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Purpose Health and social care professionals are ideally placed to identify and address gender-based violence (GBV), yet research continues to demonstrate that the subject is being poorly covered at undergraduate level. This qualitative study explored health and social care students' and educators' views on GBV education, with a view to identifying 'best practice'. We aimed to capture students' and educators' experiences and perceptions of GBV education across participating countries; how participants thought GBV should be taught/learned within their curricula; and their views on how GBV education might be 'optimized'. Methods We conducted nine focus group discussions and one semi-structured interview with 23 students and 21 academic staff across the UK, Australia and Chile. Results Thematic analysis yielded three themes: (1) GBV addressed in all but name, (2) Introduce sooner, explore later and (3) A qualitative approach to learning. Educators and students indicated that GBV is largely being overlooked or incompletely addressed within curricula. Many participants expressed a wish for the subject to be introduced early and revisited throughout their study, with content evolving as cohorts mature. Lastly, our findings indicate that GBV education could benefit from adopting a 'qualitative' approach, prioritizing survivor narratives and incorporating dialogue to facilitate student engagement. Conclusion Though time constraints and competing demands within undergraduate curricula are frequently cited as barriers to moving away from traditional didactic methods, our findings suggest that teacher-centered strategies are insufficient and, in some regards, inappropriate for GBV education. The need for a paradigm shift in GBV education is discussed., Author(s): Dana Sammut [sup.1] , Lilian Ferrer [sup.3] , Emily Gorham [sup.1] , Kelsey Hegarty [sup.2] , Jacqueline Kuruppu [sup.2] , Francisca Lopez Salvo [sup.3] , Caroline Bradbury-Jones [sup.1] Author [...]

Background Steroid-resistant nephrotic syndrome (SRNS), commonly caused by focal segmental glomerulosclerosis (FSGS), is associated with progression to stage 5 chronic kidney disease, requirement for kidney replacement therapy and a risk of disease recurrence post-kidney transplantation. Ofatumumab (OFA) is a fully humanised monoclonal antibody to CD20, with similar mechanisms of action to rituximab (RTX). Methods We report a case series of seven UK patients (five paediatric, two adult), all of whom developed FSGS recurrence after kidney transplantation and received OFA as part of their therapeutic intervention. All also received concomitant plasmapheresis. The 2-year outcome of these seven patients is reported, describing clinical course, kidney function and proteinuria. Results Four patients (all paediatric) achieved complete urinary remission with minimal proteinuria 12 months post-treatment. Three of those four also had normal graft function. Two patients showed partial remission-brief improvement to non-nephrotic proteinuria (197 mg/mmol) in one patient, maintained improvement in kidney function (estimated glomerular filtration rate 76 ml/min/1.73 m.sup.2) in the other. One patient did not demonstrate any response. Conclusions OFA may represent a useful addition to therapeutic options in the management of FSGS recurrence post-transplantation, including where RTX has shown no benefit. Concomitant plasmapheresis in all patients prevents any definitive conclusion that OFA was the beneficial intervention., Author(s): Ben C. Reynolds [sup.1] , Angela Lamb [sup.1] , Caroline A. Jones [sup.2] , Pallavi Yadav [sup.3] , Kay S. Tyerman [sup.3] , Colin C. Geddes [sup.4] Author Affiliations: [...]

Continuing professional learning is vital to early childhood professionals, and the use of digital technology can potentially reduce costs and improve access. In this study, 74 educators across 17 early childhood services in Australian urban and regional locations completed a questionnaire about their personal and professional uses of digital technology to find resources. The results indicate most early childhood educators use digital technology to construct their own professional knowledge bases, and though they make some use of formal resources around national standards, they make greater use of informal resources and discussion groups. They tend to seek practical information and activity ideas and ways to connect with other professionals, although this varies somewhat by years of professional experience, age and the socioeconomic context they work in. Results highlight early childhood educators' professional learning desires and the potential value of mobile learning for providing access to professional learning for early childhood educators working in resource-limited and geographically limited settings. Keywords Professional development, professional learning, continuing education, technology use, mobile learning, Background The Australian early childhood (EC) workforce includes educators working towards qualification, certificate- or diploma-qualified educators and university-trained teachers and differing lengths of experience in the sector, resulting in varying [...]

Cisplatin is one chemotherapeutic agent used to treat childhood cancer in numerous treatment protocols, including as a single agent. It is likely to remain in clinical use over the long term. However, cisplatin-related toxicities, including neurotoxicity and nephrotoxicity, are common, affecting treatment, day-to-day life and survival of such children. With one in 700 young adults having survived childhood cancer, patients who have completed chemotherapy that includes cisplatin can experience long-term morbidity due to treatment-related adverse reactions. A better understanding of these toxicities is essential to facilitate prevention, surveillance and management. This review article discusses the effect of cisplatin-induced nephrotoxicity (Cis-N) in children and considers the underlying mechanisms. We focus on clinical features and identification of Cis-N (e.g. investigations and biomarkers) and the importance of magnesium homeostasis and supplementation., Author(s): Chris D. Barton [sup.1] [sup.2] , Barry Pizer [sup.2] , Caroline Jones [sup.3] , Louise Oni [sup.1] [sup.3] , Munir Pirmohamed [sup.1] , Daniel B. Hawcutt [sup.1] [sup.4] Author [...]

In her Hunger Games trilogy, Suzanne Collins has created, in Katniss Everdeen, an unlikely hero who must draw from those around her in her heroic development. From her friend Gale she learns passion for justice, from fellow- tribute Peeta she learns to seek her own sense of integrity, and from mentor Haymitch she learns practical strategies of stubbornness and resistance. Drawing on dystopian and ideological theory, this article explores the importance of community even in acts of individual heroism, and considers the role of hope in providing impetus in effecting societal and political change., Dystopian fictions occupy a prominent place in the contemporary young adult canon. The popularity of Suzanne Collins's Panem trilogy, comprising The Hunger Games (2008) and its sequels, Catching Fire (2009) [...]

Background In juvenile-onset systemic lupus erythematosus (JSLE), renal involvement (lupus nephritis) is frequently seen and can result in long-term morbidity. This prospective longitudinal study aimed to identify the utility of standard and/or novel biomarkers for monitoring and predicting lupus nephritis in a real world setting. Methods Using an unselected JSLE cohort, urine samples were collected during routine clinical review. Protein concentrations of urinary monocyte chemo-attractant protein 1 (uMCP1) and neutrophil gelatinase-associated lipocalin (uNGAL) were analysed along with standard disease activity markers, and were compared with current and subsequent disease activity. Results JSLE patients (n = 64; median age 14.1 years) were seen at 3 (interquartile range: 2-5) clinical reviews over 364 (182-532) days. Multivariate analysis demonstrated uMCP1 and serum C3 as independent variables (p Keywords Lupus * Biomarker * Nephritis * MCP1 * NGAL * Lipocalin, Introduction In juvenile-onset systemic lupus erythematosus (JSLE) a preponderance of renal involvement (lupus nephritis; LN) is seen and has been described to occur in up to 80% of patients within [...]

Contemporary conceptions of female sexuality offer complexly layered and contradictory messages about girls' and young women's sexual agency, self-perception, and activity. Dominant social discourses, including those in popular media, instruct [...]

A collaboration In the summer of 2006 author Margaret Elphinstone, embarking on a novel ser in the prehistoric period (Elphinstone 2009), sought out archaeologist Caroline Wickham-Jones to discover more about [...]

Abstract Aim The aim of this study was to gain insight into registered nurses' experiences of caring for older people in the UK and Japan. Method Critical incident technique was [...]

Abstract Aim To explore the healthcare experiences of women living with domestic abuse, specifically in relation to the primary care setting. Method A qualitative study was undertaken in Scotland, comprising [...]

Traditional antibody-based affinity sensing strategies employ multiple reagents and washing steps and are unsuitable for real-time detection of analyte binding. Aptamers, on the other hand, may be designed to monitor binding events directly, in real-time, without the need for secondary labels. The goal of the present study was to design an aptamer beacon for fluorescence resonance energy transfer (FRET)based detection of interferon-gamma (IFN-[gamma])--an important inflammatory cytokine. Variants of DNA aptamer modified with biotin moieties and spacers were immobilized on avidin-coated surfaces and characterized by surface plasmon resonance (SPR). The SPR studies showed that immobilization of aptamer via the 3' end resulted in the best binding IFN-[gamma], ([K.sub.d] = 3.44 nM). This optimal aptamer variant was then used to construct a beacon by hybridizing fluorophore-labeled aptamer with an antisense oligonucleotide strand carrying a quencher. SPR studies revealed that IFN-[gamma] binding with an aptamer beacon occurred within 15 min of analyte introduction--suggesting dynamic replacement of the quencher-complementary strand by IFN-[gamma] molecules. To further highlight biosensing applications, aptamer beacon molecules were immobilized inside microfluidic channels and challenged with varying concentration of analyte. Fluorescence microscopy revealed low fluorescence in the absence of analyte and high fluorescence after introduction of IFN-[gamma]. Importantly, unlike traditional antibody-based immunoassays, the signal was observed directly upon binding of analyte without the need for multiple washing steps. The surface immobilized aptamer beacon had a linear range from 5 to 100 nM and a lower limit of detection of 5 nM IFN-[gamma]. In conclusion, we designed a FRET-based aptamer beacon for monitoring of an inflammatory cytokine--IFN-[gamma]. In the future, tiffs biosensing strategy will be employed to monitor dynamics of cytokine production by the immune cells. 10.1021/ac9025237

Abstract Steps to enhance the rigour of qualitative research are much debated in nursing research. Prolonged engagement in the field, maintaining a journal and member checks (participant feedback) can help [...]

Summary Globalisation describes the increasing economic and social interdependence between countries. This article examines globalisation in terms of the opportunities and threats it poses to health, in particular increasing rates [...]

The microarray format is being used extensively for combinatorial screening of cellular interactions with proteins, small molecules, or biomaterials. The utility of microarray-based cell cultivation approaches may be enhanced further by incorporating biosensing elements alongside the cell-adhesive ligands to enable local detection of secreted cellular products. The concept of combining cells and sensing elements in the same microarray is demonstrated in the present paper with hepatocytes serving as a model cellular system. Robotic microarraying was employed to print arrays of 300-[micro]m-diameter collagen (I) spots alongside the antibody (Ab) spots specific to liver proteins: albumin and [alpha]l-antitrypsin ([alpha]1-AT). Protein microarrays were printed onto poly(ethylene glycol) hydrogel-coated glass slides, thus eliminating nonspecific adsorption of cells or proteins. When incubated with printed microarrays, hepatocytes became localized on collagen (I) domains but did not attach on Ab spots or elsewhere on hydrogel-coated glass substrates. Liverspecific proteins secreted by hepatocytes were captured on Ab domains in the immediate vicinity of the cells, detected with a sandwich immunofluorescent assay and quantified using a microarray scanner. Importantly, hepatic albumin and [alpha]1-AT production detected in the microarray was comparable to enzyme-linked immunosorbent assay measurements of these proteins. In the future, the juxtaposition of sensing Ab regions with cell arrays will be particularly useful for the detection of local appearance or loss of phenotype of cells interacting with the printed components of the cellular microenvironment.

Malaria epidemics represent a significant public health problem in the highlands of Africa. Many of these epidemics occur in low resource settings, where the development of an effective system for malaria surveillance has been a key challenge. Between 2001 and 2006, the Highland Malaria Project (HIMAL) established a programme to develop and test a district-based surveillance system for the early detection and control of malaria epidemics in four pilot districts in Kenya and Uganda. An innovative feature of the programme was the devolution of responsibility for the detection of epidemics from the central Ministry of Health to District Health Management Teams. The implementation of the programme offered the opportunity to test both the technical aspects of the system and to examine the practical issues relating to the operation of the programme in the context of the existing health system. To investigate the attitude of key staff towards the programme, and their perceptions of its impact on their working practices, interviews were carried out among 52 health staff at district level and in the Ministries of Health in Kenya and Uganda. The transfer of responsibility for the early detection of epidemics to the districts had resulted in perceptions of individual empowerment among district-based staff. This, together with improved support supervision, was a key factor in sustaining motivation and improved surveillance. The enhanced support supervision also produced capacity benefits that extended beyond improved malaria surveillance. However, these improvements occurred in the context of increased logistical support (the provision of transport, fuel and travel allowances) which the participants believed was essential to the functioning of an effective system. With this proviso, the district-based malaria early warning system was perceived to he manageable, effective and sustainable in the context of the current health system. Keywords: East Africa Kenya Uganda Malaria epidemics Malaria early warning systems (MEWS) Surveillance Health worker perceptions Staff motivation

The effect of lycopene on macrophage foam cell formation induced by modified low-density lipoprotein (LDL) was studied. Human monocyte-derived macrophages (HMDM) were incubated with lycopene in the presence or absence of native LDL (nLDL) or LDL modified by oxidation (oxLDL), aggregation (aggLDL), or acetylation (acLDL). The cholesterol content, lipid synthesis, scavenger receptor activity, and the secretion of inflammatory [interleukin (IL)-l[beta] and tumor necrosis factor (TNF)-[alpha]] and anti-inflammatory (IL-10) cytokines was determined. Lycopene was found to decrease the synthesis of cholesterol ester in incubations without LDL or with oxLDL while triacylglycerol synthesis was reduced in the presence of oxLDL and aggLDL. Scavenger receptor activity as assessed by the uptake of acLDL was decreased by ~30% by lycopene. In addition, lycopene inhibited 1L-10 secretion by up to 74% regardless of the presence of nLDL or aggLDL but did not affect IL-1[beta] or TNF-[alpha] release. Lycopene also reduced the relative abundance of mRNA transcripts for scavenger receptor A (SR-A) in THP-1 macrophages treated with aggLDL. These findings suggest that lycopene may reduce macrophage foam cell formation induced by modified LDL by decreasing lipid synthesis and downregulating the activity and expression of SR-A. However, these effects are accompanied by impaired secretion of the anti-inflammatory cytokine IL-10, suggesting that lycopene may also exert a concomitant proinflammatory effect. low-density lipoprotein; scavenger receptors; cytokines; macrophage

While cellular micropatterning approaches are employed extensively in cell biology and tissue engineering, only a limited number of methods for analysis of local function in the context of a complex, microfabricated environment are currently available. The present study develops a novel strategy for analysis of local tissue-specific function in cellular micropatterns. Model hepatocytes (HepG2 cells) were seeded onto silane-modified glass slides containing robotically printed arrays of collagen type I. These model hepatocytes formed cell arrays with individual cell cluster dimensions (150 or 500 [micro]m) corresponding in size to the printed collagen spots. Non-parenchymal cells (3T3 fibroblasts) were added to hepatocellular micropatterns to create heterotypic cocultures. Expression of hepatic phenotype in HepG2 cells was first verified by traditional techniques including intracellular staining and ELISA for albumin. In order to evaluate local liver function in the cellular microarray, individual array members composed of ~400 hepatocytes were retrieved using laser capture microdissection and analyzed with real-time reverse transcriptase (RT)-polymerase chain reaction (PCR). Hepatic function was assessed based on expression of four genes associated with differentiated liver phenotype: albumin, transferrin, [alpha]-fetoprotein, and [alpha]1-antitrypsin. 'Titration' experiments, carried out to identify the smallest population of HepG2 cells yielding detectable mRNA levels and RT-PCR signals, showed that extraction area of 12 500 [micro][m.sup.2] (corresponding to ~70 cells) provided detectable gene expression signals. All four liver-specific genes were routinely evaluated after extraction of ~400 HepG2 from the micropatterned surfaces. Significantly, selective retrieval and subsequent analysis of tissue-specific function was demonstrated for hepatic cells micropatterned alone and in coculture with non-parenchymal cells. In the future, methods described in this study will offer the possibility to investigate dynamic and reciprocal interactions between two or more cell types positioned on a microfabricated cell culture surface. We also envision the proposed approaches to be ideally suited for cell analysis in the context of combinatorial microenvironment.

INTRODUCTION The forming of the five senses is a labor of the entire history of the world down to the present. (1) --Karl Marx Digital convergence and accelerated knowledge production [...]

In 1996, Social Science & Medicine published a review of treatment seeking for malaria (McCombie, 1996). Since that time, a significant amount of socio-behavioral research on the home management of malaria has been undertaken. In addition, recent initiatives such as Roll Back Malaria have emphasized the importance of social science inputs to malaria research and control. However, there has been a growing feeling that the potential contributions that social science could and should be making to malaria research and control have yet to be fully realized. To address these issues, this paper critically reviews and synthesizes the literature (published, unpublished and technical reports) pertaining to the home management of illness episodes of malaria in sub-Saharan Africa from 1996 to the end of 2000, and draws conclusions about the use of social science in malaria research and control The results suggest that while we have amassed increasing quantities of descriptive data on treatment seeking behavior, we still have little understanding of the rationale of drug use from the patient perspective and, perhaps more importantly, barely any information on the rationale of provider behaviors. However, the results underline the dynamic and iterative nature of treatment seeking with multiple sources of care frequently being employed during a single illness episode; and highlight the importance in decision making of gender, socioeconomic and cultural position of individuals within households and communities. Furthermore, the impact of political, structural and environmental factors on treatment seeking behaviors is starting to be recognised. Programs to address these issues may be beyond single sector (malaria control programme) interventions, but social science practice in malaria control needs to reflect a realistic appraisal of the complexities that govern human behavior and include critical appraisal and proposals for practical action. Major concerns arising from the review were the lack of evidence of 'social scientist' involvement (particularly few from endemic countries) in much of the published research; and concerns with methodological rigor. To increase the effective use of social science, we should focus on a new orientation for field research (including increased methodological rigor), address the gaps in research knowledge, strengthen the relationship between research, policy and practice; and concentrate on capacity strengthening and advocacy. Keywords: Malaria; Social science; Treatment seeking; Malaria control; Sub-Saharan Africa

Introduction (1) At the end of the nineteenth century, Angus and Robertson became agent and bookseller to the University of Sydney and the Public Library of New South Wales. (2) [...]

Background The Mesolithic occupation of Scotland began soon after the end of the last glaciation, between 10,000 and 9000 years ago. Considerable research has been undertaken in the past two [...]

C'est tres dur d'etre devant et derriere la camera. (Entretiens sur le cinematographe) Cegeste Ne vous obstinez pas, un peintre fait toujours son propre portrait. (Le Testament d'Orphee) Bien sur [...]

Byline: Caroline A. Jones (1), Lydia S. Bowden (2), Ruth Watling (2), Steven W. Ryan (2), Brian A. Judd (2) Keywords: KeywordsaaPreterm; Hypercalciuria; Bone density Abstract: In a previous study, 8 of 28 ex-preterm infants, aged 4--5 years, had increased urinary calcium excretion. The aim of this study was to confirm this finding and to determine if raised urinary calcium excretion is associated with reduced bone mineralisation. Forty-six ex-preterm children, aged 7--9 years, and 40 age- and sex-matched controls were recruited. The calcium excretion measured from 3 separate 24-h urine collections was recorded and a dietary assessment made from a diary record. Data were retrieved from the neonatal case notes and included aminoglycoside usage. Dual energy X-ray absorptiometry was used to measure bone mineral content and bone mineral density (BMD) in all children. The mean maximum 24-h urinary calcium was significantly higher in the preterm group than the term group (P=0.01). Increased calcium excretion was associated with raised neonatal aminoglycoside levels (P=0.0013). Height standard deviation score and hip BMD were significantly lower in the 21 preterm children with a 24-h urinary calcium above 4 mg/kg per day than term controls (P=0.04 and P=0.004, respectively). Urinary calcium excretion had a negative relationship with hip BMD in the preterm group (P=0.004). This difference in BMD was not observed in the 25 preterm children with normocalciuria. In the 10 preterm girls with hypercalciuria, hip BMD was lower than in control females (P=0.01). This difference in hip BMD between the 11 preterm boys with hypercalciuria and term boys was not significant (P=0.05). In conclusion, preterm children are shorter and have a lower hip BMD than those with normocalciuria. Further prospective studies are required to assess this risk and its influence on subsequent impaired bone mineralisation. Author Affiliation: (1) Institute of Child Health, Alder Hey, Liverpool, UK, GB (2) Royal Liverpool Children's Hospital, Eaton Road, Alder Hey, Liverpool, L12 2AP, UK e-mail: CAJones@doctors.org.uk Tel.: +44-151-2525221, Fax: +44-151-252 5928, GB Article note: Received: 28 September 2000 / Revised: 2 April 2001 / Accepted: 2 April 2001

The proliferation of biennials and art fairs around the world has brought with it the rise of a jet-set elite. For all their talk of working with local communities, how [...]

ONLY IN THE TWENTIETH CENTURY have the cargo cults of modernity given us handmade objects that mimic so intently the processes of industrial manufacture. Even more surprising are the rare [...]

FEW ARTISTS have had Picasso's arrogant confidence: 'I do not seek. I find.' Far more typical of modernity was the desire to align one's work with research: Constable's cloud studies, [...]

ICONIC SUBLIMATION A retrospective at the National Gallery of Art is the closest thing the American art world has to an imperial investiture, and Dan Flavin's Washington, DC, survey was [...]

Case summary A further renal ultrasound scan at the age of 6 years showed nephrocalcinosis. In view of the proteinuria, the patient was started on enalapril. The family had previously [...]

John Cage sought to remove ego from art and ending from action. His work with Buckminster Fuller and others on a 'finishing school' seems antagonistic to his nature, unless we regard it as 'finishing off' school and progressing from abstract academic to concrete world. He was a fire that sought to reclaim spaces from deadwood, clearing it for new growth. His openness to silence and the lack of self challenged and redefined the abstract expressionist ego.

Abstract Between 1996 and 2005, two of seven infants in our unit on overnight continuous-cycle peritoneal dialysis (CCPD) acquired hypothyroidism following normal thyroid function on neonatal screening. Case 1 had [...]

Byline: Michael Eisenhut (1,4), Caroline Jones (1), David Hughes (1), Simon Herrington (2), George Kokai (3) Keywords: Gemella; Focal proliferative glomerulonephritis; Renal failure; Macroscopic hematuria; Pneumonia Abstract: We describe a 13-year-old boy who developed acute renal failure associated with Gemella haemolysans pneumonia. At presentation he was found to have macroscopic hematuria associated with lobar pneumonia. Gemella haemolysans was isolated from blood cultures. Renal failure was detected on admission, progressed and dialysis was required until day 18. Renal impairment had resolved by 3 months after the initial presentation. Histopathology of a renal biopsy showed focal proliferative glomerulonephritis, but the predominant abnormality was tubular damage associated with erythrocyte casts in tubular lumina. We believe that tubular damage due to hematuria rather than the glomerular changes was the most likely cause of renal failure. Author Affiliation: (1) Royal Liverpool Children's Hospital, Eaton Road, Liverpool, L122AP, UK (2) Department of Pathology, Royal Liverpool University Hospital, Prescot Street, Liverpool, L78XP, UK (3) Department of Histopathology, Royal Liverpool Children's Hospital, Eaton Road, Liverpool, L122AP, UK (4) 5 Prestwood Crescent, Liverpool, L14 2ED, UK Article History: Registration Date: 17/10/2003 Received Date: 30/05/2003 Accepted Date: 18/09/2003 Online Date: 24/01/2004

We have examined the mechanisms regulating prostacyclin (PG[I.sub.2]) synthesis after acute exposure of human umbilical vein endothelial cells (HUVEC) to interleukin-1 [Alpha] (IL-1 [Alpha]). IL-1 [Alpha] evoked an early (30 min) release of PG[I.sub.2] and [[sup.3.H]] arachidonate that was blocked by the cytosolic phospholipase [A.sub.2] [Alpha] ([cPLA.sub.2] [Alpha]) inhibitor arachidonyl trifluoromethyl ketone. IL-1 [Alpha]-mediated activation of extracellular signal-regulated kinase 1/2 (ERK1/2; p42/[p44.sup.mapk]) coincided temporally with phosphorylation of [cPLA.sub.2] [Alpha] and with the onset of PG[I.sub.2] synthesis. The mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors, PD-98059 and U-0126, blocked IL-1 [Alpha]-induced ERK activation and partially attenuated [cPLA.sub.2] [Alpha] phosphorylation and PG[I.sub.2] release, suggesting that ERK-dependent and -independent pathways regulate [cPLA.sub.2] [Alpha] phosphorylation. SB-203580 treatment enhanced IL-1 [Alpha]-induced MEK, p42/[44.sup.mapk], and [cPLA.sub.2] [Alpha] phosphorylation but reduced thrombin-stimulated MEK and p42/[44.sup.mapk] activation. IL-1 [Alpha], but not thrombin, activated Raf-1 as assessed by immune-complex kinase assay, as did SB-203580 alone. These results show that IL-1 [Alpha] causes an acute upregulation of PG[I.sub.2] generation in HUVEC, establish a role for the MEK/ ERK/[cPLA.sub.2] [Alpha] pathway in this early release, and provide evidence for an agonist-specific cross talk between [p38.sup.mapk] and p42/[44.sup.mapk] that may reflect receptor-specific differences in the signaling elements proximal to MAPK activation. human endothelium; interleukin-1; thrombin; mitogen-activated protein kinases; cytosolic phospholipase [A.sub.2] [Alpha] prostacyclin; extracellular signal-regulated kinase

Introduction The post-war period was an era in which the institutionalisation of children in orphanages, foster care and adopted families was believed to benefit both the children and the community [...]

Thorup, Christian, Caroline L. Jones, Steven S. Gross, Leon C. Moore, and Michael S. Goligorsky. Carbon monoxide induces vasodilation and nitric oxide release but suppresses endothelial NOS. Am. J. Physiol. 277 (Renal Physiol. 46): F882-F889, 1999.--The vascular effects of carbon monoxide (CO) resemble those of nitric oxide (NO), but it is unknown whether the two messengers converge or exhibit reciprocal feedback regulation. These questions were examined in microdissected perfused renal resistance arteries (RRA) studied using NO-sensitive microelectrodes. Perfusion of RRA with buffers containing increasing concentrations of CO resulted in a biphasic release of NO. The NO response peaked at 100 [micro]M CO and then declined to virtually zero at 10 [micro]M. When a series of 50-s pulses of 100 nM CO were applied repeatedly (150-s interval), the amplitude of consecutive NO responses was diminished. NO release from RRA showed dependence on L-arginine but not D-arginine, and the responses to CO were inhibited by pretreatment with [N.sup.G]-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthases (NOS). CO (100 nM) also suppressed NO release induced by 100 [micro]M carbachol, a potent agonist for endothelial NOS (eNOS). RRA from rats in which endogenous CO production from inducible HO was elevated (cobalt chloride 12 h prior to study) also showed suppressed responses to carbachol. Furthermore, responses consistent with these findings were obtained in juxtamedullary afferent arterioles perfused in vitro, where the vasodilatory response to CO was biphasic and the response to acetylcholine was blunted. Collectively, these data suggest that the CO-induced NO release could be attributed to either stimulation of eNOS or to NO displacement from a cellular storage pool. To address this, direct in vitro measurements with an NO-selective electrode of NO production by recombinant eNOS revealed that CO dose-dependently inhibits NO synthesis. Together, the above data demonstrate that, whereas high levels of CO inhibit NOS activity and NO generation, lower concentrations of CO induce release of NO from a large intracellular pool and, therefore, may mimic the vascular effects of NO. kidney; blood vessels; endothelium; heme oxygenase; hemodynamics