Objective To measure endothelium-dependent relaxation in myometrial resistance arteries and to compare this parameter in nonpregnant and normotensive pregnant women and those with pregnancies complicated by pre-eclampsia.Design A prospective study.Setting Nottingham City Hospital.Sample Thirty-seven nonpregnant women undergoing hysterectomy and 5 1 pregnant women undergoing caesarean section, of whom there were 39 normotensive and 12 with pre-eclampsia.Methods Resistance arteries, dissected from myometrial biopsies, were mounted on a wire myograph and preconstricted with vasopressin then subjected to incremental doses of bradykinin.Results Endothelium-dependent relaxation to bradykinin was seen in the vessels of nonpregnant and normotensive pregnant women. Markedly reduced endothelium-dependent relaxation was found in the myometrial arteries from women with pre-eclampsia when compared with both nonpregnant (P < O*OOOl) and normotensive pregnant (P < 0.0001) women.Conclusion A significant loss of endothelium-dependent relaxation in myornetrial resistance arteries in pre-eclampsia may contribute to the altered vasoreactivity seen in pre-eclampsia, and particularly to the decreased placental perfusion and fetal growth retardation commonly associated with this condition.

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Objective To compare the in vitro effect of plasma from normal pregnant women and women with pre-eclampsia on the endothelium-dependent behaviour of myometrial resistance arteries from normal pregnant women. DesignSetting Nottingham City Hospital.Sample Uterine biopsy specimens were obtained from normal pregnant women delivered by elective caesarean section at term. Plasma was collected from nulliparous women with pre-eclampsia (n = 18), and from multiparous normal pregnant women (n = 18), all samples being matched for maternal age and gestation at venepuncture. Pools of plasma from women with pre-eclampsia and normal pregnant women were formed from these samples and were used in all the experiments.Methods Myometrial resistance vessels obtained from the uterine biopsies were incubated with normal pregnant plasma, plasma from women with pre-eclampsia, or without plasma. Wire myography was employed to study the effect of plasma on the endothelium-dependent behaviour of these vessels.Results Incubation of vessels from normal pregnant women with plasma from women with pre-eclampsia resulted in a significant reduction in endothelium-dependent relaxation, compared with vessels incubated either with plasma from normal pregnant women or without plasma. This alteration in endothelial function occurred after an incubation period of one hour and required a threshold concentration for its effect to become established. Removal of the vascular endothelium abolished these changes in vessel behaviour. There were no plasma-induced alterations in the endothelium-independent behaviour of the vascular smooth muscle.This study supports the hypothesis that plasma from women with pre-eclampsia is capable of altering endothelium-dependent myometrial relaxation in vessels from pregnant women.

BackgroundOvarian cancer is the second most common cancer of the female genital tract in the United Kingdom (UK), accounting for 6% of female deaths due to cancer. This cancer is associated with poor survival and there is a need for new treatments in addition to existing chemotherapy to improve survival. Potassium (K+) channels have been shown to be overexpressed in various cancers where they appear to play a role in cell proliferation and progression.ObjectivesTo determine the expression of the potassium channels Eag and HERG in ovarian cancer tissue and to assess their role in cell proliferation.MethodsThe expression of Eag and HERG potassium channels was examined in an ovarian cancer tissue microarray. Their role in cell proliferation was investigated by blocking voltage-gated potassium channels in an ovarian cancer cell line (SK-OV-3).ResultsWe show for the first time that high expression of Eag channels in ovarian cancer patients is significantly associated with poor survival (P = 0.016) unlike HERG channel expression where there was no correlation with survival. There was also a significant association of Eag staining with high tumour grade (P = 0.014) and presence of residual disease (P = 0.011). Proliferation of SK-OV-3 cells was significantly (P < 0.001) inhibited after treatment with voltage gated K+ channel blockers.ConclusionThis novel finding demonstrates a role for Eag as a prognostic marker for survival in patients with ovarian cancer.

Context: There is an unmet need to discover new treatments for Alzheimer’s disease. This study determined the anti-acetylcholinesterase (AChE) activity, DPPH free radical scavenging and antioxidant properties of Carpolobia lutea G. Don (Polygalaceae).Objective: The objective of this study is to quantify C. lutea anti-AChE, DPPH free radical scavenging, and antioxidant activities and cell cytotoxicity.Materials and methods: Plant stem, leaves and roots were subjected to sequential solvent extractions, and screened for anti-AChE activity across a concentration range of 0.02–200 μg/mL. Plant DPPH radical scavenging activity, reducing power, and total phenolic and flavonoid contents were determined, and cytotoxicity evaluated using human hepatocytes.Results:Carpolobia lutea exhibited concentration-dependent anti-AChE activity. The most potent inhibitory activity for the stem was the crude ethanol extract and hexane stem fraction oil (IC50 = 140 μg/mL); for the leaves, the chloroform leaf fraction (IC50 = 60 μg/mL); and for roots, the methanol, ethyl acetate and aqueous root fractions (IC50 = 0.3–3 μg/mL). Dose-dependent free radical scavenging activity and reducing power were observed with increasing stem, leaf or root concentration. Total phenolic contents were the highest in the stem: ∼632 mg gallic acid equivalents/g for a hexane stem fraction oil. Total flavonoid content was the highest in the leaves: ∼297 mg quercetin equivalents/g for a chloroform leaf fraction. At 1 μg/mL, only the crude ethanol extract oil was significantly cytotoxic to hepatocytes.Discussion and conclusions:Carpolobia lutea possesses anti-AChE activity and beneficial antioxidant capacity indicative of its potential development as a treatment of Alzheimer’s and other diseases characterized by a cholinergic deficit.

TREK-1 and -2 are expressed in normal ovaries and ovarian cancer. TREK-1 modulators have a significant effect on cell proliferation and apoptosis. We propose investigation of the therapeutic potential of TREK-1 blockers is warranted.

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