19 Feb

Aryl Phosphate Derivatives of Bromo-Methoxy-Azidothymidine: RESULTS(11)

The cervicovaginal region consisted of a stratified squamous epithelium overlying a vascular submucosa. The thickness of the epithelium varied depending on the stage of the estrous cycle. Similar to what was observed in the 10 vehicle alone-treated control mice, none of the 10 mice treated with WHI-07 for 5 days or 20 days revealed any inflammatory response or membrane disruption of the squamous epithelia (Fig. 7A and Table 4). By contrast, disruption of the epithelial lining, and an inflammatory response with influx of neutrophils in the squamous epithelia of cer-vicovaginal crypts, were evident in 9 of 10 mice given N-9 intravaginally (Fig. 7C and Table 4), consistent with previously published observations in rats. my canadian pharamacy

Two-color laser scanning confocal fluorescence images of the cervicovaginal epithelia of WHI-07- and N-9-treated sections with a monoclonal antibody specific to mouse neutrophils revealed absence of neutrophils in the stratified squamous epithelial crypts of WHI-07-treated specimens (Fig. 7B) and intense positive staining (green color) in the squamous epithelia of N-9-treated tissue section (Fig. 7D). Thus, evidence obtained by histopathologic and immunofluorescence studies indicates that unlike N-9 treatment, in-travaginal application of WHI-07 in a cream base does not cause any membrane disruption or an acute inflammatory response in the cervicovaginal epithelial crypts.

TABLE 4. Comparison of local toxicity to cervicovaginal epithelia of mice after repetitive intravaginal application with N-9 or WHI-07 as determined by histopathology.

Treatmenta PMNb influx Disruption of epithelia
Control
5 days 0/5 0/5
20 days 0/5 0/5
WHI-07
5 days 0/5 0/5
20 days 0/5 0/5
N-9
5 days 5/5 5/5
20 days 4/5 4/5

a Five mice in each group received 5% WHI-07 or 5% N-9 intravaginally for 5 or 20 consecutive days via a cream base. b PMN, polymorphonuclear leukocytes.

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