Inhibition of cervical ripening by local application of cyclooxygenase 2 inhibitor

Radek Bukowski, Lynn MacKay, Cordula Fittkow, Leili Shi, George Saade, Robert E. Garfield

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

OBJECTIVE: Our goal was to test the hypothesis that the previously demonstrated progesterone-independent prolongation of pregnancy in rats treated with cervical application of the cyclooxygenase 2 inhibitor nimesulide is the result of inhibition of cervical ripening. STUDY DESIGN: Timed-pregnant Sprague-Dawley rats were randomly allocated to treatment with 50 mg nimesulide or vehicle, applied daily on the cervix for 5 days (days 14-18). On day 19 the animals were humanely killed and the cervices were removed. In the first series of experiments the cervices of animals treated with nimesulide (n = 10) or vehicle (n = 10) were examined with a cervimeter, which stretches the cervical tissues in incremental steps of 0.2 mm at 1-minute intervals. A steeper slope through the linear portion of the resulting force-versus-displacement curve indicates more resistance to stretch. In the second series of experiments the cervices of animals treated with nimesulide (n = 11) or vehicle (n = 11) were examined with the Collascope optical device. The cervical content of cross-linked collagen was measured with light-induced fluorescence. The fluorescence spectrum at 390 nm (peak wavelength of the collagen spectrum) was determined. For standardization, the ratio of counts of collagen peak over reference counts was used in the final analyses as an indicator of cross-linked collagen content. RESULTS: Animals treated with cervical application of nimesulide had significantly higher resistance to stretch than controls (slope: 0.2564 ± 0.1213 vs 0.1387 ± 0.0652; P = .019). The cervical content of cross-linked collagen was not significantly different between nimesulide-treated animals and controls (light-induced fluorescence ratios: 3.2134 ± 0.7390 vs 2.7892 ± 0.8518; P = .227). CONCLUSIONS: Treatment with cervical application of the cyclooxygenase 2 inhibitor nimesulide prevents the physiologic process of cervical ripening in late pregnancy. The inhibition is not the result of changes in cross-linked collagen content. Inhibition of cervical ripening with locally administered cyclooxygenase 2 inhibitor may be a potentially valuable treatment for patients at risk for preterm delivery.

Original languageEnglish (US)
Pages (from-to)1374-1379
Number of pages6
JournalAmerican Journal of Obstetrics and Gynecology
Volume184
Issue number7
DOIs
StatePublished - 2001

Fingerprint

nimesulide
Cervical Ripening
Cyclooxygenase 2 Inhibitors
Collagen
Cervix Uteri
Fluorescence
Light
Pregnancy
Optical Devices
Progesterone
Sprague Dawley Rats

Keywords

  • Cervical ripening
  • Cyclooxygenase 2 inhibitor
  • Preterm labor

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

Inhibition of cervical ripening by local application of cyclooxygenase 2 inhibitor. / Bukowski, Radek; MacKay, Lynn; Fittkow, Cordula; Shi, Leili; Saade, George; Garfield, Robert E.

In: American Journal of Obstetrics and Gynecology, Vol. 184, No. 7, 2001, p. 1374-1379.

Research output: Contribution to journalArticle

Bukowski, Radek ; MacKay, Lynn ; Fittkow, Cordula ; Shi, Leili ; Saade, George ; Garfield, Robert E. / Inhibition of cervical ripening by local application of cyclooxygenase 2 inhibitor. In: American Journal of Obstetrics and Gynecology. 2001 ; Vol. 184, No. 7. pp. 1374-1379.
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abstract = "OBJECTIVE: Our goal was to test the hypothesis that the previously demonstrated progesterone-independent prolongation of pregnancy in rats treated with cervical application of the cyclooxygenase 2 inhibitor nimesulide is the result of inhibition of cervical ripening. STUDY DESIGN: Timed-pregnant Sprague-Dawley rats were randomly allocated to treatment with 50 mg nimesulide or vehicle, applied daily on the cervix for 5 days (days 14-18). On day 19 the animals were humanely killed and the cervices were removed. In the first series of experiments the cervices of animals treated with nimesulide (n = 10) or vehicle (n = 10) were examined with a cervimeter, which stretches the cervical tissues in incremental steps of 0.2 mm at 1-minute intervals. A steeper slope through the linear portion of the resulting force-versus-displacement curve indicates more resistance to stretch. In the second series of experiments the cervices of animals treated with nimesulide (n = 11) or vehicle (n = 11) were examined with the Collascope optical device. The cervical content of cross-linked collagen was measured with light-induced fluorescence. The fluorescence spectrum at 390 nm (peak wavelength of the collagen spectrum) was determined. For standardization, the ratio of counts of collagen peak over reference counts was used in the final analyses as an indicator of cross-linked collagen content. RESULTS: Animals treated with cervical application of nimesulide had significantly higher resistance to stretch than controls (slope: 0.2564 ± 0.1213 vs 0.1387 ± 0.0652; P = .019). The cervical content of cross-linked collagen was not significantly different between nimesulide-treated animals and controls (light-induced fluorescence ratios: 3.2134 ± 0.7390 vs 2.7892 ± 0.8518; P = .227). CONCLUSIONS: Treatment with cervical application of the cyclooxygenase 2 inhibitor nimesulide prevents the physiologic process of cervical ripening in late pregnancy. The inhibition is not the result of changes in cross-linked collagen content. Inhibition of cervical ripening with locally administered cyclooxygenase 2 inhibitor may be a potentially valuable treatment for patients at risk for preterm delivery.",
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T1 - Inhibition of cervical ripening by local application of cyclooxygenase 2 inhibitor

AU - Bukowski, Radek

AU - MacKay, Lynn

AU - Fittkow, Cordula

AU - Shi, Leili

AU - Saade, George

AU - Garfield, Robert E.

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N2 - OBJECTIVE: Our goal was to test the hypothesis that the previously demonstrated progesterone-independent prolongation of pregnancy in rats treated with cervical application of the cyclooxygenase 2 inhibitor nimesulide is the result of inhibition of cervical ripening. STUDY DESIGN: Timed-pregnant Sprague-Dawley rats were randomly allocated to treatment with 50 mg nimesulide or vehicle, applied daily on the cervix for 5 days (days 14-18). On day 19 the animals were humanely killed and the cervices were removed. In the first series of experiments the cervices of animals treated with nimesulide (n = 10) or vehicle (n = 10) were examined with a cervimeter, which stretches the cervical tissues in incremental steps of 0.2 mm at 1-minute intervals. A steeper slope through the linear portion of the resulting force-versus-displacement curve indicates more resistance to stretch. In the second series of experiments the cervices of animals treated with nimesulide (n = 11) or vehicle (n = 11) were examined with the Collascope optical device. The cervical content of cross-linked collagen was measured with light-induced fluorescence. The fluorescence spectrum at 390 nm (peak wavelength of the collagen spectrum) was determined. For standardization, the ratio of counts of collagen peak over reference counts was used in the final analyses as an indicator of cross-linked collagen content. RESULTS: Animals treated with cervical application of nimesulide had significantly higher resistance to stretch than controls (slope: 0.2564 ± 0.1213 vs 0.1387 ± 0.0652; P = .019). The cervical content of cross-linked collagen was not significantly different between nimesulide-treated animals and controls (light-induced fluorescence ratios: 3.2134 ± 0.7390 vs 2.7892 ± 0.8518; P = .227). CONCLUSIONS: Treatment with cervical application of the cyclooxygenase 2 inhibitor nimesulide prevents the physiologic process of cervical ripening in late pregnancy. The inhibition is not the result of changes in cross-linked collagen content. Inhibition of cervical ripening with locally administered cyclooxygenase 2 inhibitor may be a potentially valuable treatment for patients at risk for preterm delivery.

AB - OBJECTIVE: Our goal was to test the hypothesis that the previously demonstrated progesterone-independent prolongation of pregnancy in rats treated with cervical application of the cyclooxygenase 2 inhibitor nimesulide is the result of inhibition of cervical ripening. STUDY DESIGN: Timed-pregnant Sprague-Dawley rats were randomly allocated to treatment with 50 mg nimesulide or vehicle, applied daily on the cervix for 5 days (days 14-18). On day 19 the animals were humanely killed and the cervices were removed. In the first series of experiments the cervices of animals treated with nimesulide (n = 10) or vehicle (n = 10) were examined with a cervimeter, which stretches the cervical tissues in incremental steps of 0.2 mm at 1-minute intervals. A steeper slope through the linear portion of the resulting force-versus-displacement curve indicates more resistance to stretch. In the second series of experiments the cervices of animals treated with nimesulide (n = 11) or vehicle (n = 11) were examined with the Collascope optical device. The cervical content of cross-linked collagen was measured with light-induced fluorescence. The fluorescence spectrum at 390 nm (peak wavelength of the collagen spectrum) was determined. For standardization, the ratio of counts of collagen peak over reference counts was used in the final analyses as an indicator of cross-linked collagen content. RESULTS: Animals treated with cervical application of nimesulide had significantly higher resistance to stretch than controls (slope: 0.2564 ± 0.1213 vs 0.1387 ± 0.0652; P = .019). The cervical content of cross-linked collagen was not significantly different between nimesulide-treated animals and controls (light-induced fluorescence ratios: 3.2134 ± 0.7390 vs 2.7892 ± 0.8518; P = .227). CONCLUSIONS: Treatment with cervical application of the cyclooxygenase 2 inhibitor nimesulide prevents the physiologic process of cervical ripening in late pregnancy. The inhibition is not the result of changes in cross-linked collagen content. Inhibition of cervical ripening with locally administered cyclooxygenase 2 inhibitor may be a potentially valuable treatment for patients at risk for preterm delivery.

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