Document Detail


Preclinical evaluation of sodium cellulose sulfate (Ushercell) as a contraceptive antimicrobial agent.
MedLine Citation:
PMID:  12002445     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The spread of sexually transmitted infections (STIs) and limited methods for control of pregnancies presents high risks to the reproductive health of women. Methods controlled by women and directed toward disease prevention and contraception are needed. We report on preclinical studies of the biological properties of sodium cellulose sulfate (Ushercell) currently being developed for use as a topical contraceptive antimicrobial agent. Ushercell was evaluated with tests designed to identify its contraceptive and antimicrobial properties. Ushercell inhibits hyaluronidase (reversible; IC50 = 1.7 mg/mL), impairs sperm penetration of cervical mucus (approximately 70% inhibition at 1 mg/mL), and acts as a stimulus for acrosomal loss (IC50 = 52 ng/mL). It prevents conception in rabbits when added to spermatozoa (approximately 95% inhibition at 1 mg/mL) or when vaginally applied (complete contraception by 45 mg) before insemination. However, up to 50 mg/mL, Ushercell does not irreversibly immobilize spermatozoa, suggesting that Ushercell is not cytotoxic. Ushercell has a broad spectrum of antimicrobial activity in vitro. Inhibited microbes include human immunodeficiency viruses (different laboratory strains and clinical isolates; IC50 values range from 3 to 78 microg/mL), herpes viruses, HSV-1 (IC50 = 59 ng/mL) and HSV-2 (lC50 = 24 ng/mL), Neisseria gonorrhoeae (IC50 = 2 microg/mL), and Chlamydia trachomatis (IC50 = 78 microg/mL). In contrast, Ushercell does not inhibit growth of beneficial vaginal bacteria, Lactobacillus gasseri, at 5 mg/mL. These results suggest that the antimicrobial effects of Ushercell are selective, and not likely mediated by nonspecific cytotoxic mechanisms. These data provide the basis for further clinical development of Ushercell as a vaginal agent to prevent unplanned pregnancy and STIs.
Authors:
Robert A Anderson; Kenneth A Feathergill; Xaio-Hui Diao; Morris D Cooper; Risa Kirkpatrick; Betsy C Herold; Gustavo F Doncel; Calvin J Chany; Donald P Waller; William F Rencher; Lourens J D Zaneveld
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of andrology     Volume:  23     ISSN:  0196-3635     ISO Abbreviation:  J. Androl.     Publication Date:    2002 May-Jun
Date Detail:
Created Date:  2002-05-10     Completed Date:  2002-10-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8106453     Medline TA:  J Androl     Country:  United States    
Other Details:
Languages:  eng     Pagination:  426-38     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynecology, Rush Medical Center, Chicago, Illinois 60612, USA. randerso@rush.edu
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MeSH Terms
Descriptor/Qualifier:
Acrosome / drug effects
Animals
Anti-Bacterial Agents / pharmacology*
Antiviral Agents / pharmacology
Cellulose / analogs & derivatives*,  pharmacology*
Chlamydia Infections / prevention & control
Contraceptive Agents, Female / pharmacology*
Enzyme Inhibitors / pharmacology
HIV Infections / prevention & control
Herpes Simplex / prevention & control
Hyaluronoglucosaminidase / antagonists & inhibitors
Lactobacillus / drug effects
Male
Rabbits
Sexually Transmitted Diseases, Bacterial / prevention & control*
Spermatozoa / drug effects
Grant Support
ID/Acronym/Agency:
2 PO1 AI37940-05/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Antiviral Agents; 0/Contraceptive Agents, Female; 0/Enzyme Inhibitors; 9004-34-6/Cellulose; 9032-43-3/cellulose sulfate; EC 3.2.1.35/Hyaluronoglucosaminidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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