In this project we assessed the potential effectiveness of three vaginal microbicides myeloperoxidase delivered with lactobacilli (MPO+LB), a 0.25% chlorhexidine gluconate formulation (CHG), and octylglycerol, a lipid derived from human breast milk. For each microbicidal compound, we assessed baseline vaginal flora, pH, cytology, and colposcopy and collected cervical swabs for chlamydia detection by culture and LCR. We then added a gel containing MPO+LB, 0.25% CHG, octylglycerol, or appropriate placebo gel, while positive control animals were inoculated with chlamydia only. The gel containing MPO+LB appeared to protect 3 of 4 monkeys from chlamydial infection when assessed by culture and LCR. Vaginal flora was not adversely affected in this group of animals, and the exogenous lactobacilli were transiently detected at increased levels in some of the pretreated monkeys. The 0.25%CHG gel protected all 5 pretreated animals, while the chlamydia control animals tested pos iti ve repeatedly after inoculation. Changes in vaginal flora were minimal in all monkeys. 0.25% CHG did not adversely effect vaginal colonization by lactobacilli. Colposcopic observations revealed a brief induction of cervical and vaginal erythema in animals from both groups. Finally, the octylglycerol lipid was shown to protect 5 of 6 monkeys from chlamydial infection when assessed by culture alone, but only 1 of 6 when cervical swabs were assessed by LCR. It is possible that chlamydial infection was suppressed, delayed or rendered non-infectious by the lipid formulation. Monkeys pretreated with the lipid, as well as those given the placebo gel, developed marked changes in their vaginal flora. It is possible that this lipid, when delivered in an improved gel formulation, will prove to be more protective against infection, and less disruptive to the cervicovaginal environment. FUNDING NIH grants RR00166 and AI39061. Patton, D.L., Cosgrove Sweeney, Y.T., McKay, T.L., Clark, A.M., Rabe, L.K., and Hillier, S.L. 0.25% Chlorhexidine gluconate gel A protective topical microbicide. Sex. Trans. Dis. 25:421-424, 1998. Patton, D.L., Cosgrove Sweeney, Y.T., McKay, T.L., Clark, A.M., Rabe, L.K., and Hillier, S.L. Effects of a single application of 0.25% chlorhexidine gluconate on vaginal flora and chlamydial infection in a monkey model. Fertil. Steril. 69:584, 1998. Patton, D.L., Cosgrove Sweeney, Y.T., Clark, A.M., Rabe, L.K., Klebanoff, S.J., and Hillier, S.L. Effects of a myeloperoxidase plus lactobacillus gel on vaginal flora and chlamydial infection in a monkey model. Abstr. 13 Mtg. Int. Soc. for STD Res., Denver, Co., July 11-14, 1999. Patton, D.L., Isaacs, C.E., Cosgrove Sweeney, Y.T., Clark, A.M., Rabe, L.K., and Hillier, S.L. Effects of a gel containing the lipid octylglycerol on vaginal flora and chlamydial infection in a monkey model. Abstr. 13 Mtg. Int. Soc. for STD Res., Denver, Co., July 11-14, 1999.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000166-39
Application #
6316816
Study Section
Project Start
1976-06-01
Project End
2002-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
39
Fiscal Year
2000
Total Cost
$132,406
Indirect Cost
Name
University of Washington
Department
Type
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Pham, Amelie; Carrasco, Marisa; Kiorpes, Lynne (2018) Endogenous attention improves perception in amblyopic macaques. J Vis 18:11
Zanos, Stavros; Rembado, Irene; Chen, Daofen et al. (2018) Phase-Locked Stimulation during Cortical Beta Oscillations Produces Bidirectional Synaptic Plasticity in Awake Monkeys. Curr Biol 28:2515-2526.e4
Choi, Hannah; Pasupathy, Anitha; Shea-Brown, Eric (2018) Predictive Coding in Area V4: Dynamic Shape Discrimination under Partial Occlusion. Neural Comput 30:1209-1257
Shushruth, S; Mazurek, Mark; Shadlen, Michael N (2018) Comparison of Decision-Related Signals in Sensory and Motor Preparatory Responses of Neurons in Area LIP. J Neurosci 38:6350-6365
Raghanti, Mary Ann; Edler, Melissa K; Stephenson, Alexa R et al. (2018) A neurochemical hypothesis for the origin of hominids. Proc Natl Acad Sci U S A 115:E1108-E1116
Wool, Lauren E; Crook, Joanna D; Troy, John B et al. (2018) Nonselective Wiring Accounts for Red-Green Opponency in Midget Ganglion Cells of the Primate Retina. J Neurosci 38:1520-1540
Hasegawa, Yu; Curtis, Britni; Yutuc, Vernon et al. (2018) Microbial structure and function in infant and juvenile rhesus macaques are primarily affected by age, not vaccination status. Sci Rep 8:15867
Oleskiw, Timothy D; Nowack, Amy; Pasupathy, Anitha (2018) Joint coding of shape and blur in area V4. Nat Commun 9:466
Eberle, R; Jones-Engel, L (2017) Understanding Primate Herpesviruses. J Emerg Dis Virol 3:
McAdams, Ryan M; McPherson, Ronald J; Kapur, Raj P et al. (2017) Focal Brain Injury Associated with a Model of Severe Hypoxic-Ischemic Encephalopathy in Nonhuman Primates. Dev Neurosci 39:107-123

Showing the most recent 10 out of 320 publications