Endothelin-Dependent Vasoconstriction in Human Uterine Artery: Application to Preeclampsia

BACKGROUND: Reduced uteroplacental perfusion, the initiating event in preeclampsia, is associated with enhanced endothelin-1 (ET-1) production which feeds the vasoconstriction of uterine artery. Whether the treatments of preeclampsia were effective on ET-1 induced contraction and could reverse placental ischemia is the question addressed in this study. We investigated the effect of antihypertensive drugs used in preeclampsia and of ET receptor antagonists on the contractile response to ET-1 on human uterine arteries. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed, ex vivo, on human uterine artery samples obtained after hysterectomy. We studied variations in isometric tension of arterial rings in response to the vasoconstrictor ET-1 and evaluated the effects of various vasodilators and ET-receptor antagonists on this response. Among antihypertensive drugs, only dihydropyridines were effective in blocking and reversing the ET-1 contractile response. Their efficiency, independent of the concentration of ET-1, was only partial. Hydralazine, alpha-methyldopa and labetalol had no effect on ET-1 induced contraction which is mediated by both ET(A) and ET(B) receptors in uterine artery. ET receptors antagonists, BQ-123 and BQ-788, slightly reduced the amplitude of the response to ET-1. Combination of both antagonists was more efficient, but it was not possible to reverse the maximal ET-1-induced contraction with antagonists used alone or in combination. CONCLUSION: Pharmacological drugs currently used in the context of preeclampsia, do not reverse ET-1 induced contraction. Only dihydropyridines, which partially relax uterine artery previously contracted with ET-1, might offer interesting perspectives to improve placental perfusion

Cross-Serotype Immunity Induced by Immunization with a Conserved Rhinovirus Capsid Protein

Human rhinovirus (RV) infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broadly cross-reactive vaccine, using a mouse infection model. Regions of the VP0 (VP4+VP2) capsid protein were identified as having high homology across RVs. Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, cellular and humoral immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after infection with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies and lung memory T cells, and caused more rapid virus clearance. Conserved domains of the RV capsid therefore induce cross-reactive immune responses and represent candidates for a subunit RV vaccine

High perinatal survival in monoamniotic twins managed by prophylactic Sulindac, intensive ultrasound surveillance, and Cesarean delivery at 32 weeks’ gestation.

OBJECTIVES: Increased perinatal mortality in monoamniotic twin pregnancies is attributed to cord accidents in utero and at delivery. We evaluated the following parameters in monoamniotic pregnancies: (1) the incidence of cord entanglement; (2) the effect of sulindac on amniotic fluid volume and stability of fetal lie; and (3) the perinatal outcome with our current management paradigm. METHODS: This is a retrospective review of monoamniotic pregnancies of >or=20 weeks' gestation managed with serial ultrasound surveillance, medical amnioreduction and elective Cesarean delivery at 32 weeks' gestation. Mean amniotic fluid index (AFI) and change in AFI in monoamniotic pregnancies managed with oral sulindac was compared with 40 gestation-matched monochorionic-diamniotic controls. RESULTS: Among 44 monoamniotic pregnancies, 20 with two live structurally normal twins at 20 weeks' gestation satisfied the inclusion criteria. All fetuses survived to 28 days postnatally despite early prenatal cord entanglement in all but one case. Whereas AFI remained stable throughout gestation in the controls, the AFI fell in those patients on sulindac from a mean value of 21.0 cm (95% CI, 18.5-23.6 cm) at 20 weeks to a mean of 12.4 cm (95% CI, 10.1-14.6 cm) at 32 weeks (ANOVA P across gestation = 0.001) but mainly remained within normal limits. Fetal lie was stabilized in 11/20 cases in the monoamniotic group compared with 13/40 in the control group (P < 0.0001). CONCLUSIONS: Cord entanglement appears unpreventable, as it typically occurs in early pregnancy. Sulindac therapy reduces AFI, leads to more stable fetal lie, and may prevent intrauterine death by diminishing the risk of constricting cords that are already entangled. Perinatal survival in monoamniotic pregnancies managed by a regime of sulindac from 20 weeks' gestation, close ultrasound surveillance and elective abdominal delivery at 32 weeks' gestation seems empirically higher than that in the literature

HIV and the risk of direct obstetric complications: a systematic review and meta-analysis.

BACKGROUND: Women of reproductive age in parts of sub-Saharan Africa are faced both with high levels of HIV and the threat of dying from the direct complications of pregnancy. Clinicians practicing in such settings have reported a high incidence of direct obstetric complications among HIV-infected women, but the evidence supporting this is unclear. The aim of this systematic review is to establish whether HIV-infected women are at increased risk of direct obstetric complications. METHODS AND FINDINGS: Studies comparing the frequency of obstetric haemorrhage, hypertensive disorders of pregnancy, dystocia and intrauterine infections in HIV-infected and uninfected women were identified. Summary estimates of the odds ratio (OR) for the association between HIV and each obstetric complication were calculated through meta-analyses. In total, 44 studies were included providing 66 data sets; 17 on haemorrhage, 19 on hypertensive disorders, five on dystocia and 25 on intrauterine infections. Meta-analysis of the OR from studies including vaginal deliveries indicated that HIV-infected women had over three times the risk of a puerperal sepsis compared with HIV-uninfected women [pooled OR: 3.43, 95% confidence interval (CI): 2.00-5.85]; this figure increased to nearly six amongst studies only including women who delivered by caesarean (pooled OR: 5.81, 95% CI: 2.42-13.97). For other obstetric complications the evidence was weak and inconsistent. CONCLUSIONS: The higher risk of intrauterine infections in HIV-infected pregnant and postpartum women may require targeted strategies involving the prophylactic use of antibiotics during labour. However, as the huge excess of pregnancy-related mortality in HIV-infected women is unlikely to be due to a higher risk of direct obstetric complications, reducing this mortality will require non obstetric interventions involving access to ART in both pregnant and non-pregnant women

Guidelines for the Management of HIV Infection in Pregnant Women and the Prevention of Mother-to-Child Transmission of HIV

The prevalence of HIV infection amongst women giving birth in England and Wales has increased every year since 1990. Results from the Unlinked Anonymous Surveys of infection in pregnancy, show that in 2003, the prevalence reached one in 180 (0.56%) in inner London, one in 271 in outer London (0.37%) and one in 1,282 (0.08%) in the rest of England [1]. The majority of these women are from sub-Saharan Africa. The Department of Health policy of recommending an HIV test to every pregnant woman [2] has resulted in an increase in the proportion of these women who are aware of their diagnosis prior to delivery (more than 80% in London in 2001) and a decrease in the absolute number of infants infected in the UK [3]