BACKGROUND: Access to readily available large animal models and sensitive noninvasive techniques that can be used for the evaluation of microbicide-induced changes in tissue could significantly facilitate preclinical evaluations of microbicide safety. The sheep cervicovaginal tract, with stratified squamous epithelium similar to humans, holds promise as a large animal model used before nonhuman primates. In addition, optical coherence tomography (OCT) could enable high resolution visualization of tissue morphology and noninvasive assessment of microbicide-induced epithelial injury. METHODS: We evaluated the dose response of sheep cervicovaginal tract to benzalkonium chloride (BZK). Twenty sheep received treatment with phosphate-buffered saline or BZK solution (2%, 0.2%, or 0.02%). Pre- and posttreatment colposcopy and OCT images were collected and graded based on World Health Organization criteria and a previously reported scoring system, respectively. Biopsies were collected and the degree of epithelial injury and its thickness was assessed based on histology and OCT. RESULTS: The sheep cervicovagina exhibited anatomic and microscopic features similar to the human. Extensive loss of the epithelium was noted on colposcopy and OCT after application of 2% BZK. Colposcopy detected findings in half of sheep and OCT in all sheep treated with 0.2% BZK. OCT detected differences in the 0.02% BZK-treated group compared with controls, whereas colposcopy failed to detect any changes. CONCLUSIONS: The sheep cervicovagina is similar to humans, and exhibits dose dependent epithelial changes after BZK treatment. These findings suggest that the sheep model and OCT may become valuable tools for the safety evaluation of candidate microbicides, and warrant continued development.
BACKGROUND: Access to readily available large animal models and sensitive noninvasive techniques that can be used for the evaluation of microbicide-induced changes in tissue could significantly facilitate preclinical evaluations of microbicide safety. The sheep cervicovaginal tract, with stratified squamous epithelium similar to humans, holds promise as a large animal model used before nonhuman primates. In addition, optical coherence tomography (OCT) could enable high resolution visualization of tissue morphology and noninvasive assessment of microbicide-induced epithelial injury. METHODS: We evaluated the dose response of sheep cervicovaginal tract to benzalkonium chloride (BZK). Twenty sheep received treatment with phosphate-buffered saline or BZK solution (2%, 0.2%, or 0.02%). Pre- and posttreatment colposcopy and OCT images were collected and graded based on World Health Organization criteria and a previously reported scoring system, respectively. Biopsies were collected and the degree of epithelial injury and its thickness was assessed based on histology and OCT. RESULTS: The sheep cervicovagina exhibited anatomic and microscopic features similar to the human. Extensive loss of the epithelium was noted on colposcopy and OCT after application of 2% BZK. Colposcopy detected findings in half of sheep and OCT in all sheep treated with 0.2% BZK. OCT detected differences in the 0.02% BZK-treated group compared with controls, whereas colposcopy failed to detect any changes. CONCLUSIONS: The sheep cervicovagina is similar to humans, and exhibits dose dependent epithelial changes after BZK treatment. These findings suggest that the sheep model and OCT may become valuable tools for the safety evaluation of candidate microbicides, and warrant continued development.
Authors: Kathleen L Vincent; Brent A Bell; Susan L Rosenthal; Lawrence R Stanberry; Nigel Bourne; Yvonne T Cosgrove Sweeney; Dorothy L Patton; Massoud Motamedi Journal: Sex Transm Dis Date: 2008-03 Impact factor: 2.830
Authors: C K Mauck; M M Callahan; J Baker; K Arbogast; R Veazey; R Stock; Z Pan; C S Morrison; M Chen-Mok; D F Archer; H L Gabelnick Journal: Contraception Date: 1999-07 Impact factor: 3.375
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 Journal: J Androl Date: 2002 May-Jun
Authors: Gregg N Milligan; Kristen L Dudley; Nigel Bourne; Alisa Reece; Lawrence R Stanberry Journal: Sex Transm Dis Date: 2002-10 Impact factor: 2.830
Authors: Bradley J Catalone; Tina M Kish-Catalone; Lynn R Budgeon; Elizabeth B Neely; Maelee Ferguson; Fred C Krebs; Mary K Howett; Mohamed Labib; Robert Rando; Brian Wigdahl Journal: Antimicrob Agents Chemother Date: 2004-05 Impact factor: 5.191
Authors: P F Escobar; J L Belinson; A White; N M Shakhova; F I Feldchtein; M V Kareta; N D Gladkova Journal: Int J Gynecol Cancer Date: 2004 May-Jun Impact factor: 3.437
Authors: Carmen Radecki Breitkopf; Melissa Loza; Kathleen Vincent; Thomas Moench; Lawrence R Stanberry; Susan L Rosenthal Journal: J Empir Res Hum Res Ethics Date: 2011-09 Impact factor: 1.742
Authors: Jonathon D S Holt; David Cameron; Nicola Dias; Jeremy Holding; Alex Muntendam; Freddy Oostebring; Peter Dreier; Lisa Rohan; Jeremy Nuttall Journal: Antimicrob Agents Chemother Date: 2015-04-06 Impact factor: 5.191
Authors: Lian Duan; Michael D McRaven; Wenzhong Liu; Xiao Shu; Jianmin Hu; Cheng Sun; Ronald S Veazey; Thomas J Hope; Hao F Zhang Journal: J Biomed Opt Date: 2017-05-01 Impact factor: 3.170
Authors: Simi Gunaseelan; Philippe A Gallay; Michael D Bobardt; Charlene S Dezzutti; Timothy Esch; Richard Maskiewicz Journal: Pharm Res Date: 2012-06-27 Impact factor: 4.200
Authors: John A Moss; Marc M Baum; Amanda M Malone; Sean Kennedy; Etana Kopin; Cali Nguyen; Josh Gilman; Irina Butkyavichene; Robyn A Willis; Kathleen L Vincent; Massoud Motamedi; Thomas J Smith Journal: AIDS Date: 2012-03-27 Impact factor: 4.177
Authors: Marc M Baum; Irina Butkyavichene; Scott A Churchman; Gilbert Lopez; Christine S Miller; Thomas J Smith; John A Moss Journal: Int J Pharm Date: 2015-09-16 Impact factor: 5.875