Untargeted analysis of plasma samples from pre-eclamptic women reveals polar and apolar changes in the metabolome.

Introduction: Pre-eclampsia is a hypertensive gestational disorder that affects approximately 5% of all pregnancies.

Objectives: As the pathophysiological processes of pre-eclampsia are still uncertain, the present case-control study explored underlying metabolic processes characterising this disease.

Methods: Maternal peripheral plasma samples were collected from pre-eclamptic (n = 32) and healthy pregnant women (n = 35) in the third trimester.

Pharmacological profile of vascular activity of human stem villous arteries.

Introduction: The function of the placental vasculature differs considerably from other systemic vascular beds of the human body. A detailed understanding of the normal placental vascular physiology is the foundation to understand perturbed conditions potentially leading to placental dysfunction.

Methods: Behaviour of human stem villous arteries isolated from placentae at term pregnancy was assessed using wire myography.

Anti-acetylcholinesterase activity and antioxidant properties of extracts and fractions of Carpolobia lutea.

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).

Caspase-1-mediated cytokine release from gestational tissues, placental, and cord blood.

Distinguishing between fetal and maternal inflammatory responses is necessary for understanding the immune interplay either side of the placenta. Fetal immunity reaches maturity during extrauterine life and while basic inflammatory responses afford a certain degree of protection, fetuses are vulnerable to infection. With the discovery of inflammasomes-intracellular scaffolds that facilitate the elaboration of reactions resulting in the release of mature interleukin-1β (IL-1β)-it is necessary to consider how inflammatory stimuli are processed.

Expression and prognostic significance of the oncogenic K2P potassium channel KCNK9 (TASK-3) in ovarian carcinoma.

Background/aims: The TWIK-related acid sensitive K(+) channel-3 (TASK-3) is an oncogenic potassium channel. We investigated the expression of TASK-3 in human ovaries, examined its prognostic significance, and determined effects of TASK-3 blockers on cell proliferation and apoptosis.

Materials And Methods: Immunofluorescence and western blotting were used to investigate TASK-3 expression in two ovarian cancer cell lines, normal ovarian surface epithelium and cancer.

A role for two-pore potassium (K2P) channels in endometrial epithelial function.

The human endometrial epithelium is pivotal to menstrual cycle progression, implantation and early pregnancy. Endometrial function is directly regulated by local factors that include pH, oxygen tension and ion concentrations to generate an environment conducive to fertilization. A superfamily of potassium channels characterized by two-pore domains (K2P) and encoded by KCNK genes is implicated in the control of the cell resting membrane potential through the generation of leak currents and modulation by various physicochemical stimuli.

Regulation of GTP-binding protein (Gαs) expression in human myometrial cells: a role for tumor necrosis factor in modulating Gαs promoter acetylation by transcriptional complexes.

The onset of parturition is associated with a number of proinflammatory mediators that are themselves regulated by the nuclear factor κB (NF-κB) family of transcription factors. In this context, we previously reported that the RelA NF-κB subunit represses transcription and mRNA expression of the proquiescent Gαs gene in human myometrial cells following stimulation with the proinflammatory cytokine TNF. In the present study, we initially defined the functional consequence of this on myometrial contractility.

The role of Eag and HERG channels in cell proliferation and apoptotic cell death in SK-OV-3 ovarian cancer cell line.

Background: The voltage gated potassium (K+) channels Eag and HERG have been implicated in the pathogenesis of various cancers, through association with cell cycle changes and programmed cell death. The role of these channels in the onset and progression of ovarian cancer is unknown. An understanding of mechanism by which Eag and HERG channels affect cell proliferation in ovarian cancer cells is required and therefore we investigated their role in cell proliferation and their effect on the cell cycle and apoptosis of ovarian cancer cells.

The Eag potassium channel as a new prognostic marker in ovarian cancer.

Background: Ovarian 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.

Inhibition of tissue transglutaminase 2 attenuates contractility of pregnant human myometrium.

Premature delivery remains a serious risk factor in pregnancy, with currently licensed tocolytics unable to offer significant improvement in neonatal outcome. Further understanding of the regulators of uterine contractility is required to enable the development of novel and more effective tocolytic therapies. The transglutaminase family is a class of calcium-dependent, transamidating enzymes, of which tissue transglutaminase 2 is a multifunctional enzyme with roles in cell survival, migration, adhesion, and contractility.

Detection of EETs and HETE-generating cytochrome P-450 enzymes and the effects of their metabolites on myometrial and vascular function.

Cytochrome P-450 (CYP450) enzymes of the CYP2 and -4 family in humans metabolize arachidonic acid to generate bioactive epoxyeicosatrienenoic acids (EETs) and hydroxyeicosatetrenoic acids (HETEs). We report significantly higher levels of CYP 2J2 protein expression following the onset of labor (n = 6, P < 0.05), implying increased EET-generating capacity within the uterus.

Interleukin-1 beta secretion from cord blood mononuclear cells in vitro involves P2X 7 receptor activation.

The purinergic receptor P2X(7) is activated by extracellular adenosine 5'-triphosphate (ATP) and promotes the efficient release of interleukin-1 beta. The authors examine protein and molecular expression of the P2X(7) receptor and its ability to stimulate interleukin-1 beta release in cord blood mononuclear cells (CBMCs) from placentae of term nonlaboring and laboring women. They show both mRNA and protein (78 kDa) expression for the P2X( 7) receptor in CBMCs of parturient and nonparturient women.

Quantitative profiling of epoxyeicosatrienoic, hydroxyeicosatetraenoic, and dihydroxyeicosatetraenoic acids in human intrauterine tissues using liquid chromatography/electrospray ionization tandem mass spectrometry.

A reversed-phase liquid chromatography negative ion electrospray tandem mass spectrometry (LC/ESI-MS/MS) method was developed and validated to quantify a range of physiologically relevant eicosanoids, including 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs); 5-, 8-, 9-, 12-, and 15-hydroxyeicosatetraenoic acids (HETEs), and 5,6-, 8,15-, and 12,20-dihydroxyeicosatetraenoic acids (DiHETEs) in human intrauterine tissues. A solid-phase extraction method was employed to extract the eicosanoids, and gradient LC separation was performed on a Kromasil C(18) column. Mass spectrometric detection was performed by multiple reaction monitoring over a 31-min run time.

Hydrogen peroxide and superoxide anion modulate pregnant human myometrial contractility.

Reactive oxygen species (ROS) have the propensity to cause macromolecular damage with consequent modification of cellular function. We investigated the effects of two particular oxidants, superoxide (O2(-)) anions and hydrogen peroxide (H2O2), on oxytocin-induced myometrial contractility using biopsies from women undergoing Caesarean section at term gestation. Isometric tension recordings were performed and concentration-response curves derived after addition of test agents.

Progesterone enhances the tocolytic effect of ritodrine in isolated pregnant human myometrium.

Objective: To evaluate the effect of natural progesterone on the relaxant effect of ritodrine on pregnant human oxytocin-induced myometrial contractility.

Study Design: Isometric tension recordings were performed under physiologic conditions on isolated myometrial strips taken from low-risk term pregnant women undergoing elective cesarean section. Cumulative effects of natural progesterone (10 (-11) to 10 (-5) mol/L) on oxytocin-induced myometrial contractility were evaluated.

Relaxant action of sildenafil citrate (Viagra) on human myometrium of pregnancy.

Objective: The purpose of this study was to investigate the effect of the cyclic guanosine monophosphate phosphodiesterase 5-specific inhibitor, sildenafil citrate, on the contractions of isolated pregnant human myometrium.

Study Design: Myometrial samples were obtained from women who underwent elective cesarean delivery. Myometrial contractions that were recorded in response to sildenafil in the absence and presence of the potassium channel blocker, tetraethylammonium or the guanylate cyclase inhibitor, methylene blue (10 micromol/L) were studied.

Effects of a phosphodiesterase-5 (PDE5) inhibitor on endothelium-dependent relaxation of myometrial small arteries.

Objective: In preeclampsia, endothelium-dependent function is markedly aberrant. Myometrial resistance arteries from women with preeclampsia show a minimal, wholly nitric oxide-mediated, bradykinin-induced relaxation. Our aim was to test that phosphodiesterase 5 (PDE5) inhibition could improve endothelium-dependent function in preeclampsia.

Myometrial and placental artery reactivity alone cannot explain reduced placental perfusion in pre-eclampsia and intrauterine growth restriction.

Objectives: (1) To investigate a possible association between myometrial and placental artery vasoreactivity and perfusion at the basal and chorionic plates, respectively. (2) To confirm that myometrial arteries from women with pre-eclampsia and intrauterine growth restriction exhibit an attenuated endothelium-dependent vasodilatory response.

Methods: Women with normal pregnancy, pre-eclampsia and intrauterine growth restriction had a magnetic resonance scan to assess placental perfusion using a technique called intravoxel incoherent motion.

Vasoactive effects of neurokinin B on human blood vessels.

Objectives: Preeclampsia (PE) is a multisystem disease unique to human pregnancy. Abnormal placentation results in placental hypoperfusion leading to the secretion of a factor(s) by the placenta. Our aim was to investigate whether neurokinin B (NKB) is the circulating factor associated with PE.

Functional characteristics of chorionic plate placental arteries from normal pregnant women and women with pre-eclampsia.

Objectives: We aimed to compare placental small artery function from women with pre-eclampsia and normal pregnancy. In particular, we wished to test the hypothesis that these arteries respond differently to an endothelium-dependent vasodilator, to the presence of nitric oxide, and to the presence of cyclic monophosphate nucleotides.

Methods: A small vessel wire myograph was used to study placental arteries (200 to 550 microm).