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Effect of treatment with two intravaginal inserts on the uterine and vaginal microflora of early postpartum beef cows.

OBJECTIVE: To describe the bacterial species found within the uterus and vagina of early postpartum (10 to 20 d) beef cows treated for 14 d with (i) two intravaginal (CIDR-B) progesterone releasing inserts (C-P4; n=31); (ii) two identical but blank inserts (C-BL; n=15); (iii) untreated controls (CON; n=15). It was hypothesised that due to the locally immunosuppressive effects of progesterone on the uterus, the bacterial microflora of C-P4 would be altered by this treatment in contrast to CON and C-BL. PROCEDURE: Cows were enrolled at two intervals 7 d apart. Blood samples were collected at 0, 7 and 14 d after beginning treatments for subsequent progesterone assay. A triple guarded swabbing technique was used to collect bacteriological samples from the uterus of every cow on days 0, 7 and 14 following CIDR insertion. Swabs were also collected from the inserts and vagina of every cow on day 14. Due to the small sample sizes, only descriptive statistics were generated. RESULTS: Plasma progesterone levels were maintained at mid-luteal phase concentrations by the intravaginal progesterone releasing inserts (C-P4: 4.2 +/- 0.4 ng/mL at 7 d; 3.6 +/- 0.2 ng/mL at 14 d), although increased progesterone concentrations were found in 4/15 CON and 9/15 C-BL cows on day 14. Bacteria were isolated from 32/61 (52%) of all uterine samples collected at the time of insertion. Uterine and vaginal swabs from CON cows showed a marked reduction in isolates over time such that 14 d after insertion only 1/15 uterine swabs grew bacteria. In contrast, C-BL and C-P4 treated cows failed to show reductions in the number of uterine or vaginal isolates at 14 d after device insertion. Heavy growths of Pseudomonas aeruginosa and Actinomyces pyogenes were found on the intravaginal inserts from C-BL and C-P4 cows. Cows enrolled in the second week of the study that received intravaginal inserts (C-P4 + C-BL) were more likely to have Pseudomonas isolated from the uterus than those enrolled in week 1 (1/18 versus 14/28). CONCLUSIONS: The presence of two intravaginal inserts, regardless of hormone content, substantially altered the profile of uterine and vaginal bacteria in early postpartum beef cows. It was suspected that because of the early stage at insert application, the cervix had not involuted sufficiently to provide an adequate microbial barrier to the uterus. Pseudomonas aeruginosa was the predominant species isolated from both uterine and insert cultures after 14 d of treatment but may have been a contaminant, due to the greater proportion of cows infected with it that had been enrolled in the second week of the study.

Administration, Intravaginal↗

Accidental use of low-dose 5-fluorouracil in pregnancy.

Five percent 5-fluorouracil (5-FU), an antineoplastic agent, is often applied to the lower genital tract in the treatment of vaginal and vulvar human papillomavirus infections. Little is known regarding possible teratogenic effects from its topical use in pregnancy. Five cases of antenatal lower genital tract 5-FU use were correlated with pregnancy outcome. Topical 5-FU was applied up to 16 weeks' gestation. Intravaginal doses ranged from 1 to 2.5 g; one patient applied 5-FU to the vulva. Antenatal ultrasound performed on four patients did not show any fetal structural abnormalities. One patient underwent antenatal genetic amniocentesis that detected a 47,XXX complement of chromosomes. All the pregnancies continued without complications and with subsequent term delivery of healthy infants. The unwitting vaginal and vulvar use of 5-FU in pregnancy did not result in significant morbidity or mortality; expectant management of such pregnancies should be considered.

Abnormalities, Drug-Induced↗

Terconazole for the treatment of vulvovaginal candidiasis.

A double-blind, randomized trial was conducted to evaluate the efficacy and safety of terconazole for vulvovaginal candidiasis. Treatment consisted of daily intravaginal application of one of the following regimens: 80-mg terconazole suppositories for 3 days, miconazole nitrate suppositories for 7 days or placebo suppositories for 7 days. The terconazole and miconazole nitrate groups had significantly higher therapeutic cure rates than did the placebo group. Evaluation of vaginal secretions with microscopic examination showed no evidence of leukocyte proliferation. Proline aminopeptidase activity, present in patients who have bacterial vaginosis, could not be detected in the vaginal secretions from patients with yeast vulvovaginitis.

Administration, Intravaginal↗

[A study on chemoprevention of retinamide II from cervical precancerous lesions].

The patients with cervical precancerous lesions were double-blindly randomized into two groups. The one was treated with retinamide II (RII) suppository intravaginally and the other with placebo, once daily for 50 days as a course. The results showed precancerous lesions in 68.57% of the patients disappeared, with an overall effective rate of 74.29% after two-course treatment with RII. Its long-term curative effect approximated to that with laser beam radiation and electrocautery (P > 0.05), and differed significantly (P < 0.01) from that with common antiphlogistic. So, RII can be used as a major measure in prevention and treatment for cervical cancer in high-incidence areas in our country.

Administration, Intravaginal↗

Genital secretory immune response to chronic simian immunodeficiency virus (SIV) infection: a comparison between intravenously and genitally inoculated rhesus macaques.

The humoral and genital secretory immune response to chronic SIV infection was compared between female Rhesus macaques inoculated by i.v. or intravaginal routes. Total IgG levels in serum were 10-fold higher in SIV-infected animals when compared with uninfected controls. Vaginal washes from normal macaques contained predominantly IgA and IgG, while those from SIV-infected animals contained high levels of IgG. The SIV-infected animals had high titres of SIV-specific IgG in serum, with lower but detectable IgA and IgM responses. The genital secretory immune response to SIV was similar in intravenously and intravaginally inoculated animals. The anti-SIV response in the vaginal washes consisted mainly of IgG. Within the lamina propria of the reproductive tract of animals chronically infected with SIV there were essentially no IgA or IgG plasma cells and only a small number of IgM plasma cells, while two normal animals had large numbers of IgA plasma cells. These results suggest that the mucosal immune system of the female reproductive tract is impaired in chronic SIV infection.

Administration, Intravaginal↗

Safety and efficacy of misoprostol for induction of labour in a semi-urban hospital setting.

Most studies on the use of misoprostol for induction of labour have been carried out in well-endowed hospitals in developed countries with state-of-the-art monitoring equipment. There is need for more studies to be conducted in facilities with limited resources, if more patients are to benefit from the low cost and effectiveness of the drug. Following Ethical Committee approval, 152 women had labour induced in our maternity unit using intravaginal misoprostol. The patients were monitored clinically using the WHO model partograph with digital palpation of uterine contractions and intermittent auscultation of fetal heart with a pinard stethoscope. One hundred and thirty-five (88.8%) of the women had a vaginal delivery, while nine (5.9%) had a caesarean section for various obstetric indications. Eight cases of uterine hyperstimulation were noted but none of uterine rupture. We conclude that misoprostol can be used safely for induction of labour in less endowed hospital settings such as in developing countries, using basic clinical tools for monitoring.

Administration, Intravaginal↗

[Sensitivity test in labor induction with prostaglandin E2 vaginal tablets].

The study was designed to evaluate whether an oxytocin sensitivity test in addition to pelvic scoring would increase the predictive value concerning successful induction in cases of elective induction by means of prostaglandin (PG) E2 vaginal tablets. Furthermore we investigated if this test could lead to a further reduction in the already low rate of protracted labour and operative deliveries. In order to establish the optimal dosage we compared the endocervical application of 1.5 ml PG E2 with 3 mg intravaginal. 160 pregnant women without any risks were included at due date; 73% decided spontaneously to have labour induced by means of PG E2 tablets. In these induction groups the delivery intervals were significantly shorter and the rate of operative deliveries was reduced. The fetal outcome, however, was the same as in those women who decided to await spontaneous onset of labour. The endocervical application did not prove any better. The oxytocin sensitivity test yielded additional information about the chances of inducing labour successfully. The results confirmed again the efficacy and acceptance of this method of labour induction.

Administration, Intravaginal↗

Effect of treatment with progesterone on pregnancy rate and plasma concentrations of progesterone in Holstein cows.

Progesterone-releasing intravaginal devices inserted into the vaginas of dairy cows between d 5 to 12 (n = 28) or d 10 to 17 (n = 27) after insemination increased pregnancy rate to 60 over 30% in untreated control cows (n = 30). Plasma progesterone concentrations were increased during both progesterone treatments. Subtraction of the estimated contribution of exogenous progesterone indicated that endogenous, luteal progesterone was reduced during d 10 to 17 but not during d 5 to 12. Supplemental progesterone increased pregnancy rate but suppressed endogenous production of progesterone when administered during d 10 to 17 after insemination.

Administration, Intravaginal↗

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. III. The relationship between pregnancy rate and body weight. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

This paper investigates the relationship between pregnancy rates and body weight of 1005 women using a vaginal ring releasing 20 micrograms levonorgestrel per 24 hours. While the overall pregnancy rate at one year was 3.7%, it was found that women have an increasing risk of pregnancy with increasing body weight. For example, a woman of 40 kg has an estimated pregnancy rate of 1.7% in contrast to 9.8% for a woman of 80 kg weight.

Administration, Intravaginal↗

Influence of estrus on somatic cell count in dairy goats.

The effect of estrus on the somatic cell count (SCC) of goat's milk was examined by inducing estrus in 24 of 48 seasonally anestrus, lactating dairy goats. Goats were blocked by infection status and ranked on SCC from three preceding herd tests and randomly allocated (within block) to the following three treatment groups: a) "Short," in which an intravaginal progesterone-releasing device was inserted for 12 d plus equine chorionic gonadotropin and dinoprost tromethamine 2 d before device removal (n = 12), b) "Long," in which an intravaginal progesterone-releasing was inserted for 17 d plus equine chorionic gonadotropin on the day of device removal (n = 12), or c) "Control," in which the goats were left as untreated controls (n = 24). Bacteriological status of each gland of each goat was determined before and after synchronization (d -23 and +13) and SCC and milk volumes were determined on d -2, 0, 1, 2, 3, 4, 14, and 25, where d 0 was the day of intravaginal device removal. Goats in the Short group were in estrus before those of the Long group, who were, in turn, in estrus before the Control group. The log10 and log10 absolute SCC (SCC cells/ml x volume) were higher in the Short than in the Control group on d 1, 2, 3, and 4, whereas those of the Long group were higher than those of the Control group on d 2 and 4. These data indicate that estrus resulted in an increase in SCC, and that the increase in SCC was independent of the decline in milk volume at estrus.

Administration, Intravaginal↗

The evaluation of the local tolerance of vaginal formulations containing dapivirine using the Slug Mucosal Irritation test and the rabbit vaginal irritation test.

The purpose of this study was to evaluate the local tolerance of vaginal gels (three gels containing dapivirine, the placebo gel, and Conceptrol) with the Slug Mucosal Irritation test and to compare the results with those of the rabbit vaginal irritation test. The irritation potential on the slug mucosa was assessed by the mucus production caused by a repeated treatment for 5 successive days. Additionally, membrane damage was estimated by the protein and enzyme release. By means of a classification prediction model the formulations were classified into four irritation classes. The effect of a 10-day intravaginal application of the gels on the rabbit vaginal and cervical mucosa was evaluated by means of macroscopic and microscopic examination. The placebo and dapivirine gels induced no irritation of the slug mucosa (low mucus production and protein release, no enzyme release) and no vaginal or cervical irritation in rabbits. Conceptrol caused severe irritation of the slug mucosa (increased mucus production, protein release, and enzyme release) and irritation of the rabbit vagina and cervix. The results obtained with the Slug Mucosal Irritation test were comparable to those of the rabbit vaginal irritation test.

Administration, Intravaginal↗

Effects of induction of low plasma progesterone concentrations with a progesterone-releasing intravaginal device on follicular turnover and fertility in cattle.

The effects of concentration of progesterone in plasma on development and fertility of the first wave dominant follicle were studied in cattle. To identify a source of exogenous progesterone that would permit extension of the first wave dominant follicle, nonlactating Holstein cows (n = 6) received on day 8 of two successive oestrous cycles an injection of PGF2 alpha (25 mg) and a new (1.9 g of progesterone (Period 1)) or used (approximately 1.2 g of progesterone (Period 2)) CIDR-B device that was removed on day 17. Control cows (n = 6) received a new CIDR-B device on day 8 that was removed on day 17 and a PGF2 alpha injection (25 mg) on day 17. Ultrasonography and collection of blood samples were performed on alternate days throughout the experiment. Plasma concentrations of progesterone and oestradiol were different between treatments (P < 0.0001 and P < 0.05, respectively). The dominant follicle was maintained until day 17 and ovulated upon removal of the intravaginal device in 1 of 6, 6 of 6 and 0 of 6 in new CIDR-B, used CIDR-B and control groups, respectively (P < 0.01). The preovulatory dominant follicles were 14.2 +/- 1.6 mm, 20 +/- 1.3 mm and 10 +/- 1.3 mm, respectively (P < 0.001) on day 17. There were fewer 5-9 mm follicles in cows having a persistent dominant follicle (P < 0.01). The interval to onset of oestrus was negatively correlated with size of the dominant follicle on day 17 (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravaginal↗

Reengineering of a commercially available bovine intravaginal insert (CIDR insert) containing progesterone.

The purpose of this study was to reengineer a commercially available intravaginal insert containing 1.9 g progesterone (CIDR intravaginal insert) for a 7-day insertion period in cattle. The reengineering process resulted in a reduced initial drug load (1.38 g) and a reduction in the residual drug load following insertion, while at the same time maintaining the biological performance of the insert. The in vitro and in vivo pharmaceutical properties of the commercially available CIDR intravaginal insert were characterized initially to gain a thorough understanding of the factors that affected progesterone release from the insert. The effect of changing a selection of formulation and physical variables of the insert was also investigated (including surface area, drug load, addition of pore forming materials, silicone shore hardness and drug particle size). The knowledge gained from these studies was used to define the characteristics of the reengineered insert which was then manufactured and shown to be bioequivalent and clinically equivalent to the commercially available insert.

Administration, Intravaginal↗

Therapy of mucosal candidiasis by expression of an anti-idiotype in human commensal bacteria.

Two recombinant strains of Streptococcus gordonii, secreting or displaying a microbicidal single-chain antibody (H6), and stably colonizing rat vagina, were used to treat an experimental vaginitis caused by Candida albicans. A post-challenge intravaginal delivery of the H6-secreting strain was as efficacious as fluconazole in rapidly abating the fungal burden. Three weeks after challenge, 75% and 37.5% of the rats treated with the H6-secreting or displaying bacteria, respectively, were cured of the infection, which persisted in 100% of the animals treated with a S. gordonii strain expressing an irrelevant single-chain antibody. Thus, a human commensal bacterium can be suitably engineered to locally release a therapeutic antibody fragment.

Administration, Intravaginal↗

A period of transient viremia and occult infection precedes persistent viremia and antiviral immune responses during multiple low-dose intravaginal simian immunodeficiency virus inoculations.

In rhesus macaques, classic systemic infection, characterized by persistent viremia and seroconversion, occurred after multiple low-dose (10(3) 50% tissue culture infective doses) intravaginal (IVAG) inoculations with simian immunodeficiency virus (SIV) strain SIVmac251. Monkeys developed classic SIV infections after a variable number of low-dose IVAG exposures to SIVmac251. Once established, the systemic infection was identical to SIV infection following high-dose IVAG SIV inoculation. However, occult systemic infection characterized by transient cell-associated or cell-free viremia consistently occurred early in the series of multiple vaginal SIV exposures. Further, antiviral cellular immune responses were present prior to the establishment of a classic systemic infection in the low-dose vaginal SIV transmission model.

Administration, Intravaginal↗

The effect of vaginal pH on the efficacy of vaginal misoprostol for induction of labor.

BACKGROUND: Misoprostol was reported to be an effective agent for cervical ripening and induction of labor. Our purpose was to evaluate whether vaginal pH affected the efficacy of misoprostol for induction of labor. METHODS: The vaginal pH of 103 women admitted for induction of labor were measured. According to the vaginal pH, two groups were generated, those with a vaginal pH <5 (n= 65), and those with a vaginal pH > or =5 (n=38). All women received intravaginal misoprostol tablets, 50 microg every 4 hours up to three doses. Further medication was not given after entry into active labor or spontaneous rupture of membranes. In cases of failed induction or arrest disorders oxytocin augmentation was used. RESULTS: The average interval from start of induction to vaginal delivery was shorter, and oxytocin augmentation was required less commonly in the lower pH group. We did not find any significant difference in cesarean section rates, or incidence of adverse maternal or fetal outcome. CONCLUSION: Vaginal pH may affect the pharmacokinetics of vaginally administered misoprostol, and may cause an alteration in induction to delivery interval.

Administration, Intravaginal↗

Hydrogels containing monocaprin prevent intravaginal and intracutaneous infections with HSV-2 in mice: impact on the search for vaginal microbicides.

Hydrogel formulations containing the 1-monoglyceride of capric acid (monocaprin) possess potent in vitro microbicidal activity against HIV and HSV, Chlamydia trachomatis and Neisseria gonorrhoeae. These formulations were studied to determine whether they prevent intracutaneous and intravaginal infections of mice with HSV-2, a virus that is in vitro as sensitive to the virucidal action of the compound as is HIV. In mice intravaginal infection with HSV-2 and the associated mortality was prevented completely when the infection was carried out in the presence of a 20 mM monocaprin containing gel formulation. Similarly, virtually complete protection of lesion development and associated mortality was observed when mice were infected intracutaneously with HSV-2 in the presence of gels containing 10 or 20 mM monocaprin. No irritation or toxicity was observed following application of the gel to the skin or the vaginal mucosa. Hydrogel formulations of monocaprin could thus be pursued as vaginal microbicides for the prevention of sexual transmission of HSV, HIV and other infectious pathogens.

Administration, Intravaginal↗

Artificial insemination of Cashmere goats: effects on fertility and fecundity of intravaginal treatment, method and time of insemination, semen freezing process, number of motile spermatozoa and age of females.

The experiments, using a total of 1833 Cashmere does, were conducted to examine the effects on fertility and fecundity of intravaginal treatment for control of ovulation, time of insemination by cervical and laparoscopic methods, semen processing in pellets and straws, and number of frozen-thawed motile spermatozoa. Adult does (greater than or equal to 2.5 years) that had previously kidded were inseminated into the cervix, and maiden (kid: 6-8 months; hogget: 18 months) and adult does were inseminated laparoscopically. The rates of pregnancy determined by ultrasonic scanning (75-80 days after insemination) for cervical (Experiment 1) and laparoscopic (Experiments 2 and 3) insemination were 39.1%, 63.6% and 52.1%. The number of motile spermatozoa did not affect fertility after cervical (80, 120 and 160 x 10(6) or laparoscopic (Experiment 2: 15, 30 and 60 x 10(6); Experiment 3:5, 10 and 20 x 10(6) insemination. The method of insemination or number of motile spermatozoa did not affect fecundity. With cervical insemination, fertility and fecundity improved with increasing depth of insemination into the reproductive tract. Intravaginal sponges containing fluorogestone acetate and controlled internal drug release (CIDR) devices containing progesterone were equally effective for control of ovulation when combined with an injection of pregnant mare's serum gonadotrophin (PMSG; 200 i.u.) before insemination. Fertility was higher when does were inseminated before than after ovulation. After laparoscopic insemination, results were similar for semen frozen as pellets and in straws, and for 3-, 6- and 24-fold pre-freezing dilution of semen. For kid, hogget and adult does in Experiment 3, pregnancy rates were 34.0%, 55.4% and 63.9% and rates of fecundity were 1.17, 1.22 and 1.27 fetuses/pregnant doe.

Administration, Intravaginal↗