tretinoin and Vaginal-Diseases

Vaccines are not presently available to prevent adherence and transmission of many common pathogens at mucosal surfaces. As a result, sexually transmitted diseases were one of the most commonly reported infections in the US in 1999. New methods are needed to reduce the spread of mucosal infections. Providing nonspecific protective factors, such as lipids and retinoids found in human milk to mucosal surfaces could reduce mucosal infection caused by viruses, e.g., herpes simplex virus-1 (HSV-1) and bacteria, e.g., Pseudomonas aeruginosa. Human milk lipids enzymatically modified to produce monoglycerides were antimicrobial and inactivated enveloped viruses, as well as gram-positive and gram-negative bacteria. Enveloped viruses were inactivated in seconds following contact with antimicrobial lipids, and P. aeruginosa infectivity was reduced by 99.9% after 2 hours. Transmission of pathogens at mucosal surfaces can also be prevented using retinoids that inhibit viral replication. In a human embryonic intestinal cell line the retinoic acid (RA) derivatives all-trans-RA and 9-cis-RA (10 microg/mL) decreased the production of HSV-1 and Echo-6 viruses by 1-2 log10 over a 48-hour period. In addition, all-trans-RA inhibited HSV-1 replication in Vero cells as effectively as interferon beta, reducing viral production by 2.5log10. These studies indicate that lipids and retinoids could be part of a topical microbicide to prevent mucosal infections.

Topics: Anti-Infective Agents, Local; Antiviral Agents; Delivery, Obstetric; Female; Humans; Infections; Infectious Disease Transmission, Vertical; Milk, Human; Sexually Transmitted Diseases; Tretinoin; Vaginal Diseases; Vaginosis, Bacterial; Virus Diseases

A method is described for measuring the relative activities of vitamin A active substances based on their direct effect on the cornified vaginal epithelium of vitamin A-deficient rats. The results obtained agree well with those found in the tracheal organ culture assay. The relative activities found for several test compounds were: all-trans-retinoyl-beta-glucuronide greater than all-trans-retinoic acid greater than all-trans retinol greater than all-trans-5,6-epoxyretinoic acid. The assay is simple and inexpensive to perform, and should find use in laboratories where the equipment and personnel required for the tracheal organ culture assay are not available.

Topics: Animals; Biological Assay; Castration; Dose-Response Relationship, Drug; Epithelium; Female; Glucuronates; Rats; Tretinoin; Vaginal Diseases; Vaginal Smears; Vitamin A; Vitamin A Deficiency

The ability of the biliary metabolite retinotaurine to reverse the cornification of vaginal epithelial cells induced by vitamin A deficiency was assessed using a vaginal smear assay. Retinotaurine activity was examined following the intravaginal administration of 10(-12) mol to 10(-8) mol of this compound per vagina. This metabolite exhibited no detectable activity at any dose tested. These results show that retinotaurine cannot be more than 1% as active as all-trans-retinoic acid since retinoic acid shows a response at concentrations of 10(-10) mol per vagina. The low biological activity of this recently identified biliary metabolite suggests that it represents an excretory form of retinoic acid.

Topics: Animals; Biological Assay; Castration; Cell Differentiation; Dose-Response Relationship, Drug; Epithelium; Female; Rats; Tretinoin; Vaginal Diseases; Vaginal Smears; Vitamin A Deficiency