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KEY POINTS Maternal hypertension is associated with increased rates of pregnancy pathologies, including fetal growth restriction, due at least in part to reductions in nitric oxide (NO) bioavailability and associated vascular dysfunction. Dietary nitrate supplementation, from beetroot juice (BRJ), has been shown to increase NO bioavailability and improve cardiovascular function in both preclinical and clinical studies. This study is the first to investigate effects of dietary nitrate supplementation in a pregnant animal model. Importantly, the effects of nitrate-containing BRJ were compared with both 'placebo' (nitrate-depleted) BRJ as well as water to control for potential nitrate-independent effects. Our data show novel, nitrate-independent effects of BRJ to lower blood pressure and improve vascular function in endothelial nitric oxide synthase knockout (eNOS-/- ) mice. These findings suggest potential beneficial effects of BRJ supplementation in pregnancy, and emphasize the importance of accounting for nitrate-independent effects of BRJ in study design and interpretation. ABSTRACT Maternal hypertension is associated with adverse pregnancy outcomes, including fetal growth restriction (FGR), due in part to reductions in nitric oxide (NO) bioavailability. We hypothesized that maternal dietary nitrate administration would increase NO bioavailability to reduce systolic blood pressure (SBP), improve vascular function and increase fetal growth in pregnant endothelial NO synthase knockout (eNOS-/- ) mice, which exhibit hypertension, endothelial dysfunction and FGR. Pregnant wildtype (WT) and eNOS-/- mice were supplemented with nitrate-containing beetroot juice (BRJ+) from gestational day (GD) 12.5. Control mice received an equivalent dose of nitrate-depleted BRJ (BRJ-) or normal drinking water. At GD17.5, maternal SBP was measured; at GD18.5, maternal nitrate/nitrite concentrations, uterine artery (UtA) blood flow and endothelial function were assessed, and pregnancy outcomes were determined. Plasma nitrate concentrations were increased in both WT and eNOS-/- mice supplemented with BRJ+ (P < 0.001), whereas nitrite concentrations were increased only in eNOS-/- mice (P < 0.001). BRJ- did not alter nitrate/nitrite concentrations. SBP was lowered and UtA endothelial function was enhanced in eNOS-/- mice supplemented with either BRJ+ or BRJ-, indicating nitrate-independent effects of BRJ. Improvements in endothelial function in eNOS-/- mice were abrogated in the presence of 25 mm KCl, implicating enhanced EDH signalling in BRJ- treated animals. At GD18.5, eNOS-/- fetuses were significantly smaller than WT animals (P < 0.001), but BRJ supplementation did not affect fetal weight. BRJ may be a beneficial intervention in pregnancies associated with hypertension, endothelial dysfunction and reduced NO bioavailability. Our data showing biological effects of non-nitrate components of BRJ have implications for both interpretation of previous findings and in the design of future clinical trials.

Fetal growth restriction (FGR), where a fetus fails to reach its genetic growth potential, affects up to 8% of pregnancies and is a major risk factor for stillbirth and adulthood morbidity. There are currently no treatments for FGR, but candidate therapies include the phosphodiesterase-5 inhibitor sildenafil citrate (SC). Randomized clinical trials in women demonstrated no effect of SC on fetal growth in cases of severe early onset FGR; however, long-term health outcomes on the offspring are unknown. This study aimed to assess the effect of antenatal SC treatment on metabolic and cardiovascular health in offspring by assessing postnatal weight gain, glucose tolerance, systolic blood pressure, and resistance artery function in a mouse model of FGR, the placental-specific insulin-like growth factor 2 (PO) knockout mouse. SC was administered subcutaneously (10 mg/kg) daily from embryonic day (E)12.5. Antenatal SC treatment did not alter fetal weight or viability but increased postnatal weight gain in wild-type (WT) female offspring ( P < 0.05) and reduced glucose sensitivity in both WT ( P < 0.01) and P0 ( P < 0.05) female offspring compared with controls. Antenatal SC treatment increased systolic blood pressure in both male (WT vs. WT-SC: 117 ± 2 vs. 140 ± 3 mmHg, P < 0.0001; P0 vs. P0-SC: 113 ± 3 vs. 140 ± 4 mmHg, P < 0.0001; means ± SE) and female (WT vs. WT-SC: 121 ± 2 vs. 140 ± 2 mmHg, P < 0.0001; P0 vs. P0-SC: 117 ± 2 vs. 144 ± 4 mmHg, P < 0.0001) offspring at 8 and 13 wk of age. Increased systolic blood pressure was not attributed to altered mesenteric artery function. In utero exposure to SC may result in metabolic dysfunction and elevated blood pressure in later life. NEW & NOTEWORTHY Sildenafil citrate (SC) is currently used to treat fetal growth restriction (FGR). We demonstrate that SC is ineffective at treating FGR, and leads to a substantial increase systolic blood pressure and alterations in glucose homeostasis in offspring. We therefore urge caution and suggest that further studies are required to assess the safety and efficacy of SC in utero, in addition to the implications on long-term health.

In preeclampsia, vasospasm, oxidative stress, endothelial dysfunction, and immune dysregulation are key mediators of maternal disease. A new time-of-disease treatment is needed with the potential to treat these areas of pathophysiology. A review of the literature has indicated that metabolites of the kynurenine pathway have the potential to; (i) induce vasorelaxation of resistance arteries and reduce blood pressure; (ii) exert antioxidant effects and reduce the effects of poly-ADP ribose polymerase activation (iii) prevent endothelial dysfunction and promote endothelial nitric oxide production; (iv) cause T cell differentiation into tolerogenic regulatory T cells and induce apoptosis of pro-inflammatory Th1 cells. This has led to the hypothesis that increasing Kynurenine pathway activity may offer a new treatment strategy for preeclampsia.

Supplemental Digital Content is available in the text., Rationale: Activation of the kynurenine pathway of tryptophan catabolism by infection and inflammation contributes to the development of systemic hypotension. Commercially-available kynurenine has direct vasorelaxant effects on arteries from several species and reduces systemic blood pressure when administered to normotensive or hypertensive rats. Objectives: To determine whether kynurenine promotes relaxation of human resistance arteries from normotensive and hypertensive pregnant women and to identify the vascular mechanism of its effects. Methods and Results: In isolated omental and myometrial resistance arteries from normotensive pregnant women, kynurenine (1 mmol/L) significantly reduced U46619-induced constriction (omentum N=14, P=2.4×10−3; myometrium N=21–25, P=2.6×10−4) and relaxed preconstricted arteries (N=53, P=1.0×10−11; N=20, P=8.8×10−3). Vasorelaxation persisted following endothelium removal (N=7, P=1.6×10−4) but was completely prevented by inhibition of large-conductance Ca2+-activated K+ channels (BKCa) channels with iberiotoxin (N=9, P=5.7×10−4) or paxilline (N=10, P=2.1×10−17). Accordingly, in isolated vascular smooth muscle cells from omental arteries, kynurenine increased the BKCa current (n=5–8, P=0.022) and the amplitude of spontaneous transient outward currents (n=6, P=0.031) but did not affect spontaneous transient outward current frequency. Kynurenine also increased Ca2+ spark frequency of pressurized omental arteries (n=8, P=0.031). Vasorelaxant effects of kynurenine persisted following inhibition of ryanodine receptors (N=7, P=0.48) but were moderately reduced by inhibition of adenylate cyclase (N=9, P=0.024). In arteries from women with preeclampsia, kynurenine similarly attenuated vasoconstriction (N=15, P=1.3×10−5) and induced BKCa-mediated vasodilation (N=16, P=2.0×10−4). Vasorelaxation in response to kynurenine and a specific BKCa activator, NS11021, was absent in fetal-derived placental resistance arteries in normal pregnancy and preeclampsia. Conclusions: Kynurenine dilates systemic arteries from multiple territories via BKCa activation. Notably, the vasorelaxatory capacity of kynurenine is preserved in preeclampsia, suggesting this approach may have translational potential for the treatment of hypertension in pregnancy. The data warrant further investigation of the potential to exploit this endogenous vasorelaxant as a new treatment for hypertensive pathologies.

Aim Underlying mechanisms of poor pregnancy outcome in obese (OB) mothers (body mass index [BMI] ≥ 30 kg/m2) are unknown. Our studies demonstrate that OB pregnant women have altered myometrial artery (MA) function related to the thromboxane and nitric oxide pathways. In obesity, increased central fat mass is associated with an altered endocrine milieu. We tested the hypothesis that in OB pregnant women the omentum, a central fat store, releases factors that promote dysfunction in normal MAs. Methods Myometrial and omental adipose tissue biopsies were obtained from women with uncomplicated term pregnancies. Omental adipose tissue explants from six normal weight (NW; BMI 18.5–24.9 kg/m2) and six OB (BMI ≥ 30 kg/m2) women were cultured and the conditioned medium collected and pooled to produce NW medium and OB medium. Adipokine concentrations were measured using enzyme-linked immunosorbent assays. Wire myography was used to assess the effect of conditioned medium (NW or OB; N = 7) or leptin (100 nM; N = 5) exposure on MA responses to U46619 (thromboxane-mimetic) and bradykinin (endothelial-dependent vasodilator). Results OB medium had higher leptin and lower adiponectin levels than NW medium. U46619 and bradykinin concentration response curves shifted upwards in MAs exposed to OB medium but were unaffected by leptin. Conclusions Omental adipose tissue from OB pregnant women produced altered concentrations of adipokines. Acute OB medium exposure induced MA dysfunction, an effect not mirrored by exposure to leptin. These data suggest that an aberrant endocrine environment created by increased central adiposity in OB pregnant women induces vascular endothelial dysregulation, which may predispose them to a poor pregnancy outcome.

The endothelium is an established modulator of vascular tone; however, the recent discovery of the anti-contractile nature of perivascular adipose tissue (PVAT) suggests that the fat, which surrounds many blood vessels, can also modulate vascular tone. Both the endothelium and PVAT secrete vasoactive substances, which regulate vascular function. Many of these factors are common to both the endothelium and PVAT; therefore, this review will highlight the potential shared mechanisms in the modulation of vascular tone. Endothelial dysfunction is a hallmark of many vascular diseases, including hypertension and obesity. Moreover, PVAT dysfunction is now being reported in several cardio-metabolic disorders. Thus, this review will also discuss the mechanistic insights into endothelial and PVAT dysfunction in order to evaluate whether PVAT modulation of vascular contractility is similar to that of the endothelium in health and disease. Linked Articles This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue – Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc

Rationale: Maternal obesity pre-programmes offspring to develop obesity and associated cardiovascular disease. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the vasculature, which is reduced in hypertension and obesity. Objective: The objective of this study was to determine whether maternal obesity pre-programmes offspring to develop PVAT dysfunction in later life. Methods: Female Sprague–Dawley rats were fed a diet containing 10% (control) or 45% fat (high fat diet, HFD) for 12 weeks prior to mating and during pregnancy and lactation. Male offspring were killed at 12 or 24 weeks of age and tension in PVAT-intact or -denuded mesenteric artery segments was measured isometrically. Concentration–response curves were constructed to U46619 and norepinephrine. Results: Only 24-week-old HFD offspring were hypertensive (PM l-NMMA attenuated the anti-contractile effect of PVAT and increased contractility of PVAT-denuded arteries (PPPM A769662) was anti-contractile in PVAT-denuded (PPPP Conclusions: The diminished anti-contractile effects of PVAT in offspring of HFD dams are primarily due to release of a PVAT-derived contractile factor and reduced NO bioavailability.

Chronic hypertension in pregnancy is associated with significant adverse pregnancy outcomes, increasing the risk of pre-eclampsia, fetal growth restriction and preterm birth. Dietary nitrate, abundant in green leafy vegetables and beetroot, is reduced in vivo to nitrite and subsequently nitric oxide, and has been demonstrated to lower blood pressure, improve vascular compliance and enhance blood flow in non-pregnant humans and animals.\ud \ud The primary aims of this study were to determine the acceptability and efficacy of dietary nitrate supplementation, in the form of beetroot juice, to lower blood pressure in hypertensive pregnant women. In this double-blind, placebo-controlled feasibility trial, 40 pregnant women received either daily nitrate supplementation (70 mL beetroot juice, n = 20) or placebo (70 mL nitrate-depleted beetroot juice, n = 20) for 8 days. Blood pressure, cardiovascular function and uteroplacental blood flow was assessed at baseline and following acute (3 h) and prolonged (8 days) supplementation. Plasma and salivary samples were collected for analysis of nitrate and nitrite concentrations and acceptability of this dietary intervention was assessed based on questionnaire feedback. Dietary nitrate significantly increased plasma and salivary nitrate/nitrite concentrations compared with placebo juice (p

WHAT IS KNOWN ON THE SUBJECT?: There is increasing demand for clinical placements for pre-registration nursing students. New models of mentorship have been developed to meet the demand for clinical placements by increasing the number of students within each placement. At present there are no published research studies into the effectiveness of team mentorship utilized by pre-registration nursing students within in-patient mental health settings. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: This paper reports findings from a study that explored the experiences of mental health students within the social world of their clinical placement, adopting a new approach to practice learning where students support each other's learning. Students found their engagement in the pilot project as valuable as being exposed to the new team mentorship model which introduced them to peer-assisted learning. The learning that arose from peer-assisted learning within team mentorship appeared to provide learning opportunities that enabled students' to develop greater self-awareness and confidence. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Peer-assisted learning where students support the learning of each other, can lead to a wider range of learning opportunities for, as well as between, nursing students. In order for students to participate in care and become a "learning team," suitable in-patient mental health wards need to be identified that can support this new approach to the supervision, assessment and support of students. The establishment of team mentorship within mental health in-patient settings is dependent on the support provided by practice educators and university link lecturers to nurse mentors and coaches which in turn, determines the quality of the student experience. Abstract Introduction This paper presents findings from a study that evaluated mental health nursing students' experience of a team mentoring model called Coaching and peer-assisted learning (C-PAL). At present there are no published research studies into the effectiveness of team mentorship utilized by nursing students within in-patient mental health settings. Aim The study utilized an interpretivist methodology where the focus was on individuals in their social world. Method Two focus groups were held with fifteen students who had experienced C-PAL in four in-patient wards. Findings Students' overall experience of piloting C-PAL was positive. Learning opportunities (Theme 3) appeared to be dependent on the quality of peer support (Theme 5) which in turn, enhanced the learner experience and increased the level of student confidence (Theme 6). Less positive experiences included inadequate preparation (Theme 1), poor understanding of the model and competition for learning experiences. Implications for practice We tentatively suggest that team mentorship models such as C-PAL may be suitable for acute in-patient mental health settings. The success of C-PAL depends upon the preparation of nursing staff, mentors (Theme 4), coaches and students in relation to role expectations, shift rostering (Theme 2) and the implementation of "huddling" to promote opportunistic learning.

Background: This article presents findings from a study that sought to explore the extent to which clinical placements have an impact on nursing students' decisions regarding their first staff nurse post. Within the UK, nursing is facing a recruitment crisis with particular difficulty recruiting to areas such as primary care and care of older people. Transitioning into a new role is challenging in any occupation, but it is a particular problem in nursing where the realities of professional practice often differ from students' perception of the staff nurse role as shaped by their clinical placements. Aim: This pilot study aimed to explore the influence of practice placements on final-year adult nursing students' career decisions. Method: Qualitative and quantitative data were collected in a single phase using a questionnaire distributed to nursing students on the final day of their course. A total of 35 completed questionnaires were returned (response rate 57%). Results: Half of the participants entered the course with preconceived preferences for clinical specialisms. However, only five participants (14%) applied for first-destination posts in that specialism. The overall importance of placements in career choice increased across the three years of the programme. Although placements in all three years are important, the experiences in year 3 are pivotal, with 74% ranking these as ‘significantly influential’ in their decision-making process. Analysis of the data obtained from the free-text responses from the questionnaire suggested that working environment; the level of support provided by mentors and clinical staff; the opportunity to make a difference to patients' lives and the variety of placements, were key influences on nursing students' decision regarding their first staff nurse post. Conclusions: This study highlights the key role of practice placements in the career choices of student nurses, particularly during the final year of their programme. It shows that students are likely to apply for posts in the placement area they found to be most supportive and developmental.

Fetal growth restriction (FGR) affects 3–8% of human pregnancies. Mouse models have provided important etiological data on FGR; they permit the assessment of treatment strategies on the physiological function of both mother and her developing offspring. Our study aimed to 1) develop a method to assess vascular function in fetal mice and 2) as a proof of principle ascertain whether a high dose of sildenafil citrate (SC; Viagra) administered to the pregnant dam affected fetal vascular reactivity. We developed a wire myography methodology for evaluation of fetal vascular function in vitro using the placenta-specific insulin-like growth factor II ( Igf2) knockout mouse (P0; a model of FGR). Vascular function was determined in abdominal aortas isolated from P0 and wild-type (WT) fetuses at embryonic day (E) 18.5 of gestation. A subset of dams received SC 0.8 mg/ml via drinking water from E12.5; data were compared with water-only controls. Using wire myography, we found that fetal aortic rings exhibited significant agonist-induced contraction, and endothelium-dependent and endothelium-independent relaxation. Sex-specific alterations in reactivity were noted in both strains. Maternal treatment with SC significantly attenuated endothelium-dependent and endothelium-independent relaxation of fetal aortic rings. Mouse fetal abdominal aortas reproducibly respond to vasoactive agents. Study of these vessels in mouse genetic models of pregnancy complications may 1) help to delineate early signs of abnormal vascular reactivity and 2) inform whether treatments given to the mother during pregnancy may impact upon fetal vascular function.

This paper presents findings from an evaluation of student satisfaction with work-based learning as experienced by 57 Foundation degree (Fd) Health & Social Care students. The study participants were all employed by the National Health Service (NHS) in a range of clinical settings in the English Midlands. Three cohorts of students completed a questionnaire which sought to uncover the individual circumstances, behaviour, attitudes and beliefs of work-based learners. Students undertaking the acute care, long-term conditions, children and mental health study pathways were supported by a workplace mentor and assessor, while students studying the diagnostic radiography, radiotherapy and mammography pathways had their work-based learning supported by a clinical learning facilitator (CLF). Most of the participants were undertaking the Fd to make the transition from radiography helper or healthcare assistant (HCA) to assistant practitioner (AP). The findings distinguish the individual circumstances of students in the context of their study pathways and on the basis of their contracted hours and the role that they hoped to fill on completion of the programme. Student behaviour was characterised by the regularity with which students worked with their mentors, assessors or CLFs and their engagement in a range of work-based learning activities including practice-based assessments, knowledge and skills acquisition and, with particular regard to radiography students, the learning of new procedures. Although the level of student satisfaction with work-based learning was high, several participants perceived that their colleagues seemed reluctant to recognise them as students in their own right and lacked an awareness of the role of the AP. Participants believed that their confidence had increased and that they were playing a greater role in their clinical teams as a result of gaining knowledge and skills that had helped them to engage in new ways of working.

Introduction There are no effective therapies for pre-eclampsia (PE), which remains a leading cause of considerable materno-fetal morbidity and mortality. Statins, widely utilized in cardiovascular disease, represent a candidate therapy for PE. Determination of statins’ ability to ameliorate the observed endothelial dysfunction in PE is lacking. Objective To determine the effect of short-term pitavastatin and pravastatin exposure on chorionic plate arteries (CPAs) and omental arteries (OAs) from normal and PE pregnancies. Methods CPAs and OAs from normal pregnancy (NP; N = 43 placentas, N = 20 biopsies) and PE (N = 18 placentas, N = 5 biopsies) pregnancies were mounted on a wire myograph. Contraction was assessed with KPSS (120 mM) and thromboxane-mimetic U46619 (0.1 nM–2 μM). Arteries were incubated for 2 h with 1 μM pitavastatin or pravastatin; time-controls in parallel. U46619 dose–response curves were repeated or NO-donor SNP (1 nM–100 μM) or endothelium-dependent bradykinin (0.1–1000 nM/L) following U46619 pre-constriction. All data are mean ± SEM. Results Neither statin significantly altered vascular reactivity in NP CPAs. CPAs show blunted SNP-induced relaxation in PE vs. NP (38 ± 10% vs. 28 ± 12% respectively; p = 0.038; Two-way ANOVA). Additionally, 1μM pitavastatin attenuated PE CPAs vasoconstriction compared to control (Emax, 152 ± 30% and 165 ± 33% respectively; p = 0.013; Two-way ANOVA) but vasodilation was unaffected. In NP OAs, 1μM pravastatin reduced vasoconstriction compared to time-control (111 ± 20% and 123 ± 23% respectively; p = 0.044; Two-way ANOVA) but did not affect vasodilation. Preliminary PE OA data suggests neither statin had a significant effect on vasoconstriction or vasodilatation (P > 0.05; Two-way ANOVA; N = 5). Discussion Data suggests statins are unlikely to be deleterious to placental vascular function in NP. Pitavastatin (PE CPAs) and pravastatin (NP OAs) have the ability to blunt agonist-induced vasoconstriction. Future work will focus on whether pitavastatin and pravastatin improve endothelial function in OAs from women with PE.

ObjectivesTo characterise Chorionic Plate Artery (CPA) function in maternal obesity, and investigate whether leptin exposure reproduces the obese CPA phenotype in normal-BMI women.Study designCPA responses to the thromboxane-A2 mimetic U46619 (pre/post leptin incubation), to the nitric oxide donor sodium nitroprusside (SNP) and the occurrence of tone oscillations (pre/post leptin incubation) were assessed in 46 term placentas from women of normal (18.5–24.9) or obese (>30) Body Mass Index (BMI).Outcome measuresArea Under the dose response Curve (AUC), maximum response (Vmax), sensitivity (EC50) to U46619 (pre/post leptin) and SNP; average vessel tone, oscillation amplitude and frequency (pre/post leptin).ResultsU46619 vasoconstriction was similar between BMI categories (p > 0.05), however vasodilatation to SNP was reduced in obesity (AUC p = 0.02, Vmaxp = 0.04) compared to normal-BMI women. Leptin incubation altered responses to U46619 in both normal-BMI (EC50 at 100 ng/ml leptin; p < 0.05) and obese women (AUC at 50 ng/ml; p < 0.05) but vasomotion was unaffected (p > 0.05).ConclusionsMaternal obesity is associated with altered placental vascular function which may adversely affect placental oxygen and nutrient transport, placing the fetus at risk. Leptin incubation altered CPA vascular function but did not reproduce the obese phenotype.

Introduction The important immunoregulatory role of Kynurenine (Kyn) pathway tryptophan metabolism in the placenta is well established. Activity of this pathway is reduced in pre-eclampsia. Recently Kyn was shown to relax blood vessels and reduce blood pressure in animal models [1] . In a small study of non-pregnant humans (n = 5), Kyn relaxed omental arteries; this was attenuated by Linopirdine (Lin; 10 μM), an inhibitor of type 7 voltage-gated potassium (Kv7) channels [2] . Objectives To determine if Kyn contributes to regulation of vascular tone in systemic resistance arteries in pregnancy. Materials and methods Omental resistance arteries ( Results Treatment with 1, 3 or 6 mM Kyn dose-dependently attenuated arterial constriction to U46619 (N = 4–8, p = 0.003); greatest effect was observed at an intermediate U46619 dose of 10–7 M (change in constriction: control −0.19 ± 0.08 vs Kyn 6 mM −0.61 ± 0.13). Kyn induced relaxation of pre-constricted omental arteries (N = 7, p = 0.032; 0.70 ± 0.11 vs. 0.35 ± 0.08). Treatment with Lin 10 μM had no effect on Kyn-induced relaxation (N = 5, p = ns; 0.22 ± 0.12 vs. 0.17 ± 0.03). Conclusion This is the first study to demonstrate that Kyn has vasorelaxant effects on systemic resistance arteries in pregnancy. This supports our hypothesis that restoring Kyn pathway activity in pre-eclampsia could be a novel therapeutic target to attenuate maternal features of the disease. Kyn-induced relaxation was not inhibited by Lin 10 μM as previously reported outwith pregnancy, suggesting incomplete inhibition of Kv7 channels or an alternate compensatory mechanism.

Aim: The human fetoplacental vasculature has been suggested to be a low resistance/high flow system, but the mechanisms by which this state is achieved are unclear. Methods: This study assessed the effects of intraluminal flow and local oxygenation on isolated human placental chorionic plate arteries and veins at term using pressure myography. Results: Chorionic plate arteries and veins exhibit myogenic tone. A small but significant arterial vasodilatation was observed following exposure to hypoxia; chorionic plate veins contracted to a similar hypoxic stimulus. Under physiological conditions of pressure and oxygenation, increased luminal flow induced contraction in both chorionic plate arteries and veins. [Correction added after online publication 15th November 2011: ‘induced vasodilatation’ has been changed to ‘induced contraction’] Conclusions: Human fetoplacental vascular tone can be manipulated by local physical factors.

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was

Aims and objectives. This paper presents findings from a small piece of interpretive research into the lived experience of trained nurses who fulfilled the role of workplace mentors for Foundation degree students. The interprofessional landscape of workplace learning is also examined. Background. The participants were all employed in acute care settings in a large UK National Health Service hospital and provided mentorship to Healthcare Assistants studying the adult pathway of a Foundation degree in Health and Social Care; in preparation for the role of the Assistant Practitioner. Design. A purposive sample of eight workplace mentors (who had supported at least one Foundation degree student) were interviewed using a semi-structured questionnaire. Method. All interviews were audio recorded and subsequently transcribed. A hermeneutic phenomenological approach was used to uncover the lived experience of workplace mentors and 10 major themes were generated from the data. Results. The findings suggest that the mentorship of work-based learners presents mentors with a range of challenges that are quite different from pre-registration students given the situatedness of the learner in their clinical team. Conclusion. While the mentorship of work-based learners in busy clinical environments is challenging, the relationship between mentor and mentee appears to have greater equality due to the situatedness of the student in the clinical team. As a result workplace mentors seem to benefit from a relationship lacking in the hierarchical features that characterise traditional mentoring. Awareness of the unique experience of work-based learners and mentors needs to be raised, particularly where students are seeking to complete their Foundation degree to emerge as Assistant Practitioners. Relevance to clinical practice. Trained nurses undertaking the role of workplace mentor in support of Foundation degree students, do so to provide coaching that (in a developmental relationship), places them in the vanguard of an emerging professional group; the Assistant Practitioner.

The obesity epidemic, including childhood obesity, is rapidly gaining strength as one of the most significant challenges to the health of the global community in the 21st Century. The proportion of women who are obese at the beginning of pregnancy is also increasing. These women and their babies are at high risk of pregnancy complications, and of programming for metabolic disease in adult life. In particular, maternal obesity is associated with aberrant fetal growth, encompassing both growth restricted and large for gestational age, or macrosomic fetuses. This article considers the potential effect of obesity and adipose tissue on placental nutrient exchange mechanisms in relation to aberrant fetal growth. The review emphasizes the dearth of work on this topic to date despite its importance to current and future healthcare of the population.

Introduction Severe hypertension is a common indication for delivery amongst women with pre-eclampsia (PE), contributing to iatrogenic prematurity and its associated complications. Large-conductance calcium-activated potassium channels (BKCa), which promote vasorelaxation, are downstream targets of many vasoactive agents, including nitric oxide and angiotensin II. Estrogen-mediated increases in uterine artery BKCa activity are an important physiological adaptation to normal pregnancy. However, the role of BKCa has not been assessed in the wider systemic vasculature in either normal pregnancy or pregnancy pathologies. Outwith pregnancy, BKCa activity is reduced in association with PE risk factors, including age, hypoxia and diabetes. Furthermore, 5,6-EET, a BKCa inhibitor, is reported to be increased in the serum of women with PE. Objectives To determine the effect of BKCa activation on systemic resistance arteries of pregnant women and whether this is different in PE. Methods Resistance arteries ( Results NS11021 induced a substantial relaxation of omental resistance arteries obtained from women with either NP (N0; final relaxation Control 23 ± 8% Vs. NS11021 76 ± 4%; p Discussion Systemic arteries from women with both NP and PE relax in response to activation of BKCa channels. Direct BKCa activation provides an opportunity to bypass the inherent vascular dysfunction of PE to achieve comparable vasorelaxation in women with PE. On-going work will determine whether BKCa-activating compounds can offer a new treatment for maternal hypertension in PE.

Introduction Calcium channel blockers treat maternal hypertension in pregnancy. The effect of newer calcium channel blockers on placental vascular function remains unknown. This study aimed to determine the effect of calcium channel blockers on placental chorionic plate proximal resistance arteries in comparison to maternal omental arteries. Methods Chorionic plate and omental arteries from healthy term pregnancies delivered by caesarean section were studied using parallel wire myography (n = 80; N = 10). Arteries were normalised at 0.9 of L5.1 kPa in 5% O2 and L13.3 kPa in 20% O2 respectively, approximating physiologic vascular pressure and oxygen tension. Arteries were contracted with thromboxane-mimetic U46619 to determine and maintain optimal physiologic vascular tone (EC80). Nifedipine, Nicardipine and Clevidipine were added in incremental doses from 10–10 M to 10–5 M to create dose-dependent relaxation curves. Omental arteries were incubated for 30 min at the highest dose (10–5 M) to further evaluate full effect (n = 16; N = 4). Results Omental arteries demonstrated similar contractility to chorionic plate arteries (8.90 kPa ± 0.681 vs 8.85 kPa ± 0.603). Chorionic plate arteries did not relax with Nifedipine, Nicardipine or Clevidipine (110.73%± 7.518 vs 118.88%±9.379 vs 113.16%±5.163). Omental arteries demonstrated a trend towards larger relaxation with all calcium channel blockers at the highest dose of drug concentration. This was confirmed with highest dose incubation of omental arteries, that showed Nifedipine, Nicardipine and Clevidipine relaxed omental arteries (52.31%±16.294 vs 57.12%±8.621 vs 79.95%±14.862; One-way ANOVA, p Conclusion Chorionic plate arteries demonstrated reduced vasodilatory responses to calcium channel blockers compared to omental arteries. This suggests calcium channel blockers show limited effect on placental blood flow through proximal resistance arteries.

Objective. To determine if the phosphodiesterase type 5 inhibitor, sildenafil citrate improves endothelial-dependent relaxation of small arteries from women with preeclampsia. Methods. Myometrial and omental biopsies were taken from women participating in a randomized placebo-controlled trial using sildenafil citrate in women with preeclampsia. Vasoconstriction and endothelial-dependent relaxation of small arteries was measured utilizing wire myography. Results. Vasoconstriction and endothelial-dependent relaxation of myometrial and omental arteries were not altered in women taking sildenafil. Conclusion. Acute effects may have been lost as sildenafil administration occurred many hours prior to myography. Plasma sildenafil levels may have been lower than required for vascular response.

The UK Nuclear Decommissioning Authority (NDA) is a Non Departmental Public Body (NDPB) responsible for the remediation of the UK’s civil nuclear liabilities. To secure government funding and demonstrate that the NDA is delivering its mission, it must be able to show that it provides value for money across its estate. Value comes in many forms, such as an improved environment, hazard reduction, changes in sky line, social amenities, money, employment, and so forth. Depending on the perspective of the receiver, and their closeness to the affected area, the weighting placed on the different aspects of value will vary. Therefore, the challenge has been to get a consistent approach that measures value and is broadly acceptable to stakeholders in which different aspects are compared and decisions are made on a national basis.

Poorly controlled diabetes in pregnancy, characterized by hypo- and hyperglycemia, is associated with adverse outcomes. We hypothesized that aberrant glucose levels affect vascular function in pregnancy. The effects of glucose concentration on constriction and endothelium-dependent relaxation in uterine arteries of normal C57BL/6 mice were examined. Ex-vivo arteries from 18 pregnant and 14 non-pregnant mice were mounted on a wire myograph, constricted with phenylephrine and relaxed with incremental doses of acetylcholine, in physiological saline solution containing 5 mmol/L glucose. Arteries were then exposed to solutions with 2, 5, 8 or 12 mmol/L glucose for 30 min and constriction/relaxation repeated. On altering glucose concentrations to 2, 8 or 12 mmol/L, maximal constriction was increased in arteries from pregnant but not from non-pregnant mice (paired t-test, p

Background Adenosine triphosphate (ATP)-sensitive potassium channels (KATP) are important modulators of vascular tone. Preliminary data from our laboratory suggests that KATP channels are expressed in the fetoplacental vasculature where addition of pinacidil, a specific KATP opener, promotes relaxation. We aimed to assess the effects of KRN2391 and KRN4884 on the fetoplacental vasculature, which are putative KATP channel openers. Materials and methods Functional activity of KATP channels was assessed in chorionic plate arteries and veins using wire myography. Cromakalim-, KRN2391- and KRN4884-induced relaxations were assessed in the presence and absence of agonist-induced pretone. Cromakalim, an established KATP channel opener, acted as control. Results KRN2391 evoked significantly greater relaxation of chorionic plate arteries and veins than either KRN4884 or cromakalim. KRN2391-induced relaxation of precontracted arteries and veins was reduced in the presence of inhibitiors of the nitric oxide pathway (L-NNA or LY83583). With KRN4884, there was no contribution of nitric oxide to the induced relaxation. Conclusions We conclude that KATP channels play an important role in controlling placental vascular tone. KRN2391 induces relaxation of human placental blood vessels by activation of KATP channels and via activation of nitric oxide-dependent pathways.

Objective Endothelial dysfunction is central to the pathogenesis of pre-eclampsia (PE). This study aimed to determine if maternal characteristics, such as age, parity, BMI, smoking status and obstetric history, which affect the risk of developing pre-eclampsia, influenced endothelial function in myometrial arteries taken during an uncomplicated pregnancy. Study design As part of ongoing studies investigating endothelial function in normal and compromised pregnancies, myometrial vessels were isolated from biopsies taken at elective Caesarean section. A cohort of 119 women was identified and information regarding past pregnancy outcomes and medical history was obtained. Wire myography was used to compare endothelial-dependent relaxation in response to bradykinin between different patient groups. Results Maternal age, parity and a history of miscarriage did not affect endothelial-dependent relaxation of myometrial small arteries. Attenuated endothelial-dependent relaxation was seen in vessels taken from women with elevated BMI and enhanced relaxation was seen in women who had smoked during pregnancy. Vessels isolated from women with a history of past pregnancy complications did not show any significant difference in endothelial-dependant relaxation compared to women with uncomplicated histories. Conclusion Maternal factors may influence endothelial function in the absence of pregnancy complications. Endothelial-dependent relaxation of myometrial arteries, isolated from multiparous women with an uncomplicated index pregnancy, is comparable between women with and without a history of pregnancy complications.

Blood flow control within the fetoplacental circulation is poorly understood despite the essential role of the placenta in pregnancy. Our study compared an in vitro assessment of placental chorionic plate small artery function with in vivo measures of umbilical artery blood flow. Umbilical artery Doppler waveform analysis was performed on women (N=8) with uncomplicated pregnancies within 24 hours of delivery. Small arteries (n=25) were dissected from the placental chorionic plate from biopsies at term and studied using parallel wire myography. Chorionic plate arteries developed maintained constrictions to the thromboxane-mimetic U46619. Nitric oxide (NO) donation with the endothelial-independent agent sodium nitroprusside elicited significant relaxation compared to paired control vessels. This vasodilatation correlated significantly with both pulsatility and resistance indices measured in the umbilical artery. We conclude that Doppler indices in the umbilical artery are inversely proportional to the maximal relaxation achieved by chorionic plate small arteries in response to a NO donor.

Aim. This was an investigation to discover the lived experience of men with lower urinary tract symptoms arising from benign prostatic hyperplasic. Design. A hermeneutic phenomenological study. Methods. Approval was granted by the local Applied and Qualitative Research Ethics Committee (AQREC) prior to the commencement of the study. Data were gathered via semi-structured interviews that were audio taped, and subsequently transcribed. Each transcripted interview was analysed by the investigator and a team of ‘expert readers’. The team agreed on a total of 57 sub-themes divided into seven categories with unanimity, therefore obviating the need for participant validation. Findings. The major findings of the study suggest that men experience a broad and dramatic spectrum of phenomena while living with a benign prostate condition. This includes profound embarrassment, fear, revulsion as well as humour that require a range of methods and life adjustments to manage and contain their symptoms. Conclusions. The participant's narratives provide a thick, rich and meaningful insight into how men understand their bodies, and make sense of prostate disease; a significant men's health issue. Relevance to clinical practice. Several studies have already been published describing men's lived experience of prostate surgery for benign prostatic hyperplasia. This research has captured men's lived experience of lower urinary tract symptoms ahead of surgical intervention. Men experience a broad scope of phenomena resulting from life with a benign prostate condition that encompasses fear and embarrassment and the development of coping mechanisms and changes in life style. Recent media awareness campaigns to raise public awareness of prostate disease as a men's health issue appear to be changing how men perceive their bodies, how they converse with one another, and their help seeking behaviour.

The control of the blood flow within the fetoplacental circulation is poorly understood despite the essential role of the placenta in pregnancy. Our aim was to assess the vasoactive responses of veins from the placental chorionic plate. Biopsies were obtained from term placentae from uncomplicated pregnancies. Small veins from the chorionic plate were dissected free from surrounding tissue and studied using parallel wire myography. Human placental chorionic plate veins developed maintained constrictions to the thromboxane-mimetic U46619. Endothelium-dependent agonists did not promote venous relaxation. However, NO donation with the endothelial-independent agent, sodium nitroprusside, elicited significant relaxation. Venous constriction to U46619 and relaxation to sodium nitroprusside were modified by adjustment of media oxygen tension and normalization parameters. Human placental chorionic plate veins respond to vasoactive agents and may play a role in the control of the blood flow in the fetoplacental circulation.

The proliferation of nurstHed Initiatives arising from nurse specialist/practitioner posts In urology Is reflected In areas such as the management of bladder cancer, erectile dysfunction, stoma care, and prostate disease. The establishment of the role of urology specialist nurse In one North Oxfordshlre hospital led to the development of a nurstHed prostate assessment clinic for male patients with lower urinary tract symptoms arising from benign prostatic hyperplasia. A description of how training was conducted, and the subsequent reappraisal of competency, Is given In relation to physical examination and history-taking skills necessary for the development of this Initiative.

Introduction Maternal obesity programmes offspring to develop obesity and associated cardiovascular disease. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect in healthy blood vessels; an effect lost in male offspring of obese dams. However, the mechanism by which maternal obesity programmes PVAT dysfunction in offspring remains unknown. Methods Six week old female Sprague-Dawley rats were fed a control (10% fat) or 45% fat obesogenic diet (HFD) for 12 weeks before mating; during pregnancy and lactation. At weaning, female offspring were provided with the control diet until sacrifice at either 12 (12 wo) or 24 (24 wo) weeks of age. PVAT-denuded mesenteric arteries from pups, with or without exogenous PVAT, were mounted on a wire myograph and concentration-response curves were constructed to thromboxane A2 receptor agonist U46619 (10 nM-3 µM) ± 10 µM A769662, an activator of AMP-activated protein kinase (AMPK) ± glucosamine (an O-GlcNAcylator). Western blotting was used to asses protein expression in PVAT stimulated with or without glucosamine. Results Body weight, insulin levels and blood pressure were increased in HFD dams and their 12wo and 24 wo offspring compared to age-matched controls. Without PVAT, vessel contractions to U46619 were reduced in 12 wo offspring of HFD dams, effects mimicked in control arteries by pre-incubation with 10 mM glucosamine. PVAT from control, but not from HFD offspring, exerted an anti-contractile effect on the corresponding PVAT-denuded arteries at both ages. Pre-incubation of control PVAT with glucosamine diminished the anti-contractile effect at both ages. PVAT from HFD offspring pre-incubated with glucosamine had no effect on PVAT-denuded vessels but simultaneous AMPK activation within PVAT partially restored anti-contractile capability at both ages. Protein O-GlcNAcylation expression was increased in HFD PVAT and control PVAT incubated with glucosamine, whereas AMPK expression was decreased. Conclusions The enhanced protein O-GlcNAcylation and decreased AMPK expression in HFD PVAT may underlie the reduced anti-contractile effect of PVAT in female offspring of obese dams. Nevertheless, simultaneous AMPK activation within HFD PVAT partially restored the anti-contractile effects of PVAT.

This study directly examined endothelial function of myometrial arteries in the uterus of women with gestational diabetes mellitus (GDM), healthy pregnant and non-pregnant women. It also examined whether endothelial function was affected by the changes in glucose concentration (from 2 to 12mmol/L) that is seen in poorly controlled diabetes.Ex vivo myometrial arteries from the uterus of women with GDM (N=16) as well as healthy pregnant (N=16) and non-pregnant women (N=15) were mounted on a wire myograph. The effect of changing glucose concentrations from 5mmol/L to 2, 8 and 12mmol/L glucose for 30min was studied.Myometrial arteries from women with GDM had significantly impaired endothelium-dependent relaxation compared to those from both healthy pregnant and non-pregnant women (two-way ANOVA, p0.001). Changes in glucose concentration had no effect on constriction or endothelium-dependent relaxation in any group studied (two-way ANOVA, p0.05).Fluctuations of glucose concentrations between 2 and 12mmol/L do not affect endothelial function. Endothelial dysfunction is present in the myometrial arteries of women with GDM, an inherent defect which may be responsible for some of the complications of GDM.

Adequate blood flow provision through alterations in maternal vascular function is essential during pregnancy for optimal fetal development. Abnormal uterine vasculature adaptation, resulting in aberrant blood flow to the placenta, has been implicated as a possible cause of fetal growth restriction (FGR). Our study aimed to develop strategies to evaluate murine vascular function in pregnancy using wire myography. Main uterine artery loop and branch vessels isolated from near-term pregnant mice showed significant contraction to phenylephrine (PE). Endothelial-dependent relaxation was noted with acetylcholine (ACH). U46619 elicited significant contraction of umbilical arteries and veins, but relaxation was only demonstrable with the nitric oxide (NO) donor sodium nitroprusside (SNP). In conclusion, our data suggest that murine uteroplacental and fetoplacental arteries show distinct responses to vasoactive agents. Furthermore, this study indicates that wire myography represents a robust technique for the assessment of murine uteroplacental and fetoplacental vascular function, which will aid evaluation of mouse genetic models of FGR.

As part of its day to day business NDA must be able to demonstrate that it is delivering value for money across its entire estate, as this is essential to securing funding from government and demonstrating to stakeholders that NDA is delivering on its mission. Value comes in many forms such as an improved environment, hazard reduction, changes in sky line, social amenities, money, employment etc. Depending on the perspective of the receiver, and their closeness to the effected area, the relative weighting they place on the different aspects of value will vary. Therefore the challenge to NDA has been how to get a consistent approach to measuring value that is broadly acceptable to stakeholders and allows the different aspects of value to be compared and decisions made on a national basis. This paper describes the work undertaken by NDA to develop a Value Framework to support decision making at both the strategic and tactical level and addresses the following topics: • The relationship between the value framework and UK government guidance on business case development and options appraisal; • The development of the value framework tool kit including previous work on the NDA prioritisation process and the derivation of Safety and Environmental Detriment scores; • How NDA uses the value framework in its decision making processes.Copyright © 2009 by Crown

Healthcare assistants and support workers are beginning to access higher education programmes to expand their roles and practice. One example has been the development of the foundation degree (FD) – a 2-year diploma level course delivered via work-based learning. These undergraduate workplace learners require the support of mentors and assessors. It is proposed that traditional notions of mentorship are insufficiently attuned to the needs of work-based learners who need to prepare more for performance, rather than for practice. This argument rests on the observation that FD students are already immersed in practice and possess a wealth of experience to link to the underpinning knowledge gained from higher education. Evidence from a small piece of interpretive research is used to inform this discussion and highlight the unique needs of work-based learners within the clinical setting.

Objective: To determine whether delivery mode influences placental chorionic plate arterial and venous vascular reactivity. Methods: Normal term placentas were obtained after vaginal delivery or cesarean section. Chorionic plate arterial and venous function was assessed by wire myography. Results: Sodium nitroprusside-induced arterial relaxation increased post cesarean section at 20% oxygen. Decreased U46619-induced venous contraction was observed in vaginal deliveries at 7% oxygen. Sodium nitroprusside-induced relaxation increased in vaginal delivery at 20% oxygen. Conclusion: Delivery mode does not alter chorionic plate arterial vascular reactivity under physiological conditions, however venous reactivity was modified, a factor for consideration when interpreting functional experimental data.

Background In fetal growth restriction (FGR) abnormal umbilical artery (UA) Doppler waveform indices suggest increased vascular resistance and impaired placental blood flow. This study aimed to determine whether UA Doppler waveform indices were related to the vasoreactivity of placental chorionic plate small arteries in normal and FGR pregnancies. Materials and methods UA Doppler waveform analysis was performed 24 h before delivery in 23 normal term and 15 FGR pregnancies. Post-delivery responses of chorionic plate arteries to vasoactive agents were examined using the technique of wire myography. Results Altered vascular reactivity to agonists was demonstrated in chorionic plate arteries in FGR pregnancy. Constriction to U46619 (thromboxane mimetic) and relaxation to sodium nitroprusside (nitric oxide donor) were significantly increased in the arteries of FGR pregnancies compared with normal pregnancies. No relationship existed between Doppler indices and chorionic plate responses in normal or FGR pregnancies. Conclusions Fetoplacental vascular reactivity is altered in FGR pregnancy independently of UA Doppler waveform indices. Altered function may be additive to the pathophysiology underlying abnormal Doppler waveforms and could contribute to the inappropriate control of vascular tone in FGR.

Fetal growth restriction (FGR) affects up to 8% of all pregnancies and has massive short-term (increased fetal morbidity and mortality) and long-term (increased incidence of cardiovascular disease in adulthood) health implications. Doppler waveform analysis of pregnancies complicated by FGR suggests compromised uteroplacental circulation and placental hypoperfusion. Our aim was to determine whether myometrial small artery function was aberrant in FGR and to assess whether sildenafil citrate could improve vasodilatation in FGR pregnancies.Small arteries dissected from myometrial biopsies obtained at cesarean section from normal pregnant women (n = 27) or women whose pregnancies were complicated by FGR (n = 12) were mounted on wire myographs. Vessels were constricted (with arginine vasopressin or U46619) and relaxed (with bradykinin) before and after incubation with a phosphodiesterase-5 inhibitor, sildenafil citrate.We demonstrated increased myometrial small artery vasoconstriction and decreased endothelium-dependent vasodilatation in vessels from women whose pregnancies were complicated by FGR. Sildenafil citrate significantly reduced vasoconstriction and significantly improved relaxation of FGR small arteries.We conclude that sildenafil citrate improves endothelial function of myometrial vessels from women whose pregnancies are complicated by intrauterine growth restriction. Sildenafil citrate may offer a potential therapeutic strategy to improve uteroplacental blood flow in FGR pregnancies.

Our aim was to compare placental chorionic plate small artery function in normal pregnancies and those complicated by preeclampsia and intrauterine growth restriction. In particular we wished to test the hypothesis that the constrictive potential of placental small arteries is modified in compromised pregnancy. Biopsies were obtained from term placentas from uncomplicated pregnancies and those affected by preeclampsia and intrauterine growth restriction. Small arteries from the chorionic plate were dissected free from surrounding tissue and studied using parallel wire myography. Placental small arteries developed maintained constrictions to arginine vasopressin and the thromboxane-mimetic U46619. Arterial maximal constriction was reduced in both preeclampsia and intrauterine growth restriction. This effect was agonist independent. In intrauterine growth restriction, placental small arteries showed decreased sensitivity to U46619 but not to arginine vasopressin. Human placental chorionic plate small artery vasoconstriction is significantly reduced in compromised pregnancy, a factor that may lead to altered blood flow within the fetoplacental circulation in these conditions.

Objective The purpose of this study was to assess the involvement of rho kinase (ROK) in agonist-dependent contraction of omental, myometrial, and placental arteries of pregnant women at term. Study design Wire myography was used to assess if contractions of intact or α-toxin-permeabilized arteries obtained from women at elective cesarean section were influenced by the ROK inhibitor Y-27632. Results Western blotting indicated the presence of ROKα in each of the 3 tissue types. In intact human omental, myometrial, or placental arteries, Y-27632 dose-dependently reduced constrictions to the thromboxane-mimetic U46619. In permeabilized vessels, U46619 induced substantial Ca 2+ -sensitization of contraction that was inhibited by Y27632. The phosphatase inhibitor calyculin A induced a Ca 2+ sensitization of contraction similar to that of U46619 in permeabilized omental arteries that was unaffected by Y-27632, suggesting that ROK may signal via myosin phosphatase in these vessels. Conclusion These results are the first report of the involvement of ROK in the receptor-coupled constriction of intact and permeabilized arteries from pregnant women.

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. Study design Small arteries dissected from myometrial biopsies obtained at cesarean section from normal pregnant women (N = 22) or women with preeclampsia (N = 24) were mounted on wire or pressure myographs. Vessels were constricted (arginine vasopressin or U46619) and relaxed (bradykinin) before and after incubation with a PDE5 inhibitor, UK-343664. Results Endothelium-dependent vasodilatation was decreased in vessels from women with preeclampsia. 100 nmol/L UK-343664 did not affect normal pregnant but significantly improved relaxation of the vessels from women with preeclampsia. Conclusion A PDE5 inhibitor enhances endothelial function of myometrial vessels from women with preeclampsia, such that the behavior of these arteries approximates to those from normal women. These agents offer a potential therapeutic strategy for the management of preeclampsia.

This article examines one of the most common outpatient diagnostic procedures carried out in urology - the transrectal ultrasound (TRUS) and prostatic biopsy. Following an exploration of the aetiology, anatomy and physiology of prostate disease, an explanation is given regarding the clinical investigations that inform the decision-making process and precipitate the procedure. Technical, clinical and ethical issues will be explored before a thorough examination of the TRUS and biopsy procedure and the crucial role of the registered nurse and healthcare assistant. References are made to the elements of nursing care required throughout this most invasive of procedures. These include counselling, discharge information and the maintenance of patient dignity in relation to gender-sensitive care.

Objectives In pre-eclampsia (PE), endothelium-dependent function of myometrial small arteries is markedly attenuated. The residual PE response is wholly NO mediated. We have previously demonstrated that PDE5 inhibition can improve endothelial function in myometrial small arteries from women with PE. We aimed to assess whether the effect of PDE5 inhibition in PE was myometrial artery specific. Study design Small arteries were dissected from omental biopsies obtained at Caesarean section from normal pregnant women (NP, N = 20) and women with PE ( N = 11). Chorionic plate small arteries were dissected from NP ( N = 13) and PE ( N = 11) placentae. Vasoconstriction (arginine vasopressin or thromboxane-mimetic U46619) and endothelial-dependent relaxation were assessed by wire and pressure myography. Constriction/relaxation curves were repeated post 1 h incubation with PDE5 inhibitors UK-343664 or sildenafil citrate (0, 10 or 100 nM). Results Omental artery constriction was increased in PE. Omental vessel constriction was unaffected by PDE5 inhibition. Sildenafil citrate improved bradykinin-induced but not acetylcholine-induced relaxation of omental small arteries from NP women. PDE5 inhibition did not alter relaxation of omental arteries from women with PE. Placental small arteries were unaffected by PDE5 inhibition. Conclusion Use of PDE5 inhibitors does not significantly alter endothelial-dependent relaxation in omental or placental small arteries from PE women.