Hyperosmolar sexual lubricant causes epithelial damage in the distal colon: Potential implication for HIV transmission

被引:124
作者
Fuchs, Edward J.
Lee, Linda A.
Torbenson, Michael S.
Parsons, Teresa L.
Bakshi, Rahul P.
Guidos, Anita M.
Wahl, Richard L.
Hendrix, Craig W.
机构
[1] Johns Hopkins Univ, Sch Med, Div Clin Pharmacol, Baltimore, MD 21287 USA
[2] Johns Hopkins Univ, Sch Med, Div Gastroenterol, Dept Med, Baltimore, MD 21287 USA
[3] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA
关键词
D O I
10.1086/511279
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Many sexual lubricants are hyperosmolar. Hyperosmolar enemas induce epithelial damage, and enema use has been associated with an increased risk of HIV infection. To inform the development of rectal microbicide formulation, we evaluated the effects of hyperosmolar gels on the rectal mucosa. Methods. Two commercial lubricants were compounded into iso-osmolar and hyperosmolar mixtures ( 283 and 3429 mOsm/kg, respectively). Each gel was radiolabeled with 500 mu Ci of (99m)Technetium-diethylene triaminepentaacetic acid, and 10 mL was given rectally to 10 subjects in random sequence. Sigmoidoscopy by an endoscopist blinded to treatment assignment was performed 90 min later to obtain luminal and mucosal samples. Urine radiolabel detection was used to assess mucosal permeability. Results. Epithelial denudation 10 cm from the anus occurred to a greater degree with the hyperosmolar gel than with the iso-osmolar formulation ( median toxicity grade, 2.50 vs. 1.17 out of 3, respectively; P = .009). The hyperosmolar gel was also associated with lower isotope luminal concentration at 10 cm, compared with the iso-osmolar gel ( median, 8.9% vs. 54.6% of administered concentration, respectively). Mucosal permeability measured through 12 h was reduced with the hyperosmolar gel (P = .037). Conclusion. Rectally applied hyperosmolar gels induce greater epithelial denudation and luminal secretion than iso-osmolar gels. Because denudation plausibly increases the risk of HIV transmission, hyperosmolar gels make poor rectal microbicide formulations, and hyperosmolar sexual lubricants may increase susceptibility to HIV infection.
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页码:703 / 710
页数:8
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