Acute intrauterine infection results in an imbalance between pro- and anti-inflammatory cytokines in the pregnant rabbit.

PROBLEM: Intrauterine infection results in an increase in cytokines. This study compared the time courses for the pro- and anti-inflammatory cytokine responses in 33 pregnant rabbits at 70% gestation. Pro-inflammatory markers were activated nuclear factor-kappa B (NF-kappaB) in placenta and tumor necrosis factor-alpha (TNF-alpha) in amniotic fluid. These were compared to the anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), in placenta and uterus. METHOD OF STUDY: Does were endoscopically inoculated with Escherichia coli through their cervices and sacrificed at six intervals between 0 and 30 hr post-inoculation. RESULTS: Activated NF-kappaB, determined by electromobility gel shift assay, increased significantly 16 hr after bacterial inoculation (P < or = 0.05). This was directly mirrored by TNF-alpha concentrations, determined by bioassay, in the amniotic fluid. However, IL-1ra levels, determined by enzyme-linked immunosorbent assay, did not increase in response to infection. CONCLUSIONS: Intrauterine infection results in an imbalance between pro- and anti-inflammatory cytokines that may potentiate infection-induced preterm delivery.

Oral quinolone in the treatment of experimental polymicrobial puerperal infection in rabbits.

OBJECTIVE: To evaluate the efficacy of oral levofloxacin in the treatment of experimental polymicrobial puerperal infection in the rabbit. METHODS: Timed pregnant rabbits were anesthetized on day 29 or 30 of a 31-day gestation and 106 colony-forming units each of Escherichia coli, group B streptococcus, and Staphylococcus saccharolyticus were inoculated endoscopically in the cervices. Labor was induced with intramuscular oxytocin 16 hours later if it had not occurred spontaneously. The animals then were observed every 3 hours for fever; when a temperature of 104F was reached, treatment was begun. Animals were assigned randomly in a blinded, placebo-controlled manner to received oral levofloxacin (10 mg/kg/day) or placebo and were treated twice daily for 4-5 days. The animals were killed and necropsy was performed 4-6 hours after the last dose. Specimens for culture were taken from uterine horns, peritoneum, and blood. Levofloxacin concentrations were determined from blood samples at necropsy. Clinical cure of fever, eradication of microbes, and presence of uterine abscesses at necropsy were assessed. RESULTS: Compared with placebo-treated rabbits, levofloxacin-treated animals had a significantly greater number of clinical cures (nine of 11 versus four of 12, P=.027) and significantly more eradication of E coli (ten of 11 versus five of 12, P=.022). Four uterine abscesses were seen in 12 placebo-tested animals, compared with none of 11 levofloxacin-tested animals (P=.093). There was no difference in eradication of group B streptococcus between the two groups. No blood cultures were positive for organisms in any animal. Levofloxacin was detected in all treated animals, but at low levels (less than 1 microg/mL). CONCLUSION: Treatment of experimental puerperal infection with oral levofloxacin in rabbits resulted in significantly more clinical cures and eradication of E coli compared with treatment with placebo.

Telomerase expression in normal epithelium, reactive atypia, squamous dysplasia, and squamous cell carcinoma of the uterine cervix.

Telomerase activity has been detected in a broad range of human malignant neoplasms, and its expression may represent an essential step in the malignant transformation of tissues; however, the expression of telomerase in premalignant lesions remains relatively unexplored. We tested tissue sections of cervical squamous cell carcinomas and squamous intraepithelial lesions, samples of benign reactive atypia, and normal cervical mucosa from hysterectomy and cone biopsy specimens for the expression of telomerase. Mirror-image sections from each sample were paraffin embedded and processed for histologic analysis. The test samples of cervical tissue were crushed under liquid nitrogen, and telomerase activity was determined by the telomeric repeat amplification protocol. Telomerase activity was detected in 18 of 18 cases (100%) of invasive squamous cell carcinoma. Twenty-five of 26 samples (96%) of high-grade squamous intraepithelial lesion also tested positively for telomerase activity, including 10 of 10 samples of moderate dysplasia, 12 of 13 samples of severe dysplasia, and 3 of 3 samples of carcinoma in situ. Telomerase activity was detected in 14 of 25 samples (56%) of low-grade squamous intraepithelial lesion and in 10 of 18 samples (56%) of reactive atypia but was detected in only 9 of 50 samples (18%) of histologically normal cervical mucosa. These results suggest that telomerase expression may be a marker of premalignant and malignant squamous cell lesions of the uterine cervix, although it is also expressed in a high proportion of cases of reactive atypia.