ (p > 0.05) among the groups. In control 82.8%, in GnRH-FT-AI 91.5% and in GnRH-OE-AI 91.0% of the sows ovulated within 6 days post-weaning (p = 0.04), and had 80.6, 90.9 and 89.7% 24-day pregnancy rates (p = 0.16), respectively. In GnRH-FT-AI group 90.2%, in GnRH-OE-AI sows 89.7%, in control animals 79.9% farrowing rates were recorded (p = 0.17). Weaning to oestrus interval was 113.1 h in control, 114.1 h in GnRH-FT-AI and 112.6 h GnRH-OE-AI (p > 0.05). Duration of oestrus was significantly shorter in GnRH-FT-AI (44.9 h) and GnRH-OE-AI (48.1 h) animals, compared with the control (62.9 h) sows (p = 0.001). Similarly, the interval from oestrus to ovulation revealed significant (p = 0.004) differences between the groups (control 44.1 h, GnRH-OE-AI 34.1 h and GnRH-FT-AI 32.9 h). GnRH-FT-AI (12.5) and GnRH-OE-AI (12.6) sows had significantly higher (p = 0.01) number of total pigs born (n = 10.4) compared with control sows. GnRH-agonist-gel treatment to the sow shortens duration of oestrus, the interval from oestrus to ovulation, and may eliminate the need for oestrus detection in the hands of skilled personnel.

Administration, Intravaginal↗
PubMed1995

[Damage to condoms caused by vaginally administered drug].

A 28-year-old woman who was treated for vaginal candidiasis with Gyno-Daktarin vaginal capsules (miconazole nitrate) became pregnant because a condom used during intercourse had ruptured. Incubation in vitro with 400 and 1200 mg miconazole nitrate vaginal capsules (Gyno-Daktarin 3 and Gyno-Daktarin I), but not miconazole nitrate vaginal cream (20 mg/g), was shown to damage rubber condoms. Patients using vaginal medicines should be aware of a possible adverse effect on rubber condoms or contraceptive diaphragms and a subsequent increased risk of pregnancy or contagious diseases such as AIDS. Fatty excipients such as glycerin, paraffin, petrolatum or Witepsol may be involved.

Administration, Intravaginal↗
PubMed2001

Candida lusitaniae as an unusual cause of recurrent vaginitis and its successful treatment with intravaginal boric acid.

Increasing use of short-course antifungal therapies in patients with recurrent vulvovaginitis may enable the emergence of less-common, more resistant yeast strains as vaginal pathogens. We report the case of a patient with chronically symptomatic and repeatedly treated vaginal candidiasis whose infection was attributable to Candida lusitaniae, a previously unreported cause of candidal vaginitis.

Administration, Intravaginal↗
PubMed2006

Second-trimester pregnancy interruption with vaginal misoprostol in women with previous cesarean section.

OBJECTIVE: To describe the experience of misoprostol use for pregnancy interruption in the second trimester of women with previous cesarean section. MATERIAL AND METHOD: Seventeen pregnant women with viable fetuses and with previous cesarean section indicated for second trimester pregnancy interruption attending Maharaj Nakorn Chiang Mai Hospital were recruited. All received the same regimen of 400 mcg intravaginal misoprostol every 6 hours. The data was analyzed for demographic characteristics, the adverse outcomes, success rate, and time interval to fetal expulsion. RESULTS: The incidences of adverse outcomes were as follows, fever (47.1%), chill (23.5%), and nausea (17.6%). No uterine rupture occurred in this series at all. The rate of oxytocin use and analgesia requirement was 29.4%. Success rate of pregnancy interruption was 100%, though two of them had an abortion time of more than 48 hours. Time interval from misoprostol administration to fetal expulsion was 25.9 +/- 34. 1 hours (range 4.0-142.7 hours). CONCLUSION: This case series reaffirms the efficacy of misoprostol and suggests that misoprostol may relatively be safe even in cases with previous cesarean section. Therefore, misoprostol may be an option of pregnancy interruption in the second trimester to avoid unnecessary surgical procedure including hysterotomy. However, the safety should be tested by further studies with a larger sample size.

Abortifacient Agents, Nonsteroidal↗
PubMed2001

Gel-microemulsions as vaginal spermicides and intravaginal drug delivery vehicles.

There is a need for novel formulations to improve the bioavailability through the vaginal/rectal mucosa of microbicidal drug substances against sexually transmitted diseases. In addition, there is a need for more effective and less toxic vaginal spermicides. Here we review our recent discovery of novel gel-microemulsions (GM) as nontoxic, dual-function intravaginal spermicides, which can be used as delivery vehicles for lipophilic drug substances targeting sexually transmitted pathogens. We describe the formulation and biologic properties of 2 novel, submicron-particle-size GMs, GM-4 and GM-144, which were prepared from commonly available pharmaceutical excipients. These GMs comprising oil-in-water microemulsion and polymeric hydrogels were designed to solubilize lipophilic antiviral/antimicrobial agents and exhibited rapid spermicidal activity in human semen. Preclinical studies comparing the in vivo contraceptive efficacy of GM-4 and GM-144 versus nonoxynol-9-based detergent spermicide (Gynol II) in the rigorous rabbit model confirmed the potent contraceptive activity of these GMs. Unlike nonoxynol-9, repeated intravaginal applications of GM-4 and GM-144 in the rabbit vaginal irritation test were not associated with local inflammation or damage of the vaginal mucosa or epithelium. Furthermore, in short-term toxicity studies performed in mice, repetitive intravaginal application of spermicidal GM-4 and GM-144 for up to 13 weeks was not associated with any local, systemic, or reproductive toxicity. Spermicidal GMs have unprecedented potential as dual function microbicidal contraceptives to improve vaginal bioavailability of poorly soluble antimicrobial agents without causing significant vaginal damage.

Administration, Intravaginal↗
PubMed2003

Randomized controlled trial of vaginal misoprostol versus dinoprostone vaginal insert for labor induction.

OBJECTIVE: To compare the safety and efficacy of vaginal misoprostol versus dinoprostone vaginal inserts for cervical ripening and labor induction. METHODS: Two hundred singleton gestations with an indication for cervical ripening and induction of labor were randomized to receive either 50 microg of misoprostol intravaginally every 3 h or a 10-mg dinoprostone vaginal insert every 12 h for a maximum of 24 h. Statistical analysis included Student's t test, the Mann-Whitney U test, chi2 analysis and Fisher's exact test. RESULTS: Ninety-seven women received vaginal misoprostol while 89 women received the dinoprostone vaginal insert. Fourteen women were removed from the study after randomization. The interval from start of induction to vaginal delivery (794.5 +/-408 min vs. 1005.3 +/- 523 min; p < 0.02) was significantly shorter in the misoprostol group. Women receiving misoprostol were more likely to deliver vaginally both in < 12 h (44% vs. 12%; p < 0.0001) and < 24 h (68% vs. 38%; p < 0.001). A non-reassuring fetal heart rate tracing was the indication for 71.4% (20/28) of Cesarean deliveries in the misoprostol group compared to 40% (14/35) in the dinoprostone group (p = 0.03). There were no significant differences in neonatal outcomes. CONCLUSION: Intravaginal misoprostol and dinoprostone are safe and effective medications for use in cervical ripening before labor induction. Misoprostol results in a shorter interval from induction to delivery. However, Cesarean delivery for a non-reassuring fetal heart rate tracing was more common with misoprostol.

Administration, Intravaginal↗
PubMed2002

Mucosal immunization with inactivated human immunodeficiency virus plus CpG oligodeoxynucleotides induces genital immune responses and protection against intravaginal challenge.

Vaccines capable of protecting against sexually transmitted infections, such as human immunodeficiency virus (HIV), will depend on the induction of potent long-lasting mucosal immune responses in the genital tract. We evaluated vaginal and systemic immune responses and protection from vaginal challenge elicited after intranasal immunization of mice with inactivated glycoprotien 120-depleted HIV-1 immunogen alone or in combination with immunostimulatory CpG oligodeoxynucleotides (ODNs). Mice immunized with HIV-1 immunogen plus CpG ODN had significantly enhanced levels of anti-protein 24 immunoglobulin (Ig) G and IgA antibodies in serum and vaginal washes and increased production of beta-chemokines and interferon-gamma, compared with mice immunized with HIV-1 immunogen alone or with control ODN. Furthermore, mice intranasally immunized with HIV-1 immunogen plus CpG were protected against intravaginal challenge with a recombinant vaccinia virus expressing HIV-1 gag. These results indicate that mucosal immunization with whole-killed HIV-1 plus CpG ODN may be an effective means of inducing local immunity and protection against genital infection.

AIDS Vaccines↗
PubMed2003

Lactobacillus crispatus capsules: single-use safety study in the Macaca nemestrina model.

BACKGROUND: Lactobacillus crispatus is a part of the normal vaginal microflora of humans. GOAL: The goal of this study was to assess whether a capsule containing an H2O2-producing strain of L crispatus (CTV-05) would alter the vaginal microflora and/or epithelial tissues when applied intravaginally in the pig-tailed macaque model. STUDY DESIGN: Ten sexually mature female Macaca nemestrina were assessed at baseline for quantitative vaginal microbiology and vaginal pH and with colposcopy. One capsule containing 108 colony forming units of desiccated L crispatus CTV-05 was inserted into the vaginal fornix of each animal. Vaginal assessments were repeated on days 1 and 2 after capsule insertion. The L crispatus CTV-05 strain was identified with use of a DNA fingerprinting method. RESULTS: Before product use, four of 10 animals had detectable levels of H2O2-producing lactobacilli. L crispatus CTV-05 was detected in 1 of 10 animals on day 1 and in 3 of 10 animals on day 2 following insertion of the capsule. There were no tissue changes observed by colposcopy. Vaginal pH decreased in two animals colonized by CTV-05, from 7.0 at baseline to 4.5+/-0.5 on days 1 and 2 after product use. CONCLUSIONS: A single intravaginal application of capsules containing 108 L crispatus CTV-05 resulted in vaginal colonization in three of 10 animals 2 days after use. The absence of colposcopic changes in the vagina/cervical tissues indicates that L crispatus capsules are well tolerated.

Administration, Intravaginal↗
PubMed2005

Conceival, a novel noncontraceptive vaginal vehicle for lipophilic microbicides.

The objective of this study was to develop a nontoxic and noncontraceptive vaginal drug delivery vehicle for lipophilic anti-human immunodeficiency virus (HIV) microbicides. Three representative poorly water-soluble novel broad-spectrum anti-HIV microbicides, PHI-113, PHI-346, and PHI-443, were evaluated in 11 different solvent systems. Based on their solubility profiles, a novel nonspermicidal self-emulsifying gel (viz Conceival) composed of pharmaceutical excipients, sorbitol, polyethylene glycol 400, polysorbate 80, microcrystalline cellulose, xanthan gum, and water was optimized. Conceival enhanced the solubility of these poorly water-soluble (<0.001 mg/mL) anti-HIV drugs by at least 150- to 270-fold. Conceival was evaluated in vivo in the New Zealand white rabbit model for the preservation of sperm function based on pregnancy outcome and the potential for vaginal irritation following single and multiple intravaginal applications, respectively. Conceival administered intravaginally immediately prior to artificial insemination with semen had no adverse effects on subsequent reproductive performance, neonatal survival, or pup development when compared with untreated control group. Histologic evaluation of vaginal tissues of rabbits exposed intravaginally to Conceival for 14 consecutive days revealed lack of epithelial, submucosal, and vascular changes at the gel application site (total irritation score <3 out of a possible 16). These findings indicate that Conceival has potential to become a clinically useful, safe noncontraceptive vaginal vehicle for lipophilic microbicides.

Administration, Intravaginal↗
PubMedDate not supplied

Evaluation of the efficacy of Salmonella enteritidis oil-emulsion bacterin in an intravaginal challenge model in hens.

The efficacy of Salmonella enteritidis (SE) oil-emulsion bacterin (a commercially available vaccine) was evaluated in an intravaginal challenge model in hens producing a high rate of SE-contaminated eggs. Hens were vaccinated at 38 wk of age. A second (booster) bacterin injection was administered 4 wk later. Two weeks after the second vaccination, all hens were challenged intravaginally with 10(7) colony-forming units of SE. After challenge, 36 of 189 eggs (19.0%) in the vaccinated hens were positive for SE, and this contamination rate was significantly (P < 0.01) lower than that in the unvaccinated hens (61 of 165 eggs, 37.0%). SE was highly recovered from the cloacal and vaginal swabs of the unvaccinated and vaccinated hens, but the number of SE from the cloaca of the vaccinated hens was significantly (P < 0.05) lower than that in the unvaccinated hens at 7 days post-challenge (PC). The recoveries of SE from the spleen and ovary in the vaccinated hens were significantly (P < 0.05) lower than those in the unvaccinated hens at 7 days PC. At necropsy, SE was recovered from 2 of 15 forming eggs (13.3%) taken from the oviducts of the unvaccinated hens, whereas no SE was recovered from 17 forming eggs in the vaccinated hens. After vaccination, serum antibodies for SE in the vaccinated hens were significantly higher than those in the unvaccinated hens. Antibodies from the oviductal washing, especially immunoglobulin G isotype, in the vaccinated hens were higher than those in the unvaccinated hens after challenge. This intravaginal challenge model produced frequent contaminated eggs and clearly demonstrated the ability of the bacterin to protect against egg contamination. The present model may be a useful tool for further studies to evaluate the protective effect against SE contamination of eggs by potential vaccine candidates.

Administration, Intravaginal↗