妊高征孕妇胎盘NOS及血清中NO变化的研究

目的 探讨一氧化氮(nitric oxide, NO)在妊高征发病中的作用。方法 选取妊娠晚期或足月重度妊高征孕妇32例为研究对象(PIH组),正常足月妊娠孕妇30例为对照组;用生化法测定胎盘组织一氧化氮合成酶(NOS)活性、母血及脐血一氧化氮(NO)的终末代谢产物亚硝酸盐/硝酸盐(NO_2~-/NO_3~-)含量。结果 PIH组胎盘组织NOS活性明显低于对照组(P<0.01);PIH组母亲静脉血及脐静脉血NO_2~-/NO_3~-含量与对照组比较差异均无显著性(P>0.05),而两组内母亲静脉血NO_2~-/NO_3~-含量较脐静脉血均明显增高,差异有显著性(P<0.01)。结论 NO合成障碍可能在PIH发病中起一定的作用,母血和脐血中NO_2~-/NO_3~-含量无明显差异,尚需进一步探讨。     

Role of the l-arginine nitric oxide pathway in hypoxic fetoplacental vasoconstriction

The role of nitric oxide in hypoxic fetoplacental vasoconstriction (HFPV) was investigated using dually perfused human placental cotyledons. Standard medium (Earle's salt solution with added dextran and L-arginine) was equilibrated with 95 per cent O₂ and 5 per cent CO₂ (maternal side) and 94 per cent N₂ and 6 per cent CO₂ (fetal side). Part 1 consisted of perfusion for 1 h, then maternal perfusate equilibrated with a 95 per cent N₂ and 5 per cent CO₂ for 20 min (hypoxia), and then the original perfusion conditions resumed for 40 min. In part 2, this sequence was repeated with standard medium alone (n=6), or with added N-nitro-l-arginine methyl ester (L-NAME) (n=6), nitroglycerin (n=6), or l-NAME and nitroglycerin (n=6). When standard medium was used throughout, basal fetal perfusion pressure (30 ± 2 mmHg) and the hypoxia-induced increase in perfusion pressure (18 ± 1 mmHg) did not change significantly between parts I and 2. l-NAME increased basal perfusion pressure from 33 ± 3 to 56 ± 2 mmHg whereas perfusion pressure remained unchanged with l-NAME and nitroglycerin or nitroglycerin alone. The hypoxic vasoconstriction observed during part 1 in the L-NAME (I4 ± 3 mmHg) and the L-NAME with nitroglycerin groups (18 ± 2 mmHg) was abolished during part 2 (to - 4 ± I and 0.4 ± 0.5 mmHg, respectively) whereas nitroglycerin alone significantly blunted the response (21 ± 3 to 6 ± 1 mmHg). Results suggest that a reduction in basal NO release mediates hypoxic fetoplacental vasoconstriction in the perfused human placental cotyledon in vitro.     

Economic evaluation of birth care in low-risk women. A comparison between a midwife-led birth unit and a standard obstetric unit within the same hospital in Norway. A randomised controlled trial

Objective

to investigate the cost-effectiveness in birth care for low-risk women, in an alongside midwife-led unit (MU) compared to a standard obstetric unit (SCU) within the same hospital.

Design

economic evaluation based on the findings of a randomised trial, randomising participants either into the MU or SCU. The hospital's activity-based costing system CPP was used to estimate costs, as no data on complete resource use exists.

Setting

the Department of Obstetrics and Gynaecology, Østfold Hospital Trust, Norway.

Participants

the study population consists of 1,110 consenting healthy women, assessed to be at low-risk at spontaneous onset of labour.

Measurements

effect measures; avoided caesarean sections, instrumental vaginal deliveries, complications requiring treatment in the operating room, epidural analgesia and oxytocin augmentation. Costs (€) were calculated by costs per day multiplied with length of stay, added costs for procedures performed outside the units. The results are expressed in incremental cost-effectiveness ratios (ICER) with SCU as comparator.

Findings

total costs per stay were significantly lower for women at the MU (€1,672) compared to the SCU (€1,950, p<0.001). The ICER showed that MU was a dominant strategy (lower costs and reduction in clinical procedures) for all effect measures. Based on the sensitivity analysis, allocating low-risk women to MU significantly reduced costs, but was not a dominant strategy for all outcomes.

Key conclusions

the MU is more cost-effective than the SCU for low-risk women without prelabour preference for level of birth care provided equal capacity at the units.

Implications for practice

it is cost-effective to organise birth care for low-risk women in a separate midwife-led unit.     

Response of fetal prostanoids, nitric oxide, and ductus arteriosus to the short- and long-term antenatal administration of celecoxib, a selective cyclo-oxygenase-2 inhibitor, in the pregnant rabbit

OBJECTIVE: The purpose of this study was to test the hypothesis that the maternal administration of therapeutic doses of celecoxib would not affect ductus arteriosus patency or alter renal and hepatic prostanoids in the fetal rabbit. STUDY DESIGN: Pregnant rabbits received celecoxib from 13 to 20 days (celecoxib-A), from 13-28 days (celecoxib-B), or vehicle from 13 to 28 days by gavage. Fetal serum and lung tissue were analyzed for nitric oxide oxidation products. Fetal plasma, liver, and kidney were analyzed for prostaglandin levels. RESULTS: The ductus arteriosus was patent in both treatment groups. Celecoxib induced elevations of plasma prostaglandin E(2) production. In celecoxib-B liver and kidney, the 6-keto-prostaglandin F(1alpha) and prostaglandin F(2alpha) levels were increased, and the prostaglandin E(2) and thromboxane B(2) levels were decreased substantially. CONCLUSION: This preliminary evaluation demonstrates that the maternal administration of celecoxib does not influence fetal ductus arteriosus patency adversely in rabbits.     

Evidence supporting a role for blockade of the vascular endothelial growth factor system in the pathophysiology of preeclampsia : Young Investigator Award

Objective

Soluble vascular endothelial growth factor receptor 1 (sVEGFR-1), which antagonizes VEGF functions, has been implicated in the pathophysiology of preeclampsia. The purpose of this study was to determine whether preeclampsia is associated with a change in the plasma concentration of sVEGFR-1, and, if so, whether such a change is correlated with the severity of the disease.

Methods

A cross-sectional study was conducted to determine the concentrations of sVEGFR-1 in plasma obtained from normal pregnant women (n = 61) and patients with preeclampsia (n = 61). Plasma concentrations of sVEGFR-1 were determined by enzyme-linked immunoassay.

Results

Preeclampsia had a higher median plasma concentration of sVEGFR-1 than normal pregnancy (P < .001). The median plasma concentration of sVEGFR-1 was higher in early-onset (≤34 weeks) than late-onset (>34 weeks) preeclampsia (P = .005), and higher in severe than in mild preeclampsia (P = .002). In normal pregnancy, there was a correlation between plasma concentration of sVEGFR-1 and gestational age (r = 0.5; P < .001). In contrast, there was a negative correlation between plasma concentration of sVEGFR-1 and gestational age at the onset of preeclampsia (r = -0.5; P < .001).

Conclusion

Preeclampsia is associated with an increased plasma sVEGFR-1 concentration. The elevation of sVEGFR-1 concentration is correlated with the severity of the disease. These observations suggest the participation of VEGF and its soluble receptor in the pathophysiology of preeclampsia.     

Racial disparity in membrane response to infectious stimuli: a possible explanation for observed differences in the incidence of prematurity : Community Award Paper

Objective

This study compares the immune responsiveness of amniochorionic membranes (AC) derived from African American (AA) and white (C) women to an infectious stimulus ex vivo.

Study design

AC derived from AA and C women were placed in an organ explant culture for 48 hours and then stimulated with endotoxin. Enzyme-linked immunosorbent assay measured the concentration of matrix metalloproteinase 9 (MMP9), tumor necrosis factor-α (TNF-α), and soluble TNF receptors (sTNFR1and sTNFR2) in culture media from stimulated and unstimulated AC.

Results

The C group produced 8-fold more TNF-α after stimulation than did the AA group. Both soluble receptor (R1 and R2) production increased in the C group and decreased in the AA group after stimulation. Although the C group-derived membranes produced more MMP9 at rest, a 6-fold increase in MMP9 concentration was seen in the AA group-derived membranes after stimulation. No change in MMP9 concentration was seen after stimulation of the C group-derived membranes.

Conclusion

Although the C group produced more TNF, they also produce higher sTNFRs, which may serve a protective role. The increased MMP9 release by the AA group may be suggestive of the greater risk of premature rupture of membranes in the AA group.