Nitric oxide and carbon monoxide production and metabolism in preeclampsia.

OBJECTIVE: To elucidate the regulation of the nitric oxide (NO) and carbon monoxide (CO) pathways in preeclampsia and to evaluate the ratio of asymmetric dimethylarginine (ADMA) to symmetric dimethylarginine (SDMA) as a marker for preeclampsia. METHODS: Maternal plasma and placental samples were obtained from 20 participants with preeclampsia and 23 controls. Enzyme-linked immunosorbent assay was used to measure plasma NO, ADMA, and SDMA as well as placental NO and hemeoxygnase 1 (HO-1). Western blot was used to measure placental dimethylarginine dimethylaminotransferases (DDAH-I and DDAH-II). RESULTS: Placental DDAH-I, placental DDAH-II, placental NO, and placental HO-1 were significantly decreased in participants with preeclampsia. While ADMA and SDMA levels were decreased in preeclampsia, the ADMA-SDMA ratio was not significantly different. CONCLUSIONS: Decreased DDAH and HO with preeclampsia suggest that they are important points in the regulatory pathways of NO and CO production that are altered in preeclampsia. The ADMA-SDMA ratio is not a useful test for preeclampsia.

Vaginal versus oral indomethacin in a rabbit model for non-infection-mediated preterm birth: an alternate tocolytic approach.

OBJECTIVE: We examined the hypotheses that vaginal indomethacin is more effective for prolonging gestation, and mediates its tocolytic actions via changes in cervical matrix metalloproteinase (MMP) activity, compared to oral. STUDY DESIGN: Pregnant rabbits induced with mifepristone received oral or vaginal indomethacin; or oral or vaginal vehicle once daily for 2 days. Premature delivery, fetal ductus arteriosus, and cervical MMP activity were assessed. RESULTS: Vaginal indomethacin delayed delivery >72 hours in 100% of the rabbits, extending gestation to 28.2 +/- 0.5 (P < .01) versus 26.4 +/- 0.3, 25.8 +/- 0.5, and 26.5 +/- 0.3 days, for vaginal placebo, oral indomethacin, and oral vehicle, respectively. Fetal ductus arteriosus was patent in all groups. Vaginal indomethacin decreased MMP-1, -8, and -9 activities and increased TIMP-1 levels in the cervix. CONCLUSION: Vaginal indomethacin is more effective than oral for prolonging gestation in the rabbit. Its tocolytic effects may be mediated, in part, by alterations in cervical MMP activity.

Do placental sections accurately reflect umbilical cord nucleated red blood cell and white blood cell differential counts?

OBJECTIVE: Elevated levels of umbilical cord nucleated red blood cells (nRBCs) have been used to assess in utero hypoxia. Although the umbilical nRBC value has been the 'gold standard', umbilical blood may not be obtained at delivery. We determined if the levels of nRBCs and white blood cell (WBC) counts in fixed placental sections might serve as a proxy for cord blood values. STUDY DESIGN: Umbilical blood and placenta were collected from 25 deliveries at Harbor-UCLA Medical Center. Umbilical blood and placental sections were analyzed for nRBCs (per 100 WBC) and WBC differential, and compared with the t-test or the Mann-Whitney rank sum test. RESULTS: nRBC counts were equivalent in umbilical cord and placental sections (5 vs. 4/100 WBC). Umbilical lymphocyte and polymorphonuclear leukocyte (PMN) counts were normally distributed, averaging 35 +/- 9 and 56 +/- 2/100 WBC, respectively. Placental lymphocyte (33 +/- 2/100 WBC) and PMN (60 +/- 2/100 WBC) counts were equivalent to cord blood values. CONCLUSION: WBC differentials and nRBC counts are equivalent in umbilical cord blood and processed placental pathology sections. For infants in whom cord blood cell counts are desired though umbilical cord samples are unavailable, fixed placental sections may serve as a proxy.