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Sample records for higher endothelin relative

  1. Endothelin-1 and endothelin-3 in cirrhosis: relations to systemic and splanchnic haemodynamics

    DEFF Research Database (Denmark)

    Møller, Søren; Gülberg, V; Henriksen, Jens Henrik

    1995-01-01

    BACKGROUND/AIMS: Endothelins are isopeptides with potent vasoactive properties, but their implications in the hyperkinetic syndrome in cirrhosis are obscure. Therefore, the aim of the present study was to relate hepatic venous and circulating endothelin-1 and endothelin-3 to systemic and splanchn...... that the endothelin system is implicated in both systemic and portal haemodynamic abnormalities in cirrhosis, although this study does not allow conclusions on causal relationships....

  2. Myocardial ultrasonic backscatter in hypertension: relation to aldosterone and endothelin.

    Science.gov (United States)

    Kozàkovà, Michaela; Buralli, Simona; Palombo, Carlo; Bernini, Giampaolo; Moretti, Angelica; Favilla, Stefania; Taddei, Stefano; Salvetti, Antonio

    2003-02-01

    A disproportionate accumulation of fibrillar collagen is a characteristic feature of hypertensive heart disease, but the extent of myocardial fibrosis may differ in different models of hypertension. In experimental studies, aldosterone and endothelins emerge as important determinants of myocardial fibrosis. Changes in myocardial extracellular matrix and collagen deposition can be estimated noninvasively by analysis of the ultrasonic backscatter signal, which arises from tissue heterogeneity within the myocardium and describes myocardial texture. This study was designed to investigate the relations between myocardial integrated backscatter and circulating aldosterone and immunoreactive endothelin in human hypertension. The study population consisted of 56 subjects: 14 healthy normotensive volunteers and 42 hypertensive patients (14 with primary aldosteronism, 7 with renovascular hypertension, and 21 with essential hypertension). The patients with essential and secondary hypertension were matched for age, gender, body mass index, and blood pressure. Myocardial integrated backscatter at diastole was 19.8+/-2.0 and 20.8+/-2.9 decibels in normotensive control subjects and patients with essential hypertension and significantly higher in patients with primary aldosteronism (27.4+/-3.8 decibels, P<0.01) and renovascular hypertension (26.8+/-4.8 decibels, P<0.01). In the population as a whole, as well as in the hypertensive subpopulation, myocardial integrated backscatter was directly related to plasma aldosterone (r=0.73 and 0.71, P<0.01 for both) and immunoreactive endothelin (r=0.60 and 0.56, P<0.01 for both). The data of this study suggest that in human hypertension, circulating aldosterone and immunoreactive endothelin may induce alterations in left ventricular myocardial texture, possibly related to increased myocardial collagen content.

  3. Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension

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    Nyberg, Michael Permin; Mortensen, Stefan Peter; Hellsten, Ylva

    2013-01-01

    AIMS: Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension...... and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. METHODS: In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study...... were higher in hypertensive than normotensive individuals. Eight weeks of exercise training normalized plasma endothelin-1 levels in the hypertensive subjects and increased the protein expression of the ET(A) receptor in skeletal muscle of normotensive subjects. Similarly, individuals that had...

  4. Ghrelin restores the endothelin 1/nitric oxide balance in patients with obesity-related metabolic syndrome.

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    Tesauro, Manfredi; Schinzari, Francesca; Rovella, Valentina; Di Daniele, Nicola; Lauro, Davide; Mores, Nadia; Veneziani, Augusto; Cardillo, Carmine

    2009-11-01

    Obesity is associated with endothelial dysfunction related to decreased NO bioavailability, increased endothelin 1 vasoconstrictor activity, and decreased circulating ghrelin. Therefore, we tested whether exogenous ghrelin may have benefits to improve the balance between endothelin 1 and NO in patients with obesity-related metabolic syndrome. Vasoactive actions of endothelin 1 and NO were assessed in 8 patients with metabolic syndrome and 8 matched controls by evaluating forearm blood flow responses (strain-gauge plethysmography) to intra-arterial infusion of BQ-123 (endothelin A receptor antagonist; 10 nmol/min), followed by NG-monomethyl-L-arginine (NO synthase inhibitor; 4 micromol/min), before and after infusion of ghrelin (200 ng/min). In the absence of ghrelin, the vasodilator response to BQ-123 was greater in patients than in controls (Pghrelin decreased the vasodilator response to BQ-123 (P=0.007 versus saline) and enhanced the magnitude of changes in forearm blood flow induced by NG-monomethyl-L-arginine (P=0.003) in patients but not in controls (both P>0.05). The favorable effect of ghrelin on endothelin A-dependent vasoconstriction was likely related to the stimulation of NO production, because no change in the vascular effect of BQ-123 was observed after ghrelin (P=0.44) in 5 patients with metabolic syndrome during continuous infusion of the NO donor sodium nitroprusside (0.2 microg/min). In patients with metabolic syndrome, ghrelin has benefits to normalize the balance between vasoconstrictor (endothelin 1) and vasodilating (NO) mediators, thus suggesting that this peptide has important peripheral actions to preserve vascular homeostasis in humans.

  5. Risk Factors in Normal-Tension Glaucoma and High-Tension Glaucoma in relation to Polymorphisms of Endothelin-1 Gene and Endothelin-1 Receptor Type A Gene

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    Dominika Wróbel-Dudzińska

    2015-01-01

    Full Text Available The aim of the research is to analyse the influence of polymorphisms of endothelin-1 gene and endothelin-1 receptor type A gene on the clinical condition of patients with primary open angle glaucoma. Methods. 285 Polish patients took part in the research (160 normal-tension glaucoma and 125 high-tension glaucoma. DNA was isolated by standard methods and genotype distributions of four polymorphisms in genes encoding endothelin-1 (K198N and endothelin-1 receptor type A polymorphisms (C1222T, C70G, and G231A were determined. Genotype distributions were compared between NTG and HTG groups. The clinical condition of participants was examined for association with polymorphisms. Results. A similar frequency of occurrence of the polymorphic varieties of the studied genes was observed in patients with NTG and HTG. There is no relation between NTG risk factors and examined polymorphisms. NTG patients with TT genotype of K198N polymorphism presented with the lowest intraocular pressure in comparison to GG + GT genotype (p=0.03. In NTG patients with CC genotype of C1222T polymorphism (p=0.028 and GG of C70G polymorphism (p=0.03 the lowest values of mean blood pressure were observed. Conclusions. The studied polymorphic varieties (K198N, C1222T do have an influence on intraocular pressure as well as arterial blood pressure in NTG patients.

  6. Elevated levels of plasma Big endothelin-1 and its relation to hypertension and skin lesions in individuals exposed to arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, Ekhtear; Islam, Khairul; Yeasmin, Fouzia [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi-6205 (Bangladesh); Karim, Md. Rezaul [Department of Applied Nutrition and Food Technology, Islamic University, Kushtia-7003 (Bangladesh); Rahman, Mashiur; Agarwal, Smita; Hossain, Shakhawoat; Aziz, Abdul; Al Mamun, Abdullah; Sheikh, Afzal; Haque, Abedul; Hossain, M. Tofazzal [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi-6205 (Bangladesh); Hossain, Mostaque [Department of Medicine, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka (Bangladesh); Haris, Parvez I. [Faculty of Health and Life Sciences, De Montfort University, Leicester, LE1 9BH (United Kingdom); Ikemura, Noriaki; Inoue, Kiyoshi; Miyataka, Hideki; Himeno, Seiichiro [Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770–8514 (Japan); Hossain, Khaled, E-mail: khossain69@yahoo.com [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi-6205 (Bangladesh)

    2012-03-01

    Chronic arsenic (As) exposure affects the endothelial system causing several diseases. Big endothelin-1 (Big ET-1), the biological precursor of endothelin-1 (ET-1) is a more accurate indicator of the degree of activation of the endothelial system. Effect of As exposure on the plasma Big ET-1 levels and its physiological implications have not yet been documented. We evaluated plasma Big ET-1 levels and their relation to hypertension and skin lesions in As exposed individuals in Bangladesh. A total of 304 study subjects from the As-endemic and non-endemic areas in Bangladesh were recruited for this study. As concentrations in water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The plasma Big ET-1 levels were measured using a one-step sandwich enzyme immunoassay kit. Significant increase in Big ET-1 levels were observed with the increasing concentrations of As in drinking water, hair and nails. Further, before and after adjusting with different covariates, plasma Big ET-1 levels were found to be significantly associated with the water, hair and nail As concentrations of the study subjects. Big ET-1 levels were also higher in the higher exposure groups compared to the lowest (reference) group. Interestingly, we observed that Big ET-1 levels were significantly higher in the hypertensive and skin lesion groups compared to the normotensive and without skin lesion counterpart, respectively of the study subjects in As-endemic areas. Thus, this study demonstrated a novel dose–response relationship between As exposure and plasma Big ET-1 levels indicating the possible involvement of plasma Big ET-1 levels in As-induced hypertension and skin lesions. -- Highlights: ► Plasma Big ET-1 is an indicator of endothelial damage. ► Plasma Big ET-1 level increases dose-dependently in arsenic exposed individuals. ► Study subjects in arsenic-endemic areas with hypertension have elevated Big ET-1 levels. ► Study subjects with arsenic

  7. Validation of endothelin B receptor antibodies reveals two distinct receptor-related bands on Western blot.

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    Barr, Travis P; Kornberg, Daniel; Montmayeur, Jean-Pierre; Long, Melinda; Reichheld, Stephen; Strichartz, Gary R

    2015-01-01

    Antibodies are important tools for the study of protein expression but are often used without full validation. In this study, we used Western blots to characterize antibodies targeted to the N or C terminal (NT or CT, respectively) and the second or third intracellular loop (IL2 or IL3, respectively) of the endothelin B receptor (ETB). The IL2-targeted antibody accurately detected endogenous ETB expression in rat brain and cultured rat astrocytes by labeling a 50-kDa band, the expected weight of full-length ETB. However, this antibody failed to detect transfected ETB in HEK293 cultures. In contrast, the NT-targeted antibody accurately detected endogenous ETB in rat astrocyte cultures and transfected ETB in HEK293 cultures by labeling a 37-kDa band but failed to detect endogenous ETB in rat brain. Bands detected by the CT- or IL3-targeted antibody were found to be unrelated to ETB. Our findings show that functional ETB can be detected at 50 or 37kDa on Western blot, with drastic differences in antibody affinity for these bands. The 37-kDa band likely reflects ETB processing, which appears to be dependent on cell type and/or culture condition. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Endothelin 1 levels in relation to clinical presentation and outcome of Henoch Schonlein purpura

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    Moustaki M

    2008-09-01

    Full Text Available Abstract Background Henoch Schonlein purpura (HSP is a common vasculitis of small vessels whereas endothelin-1 (ET-1 is usually reported elevated in vasculities and systematic inflammation. The aim of the present study was to investigate whether ET-1 levels are correlated with the clinical presentation and the outcome of HSP. Methods The study sample consisted of thirty consecutive patients with HSP. An equal number of healthy patients of similar age and the same gender were served as controls. The patients' age range was 2–12.6 years with a mean ± SD = 6.3 ± 3 years. All patients had a physical examination with a renal, and an overall clinical score. Blood and urinary biochemistry, immunology investigation, a skin biopsy and ET-1 measurements in blood and urine samples were made at presentation, 1 month later and 1 year after the appearance of HSP. The controls underwent the same investigation with the exception of skin biopsy. Results ET-1 levels in plasma and urine did not differ between patients and controls at three distinct time points. Furthermore the ET-1 were not correlated with the clinical score and renal involvement was independent from the ET-1 measurements. However, the urinary ET-1 levels were a significant predictor of the duration of the acute phase of HSP (HR = 0.98, p = 0.032, CI0.96–0.99. The ET-1 levels did not correlate with the duration of renal involvement. Conclusion Urinary ET-1 levels are a useful marker for the duration of the acute phase of HSP but not for the length of renal involvement.

  9. Endothelin-1 Plasma Levels in Patients with both Retinitis Pigmentosa and Flammer Syndrome.

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    Todorova, M G; Josifova, T; Konieczka, K

    2015-04-01

    Endothelin-1 is a strong endogenous vasoconstrictor and is also an agent reducing the ocular blood flow. Patients with retinitis pigmentosa are known to have reduced ocular blood flow. This can be secondary to retinal atrophy, but may also partially result from an additional condition, such as a Flammer syndrome. The aim of the study was to investigate whether the endothelin-1 plasma levels in retinitis pigmentosa patients with and without Flammer syndrome are different. In the study we included patients with clinical signs and symptoms of retinitis pigmentosa, confirmed by electrophysiological findings. Blood samples were obtained from 6 retinitis pigmentosa patients with and 4 without Flammer syndrome. The results were related to 30 age- and sex-matched control subjects. Endothelin-1 plasma levels were determined by specific radioimmunoassay. The endothelin-1 plasma levels in retinitis pigmentosa patients with Flammer syndrome were significantly higher than those without Flammer syndrome. The mean (±SD) endothelin-1 levels (pg/mL) in retinitis pigmentosa patients with Flammer syndrome were 4.95 (±1.74), range: (2.37-6.76), whereas in patients without Flammer syndrome they were 1.10 (±0.08), range: 1.00-1.20. Our own normal values are: 1.56 (±0.30), range: (0.90-2.13). All retinitis pigmentosa patients with increased endothelin-1 plasma levels had signs and symptoms related to a Flammer syndrome, such as cold extremities, low blood pressure, reduced feeling of thirst, increased sensitivity in general, e.g., increased sensitivity to certain drugs, increased pain sensitivity and increased sense of smell. Endothelin-1 plasma levels were increased in retinitis pigmentosa patients with but not in patients without Flammer syndrome. Many questions remain open: Why so many retinitis pigmentosa patients suffer from Flammer syndrome, why is the endothelin-1 level in such patients higher than in healthy subjects with Flammer syndrome, how much of the ocular blood flow

  10. Endothelins & erectile dysfunction.

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    Ritchie, Robert; Sullivan, Mark

    2011-06-01

    Erectile dysfunction (ED) is common and a significant contributor to poor quality of life and psychosocial morbidity in men. Normal erectile function requires effective co-ordination between a number of complex neural pathways. Penile tumescence occurs in response to rapid arterial inflow to the corpora cavernosa with simultaneous venous outflow restriction due to expansion of the lacunar spaces. This process is under both central and local neuromediation. Endothelins are potent vasoconstrictor peptides that cause strong, slowly developing but sustained contraction of trabecular smooth muscles cells of the corpora cavernosa. Multiple mechanisms of action are proposed, including transmembrane calcium flux, mobilisation of inositol triphosphate sensitive intracellular calcium stores and calcium sensitisation through the Rho-Rho kinase pathway. The exact role of endothelins in the pathogenesis of ED currently remains unclear. Elevated endothelin-1 levels are found in patients with diabetes mellitus and this alone may be sufficient to cause ED. However, this is not borne out in clinical studies. The resultant elevated intracellular calcium may, however, modulate gene expression sufficiently to cause smooth muscle proliferation. Alternatively, alterations in endothelin receptor sensitivity in conditions such as diabetes and hypertension may enhance vasoconstrictor processes. Currently there is contradictory evidence for the role of endothelin receptor antagonists in ED. Animals studies suggest they inhibit corporal vasoconstriction, improve erectile function and protect against diabetes-induced smooth muscle apoptosis. However, the results of clinical studies in ED have been less promising. Uncertainty regarding the exact role of endothelin in penile erection hampers progress in this area. It is possible that the endothelin system may only be relevant to ED in certain conditions where global endothelial dysfunction exists (e.g. diabetes mellitus, systemic sclerosis) and

  11. Correlation between plasma endothelin-1 levels and severity of septic liver failure quantified by maximal liver function capacity (LiMAx test. A prospective study.

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    Magnus F Kaffarnik

    Full Text Available To investigate the relationship between the degree of liver dysfunction, quantified by maximal liver function capacity (LiMAx test and endothelin-1, TNF-α and IL-6 in septic surgical patients.28 septic patients (8 female, 20 male, age range 35-80y were prospectively investigated on a surgical intensive care unit. Liver function, defined by LiMAx test, and measurements of plasma levels of endothelin-1, TNF-α and IL-6 were carried out within the first 24 hours after onset of septic symptoms, followed by day 2, 5 and 10. Patients were divided into 2 groups (group A: LiMAx ≥100 μg/kg/h, moderate liver dysfunction; group B: LiMAx <100 μg/kg/h, severe liver dysfunction for analysis and investigated regarding the correlation between endothelin-1 and the severity of liver failure, quantified by LiMAx test.Group B showed significant higher results for endothelin-1 than patients in group A (P = 0.01, d5; 0.02, d10. For TNF-α, group B revealed higher results than group A, with a significant difference on day 10 (P = 0.005. IL-6 showed a non-significant trend to higher results in group B. The Spearman's rank correlation coefficient revealed a significant correlation between LiMAx and endothelin-1 (-0.434; P <0.001, TNF-α (-0.515; P <0.001 and IL-6 (-0.590; P <0.001.Sepsis-related hepatic dysfunction is associated with elevated plasma levels of endothelin-1, TNF-α and IL-6. Low LiMAx results combined with increased endothelin-1 and TNF-α and a favourable correlation between LiMAx and cytokine values support the findings of a crucial role of Endothelin-1 and TNF-α in development of septic liver failure.

  12. Role of endothelin in preeclampsia and hypertension following antiangiogenesis treatment.

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    Saleh, Langeza; Danser, Jan A H; van den Meiracker, Anton H

    2016-03-01

    Preeclampsia is a systemic, pregnancy-related disorder featuring hypertension and proteinuria arising from placental overproduction of soluble FMS-like tyrosine kinase-1, resulting in an antiangiogenic state because of the inhibition of the vascular endothelial growth factor (VEGF) family. Similarly, antiangiogenetic treatment aimed at targeting VEGF in patients with cancer is associated with a preeclampsia-like syndrome. In this study we discuss the pathophysiological role of an activated endothelin system in both conditions. In different experimental forms of preeclampsia, in clinical preeclampsia, and in cancer patients on antiangiogenic treatment, activation of the endothelin axis invariably occurs and this activation is directly related to the circulating level of sFlt-1 or the intensity of antiangiogenic treatment. Administration of endothelin receptor A-selective or dual endothelin receptor antagonists can prevent or largely attenuate the hypertension and proteinuria in experimental forms of preeclampsia, as well as in rats exposed to receptor tyrosine-kinase inhibitors targeting VEGF-signaling, supporting the concept that activation of the endothelin axis plays a key role in the manifestations of these disorders. Activation of the endothelin axis has now emerged as a crucial player in the manifestations of preeclampsia and following antiangiogenic treatment. As a consequence, blockade of the endothelin system may be considered as a treatment option both in preeclampsia and in antiangiogenesis-induced hypertension and renal toxicity in patients with cancer.

  13. Impact of angiotensin and endothelin converting enzymes and related bradykinin on renal functions in L-NAME hypertensive rats

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    Omar, Ali Zainal; Maulood, Ismail M.

    2017-09-01

    The renin-angiotensin system (RAS), one of the most important hormonal systems, controls the kidney functions by regulating fluid volume, and electrolyte balance. The current study included the effects of kinin-kallikrein system (KKS) and its interaction with both angiotensin converting enzyme (ACE) and endothelin converting enzyme (ECE) on some of kidney function test parameters. In the present experiment, rats were divided into six groups, the first group was infused with normal saline, the second group was L-NG-Nitroarginine methyl ester (L-NAME) treated rats, third group was bradykinin (BK), forth group was captopril (ACEi), fifth group was phosphoramidon (ECEi), sixth group was a combination of BK with phosphoramidon. L-NAME was intravenously infused for one hour to develop systematic hypertension in male rats. After one hour of infusion, the results showed that L-NAME significantly increased serum creatinine. While, it decreased glomerular filtration rate (GFR), and K+ excretion rate. Moreover, BK increased packed cell volume PCV%, serum creatinine and K+ ion concentration. While, it reduced GFR, serum Ca+2 ion concentration, K+ and Na+ excretion rates. On the other hand, captopril infusion showed its effect by reduction in GFR, serum Ca+2 ion and electrolyte excretion rates. Phosphoramidon an ECEi dramatically reduced serum Ca+2 ion, but it increased pH, GFR and Ca+2 excretion rate. The results suggested that BK and Captopril each alone severely reduces GFR value. Interestingly, inhibition of ET-1 production via phosphoramidon could markedly elevate GFR values.

  14. Elevated circulating plasma endothelin-1 concentrations in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Emmeluth, C; Henriksen, Jens Henrik

    1993-01-01

    As endothelin-1 (ET-1), a potent vasoconstricting peptide, may play a role in the circulatory derangement and renal impairment in cirrhosis, the aim of the present study was to investigate plasma concentrations of ET-1 in different vascular beds in relation to clinical and biochemical parameters...... of liver function. Median brachial venous ET-1 concentrations were substantially higher in patients with cirrhosis (3.40 pg/ml, range: 1.25-7.84, n = 24) than in controls (1.53 pg/ml, range: 0.78-2.12, n = 11) (P ....70, P plasma concentration between the liver, renal, or femoral...

  15. Endothelins in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    1996-01-01

    renal failure. Studies on liver biopsies have revealed synthesis of ET-1 in hepatic endothelial and other cells, and recent investigations have identified the hepatosplanchnic system as a major source of ET-1 and ET-3 spillover into the circulation, with a direct relation to portal venous hypertension......This review describes recent progress in the accumulation of knowledge about the endothelins (ETs), a family of vasoactive 21-amino acid polypeptides, in chronic liver disease. Particular prominence is given to the dynamics of ET-1 and ET-3 and their possible relation to the disturbed circulation...... and neurohumoral dysregulation found in cirrhosis. Recent studies have shown that the ET system is highly activated in most cirrhotic patients. Circulating ET-1 and ET-3 levels have a positive relation to the severity of the disease and fluid retention, with the highest values recorded in patients with functional...

  16. Calcitonin gene-related peptide protects the myocardium from ischemia induced by endothelin-1: intravital microscopic observation and (31)P-MR spectroscopic studies.

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    Homma, Satoshi; Kimura, Taizo; Sakai, Satoshi; Yanagi, Ken-ichi; Miyauchi, Yumi; Aonuma, Kazutaka; Miyauchi, Takashi

    2014-11-24

    Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide. We investigated the ameliorating effect of CGRP in myocardial ischemia induced by endothelin-1 (ET-1), with special emphasis on myocardial microvascular hemodynamics and levels of energy-related metabolites. The Langendorff preparations of rat isolated heart were perfused at a constant flow rate. Microvascular blood flow was also visualized in the anterior epicardium of the left ventricle by means of an intravital fluorescence microscope system. Energy-related metabolite contents in the myocardium were measured by means of (31)P-magnetic resonance spectroscopy ((31)P-MRS). Intracoronary bolus injections of CGRP caused dose-dependent decreases in coronary perfusion pressure (CPP) in the hearts exposed to ET-1 (30 pmol). The vasodilator potency of CGRP was about 10,000-fold greater than that of nitroglycerin and 1,000-fold greater than that of isobutylmethylxanthine. Vasodilation of the small-sized arterioles (10-40 μm in diameter) in response to CGRP (100 pmol) was confirmed by direct microscopic observation. After ET-1 (30 pmol) plus vehicle administration, high energy phosphates (phosphocreatine (PCr), ATP) were markedly reduced (pchanges in the myocardium (decrease in PCr) and macrohemodynamic alterations (increase in CPP, decrease in dP/dt etc.) induced by ET-1. We conclude that CGRP effectively confers hemodynamic and metabolic protections to isolated beating hearts against ET-1-induced myocardial ischemia. Copyright © 2014. Published by Elsevier Inc.

  17. Endothelins in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, S; Henriksen, Jens Henrik Sahl

    1996-01-01

    This review describes recent progress in the accumulation of knowledge about the endothelins (ETs), a family of vasoactive 21-amino acid polypeptides, in chronic liver disease. Particular prominence is given to the dynamics of ET-1 and ET-3 and their possible relation to the disturbed circulation...... renal failure. Studies on liver biopsies have revealed synthesis of ET-1 in hepatic endothelial and other cells, and recent investigations have identified the hepatosplanchnic system as a major source of ET-1 and ET-3 spillover into the circulation, with a direct relation to portal venous hypertension....... In addition, marked associations with disturbance of systemic haemodynamics and with abnormal distribution of blood volume have been reported. Although the pathophysiological importance of the ET system in chronic liver disease is not completely understood, similarities to other vasopressive...

  18. Plasma endothelin-1 and single nucleotide polymorphisms of endothelin-1 and endothelin type A receptor genes as risk factors for normal tension glaucoma.

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    Kosior-Jarecka, Ewa; Wróbel-Dudzińska, Dominika; Łukasik, Urszula; Aung, Tin; Khor, Chiea Chuen; Kocki, Janusz; Żarnowski, Tomasz

    2016-01-01

    The purpose of this study was to determine whether four single nucleotide polymorphisms (SNPs) of endothelin and endothelin receptor type A genes can constitute a risk factor for normal tension glaucoma (NTG) and high tension glaucoma (HTG). The study included 160 patients with NTG, 124 patients with HTG, and 165 healthy controls. To analyze the frequency of polymorphic variants of the endothelin EDN gene (K198N) and the endothelin receptor type A gene EDN RA (C1222T, C70G, G231A), DNA was isolated from peripheral blood, and SNP genotyping was performed using the real-time PCR (RT-PCR) method. Plasma endothelin (ET) concentrations were detected using an enzyme immunoassay. Endothelin levels were compared with genotype and allele distributions, patients' clinical status, and various risk factors for NTG. There was a significant difference between the patients with NTG and HTG and the controls (p = 0.035, p = 0.008) regarding the genotype of the C1222T and C70G polymorphism. Plasma concentrations of ET did not differ between the NTG and HTG groups, and no significant correlation with intraocular pressure (IOP), best-corrected visual acuity (BCVA), and the cup to disc ratio (c/d ratio) was seen in patients with NTG. Plasma endothelin levels showed a noticeably positive correlation with age in the NTG group (R = 0.249, p = 0.042). Higher endothelin levels corresponded to more advanced visual field damage. No statistical difference was observed between variant genotypes of K198N and the ET-1 plasma concentration in patients with NTG, whereas a slightly higher ET level was observed in the patients with HTG with the GT genotype in comparison to those with the GG genotype (p = 0.001). The C1222T polymorphism significantly affected the plasma ET level in patients with NTG. The TT genotype carriers had the highest ET level, and the CC genotype carriers the lowest (p = 0.034). The AA variant genotype of the G231A polymorphism exhibited the highest ET level, while the GG

  19. Long-lasting physiological antagonism of calcitonin gene-related peptide towards endothelin-1 in rat mesenteric arteries and human coronary arteries

    DEFF Research Database (Denmark)

    Labruijere, Sieneke; Compeer, Matthijs G; van den Bogaerdt, Antoon J

    2013-01-01

    Endothelin-1 causes long-lasting contraction via endothelin type A receptor (ETAR) in isolated rat mesenteric arteries (RMA) that cannot be readily terminated by removing the agonist, or by adding the ETAR antagonist BQ123 or the NO donor sodium nitroprusside. It could be terminated by adding......-lasting non-selective arterial smooth muscle relaxation that may add to the neuropeptide being a physiological antagonist of arterial effects of ET-1. Long-lasting, washout-resistant ET-1/ETAR interaction does not occur in HCMAs....

  20. Amygdalin improves microcirculatory disturbance and attenuates pancreatic fibrosis by regulating the expression of endothelin-1 and calcitonin gene-related peptide in rats.

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    Zhang, Xiangqun; Hu, Jiangong; Zhuo, Yuzhen; Cui, Lihua; Li, Caixia; Cui, Naiqiang; Zhang, Shukun

    2017-11-09

    The pathogenesis of chronic pancreatitis (CP) is a complex process of interaction between tissue injury and repair, which involves microcirculatory disturbance. Amygdalin, an effective component extracted from Semen Persicae (a kind of Chinese herbal medicine), can decrease blood viscosity and improve microcirculation. In this study, we investigated the therapeutic effects of amygdalin on pancreatic fibrosis in rats with CP. The rat CP model was induced by injecting dibutyltin dichloride (DBTC) into the right caudal vein. Amygdalin was administrated via the penile vein at a dose of 10 mg/(kg d) from the next day, after the induction of CP, once a day for the previous 3 days, and then once every 2 days, until the end of the experiment. Body weight was observed every 7 days. Pancreatic blood flow and histopathological changes were assessed at 28 days. The activation of pancreatic stellate cells (PSCs) was estimated by the expression of α-smooth muscle actin (α-SMA). At the same time, the expression of platelet-derived growth factor-BB (PDGF-BB), transforming growth factor β-1 (TGFβ-1), endothelin-1 (ET-1), and calcitonin gene-related peptide (CGRP) of pancreatic tissues were detected. Treatment of CP rats with amygdalin improved body weight and pancreatic blood flow, as well as alleviated pancreatic fibrosis and acinar destruction, accompanied by the down-regulation of the expressions of α-SMA, PDGF-BB, TGFβ-1, and ET-1, and the up-regulation of the CGRP's expression. Amygdalin could reduce the production of pro-fibrotic cytokines, inhibit the activation of PSCs, and attenuate pancreatic fibrosis in a rat with CP. The mechanism probably includes improving microcirculatory disturbance by regulating the production of ET-1 and CGRP. Copyright © 2017. Published by Elsevier Taiwan LLC.

  1. Targeting the ROS-HIF-1-endothelin axis as a therapeutic approach for the treatment of obstructive sleep apnea-related cardiovascular complications.

    Science.gov (United States)

    Belaidi, Elise; Morand, Jessica; Gras, Emmanuelle; Pépin, Jean-Louis; Godin-Ribuot, Diane

    2016-12-01

    Obstructive sleep apnea (OSA) is now recognized as an independent and important risk factor for cardiovascular diseases such as hypertension, coronary heart disease, heart failure and stroke. Clinical and experimental data have confirmed that intermittent hypoxia is a major contributor to these deleterious consequences. The repetitive occurrence of hypoxia-reoxygenation sequences generates significant amounts of free radicals, particularly in moderate to severe OSA patients. Moreover, in addition to hypoxia, reactive oxygen species (ROS) are potential inducers of the hypoxia inducible transcription factor-1 (HIF-1) that promotes the transcription of numerous adaptive genes some of which being deleterious for the cardiovascular system, such as the endothelin-1 gene. This review will focus on the involvement of the ROS-HIF-1-endothelin signaling pathway in OSA and intermittent hypoxia and discuss current and potential therapeutic approaches targeting this pathway to treat or prevent cardiovascular disease in moderate to severe OSA patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. 25 Years of endothelin research

    DEFF Research Database (Denmark)

    Emoto, Noriaki; Vignon-Zellweger, Nicolas; Lopes, Rhéure Alves Moreira

    2014-01-01

    of Japanese poetry originating from consisting of no more than three short verses and 27 on, or Japanese phonetic units) to describe the magic of endothelin science which they presented to the conference audience at the anniversary ceremony. The text of each haiku - both in its original language together...

  3. Elevated circulating plasma endothelin-1 concentrations in cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Emmeluth, C; Henriksen, Jens Henrik Sahl

    1993-01-01

    As endothelin-1 (ET-1), a potent vasoconstricting peptide, may play a role in the circulatory derangement and renal impairment in cirrhosis, the aim of the present study was to investigate plasma concentrations of ET-1 in different vascular beds in relation to clinical and biochemical parameters.......70, P plasma concentration between the liver, renal, or femoral...

  4. Endothelin induces two types of contractions of rat uterus: phasic contractions by way of voltage-dependent calcium channels and developing contractions through a second type of calcium channels

    Energy Technology Data Exchange (ETDEWEB)

    Kozuka, M.; Ito, T.; Hirose, S.; Takahashi, K.; Hagiwara, H.

    1989-02-28

    Effects of endothelin on nonvascular smooth muscle have been examined using rat uterine horns and two modes of endothelin action have been revealed. Endothelin (0.3 nM) caused rhythmic contractions of isolated uterus in the presence of extracellular calcium. The rhythmic contractions were completely inhibited by calcium channel antagonists. These characteristics of endothelin-induced contractions were very similar to those induced by oxytocin. Binding assays using /sup 125/I-endothelin showed that endothelin and the calcium channel blockers did not compete for the binding sites. However, endothelin was unique in that it caused, in addition to rhythmic contractions, a slowly developing monophasic contraction that was insensitive to calcium channel blockers. This developing contraction became dominant at higher concentrations of endothelin and was also calcium dependent.

  5. Plasma level of big endothelin-1 predicts the prognosis in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Wang, Yilu; Tang, Yida; Zou, Yubao; Wang, Dong; Zhu, Ling; Tian, Tao; Wang, Jizheng; Bao, Jingru; Hui, Rutai; Kang, Lianming; Song, Lei; Wang, Ji

    2017-09-15

    Cardiac remodeling is one of major pathological process in hypertrophic cardiomyopathy (HCM). Endothelin-1 has been linked to cardiac remodeling. Big endothelin-1 is the precursor of endothelin-1. A total of 245 patients with HCM were enrolled from 1999 to 2011 and partitioned to low, middle and high level groups according to their plasma big endothelin-1 levels. At baseline, significant associations were found between high level of big endothelin-1 and left atrium size, heart function and atrial fibrillation. Big endothelin-1 was positively correlated with N-terminal B-type natriuretic peptide (r=0.291, pbig endothelin-1 level was positively associated with the risks of all-cause mortality, cardiovascular death and progression to NYHA class 3 or 4 (p=0.020, 0.044 and 0.032, respectively). The rate of above events in the highest tertile were 18.1%, 15.7%, 24.2%, respectively. After adjusting for multiple factors related to survival and cardiac function, the significance remained in the association of big endothelin-1 with the risk of all-cause mortality (hazard ratio (HR)=4.94, 95% confidence interval (CI) 1.07-22.88; p=0.041) and progression to NYHA class 3 or 4 (HR=4.10, 95%CI 1.32-12.75, p=0.015). Our study showed that high level of plasma big endothelin-1 predicted prognosis for patients with HCM and it can be added to the marker panel in stratifying HCM patients for giving treatment priority to those at high risk. Copyright © 2017. Published by Elsevier B.V.

  6. Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Satwiko, Muhammad Gahan [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Ikeda, Koji [Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Nakayama, Kazuhiko [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Yagi, Keiko [Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Hocher, Berthold [Institute for Nutritional Science, University of Potsdam, Potsdam (Germany); Hirata, Ken-ichi [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Emoto, Noriaki, E-mail: emoto@med.kobe-u.ac.jp [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan)

    2015-09-25

    Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. - Highlights: • Role of endothelin-1 in pulmonary arterial hypertension (PAH) was investigated. • The endothelin-1 transgenic (ETTG) and wild type (WT) mice were analyzed. • ETTG mice spontaneously developed PAH under normoxia conditions. • SU5416 further aggravated PAH in ETTG mice. • Enhanced endothelin system activity could be a causative factor in

  7. Elevated endothelin-1 level is a risk factor for nonocclusive mesenteric ischemia.

    Science.gov (United States)

    Groesdonk, Heinrich V; Raffel, Miriam; Speer, Thimoteus; Bomberg, Hagen; Schmied, Wolfram; Klingele, Matthias; Schäfers, Hans-Joachim

    2015-05-01

    Nonocclusive mesenteric ischemia may occur after cardiac surgery, commonly in conjunction with the use of cardiopulmonary bypass. Some evidence suggests that endothelin-1 serum levels are increased in patients with mesenteric ischemia, but the association of endothelin-1 and nonocclusive mesenteric ischemia has not been studied. The objective was to investigate whether elevated levels of endothelin-1 could be found in patients exhibiting nonocclusive mesenteric ischemia. In an observational cohort study, nonocclusive mesenteric ischemia developed in 78 of 865 patients undergoing elective cardiac surgery. Control patients were identified from the cohort through 1:1 propensity score matching. Preoperative and postoperative endothelin-1 serum levels were determined by means of enzyme-linked immunosorbent assay. Odds ratios (with 95% confidence interval) were calculated by logistic regression analyses to determine the risk of endothelin-1 for the development of nonocclusive mesenteric ischemia. Patients with nonocclusive mesenteric ischemia had higher preoperative (11.3 vs 9.3 pg/mL; P = .001) and postoperative (15.7 vs 11.1 pg/mL, P mesenteric ischemia increased with each picogram/milliliter endothelin-1 level preoperatively (odds ratio, 1.29; 95% confidence interval, 1.12-1.49) and each picogram/milliliter postoperatively (odds ratio, 2.04; 95% confidence interval, 1.54-2.72). Receiver operating characteristic analyses showed that elevated endothelin-1 serum levels had a high accuracy to predict nonocclusive mesenteric ischemia (optimal cutoff value of 14.5 pg/mL, area under the curve of 0.77, sensitivity 51%, and specificity 94%). Endothelin-1 seems to predispose patients undergoing cardiac surgery to develop nonocclusive mesenteric ischemia. In addition, it may be a useful marker to identify patients at risk for nonocclusive mesenteric ischemia after cardiac surgery. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All

  8. Cerebrovascular endothelin receptor upregulation in cerebral ischemia

    DEFF Research Database (Denmark)

    Edvinsson, Lars

    2009-01-01

    either by an embolus or by local thrombosis. Several studies have shown an involvement of the endothelin system in ischemic stroke. This review aims to examine the alterations of vascular endothelin receptor expression in ischemic stroke. Furthermore, studies of the intracellular signalling pathways...... leading to the enhanced expression of vascular endothelin receptors show that both protein kinase C (PKC) and mitogen activating protein kinase (MAPK) play important roles. The results from this work provide new perspectives on the pathophysiology of ischemic stroke, and give a possible explanation...

  9. Umbilical cord blood and neonatal endothelin-1 levels in preterm newborns with and without respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    A.C.W. Benjamin

    2005-09-01

    Full Text Available Increased pulmonary vascular resistance in preterm newborn infants with respiratory distress syndrome is suggested, and endothelin-1 plays an important role in pulmonary vascular reactivity in newborns. We determined umbilical cord blood and neonatal (second sample levels of endothelin-1 in 18 preterm newborns with respiratory distress syndrome who had no clinical or echocardiographic diagnosis of pulmonary hypertension and 22 without respiratory distress syndrome (gestational ages: 31.4 ± 1.6 and 29.3 ± 2.3 weeks, respectively. Umbilical cord blood and a second blood sample taken 18 to 40 h after birth were used for endothelin-1 determination by enzyme immunoassay. Median umbilical cord blood endothelin-1 levels were similar in both groups (control: 10.9 and respiratory distress syndrome: 11.4 pg/mL and were significantly higher than in the second sample (control: 1.7 pg/mL and respiratory distress syndrome: 3.5 pg/mL, P < 0.001 for both groups. Median endothelin-1 levels in the second sample were significantly higher in children with respiratory distress syndrome than in control infants (P < 0.001. There were significant positive correlations between second sample endothelin-1 and Score for Neonatal Acute Physiology and Perinatal Extension II (r = 0.36, P = 0.02, and duration of mechanical ventilation (r = 0.64, P = 0.02. A slower decline of endothelin-1 from birth to 40 h of life was observed in newborns with respiratory distress syndrome when compared to controls. A significant correlation between neonatal endothelin-1 levels and some illness-severity signs suggests that endothelin-1 plays a role in the natural course of respiratory distress syndrome in preterm newborns.

  10. Endothelin Blockade in Diabetic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Lidia Anguiano

    2015-05-01

    Full Text Available Diabetic kidney disease (DKD remains the most common cause of chronic kidney disease and multiple therapeutic agents, primarily targeted at the renin-angiotensin system, have been assessed. Their only partial effectiveness in slowing down progression to end-stage renal disease, points out an evident need for additional effective therapies. In the context of diabetes, endothelin-1 (ET-1 has been implicated in vasoconstriction, renal injury, mesangial proliferation, glomerulosclerosis, fibrosis and inflammation, largely through activation of its endothelin A (ETA receptor. Therefore, endothelin receptor antagonists have been proposed as potential drug targets. In experimental models of DKD, endothelin receptor antagonists have been described to improve renal injury and fibrosis, whereas clinical trials in DKD patients have shown an antiproteinuric effect. Currently, its renoprotective effect in a long-time clinical trial is being tested. This review focuses on the localization of endothelin receptors (ETA and ETB within the kidney, as well as the ET-1 functions through them. In addition, we summarize the therapeutic benefit of endothelin receptor antagonists in experimental and human studies and the adverse effects that have been described.

  11. Elevated Plasma Endothelin-1 and Pulmonary Arterial Pressure in Children Exposed to Air Pollution

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Vincent, Renaud; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Barragán-Mejía, Gerardo; Garrido-García, Luis; Camacho-Reyes, Laura; Valencia-Salazar, Gildardo; Paredes, Rogelio; Romero, Lina; Osnaya, Hector; Villarreal-Calderón, Rafael; Torres-Jardón, Ricardo; Hazucha, Milan J.; Reed, William

    2007-01-01

    Background Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure. Objectives The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O3 that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures. Methods We conducted a study of 81 children, 7.9 ± 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O3 levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography. Results Mexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 μm in aerodynamic diameter (PM2.5) before endothelin-1 measurement (p = 0.03). Conclusions Chronic exposure of children to PM2.5 is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure. PMID:17687455

  12. Selective endothelin A-receptor blockade attenuates coronary microvascular dysfunction after coronary stenting in patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Nikolaos Östlund Papadogeorgos

    2009-10-01

    Full Text Available Nikolaos Östlund Papadogeorgos, Mattias Bengtsson, Majid KalaniKarolinska Institute, Department of Clinical Sciences, Department of Cardiology, Danderyd Hospital, Stockholm, SwedenBackground: Endothelin-1 may be involved in the development of diabetic microangiopathy. We studied the effect of endothelin-1 blockade on myocardial microcirculation during coronary stenting.Patients and methods: Patients with type 2 diabetes and stable coronary artery disease undergoing elective percutaneous coronary intervention (PCI were randomized to bolus dose of 500 mg bosentan (n = 4, a dual endothelin receptor blocker, or intracoronary administration of 0.03 mmol BQ123 (n = 6, a selective endothelin A-receptor blocker, or placebo (n = 5, respectively. Coronary flow reserve (CFR was measured immediately post-PCI. CFR was also measured in five nondiabetic controls post-coronary stenting.Results: Patients in the placebo group had (P < 0.05 lower values of CFR (2.3 ± 1.2 as compared to those who received endothelin blockade (n = 10; 3.1 ± 0.7 and nondiabetic controls (4.9 ± 2.3. Patients who received BQ123 showed significantly higher CFR (3.3 ± 0.5; P < 0.05 as compared to those on placebo. Nondiabetic patients had significantly higher CFR as compared to patients with diabetes (4.9 ± 2.3 and 2.8 ± 1.0, respectively; P < 0.05. Conclusion: Coronary microvascular dysfunction is present during coronary stenting in patients with type 2 diabetes and may be reversed by selective endothelin A-receptor blockade. Targeting endothelin system may be of importance in protecting the myocardium against ischemic events during elective PCI in type 2 diabetic patients.Keywords: coronary flow reserve, diabetes, endothelin-1, coronary artery disease, coronary angioplasty

  13. Reduction of Uterine Perfusion Pressure Induced Redistribution of Endothelin Receptor Type-B Between the Intima and Media Contributes to the Pathogenesis of Pregnancy-Induced Hypertension.

    Science.gov (United States)

    Sun, Yuan; Zhang, Xicheng; Chen, Zhaolei; Xu, Miao; Ou, Minghui

    2017-12-06

    Studies have shown that a change in endothelin receptor expression in the artery is related to pregnancy-induced hypertension (PIH). However, the mechanism underlying this change remains unclear. To test whether the distribution of endothelin receptor type-A (ETAR) and type-B (ETBR) plays an important role in PIH, a reduction of uterine perfusion pressure (RUPP) rat model was used to mimic some of the features of PIH; the resulting variable endothelin receptor expression was investigated in the media and intima of the aorta. Single vascular smooth muscle cells (VSMCs) were isolated from RUPP and normal pregnant (NP) rats to study the effect of ETAR and ETBR in smooth muscle cells. Compared with NP rats, RUPP rats had a significant redistribution of ETBR expression in the intima and media, while there was no significant difference in ETAR expression between the two groups. ETBR upregulation in VSMCs enhanced cellular contraction and contributed to PIH. The TNF-α plasma levels in RUPP rats were two-fold higher than those of NP rats, which upregulated the expression of ETBR in VSMCS through the NF-κB pathways in RUPP rats. Redistribution of ETBR between the media and intima played an important role in the pathogenesis of PIH. © 2017 The Author(s). Published by S. Karger AG, Basel.

  14. Health-related quality of life in pain-free or mildly symptomatic patients with metastatic hormone-resistant prostate cancer following treatment with the specific endothelin A receptor antagonist zibotentan (ZD4054).

    Science.gov (United States)

    Dawson, Nancy; Payne, Heather; Battersby, Clare; Taboada, Maria; James, Nick

    2011-01-01

    Zibotentan (ZD4054) is a specific endothelin A receptor antagonist in clinical development for the treatment of hormone-resistant prostate cancer (HRPC). In a Phase II trial in patients with pain-free or mildly symptomatic metastatic HRPC, zibotentan was well tolerated with a promising signal for prolonged overall survival compared with placebo. As part of this trial, the impact of zibotentan compared with placebo on health-related quality of life (HRQoL) was assessed. Patients were randomized to receive once-daily oral zibotentan 10 or 15 mg, or matching placebo. Patients were allocated to one of two questionnaires; the Functional Assessment of Cancer Therapy-Prostate (FACT-P) or the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), supplemented by PR25, specific for prostate cancer. Questionnaires were completed at baseline and every 4 weeks until disease progression when study treatment was discontinued. Compliance with questionnaire completion was >90% (286 of 312 patients) of the intention-to-treat population at baseline. Of baseline completers who were available for assessment (i.e., had not clinically progressed), 89% (164 of 184) and 83% (73 of 88) completed questionnaires at 12 and 24 weeks, respectively. HRQoL scores from both questionnaires were high at baseline and remained high throughout the study, with scores being similar in the zibotentan and placebo groups. However, some floor and ceiling effects were seen in the EORTC QLQ-C30 questionnaire. High-baseline HRQoL scores were maintained throughout treatment with zibotentan. The FACT-P instrument was selected to further assess the impact of zibotentan on HRQoL in the Phase III clinical trial program.

  15. Three Traditions of Democracy in Relation to American Higher Education

    Science.gov (United States)

    Sternberg, Robert J.

    2014-01-01

    The type of college or university one values most depends, at least in part, upon which of three distinct traditions of democracy in relation to American higher education one espouses. In this article, the author identifies three distinct traditions of democracy in relation to American higher education and suggests that the type of college or…

  16. [Hepatotoxicity in patients treated with endothelin receptor antagonists: systematic review and meta-analysis of randomized clinical trials].

    Science.gov (United States)

    Macías Saint-Gerons, Diego; de la Fuente Honrubia, César; Montero Corominas, Dolores; Catalá-López, Ferrán

    2014-04-22

    We evaluated the risk of hepatotoxicity associated to endothelin receptor antagonists. Systematic searches in PubMed/MEDLINE, the Cochrane Library as well as regulatory agencies websites were performed. Randomized controlled trials in patients receiving endothelin receptor antagonists (bosentan, sitaxentan or ambrisentan) in at least one treatment group were included. Prior to data extraction, definitions of hepatotoxicity were established. Effect sizes with 95% confidence intervals were calculated using random effects models. Heterogeneity was analysed using Cochran's Q and I(2) tests. Publication bias was assessed using Egger's method and funnel plots were generated. Twenty-one trials met the inclusion criteria (3,644 patients). Bosentan was the evaluated drug in 1,689 (74%) patients who received endothelin receptor antagonists. Compared with controls, relative risk for any hepatic adverse reaction was 2.92 (1.85-4.62; I(2)=30.6%). When hepatotoxicity was defined as elevations of liver alanine or aspartate aminotransferases equal or greater than 3 times the upper limit of normal, relative risk was 2.98 (1.69-5.25; I(2) = 40.9%). No evidence of publication bias was found (Egger's method: p = 0.68). Our results suggest an increased risk of hepatotoxicity in patients receiving endothelin receptor antagonists. Given the limited data available for endothelin receptor antagonists other than bosentan, it is not possible to draw firm conclusions about the individual risk associated for the remaining endothelin receptor antagonists. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  17. Endothelin-1 increases melanin synthesis in an established sheep skin melanocyte culture.

    Science.gov (United States)

    Pang, Yamiao; Geng, Jianjun; Qin, Yilong; Wang, Haidong; Fan, Ruiwen; Zhang, Ying; Li, Hongquan; Jiang, Shan; Dong, Changsheng

    2016-08-01

    The aims of the study were to establish a culture system for sheep skin melanocytes and uncover the effects of endothelin-1 on melanin synthesis in cultured melanocytes in order to provide an optimal cell system and a theoretical basis for studying the regulatory mechanism of coat color in sheep. In this study, skin punch biopsies were harvested from the dorsal region of 1-3-yr-old sheep, and skin melanocytes were then obtained by the two-step digestion using dispase II and trypsin/ethylene diamine tetraacetic acid (EDTA). The primary cultures of the melanocytes were established and characterized by dopa-staining, immunocytochemical localization of melanocyte markers, and RT-polymerase chain reaction (PCR) analysis of coat color genes. To determine the effect of endothelin-1 on proliferation and melanin synthesis of melanocytes, the cultured cells were treated with different doses of endothelin-1 (10(-7), 10(-8), 10(-9), 10(-10), and 0 mol/L), and the growth rate of melanocytes, production of melanin, expression of related genes, and location of related protein in cultured cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), ultraviolet spectrophotometry, qRT-PCR, and immunocytochemical localization, respectively. The results showed that the established melanocyte culture functions properly. Endothelin-1 treatment increased markedly the number of melanocytes and melanin content. In responding to this treatment, expressions of microphthalmia-associated transcription factor (MITF), melanocortin 1 receptor (MC1R), tyrosinase (TYR), and endothelin receptor B (EDNRB) in the melanocytes were significantly up regulated (P < 0.05). Immunocytochemical localization revealed that TYR was mainly localized in the cytoplasm. Positive staining of TYR in the melanocytes was significant. The findings demonstrated that the culture system of sheep skin melanocytes was established successfully in vitro, and endothelin-1 promotes the

  18. International Relations. International Perspectives on Higher Education Research. Volume 3

    Science.gov (United States)

    Tight, Malcolm, Ed.

    2005-01-01

    This is the third volume of International Perspectives on Higher Education Research, a series which aims to feature something of the variety of research being undertaken into higher education systems and issues outside of North America. The theme of this volume is International Relations, or how students, academics, universities and higher…

  19. The pathophysiological role of astrocytic endothelin-1

    NARCIS (Netherlands)

    Hostenbach, Stephanie; D'haeseleer, Miguel; Kooijman, Ron; De Keyser, Jacques

    In the normal central nervous system, endothelin-1 (ET-1) is found in some types of neurons, epithelial cells of the choroid plexus, and endothelial cells of microvessels, but it is usually not detectable in glial cells. However, in different pathological conditions, astrocytes adapting a reactive

  20. Endothelin-1 Gene Polymorphism and Its Level Predict the Risk of Venous Thromboembolism in Male Indian Population.

    Science.gov (United States)

    Kumari, Babita; Prabhakar, Amit; Sahu, Anita; Chatterjee, Tathagata; Tyagi, Tarun; Gupta, Neha; Nair, Velu; Ashraf, Mohammad Zahid

    2017-07-01

    Genes related to endothelial function are responsible for the regulation of vascular functions. The aim of this study is to investigate whether endothelial gene-associated polymorphism and their plasma levels can be used to predict the risk for venous thromboembolism (VTE). We studied 133 patients with VTE and 164 healthy controls. Endothelin (EDN) G8002A, EDN T1370G, EDN 3A/4A, eNOSG894T, angiotensin-converting enzyme I/D, vascular endothelial growth factor C936T, and endothelial cell protein C receptor A6936G polymorphism was genotyped by restriction fragment length polymorphism. Plasma levels of endothelin 1 (EDN1), endothelial nitric oxide synthase, and angiotensin-converting enzyme were measured by enzyme-linked immunoassay kit. The genotype and allele frequency between control and patients with VTE were significantly altered only for EDN T1370G polymorphism. The plasma EDN1 concentration was relatively higher in patients with VTE ( P = .0017) compared to healthy controls and showed an association with the EDN1 gene polymorphism in male Indian population. Logistic regression model analysis for EDN T1370G indicated a significant association between EDN G allele and occurrence of VTE. The EDN1 gene polymorphism may play a significant role in predicting individual's susceptibility toward VTE and its clinical progression.

  1. China-ASEAN Relations in Higher Education: An Analytical Framework

    Science.gov (United States)

    Welch, Anthony

    2012-01-01

    China's dramatic economic rise has tended to overshadow other wider perspectives on the developing China and Association of Southeast Asian Nations (ASEAN) relationship, including in higher education. The article examines contemporary relations between China and ASEAN, set against the longer term development of cultural and trade relations. It is…

  2. Endothelin B receptor blockade attenuates pulmonary vasodilation in oxygen-ventilated fetal lambs.

    Science.gov (United States)

    Ivy, D Dunbar; Lee, Dong-Seok; Rairigh, Robyn L; Parker, Thomas A; Abman, Steven H

    2004-01-01

    Endothelin-1 (ET-1) contributes to the regulation of pulmonary vascular tone in the normal ovine fetus and in models of perinatal pulmonary hypertension. In the fetal lamb lung, the effects of ET-1 depend on the balance of at least two endothelin receptor subtypes: ETA and ETB. ETA receptors are located on smooth muscle cells and mediate vasoconstriction and smooth muscle proliferation. Stimulation of endothelial ETB receptors causes vasodilation through release of nitric oxide and also functions to remove ET-1 from the circulation. However, whether activation of ETB receptors contributes to the fall in pulmonary vascular tone at birth is unknown. To determine the role of acute ETB receptor blockade in pulmonary vasodilation in response to birth-related stimuli, we studied the hemodynamic effects of selective ETB receptor blockade with BQ-788 during mechanical ventilation with low (<10%) and high FiO2 (100%) in near-term fetal sheep. Intrapulmonary infusion of BQ-788 did not change left pulmonary artery (LPA) blood flow and pulmonary vascular resistance (PVR) at baseline. In comparison with controls, BQ-788 treatment attenuated the rise in LPA flow with low and high FiO2 ventilation (p <0.001 vs. control for each FiO2 concentration). PVR progressively decreased during mechanical ventilation with low and high FiO2 in both groups, but PVR remained higher after BQ-788 treatment throughout the study period (p <0.001). We conclude that selective ETB receptor blockade attenuates pulmonary vasodilation at birth. We speculate that ETB receptor stimulation contributes to pulmonary vasodilation at birth in the ovine fetus.

  3. Endothelin 1 as a predictor marker for bronchopulmonary dysplasia in preterm neonates with respiratory distress syndrome.

    Science.gov (United States)

    El Shemi, M S; Tawfik, S; Khafagy, S M; Hamza, M T; Youssef, A M A

    2017-01-01

    We aimed to investigate if endothelin 1 concentration at day 3 postnatal age could be used as a predictive marker for development of bronchopulmonary dysplasia in preterm neonates with respiratory distress syndrome. This prospective observational study was done on 69 preterm neonates with gestational ages between 28 and 34 weeks and diagnosed as having respiratory distress syndrome. Serum concentrations of endothelin 1 was measured for all patients at day 3 of life and they were divided into BPD and No-BPD groups according to whether they developed bronchopulmonary dysplasia or not. A total of 17 infants were in the BPD group and 52 infants were in the No-BPD group. Serum endothelin 1 was significantly higher in the BPD group (435.39±172.88) compared with the No-BPD group (302.65±49.32) (p bronchopulmonary dysplasia with a sensitivity of 88.24%, and specificity of 61.54%. Serum endothelin 1 is significantly increased at day 3 of life in preterm neonates with respiratory distress syndrome who later develop bronchopulmonary dysplasia (BPD). It seems to be a promising predictive marker for BPD but further studies are needed to find the appropriate time for its measurement.

  4. Middle Leadership in Higher Education: A Relational Analysis

    Science.gov (United States)

    Branson, Christopher M.; Franken, Margaret; Penney, Dawn

    2016-01-01

    The paper is informed by a research study exploring middle leadership as experienced by Chairpersons of Departments within one faculty in a university in Aotearoa New Zealand. It is argued that middle leadership in higher education needs to be understood as a highly complex relational endeavour, characterised by compromises that are negotiated…

  5. The heart as an extravascular target of endothelin-1 in ...

    Science.gov (United States)

    Exposure to particulate matter air pollution has been causally linked to cardiovascular disease in humans. Several broad and overlapping hypotheses describing the biological mechanisms by which particulate matter exposure leads to cardiovascular disease and cardiac dysfunction have been explored, though linkage with specific factors or genes remains limited. Given evidence pointing to autocrine/paracrine signaling systems as modulators of cardiac dysfunction, the present review highlights the emerging role of endothelins as mediators of cardiac dysfunction following particulate matter exposure. Endothelin-1 is a small multifunctional protein expressed in the pulmonary and cardiovascular system, known for its ability to constrict blood vessels. Although endothelin-1 can also directly and indirectly (via secondary signaling events) modulate cardiac contractility, heart rate, and rhythm, research on the role of endothelins in the context of air pollution has tended to focus on the vascular effects. The plausibility of endothelin as a mechanism underlying particulate matter-induced cardiac dysfunction is further supported by the therapeutic utility of certain endothelin receptor antagonists. Extravascular effects of endothelin on the heart could better explain one mechanism by which particulate matter exposure may lead to cardiac dysfunction. We propose and support the novel hypothesis that autocrine/paracrine signaling systems, such as endothelins, mediate cardiac

  6. Reduced endothelin-3 expression in sporadic Hirschsprung disease

    NARCIS (Netherlands)

    Kenny, SE; Hofstra, RMW; Buys, CHCM; Vaillant, CR; Lloyd, DA; Edgar, DH

    Background: Enteric aganglionosis in Hirschsprung disease has been linked to genes coding for endothelin-3 (EDN3) and the endothelin B receptor (EDNRB), but there is no such linkage in most patients with sporadic Hirschsprung disease. However, the similarity between the distal colonic aganglionosis

  7. Genetic interactions between neurofibromin and endothelin receptor B in mice.

    Directory of Open Access Journals (Sweden)

    Mugdha Deo

    Full Text Available When mutations in two different genes produce the same mutant phenotype, it suggests that the encoded proteins either interact with each other, or act in parallel to fulfill a similar purpose. Haploinsufficiency of Neurofibromin and over-expression of Endothelin 3 both cause increased numbers of melanocytes to populate the dermis during mouse development, and thus we are interested in how these two signaling pathways might intersect. Neurofibromin is mutated in the human genetic disease, neurofibromatosis type 1, which is characterized by the development of Schwann cell based tumors and skin hyper-pigmentation. Neurofibromin is a GTPase activating protein, while the Endothelin 3 ligand activates Endothelin receptor B, a G protein coupled receptor. In order to study the genetic interactions between endothelin and neurofibromin, we defined the deletion breakpoints of the classical Ednrb piebald lethal allele (Ednrb(s-l and crossed these mice to mice with a loss-of-function mutation in neurofibromin, Dark skin 9 (Dsk9. We found that Neurofibromin haploinsufficiency requires Endothelin receptor B to darken the tail dermis. In contrast, Neurofibromin haploinsufficiency increases the area of the coat that is pigmented in Endothelin receptor B null mice. We also found an oncogenic mutation in the G protein alpha subunit, GNAQ, which couples to Endothelin receptor B, in a uveal melanoma from a patient with neurofibromatosis type 1. Thus, this data suggests that there is a complex relationship between Neurofibromin and Endothelin receptor B.

  8. Insulin decreases atherosclerosis by inducing endothelin receptor B expression

    DEFF Research Database (Denmark)

    Park, Kyoungmin; Mima, Akira; Li, Qian

    2016-01-01

    ) in the endothelia of Apoe(-/-) mice (Irs1/Apoe(-/-)) increased insulin signaling and function in the aorta. Atherosclerosis was significantly reduced in Irs1/ApoE(-/-) mice on diet-induced hyperinsulinemia and hyperglycemia. The mechanism of insulin's enhanced antiatherogenic actions in EC was related to remarkable......Endothelial cell (EC) insulin resistance and dysfunction, caused by diabetes, accelerates atherosclerosis. It is unknown whether specifically enhancing EC-targeted insulin action can decrease atherosclerosis in diabetes. Accordingly, overexpressing insulin receptor substrate-1 (IRS1...... induction of NO action, which increases endothelin receptor B (EDNRB) expression and intracellular [Ca(2+)]. Using the mice with knockin mutation of eNOS, which had Ser1176 mutated to alanine (AKI), deleting the only known mechanism for insulin to activate eNOS/NO pathway, we observed that IRS1...

  9. Cerebrovascular endothelin receptor upregulation in cerebral ischemia

    DEFF Research Database (Denmark)

    Edvinsson, Lars

    2009-01-01

    Stroke is a serious neurological disease and the third leading cause of death in the western world. In roughly 15 % of the cases, the cause is due to an intracranial haemorrhage, and the remaining 85 % represent ischemic strokes. Ischemic stroke is caused by the occlusion of a cerebral artery...... leading to the enhanced expression of vascular endothelin receptors show that both protein kinase C (PKC) and mitogen activating protein kinase (MAPK) play important roles. The results from this work provide new perspectives on the pathophysiology of ischemic stroke, and give a possible explanation...

  10. Establishment and characterization of porcine focal cerebral ischemic model induced by endothelin-1.

    Science.gov (United States)

    Zhang, Rui; Bertelsen, Lotte Bonde; Flø, Christian; Wang, Yan; Stødkilde-Jørgensen, Hans

    2016-12-02

    Due to well-developed Circle of Willis in pigs, it is technically challenging to make persistent focal ischemic stroke based on occlusion of cerebral arteries. Endothelin-1 could cause a focal lesion by forcing transient but strong vasoconstriction in the circumscribed injected area. Its use in porcine stroke model has drawn attention lately. However, all the porcine endothelin-1 induced models were euthanized soon after surgery. Whether the brain lesion is persistent, and whether they could cause neurological deficit are not known. This research aims to provide a more detailed characterization of endothelin-1 induced porcine cerebral ischemic model by evaluating the change of neurological function and the brain lesion monitored by MRI of the pigs. Danish Domestic pigs were randomly divided into two groups: a group receiving endothelin-1 (ET-1 group, n=6) and a sham group (n=6). After the fronto-temporal craniotomy, pigs in the ET-1 group received 200μl endothelin-1 injected within a cortical area of one cm2; pigs in the sham group received only saline injections. Neurological deficit evaluation and MRI scanning were done 24h and 72h after operation. Afterwards, hematoxylin and eosin staining was conducted to detect the morphological characteristics of the damaged brain tissue. The average performance score in the pigs of the ET-1 group was 9.67±1.03 and 9.00±1.26 respectively, at 24h and 72h after surgery, which was significantly higher than that of the pigs in sham group. The brain lesion percentage detected by MRI was 12.26±0.60%, and 10.33±0.51% respectively, at 24h and 72h after surgery in the ET-1 group. Microscopy showed extended pyknotic neuronal perikarya in neurons located in the ischemic area. The endothelin-1 induced porcine cerebral ischemic model is technically easier, and able to create cerebral ischemia severe enough to cause a functional neurological deficit as well as observable lesions on MRI. It is a suitable model for long-term cerebral

  11. HIV-1 matrix protein p17 promotes lymphangiogenesis and activates the endothelin-1/endothelin B receptor axis.

    Science.gov (United States)

    Caccuri, Francesca; Rueckert, Christine; Giagulli, Cinzia; Schulze, Kai; Basta, Daniele; Zicari, Sonia; Marsico, Stefania; Cervi, Edoardo; Fiorentini, Simona; Slevin, Mark; Guzman, Carlos A; Caruso, Arnaldo

    2014-04-01

    AIDS-related lymphomas are high grade and aggressively metastatic with poor prognosis. Lymphangiogenesis is essential in supporting proliferation and survival of lymphoma, as well as tumor dissemination. Data suggest that aberrant lymphangiogenesis relies on action of HIV-1 proteins rather than on a direct effect of the virus itself. HIV-1 matrix protein p17 was found to accumulate and persist in lymph nodes of patients even under highly active antiretroviral therapy. Because p17 was recently found to exert a potent proangiogenic activity by interacting with chemokine (C-X-C motif) receptors 1 and 2, we tested the prolymphangiogenic activity of the viral protein. Human primary lymph node-derived lymphatic endothelial cells were used to perform capillary-like structure formation, wound healing, spheroids, and Western blot assays after stimulation with or without p17. Here, we show that p17 promotes lymphangiogenesis by binding to chemokine (C-X-C motif) receptor-1 and chemokine (C-X-C motif) receptor-2 expressed on lymph node-derived lymphatic endothelial cells and activating the Akt/extracellular signal-regulated kinase signaling pathway. In particular, it was found to induce capillary-like structure formation, sprout formation from spheroids, and increase lymph node-derived lymphatic endothelial cells motility. The p17 lymphangiogenic activity was, in part, sustained by activation of the endothelin-1/endothelin receptor B axis. A Matrigel plug assay showed that p17 was able to promote the outgrowth of lymphatic vessels in vivo, demonstrating that p17 directly regulates lymphatic vessel formation. Our results suggest that p17 may generate a prolymphangiogenic microenvironment and plays a role in predisposing the lymph node to lymphoma growth and metastasis. This finding offers new opportunities to identify treatment strategies in combating AIDS-related lymphomas.

  12. Effect of hemodialysis on pulmonary function tests and plasma endothelin levels.

    Science.gov (United States)

    Safa, Javid; Noshad, Hamid; Ansarin, Khalil; Nikzad, Alireza; Saleh, Parviz; Ranjbar, Abdolmohammad

    2014-07-01

    End-stage renal disease (ESRD) is a complex illness that involves different organs including the lungs. We studied the pulmonary function tests, arterial blood gases (ABG) and plasma endothelin-1 (ET-1) levels to check whether there is any change in their levels after hemodialysis (HD) in patients with ESRD. In this cross-sectional study (from July 2009 to April 2010), 20 patients with ESRD were evaluated. ABG, spirometric parameters and plasma ET-1 were measured before and after HD in these patients. Student's t-test was performed to clarify the differences and Pearson's test was used for correlations. P forced expiratory volume (FEV1)/forced vital capacity (FVC) after HD. Plasma ET-1 levels decreased significantly after HD. Mean ET-1 before HD was 6.88 + 5.81 pg/mL while it was 3.91 + 2.76 pg/mL after HD (P = 0.009). Based on the plasma levels of ET-1, the patients were divided into two groups. The mean level of ET-1 was higher in the first group. Significant increase was seen in spirometric parameters in the second group. Our study suggests that, in patients with ESRD, plasma ET-1 level is higher than in the normal population, and this is closely related to deterioration of pulmonary function tests. Significant reduction of plasma ET-1 may be an important factor in the improvement of spiro-metry parameters after HD.

  13. Endothelin and its suspected role in the pathogenesis and possible treatment of glaucoma.

    Science.gov (United States)

    Shoshani, Yochai Z; Harris, Alon; Shoja, Mohammadali M; Rusia, Deepam; Siesky, Brent; Arieli, Yoel; Wirostko, Barbara

    2012-01-01

    To review the role of endothelin in intraocular pressure control, its effect on the trabecular meshwork (TM) and the outflow facility, effect on ocular blood flow and vascular regulation and the potential role of endothelin-1 (ET-1) antagonism in the therapeutic paradigm of glaucoma. A thorough review of the medical literature and a meta-analysis on the level of ET-1 in OAG patients in an attempt to demonstrate the evolving importance of endothelin in glaucoma. ET-1 has been identified in the plasma in concentrations that are markedly increased in a number of systemic as well as ocular pathologies such as glaucoma where underlying vascular dysfunction and pathology play a role. It has been shown that ET-1 induces human TM cell contraction in culture and that it can affect the outflow facility. Evidence indicates that systemic ET-1 regulatory mechanisms and vascular responses to it are also altered in glaucoma. Recently, several endothelin antagonists have been shown to have a potential role in glaucoma therapy. In our meta-analysis, only patients with normal tension glaucoma (NTG) (as opposed to patients with high tension glaucoma (HTG)) had significantly higher plasma ET-1 levels compared to non-glaucomatous control. High tension glaucomaHTG patients had significant higher levels of ET-1 in the aqueous humor. The potential role of ET-1 antagonism in the therapeutic paradigm of glaucoma is an exciting possible new approach in the treatment of OAG patients. In NTG, ET-1 may have both a local and systemic component of vascular dysregulation, while whereas in HTG, the role of ET-1 may be dominantly localized to ocular tissue.

  14. Is quality assurance in higher education contextually relative ...

    African Journals Online (AJOL)

    This article examines notions of quality and quality assurance in higher education. It does this by raising questions such as whether quality in higher education is the same as, for example, quality of clothing or the quality of meat in local butcheries. The article questions the assumption that if certain things, such as criteria or ...

  15. Coronary and systemic arterial physiology and immunohistochemical markers related to early coronary arterial lesions in beagle dogs given the potassium channel opener, ZD6169, or the endothelin receptor antagonist, ZD1611.

    Science.gov (United States)

    Jones, Huw Bowen; Björkman, Jan-Arne; Schofield, Jason

    2013-07-01

    We evaluated immunohistochemistry (von Willebrand Factor [vWF] or fibrinogen) and systemic and coronary arterial physiological parameters in beagle dogs to investigate early arterial lesions induced by the potassium channel opener, ZD6169, or the endothelin receptor antagonist, ZD1611. Dogs given an oral dose of ZD6169 (experiment 1) were terminated 1 day later and showed arterial and myocardial lesions. Minimal arterial lesions exhibited few condensed medial smooth muscle cells only, with others showing segmental medial necrosis occasionally with medial/adventitial acute inflammation. Intercellular immunostaining was seen in ostensibly normal tissue, where no pathology was present in conventionally stained sections. vWF and fibrinogen are valuable tools for detecting disruption of arterial integrity. In experiment 2, 2 dogs were given a single high dose of ZD6169 or ZD1611 and BP/HR monitored by conventional measures or telemetry. Substantially reduced systolic/diastolic BP and increased HR occurred within 10 min of ZD6169 infusion: ZD1611 caused minor BP decrease and HR increase. In experiment 3, both drugs given to anaesthetized dogs induced markedly exaggerated systolic phasic forward and reverse flow in left descending and right coronary arteries. Diastolic coronary artery flows were unaffected with ZD1611 and increased slightly with ZD6169. In both coronary arteries, the ZD1611-induced increase in flows paralleled decreased resistance.

  16. Higher education : Features, trends and needs in relation to sustainability

    NARCIS (Netherlands)

    Maragakis, A.; Van den Dobbelsteen, A.A.J.F.

    2013-01-01

    The progress of sustainability within higher education has steadily increased in focus over the last decade and has increasingly become a topic of academic research. With various scholars, journals and conferences exclusively dealing with the subject, a wealth of literature has been produced on best

  17. Relating secondary school to higher education honours programmes

    NARCIS (Netherlands)

    van der Valk, A.E.|info:eu-repo/dai/nl/073046868; Kleijer, C.C.; Michels, B.I.

    2017-01-01

    U-Talent Academy is part of the U-Talent programme, a collaboration between two universities and 40 schools. The aim of U-Talent is to strengthen science and mathematics (STEM) education in secondary school and in the bachelor phase of higher education by the valorization of scientific research and

  18. Evidence for the formation of endothelin by lysed red blood cells from endogenous precursor.

    Science.gov (United States)

    Tippler, B; Herbst, C; Simmet, T

    1994-12-12

    The release of endothelin from various blood cell fractions was investigated. Human as well as rat blood cell fractions homogenized by sonification were incubated in buffer for up to 60 min. Neither in platelet nor leukocyte homogenates from either species could immunoreactive endothelin be detected. In contrast, homogenates of red blood cells from both species showed a rapid and time-dependent rise of immunoreactive endothelin levels, reaching a peak at 15 min and decreasing thereafter. However, at time point 0 no immunoreactive endothelin could be detected. Reverse phase high performance liquid chromatography showed immunoreactive endothelin to consist of endothelin-1 as well as big endothelin-1. The release of immunoreactive endothelin in human and rat homogenates was concentration-dependently inhibited by the protease inhibitors, leupeptin, phosphoramidon, chymostatin and pepstatin A in order of increasing potency. Intact red blood cells did not incorporate [125I]endothelin-1 nor did they transform exogenous big endothelin-1 to endothelin-1. However, haemolysis of red blood cells with hypotonic saline (0.2%) or incubation with pore-forming staphylococcal alpha-toxin induced the release of immunoreactive endothelin into the buffer samples. Thus, apart from the indirect vasoconstrictor, haemoglobin, red blood cells can also liberate the direct vasoconstrictor, endothelin, a finding expected to be of considerable pathophysiological significance.

  19. Consensual Sexual Relations between Faculty and Students in Higher Education.

    Science.gov (United States)

    Stokes, Jerome W. D.; Vinik, D. Frank

    1994-01-01

    Reviews institutional policy and case law regarding sexual harassment and consensual sexual relations between college faculty and college students. Advises colleges to strengthen sexual-harassment policies and educate students and faculty about harassment, and to adopt a policy on consensual sexual relations between students and faculty members.…

  20. Altered states of consciousness are related to higher sexual responsiveness.

    Science.gov (United States)

    Costa, Rui M; Pestana, José; Costa, David; Wittmann, Marc

    2016-05-01

    Altered states of consciousness lead to profound changes in the sense of self, time and space. We assessed how these changes were related to sexual responsiveness during sex. 116 subjects reported (a) intensity of awareness concerning body, space and time, and (b) satisfaction, desire, arousal, and orgasm occurrence. We differentiated vaginal intercourse orgasm from noncoital orgasm. Female vaginal intercourse orgasm was further differentiated as with or without concurrent clitoral masturbation. Overall, sexual responsiveness was related to greater body awareness and lesser time and space awareness. Satisfaction, desire, and arousal were especially associated with less time awareness in women. Female orgasms during vaginal intercourse were related to greater body awareness and lesser time awareness, but noncoital orgasms were unrelated. Our findings provide empirical support for the hypotheses that altered states of consciousness with attentional absorption are strongly related to sexual responsiveness in women, and to a lesser extent in men. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Monodromy relations in higher-loop string amplitudes

    Directory of Open Access Journals (Sweden)

    S. Hohenegger

    2017-12-01

    Full Text Available New monodromy relations of loop amplitudes are derived in open string theory. We particularly study N-point (planar and non-planar one-loop amplitudes described by a world-sheet cylinder and derive a set of relations between subamplitudes of different color orderings. Various consistency checks are performed by matching α′-expansions of planar and non-planar amplitudes involving elliptic iterated integrals with the resulting periods giving rise to two sets of multiple elliptic zeta values. The latter refer to the two homology cycles on the once-punctured complex elliptic curve and the monodromy equations provide relations between these two sets of multiple elliptic zeta values. Furthermore, our monodromy relations involve new objects for which we present a tentative interpretation in terms of open string scattering amplitudes in the presence of a non-trivial gauge field flux. Finally, we provide an outlook on how to generalize the new monodromy relations to the non-oriented case and beyond the one-loop level. Comparing a subset of our results with recent findings in the literature we find therein several serious issues related to the structure and significance of monodromy phases and the relevance of missed contributions from contour integrations.

  2. Assessment of endothelin and copeptin as biomarkers for vasovagal syncope.

    Science.gov (United States)

    Rash, Arjun; McRae, Maureen; Fatehi, Jaleh; Richie, Deborah; Solbiati, Monica; Pillay, Neelan; Ulke-Lemée, Annegret; MacDonald, Justin; Sheldon, Robert

    2016-02-01

    The diagnosis of vasovagal syncope continues to be difficult despite the use of accurate histories, tilt testing and implantable loop recorders. A circulating biomarker might be useful to facilitate diagnoses. Both endothelin-1 and vasopressin are increased during positive tilt tests resulting in syncope. Copeptin is a stable cleavage product of vasopressin formation. We conducted a pilot study to assess the utility of endothelin-1 and copeptin as circulating biomarkers of vasovagal syncope. Three populations were studied: syncope patients, epilepsy patients and controls. Vasovagal syncope diagnosis was ascertained with the Calgary Syncope Score and epilepsy diagnosis was confirmed with EEG. Plasma levels of endothelin-1 were measured using by ELISA and copeptin levels were determined using an EIA kit. Asymptomatic control subjects had mean age 35 ± 11 years (7/22 male); epileptic subjects had mean age 32 ± 7 years (4/15 male); and syncope subjects had mean age 33 ± 16 years (4 of 21 male). Circulating plasma levels of endothelin-1 and copeptin were no different among the three groups. Mean concentrations of endothelin-1 were as follows: syncope, 23 ± 32 pg/mL; controls, 21 ± 17 pg/mL; and epileptics, 18 ± 12 pg/mL. Mean concentrations of copeptin were as follows: syncope, 1·29 ± 0·79 ng/mL; controls, 1·25 ± 0·79 ng/mL; and seizures, 1·23 ± 0·45 ng/mL. There were no significant correlations between syncope frequency and copeptin or endothelin-1 levels. Circulating plasma endothelin-1 and copeptin levels are not significantly different among populations of controls, syncope patients and seizure patients. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

  3. Endothelin Regulates Porphyromonas gingivalis-Induced Production of Inflammatory Cytokines.

    Directory of Open Access Journals (Sweden)

    Ga-Yeon Son

    Full Text Available Periodontitis is a very common oral inflammatory disease that results in the destruction of supporting connective and osseous tissues of the teeth. Although the exact etiology is still unclear, Gram-negative bacteria, especially Porphyromonas gingivalis in subgingival pockets are thought to be one of the major etiologic agents of periodontitis. Endothelin (ET is a family of three 21-amino acid peptides, ET-1, -2, and -3, that activate G protein-coupled receptors, ETA and ETB. Endothelin is involved in the occurrence and progression of various inflammatory diseases. Previous reports have shown that ET-1 and its receptors, ETA and ETB are expressed in the periodontal tissues and, that ET-1 levels in gingival crevicular fluid are increased in periodontitis patients. Moreover, P. gingivalis infection has been shown to induce the production of ET-1 along with other inflammatory cytokines. Despite these studies, however, the functional significance of endothelin in periodontitis is still largely unknown. In this study, we explored the cellular and molecular mechanisms of ET-1 action in periodontitis using human gingival epithelial cells (HGECs. ET-1 and ETA, but not ETB, were abundantly expressed in HGECs. Stimulation of HGECs with P. gingivalis or P. gingivalis lipopolysaccharide increased the expression of ET-1 and ETA suggesting the activation of the endothelin signaling pathway. Production of inflammatory cytokines, IL-1β, TNFα, and IL-6, was significantly enhanced by exogenous ET-1 treatment, and this effect depended on the mitogen-activated protein kinases via intracellular Ca2+ increase, which resulted from the activation of the phospholipase C/inositol 1,4,5-trisphosphate pathway. The inhibition of the endothelin receptor-mediated signaling pathway with the dual receptor inhibitor, bosentan, partially ameliorated alveolar bone loss and immune cell infiltration. These results suggest that endothelin plays an important role in P. gingivalis

  4. Enhanced expression of contractile endothelin ET(B) receptors in rat coronary artery after organ culture

    DEFF Research Database (Denmark)

    Johnsson, E.; Maddahi, A.; Wackenfors, A.

    2008-01-01

    Endothelin-1 is a potent vasoconstrictor mediating its effects via two receptor subtypes, the endothelin type A (ET(A)) preferentially situated on smooth muscle cells, mediating vasoconstriction and endothelin type B (ET(B)) mainly located on endothelial cells, mediating vasodilatation....... In cardiovascular disease and in organ culture in vitro, endothelin ET(B) receptors are up-regulated on smooth muscle cells. The objectives of the present study were to characterise the endothelin receptor-induced vasoconstriction and quantify the endothelin receptor mRNA levels and immunoreactivity in fresh...... and cultured rat coronary arteries. We demonstrate that endothelin-1 induces strong and equal concentration-dependent contractions in fresh and cultured segments from the left anterior descending coronary artery. Sarafotoxin 6c, an endothelin ET(B) receptor agonist, had negligible effect in fresh arteries...

  5. Higher entropic uncertainty relations for anti-commuting observables

    NARCIS (Netherlands)

    S.D.C. Wehner (Stephanie); A. Winter

    2007-01-01

    htmlabstractUncertainty relations lie at the very core of quantum mechanics, and form the cornerstone of essentially all quantum cryptographic applications. In particular, they play an important role in cryptographic protocols in the bounded-quantum-storage model, where proving the security of all

  6. Molecular systematics of higher primates: genealogical relations and classification.

    Science.gov (United States)

    Miyamoto, M M; Koop, B F; Slightom, J L; Goodman, M; Tennant, M R

    1988-01-01

    We obtained 5' and 3' flanking sequences (5.4 kilobase pairs) from the psi eta-globin gene region of the rhesus macaque (Macaca mulatta) and combined them with available nucleotide data. The completed sequence, representing 10.8 kilobase pairs of contiguous noncoding DNA, was compared to the same orthologous regions available for human (Homo sapiens, as represented by five different alleles), common chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla), and orangutan (Pongo pygmaeus). The nucleotide sequence for Macaca mulatta provided the outgroup perspective needed to evaluate better the relationships of humans and great apes. Pairwise comparisons and parsimony analysis of these orthologues clearly demonstrated (i) that humans and great apes share a high degree of genetic similarity and (ii) that humans, chimpanzees, and gorillas form a natural monophyletic group. These conclusions strongly favor a genealogical classification for higher primates consisting of a single family (Hominidae) with two subfamilies (Homininae for Homo, Pan, and Gorilla and Ponginae for Pongo). PMID:3174657

  7. Regulation of the neuronal norepinephrine transporter by endothelin-1 and -3 in the rat anterior and posterior hypothalamus.

    Science.gov (United States)

    Hope, Sandra I; Schmipp, Josefina; Rossi, Andres H; Bianciotti, Liliana G; Vatta, Marcelo S

    2008-12-01

    We previously reported that endothelin-1 and endothelin-3 modulate norepinephrine neuronal release and tyrosine hydroxylase activity and expression in the hypothalamus. In the present study we sought to establish the role of endothelin-1 and -3 in the regulation of norepinephrine uptake in the anterior and posterior hypothalamus. Results showed that in the anterior hypothalamus endothelin-3 increased neuronal norepinephrine uptake whereas endothelin-1 decreased it. Conversely, in the posterior hypothalamic region both endothelins diminished the neuronal uptake of the amine. Endothelins response was concentration dependent and maintained at all studied times. Endothelins also modified the kinetic and internalization of the NE neuronal transporter. In the anterior hypothalamic region endothelin-3 increased the V(max) and the B(max) whereas endothelin-1 decreased them. However, in the posterior hypothalamic region both endothelins diminished the V(max) as well as B(max). Neither endothelin-1 nor endothelin-3 modified neuronal norepinephrine transporter K(d) in the studied hypothalamic regions. These findings support that in the posterior hypothalamic region both endothelins diminished neuronal norepinephrine transporter activity by reducing the amine transporter expression on the plasmatic membrane. Conversely, in the anterior hypothalamic region endothelin-3 enhanced neuronal norepinephrine transporter activity by increasing the expression of the transporter on the presynaptic membrane, whereas endothelin-1 induced the opposite effect. Present results permit us to conclude that both endothelins play an important role in the regulation of norepinephrine neurotransmission at the presynaptic nerve endings in the hypothalamus.

  8. Altered states of consciousness are related to higher sexual responsiveness

    OpenAIRE

    Costa, Rui Miguel; Pestana, José Antonio Melo; Costa, David; Wittmann, Marc

    2016-01-01

    Altered states of consciousness lead to profound changes in the sense of self, time and space. We assessed how these changes were related to sexual responsiveness during sex. 116 subjects reported (a) intensity of awareness concerning body, space and time, and (b) satisfaction, desire, arousal, and orgasm occurrence. We differentiated vaginal intercourse orgasm from noncoital orgasm. Female vaginal intercourse orgasm was further differentiated as with or without concurrent clitoral masturbati...

  9. Endothelin-1 and Exercise Intensity in Sedentary Adolescents with Obesity

    Directory of Open Access Journals (Sweden)

    Brooke E. Starkoff

    2015-01-01

    Full Text Available Inactivity combined with obesity during adolescence increases the risk of future cardiovascular disease. The study purpose was to compare the influence of differing intensities of exercise on endothelial function in sedentary adolescents with obesity. Participants were randomized to one of two groups in a 6-week exercise intervention: moderate intensity (MOD or high intensity interval exercise (HIIE. Endothelial function was assessed pre- and post-intervention via fasted serum levels of endothelin-1 (ET-1. Pre-measures of ET-1 concentrations were elevated at baseline. No significant differences in ET-1 were found between or within exercise groups. However, in the HIIE group, ET-1 was inversely associated with percentages of age predicted maximal heart rate achieved during the intervention (p=0.035, r=-0.567. The exercise interventions did not positively change ET-1 levels, yet participants who exercised at higher intensities in the HIIE group experienced greater decreases in ET-1. Keywords: childhood obesity, endothelial function, high intensity interval exercise

  10. The insulinotropic effect of endothelin-1 is mediated by glucagon release from the islet alpha cells

    DEFF Research Database (Denmark)

    Brock, B; Gregersen, S; Kristensen, K

    1999-01-01

    The circulating concentrations of endothelin-1 (ET-1), a peptide derived from endothelium, are increased in hypertension and diabetes. Endothelin-1 has recently been shown to be an insulinotropic agent. The mechanism of action of endothelin-1 on the endocrine pancreas has not yet been clarified....

  11. Role of endothelin in the cardiovascular system.

    Science.gov (United States)

    Rodríguez-Pascual, Fernando; Busnadiego, Oscar; Lagares, David; Lamas, Santiago

    2011-06-01

    The endothelin (ET) system consists of three peptide ligands (ET-1, ET-2 and ET-3) and two G-protein-coupled receptors, ET(A) and ET(B). In the cardiovascular system, ETs, particularly ET-1, are expressed in smooth muscle cells, cardiomyocytes, fibroblasts, and notably in vascular endothelial cells. Intense research over the last 10 years has changed the original view of ET-1 as mainly a vasoconstrictor regulating blood pressure, into a biological factor regulating processes such as vascular remodeling, angiogenesis or extracellular matrix synthesis. The advent of specific (and type-selective) ET receptor antagonists has greatly fostered our knowledge of the biological function of ET-1, and has offered a potential therapeutic approach for numerous diseases including hypertension, atherosclerosis or fibrosis. In this article, we review the regulation of the expression of vascular ET-1, as well as the contribution of ET-1 to endothelial, smooth muscle and fibroblast cell function, with particular interest in the role of ET-1 in the development of cardiovascular diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Research-related intercultural higher education in satellite geodesy

    Science.gov (United States)

    Mayer, M.; Heck, B.; Krueger, C. P.

    2009-04-01

    In order to improve the education of young researchers (master degree, PhD, PostDocs) a cooperation between the Department of Geomatics (DGEOM), Federal University of Paraná (UFPR), Curitiba (Brazil) and the Geodetic Institute (GIK), University Karlsruhe (TH), Karlsruhe (Germany) was established which now exists since more than five years. The joint venture is actually called "PROBRAL: Precise positioning and height determination by means of GPS: Modeling of errors and transformation into physical heights" and focuses on research and education within the field of satellite geodesy. PROBRAL is funded by the Brazilian academic exchange service CAPES and the German academic exchange service DAAD. The geodetic aim of the research project is to validate and improve the quality of 3d positions derived from observations related to satellite navigation systems like GPS. In order to fulfill this ambitious goal sustainably, research has to be carried out in close cooperation. At the same time, e.g. to guarantee continuous success, a coordinated education has to be ensured. Besides technical education aspects key competences (e.g. language, capacity for teamwork, project management skills) are trained. Within the presentation the lessons which were learned from this project are discussed in detail.

  13. Plasma Endothelin-1 Levels in Preterm Neonatal Infants with Acute Respiratory Failure

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    D. V. Dmitriyev

    2008-01-01

    Full Text Available Increased pulmonary vascular resistance in preterm infants is associated with acute respiratory failure (ARF and at the same time endothelin-1 (E-1 plays an important role in neonatal pulmonary vascular responsiveness. Methods. Endothelin-1 levels were measured in two blood samples in 12 preterm infants with ARF and in 12 controls (at 32.2±1.3 and 29.8±1.2 weeks of gestation, respectively by enzyme immunoassay. For this, the first and second blood samples were taken at 18 to 40 hours after birth. Results. The plasma level of E-1 in the first sample did not differ between the neonates of both groups. In the second sample, significantly higher E-1 concentrations were observed in the newborns with ARF than in the controls. In the first sample, E-1 concentration were higher than in the second one in both groups (p<0.001. There was a significant positive correlation between the second E-1 sample and the SNAPPE 2 scale rating (r=0.38; p=0.02. The plasma level of E-1 in the first sample did not differ in both groups (11.9 and 12.2 pg/ml, respectively. Conclusion. Neonates with and without ARF had the similar plasma E-1 levels in the first sample, by taking into account the fact that the E-1 levels were higher in ARF than in the controls at 18 to 40 hour after birth. Increased vascular resistance in ARF may be associated with the high level of E-1. Key words: endothe-lin-1, acute respiratory failure.

  14. Association of Big Endothelin-1 with Coronary Artery Calcification.

    Science.gov (United States)

    Qing, Ping; Li, Xiao-Lin; Zhang, Yan; Li, Yi-Lin; Xu, Rui-Xia; Guo, Yuan-Lin; Li, Sha; Wu, Na-Qiong; Li, Jian-Jun

    2015-01-01

    The coronary artery calcification (CAC) is clinically considered as one of the important predictors of atherosclerosis. Several studies have confirmed that endothelin-1(ET-1) plays an important role in the process of atherosclerosis formation. The aim of this study was to investigate whether big ET-1 is associated with CAC. A total of 510 consecutively admitted patients from February 2011 to May 2012 in Fu Wai Hospital were analyzed. All patients had received coronary computed tomography angiography and then divided into two groups based on the results of coronary artery calcium score (CACS). The clinical characteristics including traditional and calcification-related risk factors were collected and plasma big ET-1 level was measured by ELISA. Patients with CAC had significantly elevated big ET-1 level compared with those without CAC (0.5 ± 0.4 vs. 0.2 ± 0.2, Panalysis, big ET-1 (Tertile 2, HR = 3.09, 95% CI 1.66-5.74, P predictive factor of the presence of CAC. There was a positive correlation of the big ET-1 level with CACS (r = 0.567, p0 and the highest tertile of big ET-1 (Pbig ET-1 level in predicting CAC was 0.83 (95% CI 0.79-0.87, pdata firstly demonstrated that the plasma big ET-1 level was a valuable independent predictor for CAC in our study.

  15. Association of Big Endothelin-1 with Coronary Artery Calcification.

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    Ping Qing

    Full Text Available The coronary artery calcification (CAC is clinically considered as one of the important predictors of atherosclerosis. Several studies have confirmed that endothelin-1(ET-1 plays an important role in the process of atherosclerosis formation. The aim of this study was to investigate whether big ET-1 is associated with CAC.A total of 510 consecutively admitted patients from February 2011 to May 2012 in Fu Wai Hospital were analyzed. All patients had received coronary computed tomography angiography and then divided into two groups based on the results of coronary artery calcium score (CACS. The clinical characteristics including traditional and calcification-related risk factors were collected and plasma big ET-1 level was measured by ELISA. Patients with CAC had significantly elevated big ET-1 level compared with those without CAC (0.5 ± 0.4 vs. 0.2 ± 0.2, P0 and the highest tertile of big ET-1 (P<0.01. The area under the receiver operating characteristic curve for the big ET-1 level in predicting CAC was 0.83 (95% CI 0.79-0.87, p<0.001, with a sensitivity of 70.6% and specificity of 87.7%.The data firstly demonstrated that the plasma big ET-1 level was a valuable independent predictor for CAC in our study.

  16. SPECIFICITY OF INNOVATION RELATED RISKS OF HIGHER SCHOOLS

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    M. S. Motyshina

    2014-01-01

    Full Text Available The paper is devoted to innovative activities of educational institutions regarded as the platform for fostering the students’ innovative potential and intellectual capacity. The authors consider the risks of innovative projects carried out in Russian universities; they analyze the biggest external challenges in the given sphere, including the fast obsolescence of knowledge, abrupt social changes, low competitiveness of Russian education in the global market, as well as the internal challenges related to insufficient qualification and advanced age of most academic staff, lack of necessary infrastructure, outdated educational paradigm, poor motivation for innovations, etc. Referring to the external and internal spheres, the author demonstrates possible risks of innovation activity in educational institutions both on the micro- and macro-level. The paper emphasizes the need for identification and classification of innovative project risks as a basis for effective prognostication and risk management. The risk classification model, developed by the author, can be used for estimating the prospects of innovative projects, and effort coordination in overcoming the adverse impact of risks зы развитию системы образования (недостаточная квалификация и преклонный возраст большинства преподавателей, отсутствие необходимой инфраструктуры и устаревшая парадигма управления, слабая нацеленность на производство инноваций и инноваторов и т. д.. В зависимости от сегмента внутренней и внешней среды представлены возможные риски инновационной деятельности вуза на микро- и макроуровнях. Очевидно, что имеющие пр

  17. Effect of hemodialysis on pulmonary function tests and plasma endothelin levels

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    Javid Safa

    2014-01-01

    Full Text Available End-stage renal disease (ESRD is a complex illness that involves different organs including the lungs. We studied the pulmonary function tests, arterial blood gases (ABG and plasma endothelin-1 (ET-1 levels to check whether there is any change in their levels after hemodialysis (HD in patients with ESRD. In this cross-sectional study (from July 2009 to April 2010, 20 patients with ESRD were evaluated. ABG, spirometric parameters and plasma ET-1 were measured before and after HD in these patients. Student′s t-test was performed to clarify the differences and Pearson′s test was used for correlations. P <0.05 was considered statistically significant. Significant reduction was seen in oxygen saturation (O 2 sat, partial pressure of carbon-dioxide (PaCO 2 and oxygen (PaO 2 after a HD session (P <0.001. Also, improvement was seen in all spirometric parameters except forced expiratory volume (FEV1/forced vital capacity (FVC after HD. Plasma ET-1 levels decreased signi-ficantly after HD. Mean ET-1 before HD was 6.88 + 5.81 pg/mL while it was 3.91 + 2.76 pg/mL after HD (P = 0.009. Based on the plasma levels of ET-1, the patients were divided into two groups. The mean level of ET-1 was higher in the first group. Significant increase was seen in spirometric parameters in the second group. Our study suggests that, in patients with ESRD, plasma ET-1 level is higher than in the normal population, and this is closely related to deterioration of pulmonary function tests. Significant reduction of plasma ET-1 may be an important factor in the improvement of spiro-metry parameters after HD.

  18. Endothelin, a peptide inhibitor of Na(+)-K(+)-ATPase in intact renaltubular epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Zeidel, M.L.; Brady, H.R.; Kone, B.C.; Gullans, S.R. (Brigham and Women' s Hospital, Boston, MA (USA))

    1989-12-01

    Endothelin, a potent vasoconstrictor released by vascular endothelial cells, can induce natriuresis in vivo. These studies examined the regulation of Na+ transport by endothelin in suspensions of rabbit proximal tubule (PT) and inner medullary collecting duct (IMCD) cells. Endothelin reduced oxygen consumption (QO2) by 18 +/- 1% in IMCD cells but did not alter QO2 in PT cells. In IMCD cells, endothelin inhibited QO2 half maximally at approximately 5 x 10(-12) M. Several lines of evidence indicate that endothelin reduces QO2 by inhibiting the Na(+)-K(+)-ATPase. (1) Endothelin gave no further inhibition of QO2 after ouabain and blunted the stimulatory effect of amphotericin B on QO2 (+29 +/- 4% in absence of endothelin, 0 +/- 5% in presence of endothelin; n = 6 preparations, P less than 0.001). (2) Endothelin inhibited ouabain-sensitive 86Rb+ uptake by 46.6 +/- 8.6% at 10 s and by 35.4 +/- 5.3% at 30 s without altering uptake at (60 min. 3) Addition of endothelin to IMCD cells induced a net K+ efflux with an initial rate of 32.2 +/- 4.8 nmol.min-1.mg protein-1, consistent with inhibition of the Na(+)-K(+)-ATPase. In contrast to the response observed in intact cells, in permeabilized IMCD cells endothelin did not inhibit ouabain-sensitive ATPase. Several observations indicated that prostaglandin E2 (PGE2) mediates endothelin inhibition of Na(+)-K(+)-ATPase activity. (1) The response to endothelin was blocked by ibuprofen in assays of QO2, net K+ flux, and 86Rb+ uptake. (2) Endothelin and PGE2 gave equivalent, nonadditive inhibition of ouabain-sensitive 86Rb+ uptake.

  19. Value of endothelin in cellular rejection after liver transplantation.

    Science.gov (United States)

    Fábrega, E; Figols, J; Dueñas, C; Crespo, J; Casafont, F; Sanchez-Antolín, G; de las Heras, G; Amado, J A; Pons-Romero, F

    1997-02-01

    Endothelin-1 is a vasoconstrictor peptide released by the vascular endothelium by various chemical and mechanical factors. Cellular rejection is one of the most common complications following orthotopic liver transplantation, endotheliitis being its most specific and consistent histological feature. To assess the role of endothelin in cellular hepatic rejection, we studied 21 cirrhotic patients undergoing elective liver transplantation. These patients were divided in two groups: Group I comprised 10 patients without cellular rejection, and Group II comprised 11 patients with cellular rejection. Endothelin was measured on day 7 after transplantation, on the day of liver biopsy, and after treatment for rejection. We found a significant increase in the plasma endothelin levels in the early postoperative period in the patients with moderate or severe cellular rejection compared with the non-rejection group. It remained significantly elevated until the clinical diagnosis of rejection was made. This value returned to baseline with successful treatment. So, the monitorization of this peptide may be of help in the diagnosis of rejection, its severity, and the evaluation of its resolution.

  20. Evaluation of Homocysteine, Lipoprotein(a) and Endothelin as ...

    African Journals Online (AJOL)

    Indians have been reported to have high prevalence rates of coronary artery disease (CAD) even in the absence of traditional risk factors. The objective of this study was to assess the role of endothelin, lipoprotein(a), homocysteine and lipid profile as markers of CAD in Indian population. It was a hospital based ...

  1. Evaluation of Homocysteine, Lipoprotein(a and Endothelin as diagnostic markers of Coronary Artery Disease in Indian population

    Directory of Open Access Journals (Sweden)

    Vandana Saini

    2013-01-01

    Full Text Available Indians have been reported to have high prevalence rates of coronary artery disease (CAD even in the absence of traditional risk factors. The objective of this study was to assess the role of endothelin, lipoprotein(a, homocysteine and lipid profile as markers of CAD in Indian population. It was a hospital based observational case-control study, which included 60 documented patients of CAD, and 50 age and sex matched controls. Routine biochemical parameters were performed. Lipoprotein(a, homocysteine and endothelin levels were estimated by enzyme linked immunosorbent assay. The levels of endothelin (9.78±0.40 pg/ml vs. 7.86±0.31 pg/ml, lipoprotein(a (51.42±1.71 mg/dl vs. 36.26±1.21 mg/dl, homocysteine (21.31±1.22 µmol/L vs. 10.41±0.844 µmol/L and LDL/HDL cholesterol ratio (4.23±0.32 vs. 2.60±0.10 were significantly higher whereas that of HDL (29.82±1.39 mg/dl vs. 40.82±6.24 mg/dl was significantly lower in patients of CAD as compared to the controls (p0.7 for all the markers. Higher levels of homocysteine, endothelin, and lipoprotein(a were independently associated with increased risk of CAD. Thus, they may be helpful in risk assessment in premature cardiovascular disease and in individuals where traditional risk factors are not present.

  2. Serum big endothelin-1 as a biomarker in oral squamous cell carcinoma patients: an analytical study.

    Science.gov (United States)

    Mankapure, Pritam Kumar; Barpande, Suresh Ramchandra; Bhavthankar, Jyoti Dilip; Mandale, Manda

    2015-10-01

    Detection of abnormally elevated levels of molecules in patients with oral cancer may be useful in early diagnosis. These markers can be included in current Histopathology grading and in TNM staging systems of Oral Squamous Cell Carcinoma (OSCC) to make it more efficient. Several pro-angiogenic molecules have been assessed for the same reason. Endothelin-1 (ET-1) is a vasoactive peptide associated with the development and spread of many solid tumors, including Squamous Cell Carcinoma (SCC), but its utility in OSCC has not been confirmed. This study aims to evaluate the role of the serum big ET-1 as a biomarker of OSCC, by correlating it with the clinical staging and the histopathological grading. Serum levels of big ET-1 measured by the sandwich Enzyme-Linked Immunosorbent Assay (ELISA) in 40 OSCC cases were compared with the levels from the control group using independent t-test. Clinical stages and histopathological grades of OSCC cases were compared in relation to their mean levels of serum big ET-1, one using the Analysis of Variance (ANOVA) test and the other the independent t-test, respectively. The significance of the mean difference between the groups was evaluated by Tukey's multiple comparison test. All statistical analyses were performed on GraphPad statistical software version 5.0. By comparing the mean of the big ET-1 concentrations of cases and controls, the independent t-test revealed significant higher big ET-1 concentration of OSCC cases when compared to controls (pbig ET-1. However, the mean of the big ET-1 concentrations of cases of grade I and of grade II did not differ statistically (p=0.729). Serum big ET-1 levels may be useful as a diagnostic tool in OSCC and as an adjunct to OSCC staging. However, its use as a prognostic marker warrants larger prospective studies.

  3. Effects of endothelin family on ANP secretion.

    Science.gov (United States)

    Yuan, Kuichang; Park, Byung Mun; Choi, Young Tae; Kim, Jong Hun; Cho, Kyung Woo; Kim, Suhn Hee

    2016-08-01

    The endothelins (ET) peptide family consists of ET-1, ET-2, ET-3, and sarafotoxin (s6C, a snake venom) and their actions appears to be different among isoforms. The aim of this study was to compare the secretagogue effect of ET-1 on atrial natriuretic peptide (ANP) secretion with ET-3 and evaluate its physiological meaning. Isolated nonbeating atria from male Sprague-Dawley rats were used to evaluate stretch-activated ANP secretion in response to ET-1, ET-2, ET-3, and s6C. Changes in mean blood pressure (MAP) were measured during acute injection of ET-1 and ET-3 with and without natriuretic peptide receptor-A antagonist (A71915) in anesthetized rats. Changes in atrial volume induced by increased atrial pressure from o to 1, 2, 4, or 6cm H2O caused proportional increases in mechanically-stimulated extracellular fluid (ECF) translocation and stretch-activated ANP secretion. ET-1 (10nM) augmented basal and stretch-activated ANP secretion in terms of ECF translocation, which was blocked by the pretreatment with ETA receptor antagonist (BQ123, 1μM) but not by ETB receptor antagonist (BQ788, 1μM). ETA receptor antagonist itself suppressed stretch-activated ANP secretion. As compared to ET-1- induced ANP secretion (3.2-fold by 10nM), the secretagogue effects of ANP secretion by ET-2 was similar (2.8-fold by 10nM) and ET-3 and s6C were less potent (1.7-fold and 1.5-fold by 100nM, respectively). Acute injection of ET-1 or ET-3 increased mean blood pressure (MAP), which was augmented in the presence of natriuretic peptide receptor-A antagonist. Therefore, we suggest that the order of secretagogue effect of ET family on ANP secretion was ET-1≥ET-2>ET-3>s6C and ET-1-induced ANP secretion negatively regulates the pressor effect of ET-1. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Endothelin receptor antagonists for pulmonary arterial hypertension.

    Science.gov (United States)

    Liu, C; Chen, J

    2006-07-19

    Pulmonary arterial hypertension (PAH) is a devastating disease, which leads to right heart failure and premature death. Pulmonary arterial hypertension can be classified into five categories according to Venice classification: (1) Idiopathic PAH; (2) Familial PAH; (3) PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts, portal hypertension, HIV infection, drugs and toxins or other (thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy); (4) PAH associated with significant venous or capillary involvement, which includes pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH); (5) Persistent pulmonary hypertension of the newborn. PAH can also be secondary to chronic hypoxic lung disease as part of the "cor-pulmonale" syndrome, and also secondary to left sided heart disease, but these conditions are usually distinguished from those listed here. To evaluate the efficacy of endothelin receptor antagonists in pulmonary arterial hypertension. A search was carried out using the CENTRAL (Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE, and the reference section of retrieved articles. Searches are current as of August 2005. Randomised controlled trials (RCTs) or quasi-randomised controlled trials involving patients with pulmonary arterial hypertension (PAH) were selected by two reviewers. Two reviewers independently selected studies; assessed study quality; and extracted data. We analysed outcomes as continuous and dichotomous data. In this updated version of the review, we added two RCTs. Altogether, five RCTs met the entry criteria of the review (reporting eight group comparisons). The studies were of short duration (12-16 weeks), recruiting a total of 482 participants. Three studies compared a non-selective ERA (bosentan) with placebo, one compared bosentan with sildenafil (a

  5. Therapeutic potential of endothelin inhibitors in canine hemangiosarcoma.

    Science.gov (United States)

    Fukumoto, Shinya; Saida, Kaname; Sakai, Hiroki; Ueno, Hiroshi; Iwano, Hidetomo; Uchide, Tsuyoshi

    2016-08-15

    Hemangiosarcoma (HSA) that originates from vascular endothelial cells is the most common splenic malignant neoplasm in dogs, as it accounts for approximately 20% of all canine soft tissue sarcomas. In this study, inhibitory effects of endothelin receptor antagonists on the growth of HSA cells were examined using cell lines established from canine HSA. The preproendothelin-1 (PPET-1), endothelin type A receptor (ETA) and endothelin type B receptor (ETB) mRNA expression levels in HSA cell lines (n=5) were analyzed quantitatively by real-time RT-PCR. These levels were compared with those in HSA tissues (n=11) and those in normal splenic tissues (n=6). ETA and ETB protein expression was examined by western blot. The production and secretion of endothelin-1 (ET-1) and big ET-1 by cell lines were analyzed by measuring the levels in the culture medium by ELISA. The inhibitory effects of endothelin receptor antagonists (ambrisentan, BQ788 and bosentan) on cell growth were evaluated by WST-8 assay. The PPET1 and ETA mRNA expression levels were elevated in HSA tissues and HSA cell lines compared with normal tissues. In cell lines, the production of ET-1 and big ET-1 peptide as well as the expression of ETA protein were detected, but the levels of ETB were not measured. Ambrisentan and bosentan inhibited growth activity in cell lines. Ambrisentan was more effective than bosentan. These findings demonstrate the importance of the ETA axis in canine HSA as well as the potential of ETA inhibitors in the treatment of canine HSA. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Gene Expression of Endothelin-1 and Endothelin Receptor A on Monocrotaline-Induced Pulmonary Hypertension in Rats After Bosentan Treatment

    Science.gov (United States)

    Lim, Kyoung Ah; Kim, Kwan Chang; Cho, Min-Sun; Lee, Bo En; Kim, Hae Soon

    2010-01-01

    Background and Objectives Endothelin (ET)-1, a potent endothelium-derived vasoconstrictor peptide, has a potential pathophysiologic role in pulmonary hypertension. Bosentan, a dual ET receptor (ETA/ETB) antagonist, is efficacious in treatment of pulmonary hypertension. The objectives of this study were to investigate the expression of ET-1 and ET receptor A (ERA) genes and to evaluate the effect of bosentan in monocrotaline (MCT)-induced pulmonary hypertension. Materials and Methods Four-week-old male Sprague-Dawley rats were treated as follows: control (n=36), subcutaneous (sc) injection of saline; MCT (n=36), sc injection of MCT (60 mg/kg); and bosentan (n=36), sc injection of MCT (60 mg/kg) plus 25 mg/kg/day bosentan orally. Results Serum ET-1 concentrations in the MCT group were higher than the control group on day 28 and 42. Quantitative analysis of peripheral pulmonary arteries revealed that the increase in medial wall thickness after MCT injection was significantly attenuated in the bosentan group on day 28 and 42. In addition, the increase in the number of intra-acinar muscular arteries after MCT injection was reduced by bosentan on day 14, 28 and 42. The levels of ET-1 and ERA gene expression were significantly increased in the MCT group compared with control group on day 5, and bosentan decreased the expression of ET-1 on day 5. Conclusion ET-1 contributes to the progression of cardiopulmonary pathology in rats with MCT-induced pulmonary hypertension. Administration of bosentan reduced ET-1 gene expression in MCT-induced pulmonary hypertension in rats. PMID:20967148

  7. G-231A and G+70C polymorphisms of endothelin receptor type-A gene could affect the psoriasis area and severity index score and endothelin 1 levels

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    Gökhan Okan

    2015-01-01

    Full Text Available Background: The etiopathogenesis of psoriasis has not been clearly elucidated although the role of chronic inflammation, imbalance between pro- and anti-inflammatory cytokines, and many immunological events have been established. Endothelin 1 (EDN1 and endothelin receptor type-A (EDNRA are implicated in the inflammatory process. The relationships between EDN1 and EDNRA polymorphisms with several diseases have been found. Aims and Objectives: This study examined the possible association of EDN1 (G5665T and T-1370G and EDNRA (G-231A and G + 70C single nucleotide polymorphisms (SNPs with the occurence of psoriasis, and evaluated the relationship between genotypes and clinical/laboratory manifestation of psoriasis. Materials and Methods: We analyzed genotype and allele distributions of the above-mentioned polymorphisms in 151 patients with psoriasis and 152 healthy controls by real-time PCR combined with melting curve analysis. Results: We did not find significant differences in the genotype and allele distributions of EDN1 T-1370G, EDNRA G-231A, and EDNRA G+70C polymorphisms between patients with psoriasis and healthy controls. Psoriasis area and severity index (PASI score of EDNRA -231 polymorphic A allele carrying subjects (AA and AA + AG was higher than that of wild homozygotes (P = 0.044 and P = 0.027, respectively. In addition, EDN1 levels in EDNRA+70 polymorphic C allele carriers (CC + CG were elevated when compared with GG genotype; however, the difference was at borderline significance (P = 0.05. Conclusion: Although there were no associations between studied polymorphisms and psoriasis susceptibility, the PASI score and EDN1 levels seem to be affected by EDNRA G-231A and G + 70C polymorphisms.

  8. NITRIC OXIDE AND ENDOTHELIN-1 IN CHILDREN WITH DIGESTIVE DISORDERS

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    I. V. Panova

    2012-01-01

    Full Text Available The important part in the group of biological compounds, participating in the regulation of the functions of the gastro-intestinal tract, is assigned to endothelial factors because of their impact on the majority of physiological and pathophysiological processes of the digestive system. The article provides information about physiological role of nitric oxide and endothelin-1 and presents a review of scientific data on the participation of nitric oxide and endothelin-1 in the pathogenesis of many digestive system diseases, emphasizing chronic inflammatory disorders of the upper gastrointestinal tract. The authors accentuate the importance of endothelium endocrine function research in children with esophagogastroduodenal disorders at the beginning of puberty, which is the critical period of ontogenesis.

  9. Vascular effects of Endothelin in Experimental lung injury

    OpenAIRE

    Persson, Björn P.

    2012-01-01

    Acute lung injury remains a frequent and life threatening consequence of severe sepsis. This thesis has investigated the role of the endothelin (ET) system in sepsis-induced lung injury, with special reference to its effects on two hallmarks of this syndrome - formation of edema and pulmonary hypertension. This was explored in a porcine endotoxin model of sepsis in vivo, as well as in vitro using isolated porcine pulmonary vessels. In paper I we show that endotoxemia vi...

  10. Correlations between plasma endothelin-1 levels and breakthrough pain in patients with cancer

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    Yan XB

    2015-12-01

    Full Text Available Xue-bin Yan, Tuo-chao Peng, Dong Huang Department of Anesthesiologist, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, People’s Republic of China Abstract: Endothelin-1 (ET-1 may be involved in driving pain in patients with advanced cancer. However, a few studies focus on the role of ET-1 in breakthrough pain (BP. The aim of this pivotal study was to explore the correlation between the plasma (ET-1 level and BP intensity. A total of 40 patients were enrolled in the study, and they were divided into two groups: BP group and non-BP group. Moreover, 20 healthy adults were used as the normal control group. Pain intensity was measured using visual analog scale (VAS scores of 1–10. Plasma ET-1 levels were detected by an ET radioimmunoassay kit. Subsequently, the correlation of ET-1 level with the VAS score and cancer types was analyzed by Pearson’s correlation coefficient. The plasma ET-1 level in the BP group (35.31±8.02 pg/mL was higher than that in the non-BP group (29.51±6.78 pg/mL and the normal control group (24.77±10.10 pg/mL, P<0.05. In addition, the VAS score in the BP group (7.45±0.82 was higher than that in the non-BP group (2.80±1.23, P<0.05. The plasma ET-1 level was positively correlated with the VAS score of the BP group (Pearson’s r=0.42. There was no significant correlation between the plasma ET-1 level and VAS score of the non-BP group (Pearson’s r=–0.22 or/and cancer types (P>0.05. The elevated plasma ET-1 levels were positively related to BP, and targeting ET-1 may provide a novel pain-reducing therapeutic treatment in BP. Keywords: visual analog scale, correlation, cancer types, background pain

  11. Higher serum asymmetric dimethylarginine is related to higher risk of heart failure in the EPIC-Potsdam study.

    Science.gov (United States)

    Wirth, Janine; Atzler, Dorothee; di Giuseppe, Romina; Cordts, Kathrin; Menzel, Juliane; Böger, Rainer H; Boeing, Heiner; Weikert, Cornelia; Schwedhelm, Edzard

    2017-01-01

    L-Arginine is the substrate of endothelial nitric oxide (NO) synthase forming NO which inherits various biological cardio-protective functions. The dimethylarginines asymmetric (ADMA) and symmetric dimethylarginine (SDMA) can impair the synthesis of NO and are elevated in patients with cardiovascular disease, including heart failure (HF). We investigated the association between dimethylarginines and HF risk in a case-cohort study of the European Prospective Investigation into Cancer and Nutrition (n = 27,548), comprising a random subcohort (n = 2224 including 19 HF cases), and all remaining HF cases (n = 176) that occurred within 8.3 years of follow-up. Serum concentrations of dimethylarginines were measured using liquid chromatography-tandem mass spectrometry. Hazards ratios (HRs) and 95% confidence intervals (CI) were estimated across quartiles and per doubling of ADMA and SDMA concentrations using Cox's proportional hazards regression. After multivariable adjustment, each doubling of ADMA was associated with a 60% higher HF risk (HR [95% CI] 1.60 [1.10-2.31]). Between SDMA and HF risk a U-shaped association was observed (HR [95% CI] for the second, third and fourth quartile compared to the first: 0.52 [0.33-0.82], 0.63 [0.40-0.99], and 0.71 [0.46-1.10], p for nonlinearity <0.01). We provide substantiated evidence for a relationship between ADMA and cardiovascular endpoints. In addition to the established relation between ADMA and myocardial infarction, our findings indicate a positive association between ADMA and HF incidence in persons without apparent myocardial infarction. Targeting the ADMA metabolism might open up new therapeutic perspective for HF prevention and treatment. Further investigations are needed to shed more light on mechanisms involved in the pathogenesis of HF related to elevated ADMA levels.

  12. Used energy-related laboratory equipment grant program for institutions of higher learning. Eligible equipment catalog

    Energy Technology Data Exchange (ETDEWEB)

    1994-07-01

    This is a listing of energy related equipment available through the Energy-Related Laboratory Equipment Grant Program which grants used equipment to institutions of higher education for energy-related research. Information included is an overview of the program, how to apply for a grant of equipment, eligibility requirements, types of equipment available, and the costs for the institution.

  13. Serum big endothelin-1 as a biomarker in oral squamous cell carcinoma patients: an analytical study

    Directory of Open Access Journals (Sweden)

    Pritam Kumar MANKAPURE

    2015-10-01

    Full Text Available Detection of abnormally elevated levels of molecules in patients with oral cancer may be useful in early diagnosis. These markers can be included in current Histopathology grading and in TNM staging systems of Oral Squamous Cell Carcinoma (OSCC to make it more efficient. Several pro-angiogenic molecules have been assessed for the same reason. Endothelin-1 (ET-1 is a vasoactive peptide associated with the development and spread of many solid tumors, including Squamous Cell Carcinoma (SCC, but its utility in OSCC has not been confirmed.Objective This study aims to evaluate the role of the serum big ET-1 as a biomarker of OSCC, by correlating it with the clinical staging and the histopathological grading.Material and Methods Serum levels of big ET-1 measured by the sandwich Enzyme-Linked Immunosorbent Assay (ELISA in 40 OSCC cases were compared with the levels from the control group using independent t-test. Clinical stages and histopathological grades of OSCC cases were compared in relation to their mean levels of serum big ET-1, one using the Analysis of Variance (ANOVA test and the other the independent t-test, respectively. The significance of the mean difference between the groups was evaluated by Tukey’s multiple comparison test. All statistical analyses were performed on GraphPad statistical software version 5.0.Results By comparing the mean of the big ET-1 concentrations of cases and controls, the independent t-test revealed significant higher big ET-1 concentration of OSCC cases when compared to controls (p<0.0001. Tukey’s multiple comparison test also revealed statistically significant difference among all OSCC stages in relation to the mean levels of serum big ET-1. However, the mean of the big ET-1 concentrations of cases of grade I and of grade II did not differ statistically (p=0.729.Conclusion Serum big ET-1 levels may be useful as a diagnostic tool in OSCC and as an adjunct to OSCC staging. However, its use as a prognostic

  14. In depth pharmacological characterization of endothelin B receptors in the rat middle cerebral artery

    DEFF Research Database (Denmark)

    Szok, D; Hansen-Schwartz, J; Edvinsson, L

    2001-01-01

    endothelin B receptor agonist sarafotoxin 6c in precontracted cerebral arteries and in the presence of the endothelin A receptor blocker FR139317 caused vasodilation in a concentration-dependent manner. Inhibition of nitric oxide synthase significantly reduced the dilation induced by sarafotoxin 6c, whereas...

  15. Upregulation of endothelin ETB receptor-mediated vasoconstriction in rat coronary artery after organ culture

    DEFF Research Database (Denmark)

    Eskesen, Karen; Edvinsson, Lars

    2006-01-01

    descending coronary arteries isolated from hearts of rats as response to application of the selective endothelin ET(B) receptor agonist, Sarafotoxin 6c and endothelin-1. In segments cultured 1 day in serum free Dulbecco's Modified Eagle's Medium, Sarafotoxin 6c induced a concentration dependent contraction......The aim of this study was to examine if endothelin ET(B) receptor-mediated contraction occurred in isolated segments of rat coronary arteries during organ culture. Presence of contractile endothelin ET(B) receptors was studied by measuring the change in isometric tension in rings of left anterior...... after culturing could be eliminated with addition of the transcriptional blocker, actinomycin D, to the culture medium or be significantly attenuated by application of the translational inhibitor, cycloheximide. The vasoconstrictor effect of endothelin-1 or to depolarisation by high K...

  16. The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy

    DEFF Research Database (Denmark)

    de Zeeuw, Dick; Coll, Blai; Andress, Dennis

    2014-01-01

    Despite optimal treatment, including renin-angiotensin system (RAS) inhibitors, patients with type 2 diabetic nephropathy have high cardiorenal morbidity and mortality related to residual albuminuria. We evaluated whether or not atrasentan, a selective endothelin A receptor antagonist, further...... reduces albuminuria when administered concomitantly with maximum tolerated labeled doses of RAS inhibitors. We enrolled 211 patients with type 2 diabetes, urine albumin/creatinine ratios of 300-3500 mg/g, and eGFRs of 30-75 ml/min per 1.73 m(2) in two identically designed, parallel, multinational, double......, respectively) and reduced albuminuria≥30% in 51% and 55% of participants, respectively. eGFR and office BP measurements did not change, whereas 24-hour systolic and diastolic BP, LDL cholesterol, and triglyceride levels decreased significantly in both treatment groups. Use of atrasentan was associated...

  17. The studio organization of pedagogical mutual relations between participants of higher school the educational process.

    OpenAIRE

    Gonchar O.V.

    2011-01-01

    The specificity of the terms "educational technology" and "studio organization of pedagogical mutual relations" is characterized. The essence of trend of the studio organization of pedagogical mutual relations between participants of higher school the educational process as one of the leading terms both of the educational process efficiency, mastery of its members mechanisms of human relationships making to achieve professional goals and humanization of human relations is revealed. It is prov...

  18. The Role of Public Relations as A Management Function in Higher Education

    OpenAIRE

    Anggreni Putri

    2018-01-01

    Nowadays, public relations in higher education institution become an integral part of the management team. It must contribute to achieve organizational goals and demonstrate an organizational accountability identified by measurable result. Placement public relations at certain positions in management has consequences in the process of implementation of the public relations function. It happened because the management, workflow and hierarchy greatly affects work patterns as well as patterns of...

  19. International Relations As A Field Of Study In The Canadian System Of Higher Education

    Directory of Open Access Journals (Sweden)

    Istomina Kateryna

    2015-06-01

    Full Text Available The research presents an attempt to investigate the current state of international relations as a field of study in the context of higher education system in Canada. It contains a general overview of the field of study, focusing predominantly on the role and function of the given academic discipline. The scientific investigation covers the issue of short historiographic review of the development of international relations as a separate academic discipline and an independent field of study at the universities of Canada since it provides better understanding of the international relations evolution as a discipline in Canadian system of higher education. It gives information on the origins of international relations discipline in Canada and first higher education establishments, which provided professional training in the international relations field. The article reviews the official normative documents in the sphere of higher education in Canada, such as Major Field of Study Classification and Classification of Instructional Programs, being theoretical basis of our analysis. The research results can be used to outline the place of international relations major among the diversity of functioning academic majors in Canada. The research also turns to the profound analysis of the information about the offered instructional programs, dedicated to professional training of international relations specialists at the universities of Canada.

  20. Endothelin receptor A -231 G>A polymorphism: no linkage to primary pediatric headache.

    Science.gov (United States)

    Lisi, Veronica; Garbo, Greta; Battistella, PierAntonio; Miccichè, Flavia; Stecca, Anna; Terrazzino, Salvatore; Franzoi, Malida; Tripoli, Elisa; Leon, Alberta; Clementi, Maurizio

    2006-03-01

    To assess whether the biallelic -231 G>A polymorphism of the endothelin type A receptor (EDNRA) gene, previously shown to be a marker of increased risk for developing migraine, has a role in the susceptibility to primary pediatric headache. Several studies suggest that endothelin has a role in migraine. A recent association study has shown that the biallelic -231 G>A polymorphism of the EDNRA gene is associated to migraine in an elderly population. A total of 126 consecutive unrelated pediatric patients affected by primary headache, classified according to the International Headache Society criteria in migraine (migraine with aura, n = 3; migraine without aura, n = 80), and tension-type headache (episodic tension-type headache, n = 36; chronic tension-type headache, n = 7) patients, were recruited to the study. Sixty-seven healthy blood donors were used as a control group. Genomic DNA was extracted from buccal swabs or blood samples and analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the above-mentioned polymorphism. Allele and genotype frequencies for primary headache patients were analyzed in comparison with the control group. No significant differences were found in the distribution of the EDNRA -231 G>A polymorphic variant when considering both genotype (migraine chi2 = 2.78, P = .25; tension-type headache chi2 = 3.58, P = .17) and allelic frequencies (migraine chi2 = 1.48, P = .22; tension-type headache chi2 = 0.39, P = .56). Furthermore, no significant genotype-related difference was found in relation to clinical features, such as age at onset, frequency, and length of the attacks. Our study shows that the -231 G>A polymorphism in the EDNRA gene is neither associated with primary juvenile headache nor significantly correlated with main clinical features characteristic of the headache pathology in pediatric settings.

  1. Endothelin as an autocrine factor in the regulation of parathyroid cells

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Yoshio; Moreira, J.E.; Aurbach, G.D.; Sakaguchi, K. (National Inst. of Health, Bethesda, MD (United States)); Orlando, C.; Maggi, M.; Brandi, M.L. (Univ. of Florence (Italy))

    1991-05-15

    Endothelin, originally purified from porcine aortic endothelial cells, is widely distributed in tissues and is recognized as a product of epithelial cells, glial cells and neurons in addition to endothelial cells. The authors found evidence by mRNA content and immunoreactivity that this peptide is synthesized in rat parathyroid epithelial cells (PT-r cells) and bovine parathyroid chief cells. The peptide synthesized by PT-r cells comigrated with synthetic endothelin 1 in reverse-phase HPLC and was diluted out in radioimmunoassay in parallel with the synthetic peptide. Bovine parathyroid endothelial cells (BPE-1 cells) did by PT-r cells and endothelin 1 peptide production were regulated by calcium. Shifts in extracellular calcium either from high to low concentrations or vice versa elicited similar evanescent increases in expression of mRNA with a peak at 1 h. Synthesis of the peptide in the medium appears to be continuously degraded or taken up by cells because its concentration in the medium showed a time course similar to that of mRNA expression. PT-r cells also bear a single class of receptors highly specific for endothelin 1, suggesting an autocrine regulation by endothelin 1 of the parathyroid. The facile regulation of endothelin concentrations in the medium by shifts in extracellular calcium concentration and possible autocrine regulation by endothelin 1 suggest that this peptide may mediate, at least in part, effects of calcium on the parathyroid system.

  2. Evidence for the endothelin system as an emerging therapeutic target for the treatment of chronic pain

    Directory of Open Access Journals (Sweden)

    Smith TP

    2014-08-01

    Full Text Available Terika P Smith,1 Tami Haymond,1 Sherika N Smith,1 Sarah M Sweitzer1,2 1Department of Pharmacology, Physiology and Neuroscience, University of South Carolina, Columbia, SC, USA; 2Department of Pharmaceutical and Administrative Sciences, Presbyterian College School of Pharmacy, Clinton, SC, USA Abstract: Many people worldwide suffer from pain and a portion of these sufferers are diagnosed with a chronic pain condition. The management of chronic pain continues to be a challenge, and despite taking prescribed medication for pain, patients continue to have pain of moderate severity. Current pain therapies are often inadequate, with side effects that limit medication adherence. There is a need to identify novel therapeutic targets for the management of chronic pain. One potential candidate for the treatment of chronic pain is therapies aimed at modulating the vasoactive peptide endothelin-1. In addition to vasoactive properties, endothelin-1 has been implicated in pain transmission in both humans and animal models of nociception. Endothelin-1 directly activates nociceptors and potentiates the effect of other algogens, including capsaicin, formalin, and arachidonic acid. In addition, endothelin-1 has been shown to be involved in inflammatory pain, cancer pain, neuropathic pain, diabetic neuropathy, and pain associated with sickle cell disease. Therefore, endothelin-1 may prove a novel therapeutic target for the relief of many types of chronic pain. Keywords: endothelin-1, acute pain, chronic pain, endothelin receptor antagonists

  3. Over, and Underexpression of Endothelin 1 and TGF-Beta Family Ligands and Receptors in Lung Tissue of Broilers with Pulmonary Hypertension

    Science.gov (United States)

    Dominguez-Avila, Norma; Ruiz-Castañeda, Gabriel; González-Ramírez, Javier; Fernandez-Jaramillo, Nora; Escoto, Jorge; Sánchez-Muñoz, Fausto; Marquez-Velasco, Ricardo; Bojalil, Rafael; Espinosa-Cervantes, Román; Sánchez, Fausto

    2013-01-01

    Transforming growth factor beta (TGFβ) is a family of genes that play a key role in mediating tissue remodeling in various forms of acute and chronic lung disease. In order to assess their role on pulmonary hypertension in broilers, we determined mRNA expression of genes of the TGFβ family and endothelin 1 in lung samples from 4-week-old chickens raised either under normal or cold temperature conditions. Both in control and cold-treated groups of broilers, endothelin 1 mRNA expression levels in lungs from ascitic chickens were higher than levels from healthy birds (P 0.05). BAMBI mRNA gene expression was lowest in birds with ascites only in the control group as compared with the values from healthy birds (P < 0.05). PMID:24286074

  4. Higher Order Relations for ADE-Type Generalized q-Onsager Algebras

    Science.gov (United States)

    Baseilhac, Pascal; Vu, Thi Thao

    2015-09-01

    Let be the fundamental generators of the generalized q-Onsager algebra introduced in Baseilhac and Belliard (Lett Math Phys 93:213-228, 2010), where is a simply laced affine Lie algebra. New relations between certain monomials of the fundamental generators—indexed by the integer —are conjectured. These relations can be seen as deformed analogs of Lusztig's rth higher order q-Serre relations associated with , which are recovered as special cases. The relations are proven for . For r generic, several supporting evidences are presented.

  5. The importance of endothelin-1 for microvascular dysfunction in diabetes

    Directory of Open Access Journals (Sweden)

    Majid Kalani

    2008-10-01

    Full Text Available Majid KalaniDepartment of Clinical Sciences Karolinska Institutet, Dept of Cardiology, Danderyd Hospital, Stockholm, SwedenAbstract: Most of the late diabetic complications such as retinopathy, nephropathy, and neuropathy, have their basis in disturbed microvascular function. Structural and functional changes in the microcirculation are present in diabetes mellitus irrespective of the organ studied, and the pathogenesis is complex. Endothelial dysfunction, characterized by an imbalance between endothelium-derived vasodilator and vasoconstrictor substances, plays an important role in the pathogenesis of diabetic microangiopathy. Increased circulating levels of endothelin-1 (ET-1, a potent vasoconstrictor peptide, has been found in patients with diabetes, and a positive correlation between plasma ET-1 levels and microangiopathy in patients with type 2 diabetes has been demonstrated. In addition to its direct vasoconstrictor effects, enhanced levels of ET-1 may contribute to endothelial dysfunction through inhibitory effects on nitric oxide (NO production. Vascular endothelial dysfunction may precede insulin resistance, although the feature of insulin resistance syndrome includes factors that have negative effects on endothelial function. Furthermore, ET-1 induces a reduction in insulin sensitivity and may take part in the development of the metabolic syndrome. In the following, the mechanisms by which ET-1 contributes to the development of diabetic microangiopathy and the potentially beneficial effect of selective ETA receptor antagonists are discussed.Keywords: endothelin-1, diabetes mellitus, microcirculation, diabetic microangiopathy, ETA-receptor antagonist

  6. Endothelin receptors as novel targets in tumor therapy

    Directory of Open Access Journals (Sweden)

    Bagnato Anna

    2004-05-01

    Full Text Available Abstract The endotelin (ET axis, that includes ET-1, ET-2, ET-3, and the ET receptors, ETA and ETB, plays an important physiological role, as modulator of vasomotor tone, tissue differentiation and development, cell proliferation, and hormone production. Recently, investigations into the role of the ET axis in mitogenesis, apoptosis inhibition, invasiveness, angiogenesis and bone remodeling have provided evidence of the importance of the ET-1 axis in cancer. Data suggest that ET-1 participates in the growth and progression of a variety of tumors such as prostatic, ovarian, renal, pulmonary, colorectal, cervical, breast carcinoma, Kaposi's sarcoma, brain tumors, melanoma, and bone metastases. ET-1 receptor antagonists beside providing ideal tools for dissecting the ET axis at molecular level have demonstrated their potential in developing novel therapeutic opportunity. The major relevance of ETA receptor in tumor development has led to an extensive search of highly selective antagonists. Atrasentan, one of such antagonists, is orally bioavailable, has suitable pharmacokinetic and toxicity profiles for clinical use. Preliminary data from clinical trials investigating atrasentan in patients with prostate cancer are encouraging. This large body of evidence demonstrates the antitumor activity of endothelin receptor antagonists and provides a rationale for the clinical evaluation of these molecules alone and in combination with cytotoxic drugs or molecular inhibitors leading to a new generation of anticancer therapies targeting endothelin receptors.

  7. Vascular function and endothelin-1: tipping the balance between vasodilation and vasoconstriction.

    Science.gov (United States)

    Nishiyama, Steven K; Zhao, Jia; Wray, D Walter; Richardson, Russell S

    2017-02-01

    Endothelin-1 (ET-1), a potent vasoconstrictor secreted by vascular endothelial cells, has been implicated in the pathophysiology of numerous cardiovascular diseases, yet the direct impact of ET-1 on vascular function remains unclear. Therefore, in seven young (23 ± 1 yr) healthy subjects, we investigated the effect of an intra-arterial infusion of ET-1 on reactive hyperemia (RH) and flow-mediated dilation (FMD) in the popliteal artery following 5 min of suprasystolic cuff occlusion. ET-1 infusion significantly attenuated basal leg blood flow (control: 62 ± 4 ml/min, ET-1: 47 ± 9 ml/min), RH [area-under-curve (AUC); control: 162 ± 15 ml, ET-1: 104 ± 16 ml], and peak RH (control: 572 ± 51 ml/min, ET-1: 412 ± 32 ml/min) (P tipping the balance between vasodilation and vasoconstriction, in favor of the latter.NEW & NOTEWORTHY Endothelin-1 (ET-1) is recognized as the body's most potent endogenous vasoconstrictor, but the impact of this peptide on vascular function is not well understood. The present study revealed that the intra-arterial administration of ET-1 impaired both microvascular and conduit vessel function of the leg in young, healthy, humans. Studies employing vascular testing in patient cohorts that experience a disease-related increase in ET-1 should thus exercise caution, as ET-1 clearly impairs vascular function. Copyright © 2017 the American Physiological Society.

  8. Threshold Concepts in Higher Education: A Synthesis of the Literature Relating to Measurement of Threshold Crossing

    Science.gov (United States)

    Nicola-Richmond, Kelli; Pépin, Geneviève; Larkin, Helen; Taylor, Charlotte

    2018-01-01

    In relation to teaching and learning approaches that improve student learning outcomes, threshold concepts have generated substantial interest in higher education. They have been described as "portals" that lead to a transformed way of understanding or thinking, enabling learners to progress, and have been enthusiastically adopted to…

  9. Understanding the African-American Student Experience in Higher Education through a Relational Dialectics Perspective

    Science.gov (United States)

    Simmons, Jake; Lowery-Hart, Russell; Wahl, Shawn T.; McBride, M. Chad

    2013-01-01

    In this study, we sought to understand African-American students' higher-education experiences in predominantly White universities. We utilized Baxter's relational dialectics theory to study components of focus-group discussions in order to understand the discourse and meaning-making process of participants. Our findings provide insight into the…

  10. Civic Mission and Social Responsibility: New Challenges for the Practice of Public Relations in Higher Education

    Science.gov (United States)

    Kantanen, Helena

    2005-01-01

    What is the civic mission of the research university in a modern society? How does it challenge the Public Relations professionals of universities? The Finnish Higher Education Evaluation Council, a specialist organ of the Ministry of Education, has conducted several university evaluations with special emphasis on the regional role of Finnish…

  11. Cui Bono? On the Relative Merits of Technology-Enhanced Learning and Teaching in Higher Education

    Science.gov (United States)

    Mykhnenko, Vlad

    2016-01-01

    This article provides evidence from a 4-year longitudinal study on the comparative use of illustrative video podcasts during Economic Geography lectures vis-à-vis traditional educational methods in order to guide pedagogic practice and future research on the relative merits of technology-enhanced learning in higher education. Key benefits derived…

  12. A Countrywide Study on Factors Influencing the Public Relations Practice in Higher Education in Taiwan

    Science.gov (United States)

    Yang, Mu-Li; Chiou, Wen-Bin

    2010-01-01

    This countrywide study was conducted to determine what organizational and individual factors have a significant impact on the performance of public relations (PR) practice in higher educational institutions in Taiwan. In this study, a purposive sampling of 600 administrative staff whose jobs involved university PR was employed, and 301 effective…

  13. Exploring Public Relations Excellence and Integrated Marketing Communications at Private, Nonprofit Higher Education Institutions

    Science.gov (United States)

    Higgins, Shannon K.

    2017-01-01

    Purpose: Many recent articles discuss the increased marketization of higher education, but few examine whether such practices are executed at their optimum level of efficiency and efficacy. This study addressed the significant lack of research in this area and answers the central question of how optimally public relations and marketing departments…

  14. International Relations as a Field of Study in the Canadian System of Higher Education

    Science.gov (United States)

    Istomina, Kateryna

    2015-01-01

    The research presents an attempt to investigate the current state of international relations as a field of study in the context of higher education system in Canada. It contains a general overview of the field of study, focusing predominantly on the role and function of the given academic discipline. The scientific investigation covers the issue…

  15. The Role of Public Relations as A Management Function in Higher Education

    Directory of Open Access Journals (Sweden)

    Anggreni Putri

    2018-01-01

    Full Text Available Nowadays, public relations in higher education institution become an integral part of the management team. It must contribute to achieve organizational goals and demonstrate an organizational accountability identified by measurable result. Placement public relations at certain positions in management has consequences in the process of implementation of the public relations function. It happened because the management, workflow and hierarchy greatly affects work patterns as well as patterns of decision making in carrying out communication tasks performed by public relations.The goal of research to find out the role and position in public relations in management education institution (university in achieving its objectives. After identification of roles and positions performance public relations firm, the study aims to evaluate the performance of public relations as part of management.This study used a qualitative descriptive research method with the study subjects were Mahendradatta University Public Relations and internal stakeholders. Data drawn from interviews with the help of the interview guide and then processed into information that can answer the research objectives.The result of the research shows that not all public relations officers in Mahendradatta University, do their role as real public relations officers. They also do not have the same understanding about the role of a public relations officer will just place public relations in same position as marketing.

  16. Higher-Loop Amplitude Monodromy Relations in String and Gauge Theory.

    Science.gov (United States)

    Tourkine, Piotr; Vanhove, Pierre

    2016-11-18

    The monodromy relations in string theory provide a powerful and elegant formalism to understand some of the deepest properties of tree-level field theory amplitudes, like the color-kinematics duality. This duality has been instrumental in tremendous progress on the computations of loop amplitudes in quantum field theory, but a higher-loop generalization of the monodromy construction was lacking. In this Letter, we extend the monodromy relations to higher loops in open string theory. Our construction, based on a contour deformation argument of the open string diagram integrands, leads to new identities that relate planar and nonplanar topologies in string theory. We write one and two-loop monodromy formulas explicitly at any multiplicity. In the field theory limit, at one-loop we obtain identities that reproduce known results. At two loops, we check our formulas by unitarity in the case of the four-point N=4 super-Yang-Mills amplitude.

  17. Higher emotional intelligence is related to lower test anxiety among students

    Science.gov (United States)

    Ahmadpanah, Mohammad; Keshavarz, Mohammadreza; Haghighi, Mohammad; Jahangard, Leila; Bajoghli, Hafez; Sadeghi Bahmani, Dena; Holsboer-Trachsler, Edith; Brand, Serge

    2016-01-01

    Background For students attending university courses, experiencing test anxiety (TA) dramatically impairs cognitive performance and success at exams. Whereas TA is a specific case of social phobia, emotional intelligence (EI) is an umbrella term covering interpersonal and intrapersonal skills, along with positive stress management, adaptability, and mood. In the present study, we tested the hypothesis that higher EI and lower TA are associated. Further, sex differences were explored. Method During an exam week, a total of 200 university students completed questionnaires covering sociodemographic information, TA, and EI. Results Higher scores on EI traits were associated with lower TA scores. Relative to male participants, female participants reported higher TA scores, but not EI scores. Intrapersonal and interpersonal skills and mood predicted low TA, while sex, stress management, and adaptability were excluded from the equation. Conclusion The pattern of results suggests that efforts to improve intrapersonal and interpersonal skills, and mood might benefit students with high TA. Specifically, social commitment might counteract TA. PMID:26834474

  18. In depth pharmacological characterization of endothelin B receptors in the rat middle cerebral artery

    DEFF Research Database (Denmark)

    Szok, D; Hansen-Schwartz, J; Edvinsson, L

    2001-01-01

    middle cerebral artery were cannulated with micropipettes, pressurized and luminally perfused. Vessel diameters were evaluated using a microscope equipped with an imaging system. Both intra- and extraluminal applications of endothelin-1 produced constriction. Intraluminal administration of a selective...

  19. Endothelin-1 downregulates Mas receptor expression in human cardiomyocytes.

    Science.gov (United States)

    Chen, Zhiheng; Tang, Yamei; Yang, Zuocheng; Liu, Shaojun; Liu, Yong; Li, Yan; He, Wei

    2013-09-01

    Endothelin-1 (ET-1) and the renin-angiotensin system (RAS) are involved in the pathogenesis of cardiac dysfunction. The Mas receptor is a functional binding site for angiotensin (Ang)‑(1-7), which is now considered a critical component of the RAS and exerts cardioprotective effects. To the best of our knowledge, the present study aimed to examine, for the first time, the effects of ET-1 on Mas expression in cultured human cardiomyocytes. Human cardiomyocytes were treated with ET-1 at different concentrations (1, 5, 10, 20 and 30 nM) for varied time periods (0.5, 1.5, 3, 4.5 or 6 h) with or without the transcription inhibitor actinomycin D, endothelin A (ETA) receptor blocker BQ123 and ETB receptor blocker BQ788, or different kinase inhibitors. ET-1 decreased the Mas mRNA level in a statistically significant dose- and time-dependent manner within 4.5 h, which was reflected in the dose-dependent downregulation of Mas promoter activity, Mas protein levels and Ang-(1-7) binding on the cell membrane. Actinomycin D (1 mg/ml), BQ123 (1 µM), p38 mitogen-activated protein kinase (MAPK) siRNA and inhibitor PD169316 (25 µM), completely eliminated the inhibitory effects of ET-1 on Mas expression in human cardiomyocytes. In conclusion, the present study demonstrated that ET-1 downregulates Mas expression at the transcription level in human cardiomyocytes via the ETA receptor by a p38 MAPK‑dependent mechanism. This study provides novel insights into the function of ET-1 and the Ang‑(1-7)/Mas axis in cardiac pathophysiology.

  20. Does coronary vasodilation after adenosine override endothelin-1-induced coronary vasoconstriction?

    Science.gov (United States)

    Loghin, Catalin; Sdringola, Stefano; Gould, K Lance

    2007-01-01

    Endothelin-1 is a powerful coronary vasoconstrictor that is overexpressed in coronary artery disease. Adenosine is a powerful coronary vasodilator used for myocardial perfusion imaging to identify flow-limiting coronary artery stenosis. Therefore, in an animal model we tested the hypothesis that intracoronary endothelin-1 may cause myocardial perfusion abnormalities by positron emission tomography (PET) at resting conditions that may persist or only partially improve after intravenous adenosine stress in the absence of myocardial scar and flow-limiting stenosis. Fourteen dogs underwent serial PET perfusion imaging with rubidium-82 before and after subselective intracoronary infusion of endothelin-1, followed by intravenous and then intracoronary adenosine. Small physiological doses of endothelin-1 infused into the mid-left circumflex coronary artery caused quantitatively significant resting perfusion abnormalities that normalized after intracoronary adenosine but not consistently after intravenous adenosine used for diagnostic imaging. After effects of adenosine abated, resting perfusion defects returned, lasting up to 5 h in some animals. Cumulative doses of endothelin-1 caused perfusion defects that did not normalize after intravenous adenosine. In an animal model without myocardial scar or flow-limiting stenosis, intracoronary endothelin-1 causes visually apparent, quantitatively significant, long-lasting myocardial perfusion defects at resting conditions that may persist or only partially improve after intravenous adenosine used for diagnostic imaging. These results may potentially explain resting perfusion abnormalities or heterogeneity by clinical PET that may persist or only partially improve after adenosine stress perfusion imaging in the absence of myocardial scar and flow-limiting stenosis.

  1. Evaluation of C-Reactive Protein, Endothelin-1, Adhesion Molecule(s, and Lipids as Inflammatory Markers in Type 2 Diabetes Mellitus Patients

    Directory of Open Access Journals (Sweden)

    Hala El-Mesallamy

    2007-01-01

    Full Text Available This study compared lipids, the product of lipid peroxidation malondialdehyde (MDA, the acute phase reactant high sensitive C-reactive protein (hsCRP, endothelin-1 (ET-1, P-selectin, intercellular adhesion molecule-1 (ICAM-1, and vascular cell adhesion molecule-1 (VCAM-1 between healthy controls, subjects with ischemic heart disease (IHD and type 2 diabetes mellitus (DM subjects who did not perform coronary artery bypass graft (CABG surgery as well as type 2 DM subjects who performed CABG. HbA1c, lipids, MDA, hsCRP, ET-1, P-selectin, ICAM-1, and VCAM-1 levels were significantly higher in the diabetic groups than in either healthy controls or IHD subjects. In the diabetic groups, there was a negative association among hsCRP and HDL-C. ET-1, ICAM-1 levels and TAG were positively correlated, as do the association between P-selectin, VCAM-1 and HbA1c%. Also a positive relation was found among hsCRP levels and ICAM-1, as well as MDA and ET-1. P-selectin and ICAM-1 were significantly positively correlated. This study indicates that increased level of oxidative stress marker, proinflammatory markers and their downstream effectors adhesion molecules occurs in type 2 DM.

  2. Higher Grades and Repeated Recurrence of Hepatic Encephalopathy May Be Related to High Serum Manganese Levels.

    Science.gov (United States)

    Kobtan, Abdelrahman A; El-Kalla, Ferial S; Soliman, Hanan H; Zakaria, Soha S; Goda, Mohamed A

    2016-02-01

    Hepatic encephalopathy is a serious complication of liver failure. Until now, the precise pathophysiologic mechanisms are not fully determined. It has been demonstrated that manganese plays an important role in the pathogenesis of hepatic encephalopathy. Therefore, we studied manganese levels in serum of cirrhotic patients with hepatic encephalopathy in relation to grading and recurrence of hepatic encephalopathy. One hundred persons were enrolled in the study, 80 cirrhotic patients with or without encephalopathy and 20 healthy controls. Hepatic encephalopathy was diagnosed clinically and by laboratory findings. Serum manganese levels were measured in all participants. The grading of hepatic encephalopathy was significantly correlated to the severity of liver dysfunction. The mean serum manganese level was significantly higher in cirrhotic patients than in controls and in cirrhotic patients with encephalopathy than in those without encephalopathy. It was also significantly higher in patients with advanced grading of hepatic encephalopathy. Serum manganese level was positively correlated to number of recurrences of encephalopathy during a 6-month follow-up period. Serum manganese levels were able to predict recurrence of hepatic encephalopathy within 6 months following the episode. Serum manganese levels are positively correlated to the modified Child-Pugh score of cirrhosis as well as grading and number of recurrences of hepatic encephalopathy. Higher manganese levels seem to be related to worsening of the condition, and its measurement may be used as a predictor of repeated recurrences.

  3. Impulsivity-related Traits Are Associated with Higher White Blood Cell Counts

    Science.gov (United States)

    Sutin, Angelina R.; Milaneschi, Yuri; Cannas, Alessandra; Ferrucci, Luigi; Uda, Manuela; Schlessinger, David; Zonderman, Alan B.; Terracciano, Antonio

    2012-01-01

    A chronically elevated white blood cell (WBC) count is a risk factor for morbidity and mortality. The present research tests whether facets of impulsivity – impulsiveness, excitement-seeking, self-discipline, and deliberation – are associated with chronically elevated WBC counts. Community-dwelling participants (N=5,652) from Sardinia, Italy, completed a standard personality questionnaire and provided blood samples concurrently and again three years later. Higher scores on impulsivity, in particular impulsiveness and excitement-seeking, were related to higher total WBC counts and higher lymphocyte counts at both time points. Impulsiveness was a predictor of chronic inflammation: For every standard deviation difference in this trait, there was an almost 25% higher risk of elevated WBC counts at both time points (OR=1.23, 95% CI=1.10–1.38). These associations were mediated, in part, by smoking and body mass index. The findings demonstrate that links between psychological processes and immunity are not limited to acute stressors; stable personality dispositions are associated with a chronic inflammatory state. PMID:22190235

  4. Smoking particles enhance endothelin A and endothelin B receptor-mediated contractions by enhancing translation in rat bronchi

    Directory of Open Access Journals (Sweden)

    Vikman Petter

    2006-03-01

    Full Text Available Abstract Background Smoking is known to cause chronic inflammatory changes in the bronchi and to contribute to airway hyper-reactivity, such as in bronchial asthma. To study the effect of smoking on the endothelin system in rat airways, bronchial segments were exposed to DMSO-soluble smoking particles (DSP from cigarette smoke, to nicotine and to DMSO, respectively. Methods Isolated rat bronchial segments were cultured for 24 hours in the presence or absence of DSP, nicotine or DMSO alone. Contractile responses to sarafotoxin 6c (a selective agonist for ETB receptors and endothelin-1 (an ETA and ETB receptor agonist were studied by use of a sensitive myograph. Before ET-1 was introduced, the ETB receptors were desensitized by use of S6c. The remaining contractility observed was considered to be the result of selective activation of the ETA receptors. ETA and ETB receptor mRNA expression was analyzed using real-time quantitative PCR. The location and concentration of ETA and ETB receptors were studied by means of immunohistochemistry together with confocal microscopy after overnight incubation with selective antibodies. Results After being cultured together with DSP for 24 hours the bronchial segments showed an increased contractility mediated by ETA and ETB receptors, whereas culturing them together with nicotine did not affect their contractility. The up-regulation of their contractility was blunted by cycloheximide treatment, a translational inhibitor. No significant change in the expression of ETA and ETB receptor mRNA through exposure to DMSO or to nicotine exposure alone occurred, although immunohistochemistry revealed a clear increase in ETA and ETB receptors in the smooth muscle after incubation in the presence of DSP. Taken as a whole, this is seen as the presence of a translation mechanism. Conclusion The increased contractility of rat bronchi when exposed to DSP appears to be due to a translation mechanism.

  5. [Single nucleotide polymorphisms in genes of endothelin-1 and receptor A associated to cardiovascular in essential hypertension].

    Science.gov (United States)

    Tamiozzo, S R; Lassen, O C; Herrera, J; Igarzabal, P; Tabares, S; Sembaj, A

    The endothelin system, for its vasoconstrictor action, is related to the development of essential hypertension (HTAe). The polymorphism analysis of their genes represents a new approach to the study of this disease. We propose to analyze the interaction between stages of essential hypertension (HTAe) and risk factors with polymorphisms 138ex1 ins/del A gene endothelin-1 (ET-1) and H323H receptor gene A ET-1 (ETRA). We included 300 patients of both sexes, unrelated, who consecutively attended the clinic hypertension medical service. Each one underwent a complete physical examination, electrocardiogram, echocardiogram, and Rx thorax. The degree of severity of hypertension was determined in stages. The determination of polymorphisms was performed by amplification followed by cutting by specific restriction enzyme from DNA obtained from peripheral blood. The 46% of patients had HTAe controlled, 17.6% had organ damage or cardiovascular, brain or kidney disease. It was observed that the 4A/4A carriers showed lower frequency of cardiovascular disease, kidney and brain (Pcardiovascular damage. Their identification could help recognize subgroups of the hypertensive patients with different risk. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. SELF ESTEEM IN RELATION TO ACADEMIC ACHIEVEMENT AMONG HIGHER SECONDARY STUDENTS

    OpenAIRE

    I. Maria Cecily; Mr. S.Justin Jebaraj

    2017-01-01

    Self - esteem is how we value ourselves; it is how we perceive our value to the world and how valuable we think we are to others. Self - esteem affects our trust in others, our relationship, our work – nearly every part of our lives. Positive self – esteem gives us the strength and flexibility to take charge of our lives and grow from our mistakes without the fear of rejection. The paper is an attempt to find to identify self-esteem in relation to academic achievement among higher secondary s...

  7. The concept of structure and content of health related trainings for higher educational establishments’ students

    Directory of Open Access Journals (Sweden)

    Kopylov Yu.A.

    2015-10-01

    Full Text Available Purpose: analysis of modern directions of physical culture education scientific and practical problems’ solution in higher educational establishment of health related orientation. Material: analysis of publications in scientific journals. Results: we have shown significance of student’s physical functioning as the basis of his motor, coordination and mental qualities’ development. Main difficulties of existing physical education practice have been cleared up. It has been found that prevailing training of physical qualities at physical culture classes does not solve the problem of students’ health strengthening. Ways to application of additional health related physical culture trainings have been shown. Transition to such trainings opens opportunities for creation a new concept, permits to effectively and relatively quickly implement its main ideas and principles in practice of HEE education. Conclusions: content of additional (health related physical culture training envisages prevailing orientation on health related, general developing and sport-recreational tasks. With it first attention shall be paid to formation of physical, psychic and social-moral health as well as to personality-oriented approach in system of individual choice of physical culture means.

  8. Leveraging People-Related Maturity Issues for Achieving Higher Maturity and Capability Levels

    Science.gov (United States)

    Buglione, Luigi

    During the past 20 years Maturity Models (MM) become a buzzword in the ICT world. Since the initial Crosby's idea in 1979, plenty of models have been created in the Software & Systems Engineering domains, addressing various perspectives. By analyzing the content of the Process Reference Models (PRM) in many of them, it can be noticed that people-related issues have little weight in the appraisals of the capabilities of organizations while in practice they are considered as significant contributors in traditional process and organizational performance appraisals, as stressed instead in well-known Performance Management models such as MBQA, EFQM and BSC. This paper proposes some ways for leveraging people-related maturity issues merging HR practices from several types of maturity models into the organizational Business Process Model (BPM) in order to achieve higher organizational maturity and capability levels.

  9. Lower zinc bioavailability may be related to higher risk of subclinical atherosclerosis in Korean adults.

    Directory of Open Access Journals (Sweden)

    Su Kyoung Jung

    Full Text Available BACKGROUND: There is a proposed link between dietary zinc intake and atherosclerosis, but this relationship remains unclear. Phytate may contribute to this relationship by influencing zinc bioavailability. OBJECTIVE: The aim of this study is to examine the relationship between zinc bioavailability and subclinical atherosclerosis in healthy Korean adults. MATERIALS AND METHODS: The present cross-sectional analysis used baseline data from the Korean multi-Rural Communities Cohort Study (MRCohort, which is a part of The Korean Genome Epidemiology Study (KoGES. A total of 5,532 subjects (2,116 men and 3,416 women aged 40 years and older were recruited from rural communities in South Korea between 2005 and 2010. Phytate:zinc molar ratio, estimated from a food-based food frequency questionnaire (FFQ of 106 food items, was used to determine zinc bioavailability, and carotid intima media thickness (cIMT and pulse wave velocity (PWV were measured to calculate the subclinical atherosclerotic index. RESULTS: We found that phytate:zinc molar ratio is positively related to cIMT in men. A higher phytate:zinc molar ratio was significantly related to an increased risk of atherosclerosis in men, defined as the 80(th percentile value of cIMT (5(th vs. 1(st quintile, OR = 2.11, 95% CI 1.42-3.15, P for trend = 0.0009, and especially in elderly men (5(th vs. 1(st quintile, OR = 2.58, 95% CI 1.52-4.37, P for trend = 0.0021. We found a positive relationship between phytate:zinc molar ratio and atherosclerosis risk among women aged 65 years or younger. Phytate:zinc molar ratio was not found to be related to PWV. CONCLUSIONS: Lower zinc bioavailability may be related to higher atherosclerosis risk.

  10. QUALITY-RELATED FUNDING IN ROMANIAN HIGHER EDUCATION THROUGHOUT 2003 – 2011: A GLOBAL ASSESSMENT

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    Gabriel-Alexandru Vîiu

    2015-12-01

    Full Text Available The article explores quality-related funding and its global outcomes in the context of Romanian higher education by focusing on the funding allocations provided to public universities throughout a period of nine years based on their institutional performance on the quality indicators integrated in the funding algorithm. Global funding allocations between universities are analysed and a summative appraisal for the entire nine-year window is provided. The article also explores the relation between quality- related funding, institutional disciplinary profiles and the results of a comprehensive evaluation conducted in 2011 by the Ministry of Education to complete a classification of the universities. The main findings indicate a low overall impact of qualityrelated funding for many institutions, but also a clear pattern in which universities focused on science, technology, engineering and mathematics overwhelmingly outperformed mixed institutions, as well as those focused on humanities, arts and social sciences. Furthermore, the global quality-related funding outcomes of the 2003 – 2011 period studied in the paper are shown to be significantly associated with the results of the 2011 classification

  11. Endothelin role in the orthostatic stress Papel da endotelina no estresse ortostático

    Directory of Open Access Journals (Sweden)

    Marli Cardoso Martins Pinge

    2008-10-01

    Full Text Available Orthostasis adoption causes hemodynamic changes. Hydrostatic opposition to the venous return, venous return reduction and cardiac output decrease act as stimuli and generate compensatory mechanisms. The central nervous system adjusts the autonomic sympathetic and parasympathetic activity. The autonomous nervous system causes a tonic and reflexive influence on the main variables of the cardiovascular system and, together with hormonal components, extends the adaptation capacity in face of postural changes. Any difficulties in this compensatory mechanism that prevents it from functioning properly may result in hypotension response failure, what, on its turn, can lead to cerebral hypoperfusion, hypoxia and loss of consciousness. Blood pressure maintenance at normal levels is important for the internal medium homeosthasis. Baroreflex plays an important role in the cardiovascular control in the short-term in the adaptation of the orthostatic stress, preventing excessive blood pressure alterations. During the orthostatic stress, neuroendocrinal changes also occur as alteration in endothelin plasma levels. Endothelin, a peptide formed by 21 amino acids, shows a powerful vasoconstrictor action. It also demonstrates that its levels in the blood are increased in response to an orthostatic stress. However, although endothelin-1 levels increase in response to an acute postural stress, its role in cardiovascular homeosthasis and its relation in the release of other hormones are still controversial and quite unknown in humans in vivo. A adoção da ortostase promove alterações hemodinâmicas. A oposição hidrostática ao retorno venoso, a redução do retorno venoso e a diminuição do débito cardíaco atua como estímulos e geram mecanismos compensatórios. O sistema nervoso central ajusta a atividade autonômica simpática e parassimpática. O sistema nervoso autônomo influencia tônica e reflexamente as principais variáveis do sistema cardiovascular

  12. Mechanisms of endothelin-1 elevation in chronic obstructive pulmonary disease patients with nocturnal oxyhemoglobin desaturation.

    Science.gov (United States)

    Trakada, G; Marangos, M; Spiropoulos, K

    2001-01-01

    Nonapneic, oxyhemoglobin desaturation associated with sleep has been described in patients with chronic obstructive pulmonary disease (COPD). Hypoxemia stimulates endothelin-1 (ET-1) secretion. Once released, ET-1 can act locally to elicit sustained pulmonary artery vasoconstriction, bronchoconstriction and activation of alveolar macrophages. The aim of this study was to examine a possible correlation between ET-1 levels and nocturnal, nonapneic, oxyhemoglobin desaturation during sleep, in patients with COPD. We examined 48 COPD patients with formal polysomnography (EEG, ECG, airflow, respiratory muscle movement, oximeter) to detect the presence of nocturnal, nonapneic, oxyhemoglobin desaturation. Twelve of them were disqualified because of inadequate sleep or sleep apnea syndrome. Nineteen of them desaturated below a baseline sleep saturation of 90% for 5 min or more, reaching a nadir saturation of at least 85%. We collected arterial samples to measure ET-1 levels, after 5 min of the first period of desaturation, in each of the 19 patients. We also collected arterial samples in the morning, before the study, to measure baseline ET-1 levels in all patients. Baseline arterial ET-1 levels during the day were very significantly higher in 'desaturator' COPD patients (2.058 +/- 0.252 pg/ml) compared to 'non-desaturator' COPD patients (1.382 +/- 0.159 pg/ml; p oxyhemoglobin desaturation. These findings are consistent with the hypothesis that ET-1 plays a very important role in the pathophysiological manifestations of COPD patients. Copyright 2001 S. Karger AG, Basel

  13. Homocysteine, endothelin-1 and nitric oxide in patients with hypertensive disorders complicating pregnancy.

    Science.gov (United States)

    Zeng, Yachang; Li, Mujun; Chen, Yue; Wang, Sumei

    2015-01-01

    To investigate the change of level of serum homocysteine (Hcy), endothelin-1 (ET-1) and nitric oxide (NO) and clinical significance in patients with HDCP. Two hundred and thirty nine patients with HDCP (137 patients with mild preeclampsia, 102 patients with severe preeclampsia) who were hospitalized between June 2012 and June 2015 and 200 normal pregnancy women in outpatient department were enrolled in our study were divided into HDCP group and control group. Serum Hcy concentration was measured by enzymatic cycling assay. ET-1 concentration was measured by enzyme linked immunosorbent assay. And no concentration was measured by nitrate reductase assay. Serum Hcy and ET-1 in HDCP group were significantly higher as compared to control group (Ppreclampsia group (P<0.05). Level of serum NO in severe preeclampsia group were significantly lower than in mild preeclampsia group (P<0.05). Spearman rank correlation analysis showed that level of serum Hcy and ET-1 was positively correlated with severity of diseases (r=0.689, 0.718, P<0.05). Level of serum NO was negatively correlated with severity of diseases (r=-0.702, P<0.05). Serum Hcy, ET-1 and NO were associated with pathogenesis of HDCP. Comprehensively measurement of them could effectively evaluate the incidence and progress of HDCP.

  14. Nicorandil improves myocardial function by regulating plasma nitric oxide and endothelin-1 in coronary slow flow

    Science.gov (United States)

    Chen, Xiuhua; Li, Shan; Huo, Xuezhen; Fu, Xiuxiu; Dong, Xiaonan

    2015-01-01

    Background Coronary slow flow (CSF) is a special coronary microvascular disorder. The pathogenesis and effective therapeutics of CSF remain unclear. This study aimed to evaluate the global and regional functions of the left ventricle (LV) and investigate the efficacy of nicorandil in patients with CSF. Patients and methods Thirty-six patients with CSF in the left anterior descending (LAD) branch and 20 patients with normal coronary arteries were included. Global and regional functions of the LV supplied by LAD were measured using conventional Doppler echocardiography and two-dimensional speckle tracking echocardiography, respectively, within 24 h after coronary angiography. Concentrations of plasma nitric oxide (NO) and endothelin-1 (ET-1) were detected using colorimetry and radioimmunoassay, respectively. The function of the LV and the levels of NO and ET-1 were also investigated before and 90 days after treatment with 15 mg/day of nicorandil. Results Compared with the control group, the early diastolic peak velocity (E), E/A ratio, and plasma NO levels were lower, whereas the late diastolic peak flow velocity (A) and plasma ET-1 levels were significantly higher in the CSF group (Pimprove chest pain symptoms and the impaired function of the LV, possibly by increasing plasma NO and reducing ET-1 in CSF. PMID:25325437

  15. Higher emotional intelligence is related to lower test anxiety among students

    Directory of Open Access Journals (Sweden)

    Ahmadpanah M

    2016-01-01

    Full Text Available Mohammad Ahmadpanah,1 Mohammadreza Keshavarz,1 Mohammad Haghighi,1 Leila Jahangard,1 Hafez Bajoghli,2 Dena Sadeghi Bahmani,3 Edith Holsboer-Trachsler,3 Serge Brand3,4 1Behavioral Disorders and Substances Abuse, Research Center, Hamadan University of Medical Sciences, Hamadan, Iran; 2Iranian National Center for Addiction Studies (INCAS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran; 3Psychiatric Clinics of the University of Basel, Center for Affective, Stress and Sleep Disorders, 4Department of Sport, Exercise and Health Science, Sport Science Section, University of Basel, Basel, Switzerland Background: For students attending university courses, experiencing test anxiety (TA dramatically impairs cognitive performance and success at exams. Whereas TA is a specific case of social phobia, emotional intelligence (EI is an umbrella term covering interpersonal and intrapersonal skills, along with positive stress management, adaptability, and mood. In the present study, we tested the hypothesis that higher EI and lower TA are associated. Further, sex differences were explored.Method: During an exam week, a total of 200 university students completed questionnaires covering sociodemographic information, TA, and EI.Results: Higher scores on EI traits were associated with lower TA scores. Relative to male participants, female participants reported higher TA scores, but not EI scores. Intrapersonal and interpersonal skills and mood predicted low TA, while sex, stress management, and adaptability were excluded from the equation.Conclusion: The pattern of results suggests that efforts to improve intrapersonal and interpersonal skills, and mood might benefit students with high TA. Specifically, social commitment might counteract TA. Keywords: test anxiety, emotional intelligence, students, interpersonal skills, intrapersonal skills

  16. Endothelin and vasopressin influence splanchnic blood flow distribution during and after cardiopulmonary bypass.

    Science.gov (United States)

    Bomberg, Hagen; Bierbach, Benjamin; Flache, Stephan; Wagner, Isabell; Gläser, Lena; Groesdonk, Heinrich V; Menger, Michael D; Schäfers, Hans-Joachim

    2013-02-01

    Gastrointestinal blood flow can be compromised during and after cardiopulmonary bypass. Endothelin has been shown to be involved in the intestinal microcirculatory disturbance of sepsis. The aim of the present study was to analyze the involvement of the endothelin system on intestinal blood flow regulation during cardiopulmonary bypass and the effect of vasopressin given during cardiopulmonary bypass. A total of 24 pigs were studied in 4 groups (n = 6): group I, sham; group II, ischemia/reperfusion with 1 hour of superior mesenteric artery occlusion; group III, cardiopulmonary bypass for 1 hour; and group IV, 1 hour of cardiopulmonary bypass plus vasopressin administration, maintaining the baseline arterial pressure. All the pigs were reperfused for 90 minutes. During the experiment, the hemodynamics and jejunal microcirculation were measured continuously. The jejunal mucosal expression of endothelin-1 and its receptor subtypes A and B were determined using polymerase chain reaction. During cardiopulmonary bypass, superior mesenteric artery flow was preserved but marked jejunal microvascular impairment occurred compared with baseline (mucosal capillary density, 192.2 ± 5.4 vs 150.8 ± 5.1 cm/cm(2); P = .005; tissue blood flow, 501.7 ± 39.3 vs 332.3 ± 27.9 AU; P = .025). The expression of endothelin-1 after cardiopulmonary bypass (3.2 ± 0.4 vs 12.2 ± 0.8 RQ, P = .006) and endothelin subtype A (0.7 ± 0.2 vs 2.4 ± 0.6 RQ; P = .01) was significantly increased compared to the sham group. Vasopressin administration during cardiopulmonary bypass led to normal capillary density (189.9 ± 3.9 vs 178.0 ± 6.3; P = .1) and tissue blood flow (501.7 ± 39.3 vs 494.7 ± 44.4 AU; P = .4) compared with baseline. The expression of endothelin-1 (3.2 ± 0.4 vs 1.8 ± 0.3 RQ; P = .3) and endothelin subtype A (0.7 ± 0.2 vs 0.9 ± 0.2 RQ; P = .5) was not different from the sham group. Cardiopulmonary bypass leads to microvascular impairment of jejunal microcirculation, which is

  17. Role of endothelin in thrombolysis in rat abdominal aorta.

    Science.gov (United States)

    Tang, Y; Yao, X; Tang, C

    1998-01-01

    The endothelium of blood vessels is of great importance in maintaining blood fluidity and modulating thrombogenesis. Endothelin (ET) participates in thrombogenesis and its role in the pathogenesis of heart diseases such as acute myocardinal infarction has been proved, but little is known about the effect of ET on thrombolysis. Using a model of thrombosis in rat abdominal aorta induced by direct current-ferric trichloride, we found that the plasma ET level was 3.7 times the baseline after lysing the thrombus with urokinase (250,000 U/kg) while 5 micrograms/kg of exogenous ET prolonged the time of thrombolysis to 115% of baseline control. Plasma ET level was six times the baseline level. Incubation of a rat aortic strip in vitro with taurine (20 mmol/L) had no effect on baseline ET release, but taurine prohibited the stimulation of thrombin and A23187 of ET release in a dose-dependent way. Plasma ET decreased between 17 and 40% after injection of taurine, which also decreased by 45% the time of lysis of thrombus. From the above data it might be concluded that ET inhibits thrombolysis and that the abnormally increasing plasma ET can be attenuated by taurine, which is beneficial to thrombolysis.

  18. Endothelins promote egg albumin-induced intestinal anaphylaxis in rats.

    Science.gov (United States)

    Shigematsu, T; Miura, S; Hirokawa, M; Hokari, R; Higuchi, H; Tsuzuki, Y; Kimura, H; Nakatsumi, R C; Serizawa, H; Saito, H; Ishii, H

    1998-08-01

    The basic mechanisms of food allergies are still unknown. The aims of this study were to investigate whether endothelins (ETs) in the intestinal mucosa are involved in the pathogenesis of intestinal anaphylaxis. Sprague-Dawley rats were sensitized to chicken egg albumin (EA) by intraperitoneal injection. Fourteen days after sensitization, EA was administered in the jejunal segments to induce intestinal anaphylaxis. Net water outflux and histamine release into loops and serum concentrations of rat mast cell protease II (RMCP-II) were determined. ET-1 and ET-3 concentrations in the jejunal mucosa were determined, and expression of the corresponding messenger RNAs was examined by competitive polymerase chain reaction. In sensitized animals, challenge with intraluminal antigen caused a significant increase in net water outflux and histamine release together with an elevation of serum RMCP-II concentrations. Mucosal concentrations of ET-1 and ET-3 and expression of their messenger RNAs were significantly increased in sensitized animals after EA challenge. Treatment with an ETA-receptor antagonist, but not an ETB-receptor antagonist, attenuated the increase in net water outflux, histamine release, and serum RMCP-II concentrations in rats with EA-induced intestinal anaphylaxis. Release of ETs in the intestinal mucosa increased in sensitized animals after EA challenge. ETs may play a significant role in the development of intestinal anaphylaxis via an ETA receptor.

  19. Big endothelin-1 level is a useful marker for predicting the presence of isolated coronary artery ectasia.

    Science.gov (United States)

    Wang, Yao; Zhang, Yan; Zhu, Cheng-Gang; Guo, Yuan-Lin; Huang, Qiao-Juan; Wu, Na-Qiong; Gao, Ying; Qing, Ping; Liu, Geng; Dong, Qian; Li, Jian-Jun

    Endothelin-1(ET-1) has been implicated in coronary artery disease (CAD) and may be associated with coronary artery ectasia (CAE). To clarify the relationship between big ET-1 and isolated CAE. We measured big ET-1 with ELISA in 216 patients (CAE, n = 72; CAD, n = 72; normal, n = 72) and evaluated the link with isolated CAE. The level of plasma big ET-1 was significantly higher in patients with isolated CAE (p Big ET-1 was strongly and independently associated with CAE by multivariate analysis (OR 95%CI: 1.026 (1.018-1.034), p = 0.000). Big ET-1 may be a useful predictor for the presence of isolated CAE.

  20. High-expanding cortical regions in human development and evolution are related to higher intellectual abilities.

    Science.gov (United States)

    Fjell, Anders M; Westlye, Lars T; Amlien, Inge; Tamnes, Christian K; Grydeland, Håkon; Engvig, Andreas; Espeseth, Thomas; Reinvang, Ivar; Lundervold, Astri J; Lundervold, Arvid; Walhovd, Kristine B

    2015-01-01

    Cortical surface area has tremendously expanded during human evolution, and similar patterns of cortical expansion have been observed during childhood development. An intriguing hypothesis is that the high-expanding cortical regions also show the strongest correlations with intellectual function in humans. However, we do not know how the regional distribution of correlations between intellectual function and cortical area maps onto expansion in development and evolution. Here, in a sample of 1048 participants, we show that regions in which cortical area correlates with visuospatial reasoning abilities are generally high expanding in both development and evolution. Several regions in the frontal cortex, especially the anterior cingulate, showed high expansion in both development and evolution. The area of these regions was related to intellectual functions in humans. Low-expanding areas were not related to cognitive scores. These findings suggest that cortical regions involved in higher intellectual functions have expanded the most during development and evolution. The radial unit hypothesis provides a common framework for interpretation of the findings in the context of evolution and prenatal development, while additional cellular mechanisms, such as synaptogenesis, gliogenesis, dendritic arborization, and intracortical myelination, likely impact area expansion in later childhood. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Higher-order cognitive training effects on processing speed-related neural activity: a randomized trial.

    Science.gov (United States)

    Motes, Michael A; Yezhuvath, Uma S; Aslan, Sina; Spence, Jeffrey S; Rypma, Bart; Chapman, Sandra B

    2017-10-12

    Higher-order cognitive training has shown to enhance performance in older adults, but the neural mechanisms underlying performance enhancement have yet to be fully disambiguated. This randomized trial examined changes in processing speed and processing speed-related neural activity in older participants (57-71 years of age) who underwent cognitive training (CT, N = 12) compared with wait-listed (WLC, N = 15) or exercise-training active (AC, N = 14) controls. The cognitive training taught cognitive control functions of strategic attention, integrative reasoning, and innovation over 12 weeks. All 3 groups worked through a functional magnetic resonance imaging processing speed task during 3 sessions (baseline, mid-training, and post-training). Although all groups showed faster reaction times (RTs) across sessions, the CT group showed a significant increase, and the WLC and AC groups showed significant decreases across sessions in the association between RT and BOLD signal change within the left prefrontal cortex (PFC). Thus, cognitive training led to a change in processing speed-related neural activity where faster processing speed was associated with reduced PFC activation, fitting previously identified neural efficiency profiles. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. [Cognitive and linguistic abilities of a boy with PVL showing relatively higher VIQ compared to PIQ].

    Science.gov (United States)

    Muramatsu, Yukako; Natsume, Jun; Nakamura, Miho

    2015-09-01

    In this study, we investigated the cognitive processing and language abilities of a 13-year-old boy with moderate periventricular leukomalacia (PVL), spastic diplegia and exotropia who had discrepant scores in the verbal intelligence quotient (VIQ) and performance intelligence quotient (PIQ) in the Wechsler Intelligence Scale for Children, third edition (VIQ; 82 > PIQ; under 40). In the Kaufman Assessment Battery for Children and Das-Naglieri Cognitive Assessment System, his performance was poor at simultaneous processing compared to sequential processing. He could not copy three-dimensional figures, and he could place only two out of eight blocks correctly in the second level models of Benton three-dimensional block construction test, showing visuospatial impairment typical of patients with PVL. Despite the relatively high score in VIQ, there was a gap among the scores of the subtests in the Illinois Test of Psycholinguistic Abilities. He tended to get low scores in tests that required visual abilities. In addition, there was also an impairment in reading fluency tested by the Diagnostic Criteria and Medical Guideline for Specific Developmental Disorders. He was much less fluent in reading syllables, words or sentences (6.0 SD or more compared to 12-year-old boys). The relatively higher score in VIQ superficially suggests adequate language ability. However, in the present study, precise investigation revealed some discrepancies even within the field of language. Thus, defining stronger and weaker points of a patient is important in order to determine optimal medical or educational approaches.

  3. Vascular endothelin ET(B) receptor-mediated contraction requires phosphorylation of ERK1/2 proteins

    DEFF Research Database (Denmark)

    Luo, Guogang; Jamali, Roya; Cao, Yong-Xiao

    2006-01-01

    In cardiovascular diseases, endothelin type B (ET(B)) receptors in arterial smooth muscle cells are upregulated. The present study revealed that organ culture of rat mesenteric artery segments enhanced endothelin ET(B) receptor-mediated contraction paralleled with increase in the receptor m...

  4. Endothelin receptor B polymorphism associated with lethal white foal syndrome in horses.

    Science.gov (United States)

    Santschi, E M; Purdy, A K; Valberg, S J; Vrotsos, P D; Kaese, H; Mickelson, J R

    1998-04-01

    Overo lethal white syndrome (OLWS) is an inherited syndrome of foals born to American Paint Horse parents of the overo coat-pattern lineage. Affected foals are totally or almost totally white and die within days from complications due to intestinal aganglionosis. Related conditions occur in humans and rodents in which mutations in the endothelin receptor B (EDNRB) gene are responsible. EDNRB is known to be involved in the developmental regulation of neural crest cells that become enteric ganglia and melanocytes. In this report we identify a polymorphism in the equine EDNRB gene closely associated with OLWS. This Ile to Lys substitution at codon 118 is located within the first transmembrane domain of this seven-transmembrane domain G-protein-coupled receptor protein. All 22 OLWS-affected foals examined were homozygous for the Lys118 EDNRB allele, while all available parents of affected foals were heterozygous. All but one of the parents also had an overo white body-spot phenotype. Solid-colored control horses of other breeds were homozygous for the Ile118 EDNRB allele. Molecular definition of the basis for OLWS in Paint Horses provides a genetic test for the presence of the Lys118 EDNRB allele and adds to our understanding of the basis for coat color patterns in the horse.

  5. Endothelin-positive mast cells in porcine renal artery and vein.

    Science.gov (United States)

    Vodenicharov, A

    2008-10-01

    For a first time the endothelin (ET)-positive mast cells were examined in the wall of kidney renal artery and vein. The specimen's were collected from six 8-month-old Danmark Landrace pigs, immediately after slaughtering. Mast cells immunopositive to ET granules were observed in the wall of both artery and vein. In the renal artery, they were found mostly between the media and the adventitia. Some mast cells were found in the media, next to smooth muscle cells. Relatively few mast cells were found in the intima and between intima and tunica media. In the renal vein a smaller number of mast cells were observed. They showed similar localization as in the renal artery. Immunopositive mast cells were established also close to endothelial cells - mostly between internal elastic membrane and basal membrane of the endothelium. In conclusion, on the basis of obtained results, presumptions for active participation of ET (most probably mainly ET-1) in the motility of the vessels' smooth muscle and for stimulation of nitric oxide release from the intimal endothelial cells were made.

  6. Elderly women with metabolic syndrome present higher cardiovascular risk and lower relative muscle strength

    Energy Technology Data Exchange (ETDEWEB)

    Farias, Darlan Lopes; Tibana, Ramires Alsamir; Teixeira, Tatiane Gomes; Vieira, Denis César Leite; Tarja, Vitor; Nascimento, Dahan da Cunha; Silva, Alessandro de Oliveira [Universidade Católica de Brasília, Brasília, DF (Brazil); Funghetto, Silvana Schwerz [Universidade de Brasília, Brasília, DF (Brazil); Coura, Maritza Alves de Sousa; Valduga, Renato [Universidade Católica de Brasília, Brasília, DF (Brazil); Karnikowski, Margô Gomes de Oliveira [Universidade de Brasília, Brasília, DF (Brazil); Prestes, Jonato [Universidade Católica de Brasília, Brasília, DF (Brazil)

    2013-07-01

    To compare the metabolic, anthropometric, arterial blood pressure, and muscle strength parameters of elderly women with and without metabolic syndrome. A case-control study with 27 (67.3±4.8 years of age, 31.0±5.0kg/m{sup 2}) elderly women with metabolic syndrome and 33 (68.8±5.6 years of age, 27.2±5.3kg/m{sup 2}) sedentary control elderly women. They were submitted to an evaluation of body composition by means of dual-energy X-ray absorptiometry and muscle strength testing with 10 maximal repetitions of knee extension. When compared to the elderly women without metabolic syndrome, those with the metabolic syndrome had higher levels for body mass (72.2±13.5 versus 63.4±14.6kg, p=0.03), body mass index (31.0±5.0 versus 27.2±5.3kg/m{sup 2,} p=0.007), fat mass (30.9±9.9 versus 24.4±8.5kg, p=0.01), systolic arterial pressure (125.1±8.2 versus 119.3±8.7mmHg, p=0.01), diastolic arterial pressure (75.5±6.9 versus 71.4±6.7mmHg, p=0.03), mean arterial pressure (92.5±6.2 versus 87.1±6.7mmHg, p=0.004), blood glucose (103.8±19.1 versus 91.1±5.9mg/dL, p=0.001), triglycerides (187.1±70.2 versus 116.3±36.7mg/dL, p=0.001), and creatine kinase (122.6±58.6 versus 89.8±32.5U/L, p=0.01); lower levels were found for fat-free mass (55.9±5.8 versus 59.3±6.7%; p=0.05), HDL-C (40.7±5.0 versus 50.5±10.1mg/dL, p=0.001), and relative muscle strength (0.53±0.14 versus 0.62±0.12, p=0.01). Elderly women with metabolic syndrome have a higher cardiovascular risk and less relative muscle strength when compared to those without metabolic syndrome. Relative muscle strength may be related to the cardiovascularr risk factors of the metabolic syndrome.

  7. VEGF Polymorphisms Related to Higher Serum Levels of Protein Identify Patients with Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Maria Eduarda Lopes Baitello

    2016-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the most common primary neoplasia of the liver. Major risk factors for hepatocellular carcinoma include chronic liver diseases, carcinogenic agents, and genetic alterations as well as vascular endothelial growth factor (VEGF involved in angiogenesis process. The aim of this study was to evaluate the association of VEGF-A (C936T and A1154G with HCC and cirrhosis, in addition to serum levels of VEGF, clinical profile, lifestyle habits, and comorbidities. A total of 346 individuals were studied: 102 with HCC (G1, 117 with cirrhosis (G2, and 127 controls (G3. Polymorphisms were analysed by PCR/RFLP and serum levels of VEGF by ELISA. Alpha error was set at 5%. The wild-type genotype of both polymorphisms prevailed (P>0.05. In G1, 23% of the patients died, with no relation to genetic profile (P>0.05. Increased VEGF level was observed in G1 and G3, related to the mutant allele of VEGF-C936T and VEGF-A1154G, respectively, and compared with the wild-type genotype (P=0.0285; P=0.0284, resp. as well as G1 versus G2 and G3 for VEGF-C936T and G1 versus G2 for VEGF-A1154G (P<0.05 for both. In conclusion, there is a relationship between mutant alleles of VEGF-C936T and VEGF-A1154G polymorphisms and higher VEGF level, making them potential markers for HCC.

  8. The Relation of Students’ Choice of Private Higher Education and Marketing Strategies in Bosnia and Herzegovina

    Directory of Open Access Journals (Sweden)

    Ozbal Okai

    2015-09-01

    Full Text Available Severe market conditions and advancing technology demand a well-planned and a strategic marketing approach in all sectors as well as in education sector. This study examined the relationship between the students’ choice and the marketing strategies of private higher education (HE in Bosnia and Herzegovina (BIH. To perceive this relation, we chose one of the private universities in Sarajevo. The study is based on a student survey which employed a questionnaire of 55 questions under 4 sub-groups and was done by 146 students. The first step of the questionnaire was determining the motives of the students to attend a private HE institution. The next part was to investigate the information sources of the students. These two steps followed the understanding of the evaluation criteria and the decision process of the students. Finally, the survey was concluded with the post enrollment observations of the students. The data obtained analyzed by SPSS software. The results revealed a strong consistency. The students were willing to have quality education and improve themselves via HE. They were using internet as a prior information source but would not make a final decision without parents’ confirmation. The overall satisfaction of the students showed that our subject university communicates with the target groups efficiently and enjoys the benefits of positive ‘word of mouth’ marketing. Finally, we addressed the marketing strategies that we reaped throughout the study to suggest a course of action to private HEIs in the conclusion part.

  9. Related research on corneal higher-order aberrations after different ways refractive surgery

    Directory of Open Access Journals (Sweden)

    Shu-Xi He

    2015-08-01

    Full Text Available AIM:To evaluate the changes of corneal high-order aberration(including Coma, Spab, RMShafter laser in situ keratomileusis(LASIKwith femtosecond laser, sub-Bowman keratomileusis(SBKand laser epithelial keratomileusis(LASEK.METHODS: Of 82 myopic patients(164 eyes, 31 patients(62 eyeswere treated by FS-LASIK, 31 patients(62 eyeswere treated by SBK, 20 patients(40 eyeswere treated by LASEK. Sirius system was used for measuring the coma aberration, spherical aberration, and high order aberration at 1, 15d,1, 3mo after surgery.RESULTS: 1Vision: The uncorrected visual acuity of the three groups had no differences(P>0.05. 2Corneal aberrations: Three kinds of surgical procedure for patients with corneal aberration had significant impact. The C7, C8, C12 and RMSh of three groups were increased significantly(P0.05. The C7, C8, C12 and RMSh were not recovered to preoperative levels after 3mo. But the increase of patients after FS-LASIK was smaller than the other two groups, with statistical significance(P0.05.CONCLUSION: Compared with SBK and LASEK,FS-LASIK has better visual acuity in the early postoperative and corneal higher-order aberrations increase is relatively small.

  10. Lack of physical activity in young children is related to higher composite risk factor score for cardiovascular disease

    DEFF Research Database (Denmark)

    Tanha, Tina; Wollmer, Per; Thorsson, Ola

    2011-01-01

    This study evaluates whether accelerometer-measured physical activity is related to higher composite risk factor scores for cardiovascular disease (CVD) in children.......This study evaluates whether accelerometer-measured physical activity is related to higher composite risk factor scores for cardiovascular disease (CVD) in children....

  11. Active endothelin is an important vasoconstrictor in acute coronary thrombi.

    Science.gov (United States)

    Adlbrecht, Christopher; Bonderman, Diana; Plass, Christian; Jakowitsch, Johannes; Beran, Gilbert; Sperker, Wolfgang; Siostrzonek, Peter; Glogar, Dietmar; Maurer, Gerald; Lang, Irene M

    2007-04-01

    Acute coronary syndrome is characterized by compromised blood flow at the epicardial and microvascular levels. We have previously shown that thrombectomy in ST-elevation myocardial infarction (STEMI) accelerates ST-segment resolution, possibly by preventing distal embolization. We hypothesized that thrombus constituents contribute to microcirculatory dysfunction. Therefore, we analyzed the molecular and cellular composition of acute coronary thrombi, and correlated vasoconstrictive mediators with the magnitude of ST-segment resolution within one hour of percutaneous coronary intervention (PCI). Fresh coronary thrombi were retrieved in 35 consecutive STEMI patients who were treated with the X-Sizer thrombectomy catheter, and thrombus cell counts and vasoconstrictor concentrations were assessed. Twelve-lead ECG recordings were analyzed prior to and one hour after PCI. Concentration of endothelin (ET) was 20.0 (7.9-52.2) fmol/ml in thrombus compared with 0.1 (0.1-0.3) fmol/ml in corresponding peripheral plasma (p < 0.0001), representing a selective 280 (70.0-510.0)-fold enrichment, exceeding enrichment of noradrenaline, angiotensin II and serotonin. Human coronary thrombus homogenates exerted vasoconstriction of porcine coronary artery rings that was inhibited by the dual ET receptor blocker tezosentan. Extracted ET (r = 0.523 p = 0.026) and number of leukocytes (r = 0.555 p = 0.017) were correlated with the magnitude of ST-segment resolution. In conclusion, the amount of active ET and white blood cells aspirated from STEMI target vessels correlated with improvement of territorial microcirculatory function as illustrated by enhanced ST-segment resolution.

  12. Brain remodelling following endothelin-1 induced stroke in conscious rats.

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    Hima C S Abeysinghe

    Full Text Available The extent of stroke damage in patients affects the range of subsequent pathophysiological responses that influence recovery. Here we investigate the effect of lesion size on development of new blood vessels as well as inflammation and scar formation and cellular responses within the subventricular zone (SVZ following transient focal ischemia in rats (n = 34. Endothelin-1-induced stroke resulted in neurological deficits detected between 1 and 7 days (P<0.001, but significant recovery was observed beyond this time. MCID image analysis revealed varying degrees of damage in the ipsilateral cortex and striatum with infarct volumes ranging from 0.76-77 mm3 after 14 days, where larger infarct volumes correlated with greater functional deficits up to 7 days (r = 0.53, P<0.05. Point counting of blood vessels within consistent sample regions revealed that increased vessel numbers correlated significantly with larger infarct volumes 14 days post-stroke in the core cortical infarct (r = 0.81, P<0.0001, core striatal infarct (r = 0.91, P<0.005 and surrounding border zones (r = 0.66, P<0.005; and r = 0.73, P<0.05. Cell proliferation within the SVZ also increased with infarct size (P<0.01 with a greater number of Nestin/GFAP positive cells observed extending towards the border zone in rats with larger infarcts. Lesion size correlated with both increased microglia and astrocyte activation, with severely diffuse astrocyte transition, the formation of the glial scar being more pronounced in rats with larger infarcts. Thus stroke severity affects cell proliferation within the SVZ in response to injury, which may ultimately make a further contribution to glial scar formation, an important factor to consider when developing treatment strategies that promote neurogenesis.

  13. Endothelin receptor antagonist and airway dysfunction in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Borst Mathias M

    2009-12-01

    Full Text Available Abstract Background In idiopathic pulmonary arterial hypertension (IPAH, peripheral airway obstruction is frequent. This is partially attributed to the mediator dysbalance, particularly an excess of endothelin-1 (ET-1, to increased pulmonary vascular and airway tonus and to local inflammation. Bosentan (ET-1 receptor antagonist improves pulmonary hemodynamics, exercise limitation, and disease severity in IPAH. We hypothesized that bosentan might affect airway obstruction. Methods In 32 IPAH-patients (19 female, WHO functional class II (n = 10, III (n = 22; (data presented as mean ± standard deviation pulmonary vascular resistance (11 ± 5 Wood units, lung function, 6 minute walk test (6-MWT; 364 ± 363.7 (range 179.0-627.0 m, systolic pulmonary artery pressure, sPAP, 79 ± 19 mmHg, and NT-proBNP serum levels (1427 ± 2162.7 (range 59.3-10342.0 ng/L were measured at baseline, after 3 and 12 months of oral bosentan (125 mg twice per day. Results and Discussion At baseline, maximal expiratory flow at 50 and 25% vital capacity were reduced to 65 ± 25 and 45 ± 24% predicted. Total lung capacity was 95.6 ± 12.5% predicted and residual volume was 109 ± 21.4% predicted. During 3 and 12 months of treatment, 6-MWT increased by 32 ± 19 and 53 ± 69 m, respectively; p Conclusion This study gives first evidence in IPAH, that during long-term bosentan, improvement of hemodynamics, functional parameters or serum biomarker occur independently from persisting peripheral airway obstruction.

  14. Vascular endothelium derived endothelin-1 is required for normal heart function after chronic pressure overload in mice.

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    Susi Heiden

    Full Text Available BACKGROUND: Endothelin-1 participates in the pathophysiology of heart failure. The reasons for the lack of beneficial effect of endothelin antagonists in heart failure patients remain however speculative. The anti-apoptotic properties of ET-1 on cardiomyocytes could be a reasonable explanation. We therefore hypothesized that blocking the pro-apoptotic TNF-α pathway using pentoxifylline could prevent the deleterious effect of the lack of ET-1 in a model for heart failure. METHODS: We performed transaortic constriction (TAC in vascular endothelial cells specific ET-1 deficient (VEETKO and wild type (WT mice (n = 5-9 and treated them with pentoxifylline for twelve weeks. RESULTS: TAC induced a cardiac hypertrophy in VEETKO and WT mice but a reduction of fractional shortening could be detected by echocardiography in VEETKO mice only. Cardiomyocyte diameter was significantly increased by TAC in VEETKO mice only. Pentoxifylline treatment prevented cardiac hypertrophy and reduction of fractional shortening in VEETKO mice but decreased fractional shortening in WT mice. Collagen deposition and number of apoptotic cells remained stable between the groups as did TNF-α, caspase-3 and caspase-8 messenger RNA expression levels. TAC surgery enhanced ANP, BNP and bcl2 expression. Pentoxifylline treatment reduced expression levels of BNP, bcl2 and bax. CONCLUSIONS: Lack of endothelial ET-1 worsened the impact of TAC-induced pressure overload on cardiac function, indicating the crucial role of ET-1 for normal cardiac function under stress. Moreover, we put in light a TNF-α-independent beneficial effect of pentoxifylline in the VEETKO mice suggesting a therapeutic potential for pentoxifylline in a subpopulation of heart failure patients at higher risk.

  15. Pediatric scalds: do cooking-related burns have a higher injury burden?

    Science.gov (United States)

    Bachier, Marielena; Hammond, Sarah E; Williams, Regan; Jancelewicz, Timothy; Feliz, Alexander

    2015-11-01

    Pediatric scald burns result in frequent emergency room visits and hospitalizations. We investigated whether cooking-related burns produce greater morbidity requiring more extensive care than noncooking burns. We performed a 6-y review at our free-standing children's hospital. Children aged burns were included. Demographics, injury pattern, treatment, and outcome (contractures and/or limited mobility and nonhealing and/or infected wounds) data were analyzed comparing cooking versus noncooking burns. The Mann-Whitney U test, a chi-square test, and the negative binomial were used to compare continuous, categorical, and count data between groups. Bivariate analysis was performed to identify risk factors among patients with adverse outcomes. We identified 308 patients; 262 (85%) cooking and 46 (15%) noncooking burns. Most patients were African-American males, with public insurance, and a median age of 2 y. Cooking burns preferentially occurred over the head, neck, and upper body; noncooking burns were distributed over the lower body (P  0.11). In subgroup analysis, semisolid and grease burns resulted in increased rates of wound contractures and/or limited mobility when compared with noncooking burns (P = 0.05 and P = 0.008, respectively). Patients with complications were more likely to have third degree burns and required more consults, longer hospitalization, and more surgical debridements and clinic visits. Most accidental scald burns occurred in young children during food preparation. Greater long-term morbidity was found in patients with semisolid and grease burns. This subset of children has a higher injury burden and requires extensive care in the acute and long-term setting. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Higher Education (Related) Choices in Portugal: Joint Decisions on Institution Type and Leaving Home

    Science.gov (United States)

    Sa, Carla; Tavares, Diana Amado; Justino, Elsa; Amaral, Alberto

    2011-01-01

    The aim of this article is twofold: to further investigate the type of higher education institution choice using individual-level data on first-year students, and to establish the link between institution choice and the decision whether to leave home. The analysis was performed for Portuguese higher education by means of a bivariate probit model.…

  17. Internationalization, Regionalization, and Soft Power: China's Relations with ASEAN Member Countries in Higher Education

    Science.gov (United States)

    Yang, Rui

    2012-01-01

    Since the late 1980s, there has been a resurgence of regionalism in world politics. Prospects for new alliances are opened up often on a regional basis. In East and Southeast Asia, regionalization is becoming evident in higher education, with both awareness and signs of a rising ASEAN+3 higher education community. The quest for regional influence…

  18. A Lower Olfactory Capacity Is Related to Higher Circulating Concentrations of Endocannabinoid 2-Arachidonoylglycerol and Higher Body Mass Index in Women.

    Science.gov (United States)

    Pastor, Antoni; Fernández-Aranda, Fernando; Fitó, Montserrat; Jiménez-Murcia, Susana; Botella, Cristina; Fernández-Real, Jose M; Frühbeck, Gema; Tinahones, Francisco J; Fagundo, Ana B; Rodriguez, Joan; Agüera, Zaida; Langohr, Klaus; Casanueva, Felipe F; de la Torre, Rafael

    2016-01-01

    The endocannabinoid (eCB) system can promote food intake by increasing odor detection in mice. The eCB system is over-active in human obesity. Our aim is to measure circulating eCB concentrations and olfactory capacity in a human sample that includes people with obesity and explore the possible interaction between olfaction, obesity and the eCB system. The study sample was made up of 161 females with five groups of body mass index sub-categories ranging from under-weight to morbidly obese. We assessed olfactory capacity with the "Sniffin´Sticks" test, which measures olfactory threshold-discrimination-identification (TDI) capacity. We measured plasma concentrations of the eCBs 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine or anandamide (AEA), and several eCB-related compounds, 2-acylglycerols and N-acylethanolamines. 2-AG and other 2-acylglycerols fasting plasma circulating plasma concentrations were higher in obese and morbidly obese subjects. AEA and other N-acylethanolamine circulating concentrations were lower in under-weight subjects. Olfactory TDI scores were lower in obese and morbidly obese subjects. Lower TDI scores were independently associated with higher 2-AG fasting plasma circulating concentrations, higher %body fat, and higher body mass index, after controlling for age, smoking, menstruation, and use of contraceptives. Our results show that obese subjects have a lower olfactory capacity than non-obese ones and that elevated fasting plasma circulating 2-AG concentrations in obesity are linked to a lower olfactory capacity. In agreement with previous studies we show that eCBs AEA and 2-AG, and their respective congeners have a distinct profile in relation to body mass index. The present report is the first study in humans in which olfactory capacity and circulating eCB concentrations have been measured in the same subjects.

  19. A Lower Olfactory Capacity Is Related to Higher Circulating Concentrations of Endocannabinoid 2-Arachidonoylglycerol and Higher Body Mass Index in Women.

    Directory of Open Access Journals (Sweden)

    Antoni Pastor

    Full Text Available The endocannabinoid (eCB system can promote food intake by increasing odor detection in mice. The eCB system is over-active in human obesity. Our aim is to measure circulating eCB concentrations and olfactory capacity in a human sample that includes people with obesity and explore the possible interaction between olfaction, obesity and the eCB system. The study sample was made up of 161 females with five groups of body mass index sub-categories ranging from under-weight to morbidly obese. We assessed olfactory capacity with the "Sniffin´Sticks" test, which measures olfactory threshold-discrimination-identification (TDI capacity. We measured plasma concentrations of the eCBs 2-arachidonoylglycerol (2-AG and N-arachidonoylethanolamine or anandamide (AEA, and several eCB-related compounds, 2-acylglycerols and N-acylethanolamines. 2-AG and other 2-acylglycerols fasting plasma circulating plasma concentrations were higher in obese and morbidly obese subjects. AEA and other N-acylethanolamine circulating concentrations were lower in under-weight subjects. Olfactory TDI scores were lower in obese and morbidly obese subjects. Lower TDI scores were independently associated with higher 2-AG fasting plasma circulating concentrations, higher %body fat, and higher body mass index, after controlling for age, smoking, menstruation, and use of contraceptives. Our results show that obese subjects have a lower olfactory capacity than non-obese ones and that elevated fasting plasma circulating 2-AG concentrations in obesity are linked to a lower olfactory capacity. In agreement with previous studies we show that eCBs AEA and 2-AG, and their respective congeners have a distinct profile in relation to body mass index. The present report is the first study in humans in which olfactory capacity and circulating eCB concentrations have been measured in the same subjects.

  20. Fluorescence Correlation Spectroscopy in Drug Discovery: Study of Alexa532-Endothelin 1 Binding to the Endothelin ETA Receptor to Describe the Pharmacological Profile of Natural Products

    Directory of Open Access Journals (Sweden)

    Catherina Caballero-George

    2012-01-01

    Full Text Available Fluorescence correlation spectroscopy and the newly synthesized Alexa532-ET1 were used to study the dynamics of the endothelin ETA receptor-ligand complex alone and under the influence of a semisynthetic selective antagonist and a fungal extract on living A10 cells. Dose-dependent increase of inositol phosphate production was seen for Alexa532-ET1, and its binding was reduced to 8% by the selective endothelin ETA antagonist BQ-123, confirming the specific binding of Alexa532-ET1 to the endothelin ETA receptor. Two different lateral mobilities of the receptor-ligand complexes within the cell membrane were found allowing the discrimination of different states for this complex. BQ-123 showed a strong binding affinity to the “inactive” receptor state characterized by the slow diffusion time constant. A similar effect was observed for the fungal extract, which completely displaced Alexa532-ET1 from its binding to the “inactive” receptor state. These findings suggest that both BQ-123 and the fungal extract act as inverse agonists.

  1. Obesity-related eating behaviors are associated with higher food energy density and higher consumption of sugary and alcoholic beverages: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Maritza Muñoz-Pareja

    Full Text Available Obesity-related eating behaviors (OREB are associated with higher energy intake. Total energy intake can be decomposed into the following constituents: food portion size, food energy density, the number of eating occasions, and the energy intake from energy-rich beverages. To our knowledge this is the first study to examine the association between the OREB and these energy components.Data were taken from a cross-sectional study conducted in 2008-2010 among 11,546 individuals representative of the Spanish population aged ≥ 18 years. Information was obtained on the following 8 self-reported OREB: not planning how much to eat before sitting down, eating precooked/canned food or snacks bought at vending machines or at fast-food restaurants, not choosing low-energy foods, not removing visible fat from meat or skin from chicken, and eating while watching TV. Usual diet was assessed with a validated diet history. Analyses were performed with linear regression with adjustment for main confounders.Compared to individuals with ≤ 1 OREB, those with ≥ 5 OREB had a higher food energy density (β 0.10; 95% CI 0.08, 0.12 kcal/g/day; p-trend<0.001 and a higher consumption of sugary drinks (β 7; 95% CI -7, 20 ml/day; p-trend<0.05 and of alcoholic beverages (β 24; 95% CI 10, 38 ml/day; p-trend<0.001. Specifically, a higher number of OREB was associated with higher intake of dairy products and red meat, and with lower consumption of fresh fruit, oily fish and white meat. No association was found between the number of OREB and food portion size or the number of eating occasions.OREB were associated with higher food energy density and higher consumption of sugary and alcoholic beverages. Avoiding OREB may prove difficult because they are firmly socially rooted, but these results may nevertheless serve to palliate the undesirable effects of OREB by reducing the associated energy intake.

  2. The vascular endothelin system in obesity and type 2 diabetes: pathophysiology and therapeutic implications.

    Science.gov (United States)

    Campia, Umberto; Tesauro, Manfredi; Di Daniele, Nicola; Cardillo, Carmine

    2014-11-24

    Obesity, the metabolic syndrome (MetS), and type 2 diabetes (T2DM) are associated with heightened cardiovascular risk. Given the vasoconstrictor and proatherogenic properties of endothelin (ET)-1, increased ET-1 activity has been postulated to participate in the derangement of adiposity-related vascular homeostasis. This concept is supported by human studies using receptor antagonists to show that the activity of endogenous ET-1 is indeed enhanced in overweight and obesity, the MetS, and T2DM. Also, increased ET-1 contributes to endothelial dysfunction related to obesity, the MetS, and T2DM, whereas decreasing ET-1 vasoconstrictor tone in these patients corrects the defective endothelium-dependent vasodilation. In addition, in patients with central adiposity and the MetS, enhanced intravascular ET-1 activity coexists with decreased nitric oxide (NO)-dependent vasodilator capacity, suggesting a prevalence of vasoconstrictor mediators in vessels of obese individuals. One mechanism evoked to explain the development of vascular abnormalities in obesity deals with the derangement of the physiological vascular effects of insulin in insulin-resistant states. Thus, in conditions of adiposity, defective insulin-mediated vasodilation leads to impaired ability of the hormone to enhance its delivery and that of substrates to peripheral tissues. An important role of ET-1 in this abnormality is supported by studies showing that upregulation of the ET-1 system impairs NO-mediated vasodilation in insulin-resistant patients, whereas NO bioactivity is restored following ET-1 antagonism. In conclusion, considerable evidence supports a mechanistic role of ET-1 in the pathophysiology of adiposity-related vascular dysfunction. Targeting the ET-1 system, therefore, might have the potential for effective cardiovascular prevention in obesity, the MetS, and T2DM. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  3. NKX2-3 transcriptional regulation of endothelin-1 and VEGF signaling in human intestinal microvascular endothelial cells.

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    Wei Yu

    Full Text Available BACKGROUND: NKX2-3 is associated with inflammatory bowel disease (IBD. NKX2-3 is expressed in microvascular endothelial cells and the muscularis mucosa of the gastrointestinal tract. Human intestinal microvascular endothelial cells (HIMECs are actively involved in the pathogenesis of IBD and IBD-associated microvascular dysfunction. To understand the cellular function of NKX2-3 and its potential role underlying IBD pathogenesis, we investigated the genes regulated by NKX2-3 in HIMEC using cDNA microarray. METHODOLOGY/PRINCIPAL FINDINGS: NKX2-3 expression was suppressed by shRNA in two HIMEC lines and gene expression was profiled by cDNA microarray. Pathway Analysis was used to identify gene networks according to biological functions and associated pathways. Validation of microarray and genes expression in intestinal tissues was assessed by RT-PCR. NKX2-3 regulated genes are involved in immune and inflammatory response, cell proliferation and growth, metabolic process, and angiogenesis. Several inflammation and angiogenesis related signaling pathways that play important roles in IBD were regulated by NKX2-3, including endothelin-1 and VEGF-PI3K/AKT-eNOS. Expression levels of NKX2-3, VEGFA, PI3K, AKT, and eNOS are increased in intestinal tissues from IBD patients and expression levels of EDN1 are decreased in intestinal tissues from IBD patients. These results demonstrated the important roles of NKX2-3, VEGF, PI3K, AKT, eNOS, and EDN1 in IBD pathogenesis. Correlation analysis showed a positive correlation between mRNA expression of NKX2-3 and VEGFA and a negative correlation between mRNA expression of NKX2-3 and EDN1 in intestinal tissues from IBD patients. CONCLUSION/RELEVANCE: NKX2-3 may play an important role in IBD pathogenesis by regulating endothelin-1 and VEGF signaling in HIMECs.

  4. A role for endothelin in the pathogenesis of hypertension : Fact or fiction?

    NARCIS (Netherlands)

    Pinto-Sietsma, SJ; Paul, M

    Endothelin-1 (ET-1) was discovered 10 years ago. Because it is one of the most potent vasoconstrictors in vivo, a pathophysiological role for the peptide as a mediator of hypertension has been postulated. Several clinical studies, however, have been unable to identify elevated ET levels in the

  5. In depth pharmacological characterization of endothelin B receptors in the rat middle cerebral artery

    DEFF Research Database (Denmark)

    Szok, D; Hansen-Schwartz, J; Edvinsson, L

    2001-01-01

    middle cerebral artery were cannulated with micropipettes, pressurized and luminally perfused. Vessel diameters were evaluated using a microscope equipped with an imaging system. Both intra- and extraluminal applications of endothelin-1 produced constriction. Intraluminal administration of a selective...... inhibition of cyclooxygenase and endothelium-derived hyperpolarizing factor did not....

  6. Systemic hemodynamic and regional circulatory effects of centrally administered endothelin-1 are mediated through ETA receptors

    NARCIS (Netherlands)

    S. Rebello (Sam); S. Roy (Santanu); P.R. Saxena (Pramod Ranjan); A. Gulati (Anil)

    1995-01-01

    textabstractCentral endothelin (ET) has been implicated in the regulation of the cardiovascular system. The effect of intracerebroventricular (i.c.v.) administration of ET-1 or IRL 1620 (5, 15 and 45 ng) on the systemic hemodynamics and regional circulation was studied in anesthetized rats using a

  7. Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells

    DEFF Research Database (Denmark)

    Chen, Qing-wen; Edvinsson, Lars; Xu, Cang-Bao

    2009-01-01

    muscle cells (VSMCs) through activation of endothelin type A (ETA) and type B (ETB) receptors. The extracellular signal-regulated kinase 1 and 2 (ERK1/2) mitogen-activated protein kinases (MAPK) are involved in ET-1-induced VSMC contraction and proliferation. This study was designed to investigate...

  8. Low density lipoprotein induces upregulation of vasoconstrictive endothelin type B receptor expression

    DEFF Research Database (Denmark)

    Xu, Cang-Bao; Zheng, Jian-Pu; Zhang, Wei

    2014-01-01

    Vasoconstrictive endothelin type B (ET(B)) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ET(B) receptor expression and if extracellular signal...

  9. Pathophysiology of the endothelin system - lessons from genetically manipulated animal models

    Directory of Open Access Journals (Sweden)

    von Websky K

    2009-01-01

    Full Text Available Abstract Shortly after discovery of ET-1 in 1988, the entire endothelin system was characterized. The endothelin system consists of the three peptides ET-1, ET-2 and ET-3, their G-protein-coupled receptors endothelin receptor A and B (ETRA and ETRB and the two endothelin-converting enzymes (ECE-1 and ECE-2. Genetically modified animal models are an important tool in biomedical research. Here we describe the key findings obtained from genetically modified animal models either over-expressing compounds of the ET system or lacking these compounds (knockout mice. Results from the different transgenic and knockout models disclose that the ET system plays a major role in embryonic development. Two ET system-dependent neural crest-driven developmental pathways become obvious: one of them being an ET-1/ETAR axis, responsible for cardio-renal function and development as well as cranial development; the other seems to be an ET-3/ETBR mediated signalling pathway. Mutations within this axis are associated with disruptions in epidermal melanocytes and enteric neurons. These findings led to the discovery of similar findings in humans with Hirschsprung disease. In adult life the ET system is most important in the cardiovascular system and plays a role in fibrotic remodelling of the heart, lung and kidney as well as in the regulation of water and salt excretion.

  10. Nitric oxide blunts the endothelin-mediated pulmonary vasoconstriction in exercising swine.

    NARCIS (Netherlands)

    B. Houweling (Birgit); D. Merkus (Daphne); M.M. Dekker (Marjolein); D.J.G.M. Duncker (Dirk)

    2005-01-01

    textabstractWe have previously shown that vasodilators and vasoconstrictors that are produced by the vascular endothelium, including nitric oxide (NO), prostanoids and endothelin (ET), contribute to the regulation of systemic and pulmonary vascular tone in swine, in particular during treadmill

  11. Endothelin-1 Regulation of exercise-induced changes in flow: Dynamic regulation of vascular tone

    NARCIS (Netherlands)

    Rapoport, R.M. (Robert M.); D. Merkus (Daphne)

    2017-01-01

    textabstractAlthough endothelin (ET)-1 is a highly potent vasoconstrictor with considerable efficacy in numerous vascular beds, the role of endogenous ET-1 in the regulation of vascular tone remains unclear. The perspective that ET-1 plays little role in the on-going regulation of vascular tone at

  12. Influence of higher BMI for hepatitis B- and C-related hepatocellular carcinomas.

    Science.gov (United States)

    Hashimoto, Masakazu; Tashiro, Hirotaka; Kobayashi, Tsuyoshi; Kuroda, Shintaro; Hamaoka, Michinori; Ohdan, Hideki

    2017-08-01

    Although obesity is associated with hepatocellular carcinoma (HCC) development, its impact on the surgical outcomes of patients with hepatitis B virus (HBV)-and hepatitis C virus (HCV)-related HCC remains unclear. We retrospectively analyzed 714 patients with HCC who underwent curative hepatectomy. Among them, the HBV-related HCC group (n = 125) and HCV-related HCC group (n = 426) were subdivided according to the presence of body mass index (BMI) ≥ 25 kg/m(2). The surgical outcomes were compared. The 5-year overall survival rate after hepatectomy in the HBV-related HCC group was significantly better than that in the HCV-related HCC group. The 5-year overall survival rates of the HBV-related HCC with and without BMI ≥ 25 kg/m(2) groups were 65 and 85%, respectively. The 5-year overall survival rates in the HCV-related HCC with and without BMI ≥ 25 kg/m(2) groups were 75 and 65%, respectively. The HBV-related HCC with BMI ≥ 25 kg/m(2) groups had a significantly worse prognosis than the HBV-related HCC without BMI ≥ 25 kg/m(2) groups, while the HCV-related HCC with BMI ≥ 25 kg/m(2) groups had a significantly better prognosis than the HCV-related HCC without BMI ≥ 25 kg/m(2) groups. Multivariate analysis revealed that BMI ≥ 25 kg/m(2) was the positive and negative prognostic factor for the surgical outcomes of patients with HBV- and HCV-related HCC, respectively. BMI ≥ 25 kg/m(2) negatively affected the surgical outcomes of patients with HBV-related HCC and positively affected those of patients with HCV-related HCC.

  13. Serum and bronchoalveolar lavage fluid endothelin-1 concentrations as diagnostic biomarkers of canine idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Krafft, E; Heikkilä, H P; Jespers, P; Peeters, D; Day, M J; Rajamäki, M M; Mc Entee, K; Clercx, C

    2011-01-01

    Diagnosis of canine idiopathic pulmonary fibrosis (IPF) is challenging. Endothelin-1 (ET1) is a biomarker of IPF in humans, but whether ET1 can detect and differentiate IPF from other canine respiratory diseases is unknown. To evaluate whether measurement of the concentration of ET1 in serum and bronchoalveolar lavage fluid (BALF) can be used to distinguish canine IPF from chronic bronchitis (CB) and eosinophilic bronchopneumopathy (EBP). Twelve dogs with IPF, 10 dogs with CB, 6 dogs with EBP, 13 privately owned healthy West Highland White Terriers (WHWT), and 9 healthy Beagle dogs. Prospective, case control study. ET1 concentration was determined by ELISA in serum and in BALF. No significant difference in serum ET1 concentration was detected between healthy Beagle dogs and WHWT. Serum ET1 concentration was higher in dogs with IPF (median interquartile range; 2.32 pg/mL, 2.05-3.38) than healthy Beagle dogs (1.28, 1.07-1.53; P < .001), healthy WHWT (1.56, 1.25-1.85; P < .001), dogs with EBP (0.94 0.68-1.01; P = .001), and dogs with CB (1.54 0.74-1.82; P = .005). BALF ET1 concentration was below the detection limit in healthy WHWT and in dogs with CB, whereas it was measurable in all dogs with IPF. A cut-off serum concentration of 1.8 pg/mL had a sensitivity of 100% and a specificity of 81.2% for detection of IPF, with an area under the receiver operating characteristic curve of 0.818. Serum ET1 can differentiate dogs with IPF from dogs with EBP or CB. ET1 can be detected in BALF of dogs with IPF. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  14. Obesity-related eating behaviors are associated with higher food energy density and higher consumption of sugary and alcoholic beverages: a cross-sectional study.

    Science.gov (United States)

    Muñoz-Pareja, Maritza; Guallar-Castillón, Pilar; Mesas, Arthur E; López-García, Esther; Rodríguez-Artalejo, Fernando

    2013-01-01

    Obesity-related eating behaviors (OREB) are associated with higher energy intake. Total energy intake can be decomposed into the following constituents: food portion size, food energy density, the number of eating occasions, and the energy intake from energy-rich beverages. To our knowledge this is the first study to examine the association between the OREB and these energy components. Data were taken from a cross-sectional study conducted in 2008-2010 among 11,546 individuals representative of the Spanish population aged ≥ 18 years. Information was obtained on the following 8 self-reported OREB: not planning how much to eat before sitting down, eating precooked/canned food or snacks bought at vending machines or at fast-food restaurants, not choosing low-energy foods, not removing visible fat from meat or skin from chicken, and eating while watching TV. Usual diet was assessed with a validated diet history. Analyses were performed with linear regression with adjustment for main confounders. Compared to individuals with ≤ 1 OREB, those with ≥ 5 OREB had a higher food energy density (β 0.10; 95% CI 0.08, 0.12 kcal/g/day; p-trendconsumption of sugary drinks (β 7; 95% CI -7, 20 ml/day; p-trendalcoholic beverages (β 24; 95% CI 10, 38 ml/day; p-trendconsumption of fresh fruit, oily fish and white meat. No association was found between the number of OREB and food portion size or the number of eating occasions. OREB were associated with higher food energy density and higher consumption of sugary and alcoholic beverages. Avoiding OREB may prove difficult because they are firmly socially rooted, but these results may nevertheless serve to palliate the undesirable effects of OREB by reducing the associated energy intake.

  15. Over, and Underexpression of Endothelin 1 and TGF-Beta Family Ligands and Receptors in Lung Tissue of Broilers with Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Norma Dominguez-Avila

    2013-01-01

    Full Text Available Transforming growth factor beta (TGFβ is a family of genes that play a key role in mediating tissue remodeling in various forms of acute and chronic lung disease. In order to assess their role on pulmonary hypertension in broilers, we determined mRNA expression of genes of the TGFβ family and endothelin 1 in lung samples from 4-week-old chickens raised either under normal or cold temperature conditions. Both in control and cold-treated groups of broilers, endothelin 1 mRNA expression levels in lungs from ascitic chickens were higher than levels from healthy birds (, whereas levels in animals with cardiac failure were intermediate. Conversely, TGFβ2 and TGFβ3 gene expression in lungs were higher in healthy animals than in ascitic animals in both groups (. TGFβ1, TβRI, and TβRII mRNA gene expression among healthy, ascitic, and chickens with cardiac failure showed no differences (. BAMBI mRNA gene expression was lowest in birds with ascites only in the control group as compared with the values from healthy birds (.

  16. Historical and Theoretical Framework of the Relation between Higher Education Institutions and the Process of Regional Economic Development

    OpenAIRE

    Alexandru Cristian Fotea; Corneliu Guțu

    2016-01-01

    Objective: The objective is to show how the relation between the higher education institutions and their surrounding environment has evolved over the centuries and how it can increase the economic competitiveness of regional and national economies. Research Design & Methods: For the literature review that illustrates the evolution of the relation between higher education institutions and its surroundings we used a qualitative analysis using various sources of information (books, articles,...

  17. Disruptive Conduct: The Impact of Disruptive Technologies on Social Relations in Higher Education

    Science.gov (United States)

    Flavin, Michael

    2016-01-01

    Higher education institutions (HEIs) have invested significantly in digital technologies for learning and teaching. However, technologies provided by HEIs have not been universally successful in terms of adoption and usage. Meanwhile, both students and lecturers use disruptive technologies to support learning and teaching. This article examines…

  18. A Critical Exploration of Changing Definitions of Public Good in Relation to Higher Education

    Science.gov (United States)

    Williams, Joanna

    2016-01-01

    Discussion of the relationship between higher education (HE) and public good can be traced to Kant's argument that universities critically held society to account. Mill, Newman and Arnold suggested knowledge itself was a public good. In the twentieth century, economists argued education could drive national technological progress. More recently…

  19. Widening the Participation into Higher Education: Examining Bourdieusian Theory in Relation to HE in the UK

    Science.gov (United States)

    Burnell, Iona

    2015-01-01

    Bourdieu's theories enable us to conceptualise and understand why some people participate in higher education and some do not. Focussing on the working class as the marginalised social group in HE, Bourdieu demonstrated how education perpetuates inequality and lack of opportunity. The theories, or "thinking tools" as he called them,…

  20. Parental Encouragement in Relation to Academic Achievement of Higher Secondary School Students

    Science.gov (United States)

    Lawrence, A. S. Arul; Barathi, C.

    2016-01-01

    Parental Encouragement refers to the general process undertaken by the parents to initiative and directs the behaviour of the children towards high academic achievement. The present study aims to probe the relationship between Parental Encouragement and Academic Achievement of Higher Secondary School Students. Survey method was employed and the…

  1. Emotional, Social, Educational Adjustment of Higher Secondary School Students in Relation to Academic Achievement

    Science.gov (United States)

    Sekar, J. Master Arul; Lawrence, A.S. Arul

    2016-01-01

    The present study aims to investigate whether there is any significant relationship between adjustment and academic achievement of higher secondary school students. In this survey study, the investigators used stratified random sampling technique for selecting the sample from the population. The stratification was done on the basis of gender and…

  2. Inequality of Higher Education in China: An Empirical Test Based on the Perspective of Relative Deprivation

    Science.gov (United States)

    Hou, Liming

    2014-01-01

    The primary goal of this paper is to examine what makes Chinese college students dissatisfied with entrance opportunities for higher education. Based on the author's survey data, we test two parameters which could be a potential cause of this dissatisfaction: 1) distributive inequality, which emphasizes the individual's dissatisfaction caused by…

  3. Reliability-Related Issues in the Context of Student Evaluations of Teaching in Higher Education

    Science.gov (United States)

    Kalender, Ilker

    2015-01-01

    Student evaluations of teaching (SET) have been the principal instrument to elicit students' opinions in higher education institutions. Many decisions, including high-stake ones, are made based on SET scores reported by students. In this respect, reliability of SET scores is of considerable importance. This paper has an argument that there are…

  4. Higher Dimensional Plane Symmetric Cosmological Models with Two-Fluid Source in General Relativity

    Science.gov (United States)

    Mete, V. G.; Umarkar, V. M.; Pund, A. M.

    2013-12-01

    We consider anisotropic, homogeneous two-fluid plane symmetric cosmological models in higher dimensions. Here one fluid represents the matter content of the universe and another fluid is chosen to model the CMB (cosmic microwave background) radiation. The radiation and matter content of the universe are in interactive phase. Also we have discussed the behaviour of fluid parameters and kinematical parameters.

  5. Evolving ASEAN-Australia Relations in Higher Education. Towards a Regional Knowledge Network?

    Science.gov (United States)

    Welch, Anthony

    2016-01-01

    Australia's attitude towards ASEAN has waxed and waned over recent decades, including in higher education. In part a reflection of tensions between its geography and history, it highlighted the question of the extent to which Australia saw itself as an Asian country (an uncertainty shared by a number of its ASEAN neighbours). Reviewing changes in…

  6. Examining Success Factors Related to ERP Implementations in Higher Education Shared Services Projects

    Science.gov (United States)

    Stoyanoff, Dawn Galadriel Pfeiffer

    2012-01-01

    This study examined the enterprise resource planning (ERP) implementations that utilized a shared services model in higher education. The purpose of this research was to examine the critical success factors which were perceived to contribute to project success. This research employed a quantitative non-experimental correlational design and the…

  7. Relating the practice of working librarian for benchmarks quality distance higher education

    Directory of Open Access Journals (Sweden)

    Cintia Kath Blank

    2013-07-01

    Full Text Available Introduction: The issue EAD has been studied now, however, it considered that with regard to the librarian's work there is still much to be debated.Objective: To contribute to insights into the activities of the librarian combined with the items listed in the "Benchmarks of Quality for Distance Higher Education."Methodology: Literature review.Results: The higher the distance is reality that is increasingly present in our society, both in the public and in particular in big cities or towns and all professionals involved in education should pay attention to the issue of quality in EAD in order to be offered an educational process that enables the full development of the student in their learning process.Conclusion: It was observed that the role of the librarian is renewed every moment, this requires ongoing professional reflection and reinvention of their skills, knowledge and techniques to better serve the users of information service.

  8. Computer and Computer Games in Relation to Children of Higher School Age

    OpenAIRE

    Urbanová, Lenka

    2010-01-01

    In this work I am giving a point of view at the problematic of children in higher school age using computers. I describe both the positive and negative aspects that influents pubescent in the context of progress of information technologies. I focused on describing the term internet, virtual reality, virtual identity and the negative aspects of internet progress, especially cyber chicane and addiction. I dissected computer games - their origins, differences and description. Also I wrote about ...

  9. Historical and Theoretical Framework of the Relation between Higher Education Institutions and the Process of Regional Economic Development

    Directory of Open Access Journals (Sweden)

    Alexandru Cristian Fotea

    2016-03-01

    Full Text Available Objective: The objective is to show how the relation between the higher education institutions and their surrounding environment has evolved over the centuries and how it can increase the economic competitiveness of regional and national economies. Research Design & Methods: For the literature review that illustrates the evolution of the relation between higher education institutions and its surroundings we used a qualitative analysis using various sources of information (books, articles, journals etc. In order to capture the contribution of higher education to sustainable development of national economies in Eastern Europe we used an empirical analysis based on the data and statistics provided by the The Global Competitiveness Report. Findings: In the context of a contemporary global “knowledge economy”, higher education institutions contribute to the economic competitiveness of regions and nations by performing quality higher education and innovation activities. Implications & Recommendations: Both theoretical literature and practical evidence show that the relation between higher education institutions and the surrounding economies have helped eachother become more competitive. More than ever, nowadays regions and nations must foster and invest in the most important institutions that provide higher education and innovation which increase the competitiveness level. Contribution & Value Added: The originality of this work lies in displaying the historical evolution of higher education in relation to its surrounding environment and  the comparative analysis of the two competitivity pillars – higher education and innovation – in Eastern Europe. Article type: research paper Keywords: higher education institutions; regional economic development; socio-economic impact; JEL codes: O1, F63

  10. Neuropsychological factors related to returning to work in patients with higher brain dysfunction.

    Science.gov (United States)

    Kai, Akiko; Hashimoto, Manabu; Okazaki, Tetsuya; Hachisuka, Kenji

    2008-12-01

    We conducted neuropsychological tests of patients with higher brain dysfunction to examine the characteristics of barriers to employment. We tested 92 patients with higher brain dysfunction (average age of 36.3 +/- 13.8 years old, ranging between 16 and 63 years old, with an average post-injury period of 35.6 +/- 67.8 months) who were hospitalized at the university hospital between February 2002 and June 2007 for further neuropsychological evaluation, conducting the Wechsler Adult Intelligence Scale-Revised (WAIS-R), Wechsler Memory Scale-Revised (WMS-R), the Rivermead Behavioral Memory Test (RBMT), Frontal Assessment Battery (FAB) and Behavioral Assessment of Dysexecutive Syndrome (BADS). The outcomes after discharge were classified between competitive employment, sheltered employment and non-employment, and the three groups were compared using one-way analysis of variance and the Scheffe test. The WAIS-R subtests were mutually compared based on the standard values of significant differences described in the WAIS-R manual. Verbal performance and full scale Intelligence Quotient (IQ) of WAIS-R were 87.7 +/- 15.6 (mean +/- standard deviation), 78.5 +/- 18.1 and 81.0 +/- 17.2, respectively, and verbal memory, visual memory, general memory, attention/concentration and delayed recall were 74.6 +/- 20.0, 76.6 +/- 21.4, 72.0 +/- 20.4, 89.0 +/- 16.5 and 65.2 +/- 20.8, respectively. The competitive employment group showed significantly higher scores in performance IQ and full IQ on the WAIS-R and verbal memory, visual memory, general memory and delayed recall on the WMS-R and RBMT than the non-employment group. The sheltered employment group showed a significantly higher score in delayed recall than the non-employment group. No difference was observed in the FAB or BADS between the three groups. In the subtests of the WAIS-R, the score for Digit Symbol-Coding was significantly lower than almost all the other subtests. For patients with higher brain dysfunction, IQ (full

  11. Print-Tuning Lateralization and Handedness : An Event-Related Potential Study in Dyslexic Higher Education Students

    NARCIS (Netherlands)

    van Setten, Ellie R. H.; Martinez-Ferreiro, Silvia; Maurits, Natasha M.; Maassen, Ben A. M.

    Despite their ample reading experience, higher education students with dyslexia still show deficits in reading and reading-related skills. Lateralized print tuning, the early sensitivity to print of the left parietal cortex signalled by the N1 event-related potential (ERP) component, differs between

  12. The Triple Shift: Student-Mothers, Identity Work and Engagement with Low-Status Vocationally Related Higher Education

    Science.gov (United States)

    Smith, Paul H.

    2017-01-01

    This paper discusses a piece of qualitative research that examined the narratives that a group of learners articulated when they discussed their experiences of studying on a relatively low-status, vocationally related higher education programme. These students were school-based teaching assistants who were undertaking foundation degree study at a…

  13. Obesity-Related Eating Behaviors Are Associated with Higher Food Energy Density and Higher Consumption of Sugary and Alcoholic Beverages: A Cross-Sectional Study

    Science.gov (United States)

    Muñoz-Pareja, Maritza; Guallar-Castillón, Pilar; Mesas, Arthur E.; López-García, Esther; Rodríguez-Artalejo, Fernando

    2013-01-01

    Objectives Obesity-related eating behaviors (OREB) are associated with higher energy intake. Total energy intake can be decomposed into the following constituents: food portion size, food energy density, the number of eating occasions, and the energy intake from energy-rich beverages. To our knowledge this is the first study to examine the association between the OREB and these energy components. Methods Data were taken from a cross-sectional study conducted in 2008–2010 among 11,546 individuals representative of the Spanish population aged ≥18 years. Information was obtained on the following 8 self-reported OREB: not planning how much to eat before sitting down, eating precooked/canned food or snacks bought at vending machines or at fast-food restaurants, not choosing low-energy foods, not removing visible fat from meat or skin from chicken, and eating while watching TV. Usual diet was assessed with a validated diet history. Analyses were performed with linear regression with adjustment for main confounders. Results Compared to individuals with ≤1 OREB, those with ≥5 OREB had a higher food energy density (β 0.10; 95% CI 0.08, 0.12 kcal/g/day; p-trendalcoholic beverages (β 24; 95% CI 10, 38 ml/day; p-trendalcoholic beverages. Avoiding OREB may prove difficult because they are firmly socially rooted, but these results may nevertheless serve to palliate the undesirable effects of OREB by reducing the associated energy intake. PMID:24204756

  14. Hyaluronan Production by Renomedullary Interstitial Cells: Influence of Endothelin, Angiotensin II and Vasopressin

    Directory of Open Access Journals (Sweden)

    Sara Stridh

    2017-12-01

    Full Text Available The content of hyaluronan (HA in the interstitium of the renal medulla changes in relation to body hydration status. We investigated if hormones of central importance for body fluid homeostasis affect HA production by renomedullary interstitial cells in culture (RMICs. Simultaneous treatment with vasopressin and angiotensin II (Ang II reduced HA by 69%. No change occurred in the mRNA expressions of hyaluronan synthase 2 (HAS2 or hyaluronidases (Hyals, while Hyal activity in the supernatant increased by 67% and CD44 expression reduced by 42%. The autocoid endothelin (ET-1 at low concentrations (10−10 and 10−8 M increased HA 3-fold. On the contrary, at a high concentration (10−6 M ET-1 reduced HA by 47%. The ET-A receptor antagonist BQ123 not only reversed the reducing effect of high ET-1 on HA, but elevated it to the same level as low concentration ET-1, suggesting separate regulating roles for ET-A and ET-B receptors. This was corroborated by the addition of ET-B receptor antagonist BQ788 to low concentration ET-1, which abolished the HA increase. HAS2 and Hyal2 mRNA did not alter, while Hyal1 mRNA was increased at all ET-1 concentrations tested. Hyal activity was elevated the most by high ET-1 concentration, and blockade of ET-A receptors by BQ123 prevented about 30% of this response. The present study demonstrates an important regulatory influence of hormones involved in body fluid balance on HA handling by RMICs, thereby supporting the concept of a dynamic involvement of interstitial HA in renal fluid handling.

  15. Endothelin-1 and psychosocial risk factors for cardiovascular disease: a systematic review.

    Science.gov (United States)

    Yammine, Luba; Kang, Duck-Hee; Baun, Mara M; Meininger, Janet C

    2014-02-01

    Psychosocial factors (i.e., social environment and emotional factors) contribute to an increased risk of cardiovascular disease (CVD). Perturbation in a potent vasoconstrictive peptide endothelin (ET)-1 could be one of the mechanisms linking psychosocial factors to CVD. Our aim was to evaluate the literature on the relationship between plasma ET-1 and psychosocial risk factors for CVD. MEDLINE and PsycINFO databases were searched for articles on human studies published in peer-reviewed English-language journals through September 2012. Of the 20 studies that met the inclusion criteria, 14 were experimental studies of acute psychological/mental challenges and 6 were observational studies of psychological and social factors. The inferences drawn from this review were as follows: a) laboratory-induced acute psychological/mental stress may result in exaggerated plasma ET-1 release in those with CVD and those at risk for CVD (positive studies: 5/10); b) chronic/episodic psychosocial factors may have a positive relationship to plasma ET-1 (positive studies: 3/5); and c) race (African American), sex (male), and individual differences in autonomic and hemodynamic responses to stress (parasympathetic withdrawal and elevated blood pressure responsiveness) may moderate the relationship between psychosocial factors and plasma ET-1. This review indicates that psychosocial risk factors for CVD are associated with elevated plasma ET-1; however, the relatively small number of studies, methodological differences, and variable assessment tools preclude definitive conclusions about the strength of the association. Specific suggestions regarding the selection of psychosocial factors, optimization of acute challenge protocols, and standardization of methods and timing of the ET-1 measures are provided.

  16. Management competencies in higher education: Perceived job importance in relation to level of training required

    Directory of Open Access Journals (Sweden)

    Ingrid L. Potgieter

    2010-03-01

    Full Text Available Orientation: The increasing changes and demands placed on higher education institutions in the 21st century and resultant impact on the roles and responsibilities of heads of department (HODs have led to an increasing emphasis on the development of core HOD management competencies.Research purpose: The aim of this article is to determine the relationship between a specific set of HOD managerial competencies identified as being important for the job and the level of training required in terms of these competencies.Motivation for the study: Research has provided evidence that HODs are often ill-prepared for their managerial role, which requires the development of specific management competencies to enable them to fulfil their roles effectively.Research design, approach and method: A non-experimental quantitative survey design approach was followed and correlational data analyses were performed. A cross-sectional sample of 41 HODs of 22 departments from various faculties of a higher education institution in Gauteng participated in this study. The Management Competency Inventory (MCI of Visser (2009 was applied as a measure.Main findings: The Pearson product-moment analysis indicated that there is a significant relationship between the competencies indicated as being important for the job and the level of training required.Practical/Managerial implications: Training needs of HODs should be formally assessed and the depth of training required in terms of the identified management competencies should be considered in the design of training programmes.Contributions/Value-add: The information obtained in this study may potentially serve as a foundation for the development of an HOD training programme in the South African higher education environment.

  17. Educational policy and its relation with the internationalization and international cooperation on higher education: Mexico case

    Directory of Open Access Journals (Sweden)

    Genoveva Amador Fierros

    2013-06-01

    Full Text Available The idea of international cooperation linked to educational processes appeared explicitly in the 1990s in Latin America. International- cooperation processes as well as higher-education internationalization in Mexico started before the existence of a State policy, which helped build consensus for the adoption of the International Cooperation for Development Act in 2011. The drive of associations of universities and individuals, such as the National Association of Universities (ANUIES and later the Consortium of Mexican Universities (CUMEX, as well as the Mexican Association for International Education (AMPEI has been key in promoting international cooperation, as a catalyst for higher-education internationalization. It is now recognized that emerging work and sharing environments need a variety of competences as well as knowledge that sometimes researchers, professors or government officials do not have. In addition, there is a need to obtain knowledge and skills that do not come through traditional teaching and learning, but through processes of interaction with the world. The internationalization of higher education appears as a strategy that can help universities improve their quality, thus strengthening the need to cooperate with similar institutions and other organizations beyond our borders. Moreover, the type of academic achievement to which internationalization processes can lead are viewed by some authors as part of the very concept of quality and educational excellence in the 21st century.There is logic in the sequence in which policies and reforms have been implemented in the field of education in different parts of the world, as certain needs that the political class sees as priorities are met: expansion of coverage and access, education quality and, finally, international cooperation. This might explain the late arrival of the International Cooperation for Development Act in Mexico, although a mixed model is emerging in Latin

  18. How Tenure in Higher Education Relates to Faculty Productivity and Retention

    Science.gov (United States)

    Manjounes, Cindy Kay

    2016-01-01

    Some public university systems are considering abolishing tenure as a cost-saving mechanism, but little is known about how this change may impact organizational outcomes related to faculty retention and research productivity. Using Almendarez' human capital theory, the purpose of this concurrent mixed methods study was to explore how tenure…

  19. The Language-Related Academic Self-Confidence of Noncitizen Students in US Higher Education

    Science.gov (United States)

    Goodnight, Melissa Rae

    2017-01-01

    For this multivariate regression study I utilized data from the Cooperative Institutional Research Program (CIRP) surveys of freshman and senior undergraduates to examine the language-related academic self-confidence (LRASC) of noncitizen students in relationship to college environmental factors like academic disengagement and assertiveness.…

  20. Body lift, drag and power are relatively higher in large-eared than in small-eared bat species

    DEFF Research Database (Denmark)

    Håkansson, Jonas; Jakobsen, Lasse; Hedenström, Anders

    2017-01-01

    than previously assumed and that the large-eared species has a higher body drag coefficient, but also produces relatively more ear/body lift than the small-eared species, in line with prior studies on model bats. The measured aerodynamic power of P. auritus was higher than predicted from...... mitigate the cost by producing aerodynamic lift. Here we compare quantitative aerodynamic measures of flight efficiency of two bat species, one large-eared (Plecotus auritus) and one small-eared (Glossophaga soricina), flying freely in a wind tunnel. We find that the body drag of both species is higher...

  1. Analysis of the Value Creation in Higher Institutions: A Relational Perspective

    Directory of Open Access Journals (Sweden)

    Raquel SÁNCHEZ-FERNÁNDEZ

    2010-10-01

    Full Text Available Despite the growing interest in value creation, a review of the relevant educational literature reveals that there is no generally accepted and empirically confirmed relational model of the student value creation process. This paper contributes in this way, analyzing several antecedents and consequences in the value creation process between graduates and their universities. We therefore study the effects of the quality of the student-professor interaction, trust, and university image on student perceived value. Moreover, we analyze the impact of perceived value on student satisfaction and loyalty. An empirical study was carried out in order to test the proposed theoretical model. The findings provide relevant academic and managerial implications for strategic decisionmaking at universities.

  2. Research on Interventions for Adolescents with Learning Disabilities: A Meta-Analysis of Outcomes Related to Higher-Order Processing.

    Science.gov (United States)

    Swanson, H. Lee

    2001-01-01

    Details meta-analysis of 58 intervention studies related to higher-order processing (i.e., problem solving) for adolescents with learning disabilities. Discusses factors that increased effect sizes: (1) measures of metacognition and text understanding; (2) instruction including advanced organizers, new skills, and extended practice; and (3)…

  3. Preferred "Learning Styles" in Students Studying Sports-Related Programmes in Higher Education in the United Kingdom

    Science.gov (United States)

    Peters, Derek; Jones, Gareth; Peters, John

    2008-01-01

    This article investigates the "preferred learning styles" and their relationship with grades for students undertaking sports-related undergraduate programmes at a higher education institution in the UK. Preferred "learning styles" in students in this discipline have been identified as auditory, kinaesthetic and group, although…

  4. Relational Aspects between ICT and the Modernization of Differentiated and Individualized Teaching of Foreign Languages in Higher Education

    Directory of Open Access Journals (Sweden)

    Niculescu Brânduşa-Oana

    2016-06-01

    Full Text Available The amplitude of the interest and of the concerns related to the identification and the setting of the foundation necessary for perfecting higher education increasingly brings the adjustment of didactic activities to the students’ particularities to the attention of educational theory and practice, with a view to forming and developing their personality.

  5. A role for endothelin in bicuculline-induced neurogenic pulmonary oedema in rats.

    OpenAIRE

    Herbst, C.; Tippler, B.; Shams, H.; Simmet, T.

    1995-01-01

    1. The possible contribution of endogenous endothelin (ET) to the pathogenesis of seizure-associated pulmonary oedema was examined in mechanically ventilated rats after intravenous bolus injection of the gamma-aminobutyric acid (GABA) antagonist, bicuculline (1.2 mg kg-1). 2. Recurrent seizure activity elicited by bicuculline injection led to rapidly developing pulmonary oedema. Within 4 min after bicuculline application (1.2 mg kg-1), arterial O2 partial pressure (PaO2) significantly dropped...

  6. Bosentan, a mixed endothelin receptor antagonist, inhibits superoxide anion-induced pain and inflammation in mice.

    Science.gov (United States)

    Serafim, Karla G G; Navarro, Suelen A; Zarpelon, Ana C; Pinho-Ribeiro, Felipe A; Fattori, Victor; Cunha, Thiago M; Alves-Filho, Jose C; Cunha, Fernando Q; Casagrande, Rubia; Verri, Waldiceu A

    2015-11-01

    Bosentan is a mixed endothelin receptor antagonist widely used to treat patients with pulmonary arterial hypertension, and the emerging literature suggests bosentan as a potent anti-inflammatory drug. Superoxide anion is produced in large amounts during inflammation, stimulates cytokine production, and thus contributes to inflammation and pain. However, it remains to be determined whether endothelin contributes to the inflammatory response triggered by the superoxide anion. The present study investigated the effects of bosentan in a mouse model of inflammation and pain induced by potassium superoxide, a superoxide anion donor. Male Swiss mice were treated with bosentan (10-100 mg/kg) by oral gavage, 1 h before potassium superoxide injection, and the inflammatory response was evaluated locally and at spinal cord (L4-L6) levels. Bosentan (100 mg/kg) inhibited superoxide anion-induced mechanical and thermal hyperalgesia, overt pain-like behavior (abdominal writhings, paw flinching, and licking), paw edema, myeloperoxidase activity (neutrophil marker) in the paw skin, and leukocyte recruitment in the peritoneal cavity. Bosentan also inhibited superoxide anion-induced interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) production, while it enhanced IL-10 production in the paw skin and spinal cord. Bosentan inhibited the reduction of antioxidant capacity (reduced glutathione, ferric reducing antioxidant power, and ABTS radical scavenging ability) induced by the superoxide anion. Finally, we demonstrated that intraplantar injection of potassium superoxide induces the mRNA expression of prepro-endothelin-1 in the paw skin and spinal cord. In conclusion, our results demonstrated that superoxide anion-induced inflammation, pain, cytokine production, and oxidative stress depend on endothelin; therefore, these responses are amenable to bosentan treatment.

  7. Venous plasma levels of endothelin-1 are not altered immediately after nitroglycerin infusion in healthy subjects

    DEFF Research Database (Denmark)

    Thomsen, L L; Iversen, Helle Klingenberg; Emmeluth, C

    1995-01-01

    before and immediately (5-30 s) after 80 min infusion of NTG (glyceryl trinitrate) or saline in 12 healthy subjects. On two different days separated by at least 1 week, NTG in four different doses, 0.015, 0.25, 1.0, and 2.0 micrograms. kg-1. min-1, or placebo (isotonic saline) was infused successively...... for 20 min each dose. During the infusion blood pressure and heart rate were measured. NTG infusion significantly decreased systolic blood pressure from 112.4 to 103.4 mmHg and pulse pressure from 39.3 to 29.5 mmHg. Heart rate increased from 62.7 to 73.1 beats. min-1. No changes in endothelin-1 plasma...... levels were induced by NTG infusion (2.4 pg.ml-1 before NTG vs. 2.7 pg.ml-1 after NTG) and placebo infusion also did not affect plasma endothelin-1. It is concluded that venous plasma levels of endothelin-1 are not altered immediately after NTG infusion....

  8. Comparison of plasma endothelin levels between osteoporotic, osteopenic and normal subjects

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    Biçimoğlu Ali

    2005-09-01

    Full Text Available Abstract Background It has been demonstrated that endothelins (ET have significant roles in bone remodeling, metabolism and physiopathology of several bone diseases. We aimed to investigate if there was any difference between the plasma ET levels of osteoporotic patients and normals. Methods 86 patients (70 women and 16 men with a mean age of 62.6 (ranges: 51–90 years were included in this study. Patients were divided into groups of osteoporosis, osteopenia and normal regarding reported T scores of DEXA evaluation according to the suggestions of World Health Organization. According to these criteria 19, 43 and 24 were normal, osteopenic and osteoporotic respectively. Then total plasma level of ET was measured in all patients with monoclonal antibody based sandwich immunoassay (EIA method. One-way analysis of variance test was used to compare endothelin values between normals, osteopenics and osteoporotics. Results Endothelin total plasma level in patients was a mean of 98.36 ± 63.96, 100.92 ± 47.2 and 99.56 ± 56.6 pg/ml in osteoporotic, osteopenic and normal groups respectively. The difference between groups was not significant (p > 0.05. Conclusion No significant differences in plasma ET levels among three groups of study participants could be detected in this study.

  9. Endothelin-converting enzymes degrade α-synuclein and are reduced in dementia with Lewy bodies.

    Science.gov (United States)

    Miners, James Scott; Love, Seth

    2017-04-01

    We have examined the roles of the endothelin-converting enzyme-1 and -2 (ECE-1 and ECE-2) in the homeostasis of α-synuclein (α-syn) and pathogenesis of Lewy body disease. The ECEs are named for their ability to convert inactive big endothelin to the vasoactive peptide endothelin-1 (EDN1). We have found that ECE-1 and ECE-2 cleave and degrade α-syn in vitro and siRNA-mediated knockdown of ECE-1 and ECE-2 in SH-SY5Y neuroblastoma cells significantly increased α-syn both intracellularly (within the cell lysate) (p Lewy body disease, we measured ECE-1 and ECE-2 levels by sandwich ELISA in post-mortem samples of cingulate cortex (a region with a predilection for Lewy body pathology) in dementia with Lewy bodies (DLB) and age-matched controls. ECE-1 (p Lewy body pathology as indicated by the level of α-syn phosphorylated at Ser129 (r = -0.54, p < 0.01 for ECE-1 and r = -0.49, p < 0.05 for ECE-2). Our novel findings suggest a role for ECEs in the metabolism of α-syn that could contribute to the development and progression of DLB. © 2017 International Society for Neurochemistry.

  10. EFFECTS OF HIGHER EDUCATION ON GLOBAL COMPETITIVENESS: REVIEWS IN RELATION WITH EUROPEAN COUNTRIES AND THE MIDDLE EAST COUNTRIES

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    HILAL YILDIRIR KESER

    2015-03-01

    Full Text Available The aim of this study is investigate the effects of higher education on global competitiveness One of the most widely accepted definition of global competitiveness is in the form of " efficiency level encompassing all of the institutions that will ensure sustainable growth in a country, policies and factors of production". Therefore the competitiveness of a country depends on the factors such as; The level of development of R & D activities and productivity, performance of various sectors, the country's trade surplus, producing goods hosting high-tech in their nature, availability of expert and skilled labor force. But one of the main points in the realization of these factors is the quality of the higher education. Higher education has an important role in the formation of qualified labour. And the qualified labour carries the competitiveness firstly of the sector and then of the country up to higher ranks by increasing the performance and productivity of the companies. The study will be discussed in the following way: firstly the context of the global competitiveness will be mentioned, secondly, the role and importance of higher education will be put forth by explaining the basic determinants of competitivenes particularly within the World Economic Forum Global Competitiveness Index. Finally, assessments will be made in relation with the situation of higher education in global competitiveness in European countries and Middle Eastern countries.

  11. Non-endothelial endothelin counteracts hypoxic vasodilation in porcine large coronary arteries

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    Fröbert Ole

    2011-05-01

    Full Text Available Abstract Background The systemic vascular response to hypoxia is vasodilation. However, reports suggest that the potent vasoconstrictor endothelin-1 (ET-1 is released from the vasculature during hypoxia. ET-1 is reported to augment superoxide anion generation and may counteract nitric oxide (NO vasodilation. Moreover, ET-1 was proposed to contribute to increased vascular resistance in heart failure by increasing the production of asymmetric dimethylarginine (ADMA. We investigated the role of ET-1, the NO pathway, the potassium channels and radical oxygen species in hypoxia-induced vasodilation of large coronary arteries. Results In prostaglandin F2α (PGF2α, 10 μM-contracted segments with endothelium, gradual lowering of oxygen tension from 95 to 1% O2 resulted in vasodilation. The vasodilation to O2 lowering was rightward shifted in segments without endothelium at all O2 concentrations except at 1% O2. The endothelin receptor antagonist SB217242 (10 μM markedly increased hypoxic dilation despite the free tissue ET-1 concentration in the arterial wall was unchanged in 1% O2 versus 95% O2. Exogenous ET-1 reversed hypoxic dilation in segments with and without endothelium, and the hypoxic arteries showed an increased sensitivity towards ET-1 compared to the normoxic controls. Without affecting basal NO, hypoxia increased NO concentration in PGF2α-contracted arteries, and an NO synthase inhibitor, L-NOARG,(300 μM, NG-nitro-L-Arginine reduced hypoxic vasodilation. NO-induced vasodilation was reduced in endothelin-contracted preparations. Arterial wall ADMA concentrations were unchanged by hypoxia. Blocking of potassium channels with TEA (tetraethylammounium chloride(10 μM inhibited vasodilation to O2 lowering as well as to NO. The superoxide scavenger tiron (10 μM and the putative NADPH oxidase inhibitor apocynin (10 μM leftward shifted concentration-response curves for O2 lowering without changing vasodilation to 1% O2. PEG (polyethylene

  12. Body lift, drag and power are relatively higher in large-eared than in small-eared bat species.

    Science.gov (United States)

    Håkansson, Jonas; Jakobsen, Lasse; Hedenström, Anders; Johansson, L Christoffer

    2017-10-01

    Bats navigate the dark using echolocation. Echolocation is enhanced by external ears, but external ears increase the projected frontal area and reduce the streamlining of the animal. External ears are thus expected to compromise flight efficiency, but research suggests that very large ears may mitigate the cost by producing aerodynamic lift. Here we compare quantitative aerodynamic measures of flight efficiency of two bat species, one large-eared (Plecotus auritus) and one small-eared (Glossophaga soricina), flying freely in a wind tunnel. We find that the body drag of both species is higher than previously assumed and that the large-eared species has a higher body drag coefficient, but also produces relatively more ear/body lift than the small-eared species, in line with prior studies on model bats. The measured aerodynamic power of P. auritus was higher than predicted from the aerodynamic model, while the small-eared species aligned with predictions. The relatively higher power of the large-eared species results in lower optimal flight speeds and our findings support the notion of a trade-off between the acoustic benefits of large external ears and aerodynamic performance. The result of this trade-off would be the eco-morphological correlation in bat flight, with large-eared bats generally adopting slow-flight feeding strategies. © 2017 The Author(s).

  13. Opposed circulating plasma levels of endothelin-1 and C-type natriuretic peptide in children with Plasmodium falciparum malaria

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    Issifou Saadou

    2008-12-01

    Full Text Available Abstract Background Molecular mechanisms involved in the pathogenesis of severe Plasmodium falciparum malaria (SM, are not yet fully understood. Both endothelin-1 (ET-1 and C-type natriuretic peptide (CNP are produced by vascular endothelium and act locally as paracrine regulators of vascular tone, ET-1 being a potent vasoconstrictor and CNP having strong vasorelaxant properties. Methods Plasma levels of ET-1 and N-terminal fragments of CNP (NT-proCNP were studied on admission and after 24 hours of treatment, using enzyme-linked-immunosorbent-assay (ELISA technique, in Gabonese children with severe falciparum malaria (SM, n = 50, with uncomplicated malaria (UM, n = 39 and healthy controls (HC, n = 25. Results Compared to HC, malaria patients had significantly higher plasma levels of ET-1 and significantly lower levels of NT-proCNP (p p p = 0.034, whereas UM was not significantly different to HC. In the SM group we found a trend towards lower ET-1 levels compared to UM (p = 0.085. Conclusion In the present study, an imbalance between the vasoconstricitve and vasorelaxant endothelium-derived substances ET-1 and CNP in the plasma of children with falciparum malaria is demonstrated, presumably in favor of vasoconstrictive and pro-inflammatory effects. These results may indicate involvement of ET-1 and CNP in malaria pathogenesis. Furthermore, results of lower ET-1 and CNP levels in SM may reflect endothelial cell damage.

  14. Endothelin-1 stimulates the release of preloaded ( sup 3 H)D-aspartate from cultured cerebellar granule cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, W.W.; Lee, C.Y.; Chuang, D.M. (NIMH Neuroscience Center, Washington, DC (USA))

    1990-03-16

    We have recently reported that endothelin-1 (ET) induces phosphoinositide hydrolysis in primary cultures of rat cerebellar granule cells. Here we found that ET in a dose-dependent manner (1-30 nM) stimulated the release of preloaded ({sup 3}H)D-aspartate from granule cells. The ET-induced aspartate release was completely blocked in the absence of extracellular Ca{sup 2+}, but was unaffected by 1 mM Co{sup 2+} or 1 microM dihydropyridine derivatives (nisoldipine and nimodipine). At higher concentration (10 microM) of nisoldipine and nimodipine, the release was partially inhibited. Short-term pretreatment of cells with phorbol 12,13-dibutyrate (PDBu) potentiated the ET-induced aspartate release, while long-term pretreatment with PDBu attenuated the release. Long-term exposure of cells to pertussis toxin (PTX), on the other hand, potentiated the ET-induced effects. Our results suggest that ET has a neuromodulatory function in the central nervous system.

  15. Endothelial dysfunction in high fructose containing diet fed rats: Increased nitric oxide and decreased endothelin-1 levels in liver tissue

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    Zeki Arı

    2010-09-01

    Full Text Available Objectives: Dietary high fructose consumption which is closely associated with endothelial dysfunction via insulin re-sistance has recently increased in developed countries. Insulin resistance has a promoter effect on many metabolic disorders such as syndrome X, polycystic ovary syndrome, Type 2 diabetes mellitus etc. Our aim in this study is to understand the impact of increased fructose intake on metabolisms of glucose, insulin and endothelial dysfunction by measuring nitric oxide (NO and endothelin-1 (ET-1 levels in hepatic tissue which is crucial in fructose metabolism.Materials and Methods: We designed an animal study to understand increased fructose intake on hepatic endothe-lium. Twenty adult male albino rats were divided into two groups; the study group (group 1, n=10 received isocaloric fructose enriched diet (fructose-fed rats, containing 18.3% protein, 60.3% fructose and 5.2% fat while the control group received purified regular chow (group 2, n=10 for 2 weeks. After feeding period, blood and hepatic tissue samples were collected and glucose, insulin, NO and ET-1 levels were analysed.Results: We found increased fasting glucose and insulin levels and impaired glucose tolerance in fructose fed rats. Higher NO and lower ET–1 levels were also detected in hepatic tissue samples of the group 1.Conclusion: Increased fructose consumption has deleterious effects on glucose tolerance, insulin resistance and may cause to endothelial dysfunction.

  16. The Association of Endothelin-1 with Markers of Arterial Stiffness in Black South African Women: The SABPA Study

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    Christine Susara du Plooy

    2015-01-01

    Full Text Available Background. Limited data exist regarding endothelin-1 (ET-1, a vasoactive contributor in vascular tone, in a population subjected to early vascular deterioration. We compared ET-1 levels and explored its association with markers of arterial stiffness in black and white South Africans. Methodology. This cross-sectional substudy included 195 black (men: n=99; women: n=95 and 197 white (men: n=99; women: n=98 South Africans. Serum ET-1 levels were measured as well as markers of arterial stiffness (blood pressure, pulse wave velocity, and arterial compliance. ET-1 levels were higher in black men and white women compared to their counterparts after adjusting for C-reactive protein. In both single and partial (adjusting for body mass index and gamma glutamyl transferase regression analyses ET-1 correlated with age, interleukin-6, high density lipoprotein cholesterol, systolic blood pressure, pulse pressure, and pulse wave velocity in black women. In multivariate regression analyses the independent association of ET-1 with systolic blood pressure (Adj. R2=0.13; β=0.28, p<0.01 and pulse pressure (Adj. R2=0.11; β=0.27, p<0.01 was confirmed in black women only. ET-1 additionally associated with interleukin-6 in black women (p<0.01. Conclusion. Our result suggests that ET-1 and its link with subclinical arteriosclerosis are potentially driven by low-grade inflammation as depicted by the association with interleukin-6 in the black female cohort.

  17. More Dose-dependent Side Effects with Mercaptopurine over Azathioprine in IBD Treatment Due to Relatively Higher Dosing.

    Science.gov (United States)

    Broekman, Mark M T J; Coenen, Marieke J H; van Marrewijk, Corine J; Wanten, Geert J A; Wong, Dennis R; Verbeek, Andre L M; Klungel, Olaf H; Hooymans, Piet M; Guchelaar, Henk-Jan; Scheffer, Hans; Derijks, Luc J J; de Jong, Dirk J

    2017-10-01

    There are substantial global differences in the preference for mercaptopurine (MP) or its prodrug azathioprine (AZA) as first-choice thiopurine to treat inflammatory bowel diseases. Studies comparing both agents are scarce. Our aim was to compare AZA and MP in thiopurine-naive patients with inflammatory bowel disease for the frequency of side effects and efficacy. Post hoc analysis of the "Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory bowel disease Clinics" (TOPIC) trial, in which thiopurine-naive patients with inflammatory bowel disease with an indication for a thiopurine were randomized for a genotype-based dose versus standard of care. For this study, Cox proportional hazard ratios (HRs) were calculated to compare AZA and MP for discontinuation rates within 5 months, incidence of hepatotoxicity, leukopenia, and gastrointestinal side effects. Treatment efficacy was compared by logistic regression. Patient characteristics were similar for patients treated with AZA (n = 494, 64.4%) and MP (n = 273, 35.6%), yet patients with MP were relatively higher dosed compared with those on AZA. Discontinuation rates within 5 months were not different, 39.3% (AZA) and 38.1% (MP), HR 0.92 (95% confidence interval, 0.72-1.17; P = 0.50); however, patients on MP were more often subjected to dose reductions (30% versus 14%, P < 0.01). Higher rates of hepatotoxicity, HR 1.93 (95% confidence interval, 1.35-2.76; P < 0.01) and leukopenia, HR 2.55 (95% confidence interval, 1.51-4.30; P < 0.01) were observed with MP, which annulled in a secondary analysis with adjustment for the higher dose and metabolite levels. Patients treated with MP were relatively higher dosed, which resulted in more dose-dependent side effects and a higher rate of dose reductions.

  18. Higher refusal rates for organ donation among older potential donors in the Netherlands: impact of the donor register and relatives.

    Science.gov (United States)

    van Leiden, Hendrik A; Jansen, Nichon E; Haase-Kromwijk, Bernadette J J M; Hoitsma, Andries J

    2010-09-27

    The availability of donor organs is considerably reduced by relatives refusing donation after death. There is no previous large-scale evaluation of the influence of the Donor Register (DR) consultation and the potential donor's age on this refusal in The Netherlands. This study examines 2101 potential organ donors identified in intensive care units between 2005 and 2008 and analyzes the association of DR consultation and subsequent refusal by relatives and the relationship with the potential donor's age. Of the 1864 potential donor cases where the DR was consulted, the DR revealed no registration in 56%, 20% registration of consent, and 18% objection. In the other 6.5% of cases, where the DR indicated that relatives had to decide, the relatives' refusal rate was significantly lower than in the absence of a DR registration (46% vs. 63%). In 6% of the cases where the DR recorded donation consent, relatives still refused donation. DR registration, objection in the DR, and the relatives' refusal rate if the DR was not decisive increased with donor age. Despite the introduction of a DR, relatives still play an equally important role in the final decision for organ donation. The general public should be encouraged to register their donation preferences in the DR and also to discuss their preferences with their families. The higher refusal rate of older potential donors means that this group should receive more information about organ donation, especially because the cohort of available donors is ageing.

  19. Plasma endothelin-1 and tumor necrosis factor-alpha concentrations in pregnant and cyclic rats after low-dose endotoxin infusion

    NARCIS (Netherlands)

    Faas, MM; Bakker, WW; Valkhof, N; Baller, JFW; Schuiling, GA

    Plasma endothelin-1 and tumor necrosis factor-alpha were determined in pregnant and cyclic rats after infusion of either endotoxin (1.0 mu g/kg of body weight) or saline solution. After endotoxin, but not after saline solution, administration there was a transient endothelin-1 response in pregnant

  20. Expression of Endothelial Nitric Oxide Synthase and Endothelin-1 in Skin Tissue from Amputated Limbs of Patients with Complex Regional Pain Syndrome

    Directory of Open Access Journals (Sweden)

    J. George Groeneweg

    2008-01-01

    Full Text Available Background and Objectives. Impaired microcirculation during the chronic stage of complex regional pain syndrome (CRPS is related to increased vasoconstriction, tissue hypoxia, and metabolic tissue acidosis in the affected limb. Endothelial dysfunction is suggested to be the main cause of diminished blood flow. The aim of this study was to examine the distribution of endothelial nitric oxide synthase (eNOS and endothelin-1(ET-1 relative to vascular density represented by the endothelial marker CD31-immunoreactivity in the skin tissue of patients with chronic CRPS. Methods. We performed immunohistochemical staining on sections of skin specimens obtained from the amputated limbs (one arm and one leg of two patients with CRPS. Results. In comparison to proximal specimens we found an increased number of migrated endothelial cells as well as an increase of eNOS activity in distal dermis specimens. Conclusions. We found indications that endothelial dysfunction plays a role in chronic CRPS.

  1. Embodying Deficiency Through 'Affective Practice': Shame, Relationality, and the Lived Experience of Social Class and Gender in Higher Education.

    Science.gov (United States)

    Loveday, Vik

    2016-12-01

    Based on empirical research with participants from working-class backgrounds studying and working in higher education in England, this article examines the lived experience of shame. Building on a feminist Bourdieusian approach to social class analysis, the article contends that 'struggles for value' within the field of higher education precipitate classed judgements, which have the potential to generate shame. Through an examination of the 'affective practice' of judgement, the article explores the contingencies that precipitate shame and the embodiment of deficiency. The article links the classed and gendered dimensions of shame with valuation, arguing that the fundamental relationality of social class and gender is not only generative of shame, but that shame helps in turn to structure both working-class experience and a view of the working classes as 'deficient'.

  2. Academic Community Consumer Assessment an Institution of Public Higher Education in Relation to Green it Practices in Organizations

    Directory of Open Access Journals (Sweden)

    Luis Hernan Contreras Pinochet

    2015-09-01

    Full Text Available The purpose of this article is understanding the consumers of the academic community community in a public higher education institution in relation to Green IT practices in organizations. This study aims to confirm the model developed by Lunardi et al. (2011 Lunardi et al. (2014 through the application of multivariate statistical technique of Structural Equation Modeling (SEM. The survey research was conducted in a public higher education institution, based in the city of Osasco, using structured questionnaire with five point likert scale options and the respondents were: the students and professors from graduate school in Business Administration, in addition to employees administrative technician education. The results confirmed the highly significant and demonstrate that the model is consistent with proper adjustment can be used in future research.

  3. Antiallodynic effect through spinal endothelin-B receptor antagonism in rat models of complex regional pain syndrome.

    Science.gov (United States)

    Kim, Yeo Ok; Kim, In Ji; Yoon, Myung Ha

    2015-01-01

    Complex regional pain syndrome (CRPS) is a very complicated chronic pain disorder that has been classified into two types (I and II). Endothelin (ET) receptors are involved in pain conditions at the spinal level. We investigated the role of spinal ET receptors in CRPS. Chronic post-ischemia pain (CPIP) was induced in male Sprague-Dawley rats as a model for CRPS-I by placing a tourniquet (O-ring) at the ankle joint for 3h, and removing it to allow reperfusion. Ligation of L5 and L6 spinal nerves to induce neuropathic pain was performed as a model for CRPS-II. After O-ring application and spinal nerve ligation, the paw withdrawal threshold was significantly decreased at injured sites. Intrathecal administration of the selective ET-B receptor antagonist BQ 788 dose-dependently increased the withdrawal threshold in both CRPS-I and CRPS-II. In contrast, ET-A receptor antagonist BQ 123 did not affect the withdrawal threshold in either CRPS type. The ET-1 levels of plasma and spinal cord increased in both CRPS types. Intrathecal BQ 788 decreased the spinal ET-1 level. These results suggest that ET-1 is involved in the development of mechanical allodynia in CRPS. Furthermore, the ET-B receptor appears to be involved in spinal cord-related CRPS. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Endothelin-1 and -3 plasma concentrations in patients with cirrhosis: role of splanchnic and renal passage and liver function

    DEFF Research Database (Denmark)

    Gerbes, A L; Møller, S; Gülberg, V

    1995-01-01

    of splanchnic and renal passage and of liver function on plasma concentrations of endothelin-1 (ET-1) and endothelin-3 (ET-3) in patients with cirrhosis compared with controls. Eighteen patients with cirrhosis and 8 normotensive controls of similar age were investigated. Arterial and venous plasma samples were......Increased as well as decreased plasma concentrations of the endothelins, endogenous vasoactive peptides, have been reported in cirrhosis. This might be caused by alterations of hepatic or renal clearance or release. Therefore, the aim of the current study was to investigate the influence...... obtained simultaneously, and ET-1 and ET-3 concentrations were determined in extracted plasma by two separate radioimmunoassays. Arterial as well as hepatic and renal venous concentrations of ET-1 in cirrhosis (17.8 +/- 0.8 pg/mL, 19.1 +/- 0.9 pg/mL, and 16.8 +/- 0.8 pg/mL) were significantly (P

  5. Preparing students for higher education and careers in agriculture and related fields: An ethnography of an urban charter school

    Science.gov (United States)

    Henry, Kesha Atasha

    This study explored the preparation of students for higher education and careers in agriculturally-related fields at an urban charter high school. The data were collected through interviews, observations, and field notes. The data were analyzed by qualitative methodology with phenomenology as the theoretical framework. Findings indicated that administrators thought it was important to incorporate agricultural science courses into urban school curricula. They stated that agricultural science courses gave urban students a different way of looking at science and helped to enhance the science and technology focus of the school. Further, agricultural science courses helped to break urban students' stereotypes about agriculture and helped to bring in more state funding for educational programs. However they thought that it was more challenging to teach agricultural science in urban versus rural schools and they focused more on Science, Technology, Engineering, and Mathematics (STEM) related careers. The students had mixed views about higher education and careers in agriculture. This was based on their limited knowledge and stereotypes about agricultural majors and career options. The students highlighted several key reasons why they chose to enroll in agricultural science courses. This included the benefits of dual science credits and the ability to earn an associate degree upon successful completion of their program. Students also loved science and appreciated the science intensive nature of the agricultural courses. Additionally, they thought that the agricultural science courses were better than the other optional courses. The results also showed that electronic media such as radio and TV had a negative impact on students' perceptions about higher education and careers in agriculturally-related fields. Conclusions and recommendations are presented.

  6. Therapeutic hypothermia activates the endothelin and nitric oxide systems after cardiac arrest in a pig model of cardiopulmonary resuscitation.

    Directory of Open Access Journals (Sweden)

    Frank Zoerner

    Full Text Available Post-cardiac arrest myocardial dysfunction is a major cause of mortality in patients receiving successful cardiopulmonary resuscitation (CPR. Mild therapeutic hypothermia (MTH is the recommended treatment after resuscitation from cardiac arrest (CA and is known to exert neuroprotective effects and improve short-term survival. Yet its cytoprotective mechanisms are not fully understood. In this study, our aim was to determine the possible effect of MTH on vasoactive mediators belonging to the endothelin/nitric oxide axis in our porcine model of CA and CPR. Pigs underwent either untreated CA or CA with subsequent CPR. After state-of-the-art resuscitation, the animals were either left untreated, cooled between 32-34 °C after ROSC or treated with a bolus injection of S-PBN (sodium 4-[(tert-butylimino methyl]benzene-3-sulfonate N-oxide until 180 min after ROSC, respectively. The expression of endothelin 1 (ET-1, endothelin converting enzyme 1 (ECE-1, and endothelin A and B receptors (ETAR and ETBR transcripts were measured using quantitative real-time PCR while protein levels for the ETAR, ETBR and nitric oxide synthases (NOS were assessed using immunohistochemistry and Western Blot. Our results indicated that the endothelin system was not upregulated at 30, 60 and 180 min after ROSC in untreated postcardiac arrest syndrome. Post-resuscitative 3 hour-long treatments either with MTH or S-PBN stimulated ET-1, ECE-1, ETAR and ETBR as well as neuronal NOS and endothelial NOS in left ventricular cardiomyocytes. Our data suggests that the endothelin and nitric oxide pathways are activated by MTH in the heart.

  7. International mobility placements enable students and staff in Higher Education to enhance transversal and employability-related skills.

    Science.gov (United States)

    Standley, Henrietta J

    2015-10-01

    Internationalization has commanded an ever-more prominent position in higher education over recent years, and is now firmly entrenched. While academia has long been outward looking-international research collaborations, conferences and student exchanges are well-established practices-it is relatively recently that internationalization has become a goal in its own right, rather than a consequence of normal academic activity. There are multiple interdependent drivers behind this: a focus on graduate employability and development of broad competencies and transferable skills in addition to subject-specific training, 'international awareness' being confirmed as a graduate attribute that is highly valued by employers, the availability of detailed information enabling prospective students to choose between Higher Education Institutions on the basis of their international opportunities and graduate employment rates, increasing competition between Institutions to attract the best students and to ascend national and international league tables, and (both driving and reflecting these trends) national policy frameworks. This minireview focuses on two aspects of internationalization of direct relevance to microbiology students and academic staff in a typical Higher Education Institution: student research placements overseas, and the impact of international mobility on teaching practice and the student experience. Practical strategies for developing intercultural awareness and enhancing employability are highlighted. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma.

    Directory of Open Access Journals (Sweden)

    Alena Z Minton

    Full Text Available Glaucoma is an optic neuropathy, commonly associated with elevated intraocular pressure (IOP characterized by optic nerve degeneration, cupping of the optic disc, and loss of retinal ganglion cells which could lead to loss of vision. Endothelin-1 (ET-1 is a 21-amino acid vasoactive peptide that plays a key role in the pathogenesis of glaucoma; however, the receptors mediating these effects have not been defined. In the current study, endothelin B (ET(B receptor expression was assessed in vivo, in the Morrison's ocular hypertension model of glaucoma in rats. Elevation of IOP in Brown Norway rats produced increased expression of ET(B receptors in the retina, mainly in retinal ganglion cells (RGCs, nerve fiber layer (NFL, and also in the inner plexiform layer (IPL and inner nuclear layer (INL. To determine the role of ET(B receptors in neurodegeneration, Wistar-Kyoto wild type (WT and ET(B receptor-deficient (KO rats were subjected to retrograde labeling with Fluoro-Gold (FG, following which IOP was elevated in one eye while the contralateral eye served as control. IOP elevation for 4 weeks in WT rats caused an appreciable loss of RGCs, which was significantly attenuated in KO rats. In addition, degenerative changes in the optic nerve were greatly reduced in KO rats compared to those in WT rats. Taken together, elevated intraocular pressure mediated increase in ET(B receptor expression and its activation may contribute to a decrease in RGC survival as seen in glaucoma. These findings raise the possibility of using endothelin receptor antagonists as neuroprotective agents for the treatment of glaucoma.

  9. Remote indigenous peritoneal dialysis patients have higher risk of peritonitis, technique failure, all-cause and peritonitis-related mortality.

    Science.gov (United States)

    Lim, Wai H; Boudville, Neil; McDonald, Stephen P; Gorham, Gillian; Johnson, David W; Jose, Matthew

    2011-10-01

    The number of indigenous patients with end-stage kidney disease (ESKD) is increasing in Australia, reflecting a similar trend in other countries. Because many indigenous patients live in remote areas, peritoneal dialysis (PD) is often preferred. Compared to non-indigenous PD patients, indigenous patients have increased complication rates but the effect of residential locations on outcomes remains unclear. The aim of this study is to examine the association between race and PD outcomes stratified by location. Using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, all adult ESKD patients commencing PD in Australia between 1995 and 2008 were included. Patients were stratified as non-indigenous or indigenous race and were grouped according to their residential location, the latter stratified into metropolitan, regional and remote areas. Outcomes evaluated included peritonitis, technique failure, peritonitis-related and all-cause mortality. Regional and/or remote PD patients generally have a greater risk peritonitis-related complications and/or mortality compared to metropolitan patients. However, remote indigenous PD patients had the greatest risk of all PD-related complications, including all-cause and peritonitis-related mortality. This registry analysis demonstrates that non-metropolitan PD patients, especially remote indigenous patients, have higher complication rates, suggesting that environmental factors are important in determining PD outcomes.

  10. Association of Elevated Plasma Endothelin-1 Levels With Pulmonary Hypertension, Mortality, and Heart Failure in African American Individuals: The Jackson Heart Study.

    Science.gov (United States)

    Jankowich, Matthew D; Wu, Wen-Chih; Choudhary, Gaurav

    2016-07-01

    Despite pathophysiological links between endothelin-1 and pulmonary vascular remodeling, to our knowledge, the association between plasma endothelin-1 levels and pulmonary hypertension has not been studied in the general population. Also, whether endothelin-1 can predict future heart failure and mortality, outcomes that are associated with pulmonary hypertension, in a population cohort is unclear. To determine whether elevated plasma endothelin-1 levels are associated with pulmonary hypertension, mortality, and heart failure. Data from the Jackson Heart Study, a longitudinal, prospective observational cohort study of heart disease in African American individuals from Jackson, Mississippi, were analyzed. The community population sample was limited to participants with detectable tricuspid regurgitation on echocardiography. The study participants included self-identified African American individuals with plasma endothelin-1 levels and tricuspid regurgitation on echocardiogram (n = 3223) at the time of first examination (2000-2004). The analysis of the data began on April 14, 2014, and was completed on February 23, 2016. Log-transformed plasma endothelin-1 level. Cross-sectional analysis: presence of pulmonary hypertension (defined as an elevated pulmonary artery systolic pressure >40 mm Hg on echocardiogram). Longitudinal outcomes were all-cause mortality (median follow-up, 7.75 years) and heart failure admissions (median follow-up, 5.32 years). Of the 3223 participants enrolled in the study, 1051 were men (32.6%). Mean (SD) endothelin-1 levels were 1.36 (0.64) pg/mL; 217 of 3223 cohort members (6.7%) had pulmonary hypertension. After adjusting for potential confounders, log-transformed endothelin-1 levels were associated with increased odds of pulmonary hypertension (adjusted odds ratio per log increment in endothelin-1, 1.66; 95% CI, 1.16-2.37). Log-transformed endothelin-1 levels were associated with mortality (adjusted hazard ratio per log increment in

  11. Effect of hemodialysis on pulmonary function tests and plasma endothelin levels

    OpenAIRE

    Javid Safa; Hamid Noshad; Khalil Ansarin; Alireza Nikzad; Parviz Saleh; Abdolmohammad Ranjbar

    2014-01-01

    End-stage renal disease (ESRD) is a complex illness that involves different organs including the lungs. We studied the pulmonary function tests, arterial blood gases (ABG) and plasma endothelin-1 (ET-1) levels to check whether there is any change in their levels after hemodialysis (HD) in patients with ESRD. In this cross-sectional study (from July 2009 to April 2010), 20 patients with ESRD were evaluated. ABG, spirometric parameters and plasma ET-1 were measured before and after HD in these ...

  12. Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Edvinsson Lars

    2009-07-01

    Full Text Available Abstract Background Endothelin-1 (ET-1 is a potent vasoactive peptide, which induces vasoconstriction and proliferation in vascular smooth muscle cells (VSMCs through activation of endothelin type A (ETA and type B (ETB receptors. The extracellular signal-regulated kinase 1 and 2 (ERK1/2 mitogen-activated protein kinases (MAPK are involved in ET-1-induced VSMC contraction and proliferation. This study was designed to investigate the ETA and ETB receptor intracellular signaling in human VSMCs and used phosphorylation (activation of ERK1/2 as a functional signal molecule for endothelin receptor activity. Results Subconfluent human VSMCs were stimulated by ET-1 at different concentrations (1 nM-1 μM. The activation of ERK1/2 was examined by immunofluorescence, Western blot and phosphoELISA using specific antibody against phosphorylated ERK1/2 protein. ET-1 induced a concentration- and time- dependent activation of ERK1/2 with a maximal effect at 10 min. It declined to baseline level at 30 min. The ET-1-induced activation of ERK1/2 was completely abolished by MEK1/2 inhibitors U0126 and SL327, and partially inhibited by the MEK1 inhibitor PD98059. A dual endothelin receptor antagonist bosentan or the ETA antagonist BQ123 blocked the ET-1 effect, while the ETB antagonist BQ788 had no significant effect. However, a selective ETB receptor agonist, Sarafotoxin 6c (S6c caused a time-dependent ERK1/2 activation with a maximal effect by less than 20% of the ET-1-induced activation of ERK1/2. Increase in bosentan concentration up to 10 μM further inhibited ET-1-induced activation of ERK1/2 and had a stronger inhibitory effect than BQ123 or the combined use of BQ123 and BQ788. To further explore ET-1 intracellular signaling, PKC inhibitors (staurosporin and GF109203X, PKC-delta inhibitor (rottlerin, PKA inhibitor (H-89, and phosphatidylinositol 3-kinase (PI3K inhibitor (wortmannin were applied. The inhibitors showed significant inhibitory effects on ET-1

  13. Low Soluble Fms-Like Tyrosine Kinase-1, Endoglin, and Endothelin-1 Levels in Women With Confirmed or Suspected Preeclampsia Using Proton Pump Inhibitors.

    Science.gov (United States)

    Saleh, Langeza; Samantar, Raaho; Garrelds, Ingrid M; van den Meiracker, Anton H; Visser, Willy; Danser, A H Jan

    2017-09-01

    Patients with preeclampsia display elevated placenta-derived sFlt-1 (soluble Fms-like tyrosine kinase-1) and endoglin levels and decreased placental growth factor levels. Proton pump inhibitors (PPIs) decrease trophoblast sFlt-1 and endoglin secretion in vitro. PPIs are used during pregnancy to combat reflux disease. Here, we investigated whether PPIs affect sFlt-1 in women with confirmed/suspected preeclampsia, making use of a prospective cohort study involving 430 women. Of these women, 40 took PPIs (6 esomeprazole, 32 omeprazole, and 2 pantoprazole) for 8 to 45 (median 29) days before sFlt-1 measurement. Measurements were only made once, at study entry between weeks 20 and 41 (median 33 weeks). PPI use was associated with lower sFlt-1 levels, with no change in placental growth factor levels, both when compared with all non-PPI users and with 80 gestational age-matched controls selected from the non-PPI users. No sFlt-1/placental growth factor alterations were observed in women using ferrous fumarate or macrogol while, as expected, women using antihypertensive medication displayed higher sFlt-1 levels and lower placental growth factor levels. The PPI use-associated decrease in sFlt-1 was independent of the application of antihypertensive drugs and also occurred when restricting our analysis to patients with hypertensive disease of pregnancy at study entry. PPI users displayed more cases with preexisting proteinuria, less gestational hypertension, and a lower number of neonatal sepsis cases. Finally, their plasma endoglin and endothelin-1 levels were lower while sFlt-1 levels correlated positively with both. In conclusion, PPI use associates with low sFlt-1, endoglin, and endothelin-1 levels, warranting prospective trials to investigate the therapeutic potential of PPIs in preeclampsia. © 2017 American Heart Association, Inc.

  14. Treatment of experimental human breast cancer and lung cancer brain metastases in mice by macitentan, a dual antagonist of endothelin receptors, combined with paclitaxel.

    Science.gov (United States)

    Lee, Ho Jeong; Hanibuchi, Masaki; Kim, Sun-Jin; Yu, Hyunkyung; Kim, Mark Seungwook; He, Junqin; Langley, Robert R; Lehembre, François; Regenass, Urs; Fidler, Isaiah J

    2016-04-01

    We recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lung cancer brain metastases. The effect of macitentan on astrocyte- and brain endothelial cell-mediated chemoprotective properties was measured in cytotoxic assays. We compared survival of mice bearing established MDA-MB-231 breast cancer or PC-14 non-small cell lung cancer (NSCLC) brain metastases that were treated with vehicle, macitentan, paclitaxel, or macitentan plus paclitaxel. Cell division, apoptosis, tumor vasculature, and expression of survival-related proteins were assessed by immunofluorescent microscopy. Cancer cells and tumor-associated endothelial cells expressed activated forms of AKT and MAPK in vehicle- and paclitaxel-treated groups in both metastasis models, but these proteins were downregulated in metastases of mice that received macitentan. The survival-related proteins Bcl2L1, Gsta5, and Twist1 that localized to cancer cells and tumor-associated endothelial cells in vehicle- and paclitaxel-treated tumors were suppressed by macitentan. Macitentan or paclitaxel alone had no effect on survival. However, when macitentan was combined with paclitaxel, we noted a significant reduction in cancer cell division and marked apoptosis of both cancer cells and tumor-associated endothelial cells. Moreover, macitentan plus paclitaxel therapy significantly increased overall survival by producing complete responses in 35 of 35 mice harboring brain metastases. Dual antagonism of ETAR and ETBR signaling sensitizes experimental brain metastases to paclitaxel and may represent a new therapeutic option for patients with brain metastases. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved

  15. Big endothelin-1 and nitric oxide in hypertensive elderly patients with and without obstructive sleep apnea-hypopnea syndrome.

    Science.gov (United States)

    Anunciato, Iara Felicio; Lobo, Rômulo Rebouças; Coelho, Eduardo Barbosa; Verri, Waldiceu Aparecido; Eckeli, Alan Luiz; Evora, Paulo Roberto Barbosa; Nobre, Fernando; Moriguti, Júlio César; Ferriolli, Eduardo; Lima, Nereida Kilza da Costa

    2013-10-01

    The role of oxidative stress in hypertensive elderly patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) is unknown. The purpose was to evaluate the levels of big endothelin-1 (Big ET-1) and nitric oxide (NO) in elderly hypertensive patients with and without moderate to severe OSAHS. Volunteers were hospitalized for 24 h. We obtained the following data: body mass index (BMI); 24-ambulatory blood pressure monitoring; and current medication. Arterial blood was collected at 7 pm and 7 am for determining plasma NO and Big ET-1 levels. Pulse oximetry was performed during sleep. Pearson's or Spearman's correlation and univariate analysis of variance were used for statistical analysis. We studied 25 subjects with OSAHS (group 1) and 12 without OSAHS (group 2) aged 67.0 ± 6.5 years and 67.8 ± 6.8 years, respectively. No significant differences were observed between the groups in BMI; number of hours of sleep; 24-h systolic and diastolic BPs; awake BP, sleep BP and medications to control BP between groups. No differences were detected in plasma Big ET-1 and NO levels at 19:00 h, but plasma Big ET-1 levels at 7:00 h were higher in group 1 (p =0.03). In group 1, a negative correlation was also observed between the mean arterial oxyhemoglobin saturation level, 24-h systolic BP (p = 0.03, r = -0.44), and Big ET-1 (p = 0.04, r = -0.41). On comparing elderly hypertensive patients with and without OSAHS having similar BP and BMI, we observed higher Big ET-1 levels After sleep in the OSAHS group. NO levels did not differ between the hypertensive patients with or without OSAHS.

  16. Modulation of rhodopsin gene expression and signaling mechanisms evoked by endothelins in goldfish and murine pigment cell lines

    Directory of Open Access Journals (Sweden)

    G.J.D. Lopes

    2010-09-01

    Full Text Available Endothelins (ETs and sarafotoxins (SRTXs belong to a family of vasoconstrictor peptides, which regulate pigment migration and/or production in vertebrate pigment cells. The teleost Carassius auratus erythrophoroma cell line, GEM-81, and Mus musculus B16 melanocytes express rhodopsin, as well as the ET receptors, ETB and ETA, respectively. Both cell lines are photoresponsive, and respond to light with a decreased proliferation rate. For B16, the doubling time of cells kept in 14-h light (14L:10-h darkness (10D was higher compared to 10L:14D, or to DD. The doubling time of cells kept in 10L:14D was also higher compared to DD. Using real-time PCR, we demonstrated that SRTX S6c (12-h treatment, 100 pM and 1 nM; 24-h treatment, 1 nM and ET-1 (12-h treatment, 10 and 100 pM; 24- and 48-h treatments, 100 pM increased rhodopsin mRNA levels in GEM-81 and B16 cells, respectively. This modulation involves protein kinase C (PKC and the mitogen-activated protein kinase cascade in GEM-81 cells, and phospholipase C, Ca2+, calmodulin, a Ca2+/calmodulin-dependent kinase, and PKC in B16 cells. Cells were kept under constant darkness throughout the gene expression experiments. These results show that rhodopsin mRNA levels can be modulated by SRTXs/ETs in vertebrate pigment cells. It is possible that SRTX S6c binding to the ETB receptors in GEM-81 cells, and ET-1 binding to ETA receptors in B16 melanocytes, although activating diverse intracellular signaling mechanisms, mobilize transcription factors such as c-Fos, c-Jun, c-Myc, and neural retina leucine zipper protein. These activated transcription factors may be involved in the positive regulation of rhodopsin mRNA levels in these cell lines.

  17. Higher organ donation consent rates by relatives of potential uncontrolled donors versus potential controlled donors after death.

    Science.gov (United States)

    Wind, Jentina; van Mook, Walther N K A; Willems, Monique E C; van Heurn, L W Ernest

    2012-11-01

    Refusal to consent to organ donation is an important cause of the persisting gap between the number of potential organ donors and effectuated donors. In the Netherlands, organ donors include both uncontrolled donors: donors who die unexpectedly after cardiac death (DCD), after failed resuscitation and donors in whom death can be expected and donors after brain death, and controlled DCD donors: those who die after the withdrawal of treatment. Different donor type implies a different setting in which relatives are requested to consent to organ donation. It is unknown whether the setting influences the eventual decision for donation or not. Therefore, we compared the consent rate in potential donors who died unexpectedly (UD group) and in whom death was expected. A total of 523 potential organ donors between 2003 and 2011 in the 715-bed Maastricht University Medical Centre, the Netherlands were included. Both the patients' registration in the national donor register (DR) and the relatives' refusal rate in the two groups were retrospectively assessed using data from the donation application database. There were 109 unexpected and 414 expected potential donors The potential donors in the UD group were younger (mean age 52 versus 55 years, P = 0.032) and more often male (68 versus 52%, P = 0.003). There were no significant differences in registration in the DR between the groups. The relatives' consent rate in non-registered potential donors, or those who mandated the relatives for that decision, was higher in the UD group (53 versus 29%, P organ donation. The relatives of potential donors who died unexpectedly consented more often to donation than those in whom death was expected.

  18. Dietary intake of fat and fibre according to reference values relates to higher gut microbiota richness in overweight pregnant women.

    Science.gov (United States)

    Röytiö, Henna; Mokkala, Kati; Vahlberg, Tero; Laitinen, Kirsi

    2017-09-01

    The diet-microbiota-metabolism relationships during pregnancy are mostly unknown. We explored the effect of the habitual diet and adherence to the dietary reference values on gut microbiota composition and diversity. Further, the association of gut microbiota with serum lipidomics and low-grade inflammation was evaluated. Overweight and obese women (BMI 30·7 (sd 4·4) kg/m2, n 100) were studied at early pregnancy (≤17 weeks). Intakes of nutrients were calculated from 3-d food diaries. Faecal microbiota composition was analysed using 16S rRNA gene sequencing. Fasting serum lipidomic profiles were determined by NMR. High-sensitivity C-reactive protein, glycoprotein acetylation (GlycA) and lipopolysaccharide activity were used as markers for low-grade inflammation. The recommended dietary intake of fibre and fat was related to higher gut microbiota richness and lower abundance of Bacteroidaceae. Correlations were observed between gut microbiota richness and GlycA and between a few microbiota genera and serum lipoprotein particles. As a conclusion, adherence to the dietary reference intake of fat and fibre was associated with beneficial gut microbiota composition, which again contributed to lipidomic profile. Higher gut microbiota richness and nutrient intakes were linked to a lower level of low-grade inflammation marker GlycA. This finding offers novel insights and opportunities for dietary modification during pregnancy with potential of improving the health of the mother and the child.

  19. Information and Communication Technology Use Is Related to Higher Well-Being Among the Oldest-Old.

    Science.gov (United States)

    Sims, Tamara; Reed, Andrew E; Carr, Dawn C

    2017-09-01

    Older adults often prioritize socially meaningful goals over informational goals. Thus, we predicted that using information and communication technology (ICT) in service of socially meaningful versus informational goals relates to higher well-being among the oldest-old. We surveyed 445 adults aged 80+ (mean = 84, range = 80-93; 64% female; 26% non-White) online or via telephone. Participants reported motivations for ICT use (connect with others, learn new information) and rated their psychological and physical well-being (i.e., life satisfaction, loneliness, goal attainment, subjective health, functional limitations). We conducted regression and mediation analyses to test our hypothesis. Participants used ICT more to connect with friends/family (M = 3.66, SD = 1.28) than to learn information (M = 2.61, SD = 1.44), p < .001. Overall, ICT use predicted higher well-being across outcomes, ps ≤ .008. Motivations for use differentially mediated these effects: Social motivations mediated the relationships between ICT use and psychological well-being, whereas informational motivations mediated the relationships between ICT use and physical well-being. Older adults aged 80+ use ICT less than other generations, but may have much to gain. Using social versus informational technologies may enhance multiple aspects of well-being in different ways during very late life. Highlighting such benefits may increase ICT adoption among the oldest-old.

  20. Relating renormalizability of D-dimensional higher-order electromagnetic and gravitational models to the classical potential at the origin

    Science.gov (United States)

    Accioly, Antonio; Correia, Gilson; de Brito, Gustavo P.; de Almeida, José; Herdy, Wallace

    2017-03-01

    Simple prescriptions for computing the D-dimensional classical potential related to electromagnetic and gravitational models, based on the functional generator, are built out. These recipes are employed afterward as a support for probing the premise that renormalizable higher-order systems have a finite classical potential at the origin. It is also shown that the opposite of the conjecture above is not true. In other words, if a higher-order model is renormalizable, it is necessarily endowed with a finite classical potential at the origin, but the reverse of this statement is untrue. The systems used to check the conjecture were D-dimensional fourth-order Lee-Wick electrodynamics, and the D-dimensional fourth- and sixth-order gravity models. A special attention is devoted to New Massive Gravity (NMG) since it was the analysis of this model that inspired our surmise. In particular, we made use of our premise to resolve trivially the issue of the renormalizability of NMG, which was initially considered to be renormalizable, but it was shown some years later to be non-renormalizable. We remark that our analysis is restricted to local models in which the propagator has simple and real poles.

  1. Overexpression of endothelin B receptor in glioblastoma: a prognostic marker and therapeutic target?

    KAUST Repository

    Vasaikar, Suhas

    2018-02-06

    BackgroundGlioblastoma (GBM) is the most common malignant brain tumor with median survival of 12-15 months. Owing to uncertainty in clinical outcome, additional prognostic marker(s) apart from existing markers are needed. Since overexpression of endothelin B receptor (ETBR) has been demonstrated in gliomas, we aimed to test whether ETBR is a useful prognostic marker in GBM and examine if the clinically available endothelin receptor antagonists (ERA) could be useful in the disease treatment.MethodsData from The Cancer Genome Atlas and the Gene Expression Omnibus database were analyzed to assess ETBR expression. For survival analysis, glioblastoma samples from 25 Swedish patients were immunostained for ETBR, and the findings were correlated with clinical history. The druggability of ETBR was assessed by protein-protein interaction network analysis. ERAs were analyzed for toxicity in in vitro assays with GBM and breast cancer cells.ResultsBy bioinformatics analysis, ETBR was found to be upregulated in glioblastoma patients, and its expression levels were correlated with reduced survival. ETBR interacts with key proteins involved in cancer pathogenesis, suggesting it as a druggable target. In vitro viability assays showed that ERAs may hold promise to treat glioblastoma and breast cancer.ConclusionsETBR is overexpressed in glioblastoma and other cancers and may be a prognostic marker in glioblastoma. ERAs may be useful for treating cancer patients.

  2. Low levels of plasma endothelin-1 in patients with retinitis pigmentosa

    Directory of Open Access Journals (Sweden)

    Hiroshi Ohguro

    2010-06-01

    Full Text Available Hiroshi Ohguro1, Yukihiko Mashima2, Mitsuru Nakazawa31Department of Ophthalmology, Sapporo Medical University School of Medicine, 2Department of Ophthalmology, Keio University School of Medicine, 3Department of Ophthalmology, Hirosaki University School of Medicine, JapanPurpose: The aim of this study was to elucidate the role of endothelin-1 (ET-1 in the pathophysiology of retinitis pigmentosa (RP.Methods: Plasma ET-1 levels and ophthalmic features in 50 RP patients were compared with those in 20 healthy-eye control subjects. Plasma ET-1 concentrations were determined using a commercially available enzyme-linked immunosorbent assay kit.Results: Mean plasma ET-1 levels of RP patients (1.88 ± 0.56 pg/mL were significantly lower than those of control subjects (2.30 ± 0.30 pg/mL, Mann-Whitney’s U test; P < 0.01. However, ET-1 concentrations varied markedly in each patient. Among RP patients, a significant correlation of ET-1 concentrations was not observed in terms of its hereditary forms or other clinical factors.Conclusion: ET-1 may be important in the pathogenesis of RP, and measurement of its plasma concentrations may also contribute to additional insights into the retinal hemodynamics of RP.Keywords: endothelin-1, retinitis pigmentosa, retinal hemodynamics

  3. Disruption of the endothelin A receptor in the nephron causes mild fluid volume expansion

    Directory of Open Access Journals (Sweden)

    Stuart Deborah

    2012-12-01

    Full Text Available Abstract Background Endothelin, via endothelin A receptors (ETA, exerts multiple pathologic effects that contribute to disease pathogenesis throughout the body. ETA antagonists ameliorate many experimental diseases and have been extensively utilized in clinical trials. The utility of ETA blockers has been greatly limited, however, by fluid retention, sometimes leading to heart failure or death. To begin to examine this issue, the effect of genetic disruption of ETA in the nephron on blood pressure and salt handling was determined. Methods Mice were generated with doxycycline-inducible nephron-specific ETA deletion using Pax8-rtTA and LC-1 transgenes on the background of homozygous loxP-flanked ETA alleles. Arterial pressure, Na metabolism and measures of body fluid volume status (hematocrit and impedance plethysmography were assessed. Results Absence of nephron ETA did not alter arterial pressure whether mice were ingesting a normal or high Na diet. Nephron ETA disruption did not detectably affect 24 hr Na excretion or urine volume regardless of Na intake. However, mice with nephron ETA knockout that were fed a high Na diet had mild fluid retention as evidenced by an increase in body weight and a fall in hematocrit. Conclusions Genetic deletion of nephron ETA causes very modest fluid retention that does not alter arterial pressure. Nephron ETA, under normal conditions, likely do not play a major role in regulation of Na excretion or systemic hemodynamics.

  4. Endothelin receptor antagonist prevents parathyroid cell proliferation of low calcium diet-induced hyperparathyroidism in rats.

    Science.gov (United States)

    Kanesaka, Y; Tokunaga, H; Iwashita, K; Fujimura, S; Naomi, S; Tomita, K

    2001-01-01

    Secondary hyperparathyroidism, one of the most frequently encountered disorders of the calcium homeostasis, is characterized by an increase in parathyroid epithelial (PT) cell number, which is crucial from a functional viewpoint. However, it is still unknown what factors are involved in PT cell proliferation. Endothelin-1 (ET-1), a vasoconstrictive peptide, has been shown to act as a mitogen in a variety of cell types. Rat PT cells are reported to synthesize ET-1 and possess its receptors. To test the hypothesis that ET-1 plays a role in PT cell proliferation, we used rat test subjects fed a low calcium diet for 8 weeks (low Ca rats). The number of the proliferating PT cells, measured by proliferating cell nuclear antigen immunostaining, was significantly increased, with striking immunoreactivity of ET-1 in the low Ca rats. An endothelin receptor antagonist, bosentan (100 mg/kg.day), prevented any increase in the proliferation of PT cells in the low Ca rats (14.3 +/- 2.7/1000 PT cells with no bosentan; 2.1 +/- 1.3 with bosentan; P hyperparathyroidism.

  5. Role of endothelin-1 and cyclic nucleotides in ischemia/reperfusion-mediated microvascular leak.

    Science.gov (United States)

    Ramirez, René; Chong, Terry; Curran, Brian; Victorino, Gregory P

    2006-03-01

    A consequence of ischemia/reperfusion (IR) is endothelial barrier dysfunction and intravascular volume loss. The purposes of our study are to explore the impact of: 1) cyclic guanosine monophosphate (cGMP) synthesis inhibition, 2) cyclic adenosine monophosphate (cAMP) synthesis inhibition, 3) treatment with endothelin-1, and 4) endothelin-1 (ET-1)-mediated cAMP changes on IR-induced fluid leak. We hypothesize that IR-mediated microvascular fluid leak results from increased cGMP activity and ET-1 decreases IR-induced fluid leak via cAMP. A micro-cannulation technique was used to determine fluid leak or hydraulic permeability (Lp) in rat mesenteric venules. Lp was measured during IR and after treatment with 1) cGMP synthesis inhibitor (LY83583,10 micromol/L) 2) cAMP synthesis inhibitor (2',5'dideoxyadenosine,10 micromol/L), 3) ET-1 (80 pM), and 4) cAMP synthesis inhibitor plus ET-1 (n=6 in each group; Lp represented as mean+/-standard error of the mean; units 10-cm/sec/cmH2O). IR resulted in an increase in Lp (Lp=7.07+/-0.20) sevenfold above baseline (1.05+/-0.31) (pcentral role as a mediator of IR-induced postcapillary venular leak. ET-1 mildly decreased leak. Furthermore, ET-1 may not exert its effects on microvascular fluid leak during IR via cAMP.

  6. Effects of marathon running on cardiac markers and endothelin-1 in EIH athletes.

    Science.gov (United States)

    Kim, Y J; Shin, Y O; Lee, Y H; Jee, H M; Shin, K A; Goh, C W; Kim, C H; Min, Y K; Yang, H M; Lee, J B

    2013-09-01

    The aim of the present study was to determine the changes in cardiac makers and endothelin-1 (ET-1) in marathoners with exercise induced hypertension compared to normotensive controls before and after running a marathon. Among a total of 70 volunteers, 10 marathoners with systolic blood pressure (SBP) greater than 210 mmHg during a treadmill exercise stress test were selected as an exercise-induced hypertension group (EIH) and 10 marathoners with normal SBP were selected as a control group (CON). Blood was collected from all volunteers 2 h before and immediately after a marathon: creatinine kinase (CK), CK-MB, cardiac tropoin-I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), and endothelin-1(ET-1). Cardiac markers, CK, CK-MB, and CK-MB/CK ratio significantly increased in both EIH and CON; significance was not observed between the groups. Significant increases were not observed in high sensitive-C reactive protein (hs-CRP) after the race nor between the groups. Significant increases in cTnI and NT-proBNP were observed after the race in both groups. In addition, EIH showed greater increase than CON after the race. In conclusion, increased vascular tone in EIH during a marathon increased blood pressure and myocardial burden which in turn increased myocardial cell membrane permeability to further increase myocardial tension to the point of cTnI release. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells

    DEFF Research Database (Denmark)

    Chen, Qing-wen; Edvinsson, Lars; Xu, Cang-Bao

    2009-01-01

    the ETA and ETB receptor intracellular signaling in human VSMCs and used phosphorylation (activation) of ERK1/2 as a functional signal molecule for endothelin receptor activity. RESULTS: Subconfluent human VSMCs were stimulated by ET-1 at different concentrations (1 nM-1 microM). The activation of ERK1....../2 was examined by immunofluorescence, Western blot and phosphoELISA using specific antibody against phosphorylated ERK1/2 protein. ET-1 induced a concentration- and time- dependent activation of ERK1/2 with a maximal effect at 10 min. It declined to baseline level at 30 min. The ET-1-induced activation of ERK1....../2 was completely abolished by MEK1/2 inhibitors U0126 and SL327, and partially inhibited by the MEK1 inhibitor PD98059. A dual endothelin receptor antagonist bosentan or the ETA antagonist BQ123 blocked the ET-1 effect, while the ETB antagonist BQ788 had no significant effect. However, a selective ETB receptor...

  8. The Endothelin Type A Receptor as a Potential Therapeutic Target in Preeclampsia.

    Science.gov (United States)

    Bakrania, Bhavisha; Duncan, Jeremy; Warrington, Junie P; Granger, Joey P

    2017-02-28

    Preeclampsia (PE) is a disorder of pregnancy typically characterized by new onset hypertension after gestational week 20 and proteinuria. Although PE is one of the leading causes of maternal and perinatal morbidity and death worldwide, the mechanisms of the pathogenesis of the disease remain unclear and treatment options are limited. However, there is increasing evidence to suggest that endothelin-1 (ET-1) plays a critical role in the pathophysiology of PE. Multiple studies report that ET-1 is increased in PE and some studies report a positive correlation between ET-1 and the severity of symptoms. A number of experimental models of PE are also associated with elevated tissue levels of prepro ET-1 mRNA. Moreover, experimental models of PE (placental ischemia, sFlt-1 infusion, Tumor necrosis factor (TNF) -α infusion, and Angiotensin II type 1 receptor autoantibody (AT1-AA) infusion) have proven to be susceptible to Endothelin Type A (ET A ) receptor antagonism. While the results are promising, further work is needed to determine whether ET antagonists could provide an effective therapy for the management of preeclampsia.

  9. Factors influencing the intention to use social media for work-related purposes at a South African higher education institution

    Directory of Open Access Journals (Sweden)

    Liezel Cilliers

    2017-01-01

    Full Text Available Orientation: The rapid development of information communication technology (ICT has changed much of contemporary society. ICT’s influence extends to the working context with ramifications not only for employees but also for the entire organisation.Research purpose: The primary purpose of this research was to investigate the behavioural intention of a sample of employees at a traditional higher education institution to make use of social media within the workplace.Motivation for the study: Social media has become a common tool within society for communication and networking purposes. An understanding of the factors that influence behavioural intention to use social media within the workplace can assist the organisation to better manage social media usage within the workplace.Research design, approach and method: The research adopted the positivism paradigm with a quantitative research approach. The data were analysed making use of exploratory factor analysis and multiple regression analysis. A traditional higher education institution was chosen as the research site for the study, relying on a convenience sample (n = 134 and data gathered using the work-related social media scale and behavioural intention to use scale.Main findings: Although most employees make use of social media for problem-solving and communication purposes already in the workplace, organisations should allow their employees to help manage their reputation on social media.Practical and managerial implications: An understanding of the factors that influence behavioural intention to use social media within the workplace can serve as a useful precursor for both employee and organisational-specific interventions. This study has specific relevance to the use of ICT platforms, such as social media, in traditional higher education institutions in South Africa. The study’s results are therefore useful to both employees as end-users and managers as drivers of such interventions in

  10. CPU0213, a novel endothelin type A and type B receptor antagonist, protects against myocardial ischemia/reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Z.Y. Wang

    2011-11-01

    Full Text Available The efficacy of endothelin receptor antagonists in protecting against myocardial ischemia/reperfusion (I/R injury is controversial, and the mechanisms remain unclear. The aim of this study was to investigate the effects of CPU0123, a novel endothelin type A and type B receptor antagonist, on myocardial I/R injury and to explore the mechanisms involved. Male Sprague-Dawley rats weighing 200-250 g were randomized to three groups (6-7 per group: group 1, Sham; group 2, I/R + vehicle. Rats were subjected to in vivo myocardial I/R injury by ligation of the left anterior descending coronary artery and 0.5% sodium carboxymethyl cellulose (1 mL/kg was injected intraperitoneally immediately prior to coronary occlusion. Group 3, I/R + CPU0213. Rats were subjected to identical surgical procedures and CPU0213 (30 mg/kg was injected intraperitoneally immediately prior to coronary occlusion. Infarct size, cardiac function and biochemical changes were measured. CPU0213 pretreatment reduced infarct size as a percentage of the ischemic area by 44.5% (I/R + vehicle: 61.3 ± 3.2 vs I/R + CPU0213: 34.0 ± 5.5%, P < 0.05 and improved ejection fraction by 17.2% (I/R + vehicle: 58.4 ± 2.8 vs I/R + CPU0213: 68.5 ± 2.2%, P < 0.05 compared to vehicle-treated animals. This protection was associated with inhibition of myocardial inflammation and oxidative stress. Moreover, reduction in Akt (protein kinase B and endothelial nitric oxide synthase (eNOS phosphorylation induced by myocardial I/R injury was limited by CPU0213 (P < 0.05. These data suggest that CPU0123, a non-selective antagonist, has protective effects against myocardial I/R injury in rats, which may be related to the Akt/eNOS pathway.

  11. Disability rights in Higher Education Programs: The case of medical schools and other health-related disciplines.

    Science.gov (United States)

    Liasidou, Anastasia; Mavrou, Katerina

    2017-10-01

    Recognising and respecting the human rights of persons with disabilities constitutes an integral element of a democratic society. This caveat has been long articulated in health professionals' rhetoric on the importance of embedding a human rights discourse in the protection and promotion of individual and global health. Having signed and ratified the International Convention on the Rights of Persons with Disabilities (UNCRPD), state parties are expected to educate doctors and other health professionals to understand the human rights dimension of disability. This article is concerned with exploring the extent to which the programmes and curriculum outlines in medical schools and other health-related academic disciplines are informed by concerns about promoting disability rights education. Further, it discusses some future directions for monitoring the implementation of a disability rights discourse and suggests some ways in which a rights-based approach to disability can be incorporated in higher education programmes and curricula for health-related disciplines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria.

    Directory of Open Access Journals (Sweden)

    Brandi D Freeman

    2016-03-01

    Full Text Available Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria.

  13. Cardiac Metabolic Deregulation Induced by the Tyrosine Kinase Receptor Inhibitor Sunitinib is rescued by Endothelin Receptor Antagonism

    Science.gov (United States)

    Sourdon, Joevin; Lager, Franck; Viel, Thomas; Balvay, Daniel; Moorhouse, Rebecca; Bennana, Evangeline; Renault, Gilles; Tharaux, Pierre-Louis; Dhaun, Neeraj; Tavitian, Bertrand

    2017-01-01

    The growing field of cardio-oncology addresses the side effects of cancer treatment on the cardiovascular system. Here, we explored the cardiotoxicity of the antiangiogenic therapy, sunitinib, in the mouse heart from a diagnostic and therapeutic perspective. We showed that sunitinib induces an anaerobic switch of cellular metabolism within the myocardium which is associated with the development of myocardial fibrosis and reduced left ventricular ejection fraction as demonstrated by echocardiography. The capacity of positron emission tomography with [18F]fluorodeoxyglucose to detect the changes in cardiac metabolism caused by sunitinib was dependent on fasting status and duration of treatment. Pan proteomic analysis in the myocardium showed that sunitinib induced (i) an early metabolic switch with enhanced glycolysis and reduced oxidative phosphorylation, and (ii) a metabolic failure to use glucose as energy substrate, similar to the insulin resistance found in type 2 diabetes. Co-administration of the endothelin receptor antagonist, macitentan, to sunitinib-treated animals prevented both metabolic defects, restored glucose uptake and cardiac function, and prevented myocardial fibrosis. These results support the endothelin system in mediating the cardiotoxic effects of sunitinib and endothelin receptor antagonism as a potential therapeutic approach to prevent cardiotoxicity. Furthermore, metabolic and functional imaging can monitor the cardiotoxic effects and the benefits of endothelin antagonism in a theranostic approach. PMID:28824714

  14. Differences in endothelin receptor types in the vasculature of Bothrops jararaca (Viperidae) and Oxyrhopus guibei (Colubridae) snakes.

    Science.gov (United States)

    Mesquita, Lívia S M; Frias, Flávia T; Carmona, Eurídice; Borgheresi, Rosa A M B

    2008-07-01

    Endothelins (ETs) are vasoactive peptides evolutionary well conserved that exert their effects through two specific receptors (ET(A) and ET(B)) widely distributed in all vertebrates. In snakes, the presence and function of endothelins and their receptors are still scarcely described. We have recently demonstrated the presence of ET(A) and ET(B2) receptors in the snake Bothrops jararaca (Bj). In the present work we showed that distinctively from Bj, the vascular contraction induced by endothelin in Oxyrhopus guibei (Og) snake is mediated only by ET(A) receptors. Selective ET(B) agonists (SRTX-c and IRL(1620)) and antagonists (IRL(1038) and BQ(788)) were ineffective in Og preparations of isolated aorta. We also showed that ET-1 response on Og arterial blood pressure was monophasic hypertensive as opposed to biphasic (hypotension followed by hypertension) in Bj. Furthermore, we characterized the relaxing properties of endothelin receptor ET(B1) in pre-contracted aorta preparations. We showed that IRL(1620) induced relaxation of pre-contracted Bj aorta but was ineffective in relaxing Og preparations. IRL(1620) relaxing effect on Bj aorta was abolished by l-NAME, indicating involvement of NO release, and was reduced by selective ET(B) antagonists. Our findings suggest that Og snake has a more primitive spectrum of ET receptors (only ET(A) receptor) than Bj (presence of ET(A), ET(B1) and ET(B2) receptors).

  15. Increased mortality with elevated plasma endothelin-1 in acute heart failure : an ASCEND-HF biomarker substudy

    NARCIS (Netherlands)

    Perez, Antonio L.; Grodin, Justin L.; Wu, Yuping; Hernandez, Adrian F.; Butler, Javed; Metra, Marco; Felker, G. Michael; Voors, Adriaan A.; McMurray, John J.; Armstrong, Paul W.; Starling, Randall C.; O'Connor, Christopher M.; Tang, W. H. Wilson

    AimsEndothelin-1 (ET-1) is an endogenous vasoconstrictor implicated in pulmonary and systemic hypertension, as well as ventricular dysfunction, through effects on vascular smooth muscle, the kidneys, and cardiomyocytes. We aimed to determine the association between serial ET-1 levels and acute heart

  16. Effect of breed on plasma endothelin-1 concentration, plasma renin activity, and serum cortisol concentration in healthy dogs

    DEFF Research Database (Denmark)

    Höglund, K.; Lequarré, A.-S.; Ljungvall, I.

    2016-01-01

    BACKGROUND: There are breed differences in several blood variables in healthy dogs. OBJECTIVE: Investigate breed variation in plasma endothelin-1 (ET-1) concentration, plasma renin activity, and serum cortisol concentration. ANIMALS: Five-hundred and thirty-one healthy dogs of 9 breeds examined a...

  17. Sustained Ca2+ signaling and delayed internalization associated with endothelin receptor heterodimers linked through a PDZ finger.

    Science.gov (United States)

    Evans, Nathan J; Walker, Jeffery W

    2008-08-01

    G protein-coupled receptors (GPCRs), including endothelin receptor A (ETA) and B (ETB), may form dimers or higher-order oligomers that profoundly influence signaling. Here we examined a PDZ finger motif within the C-terminus of ETA and its role in heterodimerization with ETB, and in homodimerization with itself, when expressed in HEK293 cells. Receptor dimerization was monitored by (i) fluorescence resonance energy transfer (FRET) between cyan fluorescent protein (CFP) (FRET donor) and tetracysteine/FlAsH (FRET acceptor) fused to the C-termini of ET receptors, and (ii) coimmunoprecipitation of ET receptors after mild detergent solubilization. Mutations in a PDZ finger motif at threonine403/serine404 eliminated FRET and reduced coimmunoprecipitation of heterodimers and homodimers. Functional consequences were evaluated by measuring mobilization of intracellular Ca2+ and internalization of receptors in response to a 10 nmol/L ET-1 challenge. PDZ mutations converted a sustained Ca2+ signal mediated by ETA:ETB heterodimers into a transient response, similar to that observed for homodimers or monomers. Heterodimers containing PDZ mutations were seen to internalize in a similar time domain (approximately 5 min) to the transient Ca2+ elevation and with similar kinetics to internalization of ETA homodimers or monomers. Without the PDZ mutations, heterodimers did not internalize over 15 min, suggesting the intriguing possibility that sustained Ca2+ signaling was a consequence (at least in part) of delayed internalization. The results are consistent with structural models of ETA-receptor dimerization that place threonine403/serine404 of the PDZ finger motif at the interaction interface between heterodimers and homodimers. Sustained Ca2+ signaling and delayed endocytosis of ETA:ETB heterodimers argues strongly for a unique dimer interface that impacts transmembrane signaling and internalization.

  18. Evaluation of somatostatin, CXCR4 chemokine and endothelin A receptor expression in a large set of paragangliomas

    Science.gov (United States)

    Kaemmerer, Daniel; Sänger, Jörg; Arsenic, Ruza; D’Haese, Jan G.; Neumann, Jens; Schmitt-Graeff, Annette; Wirtz, Ralph Markus; Schulz, Stefan; Lupp, Amelie

    2017-01-01

    Paragangliomas are predominantly benign tumors, but in some cases invasive growth and also metastasis are observed. Given the limited number of nonsurgical treatment options, novel target structures for diagnostics and therapy of this tumor entity are urgently needed. In the present study, expression of all five somatostatin receptor (SST) subtypes, chemokine receptor CXCR4 and endothelin receptor type A (ETA) was assessed by means of immunohistochemistry in a total of 66 paraffin-embedded paraganglioma samples from 55 patients. The stainings were rated by means of the Immunoreactive Score and correlated to clinical data and to succinate dehydrogenase subunit B (SDHB) expression. SST2A was by far the most prominent receptor in the paragangliomas investigated. It was present in 89% of the tumors at a high intensity, followed by SST5, SST3, SST1 and SST4, which were detected in 47%, 35%, 35% and 13% of the samples, respectively. SDHB positive tumors exhibited significantly higher SST2A and SST3 expression as compared to SDHB negative cases. There was no correlation between SST and Ki-67 expression or grading of the tumors and no difference in SST expression between primary tumors and metastases. Cell surface expression of CXCR4 and ETA was detected only in few samples. On tumor capillaries, however, exceptionally strong staining for these two receptors was noticed in the vast majority of the tumors. In conclusion, paragangliomas are well suited for SST2A-based diagnostics and treatment modalities. An indirect targeting of these highly vascularized tumors via CXCR4 or ETA may also represent a promising future strategy. PMID:29163802

  19. Calcium dobesilate reduces endothelin-1 and high-sensitivity C-reactive protein serum levels in patients with diabetic retinopathy.

    Science.gov (United States)

    Javadzadeh, Alireza; Ghorbanihaghjo, Amir; Adl, Farzad Hami; Andalib, Dima; Khojasteh-Jafari, Hassan; Ghabili, Kamyar

    2013-01-01

    To determine the benefits of calcium dobesilate (CaD) administration on endothelial function and inflammatory status in patients with diabetic retinopathy through measurement of serum levels of endothelin-1 and high-sensitivity C-reactive protein (hsCRP). In a double-blind, randomized clinical trial, 90 patients with either severe nonproliferative or proliferative diabetic retinopathy and with blood glucose level of 120-200 mg/dl were randomly allocated to treatment with either CaD tablets (500 mg daily) or placebo for 3 months. Visual acuity, intraocular pressure, and macular status were performed before the study. The serum levels of endothelin-1 and hsCRP were evaluated in both groups before and at the third month of the trial. The median serum level of hsCRP significantly differed between the groups 3 months following the CaD or placebo administration (2.2 mg/l in the CaD group versus 3.7 mg/l in the placebo group, p=0.01). The mean endothelin-1 serum level was 0.69±0.32 pg/ml in the CaD group and 0.86±0.30 pg/ml in the placebo group (p=0.01). Furthermore, in the CaD group, the serum levels of both endothelin-1 and hsCRP were significantly decreased 3 months after administration of CaD (p<0.001). Administration of the CaD in the patients with diabetic retinopathy may reduce the serum levels of endothelin-1 and hsCRP. This might imply amelioration of the endothelial function and inflammatory status following CaD therapy in these patients.

  20. Insulin decreases atherosclerosis by inducing endothelin receptor B expression

    DEFF Research Database (Denmark)

    Park, Kyoungmin; Mima, Akira; Li, Qian

    2016-01-01

    Endothelial cell (EC) insulin resistance and dysfunction, caused by diabetes, accelerates atherosclerosis. It is unknown whether specifically enhancing EC-targeted insulin action can decrease atherosclerosis in diabetes. Accordingly, overexpressing insulin receptor substrate-1 (IRS1......) in the endothelia of Apoe(-/-) mice (Irs1/Apoe(-/-)) increased insulin signaling and function in the aorta. Atherosclerosis was significantly reduced in Irs1/ApoE(-/-) mice on diet-induced hyperinsulinemia and hyperglycemia. The mechanism of insulin's enhanced antiatherogenic actions in EC was related to remarkable...... overexpression in the endothelia of Aki/ApoE(-/-) mice significantly decreased atherosclerosis. Interestingly, endothelial EDNRB expression was selectively reduced in intima of arteries from diabetic patients and rodents. However, endothelial EDNRB expression was upregulated by insulin via P13K/Akt pathway...

  1. Reef Sharks Exhibit Site-Fidelity and Higher Relative Abundance in Marine Reserves on the Mesoamerican Barrier Reef

    Science.gov (United States)

    Bond, Mark E.; Babcock, Elizabeth A.; Pikitch, Ellen K.; Abercrombie, Debra L.; Lamb, Norlan F.; Chapman, Demian D.

    2012-01-01

    Carcharhinid sharks can make up a large fraction of the top predators inhabiting tropical marine ecosystems and have declined in many regions due to intense fishing pressure. There is some support for the hypothesis that carcharhinid species that complete their life-cycle within coral reef ecosystems, hereafter referred to as “reef sharks”, are more abundant inside no-take marine reserves due to a reduction in fishing pressure (i.e., they benefit from marine reserves). Key predictions of this hypothesis are that (a) individual reef sharks exhibit high site-fidelity to these protected areas and (b) their relative abundance will generally be higher in these areas compared to fished reefs. To test this hypothesis for the first time in Caribbean coral reef ecosystems we combined acoustic monitoring and baited remote underwater video (BRUV) surveys to measure reef shark site-fidelity and relative abundance, respectively. We focused on the Caribbean reef shark (Carcharhinus perezi), the most common reef shark in the Western Atlantic, at Glover's Reef Marine Reserve (GRMR), Belize. Acoustically tagged sharks (N = 34) were detected throughout the year at this location and exhibited strong site-fidelity. Shark presence or absence on 200 BRUVs deployed at GRMR and three other sites (another reserve site and two fished reefs) showed that the factor “marine reserve” had a significant positive effect on reef shark presence. We rejected environmental factors or site-environment interactions as predominant drivers of this pattern. These results are consistent with the hypothesis that marine reserves can benefit reef shark populations and we suggest new hypotheses to determine the underlying mechanism(s) involved: reduced fishing mortality or enhanced prey availability. PMID:22412965

  2. Reef sharks exhibit site-fidelity and higher relative abundance in marine reserves on the Mesoamerican Barrier Reef.

    Science.gov (United States)

    Bond, Mark E; Babcock, Elizabeth A; Pikitch, Ellen K; Abercrombie, Debra L; Lamb, Norlan F; Chapman, Demian D

    2012-01-01

    Carcharhinid sharks can make up a large fraction of the top predators inhabiting tropical marine ecosystems and have declined in many regions due to intense fishing pressure. There is some support for the hypothesis that carcharhinid species that complete their life-cycle within coral reef ecosystems, hereafter referred to as "reef sharks", are more abundant inside no-take marine reserves due to a reduction in fishing pressure (i.e., they benefit from marine reserves). Key predictions of this hypothesis are that (a) individual reef sharks exhibit high site-fidelity to these protected areas and (b) their relative abundance will generally be higher in these areas compared to fished reefs. To test this hypothesis for the first time in Caribbean coral reef ecosystems we combined acoustic monitoring and baited remote underwater video (BRUV) surveys to measure reef shark site-fidelity and relative abundance, respectively. We focused on the Caribbean reef shark (Carcharhinus perezi), the most common reef shark in the Western Atlantic, at Glover's Reef Marine Reserve (GRMR), Belize. Acoustically tagged sharks (N = 34) were detected throughout the year at this location and exhibited strong site-fidelity. Shark presence or absence on 200 BRUVs deployed at GRMR and three other sites (another reserve site and two fished reefs) showed that the factor "marine reserve" had a significant positive effect on reef shark presence. We rejected environmental factors or site-environment interactions as predominant drivers of this pattern. These results are consistent with the hypothesis that marine reserves can benefit reef shark populations and we suggest new hypotheses to determine the underlying mechanism(s) involved: reduced fishing mortality or enhanced prey availability.

  3. Reef sharks exhibit site-fidelity and higher relative abundance in marine reserves on the Mesoamerican Barrier Reef.

    Directory of Open Access Journals (Sweden)

    Mark E Bond

    Full Text Available Carcharhinid sharks can make up a large fraction of the top predators inhabiting tropical marine ecosystems and have declined in many regions due to intense fishing pressure. There is some support for the hypothesis that carcharhinid species that complete their life-cycle within coral reef ecosystems, hereafter referred to as "reef sharks", are more abundant inside no-take marine reserves due to a reduction in fishing pressure (i.e., they benefit from marine reserves. Key predictions of this hypothesis are that (a individual reef sharks exhibit high site-fidelity to these protected areas and (b their relative abundance will generally be higher in these areas compared to fished reefs. To test this hypothesis for the first time in Caribbean coral reef ecosystems we combined acoustic monitoring and baited remote underwater video (BRUV surveys to measure reef shark site-fidelity and relative abundance, respectively. We focused on the Caribbean reef shark (Carcharhinus perezi, the most common reef shark in the Western Atlantic, at Glover's Reef Marine Reserve (GRMR, Belize. Acoustically tagged sharks (N = 34 were detected throughout the year at this location and exhibited strong site-fidelity. Shark presence or absence on 200 BRUVs deployed at GRMR and three other sites (another reserve site and two fished reefs showed that the factor "marine reserve" had a significant positive effect on reef shark presence. We rejected environmental factors or site-environment interactions as predominant drivers of this pattern. These results are consistent with the hypothesis that marine reserves can benefit reef shark populations and we suggest new hypotheses to determine the underlying mechanism(s involved: reduced fishing mortality or enhanced prey availability.

  4. Endothelin receptor B antagonists decrease glioma cell viability independently of their cognate receptor

    Directory of Open Access Journals (Sweden)

    Patterson Paul H

    2008-11-01

    Full Text Available Abstract Background Endothelin receptor antagonists inhibit the progression of many cancers, but research into their influence on glioma has been limited. Methods We treated glioma cell lines, LN-229 and SW1088, and melanoma cell lines, A375 and WM35, with two endothelin receptor type B (ETRB-specific antagonists, A-192621 and BQ788, and quantified viable cells by the capacity of their intracellular esterases to convert non-fluorescent calcein AM into green-fluorescent calcein. We assessed cell proliferation by labeling cells with carboxyfluorescein diacetate succinimidyl ester and quantifying the fluorescence by FACS analysis. We also examined the cell cycle status using BrdU/propidium iodide double staining and FACS analysis. We evaluated changes in gene expression by microarray analysis following treatment with A-192621 in glioma cells. We examined the role of ETRB by reducing its expression level using small interfering RNA (siRNA. Results We report that two ETRB-specific antagonists, A-192621 and BQ788, reduce the number of viable cells in two glioma cell lines in a dose- and time-dependent manner. We describe similar results for two melanoma cell lines. The more potent of the two antagonists, A-192621, decreases the mean number of cell divisions at least in part by inducing a G2/M arrest and apoptosis. Microarray analysis of the effects of A-192621 treatment reveals up-regulation of several DNA damage-inducible genes. These results were confirmed by real-time RT-PCR. Importantly, reducing expression of ETRB with siRNAs does not abrogate the effects of either A-192621 or BQ788 in glioma or melanoma cells. Furthermore, BQ123, an endothelin receptor type A (ETRA-specific antagonist, has no effect on cell viability in any of these cell lines, indicating that the ETRB-independent effects on cell viability exhibited by A-192621 and BQ788 are not a result of ETRA inhibition. Conclusion While ETRB antagonists reduce the viability of glioma cells

  5. Chlorella 11-Peptide Inhibits the Production of Macrophage-Induced Adhesion Molecules and Reduces Endothelin-1 Expression and Endothelial Permeability

    Science.gov (United States)

    Shih, Mei Fen; Chen, Lih Chi; Cherng, Jong Yuh

    2013-01-01

    The inflammation process in large vessels involves the up-regulation of vascular adhesion molecules such as endothelial cell selectin (E-selectin), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) which are also known as the markers of atherosclerosis. We have reported that Chlorella 11-peptide exhibited effective anti-inflammatory effects. This peptide with an amino sequence Val-Glu-Cys-Tyr-Gly-Pro-Asn-Arg-Pro-Gln-Phe was further examined for its potential in preventing atherosclerosis in this study. In particular, the roles of Chlorella 11-peptide in lowering the production of vascular adhesion molecules, monocyte chemoattractant protein (MCP-1) and expression of endothelin-1 (ET-1) from endothelia (SVEC4-10 cells) were studied. The production of E-selectin, ICAM-1, VCAM-1 and MCP-1 in SVEC4-10 cells was measured with ELISA. The mRNA expression of ET-1 was analyzed by RT-PCR and agarose gel. Results showed that Chlorella 11-peptide significantly suppressed the levels of E-selectin, ICAM, VCAM, MCP-1 as well as ET-1 gene expression. The inhibition of ICAM-1 and VCAM-1 production by Chlorella 11-peptide was reversed in the presence of protein kinase A inhibitor (H89) which suggests that the cAMP pathway was involved in the inhibitory cause of the peptide. In addition, this peptide was shown to reduce the extent of increased intercellular permeability induced by combination of 50% of lipopolysaccharide (LPS)-activated RAW 264.7 cells medium and 50% normal SEVC cell culture medium (referred to as 50% RAW-conditioned medium). These data demonstrate that Chlorella 11-peptide is a promising biomolecule in preventing chronic inflammatory-related vascular diseases. PMID:24129228

  6. Red wine polyphenols prevent endothelial dysfunction induced by endothelin-1 in rat aorta: role of NADPH oxidase.

    Science.gov (United States)

    López-Sepúlveda, Rocío; Gómez-Guzmán, Manuel; Zarzuelo, Maria José; Romero, Miguel; Sánchez, Manuel; Quintela, Ana María; Galindo, Pilar; O'Valle, Francisco; Tamargo, Juan; Pérez-Vizcaíno, Francisco; Duarte, Juan; Jiménez, Rosario

    2011-04-01

    RWPs (red wine polyphenols) exert antihypertensive effects and improve endothelial function by reducing the plasma levels of ET-1 (endothelin-1) and the subsequent vascular production of O(2)(•-) (superoxide anion). Our present study was designed to evaluate whether RWPs act directly in the vascular wall improving endothelial dysfunction and O(2)(•-) production induced by ET-1 and to analyse the compounds responsible for these protective effects. We incubated rat isolated aortic rings in the presence or absence of ET-1 (10 nM) and RWPs (10(-4) to 10(-2) g/l) or catechin (0.2 μM), epicatechin (10 μM) and resveratrol (0.1 μM). ET-1 reduced the relaxant responses to acetylcholine, increased intracellular O(2)(•-) production, NADPH oxidase activity and protein expression of NADPH oxidase subunit p47phox. All these changes were prevented by RWPs. The preventive effects of RWPs were unaffected by co-incubation with either ICI-182780, an ER (oestrogen receptor) antagonist, or GW9662, a PPARγ (peroxisome-proliferator-activated receptor γ) antagonist. RWPs inhibited the phosphorylation of the mitogen-activated protein kinase, ERK1/2 (extracellular signal-regulated kinase 1/2), a key regulator of p47phox expression in response to ET-1. When the isolated polyphenols were tested, at the concentrations found in 10(-2) g/l RWPs, only epicatechin prevented endothelial dysfunction and all biochemical changes induced by ET-1 in the vascular wall. Taken together, these results indicate that RWPs prevent ET-1-induced vascular O(2)(•-) production by reducing overexpression of p47phox and the subsequent increased NADPH oxidase activity, leading to improvement in endothelial function. The effects of RWPs appear to be independent of ER and PPARγ activation and are related to ERK1/2 inhibition.

  7. Preoperative Pain, Symptoms, and Psychological Factors related to Higher Acute Pain Trajectories during Hospitalization for Total Knee Arthroplasty.

    Directory of Open Access Journals (Sweden)

    Maren Falch Lindberg

    Full Text Available Unrelieved postoperative pain after total knee arthroplasty (TKA is a significant problem. This longitudinal study investigated how preoperative pain intensity, as well as a comprehensive list of preoperative and perioperative factors, influenced the severity of acute average and worst pain after TKA.Prior to surgery, 203 patients completed a demographic questionnaire, Lee Fatigue Scale, Fatigue Severity Scale, Hospital Anxiety and Depression Scale, and Brief Illness Perception Questionnaire. Brief Pain Inventory was completed prior to surgery as well as through postoperative days (POD 0 to 4. Clinical data were extracted from medical records.Several factors were associated with higher levels of preoperative and postoperative pain. Lower preoperative average and worst pain intensity scores were associated with increases in average and worst postoperative pain from POD1 to POD4. A higher number of comorbidities, higher C-reactive protein values, and higher pain interference with function were associated with higher preoperative levels of average pain. Older age, higher fatigue levels, and higher scores on identity and emotional responses to osteoarthritis (OA were associated with higher preoperative levels of worst pain. Lower perceived consequences of OA were associated with higher pain from POD1 to POD4. Males and patients with lower preoperative scores for average pain had higher worst pain following surgery.Patients at higher risk for more severe postoperative pain can be identified through an assessment of pain and other risk factors identified in this study. Future research needs to test the efficacy of interventions that modify patients' perceptions of living with OA and pain intensity before surgery on short and long term postoperative outcomes.

  8. Preoperative Pain, Symptoms, and Psychological Factors related to Higher Acute Pain Trajectories during Hospitalization for Total Knee Arthroplasty.

    Science.gov (United States)

    Lindberg, Maren Falch; Miaskowski, Christine; Rustøen, Tone; Rosseland, Leiv Arne; Paul, Steven M; Lerdal, Anners

    2016-01-01

    Unrelieved postoperative pain after total knee arthroplasty (TKA) is a significant problem. This longitudinal study investigated how preoperative pain intensity, as well as a comprehensive list of preoperative and perioperative factors, influenced the severity of acute average and worst pain after TKA. Prior to surgery, 203 patients completed a demographic questionnaire, Lee Fatigue Scale, Fatigue Severity Scale, Hospital Anxiety and Depression Scale, and Brief Illness Perception Questionnaire. Brief Pain Inventory was completed prior to surgery as well as through postoperative days (POD) 0 to 4. Clinical data were extracted from medical records. Several factors were associated with higher levels of preoperative and postoperative pain. Lower preoperative average and worst pain intensity scores were associated with increases in average and worst postoperative pain from POD1 to POD4. A higher number of comorbidities, higher C-reactive protein values, and higher pain interference with function were associated with higher preoperative levels of average pain. Older age, higher fatigue levels, and higher scores on identity and emotional responses to osteoarthritis (OA) were associated with higher preoperative levels of worst pain. Lower perceived consequences of OA were associated with higher pain from POD1 to POD4. Males and patients with lower preoperative scores for average pain had higher worst pain following surgery. Patients at higher risk for more severe postoperative pain can be identified through an assessment of pain and other risk factors identified in this study. Future research needs to test the efficacy of interventions that modify patients' perceptions of living with OA and pain intensity before surgery on short and long term postoperative outcomes.

  9. The Role of Trust in Creating Value and Student Loyalty in Relational Exchanges between Higher Education Institutions and Their Students

    Science.gov (United States)

    Carvalho, Sergio W.; de Oliveira Mota, Marcio

    2010-01-01

    The globalization of educational services and the increasing competition coming from the private sector have forced higher education institutions to market their programs more aggressively and to look at student loyalty as the key for future success. Student loyalty to higher education institutions represents not only a more stable financial basis…

  10. Issues Related to Higher Education in Sub-Saharan Africa. World Bank Staff Working Papers No. 780.

    Science.gov (United States)

    Hinchliffe, Keith

    Higher education in Sub-Saharan African countries is examined. Attention is directed to the development of higher education in sub-Saharan African countries since the early 1960s, as well as criticisms currently directed at the sector, and the economic and budgetary environment for resource allocation. The labor market for African college…

  11. Endothelin-1 stimulates insulin secretion by direct action on the islets of Langerhans in mice

    DEFF Research Database (Denmark)

    Gregersen, S; Thomsen, J L; Brock, B

    1996-01-01

    Endothelin-1 (ET-1), a potent endothelium-derived vasoconstrictor peptide, is secreted in response to insulin. Elevated circulating ET-1 levels have been found in patients with diabetes mellitus and vascular dysfunction. The question arises whether ET-1 acts as a direct modulator of insulin...... secretion. To test this, we studied the effects of ET-1 on isolated mouse islets of Langerhans. ET-1 (1 nmol/l-1 mumol/l) dose-dependently stimulated insulin secretion from islets incubated in the presence of 16.7 mmol/l glucose (p ... was found at 3.3 mmol/l glucose. Furthermore, ET-1 induced a large, transient increase in glucose-stimulated insulin secretion during islet perifusion in the presence (p

  12. Synthesis and in vivo evaluation of a PET radioligand for imaging the endothelin-A receptor

    Energy Technology Data Exchange (ETDEWEB)

    Mathews, William B. [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States)]. E-mail: bmathews@petscan.nm.jhu.edu; Zober, Tamas G. [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Ravert, Hayden T. [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Scheffel, Ursula [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Hilton, John [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Sleep, Darryl [Abbott Laboratories, Abbott Park, IL 60064 (United States); Dannals, Robert F. [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Szabo, Zsolt [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States)

    2006-01-15

    The endothelin-A receptor ligand Atrasentan (ABT-627) was radiolabeled by {sup 11}C-methylaton of the desmethyl precursor in phenolate form. In mice, the highest uptake of [{sup 11}C]ABT-627 was in the liver, kidneys and lungs. No significant binding was observed in mouse brain or heart. PET studies in a baboon, however, showed accumulation in the myocardium and lungs with a tissue/blood equilibrium reached at 40 min postinjection. Between 35 and 75 min, the heart/blood and lung/blood ratios were 1.72 and 1.31, respectively. Pretreatment with a 0.39 mg/kg dose of unlabeled ABT-627 inhibited the uptake of the tracer by 53-54% in both the myocardium and lungs at 65 min.

  13. Modulatory effect of endothelin-1 and -3 on neuronal norepinephrine release in the rat posterior hypothalamus.

    Science.gov (United States)

    Di Nunzio, Andrea S; Legaz, Guillermina; Rodano, Valeria; Bianciotti, Liliana G; Vatta, Marcelo S

    2004-04-15

    Based upon the existence of high density of ET-receptors on catecholaminergic neurons of the hypothalamus, we studied the effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) on neuronal norepinephrine (NE) release in the rat posterior hypothalamus. The intracellular pathways and receptors involved were also investigated. Neuronal NE release was enhanced by ET-1 and ET-3 (10 etaM). The selective antagonists of subtype A and B ET receptors (ETA, ETB) (100 etaM BQ-610 and 100 etaM BQ-788, respectively) abolished the increase induced by ET-1 but not by ET-3. The PLC inhibitor, U73122 (10 microM), abolished ET-1 and ET-3 response. GF-109203X (100 etaM) (PKC inhibitor) blocked the increase in NE release produced by ET-3 and partially blocked ET-1 response. The inositol 1,4,5-trisphosphate-induced calcium release inhibitor, 42 microM 2-APB, inhibited the stimulatory effect induced by ET-3 but not by ET-1. The PKA inhibitor, 500 etaM H-89, blocked the increase in neuronal NE release evoked by ET-1 but not by ET-3. Our results showed that ET-1 as well as ET-3 displayed an excitatory neuromodulatory effect on neuronal NE release in the rat posterior hypothalamus. ET-1 through an atypical ETA or ETB receptor activated the PLC/PKC signalling pathway as well as the cAMP pathway, whereas ET-3 through a non-ETA/non-ETB receptor activated the phosphoinositide pathway. Both ETs would enhance the sympathoexcitatory response elicited by the posterior hypothalamus and thus participate in cardiovascular regulation.

  14. Role of endothelin-1 in mediating changes in cardiac sympathetic nerve activity in heart failure.

    Science.gov (United States)

    Abukar, Yonis; May, Clive N; Ramchandra, Rohit

    2016-01-01

    Heart failure (HF) is associated with increased sympathetic nerve activity to the heart (CSNA), which is directly linked to mortality in HF patients. Previous studies indicate that HF is associated with high levels of plasma endothelin-1 (ET-1), which correlates with the severity of the disease. We hypothesized that blockade of endothelin receptors would decrease CSNA. The effects of intravenous tezosentan (a nonselective ETA and ETB receptor antagonist) (8 mg·kg(-1)·h(-1)) on resting levels of CSNA, arterial pressure, and heart rate were determined in conscious normal sheep (n = 6) and sheep with pacing-induced HF (n = 7). HF was associated with a significant decrease in ejection fraction (from 74 ± 2% to 38 ± 1%, P < 0.001) and a significant increase in resting levels of CSNA burst incidence (from 56 ± 11 to 87 ± 2 bursts/100 heartbeats, P < 0.01). Infusion of tezosentan for 60 min significantly decreased resting mean aterial pressure (MAP) in both normal and HF sheep (-8 ± 4 mmHg and -4 ± 3 mmHg, respectively; P < 0.05). This was associated with a significant decrease in CSNA (by 25 ± 26% of control) in normal sheep, but there was no change in CSNA in HF sheep. Calculation of spontaneous baroreflex gain indicated significant impairment of the baroreflex control of HR after intravenous tezosentan infusion in normal animals but no change in HF animals. These data suggest that endogenous levels of ET-1 contribute to the baseline levels of CSNA in normal animals, but this effect is absent in HF. Copyright © 2016 the American Physiological Society.

  15. Nitric oxide blunts the endothelin-mediated pulmonary vasoconstriction in exercising swine

    Science.gov (United States)

    Houweling, Birgit; Merkus, Daphne; Dekker, Marjolein MD; Duncker, Dirk J

    2005-01-01

    We have previously shown that vasodilators and vasoconstrictors that are produced by the vascular endothelium, including nitric oxide (NO), prostanoids and endothelin (ET), contribute to the regulation of systemic and pulmonary vascular tone in swine, in particular during treadmill exercise. Since NO and prostanoids can modulate the release of ET, and vice versa, we investigated the integrated endothelial control of pulmonary vascular resistance in exercising swine. Specifically, we tested the hypothesis that increased NO and prostanoid production during exercise limits the vasoconstrictor influence of ET, so that loss of these vasodilators results in exaggerated ET-mediated vasoconstriction during exercise. Fifteen instrumented swine were exercised on a treadmill at 0–5 km h−1 before and during ETA/ETB receptor blockade (tezosentan, 3 mg kg−1i.v.) in the presence and absence of inhibition of NO synthase (Nω-nitro-l-arginine, 20 mg kg−1i.v.) and/or cyclo-oxygenase (indometacin, 10 mg kg−1i.v.). In the systemic circulation, ET receptor blockade decreased vascular resistance at rest, which waned with increasing exercise intensity. Prior inhibition of either NO or prostanoid production augmented the vasodilator effect of ET receptor blockade, and these effects were additive. In contrast, in the pulmonary bed, ET receptor blockade had no effect under resting conditions, but decreased pulmonary vascular resistance during exercise. Prior inhibition of NO synthase enhanced the pulmonary vasodilator effect of ET receptor blockade, particularly during exercise, whereas inhibition of prostanoids had no effect, even after prior NO synthase inhibition. In conclusion, endogenous endothelin limits pulmonary vasodilatation in response to treadmill exercise. This vasoconstrictor influence is blunted by NO but not by prostanoids. PMID:16081484

  16. VIP and endothelin receptor antagonist: An effective combination against experimental pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Szema Anthony M

    2011-10-01

    Full Text Available Abstract Background Pulmonary Arterial Hypertension (PAH remains a therapeutic challenge, and the search continues for more effective drugs and drug combinations. We recently reported that deletion of the vasoactive intestinal peptide (VIP gene caused the spontaneous expression of a PH phenotype that was fully corrected by VIP. The objectives of this investigation were to answer the questions: 1 Can VIP protect against PH in other experimental models? and 2 Does combining VIP with an endothelin (ET receptor antagonist bosentan enhance its efficacy? Methods Within 3 weeks of a single injection of monocrotaline (MCT, s.c. in Sprague Dawley rats, PAH developed, manifested by pulmonary vascular remodeling, lung inflammation, RV hypertrophy, and death within the next 2 weeks. MCT-injected animals were either untreated, treated with bosentan (p.o. alone, with VIP (i.p. alone, or with both together. We selected this particular combination upon finding that VIP down-regulates endothelin receptor expression which is further suppressed by bosentan. Therapeutic outcomes were compared as to hemodynamics, pulmonary vascular pathology, and survival. Results Treatment with VIP, every other day for 3 weeks, begun on the same day as MCT, almost totally prevented PAH pathology, and eliminated mortality for 45 days. Begun 3 weeks after MCT, however, VIP only partially reversed PAH pathology, though more effectively than bosentan. Combined therapy with both drugs fully reversed the pathology, while preventing mortality for at least 45 days. Conclusions 1 VIP completely prevented and significantly reversed MCT-induced PAH; 2 VIP was more effective than bosentan, probably because it targets a wider range of pro-remodeling pathways; and 3 combination therapy with VIP plus bosentan was more effective than either drug alone, probably because both drugs synergistically suppressed ET-ET receptor pathway.

  17. Endothelin-1 signalling controls early embryonic heart rate in vitro and in vivo.

    Science.gov (United States)

    Karppinen, S; Rapila, R; Mäkikallio, K; Hänninen, S L; Rysä, J; Vuolteenaho, O; Tavi, P

    2014-02-01

    Spontaneous activity of embryonic cardiomyocytes originates from sarcoplasmic reticulum (SR) Ca(2+) release during early cardiogenesis. However, the regulation of heart rate during embryonic development is still not clear. The aim of this study was to determine how endothelin-1 (ET-1) affects the heart rate of embryonic mice, as well as the pathway through which it exerts its effects. The effects of ET-1 and ET-1 receptor inhibition on cardiac contraction were studied using confocal Ca(2+) imaging of isolated mouse embryonic ventricular cardiomyocytes and ultrasonographic examination of embryonic cardiac contractions in utero. In addition, the amount of ET-1 peptide and ET receptor a (ETa) and b (ETb) mRNA levels were measured during different stages of development of the cardiac muscle. High ET-1 concentration and expression of both ETa and ETb receptors was observed in early cardiac tissue. ET-1 was found to increase the frequency of spontaneous Ca(2+) oscillations in E10.5 embryonic cardiomyocytes in vitro. Non-specific inhibition of ET receptors with tezosentan caused arrhythmia and bradycardia in isolated embryonic cardiomyocytes and in whole embryonic hearts both in vitro (E10.5) and in utero (E12.5). ET-1-mediated stimulation of early heart rate was found to occur via ETb receptors and subsequent inositol trisphosphate receptor activation and increased SR Ca(2+) leak. Endothelin-1 is required to maintain a sufficient heart rate, as well as to prevent arrhythmia during early development of the mouse heart. This is achieved through ETb receptor, which stimulates Ca(2+) leak through IP3 receptors. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  18. Up-Regulation of Endothelin Receptors Induced by Cigarette Smoke — Involvement of MAPK in Vascular and Airway Hyper-Reactivity

    Directory of Open Access Journals (Sweden)

    Yaping Zhang

    2010-01-01

    Full Text Available Cigarette smoke exposure is well known to cause cardiovascular and airway diseases, both of which are leading causes of death and disability in the world. However, the molecular mechanisms that link cigarette smoke to cardiovascular and airway diseases are not fully understood. Vascular and airway hyper-reactivity plays an important role in the pathogenesis of cardiovascular and airway diseases. Recent studies have demonstrated that endothelin receptor up-regulation mediates vascular and airway hyper-reactivity in response to endothelin-1 (ET-1, endothelin receptor agonist in cardiovascular and airway diseases. In the vasculature and airways, the main functional consequences of up-regulated endothelin receptors by cigarette smoke exposure are enhanced contraction and proliferation of the smooth muscle cells, which subsequently result in abnormal contraction (spasm and adverse proliferation (remodeling of the vasculature and airways. The structural alteration by adverse remodeling involves changes in cell growth, cell death, cell migration, and production or degradation of the extracellular matrix. This review focuses on cigarette smoke exposure that induces activation of intracellular mitogen-activated protein kinase (MAPK and subsequently results in the up-regulation of endothelin receptors in the vasculature and airways, which mediates vascular and airway hyper-reactivity, one of the important pathogenic characteristics of cardiovascular and airway diseases. Understanding the molecular mechanisms of how cigarette smoke causes up-regulation of endothelin receptors in the vasculature and airways may provide new strategies for the treatment of cigarette smoke—associated cardiovascular and lung diseases.

  19. Smoking is Associated with Higher Disease-related Costs and Lower Health-related Quality of Life in Inflammatory Bowel Disease.

    Science.gov (United States)

    Severs, M; Mangen, M-J J; van der Valk, M E; Fidder, H H; Dijkstra, G; van der Have, M; van Bodegraven, A A; de Jong, D J; van der Woude, C J; Romberg-Camps, M J L; Clemens, C H M; Jansen, J M; van de Meeberg, P C; Mahmmod, N; Ponsioen, C Y; Vermeijden, J R; van der Meulen-de Jong, A E; Pierik, M; Siersema, P D; Oldenburg, B

    2017-03-01

    Smoking affects the course of inflammatory bowel disease [IBD]. We aimed to study the impact of smoking on IBD-specific costs and health-related quality-of-life [HrQoL] among adults with Crohn's disease [CD] and ulcerative colitis [UC]. A large cohort of IBD patients was prospectively followed during 1 year using 3-monthly questionnaires on smoking status, health resources, disease activity and HrQoL. Costs were calculated by multiplying used resources with corresponding unit prices. Healthcare costs, patient costs, productivity losses, disease course items and HrQoL were compared between smokers, never-smokers and ex-smokers, adjusted for potential confounders. In total, 3030 patients [1558 CD, 1054 UC, 418 IBD-unknown] were enrolled; 16% smoked at baseline. In CD, disease course was more severe among smokers. Smoking was associated with > 30% higher annual societal costs in IBD (€7,905 [95% confidence interval €6,234 - €9,864] vs €6,017 [€5,186 - €6,946] in never-smokers and €5,710 [€4,687 - €6,878] in ex-smokers, p = 0.06 and p = 0.04, respectively). In CD, smoking patients generated the highest societal costs, primarily driven by the use of anti-tumour necrosis factor compounds. In UC, societal costs of smoking patients were comparable to those of non-smokers. Societal costs of IBD patients who quitted smoking > 5 years before inclusion were lower than in patients who quitted within the past 5 years (€ 5,135 [95% CI €4,122 - €6,303] vs €9,342 [€6,010 - €12,788], p = 0.01). In both CD and UC, smoking was associated with a lower HrQoL. Smoking is associated with higher societal costs and lower HrQoL in IBD patients. Smoking cessation may result in considerably lower societal costs.

  20. Khat Chewing among Students of Higher Education in Jazan Region, Saudi Arabia: Prevalence, Pattern, and Related Factors

    Directory of Open Access Journals (Sweden)

    Rashad Mohammed Alsanosy

    2013-01-01

    Full Text Available Objectives. (1 To estimate the prevalence and behavioral patterns of Khat chewing and (2 to investigate factors that influenced the pattern of Khat use among undergraduate students in different higher education institutions in Jazan region, Saudi Arabia. Materials and Methods. A cross-sectional study using a pretested structured self-administered quantitative questionnaire was used to collect data. SPSS version 17 software program was used for data analysis. Results. The overall current Khat chewing prevalence among higher education students was found to be 23.1%, significantly higher among males at 38.5% than among females at 2.1% . Lifetime Khat chewer students were 24.8% for males at 40.5%, significantly higher compared with females at 3.7% . Univariate analysis revealed that the gender of student, smoking status of student, a friend’s smoking, and Khat chewing were associated with a significant high risk of Khat chewing (   for all. Conclusions. The use of Khat trend is increasing among higher education students in Jazan region. A multilevel, value based, comprehensive, and strategic long-term intervention plan is needed. The comprehensive plan may include social interventions geared by creating recreations alternatives and opportunities for youth and a critical review for current authorities’ interventions and services.

  1. Khat chewing among students of higher education in Jazan region, Saudi Arabia: prevalence, pattern, and related factors.

    Science.gov (United States)

    Alsanosy, Rashad Mohammed; Mahfouz, Mohamed Salih; Gaffar, Abdelrahim Mutwakel

    2013-01-01

    (1) To estimate the prevalence and behavioral patterns of Khat chewing and (2) to investigate factors that influenced the pattern of Khat use among undergraduate students in different higher education institutions in Jazan region, Saudi Arabia. A cross-sectional study using a pretested structured self-administered quantitative questionnaire was used to collect data. SPSS version 17 software program was used for data analysis. The overall current Khat chewing prevalence among higher education students was found to be 23.1%, significantly higher among males at 38.5% than among females at 2.1% (P < 0.001). Lifetime Khat chewer students were 24.8% for males at 40.5%, significantly higher compared with females at 3.7% (P < 0.001). Univariate analysis revealed that the gender of student, smoking status of student, a friend's smoking, and Khat chewing were associated with a significant high risk of Khat chewing (P < 0.001   for all). The use of Khat trend is increasing among higher education students in Jazan region. A multilevel, value based, comprehensive, and strategic long-term intervention plan is needed. The comprehensive plan may include social interventions geared by creating recreations alternatives and opportunities for youth and a critical review for current authorities' interventions and services.

  2. Observation of Two Types of Behaviors of Financial Bubbles and the Related Higher-Order Potential Forces

    Science.gov (United States)

    Watanabe, K.; Takayasu, H.; Takayasu, M.

    Market prices are known to be well described by the random walk modelin a time-dependent potential force whose center is given by the trace of the random walker [Physica A 370 (2006), 91]. We analytically show that the higher-order potential force determines the dynamic price behaviors of the single-exponential growth and the double exponential growth. We confirm the existence of such price behaviors in real financial data and we observe the higher-order potential forces in some periods.

  3. The vascular endothelial growth factor receptor inhibitor sunitinib causes a preeclampsia-like syndrome with activation of the endothelin system

    DEFF Research Database (Denmark)

    Kappers, Mariëtte H W; Smedts, Frank M M; Horn, Thomas

    2011-01-01

    Angiogenesis inhibition is an established treatment for several tumor types. Unfortunately, this therapy is associated with adverse effects, including hypertension and renal toxicity, referred to as "preeclampsia." Recently, we demonstrated in patients and in rats that the multitarget tyrosine...... kinase inhibitor sunitinib induces a rise in blood pressure (BP), renal dysfunction, and proteinuria associated with activation of the endothelin system. In the current study we investigated the effects of sunitinib on rat renal histology, including the resemblance with preeclampsia, as well as the roles...... of preeclampsia, which was partly reversible after sunitinib discontinuation. The histological abnormalities were accompanied by an increase in urinary excretion of endothelin 1 and diminished NO metabolite excretion. In rats on sunitinib alone, BP increased (¿BP: 31.6±0.9 mm Hg). This rise could largely...

  4. The vascular endothelial growth factor receptor inhibitor sunitinib causes a preeclampsia-like syndrome with activation of the endothelin system

    DEFF Research Database (Denmark)

    Kappers, Mariëtte H W; Smedts, Frank M M; Horn, Thomas

    2011-01-01

    Angiogenesis inhibition is an established treatment for several tumor types. Unfortunately, this therapy is associated with adverse effects, including hypertension and renal toxicity, referred to as "preeclampsia." Recently, we demonstrated in patients and in rats that the multitarget tyrosine...... kinase inhibitor sunitinib induces a rise in blood pressure (BP), renal dysfunction, and proteinuria associated with activation of the endothelin system. In the current study we investigated the effects of sunitinib on rat renal histology, including the resemblance with preeclampsia, as well as the roles...... of preeclampsia, which was partly reversible after sunitinib discontinuation. The histological abnormalities were accompanied by an increase in urinary excretion of endothelin 1 and diminished NO metabolite excretion. In rats on sunitinib alone, BP increased (ΔBP: 31.6±0.9 mm Hg). This rise could largely...

  5. Effective prophylaxis of visual and neurological disturbances with an anti-endothelin drug: analysis of 1642 sclerotherapy sessions

    Directory of Open Access Journals (Sweden)

    Alessandro Frullini

    2016-12-01

    Full Text Available In the literature cases of stroke and transient neurological symptoms have been described after sclerotherapy for chronic venous disease The initial interpretation of these phenomena was that of a micro air embolism in association with a patent foramen ovale. This explanation did not always manage to justify all neurological manifestations. Recent theories have demonstrated that in the area of sclerosis, a significant amount of endothelin 1. We carried out a retrospective assessment of sclerotherapy case studies on 540 patients at ten phlebological centres to search for a relationship between the use of aminaftone (a venotropic drug with demonstrated anti-endothelin action and the occurrence of side effects after sclerotherapy was performed. Significant reduction of side effects was observed in sclerotherapy for teleangectasias and in patients with migraine history.

  6. High arterial compliance in cirrhosis is related to low adrenaline and elevated circulating calcitonin gene related peptide but not to activated vasoconstrictor systems

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren; Schifter, S

    2001-01-01

    catecholamines, renin activity, endothelin-1, and calcitonin gene related peptide (CGRP) at baseline and during oxygen inhalation. RESULTS: COMP(art) was significantly increased in cirrhotic patients compared with controls (1.32 v 1.06 ml/mm Hg; p....53; prenin activity, or endothelin-1. COMP(art) was positively related to plasma volume (r=0.50; p... to COMP(art) disappeared. The relation of COMP(art) to CGRP and circulatory variables remained unchanged. CONCLUSION: Elevated arterial compliance in cirrhosis is related to low adrenaline, high CGRP, and systemic hyperdynamics but not to indicators of the activated vasoconstrictor systems (noradrenaline...

  7. Characteristics Expected in Fields of Higher Education and Gender Stereotypical Traits Related to Academic Success: A Mirror Effect

    Science.gov (United States)

    Verniers, Catherine; Martinot, Delphine

    2015-01-01

    The aim of the present study was to test whether the content of a gender stereotype concerning general academic achievement matched the characteristics deemed to predict success in the fields of higher education dominated by women and men respectively. A sample of 207 undergraduate students rated the extent to which characteristics ascribed to…

  8. Multiple, Relational and Emotional Mobilities: Understanding Student Mobilities in Higher Education as More than "Staying Local" and "Going Away"

    Science.gov (United States)

    Finn, Kirsty

    2017-01-01

    This paper advances theorising around student geographies in higher education (HE). It extends recent work, which has problematised the primacy of social class and binary thinking about student mobilities, and presents local/non-local experiences and im/mobility as a defining dualism. Drawing on a qualitative longitudinal study of women's…

  9. The Relations between Lower and Higher Level Comprehension Skills and Their Role in Prediction of Early Reading Comprehension

    Science.gov (United States)

    Silva, Macarena; Cain, Kate

    2015-01-01

    This study of 4- to 6-year-olds had 2 aims: first, to determine how lower level comprehension skills (receptive vocabulary and grammar) and verbal memory support early higher level comprehension skills (inference and literal story comprehension), and second, to establish the predictive power of these skills on subsequent reading comprehension.…

  10. Do Diligent Students Perform Better? Complex Relations between Student and Course Characteristics, Study Time, and Academic Performance in Higher Education

    Science.gov (United States)

    Masui, Chris; Broeckmans, Jan; Doumen, Sarah; Groenen, Anne; Molenberghs, Geert

    2014-01-01

    Research has reported equivocal results regarding the relationship between study time investment and academic performance in higher education. In the setting of the active, assignment-based teaching approach at Hasselt University (Belgium), the present study aimed (a) to further clarify the role of study time in academic performance, while taking…

  11. The Use of Critical Thinking in Higher Education in Relation to the International Student: Shifting Policy and Practice

    Science.gov (United States)

    Hammersley-Fletcher, Linda; Hanley, Christopher

    2016-01-01

    Academic staff working within Western higher education institutions (HEIs), have a responsibility to encourage the continuous critique of knowledge and values, expressed both within the curriculum that they deliver and within society more widely. Critical thinking is often regarded as the hallmark of a good education. Atkinson however raised…

  12. Korean Mature Women Students' Various Subjectivities in Relation to Their Motivation for Higher Education: Generational Differences amongst Women

    Science.gov (United States)

    Lee, Sunghoe

    2014-01-01

    This qualitative case study attempts to conceptualize certain "patterns" and "processes" of which 28 mature women undergraduates give meanings to their motivation for higher education in their life contexts. Particular attention has been paid to include diverse groups of women according to their age, prior educational…

  13. Higher Education Issues in the 102nd Congress. A Guide for College and University Presidents and Government Relations Officers.

    Science.gov (United States)

    American Council on Education, Washington, DC.

    This document outlines the issues of importance to higher education that face the 102nd Congress of the United States Government of which three have paramount importance: (1) securing adequate funding of student assistance programs; (2) assuring tax policies which provide maximum incentives to enlarge the nation's technical and professional skills…

  14. The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney.

    Directory of Open Access Journals (Sweden)

    María F Albertoni Borghese

    Full Text Available Renal development in rodents, unlike in humans, continues during early postnatal period. We aimed to evaluate whether the pharmacological inhibition of Endothelin system during this period affects renal development, both at structural and functional level in male and female rats. Newborn rats were treated orally from postnatal day 1 to 20 with vehicle or bosentan (Actelion, 20 mg/kg/day, a dual endothelin receptor antagonist (ERA. The animals were divided in 4 groups: control males, control females, ERA males and ERA females. At day 21, we evaluated renal function, determined the glomerular number by a maceration method and by morphometric analysis and evaluated possible structural renal alterations by three methods: 〈alpha〉-Smooth muscle actin (α-SMA immunohistochemistry, Masson's trichrome and Sirius red staining. The pharmacological inhibition of Endothelin system with a dual ERA during the early postnatal period of the rat did not leads to renal damage in the kidneys of male and female rats. However, ERA administration decreased the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increased the proteinuria. These effects could predispose to hypertension or renal diseases in the adulthood. On the other hand, these effects were more pronounced in male rats, suggesting that there are sex differences that could be greater later in life. These results provide evidence that Endothelin has an important role in rat renal postnatal development. However these results do not imply that the same could happen in humans, since human renal development is complete at birth.

  15. Involvement of calcium-calmodulin-dependent protein kinase II in endothelin receptor expression in rat cerebral arteries.

    Science.gov (United States)

    Waldsee, Roya; Ahnstedt, Hilda; Eftekhari, Sajedeh; Edvinsson, Lars

    2010-03-01

    Experimental cerebral ischemia and organ culture of cerebral arteries result in the enhanced expression of endothelin ET(B) receptors in smooth muscle cells via increased transcription. The present study was designed to evaluate the involvement of calcium-calmodulin-dependent protein kinase (CAMK) in the transcriptional expression of endothelin receptors after organ culture. Rat basilar arteries were incubated for 24 h with or without the CAMK inhibitor KN93 or ERK1/2 inhibitor U0126. The contractile responses to endothelin-1 (ET-1; ET(A) and ET(B) receptor agonist) and sarafotoxin 6c (S6c; ET(B) receptor agonist) were studied using a sensitive myograph. The mRNA levels of the ET(A) and ET(B) receptors and CAMKII were determined by real-time PCR, and their protein levels were evaluated by immunohistochemistry and Western blot. The mRNA levels of CAMKII and the ET(B) receptor increased during organ culture, but there was no change in the expression of the ET(A) receptor. This effect was abolished by coincubation with KN93 or U0126. In functional studies, both inhibitors attenuated the S6c-induced contraction. Incubating the arteries with KN93, but not U0126, decreased the amount of phosphorylated CAMKII. The inhibitors had no effect on the levels of myosin light chain during organ culture, as measured by Western blot. CAMKII is involved in the upregulation of the endothelin ET(B) receptor and interacts with the ERK1/2 pathway to enhance receptor expression. CAMKII has no effect on the contractile apparatus in rat cerebral arteries.

  16. Inhibition of CPU0213, a Dual Endothelin Receptor Antagonist, on Apoptosis via Nox4-Dependent ROS in HK-2 Cells

    Directory of Open Access Journals (Sweden)

    Qing Li

    2016-06-01

    Full Text Available Background/Aims: Our previous studies have indicated that a novel endothelin receptor antagonist CPU0213 effectively normalized renal function in diabetic nephropathy. However, the molecular mechanisms mediating the nephroprotective role of CPU0213 remain unknown. Methods and Results: In the present study, we first detected the role of CPU0213 on apoptosis in human renal tubular epithelial cell (HK-2. It was shown that high glucose significantly increased the protein expression of Bax and decreased Bcl-2 protein in HK-2 cells, which was reversed by CPU0213. The percentage of HK-2 cells that showed Annexin V-FITC binding was markedly suppressed by CPU0213, which confirmed the inhibitory role of CPU0213 on apoptosis. Given the regulation of endothelin (ET system to oxidative stress, we determined the role of redox signaling in the regulation of CPU0213 on apoptosis. It was demonstrated that the production of superoxide (O2-. was substantially attenuated by CPU0213 treatment in HK-2 cells. We further found that CPU0213 dramatically inhibited expression of Nox4 protein, which gene silencing mimicked the role of CPU0213 on the apoptosis under high glucose stimulation. We finally examined the role of CPU0213 on ET-1 receptors and found that high glucose-induced protein expression of endothelin A and B receptors was dramatically inhibited by CPU0213. Conclusion: Taken together, these results suggest that this Nox4-dependenet O2- production is critical for the apoptosis of HK-2 cells in high glucose. Endothelin receptor antagonist CPU0213 has an anti-apoptosis role through Nox4-dependent O2-.production, which address the nephroprotective role of CPU0213 in diabetic nephropathy.

  17. The role of the biomarker and the genetic polymorphism of endothelin-1 in pulmonary arterial hypertension among Egyptians

    Directory of Open Access Journals (Sweden)

    Emad Ibrahim

    2012-10-01

    Conclusions: In conclusion, our findings suggest a potential link between endothelin-1 level and specific genotypes in the EDN1 gene and susceptibility for PAH with a worse haemodynamic profile. Further investigations are warranted to understand the molecular basis and to confirm the potential clinical importance of these findings on larger cohorts of patients with PAH. This will impact on the management of PAH of Egyptian patients in the near future.

  18. Inhibition of CPU0213, a Dual Endothelin Receptor Antagonist, on Apoptosis via Nox4-Dependent ROS in HK-2 Cells

    OpenAIRE

    Qing Li; Ji Li; Hua Shao; Xiao-Xue Li; Feng Yu; Ming Xu

    2016-01-01

    Background/Aims: Our previous studies have indicated that a novel endothelin receptor antagonist CPU0213 effectively normalized renal function in diabetic nephropathy. However, the molecular mechanisms mediating the nephroprotective role of CPU0213 remain unknown. Methods and Results: In the present study, we first detected the role of CPU0213 on apoptosis in human renal tubular epithelial cell (HK-2). It was shown that high glucose significantly increased the protein expression of Bax and de...

  19. Endothelial nitric oxide synthase-enhancing G-protein coupled receptor antagonist inhibits pulmonary artery hypertension by endothelin-1-dependent and endothelin-1-independent pathways in a monocrotaline model

    Directory of Open Access Journals (Sweden)

    Chung-Pin Liu

    2014-06-01

    Full Text Available This study investigates whether endothelin-1 (ET-1 mediates monocrotaline (MCT-induced pulmonary artery hypertension (PAH and right ventricular hypertrophy (RVH, and if so, whether the G-protein coupled receptor antagonist KMUP-1 (7-{2-[4-(2-chlorobenzenepiperazinyl]ethyl}-1,3-dimethylxanthine inhibits ET-1-mediated PA constriction and the aforementioned pathological changes. In a chronic rat model, intraperitoneal MCT (60 mg/kg induced PAH and increased PA medial wall thickening and RV/left ventricle + septum weight ratio on Day 21 after MCT injection. Treatment with sublingual KMUP-1 (2.5 mg/kg/day for 21 days prevented these changes and restored vascular endothelial nitric oxide synthase (eNOS immunohistochemical staining of lung tissues. Western blotting analysis demonstrated that KMUP-1 enhanced eNOS, soluble guanylate cyclase, and protein kinase G levels, and reduced ET-1 expression and inactivated Rho kinase II (ROCKII in MCT-treated lung tissue over long-term administration. In MCT-treated rats, KMUP-1 decreased plasma ET-1 on Day 21. KMUP-1 (3.6 mg/kg maximally appeared at 0.25 hours in the plasma and declined to basal levels within 24 hours after sublingual administration. In isolated PA of MCT-treated rats, compared with control and pretreatment with l-NG-nitroarginine methyl ester (100 μM, KMUP-1 (0.1–100 μM inhibited ET-1 (0.01 μM-induced vasoconstriction. Endothelium-denuded PA sustained higher contractility in the presence of KMUP-1. In a 24-hour culture of smooth muscle cells (i.e., PA smooth muscle cells or PASMCs, KMUP-1 (0.1–10 μM inhibited RhoA- and ET-1-induced RhoA activation. KMUP-1 prevented MCT-induced PAH, PA wall thickening, and RVH by enhancing eNOS and suppressing ET-1/ROCKII expression. In vitro, KMUP-1 inhibited ET-1-induced PA constriction and ET-1-dependent/independent RhoA activation of PASMCs. In summary, KMUP-1 attenuates ET-1-induced/ET-1-mediated PA constriction, and could thus aid in

  20. Preferential recruitment of neutrophils by endothelin-1 in acute lung inflammation induced by lipopolysaccharide or cigarette smoke

    Directory of Open Access Journals (Sweden)

    Tapan Bhavsar

    2008-10-01

    Full Text Available Tapan Bhavsar, Xing Jian Liu, Hardik Patel, Ralph Stephani, Jerome O CantorSt John’s University, School of Pharmacy and Allied Health Sciences, New York, USAAbstract: This study examined the role of endothelin-1 (ET-1 in recruiting inflammatory cells to the lung after induction of injury with either lipopolysaccharide (LPS or cigarette smoke. Hamsters injected with either ET-1 or its precursor peptide (Big ET-1 prior to treatment with LPS or cigarette smoke had markedly increased concentrations of neutrophils in bronchoalveolar lavage fluid (BALF despite a reduction in total numbers of BALF leukocytes. Furthermore, the effect of ET-1 on smoke-exposed animals was reversed by addition of an endothelin-A receptor antagonist. These results are consistent with preferential recruitment of neutrophils by ET-1, and suggest that inhibition of this proinfl ammatory mediator may decrease acute pulmonary inflammation associated with cigarette smoke and other pulmonary toxins.Keywords: endothelin, lipopolysaccahride, cigarette smoke, neutrophils, lung

  1. Selective endothelin-1 receptor type A inhibition in subjects undergoing cardiac surgery with preexisting left ventricular dysfunction: Influence on early postoperative hemodynamics.

    Science.gov (United States)

    Toole, John M; Ikonomidis, John S; Szeto, Wilson Y; Zellner, James L; Mulcahy, John; Deardorff, Rachael L; Spinale, Francis G

    2010-03-01

    A robust release of endothelin-1 with subsequent endothelin-A subtype receptor activation occurs in patients after cardiac surgery requiring cardiopulmonary bypass. Increased endothelin-A subtype receptor activation has been identified in patients with poor left ventricular function (reduced ejection fraction). Accordingly, this study tested the hypothesis that a selective endothelin-A subtype receptor antagonist administered perioperatively would favorably affect post-cardiopulmonary bypass hemodynamic profiles in patients with a preexisting poor left ventricular ejection fraction. Patients (n = 29; 66 +/- 2 years) with a reduced left ventricular ejection fraction (37% +/- 2%) were prospectively randomized in a blinded fashion, at the time of elective coronary revascularization or valve replacement requiring cardiopulmonary bypass, to infusion of the highly selective and potent endothelin-A subtype receptor antagonist sitaxsentan at 1 or 2 mg/kg (intravenous bolus; n = 9, 10 respectively) or vehicle (saline; n = 10). Infusion of the endothelin-A subtype receptor antagonist/vehicle was performed immediately before separation from cardiopulmonary bypass and again at 12 hours after cardiopulmonary bypass. Endothelin and hemodynamic measurements were performed at baseline, at separation from cardiopulmonary bypass (time 0), and at 0.5, 6, 12, and 24 hours after cardiopulmonary bypass. Baseline plasma endothelin (4.0 +/- 0.3 fmol/mL) was identical across all 3 groups, but when compared with preoperative values, baseline values obtained from age-matched subjects with a normal left ventricular ejection fraction (n = 37; left ventricular ejection fraction > 50%) were significantly increased (2.9 +/- 0.2 fmol/mL, P time 0, systemic vascular resistance changed in an equivalent fashion in the post-cardiopulmonary bypass period, but a significant endothelin-A subtype receptor antagonist effect was observed for pulmonary vascular resistance (analysis of variance; P < .05). For

  2. The relations between lower and higher level comprehension skills and their role in prediction of early reading comprehension

    OpenAIRE

    Silva, Macarena; Cain, Kate

    2015-01-01

    This study of 4- to 6-year-olds had two aims. First to determine how lower-level comprehension skills (receptive vocabulary and grammar) and verbal memory support early higher-level comprehension skills (inference and literal story comprehension). Second to establish the predictive power of these skills on subsequent reading comprehension. Eighty-two children completed assessments of nonverbal ability, receptive vocabulary and grammar, verbal short-term memory, and inferential and literal com...

  3. Two-dimensional Yang-Mills theory: perturbative and instanton contributions, and its relation to QCD in higher dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Bassetto, A

    2000-06-01

    Two different scenarios (light-front and equal-time) are possible for Yang-Mills theories in two dimensions. The exact q-barq-potential can be derived in perturbation theory starting from the light-front vacuum, but requires essential instanton contributions in the equal-time formulation. In higher dimensions no exact result is available and, paradoxically, only the latter formulation (equal-time) is acceptable, at least in a perturbative context.

  4. Higher glucose level can enhance the H. pylori adhesion and virulence related with type IV secretion system in AGS cells.

    Science.gov (United States)

    Sheu, Shew-Meei; Cheng, Hsin; Kao, Cheng-Ye; Yang, Yao-Jong; Wu, Jiunn-Jong; Sheu, Bor-Shyang

    2014-10-09

    Hyperglycemia increases the risk of gastric cancer in H. pylori-infected patients. High glucose could increase endothelial permeability and cancer-associated signaling. These suggest high glucose may affect H. pylori or its infected status.We used two strains to investigate whether H. pylori growth, viability, adhesion and CagA-phosphorylation level in the infected-AGS cells were influenced by glucose concentration (100, 150, and 200 mg/dL). The growth curves of both strains in 200 mg/dL of glucose were maintained at the highest optimal density after 48 h and the best viability of both strains were retained in the same glucose condition at 72 h. Furthermore, adhesion enhancement of H. pylori was significantly higher in 200 mg/dL of glucose as compared to that in 100 and 150 mg/dL (p H. pylori growth and viability after 48 h. H. pylori adhesion and CagA increased to further facilitate the enhancement of cell-associated CagA and phosphorylated CagA in higher glucose conditions.

  5. CPU 86017, p-chlorobenzyltetrahydroberberine chloride, attenuates monocrotaline-induced pulmonary hypertension by suppressing endothelin pathway.

    Science.gov (United States)

    Zhang, Tian-tai; Cui, Bing; Dai, De-zai; Su, Wei

    2005-11-01

    To elucidate the involvement of the endothelin (ET) pathway in the pathogenesis of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and the therapeutic effect of CPU 86017 (p-chlorobenzyltetrahydroberberine chloride) in rats. Rats were injected with a single dose (60 mg/kg, sc) of MCT and given CPU 86017 (20, 40, and 80 mg/kg-1/d-1, po) or saline for 28 d. The hemodynamics, mRNA expression, and vascular activity were evaluated. Right ventricular systolic pressure and central venous pressures were elevated markedly in the PAH model and decreased by CPU 86017. In the PAH group, the endothelin-1 (ET-1) in serum and lungs was dramatically increased by 54% (79.9 pg/mL, PCPU 86017 decreased the content of ET-1 to the normal level in lung tissue, but was less effective in serum. The level of NO was significantly increased in CPU 86017 at 80 and 40 mg/kg-1/d-1 groups in tissue, whereas the difference in serum was not significant. A significant reduction in MDA production and an increase in the SOD activity in the serum and lungs was observed in all three CPU 86017 groups. CPU 86017 80 mg/kg-1/d-1 po increased the activity of cNOS by 33% (PCPU 86017 groups, and preproET-1 mRNA abundance was also reduced notably in CPU 86017 80 mg/kg-1/d-1 group vs the PAH group. The KCl-induced vasoconstrictions in the calcium-free medium decreased markedly in PAH group but recovered partially after CPU 86017 intervention. The constrictions in the presence of Ca(2+) was not improved by CPU 86017. The phenylephrine-induced vasoconstrictions in the calcium-free medium decreased markedly in PAH group but not recovered after CPU 86017 intervention. The constrictions in the presence of Ca(2+) completely returned to the normal after CPU 86017 intervention. CPU 86017 suppressed MCT-induced PAH mainly through an indirect suppression of the ET-1 system, which was involved in the pathogenesis of the disease.

  6. Higher refusal rates for organ donation among older potential donors in the Netherlands: impact of the donor register and relatives.

    NARCIS (Netherlands)

    Leiden, H.A. van; Jansen, N.E.; Haase-Kromwijk, B.J.; Hoitsma, A.J.

    2010-01-01

    BACKGROUND: The availability of donor organs is considerably reduced by relatives refusing donation after death. There is no previous large-scale evaluation of the influence of the Donor Register (DR) consultation and the potential donor's age on this refusal in The Netherlands. METHODS: This study

  7. Does a reduction in alcohol use by Dutch high school students relate to higher use of tobacco and cannabis?

    NARCIS (Netherlands)

    C.E. Verhagen (Claudia E.); D. Uitenbroek (Daan); E.J. Schreuders (Emilie J.); S. El Messaoudi (Sabah); M.L.A. De Kroon (Marlou L.A.)

    2015-01-01

    textabstractBackground: Substance use of adolescents was investigated in a region around Amsterdam, the Netherlands, in the period 2005-2009. The study was intended to find out to what extent behaviour related to different substances are interrelated and how trends develop in different subgroups.

  8. Educational Technology-Related Performance of Teaching Faculty in Higher Education: Implications for eLearning Management

    Science.gov (United States)

    Larbi-Apau, Josephine A.; Guerra-Lopez, Ingrid; Moseley, James L.; Spannaus, Timothy; Yaprak, Attila

    2017-01-01

    The study examined teaching faculty's educational technology-related performances (ETRP) as a measure for predicting eLearning management in Ghana. A total of valid data (n = 164) were collected and analyzed on applied ISTE-NETS-T Performance Standards using descriptive and ANOVA statistics. Results showed an overall moderate performance with the…

  9. Does a reduction in alcohol use by Dutch high school students relate to higher use of tobacco and cannabis?

    NARCIS (Netherlands)

    Verhagen, Claudia E.; Uitenbroek, Daan G.; Schreuders, Emilie J.; El Messaoudi, Sabah; de Kroon, Marlou L. A.

    2015-01-01

    Background: Substance use of adolescents was investigated in a region around Amsterdam, the Netherlands, in the period 2005-2009. The study was intended to find out to what extent behaviour related to different substances are interrelated and how trends develop in different subgroups. Methods: Two

  10. Do new production concepts and a new management of employment relations, yield higher employee performance and low job strain?

    NARCIS (Netherlands)

    Kraan, K.; Oeij, P.

    2006-01-01

    In this article old versus new production concepts (NPCs) and employment relation instruments, are studied, separately and in combination, to find out which yield high employee performance and low job strain. Therefore, in 2005, TNO conducted coupled surveys among 149 supervisors and employees. In

  11. Strategic Planning, Marketing & Public Relations, and Fund-Raising in Higher Education: Perspectives, Readings, and Annotated Bibliography.

    Science.gov (United States)

    Ryans, Cynthia C.; Shanklin, William L.

    Perspectives on college and university strategic planning, marketing and public relations, and fund-raising are offered. Also included are previously published journal articles by experts in this area, annotated bibliographies of books and journal articles on these subjects, author/title and subject indexes, and a directory of publishers. Three…

  12. Higher language ability is related to angular gyrus activation increase during semantic processing, independent of sentence incongruency

    Directory of Open Access Journals (Sweden)

    Helene eVan Ettinger-Veenstra

    2016-03-01

    Full Text Available This study investigates the relation between individual language ability and neural semantic processing abilities. Our aim was to explore whether high-level language ability would correlate to decreased activation in language-specific regions or rather increased activation in supporting language regions during processing of sentences. Moreover, we were interested if observed neural activation patterns are modulated by semantic incongruency similarly to previously observed changes upon syntactic congruency modulation. We investigated 27 healthy adults with a sentence reading task - which tapped language comprehension and inference, and modulated sentence congruency - employing functional magnetic resonance imaging. We assessed the relation between neural activation, congruency modulation, and test performance on a high-level language ability assessment with multiple regression analysis. Our results showed increased activation in the left-hemispheric angular gyrus extending to the temporal lobe related to high language ability. This effect was independent of semantic congruency, and no significant relation between language ability and incongruency modulation was observed. Furthermore, a significant increase of activation in the inferior frontal gyrus bilaterally when the sentences were incongruent, indicating that processing incongruent sentences was more demanding than processing congruent sentences and required increased activation in language regions. The correlation of high-level language ability with increased rather than decreased activation in the left angular gyrus, a region specific for language processing is opposed to what the neural efficiency hypothesis would predict. We can conclude that there is no evidence found for an interaction between semantic congruency related brain activation and high-level language performance, even though the semantic incongruent condition shows to be more demanding and evoking more neural activation.

  13. Involvement of organic anion transporting polypeptide 1a5 (Oatp1a5) in the intestinal absorption of endothelin receptor antagonist in rats

    DEFF Research Database (Denmark)

    Tani, Takeshi; Gram, Luise K; Arakawa, Hiroshi

    2008-01-01

    PURPOSE: To assess the contribution of organic anion transporting polypeptide 1a5 (Oatp1a5/Oatp3) in the intestinal absorption of an orally active endothelin receptor antagonist, (+)-(5S,6R,7R)-2-butyl-7-[2-((2S)-2-carboxypropyl)-4-methoxyphenyl]-5-(3,4-methylene-dioxyphenyl)cyclopenteno[1,2-b......]pyridine-6-carboxylic acid (compound-A) in rats. METHODS: Uptakes of [(14)C]compound-A by Oatp1a5-expressing Xenopus laevis oocytes and isolated rat enterocytes were evaluated. RESULTS: The uptake of compound-A by Oatp1a5-expressing oocytes was significantly higher than that by water-injected oocytes...... and Oatp1a5-mediated uptake was saturable with K(m) value of 116 microM. Compound-A was taken up into isolated enterocytes in time- and concentration-dependent manners and the estimated K(m) value was 83 microM, which was close to that for the Oatpt1a5-mediated uptake in oocytes. Both uptakes of compound...

  14. Does Prison Crowding Predict Higher Rates of Substance Use Related Parole Violations? A Recurrent Events Multi-Level Survival Analysis.

    Science.gov (United States)

    Ruderman, Michael A; Wilson, Deirdra F; Reid, Savanna

    2015-01-01

    This administrative data-linkage cohort study examines the association between prison crowding and the rate of post-release parole violations in a random sample of prisoners released with parole conditions in California, for an observation period of two years (January 2003 through December 2004). Crowding overextends prison resources needed to adequately protect inmates and provide drug rehabilitation services. Violence and lack of access to treatment are known risk factors for drug use and substance use disorders. These and other psychosocial effects of crowding may lead to higher rates of recidivism in California parolees. Rates of parole violation for parolees exposed to high and medium levels of prison crowding were compared to parolees with low prison crowding exposure. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox model for recurrent events. Our dataset included 13070 parolees in California, combining individual level parolee data with aggregate level crowding data for multilevel analysis. Comparing parolees exposed to high crowding with those exposed to low crowding, the effect sizes from greatest to least were absconding violations (HR 3.56 95% CI: 3.05-4.17), drug violations (HR 2.44 95% CI: 2.00-2.98), non-violent violations (HR 2.14 95% CI: 1.73-2.64), violent and serious violations (HR 1.88 95% CI: 1.45-2.43), and technical violations (HR 1.86 95% CI: 1.37-2.53). Prison crowding predicted higher rates of parole violations after release from prison. The effect was magnitude-dependent and particularly strong for drug charges. Further research into whether adverse prison experiences, such as crowding, are associated with recidivism and drug use in particular may be warranted.

  15. Torsional resonance mode magnetic force microscopy: enabling higher lateral resolution magnetic imaging without topography-related effects.

    Science.gov (United States)

    Kaidatzis, A; García-Martín, J M

    2013-04-26

    We present experimental work that reveals the benefits of performing magnetic force microscopy measurements employing the torsional resonance mode of cantilever oscillation. This approach provides two clear advantages: the ability of performing magnetic imaging without topography-related interference and the significant lateral resolution improvement (approximately 15%). We believe that this work demonstrates a significant improvement to a versatile magnetic imaging technique widely used in academia and in industry.

  16. [Elevated expression of endothelin 2 in lung tissues of asthmatic rats after exposed to cigarette smoke and its mechanism].

    Science.gov (United States)

    Han, Fangfang; Zhu, Shuyang; Chen, Bi; Li, Jingjing

    2017-08-01

    Objective To study the effect of cigarette smoke exposure on the expression of endothelin 2 (ET-2) in bronchial epithelium of asthmatic rats. Methods Asthma models were established through intraperitoneal injection of 1 mL chicken ovalbumin (OVA)/Al(OH)3 mixture (asthma model group, n=6); based on the asthma models, exposure to smoking gas lasted four weeks with 10 cigarettes per day (smoke-exposed asthma group, n=6); based on the smoke-exposed asthma models, the rats were treated with intraperitoneal injection of dexamethasone 2 mg/(kg.d), intragastric administration of ET receptor inhibitor bosentan 100 mg/(kg.d) and combined use, respectively named dexamethasone treated group, bosentan treated group, and dexamethasone-bosentan treated group, 6 rats in every group. What's more, other 6 rats were only subjected to intraperitoneal injection of 1 mL normal saline as normal controls; in addition to the injection of saline, cigarette smoke control group (n=6) was set up by the exposure to smoking gas for four weeks with 10 cigarettes per day. Bronchoalveolar lavage fluid (BALF) was collected from the upper lobe of the left lung for cell counting and classification. Pathological changes of the right upper lung lobe tissues were observed by HE staining. In other lung tissues, the expression of JNK1/2 was detected by Western blotting; ET-2 was tested by Western blotting and immunohistochemistry; thiobarbituric acid reactive substances (TBARS) assay and trace enzyme standard method were used to measure malondialdehyde (MDA) and glutathione (GSH), respectively. Results Compared with normal control group, the number of airway inflammation cells increased in the BALF, and the expressions of ET-2, JNK1/2, MDA and GSH increased in the lung tissues of cigarette smoke control group, asthma model group and cigarette smoke-exposed asthma group. Compared with cigarette smoke-exposed asthma group, the number of airway inflammation cells decreased in the BALF, and the expressions of

  17. A zebrafish screen for craniofacial mutants identifies wdr68 as a highly conserved gene required for endothelin-1 expression

    Directory of Open Access Journals (Sweden)

    Amsterdam Adam

    2006-06-01

    Full Text Available Abstract Background Craniofacial birth defects result from defects in cranial neural crest (NC patterning and morphogenesis. The vertebrate craniofacial skeleton is derived from cranial NC cells and the patterning of these cells occurs within the pharyngeal arches. Substantial efforts have led to the identification of several genes required for craniofacial skeletal development such as the endothelin-1 (edn1 signaling pathway that is required for lower jaw formation. However, many essential genes required for craniofacial development remain to be identified. Results Through screening a collection of insertional zebrafish mutants containing approximately 25% of the genes essential for embryonic development, we present the identification of 15 essential genes that are required for craniofacial development. We identified 3 genes required for hyomandibular development. We also identified zebrafish models for Campomelic Dysplasia and Ehlers-Danlos syndrome. To further demonstrate the utility of this method, we include a characterization of the wdr68 gene. We show that wdr68 acts upstream of the edn1 pathway and is also required for formation of the upper jaw equivalent, the palatoquadrate. We also present evidence that the level of wdr68 activity required for edn1 pathway function differs between the 1st and 2nd arches. Wdr68 interacts with two minibrain-related kinases, Dyrk1a and Dyrk1b, required for embryonic growth and myotube differentiation, respectively. We show that a GFP-Wdr68 fusion protein localizes to the nucleus with Dyrk1a in contrast to an engineered loss of function mutation Wdr68-T284F that no longer accumulated in the cell nucleus and failed to rescue wdr68 mutant animals. Wdr68 homologs appear to exist in all eukaryotic genomes. Notably, we found that the Drosophila wdr68 homolog CG14614 could substitute for the vertebrate wdr68 gene even though insects lack the NC cell lineage. Conclusion This work represents a systematic

  18. Women's higher risk with N-6 PUFA vs. men's relative advantage: an "N-6 gender nutrition paradox" hypothesis.

    Science.gov (United States)

    Shapira, Niva

    2012-07-01

    The "Israeli Paradox" (1996) of low national health rankings despite adequate diet - attributed to high dietary n-6 polyunsaturated fatty acids (PUFA) - coincided with long-observed dichotomies between women's worse international status vs. men's advantage. This raised the possibility of a gender link to high n-6 risk potentially explaining both national phenomena. Israeli women's disadvantage was shown by worse international rankings, i.e., life expectancy (LE)--11th vs. men's 3rd-best/22 countries (2000), and 14th vs. 6th/34 (2010); and all-cause and all-cancer mortality--both 15th vs. 2nd-best/22 (2000), and 15th vs. 6th/22 and 12th vs. 2nd-best/22 (2010). Cancer mortality rates for breast were 21.8% above vs. prostate 30.4% below Eur-A (27 country) averages (2005). Gender gaps/ ratios were smaller than European Union-15 averages, i.e., for LE at birth by 34.4-26.4% (2000-2010), respectively, and at 65 years 45.9-35.3%; all-cause mortality by 43.3-33.4%, and all-cancer 65.2-58.7%. The Israeli diet was mostly close to guidelines, but n-6 intake (10-12% kcal) was much higher than recommended and traditional "Mediterranean diet" levels. Research showing females' greater potential for conversion of PUFA to long-chain PUFA (LCPUFA) may suggest increased production of n-6 eicosanoids with known proinflammatory/oxidative/carcinogenic potential. An "Israeli N-6 Gender Nutrition Paradox" hypothesis is suggested here for the first time, associating women's higher risk and lead in the national "paradox" with greater potential for n-6 conversion to pro-inflammatory/oxidative/carcinogenic eicosanoids compared to men. This may also exacerbate women's risk associated with genetic predisposition (i.e., BRCA) and/or sociopolitical stress. Global abandonment of traditional diets/foods together with increasing n-6 consumption and western disease rates emphasize the importance of considering gender nutrition in epidemiology and preventive strategies.

  19. Effects of CPU 86017 (chlorobenzyltetrahydroberberine chloride) and its enantiomers on thyrotoxicosis-induced overactive endothelin-1 system and oxidative stress in rat testes.

    Science.gov (United States)

    Tang, XiaoYun; Qi, MinYou; Dai, DeZai; Zhang, Can

    2006-08-01

    To study the effects of CPU 86017, a berberine derivative, and its four enantiomers on thyrotoxicosis-induced oxidative stress and the excessive endothelin-1 system in rat testes. Adult male SD rats were given high-dose L-thyroxin (0.2 mg/kg subcutaneously) once daily for 10 days to develop thyrotoxicosis. Subsets of the rats were treated with CPU 86017 or its four enantiomers (SR, SS, RS, and RR) once daily from day 6 to day 10. The alterations of redox, nitric oxide synthase, and endothelin-1 system in testes were examined by spectrophotometry and reverse transcriptase-polymerase chain reaction assay. After 10 days of high-dose L-thyroxin administration, increased mRNA expression of prepro-endothelin-1 and endothelin-converting enzyme was observed in the rat testes, accompanied by an elevated inducible nitric oxide synthase activity and oxidative stress. CPU 86017 and its enantiomer SR significantly improved these abnormalities. High-dose L-thyroxin results in an overactive endothelin-1 system and oxidative stress in adult rat testis. CPU 86017 and its enantiomer SR suppressed the excessive ET-1 system by improving oxidative stress, and SR exhibited more potent efficacy than CPU 86017 and other enantiomers.

  20. Severity of anxiety and depression are related to a higher perception of adverse effects of antiepileptic drugs.

    Science.gov (United States)

    Gómez-Arias, Bety; Crail-Meléndez, Daniel; López-Zapata, Rosario; Martínez-Juárez, Iris E

    2012-10-01

    After reviewing the negative effects of antiepileptic drugs (AEDs) on general health and quality of life, the Commission on Outcome Measurement from the International League Against Epilepsy (ILAE) recommended incorporating reliable and valid tools in clinical essays in order to achieve a more accurate assessment of the subjective adverse effects rate and disease severity when using AEDs. The aim of this study was to correlate the severity of adverse effects of AEDs, with the presence of anxiety and depression in patients with epilepsy. The Spanish version of the Liverpool Adverse Events Profile (LAEP) and the hospital anxiety and depression scale (HADS) were applied on 130 consecutive outpatients with epilepsy from the epilepsy clinic at the Mexico's National Institute of Neurology and Neurosurgery. A correlation analysis was carried out to determine if the presence of depression and anxiety was related to the adverse effects of AEDs. The relation between LAEP scores with other epidemiological variables was also assessed. Our study found a positive correlation between the LAEP and the HADS scores (p anxiety and depression in patients with epilepsy. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  1. Targeting endothelin-1 receptor/β-arrestin1 network for the treatment of ovarian cancer.

    Science.gov (United States)

    Rosanò, Laura; Cianfrocca, Roberta; Sestito, Rosanna; Tocci, Piera; Di Castro, Valeriana; Bagnato, Anna

    2017-10-01

    Endothelin-1 receptor (ET-1R)/β-arrestin1 (β-arr1) signaling is dysregulated in ovarian cancer. This signaling circuit enables cancer cells to engage several signaling and transcriptional networks that are pervasively intertwined, and represent a potential therapeutic target for developing novel agents for ovarian cancer treatment. Areas covered: In this article, we discuss the role of the signaling network between ET-1R and key pathways mediated by the scaffold protein β-arr1, as part of signaling complex, or as a transcription co-activator, promoting precise control of transcription of different genes, including ET-1. Therefore ET-1R/β-arr1 is an actionable node involved in the activation of a persistent feedback loop that contributes to bypass signaling. Targeting ET-1R empowering this circuit can represent a necessary measure to reach clinical efficacy. Preclinical studies demonstrate that blocking ET-1R by FDA approved dual ETAR/ETBR antagonist prevents β-arr1 network formation, offering a novel therapeutic strategy in ovarian cancer patients. Expert opinion: The information provided in this review about the ET-1R/β-arr1 hub represents an invaluable tool for both identifying the interconnected pathways involved in ovarian cancer and targeting them more effectively. The new perspective arising from ET-1R therapeutics will likely prompt a valuable frame for the design of new promising combinatorial therapy, blocking compensatory networks.

  2. Interlimb Dynamic after Unilateral Focal Lesion of the Cervical Dorsal Corticospinal Tract with Endothelin-1

    Directory of Open Access Journals (Sweden)

    Walther A. Carvalho

    2017-10-01

    Full Text Available Handedness is one of the most recognized lateralized behavior in humans. Usually, it is associated with manual superiority regarding performance proficiency. For instance, more than 90% of the human population is considered more skilled with the right hand, which is controlled by the left hemisphere, than with the left. However, during the performance of bimanual tasks, the two hands usually assume asymmetric roles, with one hand acting on objects while the other provides support, stabilizing the object. Traditionally, the role of the two hands is viewed as fixed. However, several studies support an alternate view with flexible assignments for the two hands depending on the task. The supporting role of the hand depends on a closed loop pathway based on proprioceptive inputs from the periphery. The circuit’s efferent arm courses through the dorsal corticospinal tract (dCST in rodents and terminate on spinal cord interneurons which modulate the excitability of motoneurons in the ventral horn. In the present work, we developed an experimental model of unilateral lesion targeting the cervical dCST with microinjections of the vasoconstrictor endothelin-1 (ET-1 to evaluate the degree of flexibility of forelimb assignment during a food manipulation task. Our results show that just 3 days after unilateral corticospinal tract (CST injury in the cervical region, rats display severe motor impairment of the ipsilateral forepaw together with a remarkable reversal of motor assignment between the forelimbs.

  3. The Matrix Metalloproteases and Endothelin-1 in Infection-Associated Preterm Birth

    Directory of Open Access Journals (Sweden)

    Nicole S. Olgun

    2010-01-01

    Full Text Available Preterm birth (PTB is clinically defined as any delivery which occurs before the completion of 37 weeks of gestation, and is currently the most important problem in obstetrics. In the United States, PTB accounts for 12-13% of all live births, and, with the exception of fetuses suffering from anomalies, is the primary cause of perinatal mortality. While the risk factors for PTB are numerous, the single most common cause is intrauterine infection. As there is currently no FDA-approved therapy for infection-associated PTB, understanding the pathogenesis of preterm labor (PTL and delivery should be given high priority. The matrix metalloproteinases (MMPs are a family of enzymes that have been implicated in normal parturition as well as infection-triggered rupture of membranes and preterm birth. Several lines of evidence also suggest a role for endothelin-1 (ET-1 in infection-associated preterm delivery. This paper focuses on the evidence that the MMPs and ET-1 act in the same molecular pathway in preterm birth.

  4. [Endothelin-1 receptors of the normal adrenal gland and adrenal tumors in human].

    Science.gov (United States)

    Tang, X; Zeng, Z; Zhang, R

    1996-07-01

    Endothelin-1 (ET-1) receptors of normal adrenal gland (ADR, 6 cases), aldosterone-producing adenoma (APA, 5 cases), idiopathic hyperaldosteronism (IHA, 4 cases) and pheochromocytoma (PHE, 6 cases) in human were measured by radioligand binding assay (RBA) of receptors. Binding studies using 125I-ET-1 as a radio ligand showed the presence of a single class of high-affinity binding sites for ET-1 in all of the above tissues. The values of dissociation constant (Kd) of ET-1 for its receptor were similar in ADR, APA and IHA (28.3 +/- 2.5, 27.9 +/- 6.1, 27.7 +/- 1.9 pmol/L, respectively), but the maximal binding capacity (Bmax) of ET receptor tended to be lower in APA tissue (107.2 +/- 13.2 fmol/mg protein) in comparison with ADR (P role of ET-1 in the paracrine-autocrine regulation of aldosterone and catecholamine secretion in the adrenal and adrenal tumors.

  5. Comparative effects of endothelin and phorbol 12-13 dibutyrate in rat aorta

    Energy Technology Data Exchange (ETDEWEB)

    Auguet, M.; Delaflotte, S.; Chabrier, P.E.; Braquet, P. (Institut Henri Beaufour Research Labs., Cedex (France))

    1989-01-01

    The vasoconstrictive properties of endothelin (ET-1) and the protein kinase C activator, phorbol 12-13 dibutyrate (PDB) were comparatively investigated in isolated rat aorta. ET-1 and PDB induced a slowly developing sustained contraction in endothelium denuded aorta. Maximal contractions induced by ET-1 and PDB were unaffected by diltiazem. Substantial contraction to ET-1 and PDB remained in calcium-free medium. Contractions of ET-1 and PDB in calcium-free medium were unaffected by intracellular calcium depletion induced by phenylephrine. Following the response to ET-1 and PDB in a calcium-free medium, an additional sustained was observed after calcium was added to the bath. The protein kinase C inhibitor, H7 was more potent in inhibiting contractions induced by phenylephrine and KCl than the ones elicited by ET-1 and PDB. The other protein kinase C inhibitors i.e. staurosporine and phloretin inhibited to a similar extent all the agonists tested. These results suggest that protein kinase C may play an important role in mediating the contraction to ET-1 in rat aorta.

  6. Common mechanism in endothelin-3 and PAF receptor function for anti-inflammatory responses.

    Science.gov (United States)

    Sato, Akira; Ebina, Keiichi

    2013-10-15

    Platelet-activating factor (PAF) is a potent lipid mediator that is implicated in numerous inflammatory diseases. Under inflammatory conditions, PAF is biosynthesized through the remodelling pathway and elicits many inflammatory responses through binding to its specific PAF receptor. Endogenous bioactive endothelins (ETs: ET-1, -2, and -3) are also considered potent inflammatory mediators that play a critical role in many inflammatory diseases. In this perspective, we provide a brief overview of possible common mechanisms in ETs and PAF receptor function for inflammatory responses. Accumulating evidence strongly suggests that ET-3, but not ET-1 and ET-2, can attenuate PAF-induced inflammation through direct binding of the Tyr-Lys-Asp (YKD) region in the peptide to PAF and its metabolite/precursor lyso-PAF, followed by inhibition of binding between PAF and its receptor. Additionally, YKD sequence-containing peptides may be useful as a novel type of anti-inflammatory drugs targeting this mechanism. These findings should lead to new treatment strategies for numerous inflammatory diseases by targeting the common mechanism in ET and PAF receptor function. © 2013 Elsevier B.V. All rights reserved.

  7. NO and prostanoids blunt endothelin-mediated coronary vasoconstrictor influence in exercising swine.

    Science.gov (United States)

    Merkus, Daphne; Sorop, Oana; Houweling, Birgit; Boomsma, Frans; van den Meiracker, Anton H; Duncker, Dirk J

    2006-11-01

    Withdrawal of the endothelin (ET)-mediated vasoconstrictor influence contributes to metabolic coronary vasodilation during exercise. Because production of nitric oxide (NO) and prostanoids increases with increasing shear stress and because NO and prostanoids are able to modify the release of ET, we hypothesized that the withdrawal of ET-mediated coronary vasoconstriction during exercise is mediated through NO and/or prostanoids. To test this hypothesis, 19 chronically instrumented swine were studied at rest and while running on a treadmill up to 85-90% of maximal heart rate. Blockade of ET(A)/ET(B) receptors with tezosentan resulted in an increase in coronary venous O(2) levels (i.e., in coronary vasodilation) at rest, which waned at increasing levels of exercise intensity. Inhibition of either NO synthase [N(omega)-nitro-l-arginine (l-NNA)] or cyclooxygenase (indomethacin) did not affect the response to tezosentan under resting conditions but unmasked a vasodilator response to tezosentan during exercise. The vasodilator response to tezosentan during exercise increased progressively after combined administration of l-NNA and indomethacin. These findings suggest that NO and prostanoids act synergistically to inhibit the vasoconstrictor influence of ET on the coronary circulation during exercise, thereby facilitating the exercise-induced vasodilation of coronary resistance vessels.

  8. Endothelin-1 Regulation of Exercise-Induced Changes in Flow: Dynamic Regulation of Vascular Tone

    Directory of Open Access Journals (Sweden)

    Robert M. Rapoport

    2017-10-01

    Full Text Available Although endothelin (ET-1 is a highly potent vasoconstrictor with considerable efficacy in numerous vascular beds, the role of endogenous ET-1 in the regulation of vascular tone remains unclear. The perspective that ET-1 plays little role in the on-going regulation of vascular tone at least under physiologic conditions is supported by findings that potential ET-1 constriction is minimized by the release of the vasodilator and ET-1 synthesis inhibitor, nitric oxide (NO. Indeed, ET-1 release and constriction is self-limited by ET-1-induced, endothelial ETB receptor-mediated release of NO. Moreover, even if the balance between ET-1 and NO were reversed as the result of lowered NO activity, as occurs in a number of pathophysiologies associated with endothelial dysfunction, the well-known resistance of ET-1 constriction to reversal (as determined with exogenous ET-1 precludes ET-1 in the dynamic, i.e., moment-to-moment, regulation of vascular tone. On the other hand, and as presently reviewed, findings of ET-1-dependent modulation of organ blood flow with exercise under physiologic conditions demonstrate the dynamic regulation of vascular tone by ET-1. We speculate that this regulation is mediated at least in part through changes in ET-1 synthesis/release caused by pulsatile flow-induced shear stress and NO.

  9. Prognostic significance of elevated endothelin-1 levels in patients with colorectal cancer.

    Science.gov (United States)

    Arun, C; London, N J M; Hemingway, D M

    2004-01-01

    Prognostic factors from clinical, laboratory and pathological data of patients with colorectal cancer are essential to identify high-risk groups to whom beneficial adjuvant therapy could be given. Endothelin-1, a growth factor, has been associated with the development and spread of solid tumours. This prospective study was performed to determine whether preoperative plasma big ET-1 levels might be useful as a prognostic indicator in patients with colorectal carcinoma. Sixty-five consecutive patients with colorectal cancer confirmed by biopsy were included prospectively into this study over a 12-month period. Plasma samples from a peripheral vein were obtained prior to surgery. Univariate analysis of survival using age ( 70 years), sex, Dukes' stage (A&B versus C), tumour size ( 50 mm), vascular invasion and plasma big ET-1 levels was performed and significant factors were then analysed with the Cox regression model. Three variables, age, Dukes' tumour stage and plasma big ET-1 levels, were found to have prognostic significance (p70 years (p=0.02), Dukes' C tumours (p=0.04) and plasma big ET-1 levels >4.2 pg/mL (p=0.02). The Cox regression model identified the same three variables as having independent prognostic value for overall survival. Preoperative plasma big ET-1 levels may be useful in predicting overall survival in patients with colorectal cancer. Plasma big ET-1 levels may be useful in the selection of high-risk lymph node-negative patients with colorectal cancer for adjuvant therapy.

  10. A Complex Genomic Rearrangement Involving the Endothelin 3 Locus Causes Dermal Hyperpigmentation in the Chicken

    Science.gov (United States)

    Dorshorst, Ben; Molin, Anna-Maja; Rubin, Carl-Johan; Johansson, Anna M.; Strömstedt, Lina; Pham, Manh-Hung; Chen, Chih-Feng; Hallböök, Finn; Ashwell, Chris; Andersson, Leif

    2011-01-01

    Dermal hyperpigmentation or Fibromelanosis (FM) is one of the few examples of skin pigmentation phenotypes in the chicken, where most other pigmentation variants influence feather color and patterning. The Silkie chicken is the most widespread and well-studied breed displaying this phenotype. The presence of the dominant FM allele results in extensive pigmentation of the dermal layer of skin and the majority of internal connective tissue. Here we identify the causal mutation of FM as an inverted duplication and junction of two genomic regions separated by more than 400 kb in wild-type individuals. One of these duplicated regions contains endothelin 3 (EDN3), a gene with a known role in promoting melanoblast proliferation. We show that EDN3 expression is increased in the developing Silkie embryo during the time in which melanoblasts are migrating, and elevated levels of expression are maintained in the adult skin tissue. We have examined four different chicken breeds from both Asia and Europe displaying dermal hyperpigmentation and conclude that the same structural variant underlies this phenotype in all chicken breeds. This complex genomic rearrangement causing a specific monogenic trait in the chicken illustrates how novel mutations with major phenotypic effects have been reused during breed formation in domestic animals. PMID:22216010

  11. Candesartan pretreatment is cerebroprotective in a rat model of endothelin-1-induced middle cerebral artery occlusion

    Science.gov (United States)

    Mecca, Adam P.; O’Connor, Timothy E.; Katovich, Michael J.; Sumners, Colin

    2009-01-01

    Endogenous levels of angiotensin II (Ang II) are increased in the cortex and hypothalamus following stroke, and Ang II type 1 receptor blockers (ARBs) have been shown to attenuate the deleterious effects in animal stroke models using middle cerebral artery (MCA) intraluminal occlusion procedures. However, the endothelin-1 (ET-1)-induced middle cerebral artery occlusion (MCAO) model of cerebral ischaemia is thought to more closely mimic the temporal events of an embolic stroke. This method provides rapid occlusion of the MCA and a gradual reperfusion that lasts for 16–22 h. The aim of the present study was to evaluate whether systemic administration of an ARB prior to ET-1-induced MCAO would provide cerebroprotection during this model of ischaemic stroke. Injection of 3 μl of 80 μm ET-1 adjacent to the MCA resulted in complete occlusion of the vessel that resolved over a period of 30–40 min. Following ET-1-induced MCAO, rats had significant neurological impairment, as well as an infarct that consisted of 30% of the ipsilateral grey matter. Systemic pretreatment with 0.2 mg kg−1 day−1 candesartan for 7 days attenuated both the infarct size and the neurological deficits caused by ET-1-induced MCAO without altering blood pressure. This study confirms the cerebroprotective properties of ARBs during ischaemic stroke and validates the ET-1-induced MCAO model for examination of the role of the brain renin–angiotensin system in ischaemic stroke. PMID:19429641

  12. Rat white matter injury model induced by endothelin-1 injection: technical modification and pathological evaluation.

    Science.gov (United States)

    Ono, Hideaki; Imai, Hideaki; Miyawaki, Satoru; Nakatomi, Hirofumi; Saito, Nobuhito

    2016-01-01

    White matter injury is an important cause of functional disability of the brain. We comprehensively analyzed a modified endothelin-1 (ET‑1) injection-induced white matter injury model in the rat which is very valuable for investigating the underlying mechanisms of subcortical ischemic stroke. ET-1 was stereotactically injected into the internal capsule of the rat. To avoid complications with leakage of ET-1 into the lateral ventricle, the safest trajectory angle to the target was established. Rats with white matter injury were extensively evaluated for structural changes and functional sequelae, using motor function tests, magnetic resonance (MR) imaging, histopathology evolution, volume estimation of the lesion, and neuroanatomical identification of affected neurons using the retrograde tracer hydroxystilbamidine. Optimization of the trajectory of the ET-1 injection needle provided excellent survival rate. MR imaging visualized the white matter injury 2 days after surgery. Motor function deficit appeared temporarily after the operation. Histological studies confirmed damage of axons and myelin sheaths followed by inflammatory reaction and gliosis similar to lacunar infarction, with lesion volume of less than 1% of the whole brain. Hydroxystilbamidine injected into the lesion revealed wide spatial distribution of the affected neuronal population. Compared with prior ET-1 injection models, this method induced standardized amount of white matter damage and temporary motor function deficit in a reproducible and safe manner. The present model is valuable for studying the pathophysiology of not only ischemia, but a broader set of white matter damage conditions in the lissencephalic brain.

  13. Quantitative Erythrocyte Omega-3 EPA Plus DHA Levels are Related to Higher Regional Cerebral Blood Flow on Brain SPECT.

    Science.gov (United States)

    Amen, Daniel G; Harris, William S; Kidd, Parris M; Meysami, Somayeh; Raji, Cyrus A

    2017-01-01

    The interrelationships between omega-3 fatty acids status, brain perfusion, and cognition are not well understood. To evaluate if SPECT brain imaging of cerebral perfusion and cognition varies as a function of omega-3 fatty acid levels. A random sample of 166 study participants was drawn from a psychiatric referral clinical for which erythrocyte quantification of omega-3 eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) (the Omega-3 Index) was available. Quantitative brain SPECT was done on 128 regions based on a standard anatomical Atlas. Persons with erythrocyte EPA+DHA concentrations were dichotomized based on membership in top 50th percentile versus bottom 50th percentile categories. Two-sample t-tests were done to identify statistically significant differences in perfusion between the percentile groups. Partial correlations were modeled between EPA+DHA concentration and SPECT regions. Neurocognitive status was assessed using computerized testing (WebNeuro) and was separately correlated to cerebral perfusion on brain SPECT imaging and omega-3 EPA+DHA levels. Partial correlation analyses showed statistically significant relationships between higher omega-3 levels and cerebral perfusion were in the right parahippocampal gyrus (r = 0.20, p = 0.03), right precuneus (r = 0.20, p = 0.03), and vermis subregion 6 (p = 0.21, p = 0.03). Omega-3 Index levels separately correlated to the feeling subsection of the WebNeuro (r = 0.25, p = 0.01). Quantitative omega-3 EPA+DHA erythrocyte concentrations are independently correlated with brain perfusion on SPECT imaging and neurocognitive tests. These results have implications for the role of omega-3 fatty acids toward contributing to cognitive reserve.

  14. Higher prevalence of childbirth related fear in foreign born pregnant women--findings from a community sample in Sweden.

    Science.gov (United States)

    Ternström, Elin; Hildingsson, Ingegerd; Haines, Helen; Rubertsson, Christine

    2015-04-01

    to investigate the prevalence of childbirth related fear (CBRF) in early pregnancy among both Swedish born and foreign born women living in Sweden. a cross sectional prevalence study. Data was collected by a questionnaire, which was available in Swedish and eight other languages. a university hospital in the middle of Sweden. the recruitment took place during a two month period where the participating women completed the Fear of Birth Scale (FOBS) in mid-pregnancy. prevalence of CBRF, the cut-point of 60 and above. Odds ratios with a 95% confidence interval were calculated between women born in Sweden and women born in a foreign country. Stratified analyses were also performed separately for Swedish born and foreign born women. in total 606 women completed the survey, 78% were born in Sweden and 22% were born in a foreign country. About 22% of the total sample scored 60 or more on the FOBS-scale. Almost 18% (n=85) of the women born in Sweden reported CBRF whereas 37 % (n=49) of the foreign born women reported CBRF. Being born outside Sweden (OR 2.7; CI 1.7-4.0) and expecting the first baby (OR 1.9; CI 1.3-2.8) were associated with CBRF. There were no differences in age, civil status or level of education between women with or without FOBS≥60. However, a stratified analysis showed that primiparas born in a foreign country (OR 3.8; CI 1.8-8.0) were more likely to score 60 or more on the FOBS-scale compared to multiparas born in a foreign country. childbirth related fear was almost three times as common among foreign born women when compared to Swedish women. Foreign born childbearing women are an extremely vulnerable group who need culturally sensitive and targeted support from caregivers. Further research is needed to clearly identify the components of women׳s childbirth related fear in various ethnic groups. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Reduced Regional Homogeneity in Bilateral Frontostriatal System Relates to Higher Impulsivity Behavior in Codeine-Containing Cough Syrups Dependent Individuals

    Science.gov (United States)

    Lv, Xiaofei; Su, Huanhuan; Zhuo, Fuzhen; Han, Lujun; Zhang, Xuelin

    2013-01-01

    Background In the past twenty years, codeine-containing cough syrups (CCS) was recognized as a new type of addictive drugs. However, the exact neurobiologic mechanisms underlying CCS-dependence are still ill-defined. The aims of this study are to identify CCS-related modulations of neural activity during the resting-state in CCS-dependent individuals and to investigate whether these changes of neural activity can be related to duration of CCS use, the first age of CCS use and impulse control deficits in CCS-dependent individuals. We also want to observe the impact of gray matter deficits on these functional results. Methodology/Principal Findings Thirty CCS-dependent individuals and 30 control subjects participated. Resting-state functional MRI was performed by using gradient-echo echo-planar imaging sequence. Regional homogeneity (ReHo) was calculated by using REST software. Voxel-based analysis of the ReHo maps between controls and CCS-dependent groups was performed using two-sample t tests (p<0.05, corrected for multiple comparisons). The Barratt Impulsiveness Scale 11 (BIS.11) was surveyed to assess participants' impulsivity trait soon after MR examination. Abnormal clusters revealed by group comparison were extracted and correlated with impulsivity, duration of CCS use, and age of first CCS use. ReHo was diminished in the bilateral medial orbitofrontal cortex (mOFC) and left dorsal striatum in CCS-dependent individuals. There were negative correlations between mean ReHo in the bilateral medial OFC, left dorsal striatum and duration of CCS use, BIS.11 total scores, and the subscale of attentional impulsivity in CCS-dependent individuals. There was a significantly positive correlation between mean ReHo in the left dorsal striatum and age of first CCS use in CCS-dependent individuals. Importantly, these results still remain significant after statistically controlling for the regional gray matter deficits. Conclusion Resting-state abnormalities in CCS

  16. Major amyloid-β-degrading enzymes, endothelin-converting enzyme-2 and neprilysin, are expressed by distinct populations of GABAergic interneurons in hippocampus and neocortex.

    Science.gov (United States)

    Pacheco-Quinto, Javier; Eckman, Christopher B; Eckman, Elizabeth A

    2016-12-01

    Impaired clearance of amyloid-β peptide (Aβ) has been postulated to significantly contribute to the amyloid accumulation typical of Alzheimer's disease. Among the enzymes known to degrade Aβ in vivo are endothelin-converting enzyme (ECE)-1, ECE-2, and neprilysin (NEP), and evidence suggests that they regulate independent pools of Aβ that may be functionally significant. To better understand the differential regulation of Aβ concentration by its physiological degrading enzymes, we characterized the cell and region-specific expression pattern of ECE-1, ECE-2, and NEP by in situ hybridization and immunohistochemistry in brain areas relevant to Alzheimer's disease. In contrast to the broader distribution of ECE-1, ECE-2 and NEP were found enriched in GABAergic neurons. ECE-2 was majorly expressed by somatostatin-expressing interneurons and was active in isolated synaptosomes. NEP messenger RNA was found mainly in parvalbumin-expressing interneurons, with NEP protein localized to perisomatic parvalbuminergic synapses. The identification of somatostatinergic and parvalbuminergic synapses as hubs for Aβ degradation is consistent with the possibility that Aβ may have a physiological function related to the regulation of inhibitory signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Gastric bypass does not normalize obesity-related changes in ghrelin profile and leads to higher acylated ghrelin fraction.

    Science.gov (United States)

    Barazzoni, Rocco; Zanetti, Michela; Nagliati, Carlo; Cattin, Maria Rosa; Ferreira, Clara; Giuricin, Michela; Palmisano, Silvia; Edalucci, Elisabetta; Dore, Franca; Guarnieri, Gianfranco; de Manzini, Nicolò

    2013-04-01

    Gastric bypass (GBP) lowers food intake, body weight, and insulin resistance in severe obesity (SO). Ghrelin is a gastric orexigenic and adipogenic hormone contributing to modulate energy balance and insulin action. Total plasma ghrelin (T-Ghr) level is low and inversely related to body weight and insulin resistance in moderately obese patients, but these observations may not extend to the orexigenic acylated form (A-Ghr) whose plasma concentration increase in moderate obesity. We investigated the impact of GBP on plasma T-, A-, and A/T-Ghr in SO patients (n = 28, 20 women), with measurements at baseline and 1, 3, 6, and 12 months after surgery. Additional cross-sectional comparison was performed between nonobese, moderately obese, and SO individuals before GBP and at the end of the follow-up period. Before GBP, SO had lowest T-Ghr and highest A/T-Ghr profile compared with both nonobese and moderately obese individuals. Lack of early (0-3 months from GBP) T-Ghr changes masked a sharp increase in A-Ghr and A/T-Ghr profile (P elevated following later increments (6-12 months) of both T- and A-Ghr (P masks elevation of A/T-Ghr, that is stabilized after later increments of both T- and A-hormones. GBP does not normalize the obesity-associated elevated A/T-Ghr ratio, instead resulting in enhanced A-Ghr excess. Excess A-Ghr is unlikely to contribute to, and might limit, the common GBP-induced declines of appetite, body weight, and insulin resistance. Copyright © 2012 The Obesity Society.

  18. Understanding the Relative Contributions of Lower-Level Word Processes, Higher-Level Processes, and Working Memory to Reading Comprehension Performance in Proficient Adult Readers

    Science.gov (United States)

    Hannon, Brenda

    2012-01-01

    Although a considerable amount of evidence has been amassed regarding the contributions of lower-level word processes, higher-level processes, and working memory to reading comprehension, little is known about the relationships among these sources of individual differences or their relative contributions to reading comprehension performance. This…

  19. The effect of the phytoestrogen genistein on plasma nitric oxide concentrations, endothelin-1 levels and endothelium dependent vasodilation in postmenopausal women.

    Science.gov (United States)

    Squadrito, Francesco; Altavilla, Domenica; Morabito, Nunziata; Crisafulli, Alessandra; D'Anna, Rosario; Corrado, Francesco; Ruggeri, Pietro; Campo, Giuseppe M; Calapai, Gioacchino; Caputi, Achille P; Squadrito, Giovanni

    2002-08-01

    The phytoestrogen genistein improves endothelial dysfunction in ovariectomized rats through a nitric oxide-dependent mechanism. We investigated whether genistein alters the balance between the nitric oxide products and endothelin-1 and influences endothelium-dependent vasodilation in postmenopausal women. Sixty healthy postmenopausal women were enrolled in the study. A double-blind, placebo controlled, randomized design was employed. After a 4-week stabilization on a standard fat-reduced diet, participants to the study were randomly assigned to receive either genistein (n=30; 54 mg/day) or placebo (n=30). Flow-mediated, endothelium-dependent vasodilation of the brachial artery, plasma nitric oxide breakdown products and endothelin-1 levels were measured at baseline and after 6 months of genistein therapy. The mean baseline level of nitrites/nitrates was 22+/-10 micromol/l and increased to 41+/-10 micromol/ml after 6 months of treatment. The mean baseline plasma endothelin-1 level was 14+/-4 pg/ml and decreased to 7+/-1 pg/ml following 6 months of treatment with genistein. The mean baseline ratio of nitric oxide to endothelin also significantly increased at the end of treatment. Flow-mediated, endothelium-dependent vasodilation of the brachial artery was 3.9+/-0.8 mm at baseline and increased to 4.4+/-0.7 mm after 6 months of treatment. Placebo-treated women showed no changes in plasma nitrites/nitrates, endothelin-1 levels and flow-mediated vasodilation. Genistein therapy improves flow-mediated endothelium dependent vasodilation in healthy postmenopausal women. This improvement may be mediated by a direct effect of genistein on the vascular function and could be the result of an increased ratio of nitric oxide to endothelin.

  20. Polymorphism of the endothelin-1 gene (rs5370 is a potential contributor to sickle cell disease pathophysiology

    Directory of Open Access Journals (Sweden)

    Kristen G. Navarro

    2016-12-01

    Full Text Available Sickle cell disease has been shown to demonstrate extensive variability in disease severity among and between individuals, the variability highlighted by differing genetic haplotypes. Despite the abundance of reports of functional significance due to polymorphisms of endothelial nitric oxide synthase (eNOS and endothelin-1 (ET-1 genes, the role of these polymorphisms in mediating sickle cell disease pathophysiology among African Americans is presently unclear. To deconvolute their potential significance among African Americans with sickle cell disease, we examined the genetic diversity and haplotype frequency of eNOS and ET-1 polymorphisms in disease (n = 331 and control (n = 379 groups, with a polymerase–chain reaction restriction fragment length polymorphism assay. We report that genotypic and allelic frequencies of eNOS variants are not significantly different between groups. eNOS homozygote mutants, which had been shown to have clinical significance elsewhere, showed no statistical significance in our study. On the other hand, and contrary to previous report among Africans with sickle cell disease, the endothelin-1 homozygous mutant variant showed significant difference in genotypic (p = 2.84E-12 and allelic frequencies (p = 2.20E-16 between groups. The most common haplotype is the combination of T786C homozygote wild-type variant with homozygote mutant variants of G5665T (ET-1 and Glu298Asp (eNOS. These results show that endothelin-1 (rs5370 polymorphism, rather than endothelial nitric oxide synthase polymorphism might play a significant role in disease severity or individual clinical outcomes among African Americans with sickle cell disease. This would have profound implications for designing and/or advancing personalized care for sickle cell patients and relieving disease complications.

  1. Stretch induced endothelin-1 secretion by adult rat astrocytes involves calcium influx via stretch-activated ion channels (SACs)

    Energy Technology Data Exchange (ETDEWEB)

    Ostrow, Lyle W., E-mail: lostrow1@jhmi.edu [Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205 (United States); Suchyna, Thomas M.; Sachs, Frederick [Department of Physiology and Biophysical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States)

    2011-06-24

    Highlights: {yields} Endothelin-1 expression by adult rat astrocytes correlates with cell proliferation. {yields} Stretch-induced ET-1 is inhibited by GsMtx-4, a specific inhibitor of Ca{sup 2+} permeant SACs. {yields} The less specific SAC inhibitor streptomycin also inhibits ET-1 secretion. {yields} Stretch-induced ET-1 production depends on a calcium influx. {yields} SAC pharmacology may provide a new class of therapeutic agents for CNS pathology. -- Abstract: The expression of endothelins (ETs) and ET-receptors is often upregulated in brain pathology. ET-1, a potent vasoconstrictor, also inhibits the expression of astrocyte glutamate transporters and is mitogenic for astrocytes, glioma cells, neurons, and brain capillary endothelia. We have previously shown that mechanical stress stimulates ET-1 production by adult rat astrocytes. We now show in adult astrocytes that ET-1 production is driven by calcium influx through stretch-activated ion channels (SACs) and the ET-1 production correlates with cell proliferation. Mechanical stimulation using biaxial stretch (<20%) of a rubber substrate increased ET-1 secretion, and 4 {mu}M GsMTx-4 (a specific inhibitor of SACs) inhibited secretion by 30%. GsMTx-4 did not alter basal ET-1 levels in the absence of stretch. Decreasing the calcium influx by lowering extracellular calcium also inhibited stretch-induced ET-1 secretion without effecting ET-1 secretion in unstretched controls. Furthermore, inhibiting SACs with the less specific inhibitor streptomycin also inhibited stretch-induced ET-1 secretion. The data can be explained with a simple model in which ET-1 secretion depends on an internal Ca{sup 2+} threshold. This coupling of mechanical stress to the astrocyte endothelin system through SACs has treatment implications, since all pathology deforms the surrounding parenchyma.

  2. NF-kappaB signaling mediates vascular smooth muscle endothelin type B receptor expression in resistance arteries

    DEFF Research Database (Denmark)

    Zheng, Jian-Pu; Zhang, Yaping; Edvinsson, Lars

    2010-01-01

    Vascular smooth muscle cells (SMC) endothelin type B (ET(B)) receptor upregulation results in strong vasoconstriction and reduction of local blood flow. We hypothesizes that the underlying molecular mechanisms involve transcriptional factor nuclear factor-kappaB (NF-kappaB) pathway. ET(B) receptor...... upregulation and activation of NF-kappaB were studied at functional contraction (in vitro myograph), mRNA (real-time PCR), and protein (Western blot and immunocytochemistry) levels during organ culture of rat mesenteric arteries. Organ culture of the artery segments induced a time-dependent strong contractile...

  3. Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease

    DEFF Research Database (Denmark)

    Dimitrijevic, Ivan; Edvinsson, Lars; Chen, Qingwen

    2009-01-01

    expression in subcutaneous arteries from patients with different degrees of ischemic heart disease. METHODS: Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG) surgery because of ischemic heart disease (n = 15), patients with angina...... pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A (ETA) and type B (ETB), and angiotensin type 1 (AT1) and type 2 (AT2) receptors expression and function were examined using immunohistochemistry, Western blot and in vitro...

  4. Plasma endothelin-1 levels in patients with resistant hypertension: effects of renal sympathetic denervation.

    Science.gov (United States)

    Petramala, Luigi; Olmati, Federica; Mancone, Massimo; Concistré, Antonio; Galassi, Matteo; Marinelli, Cristiano; Tonnarini, Gianfranco; Lucia, Piernatale; Costi, Umberto; Iannucci, Gino; Sardella, Gennaro; Letizia, Claudio

    2017-08-01

    Resistant arterial hypertension (RHT) is defined as poor controlled blood pressure (BP) despite optimal doses of three or more antihypertensive agents, including a diuretic. In the development of RHT, hyperactivity of sympathetic (SNS) and renin-angiotensin-aldosterone (SRAA) systems are involved, and SNS is a potent stimulator of vasoactive endothelin-1 (ET-1) peptide. Renal sympathetic denervation (RSD) through disrupting renal afferent and efferent nerves attenuates SNS activity. We carried out pilot study investigating the effect of RSD on BP and plasma ET-1 levels in consecutive 9 RHT patients (7 male and 2 female, mean age of 56 ± 13.3). After 12 months of the RSD, we observed a significant reduction of BP office, 24-h ambulatory BP monitoring (ABPM) (p RSD significantly decreased plasma ET-1 levels in both renal artery (at right from 21.8 ± 4.1 to 16.8 ± 2.9 pg/ml; p = 0.004; at left from 22.1 ± 3.7 to 18.9 ± 3.3 pg/ml; p = 0.02). We observed positive correlations between plasma renal arteries ET-1 levels and systolic BP values at ABPM [Global-SBP (r = 0.58; p RSD on BP values in patients with RHT, and showed a possible physio-pathological role of ET-1. KEY MESSAGES RSD is associated to a significant reduction of plasma ET-1 levels, representing an useful tool into reduction of BP in RHT patients.

  5. Endothelin potentiates TRPV1 via ETA receptor-mediated activation of protein kinase C

    Directory of Open Access Journals (Sweden)

    Furkert Jens

    2007-11-01

    Full Text Available Abstract Background Endothelin-1 (ET-1 both stimulates nociceptors and sensitizes them to noxious stimuli, an effect probably mediated by the ETA receptor (ETAR expressed in sensory neurons. The cellular mechanisms of this ET-1-mediated effect are only poorly understood. TRPV1, the heat-, pH- and capsaicin-sensitive cation channel already known to be modulated by a number of cellular mediators released in response to noxious stimuli and during inflammation, is a potential target for the action of ET-1. Results We studied the effects of ET-1 on TRPV1 in sensory neurons from the dorsal root ganglion (DRG and in HEK293 cells coexpressing TRPV1 and the ETAR. Specific 125I-ET-1 binding sites (817 ± 92 fmol/mg were detected in membrane preparations of DRG with an ETAR/ETBR ratio of 60:40. In an immunofluorescence analysis, coexpression of TRPV1 and the ETAR was found in a subpopulation of primary sensory neurons. ET-1 strongly potentiated capsaicin-induced TRPV1 currents in some neurons, and in HEK293 cells co-expressing TRPV1 and the ETAR. Weaker potentiation was observed in HEK293 cells coexpressing TRPV1 and the ETBR. ETAR activation also increased responses to low pH and heat. In HEK293 cells, strong potentiation of TRPV1 like that induced by ET-1 via the ETAR could be induced by PKC activation, but not with activators of the adenylyl cyclase or the PKA pathway. Furthermore, inhibition of PKC with bisindolylmaleimide X (BIM X or mutation of the PKC phosphorylation site S800 completely prevented ETAR-mediated potentiation. Conclusion We conclude that ET-1 potentiates TRPV1 by a PKC-dependent mechanism and that this could play a major role in the algogenic and hyperalgesic effects of ET-1 described in previous studies.

  6. Peripheral endothelin B receptor agonist-induced antinociception involves endogenous opioids in mice.

    Science.gov (United States)

    Quang, Phuong N; Schmidt, Brian L

    2010-05-01

    Endothelin-1 (ET-1) produced by various cancers is known to be responsible for inducing pain. While ET-1 binding to ETAR on peripheral nerves clearly mediates nociception, effects from binding to ETBR are less clear. The present study assessed the effects of ETBR activation and the role of endogenous opioid analgesia in carcinoma pain using an orthotopic cancer pain mouse model. mRNA expression analysis showed that ET-1 was nearly doubled while ETBR was significantly down-regulated in a human oral SCC cell line compared to normal oral keratinocytes (NOK). Squamous cell carcinoma (SCC) cell culture treated with an ETBR agonist (10(-4)M, 10(-5)M, and 10(-6) M BQ-3020) significantly increased the production of beta-endorphin without any effects on leu-enkephalin or dynorphin. Cancer inoculated in the hind paw of athymic mice with SCC induced significant pain, as indicated by reduction of paw withdrawal thresholds in response to mechanical stimulation, compared to sham-injected and NOK-injected groups. Intratumor administration of 3mg/kg BQ-3020 attenuated cancer pain by approximately 50% up to 3h post-injection compared to PBS-vehicle and contralateral injection, while intratumor ETBR antagonist BQ-788 treatment (100 and 300microg/kg and 3mg/kg) had no effects. Local naloxone methiodide (500microg/kg) or selective mu-opioid receptor antagonist (CTOP, 500microg/kg) injection reversed ETBR agonist-induced antinociception in cancer animals. We propose that these results demonstrate that peripheral ETBR agonism attenuates carcinoma pain by modulating beta-endorphins released from the SCC to act on peripheral opioid receptors found in the cancer microenvironment. Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  7. A role for endothelin in bicuculline-induced neurogenic pulmonary oedema in rats.

    Science.gov (United States)

    Herbst, C; Tippler, B; Shams, H; Simmet, T

    1995-07-01

    1. The possible contribution of endogenous endothelin (ET) to the pathogenesis of seizure-associated pulmonary oedema was examined in mechanically ventilated rats after intravenous bolus injection of the gamma-aminobutyric acid (GABA) antagonist, bicuculline (1.2 mg kg-1). 2. Recurrent seizure activity elicited by bicuculline injection led to rapidly developing pulmonary oedema. Within 4 min after bicuculline application (1.2 mg kg-1), arterial O2 partial pressure (PaO2) significantly dropped from 17.49 +/- 1.20 kPa to 7.51 +/- 2.21 kPa (P 0.05) after phosphoramidon pretreatment. In contrast, vehicle-treated animals that received bicuculline showed both significant hypercapnia as well as profound hypoxia. Phosphoramidon significantly diminished the maximum increase in Paw by 76.7 +/- 12.4% (P 0.05) in BQ-123-treated animals. In contrast, vehicle-treated animals that received bicuculline exhibited significant hypercapnia as well as profound hypoxia. BQ-123 significantly reduced the increase in Paw by 51.3 +/- 12.8% (P < 0.01). It affected MABP only slightly and had no effect on the acidosis.6. These results suggest that ET peptides play a significant role in this model of neurogenic pulmonary oedema and may act as mediators of respiratory distress. The deleterious effects of endogenous ET in this model are primarily mediated via the ETA receptor, for they were inhibited by the ETA receptor antagonist, BQ-123. ETA receptor antagonists may therefore be of potential therapeutic value in respiratory distress.

  8. Knockout of endothelial cell-derived endothelin-1 attenuates skin fibrosis but accelerates cutaneous wound healing.

    Directory of Open Access Journals (Sweden)

    Katsunari Makino

    Full Text Available Endothelin (ET-1 is known for the most potent vasoconstrictive peptide that is released mainly from endothelial cells. Several studies have reported ET-1 signaling is involved in the process of wound healing or fibrosis as well as vasodilation. However, little is known about the role of ET-1 in these processes. To clarify its mechanism, we compared skin fibrogenesis and wound repair between vascular endothelial cell-specific ET-1 knockout mice and their wild-type littermates. Bleomycin-injected fibrotic skin of the knockout mice showed significantly decreased skin thickness and collagen content compared to that of wild-type mice, indicating that bleomycin-induced skin fibrosis is attenuated in the knockout mice. The mRNA levels of transforming growth factor (TGF-β were decreased in the bleomycin-treated skin of ET-1 knockout mice. On the other hand, skin wound healing was accelerated in ET-1 knockout mice, which was indicated by earlier granulation tissue reduction and re-epithelialization in these mice. The mRNA levels of TGF-β, tumor necrosis factor (TNF-α and connective tissue growth factor (CTGF were reduced in the wound of ET-1 knockout mice. In endothelial ET-1 knockout mouse, the expression of TNF-α, CTGF and TGF-β was down-regulated. Bosentan, an antagonist of dual ET receptors, is known to attenuate skin fibrosis and accelerate wound healing in systemic sclerosis, and such contradictory effect may be mediated by above molecules. The endothelial cell-derived ET-1 is the potent therapeutic target in fibrosis or wound healing, and investigations of the overall regulatory mechanisms of these pathological conditions by ET-1 may lead to a new therapeutic approach.

  9. Endothelin-receptor antagonist can reduce blood pressure in patients with hypertension: a meta-analysis.

    Science.gov (United States)

    Yuan, Wenming; Cheng, Genyang; Li, Bin; Li, Yansheng; Lu, Shan; Liu, Dong; Xiao, Jing; Zhao, Zhanzheng

    2017-06-01

    The aim of this meta-analysis was to assess the effectiveness and safety of endothelin-receptor antagonist (ERA) in the patients with hypertension. Searches of the PubMed, EMBASE, and CENTRAL databases were conducted to include all the randomized control trials (RCTs). Eighteen trials including 4898 patients were used in the meta-analysis, of which nine were classified as low risk of bias and the other nine as unclear risk of bias. There was no statistically significant difference in all-cause mortality between ERA and placebo groups [6 trials, fixed effects model, RR 1.53 (0.89-2.62); random effects model, RR 1.45 (0.84-2.52)]. ERA significantly reduced 24-h ambulatory blood pressure and sitting blood pressure in patients with hypertension [5 trials, 24-h SBP: WMD -7.65 (-8.95 to -6.36), 24-h DBP: WMD -5.92 (-7.50 to -4.33); 18 trials, SBP: WMD -6.12 (-7.87 to -4.36), DBP: WMD -3.81 (-4.82 to -2.80)]. However, ERA had more adverse events [within 24 h: 3 trials, RR 1.16 (0.82-1.65); after 24 h, 13 trials, RR 1.21 (1.08-1.36)] and severe adverse events than placebo controls [SAE: 9 trials, RR 1.34 (1.13-1.60)]. In addition, there is a potential need for further RCTs that focus on the use of ERA in patients with hypertension.

  10. Serum big endothelin-1 as a clinical marker for cardiopulmonary and neoplastic diseases in dogs.

    Science.gov (United States)

    Fukumoto, Shinya; Hanazono, Kiwamu; Miyasho, Taku; Endo, Yoshifumi; Kadosawa, Tsuyoshi; Iwano, Hidetomo; Uchide, Tsuyoshi

    2014-11-24

    Many studies of human subjects have demonstrated the utility of assessing serum levels of endothelin-1 (ET-1) and big ET-1 as clinical biomarkers in cardiopulmonary and neoplastic diseases. In this study we explored the feasibility of using serum big ET-1 as a reliable veterinary marker in dogs with various cardiopulmonary and neoplastic diseases. Serum big ET-1 levels were measured by ELISA in dogs with cardiopulmonary (n=21) and neoplastic diseases (n=57). Dogs exhibiting cardiopulmonary disease were divided into two groups based on the velocity of tricuspid valve regurgitation (3.0>m/s) measured by ultrasound: without and with pulmonary hypertension. Big ET-1 levels for the dogs with the diseases were compared with levels in normal healthy dogs (n=17). Dogs with cardiopulmonary disease (4.6±4.6 pmol/l) showed a significantly (Pdogs (1.1±0.53 pmol/l). Serum levels in the dogs with pulmonary hypertension (6.2±5.3 pmol/l) were significantly (Ppulmonary hypertension (2.0±0.6 pmol/l). Dogs with hemangiosarcoma (5.6±2.2 pmol/l), adenocarcinoma (2.0±1.8 pmol/l), histiocytic sarcoma (3.3±1.9 pmol/l), chondrosarcoma or osteosarcoma (3.0±1.6 pmol/l) and hepatocellular carcinoma (2.7±1.8 pmol/l) showed significantly (Pdogs. These findings point to the potential of serum big ET-1 as a clinical marker for cardiopulmonary and neoplastic diseases in dogs. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Endothelin-1 stimulates catalase activity through the PKCδ mediated phosphorylation of Serine 167

    Science.gov (United States)

    Rafikov, Ruslan; Kumar, Sanjiv; Aggarwal, Saurabh; Hou, Yali; Kangath, Archana; Pardo, Daniel; Fineman, Jeffrey R.; Black, Stephen M.

    2013-01-01

    Our previous studies have shown that endothelin-1 (ET-1) stimulates catalase activity in endothelial cells and lambs with acute increases in pulmonary blood flow (PBF), without altering gene expression. The purpose of this study was to investigate the molecular mechanism by which this occurs. Exposing pulmonary arterial endothelial cells (PAEC) to ET-1 increased catalase activity and decreased cellular hydrogen peroxide (H2O2) levels. These changes correlated with an increase in serine phosphorylated catalase. Using the inhibitory peptide δV1.1, this phosphorylation was shown to be PKCδ dependent. Mass spectrometry identified serine167 as the phosphorylation site. Site-directed mutagenesis was used to generate a phospho-mimic (S167D) catalase. Activity assays using recombinant protein purified from E.coli or transiently transfected COS-7 cells, demonstrated that S167D-catalase had an increased ability to degrade H2O2 compared to the wildtype enzyme. Using a phospho-specific antibody, we were able to verify that pS167 catalase levels are modulated in lambs with acute increases in PBF in the presence and absence of the ET receptor antagonist, tezosentan. S167 is being located on the dimeric interface suggesting it could be involved in regulating the formation of catalase tetramers. To evaluate this possibility we utilized analytical gel-filtration to examine the multimeric structure of recombinant wildtype- and S167D-catalase. We found that recombinant wildtype catalase was present as a mixture of monomers and dimers while S167D catalase was primarily tetrameric. Further, the incubation of wildtype catalase with PKCδ was sufficient to convert wildtype catalase into a tetrameric structure. In conclusion, this is the first report indicating that the phosphorylation of catalase regulates its multimeric structure and activity. PMID:24211614

  12. Endothelin-A Receptor Antagonism after Renal Angioplasty Enhances Renal Recovery in Renovascular Disease

    Science.gov (United States)

    Tullos, Nathan; Stewart, Nicholas J.; Surles, Bret

    2015-01-01

    Percutaneous transluminal renal angioplasty/stenting (PTRAS) is frequently used to treat renal artery stenosis and renovascular disease (RVD); however, renal function is restored in less than one half of the cases. This study was designed to test a novel intervention that could refine PTRAS and enhance renal recovery in RVD. Renal function was quantified in pigs after 6 weeks of chronic RVD (induced by unilateral renal artery stenosis), established renal damage, and hypertension. Pigs with RVD then underwent PTRAS and were randomized into three groups: placebo (RVD+PTRAS), chronic endothelin-A receptor (ET-A) blockade (RVD+PTRAS+ET-A), and chronic dual ET-A/B blockade (RVD+PTRAS+ET-A/B) for 4 weeks. Renal function was again evaluated after treatments, and then, ex vivo studies were performed on the stented kidney. PTRAS resolved renal stenosis, attenuated hypertension, and improved renal function but did not resolve renal microvascular rarefaction, remodeling, or renal fibrosis. ET-A blocker therapy after PTRAS significantly improved hypertension, microvascular rarefaction, and renal injury and led to greater recovery of renal function. Conversely, combined ET-A/B blockade therapy blunted the therapeutic effects of PTRAS alone or PTRAS followed by ET-A blockade. These data suggest that ET-A receptor blockade therapy could serve as a coadjuvant intervention to enhance the outcomes of PTRAS in RVD. These results also suggest that ET-B receptors are important for renal function in RVD and may contribute to recovery after PTRAS. Using clinically available compounds and techniques, our results could contribute to both refinement and design of new therapeutic strategies in chronic RVD. PMID:25377076

  13. Endothelin-A receptor blockade slows the progression of renal injury in experimental renovascular disease.

    Science.gov (United States)

    Kelsen, Silvia; Hall, John E; Chade, Alejandro R

    2011-07-01

    Endothelin (ET)-1, a potent renal vasoconstrictor with mitogenic properties, is upregulated by ischemia and has been shown to induce renal injury via the ET-A receptor. The potential role of ET-A blockade in chronic renovascular disease (RVD) has not, to our knowledge, been previously reported. We hypothesized that chronic ET-A receptor blockade would preserve renal hemodynamics and slow the progression of injury of the stenotic kidney in experimental RVD. Renal artery stenosis, a major cause of chronic RVD, was induced in 14 pigs and observed for 6 wk. In half of the pigs, chronic ET-A blockade was initiated (RVD+ET-A, 0.75 mg·kg(-1)·day(-1)) at the onset of RVD. Single-kidney renal blood flow, glomerular filtration rate, and perfusion were quantified in vivo after 6 wk using multidetector computer tomography. Renal microvascular density was quantified ex vivo using three-dimensional microcomputer tomography, and growth factors, inflammation, apoptosis, and fibrosis were determined in renal tissue. The degree of stenosis and increase in blood pressure were similar in RVD and RVD+ET-A pigs. Renal hemodynamics, function, and microvascular density were decreased in the stenotic kidney but preserved by ET-A blockade, accompanied by increased renal expression of vascular endothelial growth factor, hepatocyte growth factor, and downstream mediators such as phosphorilated-Akt, angiopoietins, and endothelial nitric oxide synthase. ET-A blockade also reduced renal apoptosis, inflammation, and glomerulosclerosis. This study shows that ET-A blockade slows the progression of renal injury in experimental RVD and preserves renal hemodynamics, function, and microvascular density in the stenotic kidney. These results support a role for ET-1/ET-A as a potential therapeutic target in chronic RVD.

  14. Lactoferrin- Endothelin-1 Axis Contributes to the Development and Invasiveness of Triple Negative Breast Cancer Phenotypes

    Science.gov (United States)

    Ha, Ngoc-Han; Nair, Vasudha; Reddy, Divijendra Natha Sirigiri; Mudvari, Prakriti; Ohshiro, Kazufumi; Ghanta, Krishna Sumanth; Pakala, Suresh B.; Li, Da-Qiang; Costa, Luis; Lipton, Allan; Badwe, Rajendra A.; Fuqua, Suzanne; Wallon, Margaretha; Prendergast, George C.; Kumar, Rakesh

    2013-01-01

    Triple-negative breast cancer (TNBC) is characterized by the lack of expression of ERα, PR and HER-2 receptors and the pathway(s) responsible for this downregulation and thus aggressiveness, remains unknown. Here we discovered that lactoferrin (Lf) efficiently downregulates the levels of ERα, PR and HER-2 receptors in a proteasome-dependent manner in breast cancer cells, and accounts for the loss of responsiveness to ER- or HER-2- targeted therapies. Further we found that Lf increases migration and invasiveness of both non-TNBC and TNBC cell lines. We discovered that Lf directly stimulates the transcription of endothelin-1 (ET-1), a secreted pro-invasive polypeptide that acts through a specific receptor ET(A)R, leading to secretion of bioactive ET-1 peptide. Interestingly, a therapeutic ET-1 receptor antagonist drug completely blocked Lf-dependent motility and invasiveness of breast cancer cells. Physiologic significance of this newly discovered Lf-ET-1 axis in the manifestation of TNBC phenotypes is revealed by elevated plasma and tissue Lf and ET-1 levels in TNBC patients as compared to those in ER+ cases. These findings describe the first physiologically relevant polypeptide as a functional determinant of downregulating all three therapeutic receptors in breast cancer which utilizes another secreted ET-1 system to confer invasiveness. Results presented here provide proof-of-principle evidence in support of therapeutic effectiveness of ET-1 receptor antagonist to completely block the Lf-induced motility and invasiveness of the TNBC as well as non-TBNC cells, and thus, opening a remarkable opportunity to treat TNBC by targeting the Lf-ET-1 axis using an approved developmental drug. PMID:22006997

  15. Role of endothelin-1-dependent up-regulation of leptin in oral mucosal repair.

    Science.gov (United States)

    Slomiany, B L; Slomiany, A

    2005-12-01

    Leptin, a multifunctional hormone that regulates food intake and energy expenditure, has emerged recently as an important modulator of inflammatory cascades associated with wound healing. In this study, we applied the animal model of buccal mucosal ulcer to investigate the role of endothelin-1 (ET-1) and leptin in soft oral tissue repair. Using groups of rats with experimentally induced buccal mucosal ulcers we show that ulcer onset was characterized by a marked increase in the mucosal level of ET-1 and leptin. However, while the ET-1 level gradually declined with healing, the mucosal level of leptin increased reaching maximum expression on the 4th day of healing. Therapeutic administration of phosphoramidon, an inhibitor of ECE-1 activity, not only led to a 53.2% drop in the ET-1, but also produced a dose-dependent reduction (up to 50.9%) in the mucosal level of leptin and up to 42.3% decline in the rate of ulcer healing. A marked drop (54.2%) in the mucosal level of leptin and the reduction (46.8%) in the rate of ulcer healing was also attained in the presence of ETA receptor antagonist BQ610 administration, but not the ETB receptor antagonist BQ788. Moreover, administration of ERK inhibitor, PD98059 in the presence of ETB receptor antagonist, but not the ETA receptor antagonist, caused the reduction the mucosal leptin level as well as a decline in the rate of ulcer healing. Our findings are the first to implicate the requirement for both ET-1 and leptin in orderly progression of the events of soft oral tissue repair. We also show that ET-1 is a key factor in up-regulation of leptin production associated with oral mucosal ulcer healing , and that the effect of ET-1 on leptin production is a consequence of ETA receptor activation and subsequent signaling through MAPK/ERK.

  16. Endothelin-dependent vasoconstriction in human uterine artery: application to preeclampsia.

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    Clotilde Dechanet

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

  17. Plasma big endothelin-1 levels at admission and future cardiovascular outcomes: A cohort study in patients with stable coronary artery disease.

    Science.gov (United States)

    Zhou, Bing-Yang; Guo, Yuan-Lin; Wu, Na-Qiong; Zhu, Cheng-Gang; Gao, Ying; Qing, Ping; Li, Xiao-Lin; Wang, Yao; Dong, Qian; Liu, Geng; Xu, Rui Xia; Cui, Chuan-Jue; Sun, Jing; Li, Jian-Jun

    2017-03-01

    Big endothelin-1 (ET-1) has been proposed as a novel prognostic indicator of acute coronary syndrome, while its predicting role of cardiovascular outcomes in patients with stable coronary artery disease (CAD) is unclear. A total of 3154 consecutive patients with stable CAD were enrolled and followed up for 24months. The outcomes included all-cause death, non-fatal myocardial infarction, stroke and unplanned revascularization (percutaneous coronary intervention and coronary artery bypass grafting). Baseline big ET-1 was measured using sandwich enzyme immunoassay method. Cox proportional hazard regression analysis and Kaplan-Meier analysis were used to evaluate the prognostic value of big ET-1 on cardiovascular outcomes. One hundred and eighty-nine (5.99%) events occurred during follow-up. Patients were divided into two groups: events group (n=189) and non-events group (n=2965). The results indicated that the events group had higher levels of big ET-1 compared to non-events group. Multivariable Cox proportional hazard regression analysis showed that big ET-1 was positively and statistically correlated with clinical outcomes (Hazard Ratio: 1.656, 95% confidence interval: 1.099-2.496, p=0.016). Additionally, the Kaplan-Meier analysis revealed that patients with higher big ET-1 presented lower event-free survival (p=0.016). The present study firstly suggests that big ET-1 is an independent risk marker of cardiovascular outcomes in patients with stable CAD. And more studies are needed to confirm our findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Associative learning as higher order cognition: Learning in human and nonhuman animals from the perspective of propositional theories and relational frame theory.

    Science.gov (United States)

    De Houwer, Jan; Hughes, Sean; Barnes-Holmes, Dermot

    2016-08-01

    We aim to provide a new perspective on the old debate about whether evidence for higher order cognition in nonhuman animals can be reinterpreted in terms of associative learning. Our starting point is the idea that associative learning is best thought of as an effect (i.e., the impact of paired events on behavior) rather than a specific mental process (e.g., the formation of associations). This idea allows us to consider (a) propositional theories according to which associative learning is mediated by higher order mental processes akin to problem solving and (b) relational frame theory that allows one to think of seemingly simple associative learning effects as instances of a complex phenomenon known as arbitrarily applicable relational responding. Based on these 2 theories, we argue that (a) higher order cognition and associative learning are not necessarily mutually exclusive and (b) a more sophisticated conceptualization of higher order cognition is warranted. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  19. Higher education

    OpenAIRE

    Wolter, Andrä

    2009-01-01

    During the last five years higher education research in Germany seems to be in a significant upturn. This is a side effect partly of the obvious boom of empirical educational research in general and partly of the reform movement that has affected the German higher education system since middle of the 1990s. The demand for data in the field of higher education will increase considerably in future. The available data infrastructure for higher education research in Germany consists of two comple...

  20. Status epilepticus induces vasogenic edema via tumor necrosis factor-α/ endothelin-1-mediated two different pathways.

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    Ji-Eun Kim

    Full Text Available Status epilepticus (SE induces vasogenic edema in the piriform cortex with disruptions of the blood-brain barrier (BBB. However, the mechanisms of vasogenic edema formation following SE are still unknown. Here we investigated the endothelin B (ETB receptor-mediated pathway of SE-induced vasogenic edema. Following SE, the release of tumor necrosis factor-α (TNF-α stimulated endothelin-1 (ET-1 release and expression in neurons and endothelial cells. In addition, TNF-α-induced ET-1 increased BBB permeability via ETB receptor-mediated endothelial nitric oxide synthase (eNOS activation in endothelial cells. ETB receptor activation also increased intracellular reactive oxygen species by NADPH oxidase production in astrocytes. These findings suggest that SE results in BBB dysfunctions via endothelial-astroglial interactions through the TNF-α-ET-1-eNOS/NADPH oxidase pathway, and that these ETB receptor-mediated interactions may be an effective therapeutic strategy for vasogenic edema in various neurological diseases.

  1. Anti-hypotensive treatment and endothelin blockade synergistically antagonize exercise fatigue in rats under simulated high altitude.

    Directory of Open Access Journals (Sweden)

    Daniel Radiloff

    Full Text Available Rapid ascent to high altitude causes illness and fatigue, and there is a demand for effective acute treatments to alleviate such effects. We hypothesized that increased oxygen delivery to the tissue using a combination of a hypertensive agent and an endothelin receptor A antagonist drugs would limit exercise-induced fatigue at simulated high altitude. Our data showed that the combination of 0.1 mg/kg ambrisentan with either 20 mg/kg ephedrine or 10 mg/kg methylphenidate significantly improved exercise duration in rats at simulated altitude of 4,267 m, whereas the individual compounds did not. In normoxic, anesthetized rats, ephedrine alone and in combination with ambrisentan increased heart rate, peripheral blood flow, carotid and pulmonary arterial pressures, breathing rate, and vastus lateralis muscle oxygenation, but under inspired hypoxia, only the combination treatment significantly enhanced muscle oxygenation. Our results suggest that sympathomimetic agents combined with endothelin-A receptor blockers offset altitude-induced fatigue in rats by synergistically increasing the delivery rate of oxygen to hypoxic muscle by concomitantly augmenting perfusion pressure and improving capillary conductance in the skeletal muscle. Our findings might therefore serve as a basis to develop an effective treatment to prevent high-altitude illness and fatigue in humans.

  2. Antenatal betamethasone has a sex-dependent effect on the in vivo response to endothelin in adult sheep

    Science.gov (United States)

    Lee, Jeong-Heon; Zhang, Jie; Flores, Lourdes; Rose, James C.; Massmann, G. Angela

    2013-01-01

    Antenatal steroid administration is associated with multiple cardiometabolic alterations, including hypertension; however, the mechanisms underlying this phenomenon are unclear. The aim of the present study was to ascertain, in vivo, the contribution of the endothelin system to the development of hypertension in the adult offspring and the signaling pathway involved. Pregnant sheep were treated with two doses of betamethasone (n = 23) or vehicle (n = 22) at 80 days (∼0.55) gestation and allowed to deliver at term. Adult sheep were chronically instrumented under general anesthesia to place vascular catheters and a femoral artery flow probe. Blood pressure and flow were recorded continuously, and femoral artery vascular resistance was calculated before and during administration of endothelin 1 (ET-1). Selective blockers (dantrolene, BQ123, niacinamide) or saline were administered simultaneously. Betamethasone-exposed animals exhibited a significant elevation in mean blood pressure (female: 98 ± 1.8 vs. 92 ± 2.1; males: 97 ± 3.4 vs. 90 ± 2.3; mmHg; P niacinamide (F = 6.6; P niacinamide and BQ123, as well as of dantrolene abolished the betamethasone effect on vascular resistance. No significant differences in mRNA expression of ETA or ETB in endothelial or smooth muscle cells of resistance-size arteries were observed. We conclude that the betamethasone effect on vascular resistance is mediated by an enhanced response to ET-1 through ETA receptor via the cyclic ADPR/ryanodine pathway. PMID:23408033

  3. Novel (E)-alpha-[(1H-indol-3-yl)methylene]benzeneacetic acids as endothelin receptor ligands.

    Science.gov (United States)

    Pittalà, Valeria; Romeo, Giuseppe; Materia, Luisa; Salerno, Loredana; Siracusa, Maria Angela; Modica, Maria; Mereghetti, Ilario; Cagnotto, Alfredo; Russo, Filippo

    2005-09-01

    Endothelin-1 (ET-1), a peptide of 21 amino acid residues, is the most potent vasoconstrictor substance known and now it is understood to be one of a family of three mammalian vasoactive peptides that also includes ET-2 and ET-3. The endothelins (ETs) affect multiple organ systems and seem to be involved in the pathogenesis of many diseases such as hypertension, pulmonary hypertension, atherosclerosis, apoptosis inhibition and angiogenesis. The ETs exert their effects via activation of two distinct G-protein coupled receptor subtypes termed ET(A) and ET(B). To date a number of ET receptor ligands with good affinity and selectivity is known, nevertheless these compounds belong only to few chemical classes. The aim of this work was the identification of a "hit compound" with novel chemical structure, endowed with reasonable ET affinity and selectivity. Accordingly, a new class of (E)-alpha-[(1H-indol-3-yl)methylene]benzeneacetic acid derivatives (1-23) was synthesized for evaluation of their binding profiles.

  4. The Cortisol Paradox of Trauma-Related Disorders: Lower Phasic Responses but Higher Tonic Levels of Cortisol Are Associated with Sexual Abuse in Childhood.

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    Inga Schalinski

    Full Text Available Inconsistent findings exist for the activity of the hypothalamic-pituitary-adrenal (HPA axis in patients with stress related disorders. Recent studies point towards early life stress as a potential modulator.We investigated the impact of childhood sexual abuse on phasic (saliva cortisol reactivity and tonic (hair cortisol regulation. Furthermore, we assessed predictors on cortisol accumulation in hair. Women (N = 43 with stress-related disorders underwent a standardized assessment of idiographic adverse and traumatic experiences and psychopathology, while measuring salivary cortisol and, heart rate and blood pressure.Comparing women with and without childhood sexual abuse revealed lower rates of responders and distinct levels of salivary cortisol to the interview in conjunction with a lower heart rate for the abused group. Childhood adversities, traumatic experiences, and depression contributed to higher hair cortisol levels.Our finding of lower response rate and distinct salivary cortisol pattern in individuals with childhood sexual abuse compared to individuals without early sexual abuse supports the role of environmental programming for the HPA axis. Both, childhood adversities and traumatic stress emerge as crucial factors for long-term cortisol secretion. Lower or suppressed phasic cortisol responses to trauma-related stimuli may therefore be associated with higher tonic values. Thus, early exposure to adversities may result in a biological distinct phenotype in adult patients with stress-related disorders.

  5. Cytokines and growth factors modify the upregulation of contractile endothelin ET(A) and ET(B) receptors in rat cerebral arteries after organ culture

    DEFF Research Database (Denmark)

    Ahnstedt, H; Stenman, E; Cao, L

    2012-01-01

    Experimental cerebral ischaemia and organ culture of cerebral arteries induce an increased endothelin ET(B) receptor-mediated contraction. The aim of this study was to examine whether cytokines and growth factors, known to be activated in ischaemia, can influence the expression and function of en...

  6. Endothelin-1 Gene Polymorphisms rs5370, rs1476046, and rs3087459 are not Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus

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    Šeruga Maja

    2017-09-01

    Full Text Available Background: Diabetic nephropathy (DN is a major microvascular complication of type 2 diabetes mellitus (T2DM. Several lines of evidence implicate the endothelin (ET system in the pathophysiology of DN. The aim of the present study was to analyze if genetic polymorphisms of the ET-1 (EDN1 gene affect susceptibility to DN in Caucasians with T2DM.

  7. Low concentrations of lithium and cyclooxygenase inhibitors enhance endothelin-1 (ET-1)-induced contractions in human temporal artery, but not in porcine ophthalmic artery.

    Science.gov (United States)

    Bakken, I J; Vincent, M B; White, L R; Cappelen, J; Skaanes, K O; Sjaastad, O

    1992-11-01

    Endothelins are a recently discovered group of potent vasoconstrictor peptides synthesized by endothelial cells and other tissues in various species, which seem to participate in the regulation of vascular tonus. Abnormalities in vasoactivity in the head may be an important event in headache pathophysiology, although the mechanisms responsible for such constrictions and/or dilations are not known. The endothelium and its constrictor peptide, endothelin, may play a key role in such mechanisms. Of the various drugs used in the treatment of headache, lithium is an accepted treatment for cluster headache, and indomethacin is the drug of choice for the associated condition chronic paroxysmal hemicrania. The mechanism of action of these drugs in these headaches is not known. Due to the possible involvement of endothelin in headache disorders, the objective of this study was to verify the effects of lithium and cyclooxygenase inhibitors (indomethacin, acetylsalicylic acid and naproxen) on endothelin-1 (ET-1)-induced contractions in isolated human temporal arteries and porcine ophthalmic arteries. It was found that all drugs increased the (ET-1)-induced contractions in human temporal arteries. Conversely, there were no significant changes induced by the drugs in porcine ophthalmic arteries. These results are consistent with the variation of activity often seen in different vascular beds and between species. The potential importance of such reactions for the understanding of vascular changes putatively involved in headache development and treatment is discussed.

  8. Dual neural endopeptidase/endothelin-converting [corrected] enzyme inhibition improves endothelial function in mesenteric resistance arteries of young spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Lemkens, Pieter; Nelissen, Jelly; Meens, Merlijn J P M T

    2012-01-01

    through cleavage of big ET1 by endothelin-converting enzyme (ECE) and neutral endopeptidase (NEP). METHOD: We investigated whether the dual NEP/ECE inhibitor SOL1 improves resistance artery function and structure in 12 weeks old spontaneously hypertensive rats (SHRs) and whether arterial structural...

  9. Impact of endothelin blockade on acute exercise-induced changes in blood flow and endothelial function in type 2 diabetes mellitus.

    NARCIS (Netherlands)

    Schreuder, T.H.A.; Lotringen, J.H. van; Hopman, M.T.E.; Thijssen, D.H.J.

    2014-01-01

    Positive vascular effects of exercise training are mediated by acute increases in blood flow. Type 2 diabetes patients show attenuated exercise-induced increases in blood flow, possibly mediated by the endothelin pathway, preventing an optimal stimulus for vascular adaptation. We examined the impact

  10. LPS from Porphyromonas gingivalis increases the sensitivity of contractile response mediated by endothelin-B (ET(B)) receptors in cultured endothelium-intact rat coronary arteries

    DEFF Research Database (Denmark)

    Ghorbani, Bahareh; Holmstrup, Palle; Edvinsson, Lars

    2010-01-01

    The purpose of our study was to examine if lipopolysaccharide (LPS) from Porphyromonas gingivalis (P.g.) modifies the vasomotor responses to Endothelin-1 (ET-1) and Sarafotoxin 6c (S6c) in rat coronary arteries. The arteries were studied directly or following organ culture for 24h in absence...

  11. Effects of tissue age, presence of neurones and endothelin-3 on the ability of enteric neurone precursors to colonize recipient gut: implications for cell-based therapies.

    Science.gov (United States)

    Hotta, R; Anderson, R B; Kobayashi, K; Newgreen, D F; Young, H M

    2010-03-01

    BACKGROUND Most enteric neurones arise from neural crest cells that originate in the post-otic hindbrain, and migrate into and along the developing gastrointestinal tract. There is currently great interest in the possibility of cell therapy to replace diseased or absent enteric neurones in patients with enteric neuropathies, such as Hirschsprung's disease. However, it is unclear whether neural crest stem/progenitor cells will be able to colonize colon (i) in which the mesenchyme has differentiated into distinct layers, (ii) that already contains enteric neurones or (iii) that lacks a gene expressed by the gut mesenchyme, such as endothelin-3 (Et-3). METHODS Co-cultures were used to examine the ability of enteric neural crest-derived cells (ENCCs) from E11.5 mouse gut to colonize a variety of recipient hindguts. KEY RESULTS Enteric neural crest-derived cells migrated and gave rise to neurones in E14.5 and E16.5 aneural colon in which the external muscle layers had differentiated, but they did not migrate as far as in younger colon. There was no evidence of altered ENCC proliferation, cell death or neuronal differentiation in older recipient explants. Enteric neural crest-derived cells failed to enter most recipient E14.5 and E16.5 colon explants already containing enteric neurones, and the few that did showed very limited migration. Finally, ENCCs migrated a shorter distance and a higher proportion expressed the pan-neuronal marker, Hu, in recipient E11.5 Et-3(-/-) colon compared to wild-type recipient colon. CONCLUSIONS & INFERENCES Age and an absence of Et-3 from the recipient gut both significantly reduced but did not prevent ENCC migration, but the presence of neurones almost totally prevented ENCC migration.

  12. An intact SAM-dependent methyltransferase fold is encoded by the human endothelin-converting enzyme-2 gene

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    Tempel, W.; Wu, H.; Dombrovsky, L.; Zeng, H.; Loppnau, P.; Zhu, H.; Plotnikov, A.N.; Bochkarev, A.; (Toronto)

    2010-08-17

    A recent survey of protein expression patterns in patients with Alzheimer's disease (AD) has identified ece2 (chromosome: 3; Locations: 3q27.1) as the most significantly downregulated gene within the tested group. ece2 encodes endothelin-converting enzyme ECE2, a metalloprotease with a role in neuropeptide processing. Deficiency in the highly homologous ECE1 has earlier been linked to increased levels of AD-related {beta}-amyloid peptide in mice, consistent with a role for ECE in the degradation of that peptide. Initially, ECE2 was presumed to resemble ECE1, in that it comprises a single transmembrane region of {approx}20 residues flanked by a small amino-terminal cytosolic segment and a carboxy-terminal lumenar peptidase domain. The carboxy-terminal domain has significant sequence similarity to both neutral endopeptidase, for which an X-ray structure has been determined, and Kell blood group protein. After their initial discovery, multiple isoforms of ECE1 and ECE2 were discovered, generated by alternative splicing of multiple exons. The originally described ece2 transcript, RefSeq NM{_}174046, contains the amino-terminal cytosolic portion followed by the transmembrane region and peptidase domain (Fig. 1, isoform B). Another ece2 transcript, available from the Mammalian Gene Collection under MGC2408 (Fig. 1, isoform C), RefSeq accession NM{_}032331, is predicted to be translated into a 255 residue peptide with low but detectable sequence similarity to known S-adenosyl-L-methionine (SAM)-dependent methyltransferases (SAM-MTs), such as the hypothetical protein TT1324 from Thermus thermophilis, PDB code 2GS9, which shares 30% amino acid sequence identity with ECE2 over 138 residues of the sequence. Intriguingly, another 'elongated' ece2 transcript (Fig. 1, isoform A) (RefSeq NM{_}014693) contains an amino-terminal portion of the putative SAM-MT domain, the transmembrane domain, and the protease domain. This suggests the possibility for coexistence of

  13. Embodying Deficiency Through ‘Affective Practice’: Shame, Relationality, and the Lived Experience of Social Class and Gender in Higher Education

    Science.gov (United States)

    Loveday, Vik

    2015-01-01

    Based on empirical research with participants from working-class backgrounds studying and working in higher education in England, this article examines the lived experience of shame. Building on a feminist Bourdieusian approach to social class analysis, the article contends that ‘struggles for value’ within the field of higher education precipitate classed judgements, which have the potential to generate shame. Through an examination of the ‘affective practice’ of judgement, the article explores the contingencies that precipitate shame and the embodiment of deficiency. The article links the classed and gendered dimensions of shame with valuation, arguing that the fundamental relationality of social class and gender is not only generative of shame, but that shame helps in turn to structure both working-class experience and a view of the working classes as ‘deficient’. PMID:28018006

  14. Cerebral amyloid angiopathy-related inflammation presenting with steroid-responsive higher brain dysfunction: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Maeda Yasushi

    2011-09-01

    Full Text Available Abstract A 56-year-old man noticed discomfort in his left lower limb, followed by convulsion and numbness in the same area. Magnetic resonance imaging (MRI showed white matter lesions in the right parietal lobe accompanied by leptomeningeal or leptomeningeal and cortical post-contrast enhancement along the parietal sulci. The patient also exhibited higher brain dysfunction corresponding with the lesions on MRI. Histological pathology disclosed β-amyloid in the blood vessels and perivascular inflammation, which highlights the diagnosis of cerebral amyloid angiopathy (CAA-related inflammation. Pulse steroid therapy was so effective that clinical and radiological findings immediately improved. CAA-related inflammation is a rare disease, defined by the deposition of amyloid proteins within the leptomeningeal and cortical arteries associated with vasculitis or perivasculitis. Here we report a patient with CAA-related inflammation who showed higher brain dysfunction that improved with steroid therapy. In cases with atypical radiological lesions like our case, cerebral biopsy with histological confirmation remains necessary for an accurate diagnosis.

  15. Dogs cannot bark: event-related brain responses to true and false negated statements as indicators of higher-order conscious processing.

    Science.gov (United States)

    Herbert, Cornelia; Kübler, Andrea

    2011-01-01

    The present study investigated event-related brain potentials elicited by true and false negated statements to evaluate if discrimination of the truth value of negated information relies on conscious processing and requires higher-order cognitive processing in healthy subjects across different levels of stimulus complexity. The stimulus material consisted of true and false negated sentences (sentence level) and prime-target expressions (word level). Stimuli were presented acoustically and no overt behavioral response of the participants was required. Event-related brain potentials to target words preceded by true and false negated expressions were analyzed both within group and at the single subject level. Across the different processing conditions (word pairs and sentences), target words elicited a frontal negativity and a late positivity in the time window from 600-1000 msec post target word onset. Amplitudes of both brain potentials varied as a function of the truth value of the negated expressions. Results were confirmed at the single-subject level. In sum, our results support recent suggestions according to which evaluation of the truth value of a negated expression is a time- and cognitively demanding process that cannot be solved automatically, and thus requires conscious processing. Our paradigm provides insight into higher-order processing related to language comprehension and reasoning in healthy subjects. Future studies are needed to evaluate if our paradigm also proves sensitive for the detection of consciousness in non-responsive patients.

  16. Higher frequency of cagA EPIYA-C Phosphorylation Sites in H. pylori strains from first-degree relatives of gastric cancer patients

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    Queiroz Dulciene MM

    2012-08-01

    Full Text Available Abstract Background To evaluate the prevalence of more virulent H. pylori genotypes in relatives of gastric cancer patients and in patients without family histories of gastric cancer. Methods We evaluated prospectively the prevalence of the infection by more virulent H. pylori strains in 60 relatives of gastric cancer patients comparing the results with those obtained from 49 patients without family histories of gastric cancer. H. pylori status was determined by the urease test, histology and presence of H. pylori ureA. The cytotoxin associated gene (cagA, the cagA-EPIYA and vacuolating cytotoxin gene (vacA were typed by PCR and the cagA EPIYA typing was confirmed by sequencing. Results The gastric cancer relatives were significant and independently more frequently colonized by H. pylori strains with higher numbers of CagA-EPIYA-C segments (OR = 4.23, 95%CI = 1.53–11.69 and with the most virulent s1m1 vacA genotype (OR = 2.80, 95%CI = 1.04–7.51. Higher numbers of EPIYA-C segments were associated with increased gastric corpus inflammation, foveolar hyperplasia and atrophy. Infection by s1m1 vacA genotype was associated with increased antral and corpus gastritis. Conclusions We demonstrated that relatives of gastric cancer patients are more frequently colonized by the most virulent H. pylori cagA and vacA genotypes, which may contribute to increase the risk of gastric cancer.

  17. Celecoxib, but not indomethacin, ameliorates the hypertensive and perivascular fibrotic actions of cyclosporine in rats: Role of endothelin signaling

    Energy Technology Data Exchange (ETDEWEB)

    El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com [Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University (Egypt); Helmy, Maged W. [Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University (Egypt); Ali, Rabab M.; El-Gowelli, Hanan M. [Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University (Egypt)

    2015-04-01

    The immunosuppressant drug cyclosporine (CSA) is used with nonsteroidal antiinflammatory drugs (NSAIDs) in arthritic conditions. In this study, we investigated whether NSAIDs modify the deleterious hypertensive action of CSA and the role of endothelin (ET) receptors in this interaction. Pharmacologic, protein expression, and histopathologic studies were performed in rats to investigate the roles of endothelin receptors (ET{sub A}/ET{sub B}) in the hemodynamic interaction between CSA and two NSAIDs, indomethacin and celecoxib. Tail-cuff plethysmography measurements showed that CSA (20 mg kg{sup −1} day{sup −1}, 10 days) increased systolic blood pressure (SBP) and heart rate (HR). CSA hypertension was associated with renal perivascular fibrosis and divergent changes in immunohistochemical signals of renal arteriolar ET{sub A} (increases) and ET{sub B} (decreases) receptors. While these effects of CSA were preserved in rats treated concomitantly with indomethacin (5 mg kg{sup −1} day{sup −1}), celecoxib (10 mg kg{sup −1} day{sup −1}) abolished the pressor, tachycardic, and fibrotic effects of CSA and normalized the altered renal ET{sub A}/ET{sub B} receptor expressions. Selective blockade of ET{sub A} receptors by atrasentan (5 mg kg{sup −1} day{sup −1}) abolished the pressor response elicited by CSA or CSA plus indomethacin. Alternatively, BQ788 (ET{sub B} receptor blocker, 0.1 mg kg{sup −1} day{sup −1}) caused celecoxib-sensitive elevations in SBP and potentiated the pressor response evoked by CSA. Together, the improved renovascular fibrotic and endothelin receptor profile (ET{sub A} downregulation and ET{sub B} upregulation) mediate, at least partly, the protective effect of celecoxib against the hypertensive effect of CSA. Clinically, the use of celecoxib along with CSA in the management of arthritic conditions might provide hypertension-free regimen. - Highlights: • Chronic CSA causes hypertension and renal perivascular fibrosis in rats.

  18. Repeat low-level blast exposure increases transient receptor potential vanilloid 1 (TRPV1 and endothelin-1 (ET-1 expression in the trigeminal ganglion.

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    Elaine D Por

    Full Text Available Blast-associated sensory and cognitive trauma sustained by military service members is an area of extensively studied research. Recent studies in our laboratory have revealed that low-level blast exposure increased expression of transient receptor potential vanilloid 1 (TRPV1 and endothelin-1 (ET-1, proteins well characterized for their role in mediating pain transmission, in the cornea. Determining the functional consequences of these alterations in protein expression is critical to understanding blast-related sensory trauma. Thus, the purpose of this study was to examine TRPV1 and ET-1 expression in ocular associated sensory tissues following primary and tertiary blast. A rodent model of blast injury was used in which anesthetized animals, unrestrained or restrained, received a single or repeat blast (73.8 ± 5.5 kPa from a compressed air shock tube once or daily for five consecutive days, respectively. Behavioral and functional analyses were conducted to assess blast effects on nocifensive behavior and TRPV1 activity. Immunohistochemistry and Western Blot were also performed with trigeminal ganglia (TG to determine TRPV1, ET-1 and glial fibrillary associated protein (GFAP expression following blast. Increased TRPV1, ET-1 and GFAP were detected in the TG of animals exposed to repeat blast. Increased nocifensive responses were also observed in animals exposed to repeat, tertiary blast as compared to single blast and control. Moreover, decreased TRPV1 desensitization was observed in TG neurons exposed to repeat blast. Repeat, tertiary blast resulted in increased TRPV1, ET-1 and GFAP expression in the TG, enhanced nociception and decreased TRPV1 desensitization.

  19. Hypoxia-inducible factor-1α, vascular endothelial growth factor, inducible nitric oxide synthase, and endothelin-1 expression correlates with angiogenesis in congenital heart disease

    Directory of Open Access Journals (Sweden)

    Hsin-Ling Yin

    2016-07-01

    Full Text Available In Taiwan, the average prevalence of congenital heart disease (CHD is 13.08/1000 live births. Most children with CHD die before the age of 5 years; therefore, identifying treatment methods to extend the life of CHD patients is an important issue in clinical practice. The objective of this study is to evaluate the roles of hypoxia-inducible factor-1α (HIF-1α, vascular endothelial growth factor (VEGF, inducible nitric oxide synthase (iNOS, endothelin-1 (ET-1, and CD34 in CHD autopsy cases in comparison with autopsy cases without CHD. The study included 19 autopsy cases, which were divided into the following four groups: acyanotic CHD (n = 11, cyanotic CHD (n = 3, CHD associated with chromosomal abnormalities (n = 3, and complex CHD (n = 2. Heart specimens obtained from 10 autopsy cases without CHD were included as controls. Our results indicated that high percentages of HIF-1α (100%, VEGF (89.5%, iNOS (78.9%, and ET-1 (84.2% expressions were observed in CHD autopsy cases and this was found to be significant. HIF-1α induced by hypoxia could play a potential role in relating downstream gene expressions in CHD patients. Upregulation of VEGF by HIF-1α could play an important role in triggering angiogenesis to protect myocardial cell survival in a hypoxic microenvironment. Therefore, HIF-1α could be a significant prognosis marker in CHD and be a prospective candidate in the development of target therapy in cardiovascular diseases.

  20. Organized Sport Participation Is Associated with Higher Levels of Overall Health-Related Physical Activity in Children (CHAMPS Study-DK)

    Science.gov (United States)

    Hebert, Jeffrey J.; Møller, Niels C.; Andersen, Lars B.; Wedderkopp, Niels

    2015-01-01

    Introduction Many children fail to meet international guideline recommendations for health-related activity (≥60 minutes/day of moderate-to-vigorous physical activity [MVPA]), and intervention studies to date have reported negligible effects. Objective Explore the associations of organized leisure-time sport participation with overall physical activity levels and health-related physical activity guideline concordance. Methods This prospective cohort study was nested in the Childhood Health, Activity, and Motor Performance School Study Denmark. Study participants were a representative sample of 1124 primary school students. Organized leisure-time sport participation was reported via text messaging and physical activity was objectively measured over seven days with accelerometry. Associations between sport participation and physical activity level were explored with multilevel mixed-effects regression models and reported with beta coefficients (b) and adjusted odds ratios (aOR). Results Participants were 53% female, with mean(SD) age = 8.4(1.4) years. Boys were more active than girls (psports (gymnastics, basketball, volleyball) were inconsistent. Conclusions Many children, particularly girls and those in higher grade levels do not adhere to health-related physical activity recommendations. Organized leisure-time sport participation may be a viable strategy to increase overall health-related physical activity levels and international guideline concordance in children. PMID:26262678

  1. Higher serum cholesterol is associated with intensified age-related neural network decoupling and cognitive decline in early- to mid-life.

    Science.gov (United States)

    Spielberg, Jeffrey M; Sadeh, Naomi; Leritz, Elizabeth C; McGlinchey, Regina E; Milberg, William P; Hayes, Jasmeet P; Salat, David H

    2017-06-01

    Mounting evidence indicates that serum cholesterol and other risk factors for cardiovascular disease intensify normative trajectories of age-related cognitive decline. However, the neural mechanisms by which this occurs remain largely unknown. To understand the impact of cholesterol on brain networks, we applied graph theory to resting-state fMRI in a large sample of early- to mid-life Veterans (N = 206, Meanage  = 32). A network emerged (centered on the banks of the superior temporal sulcus) that evidenced age-related decoupling (i.e., decreased network connectivity with age), but only in participants with clinically-elevated total cholesterol (≥180 mg/dL). Crucially, decoupling in this network corresponded to greater day-to-day disability and mediated age-related declines in psychomotor speed. Finally, examination of network organization revealed a pattern of age-related dedifferentiation for the banks of the superior temporal sulcus, again present only with higher cholesterol. More specifically, age was related to decreasing within-module communication (indexed by Within-Module Degree Z-Score) and increasing between-module communication (indexed by Participation Coefficient), but only in participants with clinically-elevated cholesterol. Follow-up analyses indicated that all findings were driven by low-density lipoprotein (LDL) levels, rather than high-density lipoprotein (HDL) or triglycerides, which is interesting as LDL levels have been linked to increased risk for cardiovascular disease, whereas HDL levels appear inversely related to such disease. These findings provide novel insight into the deleterious effects of cholesterol on brain health and suggest that cholesterol accelerates the impact of age on neural trajectories by disrupting connectivity in circuits implicated in integrative processes and behavioral control. Hum Brain Mapp 38:3249-3261, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. Q-T interval (QTc) in patients with cirrhosis: relation to vasoactive peptides and heart rate

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Gülberg, V.; Fuglsang, Stefan

    2007-01-01

    OBJECTIVE: Prolonged Q-T interval (QT) has been reported in patients with cirrhosis who also exhibit profound abnormalities in vasoactive peptides and often present with elevated heart rate (HR). The aim of this study was to relate QT to the circulating level of endothelins (ET-1 and ET-3...

  3. VSM growth is stimulated in sympathetic neuron/VSM cocultures: role of TGF-beta2 and endothelin.

    Science.gov (United States)

    Damon, D H

    2000-02-01

    Sympathetic nerves are purported to stimulate blood vessel growth. The mechanism(s) underlying this stimulation has not been determined. With use of an in vitro coculture model, the present study tests the hypothesis that sympathetic neurons stimulate the growth of vascular smooth muscle (VSM) and evaluates potential mechanisms mediating this stimulation. Sympathetic neurons isolated from superior cervical ganglia (SCG) stimulated the growth of VSM. Growth of VSM in the presence of SCG (856 +/- 81%) was significantly greater than that in the absence of SCG (626 +/- 66%, P VSM growth in transwell cocultures. An antibody that neutralized the activity of transforming growth factor-beta2 (TGF-beta2) inhibited SCG stimulation of VSM growth in coculture. SCG stimulation of VSM growth was also inhibited by an endothelin A receptor antagonist. These data suggest novel mechanisms for sympathetic modulation of vascular growth that may play a role in the physiological and/or pathological growth of the vasculature.

  4. Relaxing Responses to Hydrogen Peroxide and Nitric Oxide in Human Pericardial Resistance Arteries Stimulated with Endothelin-1

    DEFF Research Database (Denmark)

    Leurgans, Thomas M; Bloksgaard, Maria; Irmukhamedov, Akhmadjon

    2017-01-01

    In human pericardial resistance arteries, effects of the endothelium-dependent vasodilator bradykinin are mediated by NO during contraction induced by K(+) or the TxA2 analogue U46619 and by H2 O2 during contraction by endothelin-1 (ET-1), respectively. We tested the hypotheses that ET-1 reduces...... relaxing effects of NO and increases those of H2 O2 in resistance artery smooth muscle of patients with cardiovascular disease. Arterial segments, dissected from the parietal pericardium of 39 cardiothoracic surgery patients, were studied by myography during amplitude-matched contractions induced by K......(+) , the TXA2 analogue U46619 or ET-1. Effects of the NO-donor Na-nitroprusside (SNP) and of exogenous H2 O2 were recorded in absence and presence of inhibitors of cyclooxygenases, NO-synthases and small and intermediate conductance calcium-activated K(+) channels. During contractions induced by either...

  5. A causal role for endothelin-1 in the vascular adaptation to skeletal muscle deconditioning in spinal cord injury.

    Science.gov (United States)

    Thijssen, Dick H J; Ellenkamp, Reinier; Kooijman, Miriam; Pickkers, Peter; Rongen, Gerard A; Hopman, Maria T E; Smits, Paul

    2007-02-01

    Endothelin-1 (ET-1) contributes to the increased peripheral resistance in heart failure and hypertension. Physical inactivity is associated with cardiovascular disease and characterized by increased vascular tone. In this study, we assess the contribution of ET-1 to the increased vascular tone in the extremely deconditioned legs of spinal cord-injured (SCI) individuals before and after exercise training. In 8 controls and 8 SCI individuals, bilateral thigh blood flow was measured by plethysmography before and during the administration of an ET(A)/ET(B)-receptor blocker into the femoral artery. In SCI, this procedure was repeated after 6 weeks of electro-stimulated training. In a subset of SCI (n=4), selective ET(A)-receptor blockade was performed to determine the role of the ET(A)-receptors. In controls, dual ET-receptor blockade increased leg blood flow at the infused side (10%, PPhysical training reverses the ET-1-pathway, which normalizes basal leg vascular tone.

  6. Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease

    DEFF Research Database (Denmark)

    Dimitrijevic, Ivan; Edvinsson, Marie-Louise; Chen, Qingwen

    2009-01-01

    pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A (ETA) and type B (ETB), and angiotensin type 1 (AT1) and type 2 (AT2) receptors expression and function were examined using immunohistochemistry, Western blot and in vitro...... in the healthy controls (100% +/- 28%). The data was confirmed by Western blotting. Arteries from CABG patients showed increased vasoconstriction upon administration of the selective ETB receptor agonist sarafotoxin S6c, compared to healthy controls (P ...%). The increased AT1 receptor expression was confirmed by Western blotting. Myograph experiment did however not show any change in vasoconstriction to angiotensin II in CABG patients compared to healthy controls (P = n.s). CONCLUSION: The results demonstrate, for the first time, upregulation of ETB and AT1...

  7. NF-kappaB signaling mediates vascular smooth muscle endothelin type B receptor expression in resistance arteries

    DEFF Research Database (Denmark)

    Zheng, Jian-Pu; Zhang, Yaping; Edvinsson, Lars

    2010-01-01

    upregulation and activation of NF-kappaB were studied at functional contraction (in vitro myograph), mRNA (real-time PCR), and protein (Western blot and immunocytochemistry) levels during organ culture of rat mesenteric arteries. Organ culture of the artery segments induced a time-dependent strong contractile......Vascular smooth muscle cells (SMC) endothelin type B (ET(B)) receptor upregulation results in strong vasoconstriction and reduction of local blood flow. We hypothesizes that the underlying molecular mechanisms involve transcriptional factor nuclear factor-kappaB (NF-kappaB) pathway. ET(B) receptor...... response to sarafotoxin 6c in parallel with enhanced expression of ET(B) receptor mRNA and protein in the SMC. Western blot experiments demonstrated that phosphorylation of NF-kappaB p65 was time-dependently induced during organ culture starting at 1h. In addition, cytoplasmic IkB degradation occurred...

  8. Organized Sport Participation Is Associated with Higher Levels of Overall Health-Related Physical Activity in Children (CHAMPS Study-DK).

    Science.gov (United States)

    Hebert, Jeffrey J; Møller, Niels C; Andersen, Lars B; Wedderkopp, Niels

    2015-01-01

    Many children fail to meet international guideline recommendations for health-related activity (≥60 minutes/day of moderate-to-vigorous physical activity [MVPA]), and intervention studies to date have reported negligible effects. Explore the associations of organized leisure-time sport participation with overall physical activity levels and health-related physical activity guideline concordance. This prospective cohort study was nested in the Childhood Health, Activity, and Motor Performance School Study Denmark. Study participants were a representative sample of 1124 primary school students. Organized leisure-time sport participation was reported via text messaging and physical activity was objectively measured over seven days with accelerometry. Associations between sport participation and physical activity level were explored with multilevel mixed-effects regression models and reported with beta coefficients (b) and adjusted odds ratios (aOR). Participants were 53% female, with mean(SD) age = 8.4(1.4) years. Boys were more active than girls (pparticipation at any frequency was associated with greater overall MVPA (b[95% CI] = 0.66[0.20,1.13] to 2.44[1.44,3.44]). Depending on participation frequency, this equates to 5-20 minutes more MVPA on the average day and 3 to 15 fold increased odds of achieving recommended levels of health-related physical activity (aOR[95%CI] = 3.04[1.49,6.19] to 14.49[1.97,106.56]). Similar associations were identified among children playing handball at least twice per week. Relationships with other sports (gymnastics, basketball, volleyball) were inconsistent. Many children, particularly girls and those in higher grade levels do not adhere to health-related physical activity recommendations. Organized leisure-time sport participation may be a viable strategy to increase overall health-related physical activity levels and international guideline concordance in children.

  9. Higher maternal serum concentrations of nicotinamide and related metabolites in late pregnancy are associated with a lower risk of offspring atopic eczema at age 12 months.

    Science.gov (United States)

    El-Heis, S; Crozier, S R; Robinson, S M; Harvey, N C; Cooper, C; Inskip, H M; Godfrey, K M

    2016-10-01

    Evidence that atopic eczema partly originates in utero is increasing, with some studies linking the risk of developing the condition with aspects of maternal diet during pregnancy. Nicotinamide, a naturally occurring nutrient that is maintained through the dietary intakes of vitamin B3 and tryptophan, has been used in the treatment of some skin conditions including atopic eczema. To examine the relation of maternal serum concentrations of nicotinamide and related tryptophan metabolites to the risk of atopic eczema in the offspring. Within the UK Southampton Women Survey, infantile atopic eczema at ages 6 and 12 months was ascertained (modified UK Working Party Criteria for the Definition of Atopic Dermatitis). Maternal serum levels of kynurenine, kynurenic acid, anthranilic acid, tryptophan, nicotinamide and N1-methylnicotinamide were measured in late pregnancy by mass spectrometry (n = 497) and related to the odds ratio of infantile atopic eczema. Maternal nicotinamide and related metabolite concentrations were not associated with offspring atopic eczema at age 6 months. Higher concentrations of nicotinamide and anthranilic acid were, however, associated with a lower risk of eczema at age 12 months (odds ratios 0.69, 95% CI 0.53-0.91/SD change, P = 0.007 and 0.63, 0.48-0.83, P = 0.001, respectively). The associations were robust to adjustment for potentially confounding variables. This is the first study linking maternal serum concentrations of nicotinamide and related metabolites to the risk of atopic eczema in the offspring. The findings point to potentially modifiable maternal influences on this complex and highly prevalent condition. © 2016 John Wiley & Sons Ltd.

  10. Organized Sport Participation Is Associated with Higher Levels of Overall Health-Related Physical Activity in Children (CHAMPS Study-DK.

    Directory of Open Access Journals (Sweden)

    Jeffrey J Hebert

    Full Text Available Many children fail to meet international guideline recommendations for health-related activity (≥60 minutes/day of moderate-to-vigorous physical activity [MVPA], and intervention studies to date have reported negligible effects.Explore the associations of organized leisure-time sport participation with overall physical activity levels and health-related physical activity guideline concordance.This prospective cohort study was nested in the Childhood Health, Activity, and Motor Performance School Study Denmark. Study participants were a representative sample of 1124 primary school students. Organized leisure-time sport participation was reported via text messaging and physical activity was objectively measured over seven days with accelerometry. Associations between sport participation and physical activity level were explored with multilevel mixed-effects regression models and reported with beta coefficients (b and adjusted odds ratios (aOR.Participants were 53% female, with mean(SD age = 8.4(1.4 years. Boys were more active than girls (p<0.001, and physical activity levels and guideline concordance decreased with age (p<0.001. Soccer participation at any frequency was associated with greater overall MVPA (b[95% CI] = 0.66[0.20,1.13] to 2.44[1.44,3.44]. Depending on participation frequency, this equates to 5-20 minutes more MVPA on the average day and 3 to 15 fold increased odds of achieving recommended levels of health-related physical activity (aOR[95%CI] = 3.04[1.49,6.19] to 14.49[1.97,106.56]. Similar associations were identified among children playing handball at least twice per week. Relationships with other sports (gymnastics, basketball, volleyball were inconsistent.Many children, particularly girls and those in higher grade levels do not adhere to health-related physical activity recommendations. Organized leisure-time sport participation may be a viable strategy to increase overall health-related physical activity levels and

  11. Higher bone turnover is related to spinal radiographic damage and low bone mineral density in ankylosing spondylitis patients with active disease: a cross-sectional analysis.

    Directory of Open Access Journals (Sweden)

    Suzanne Arends

    Full Text Available INTRODUCTION: Ankylosing spondylitis (AS is characterized by excessive bone formation and bone loss. Our aim was to investigate the association of bone turnover markers (BTM with spinal radiographic damage and bone mineral density (BMD in AS patients with active disease. METHODS: 201 consecutive AS outpatients of the Groningen Leeuwarden AS (GLAS cohort were included. Serum markers of bone resorption (C-telopeptides of type-I collagen, sCTX and bone formation (procollagen type-I N-terminal peptide, PINP; bone-specific alkaline phosphatase, BALP were measured. Z-scores were used to correct for the normal influence that age and gender have on bone turnover. Radiographs were scored by two independent readers according to modified Stoke AS Spinal Score (mSASSS. The presence of complete bridging (ankylosis of at least two vertebrae was considered as measure of more advanced radiographic damage. Low BMD was defined as lumbar spine and/or hip BMD Z-score ≤ -1. RESULTS: Of the 151 patients with complete data, 52 (34% had ≥ 1 complete bridge, 49 (33% had ≥ 1 syndesmophyte (non-bridging, and 50 (33% had no syndesmophytes. 66 (44% had low BMD. Patients with bridging had significantly higher sCTX and PINP Z-scores than patients without bridging (0.43 vs. -0.55 and 0.55 vs. 0.04, respectively. Patients with low BMD had significantly higher sCTX Z-score than patients with normal BMD (-0.08 vs. -0.61. After correcting for gender, symptom duration, and CRP, sCTX Z-score remained significantly related to the presence of low BMD alone (OR: 1.60, bridging alone (OR: 1.82, and bridging in combination with low BMD (OR: 2.26. CONCLUSIONS: This cross-sectional study in AS patients with active and relatively long-standing disease demonstrated that higher serum levels of sCTX, and to a lesser extent PINP, are associated with the presence of complete bridging. sCTX was also associated with low BMD. Longitudinal studies are needed to confirm that serum levels of s

  12. Higher bone turnover is related to spinal radiographic damage and low bone mineral density in ankylosing spondylitis patients with active disease: a cross-sectional analysis.

    Science.gov (United States)

    Arends, Suzanne; Spoorenberg, Anneke; Efde, Monique; Bos, Reinhard; Leijsma, Martha K; Bootsma, Hendrika; Veeger, Nic J G M; Brouwer, Elisabeth; van der Veer, Eveline

    2014-01-01

    Ankylosing spondylitis (AS) is characterized by excessive bone formation and bone loss. Our aim was to investigate the association of bone turnover markers (BTM) with spinal radiographic damage and bone mineral density (BMD) in AS patients with active disease. 201 consecutive AS outpatients of the Groningen Leeuwarden AS (GLAS) cohort were included. Serum markers of bone resorption (C-telopeptides of type-I collagen, sCTX) and bone formation (procollagen type-I N-terminal peptide, PINP; bone-specific alkaline phosphatase, BALP) were measured. Z-scores were used to correct for the normal influence that age and gender have on bone turnover. Radiographs were scored by two independent readers according to modified Stoke AS Spinal Score (mSASSS). The presence of complete bridging (ankylosis of at least two vertebrae) was considered as measure of more advanced radiographic damage. Low BMD was defined as lumbar spine and/or hip BMD Z-score ≤ -1. Of the 151 patients with complete data, 52 (34%) had ≥ 1 complete bridge, 49 (33%) had ≥ 1 syndesmophyte (non-bridging), and 50 (33%) had no syndesmophytes. 66 (44%) had low BMD. Patients with bridging had significantly higher sCTX and PINP Z-scores than patients without bridging (0.43 vs. -0.55 and 0.55 vs. 0.04, respectively). Patients with low BMD had significantly higher sCTX Z-score than patients with normal BMD (-0.08 vs. -0.61). After correcting for gender, symptom duration, and CRP, sCTX Z-score remained significantly related to the presence of low BMD alone (OR: 1.60), bridging alone (OR: 1.82), and bridging in combination with low BMD (OR: 2.26). This cross-sectional study in AS patients with active and relatively long-standing disease demonstrated that higher serum levels of sCTX, and to a lesser extent PINP, are associated with the presence of complete bridging. sCTX was also associated with low BMD. Longitudinal studies are needed to confirm that serum levels of sCTX can serve as objective marker for bone-related

  13. Higher Education.

    Science.gov (United States)

    Hendrickson, Robert M.

    This chapter reviews litigation in higher education for 1986. The first section discusses the relationship between postsecondary institutions and various governmental agencies, in which litigation covers questions on the authority of boards, access to information through sunshine laws, questions of tax exempt status, and issues of accreditation.…

  14. Higher incidence of rheumatoid arthritis in patients with symptomatic osteoarthritis or osteoarthritis-related surgery: a nationwide, population-based, case-control study in Taiwan.

    Science.gov (United States)

    Lu, Ming-Chi; Liu, Keng-Chang; Lai, Ning-Sheng; Koo, Malcolm

    2015-12-18

    To investigate the risk of incident rheumatoid arthritis in patients with symptomatic osteoarthritis or osteoarthritis-related surgery using a nationwide health claims database. A nationwide, population-based, case-control study. Taiwan's National Health Insurance Research Database. A total of 1147 patients (aged 20-100 years) with rheumatoid arthritis and 5735 controls who were frequency-matched for sex, 10-year age interval and year of catastrophic illness certificate application date (index year) were identified. All participants were retrospectively traced, up to 14 years prior to their index year, for diagnosis of osteoarthritis or osteoarthritis-related surgery. Multivariate logistic regression analyses were conducted to quantify the association between rheumatoid arthritis and osteoarthritis. The risks of rheumatoid arthritis were significantly higher in patients with symptomatic osteoarthritis (adjusted OR=5.24, posteoarthritis-related surgery (adjusted OR=2.27, prisk of rheumatoid arthritis in Taiwanese patients with symptomatic osteoarthritis. Our findings were consistent with the hypothesis that osteoarthritis might be a triggering factor of rheumatoid arthritis in environment-sensitised and genetically susceptible individuals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. Resveratrol inhibits the intracellular calcium increase and angiotensin/endothelin system activation induced by soluble uric acid in mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Albertoni, G.; Schor, N. [Divisão de Nefrologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2014-10-24

    Resveratrol (Resv) is natural polyphenol found in grapes. This study evaluated the protective effect of Resv against the effects of uric acid (UA) in immortalized human mesangial cells (ihMCs). ihMCs were preincubated with Resv (12.5 µM) for 1 h and treated with UA (10 mg/dL) for 6 or 12 h. The intracellular calcium concentration [Ca{sup 2+}]i was quantified by fluorescence using flow cytometry. Angiotensinogen (AGT) and pre-pro endothelin-1 (ppET-1) mRNA were assayed by quantitative real-time RT-PCR. Angiotensin II (AII) and endothelin-1 (ET-1) were assayed by ELISA. UA significantly increased [Ca{sup 2+}]i. Pre-incubation with Resv significantly reduced the change in [Ca{sup 2+}]i induced by UA. Incubation with UA for 6 or 12 h also increased AGT mRNA expression and AII protein synthesis. Resv blunted these increases in AGT mRNA expression and AII protein. Incubation with UA in the ihMCs increased ppET-1 expression and ET-1 protein synthesis at 6 and 12 h. When ihMCs were pre-incubated with Resv, UA had a significantly diminished effect on ppET-1 mRNA expression and ET-1 protein synthesis at 6 and 12 h, respectively. Our results suggested that UA triggers reactions including AII and ET-1 production in mesangial cells. The renin-angiotensin system may contribute to the pathogenesis of renal function and chronic kidney disease. Resv can minimize the impact of UA on AII, ET-1 and the increase of [Ca{sup 2+}]i in mesangial cells, suggesting that, at least in part, Resv can prevent the effects of soluble UA in mesangial cells.

  16. Myoendothelial coupling in the mesenteric arterial bed; segmental differences and interplay between nitric oxide and endothelin-1

    Science.gov (United States)

    Hilgers, RHP; De Mey, JGR

    2009-01-01

    Background and purpose: We tested the hypothesis that activated arterial smooth muscle (ASM) stimulates endothelial vasomotor influences via gap junctions and that the significance of this myoendothelial coupling increases with decreasing arterial diameter. Experimental approach: From WKY rats, first-, second-, third-and fourth-order branches of the superior mesenteric artery (MA1, MA2, MA3 and MA4 respectively) were isolated and mounted in wire-myographs to record vasomotor responses to 0.16–20 µmol·L−1 phenylephrine. Key results: Removal of endothelium increased the sensitivity (pEC50) to phenylephrine in all arteries. The nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) (100 µmol·L−1) did not modify pEC50 to phenylephrine in all denuded arteries, and increased it in intact MA1, MA2 and MA3 to the same extent as denudation. However, in intact MA4, the effect of L-NAME was significantly larger (ΔpEC50 0.57 ± 0.02) than the effect of endothelium removal (ΔpEC50 0.20 ± 0.06). This endothelium-dependent effect of L-NAME in MA4 was inhibited by (i) steroidal and peptidergic uncouplers of gap junctions; (ii) a low concentration of the NO donor sodium nitroprusside; and (iii) by the endothelin-receptor antagonist bosentan. It was also observed during contractions induced by (i) calcium channel activation (BayK 8644, 0.001–1 µmol·L−1); (ii) depolarization (10–40 mmol·L−1 K+); and (iii) sympathetic nerve stimulation (0.25–32 Hz). Conclusions and implications: These pharmacological observations indicated feedback control by endothelium of ASM reactivity involving gap junctions and a balance between endothelium-derived NO and endothelin-1. This myoendothelial coupling was most prominent in distal resistance arteries. PMID:19302591

  17. Significance of the Melanocortin 1 and Endothelin B Receptors in Melanocyte Homeostasis and Prevention of Sun-Induced Genotoxicity

    Science.gov (United States)

    Swope, Viki B.; Abdel-Malek, Zalfa A.

    2016-01-01

    The membrane bound melanocortin 1 receptor (MC1R), and the endothelin B receptor (ENDBR) are two G-protein coupled receptors that play important roles in constitutive regulation of melanocytes and their response to ultraviolet radiation (UVR), the main etiological factor for melanoma. The human MC1R is a Gs protein-coupled receptor, which is activated by its agonists α-melanocyte stimulating hormone (α-melanocortin; α-MSH) and adrenocorticotropic hormone (ACTH). The ENDBR is a Gq coupled-receptor, which is activated by Endothelin (ET)-3 during embryonic development, and ET-1 postnatally. Pigmentation and the DNA repair capacity are two major factors that determine the risk for melanoma. Activation of the MC1R by its agonists stimulates the synthesis of eumelanin, the dark brown photoprotective pigment. In vitro studies showed that α-MSH and ET-1 interact synergistically in the presence of basic fibroblast growth factor to stimulate human melanocyte proliferation and melanogenesis, and to inhibit UVR-induced apoptosis. An important function of the MC1R is reduction of oxidative stress and activation of DNA repair pathways. The human MC1R is highly polymorphic, and MC1R variants, particularly those that cause loss of function of the expressed receptor, are associated with increased melanoma risk independently of pigmentation. These variants compromise the DNA repair and antioxidant capacities of human melanocytes. Recently, activation of ENDBR by ET-1 was reported to reduce the induction and enhance the repair of UVR-induced DNA photoproducts. We conclude that α-MSH and ET-1 and their cognate receptors MC1R and ENDBR reduce the risk for melanoma by maintaining genomic stability of melanocytes via modulating the DNA damage response to solar UVR. Elucidating the response of melanocytes to UVR should improve our understanding of the process of melanomagenesis, and lead to effective melanoma chemoprevention, as well as therapeutic strategies. PMID:27582758

  18. Significance of the Melanocortin 1 and Endothelin B Receptors in Melanocyte Homeostasis and Prevention of Sun-Induced Genotoxicity

    Directory of Open Access Journals (Sweden)

    Zalfa A. Abdel-Malek

    2016-08-01

    Full Text Available The membrane bound melanocortin 1 receptor (MC1R, and the endothelin B receptor (ENDBR are two G-protein coupled receptors that play important roles in constitutive regulation of melanocytes and their response to ultraviolet radiation (UVR, the main etiological factor for melanoma. The human MC1R is a Gs protein-coupled receptor, which is activated by its agonists α-melanocyte stimulating hormone (α-melanocortin; α-MSH and adrenocorticotropic hormone (ACTH. The ENDBR is a Gq coupled-receptor, which is activated by Endothelin (ET-3 during embryonic development, and ET-1 postnatally. Pigmentation and the DNA repair capacity are two major factors that determine the risk for melanoma. Activation of the MC1R by its agonists stimulates the synthesis of eumelanin, the dark brown photoprotective pigment. In vitro studies showed that α-MSH and ET-1 interact synergistically in the presence of basic fibroblast growth factor (bFGF to stimulate human melanocyte proliferation and melanogenesis, and to inhibit UVR-induced apoptosis. An important function of the MC1R is reduction of oxidative stress and activation of DNA repair pathways. The human MC1R is highly polymorphic, and MC1R variants, particularly those that cause loss of function of the expressed receptor, are associated with increased melanoma risk independently of pigmentation. These variants compromise the DNA repair and antioxidant capacities of human melanocytes. Recently, activation of ENDBR by ET-1 was reported to reduce the induction and enhance the repair of UVR-induced DNA photoproducts. We conclude that α-MSH and ET-1 and their cognate receptors MC1R and ENDBR reduce the risk for melanoma by maintaining genomic stability of melanocytes via modulating the DNA damage response to solar UVR. Elucidating the response of melanocytes to UVR should improve our understanding of the process of melanomagenesis, and lead to effective melanoma chemoprevention, as well as therapeutic strategies.

  19. Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognitive responses in urban children.

    Directory of Open Access Journals (Sweden)

    Lilian eCalderon-Garciduenas

    2013-08-01

    Full Text Available Air pollution exposures are linked to systemic inflammation, cardiovascular and respiratory morbidity and mortality, neuroinflammation and neuropathology in young urbanites. In particular, most Mexico City Metropolitan Area (MCMA children exhibit subtle cognitive deficits, and neuropathology studies show 40% of them exhibiting frontal tau hyperphosphorylation and 51% amyloid-β diffuse plaques (compared to 0% in low pollution control children. We assessed whether a short cocoa intervention can be effective in decreasing plasma endothelin 1 (ET-1 and/or inflammatory mediators in MCMA children. Thirty g of dark cocoa with 680 mg of total flavonols were given daily for 10.11± 3.4 days (range 9 to 24 days to 18 children (10.55yrs, SD =1.45; 11F/7M. Key metabolite ratios in frontal white matter and in hippocampus pre and during cocoa intervention were quantified by magnetic resonance spectroscopy. ET-1 significantly decreased after cocoa treatment (p=0.0002. Fifteen children (83% showed a marginally significant individual improvement in one or both of the applied simple short memory tasks. Endothelial dysfunction is a key feature of exposure to particulate matter and decreased endothelin-1 bioavailability is likely useful for brain function in the context of air pollution. Our findings suggest that cocoa interventions may be critical for early implementation of neuroprotection of highly exposed urban children. Multi-domain nutraceutical interventions could limit the risk for endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, cognitive deficits, structural volumetric detrimental brain effects, and the early development of the neuropathological hallmarks of Alzheimer’s and Parkinson’s diseases.

  20. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yan-Jie [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Juan, Chi-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Kwok, Ching-Fai [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hsu, Yung-Pei [Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Shih, Kuang-Chung [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Chen, Chin-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Ho, Low-Tone, E-mail: ltho@vghtpe.gov.tw [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China)

    2015-05-08

    Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET{sub A}R during insulin resistance, ET{sub A}R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET{sub A}R expression, but not ET{sub B}R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET{sub A}R pathway

  1. Role of endothelin receptor activation in secondary pulmonary hypertension in awake swine after myocardial infarction

    Science.gov (United States)

    Houweling, Birgit; Merkus, Daphne; Sorop, Oana; Boomsma, Frans; Duncker, Dirk J

    2006-01-01

    We previously observed that pulmonary hypertension secondary to myocardial infarction (MI) in swine is characterized by elevated plasma endothelin (ET) levels and pulmonary vascular resistance (PVR). Consequently, we tested the hypothesis that an increased ET-mediated vasoconstrictor influence contributes to secondary pulmonary hypertension after MI and investigated the involvement of ETA and ETB receptor subtypes. Chronically instrumented swine with (MI swine; n = 25) or without (normal swine; n = 19) MI were studied at rest and during treadmill exercise (up to 4 km h−1), in the absence and presence of the ETA antagonist EMD 122946 or the mixed ETA/ETB antagonist tezosentan. In normal swine, exercise caused a small decrease in PVR. ETA blockade had no effect on PVR at rest or during exercise. Conversely, ETA/ETB blockade decreased PVR but only during exercise (at 4 km h−1, from 3.0 ± 0.1 to 2.3 ± 0.1 mmHg min l−1; P ≤ 0.05). MI increased pulmonary arterial pressure and PVR both at rest and during exercise (both P ≤ 0.05). The increased pulmonary arterial pressure correlated with the increased plasma ET levels in resting MI swine (r = 0.71; P ≤ 0.01). Furthermore, the pulmonary vasoconstrictor response to ET-1 infusion was enhanced after MI (P ≤ 0.05). ETA/ETB blockade decreased PVR in MI swine from 3.6 ± 0.3 to 3.1 ± 0.5 mmHg min l−1 at rest and from 3.4 ± 0.3 to 2.4 ± 0.2 mmHg min l−1 during exercise at 4 km h−1 (both P ≤ 0.05). This increased response to mixed ETA/ETB blockade in MI compared to normal swine appeared to be the result of an increased ETA-mediated vasoconstriction, as ETA blockade decreased PVR in MI swine from 3.4 ± 0.4 to 2.8 ± 0.2 mmHg min l−1 at rest and from 3.1 ± 0.3 to 2.6 ± 0.2 mmHg min l−1 at 4 km h−1 (both P ≤ 0.05). In conclusion, increased plasma ET levels together with increased pulmonary resistance vessel responsiveness to ET result in an exaggerated pulmonary vasoconstrictor influence of ET in

  2. Confirmation of translatability and functionality certifies the dual endothelin1/VEGFsp receptor (DEspR) protein.

    Science.gov (United States)

    Herrera, Victoria L M; Steffen, Martin; Moran, Ann Marie; Tan, Glaiza A; Pasion, Khristine A; Rivera, Keith; Pappin, Darryl J; Ruiz-Opazo, Nelson

    2016-06-14

    In contrast to rat and mouse databases, the NCBI gene database lists the human dual-endothelin1/VEGFsp receptor (DEspR, formerly Dear) as a unitary transcribed pseudogene due to a stop [TGA]-codon at codon#14 in automated DNA and RNA sequences. However, re-analysis is needed given prior single gene studies detected a tryptophan [TGG]-codon#14 by manual Sanger sequencing, demonstrated DEspR translatability and functionality, and since the demonstration of actual non-translatability through expression studies, the standard-of-excellence for pseudogene designation, has not been performed. Re-analysis must meet UNIPROT criteria for demonstration of a protein's existence at the highest (protein) level, which a priori, would override DNA- or RNA-based deductions. To dissect the nucleotide sequence discrepancy, we performed Maxam-Gilbert sequencing and reviewed 727 RNA-seq entries. To comply with the highest level multiple UNIPROT criteria for determining DEspR's existence, we performed various experiments using multiple anti-DEspR monoclonal antibodies (mAbs) targeting distinct DEspR epitopes with one spanning the contested tryptophan [TGG]-codon#14, assessing: (a) DEspR protein expression, (b) predicted full-length protein size, (c) sequence-predicted protein-specific properties beyond codon#14: receptor glycosylation and internalization, (d) protein-partner interactions, and (e) DEspR functionality via DEspR-inhibition effects. Maxam-Gilbert sequencing and some RNA-seq entries demonstrate two guanines, hence a tryptophan [TGG]-codon#14 within a compression site spanning an error-prone compression sequence motif. Western blot analysis using anti-DEspR mAbs targeting distinct DEspR epitopes detect the identical glycosylated 17.5 kDa pull-down protein. Decrease in DEspR-protein size after PNGase-F digest demonstrates post-translational glycosylation, concordant with the consensus-glycosylation site beyond codon#14. Like other small single-transmembrane proteins, mass

  3. Higher education is not associated with greater cortical thickness in brain areas related to literacy or intelligence in normal aging or mild cognitive impairment.

    Science.gov (United States)

    Pillai, Jagan A; McEvoy, Linda K; Hagler, Donald J; Holland, Dominic; Dale, Anders M; Salmon, David P; Galasko, Douglas; Fennema-Notestine, Christine

    2012-01-01

    Education may reduce risk of dementia through passive reserve, by increasing neural substrate. We tested the hypotheses that education is associated with thicker cortex and reduced rates of atrophy in brain regions related to literacy and intellectual ability. Healthy older adults and those with mild cognitive impairment were categorized into high (≥18 years) and low (≤13 years) education groups. Higher education was associated with thinner cortices in several areas, but one-year atrophy rates in these areas did not differ by education group. These results do not support a passive reserve model in which early-life education protects against dementia by increasing cortical thickness. Connectivity and synaptic efficiency or other lifestyle factors may more directly reflect cognitive reserve.

  4. Greater Independence in Activities of Daily Living is Associated with Higher Health-Related Quality of Life Scores in Nursing Home Residents with Dementia

    Directory of Open Access Journals (Sweden)

    Charice S. Chan

    2015-06-01

    Full Text Available Health-related quality of life (HRQL for nursing home residents is important, however, the concept of quality of life is broad, encompasses many domains and is difficult to assess in people with dementia. Basic activities of daily living (ADL are measured routinely in nursing homes using the Resident Assessment Instrument-Minimum Data Set Version 2.0 (RAI-MDS and Functional Independence Measure (FIM instrument. We examined the relationship between HRQL and ADL to assess the future possibility of ADL dependency level serving as a surrogate measure of HRQL in residents with dementia. To assess ADL, measures derived from the RAI-MDS and FIM data were gathered for 111 residents at the beginning of our study and at 6-month follow-up. Higher scores for independence in ADL were correlated with higher scores for a disease-specific HRQL measure, the Quality of Life—Alzheimer’s Disease Scale. Preliminary evidence suggests that FIM-assessed ADL is associated with HRQL for these residents. The associations of the dressing and toileting items with HRQL were particularly strong. This finding suggests the importance of ADL function in HRQL. The RAI-MDS ADL scales should be used with caution to evaluate HRQL.

  5. Substantially Higher and Earlier Occurrence of Anti-Tuberculosis Drug-Related Adverse Reactions in HIV Coinfected Tuberculosis Patients: A Matched-Cohort Study.

    Science.gov (United States)

    Matono, Takashi; Nishijima, Takeshi; Teruya, Katsuji; Morino, Eriko; Takasaki, Jin; Gatanaga, Hiroyuki; Kikuchi, Yoshimi; Kaku, Mitsuo; Oka, Shinichi

    2017-11-01

    Little information exists on the frequency, severity, and timing of first-line anti-tuberculosis drug-related adverse events (TB-AEs) in HIV-tuberculosis coinfected (HIV-TB) patients in the antiretroviral therapy (ART) era. This matched-cohort study included HIV-TB patients as cases and HIV-uninfected tuberculosis (non-HIV-TB) patients as controls. Tuberculosis was culture-confirmed in both groups. Cases were matched to controls in a 1:4 ratio on age, sex, and year of diagnosis. TB-AEs were defined as Grade 2 or higher requiring drug discontinuation/regimen change. From 2003 to 2015, 94 cases and 376 controls were analyzed (95% men, 98% Asians). Standard four-drug combination therapy was initiated in 91% of cases and 89% of controls (p = 0.45). Cases had a higher frequency of TB-AE [51% (48/94) vs. 10% (39/376), p tuberculosis treatment. HIV infection was an independent risk factor for TB-AEs in the multivariate Cox analysis [adjusted HR (aHR): 6.96; 95% confidence interval: 3.93-12.3]. TB-AEs occurred more frequently in HIV-TB than in non-HIV-TB patients, and were more severe. The majority of TB-AEs occurred within 4 weeks of initiating anti-tuberculosis treatment. Because TB-AEs may delay ART initiation, careful monitoring during this period is warranted in coinfected patients.

  6. Work-related stress in midlife is associated with higher number of mobility limitation in older age-results from the FLAME study.

    Science.gov (United States)

    Kulmala, Jenni; Hinrichs, Timo; Törmäkangas, Timo; von Bonsdorff, Mikaela B; von Bonsdorff, Monika E; Nygård, Clas-Håkan; Klockars, Matti; Seitsamo, Jorma; Ilmarinen, Juhani; Rantanen, Taina

    2014-01-01

    The aim of this study is to investigate whether work-related stress symptoms in midlife are associated with a number of mobility limitations during three decades from midlife to late life. Data for the study come from the Finnish Longitudinal Study of Municipal Employees (FLAME). The study includes a total of 5429 public sector employees aged 44-58 years at baseline who had information available on work-related stress symptoms in 1981 and 1985 and mobility limitation score during the subsequent 28-year follow-up. Four midlife work-related stress profiles were identified: negative reactions to work and depressiveness, perceived decrease in cognition, sleep disturbances, and somatic symptoms. People with a high number of stress symptoms in 1981 and 1985 were categorized as having constant stress. The number of self-reported mobility limitations was computed based on an eight-item list of mobility tasks presented to the participants in 1992, 1997, and 2009. Data were analyzed using joint Poisson regression models. The study showed that depending on the stress profile, persons suffering from constant stress in midlife had a higher risk of 30-70 % for having one more mobility limitation during the following 28 years compared to persons without stress after adjusting for mortality, several lifestyle factors, and chronic conditions. A less pronounced risk increase (20-40 %) was observed for persons with occasional symptoms. The study suggests that effective interventions aiming to reduce work-related stress should focus on both primary and secondary prevention.

  7. Overaccumulation of higher polyamines in ripening transgenic tomato fruit revives metabolic memory, upregulates anabolism-related genes, and positively impacts nutritional quality.

    Science.gov (United States)

    Mattoo, Autar K; Chung, Sang Ho; Goyal, Ravinder K; Fatima, Tahira; Solomos, Theophanes; Srivastava, Alka; Handa, Avtar K

    2007-01-01

    Vegetables and fruits are essential components of the human diet as they are sources of vitamins, minerals, and fiber and provide antioxidants that prevent chronic diseases. Our goal is to improve durable nutritional quality of tomato fruit. We developed transgenic tomatoes expressing yeast S-adenosylmethionine decarboxylase (ySAMdc) gene driven by a fruit-specific E8 promoter to investigate the role of polyamines in fruit metabolism. Stable integration of E8-ySAMdc chimeric gene in tomato genome led to ripening-specific accumulation of polyamines, spermidine (Spd) and spermine (Spm), which in turn affected higher accumulation of glutamine, asparagine, and organic acids in the red fruit with significant decrease in the contents of valine, aspartate, sucrose, and glucose. The metabolite profiling analysis suggests that Spd/Spm are perceived as "signaling" organic-N metabolites by the fruit cells, resulting in the stimulation of carbon sequestration; enhanced synthesis of biomolecules; increased acid to sugar ratio, a good attribute for the fruit flavor; and in the accumulation of another "vital amine," choline, which is an essential micronutrient for brain development. A limited transcriptome analysis of the transgenic fruit that accumulate higher polyamines revealed a large number of differentially expressed genes, about 55% of which represented discrete functional categories, and the remaining 45% were novel, unknown, or unclassified: amino acid biosynthesis, carotenoid biosynthesis, cell wall metabolism, chaperone family, flavonoid biosynthesis, fruit ripening, isoprenoid biosynthesis, polyamine biosynthesis, signal transduction, stress/defense-related, transcription, translation, and vacuolar function. There was a good correspondence between some gene transcripts and their protein products, but not in the case of the tonoplast intrinsic protein, which showed post-transcriptional regulation. Higher metabolic activity of the transgenic fruit is reflected in higher

  8. Happiness in Higher Education

    Science.gov (United States)

    Elwick, Alex; Cannizzaro, Sara

    2017-01-01

    This paper investigates the higher education literature surrounding happiness and related notions: satisfaction, despair, flourishing and well-being. It finds that there is a real dearth of literature relating to profound happiness in higher education: much of the literature using the terms happiness and satisfaction interchangeably as if one were…

  9. Physical activity level in people with age related white matter changes correlates to better motor performance, lower comorbidity and higher cognitive level.

    Science.gov (United States)

    Pettersson, Anna F; Wahlund, Lars-Olof; Bronge, Lena; Olsson, Elisabeth; Amberla, Kaarina; Baezner, Hansjoerg; Crisby, Milita

    2017-07-12

    Physical activity plays a pivotal role in the development of disability and may modify the negative effect of vascular risk factors on progression of both cardio and cerebrovascular disorders. The aim of this study was to evaluate the activity level in people with age-related white matter changes as identified on magnetic resonance imaging (MRI) in relation to motor performance, cognition and perceived health. Data came from the first year follow up of one participating centers of the LADIS study. Fifty one subjects were first enrolled in the study. Complete first year follow up data was available for 41 subjects. Information on comorbidity, physical activity level, physical function, cognition, level of white matter changes and perceived health was collected. Physical activity level was classified with a yes or no question and with the Frenchay Activities Index (FAI). Only 36% of the subjects in this study were physically active according to the yes/no question. 27.5% of the subjects were active according to the FAI score which evaluates the everyday activities. Being active discriminated subjects with better physical function. Subjects active according to the FAI score had a higher cognitive level (p ≤ 0.01), lower comorbidity (p = 0.02) and performed better on all motor function tasks as assessed by walking speed (p ≤ 0.01) and the Short Physical Performance battery (SPPB) (p ≤ 0.01). Being physically active seems to be a long term protective factor. In our study, the majority of subjects with Age Related White Mattter Changes (ARWMC) with no or mild Instrumental Activity of Daily Living (IADL) disability did not attain recommended level of activity at first year follow up. Whether or not increasing physical activity may slow down cognitive decline and lessen development of disability in physically inactive subjects with manifest ARWC remains to be studied. not applicable.

  10. Sharply higher rates of iron deficiency in obese Mexican women and children are predicted by obesity-related inflammation rather than by differences in dietary iron intake.

    Science.gov (United States)

    Cepeda-Lopez, Ana C; Osendarp, Saskia Jm; Melse-Boonstra, Alida; Aeberli, Isabelle; Gonzalez-Salazar, Francisco; Feskens, Edith; Villalpando, Salvador; Zimmermann, Michael B

    2011-05-01

    Obese individuals may be at increased risk of iron deficiency (ID), but it is unclear whether this is due to poor dietary iron intakes or to adiposity-related inflammation. The aim of this study was to examine the relations between body mass index (BMI), dietary iron, and dietary factors affecting iron bioavailability, iron status, and inflammation [C-reactive protein (CRP)] in a transition country where obesity and ID are common. Data from the 1999 Mexican Nutrition Survey, which included 1174 children (aged 5-12 y) and 621 nonpregnant women (aged 18-50 y), were analyzed. The prevalence of obesity was 25.3% in women and 3.5% in children. The prevalence of ID was significantly (P obese women and children compared with normal-weight subjects [odds ratios (95% CIs): 1.92 (1.23, 3.01) and 3.96 (1.34, 11.67) for women and children, respectively]. Despite similar dietary iron intakes in the 2 groups, serum iron concentrations were lower in obese women than in normal-weight women (62.6 ± 29.5 compared with 72.4 ± 34.6 μg/dL; P = 0.014), and total-iron-binding capacity was higher in obese children than in normal-weight children (399 ± 51 compared with 360 ± 48 μg/dL; P obese women and children were 4 times those of their normal-weight counterparts (P obese Mexican women and children was 2-4 times that of normal-weight individuals at similar dietary iron intakes. This increased risk of ID may be due to the effects of obesity-related inflammation on dietary iron absorption. Thus, ID control efforts in Mexico may be hampered by increasing rates of adiposity in women and children.

  11. Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting.

    Science.gov (United States)

    Natarajan, Pradeep; Young, Robin; Stitziel, Nathan O; Padmanabhan, Sandosh; Baber, Usman; Mehran, Roxana; Sartori, Samantha; Fuster, Valentin; Reilly, Dermot F; Butterworth, Adam; Rader, Daniel J; Ford, Ian; Sattar, Naveed; Kathiresan, Sekar

    2017-05-30

    Relative risk reduction with statin therapy has been consistent across nearly all subgroups studied to date. However, in analyses of 2 randomized controlled primary prevention trials (ASCOT [Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm] and JUPITER [Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin]), statin therapy led to a greater relative risk reduction among a subgroup at high genetic risk. Here, we aimed to confirm this observation in a third primary prevention randomized controlled trial. In addition, we assessed whether those at high genetic risk had a greater burden of subclinical coronary atherosclerosis. We studied participants from a randomized controlled trial of primary prevention with statin therapy (WOSCOPS [West of Scotland Coronary Prevention Study]; n=4910) and 2 observational cohort studies (CARDIA [Coronary Artery Risk Development in Young Adults] and BioImage; n=1154 and 4392, respectively). For each participant, we calculated a polygenic risk score derived from up to 57 common DNA sequence variants previously associated with coronary heart disease. We compared the relative efficacy of statin therapy in those at high genetic risk (top quintile of polygenic risk score) versus all others (WOSCOPS), as well as the association between the polygenic risk score and coronary artery calcification (CARDIA) and carotid artery plaque burden (BioImage). Among WOSCOPS trial participants at high genetic risk, statin therapy was associated with a relative risk reduction of 44% (95% confidence interval [CI], 22-60; Pstatin therapy was 3.6% (95% CI, 2.0-5.1) among those in the high genetic risk group and 1.3% (95% CI, 0.6-1.9) in all others. Each 1-SD increase in the polygenic risk score was associated with 1.32-fold (95% CI, 1.04-1.68) greater likelihood of having coronary artery calcification and 9.7% higher (95% CI, 2.2-17.8) burden of carotid plaque. Those at high genetic risk have a greater

  12. Higher education does not protect against firework-related injuries: a review of the economic burden and the risk factors of firework-related injuries in the capital of Iran.

    Science.gov (United States)

    Saadat, S; Mafi, M; Smith, G A

    2012-01-01

    To examine the incidence and risk factors of firework-related injuries during the Last Wednesday Eve Festival in Tehran, Iran, with a focus on the association of socio-economic status and educational level with the use of fireworks and the incidence of firework-related injury. Cross-sectional household survey. Using a random cluster sampling approach, a household survey was conducted in Greater Tehran in April 2008. During a structured interview with an adult member of the household, questions were asked about the use of fireworks and any firework-related injuries sustained by household members during the preceding festival. Data were gathered on expenditure on fireworks, medical treatment of firework-related injuries, length of hospital stay for the treatment of these injuries, and damage to personal property by fireworks. The survey included 2456 households in Greater Tehran. At least one member of 18% of these households had used fireworks during the Last Wednesday Eve Festival in 2008. The overall incidence of firework-related injuries was 100 per 100,000 population (95% confidence interval 37-163). The use of fireworks was less common among parents and more common among male children. Individuals who used fireworks were younger than non-users. Younger age and use of fireworks were associated with firework-related injuries (P < 0.05). The mean household expenditure on fireworks was US$1.62. Among the households that had bought fireworks, the mean expenditure was US$9.40 (standard deviation US$16.34). Thirty-two households (1.3%) reported damage to personal property due to fireworks during the festival costing US$3.30-167.20. The regional price of housing in the study area was correlated with the educational level of the head of the household. Higher educational level of the head of the household was associated with participation in firework activities by household members, expenditure on fireworks, and the amount of financial loss due to fireworks (all P

  13. Stimuli of sensory-motor nerves terminate arterial contractile effects of endothelin-1 by CGRP and dissociation of ET-1/ET(A)-receptor complexes

    DEFF Research Database (Denmark)

    Meens, Merlijn J P M T; Compeer, Matthijs G; Hackeng, Tilman M

    2010-01-01

    BACKGROUND: Endothelin-1 (ET-1), a long-acting paracrine mediator, is implicated in cardiovascular diseases but clinical trials with ET-receptor antagonists were not successful in some areas. We tested whether the quasi-irreversible receptor-binding of ET-1 (i) limits reversing effects of the ant...... at an antagonist-insensitive site of the receptor and (ii) are selectively terminated by endogenously released CGRP. Hence, natural stimuli of sensory-motor nerves that stimulate release of endogenous CGRP can be considered for therapy of diseases involving ET-1.......BACKGROUND: Endothelin-1 (ET-1), a long-acting paracrine mediator, is implicated in cardiovascular diseases but clinical trials with ET-receptor antagonists were not successful in some areas. We tested whether the quasi-irreversible receptor-binding of ET-1 (i) limits reversing effects...

  14. Endothelin B Receptors on Primary Chicken Müller Cells and the Human MIO-M1 Müller Cell Line Activate ERK Signaling via Transactivation of Epidermal Growth Factor Receptors

    Science.gov (United States)

    Harun-Or-Rashid, Mohammad; Konjusha, Dardan; Galindo-Romero, Caridad

    2016-01-01

    Injury to the eye or retina triggers Müller cells, the major glia cell of the retina, to dedifferentiate and proliferate. In some species they attain retinal progenitor properties and have the capacity to generate new neurons. The epidermal growth factor receptor (EGFR) system and extracellular signal-regulated kinase (ERK) signaling are key regulators of these processes in Müller cells. The extracellular signals that modulate and control these processes are not fully understood. In this work we studied whether endothelin receptor signaling can activate EGFR and ERK signaling in Müller cells. Endothelin expression is robustly upregulated at retinal injury and endothelin receptors have been shown to transactivate EGFRs in other cell types. We analyzed the endothelin signaling system in chicken retina and cultured primary chicken Müller cells as well as the human Müller cell line MIO-M1. The Müller cells were stimulated with receptor agonists and treated with specific blockers to key enzymes in the signaling pathway or with siRNAs. We focused on endothelin receptor mediated transactivation of EGFRs by using western blot analysis, quantitative reverse transcriptase PCR and immunocytochemistry. The results showed that chicken Müller cells and the human Müller cell line MIO-M1 express endothelin receptor B. Stimulation by the endothelin receptor B agonist IRL1620 triggered phosphorylation of ERK1/2 and autophosphorylation of (Y1173) EGFR. The effects could be blocked by Src-kinase inhibitors (PP1, PP2), EGFR-inhibitor (AG1478), EGFR-siRNA and by inhibitors to extracellular matrix metalloproteinases (GM6001), consistent with a Src-kinase mediated endothelin receptor response that engage ligand-dependent and ligand-independent EGFR activation. Our data suggest a mechanism for how injury-induced endothelins, produced in the retina, may modulate the Müller cell responses by Src-mediated transactivation of EGFRs. The data give support to a view in which endothelins

  15. Endothelin B Receptors on Primary Chicken Müller Cells and the Human MIO-M1 Müller Cell Line Activate ERK Signaling via Transactivation of Epidermal Growth Factor Receptors.

    Directory of Open Access Journals (Sweden)

    Mohammad Harun-Or-Rashid

    Full Text Available Injury to the eye or retina triggers Müller cells, the major glia cell of the retina, to dedifferentiate and proliferate. In some species they attain retinal progenitor properties and have the capacity to generate new neurons. The epidermal growth factor receptor (EGFR system and extracellular signal-regulated kinase (ERK signaling are key regulators of these processes in Müller cells. The extracellular signals that modulate and control these processes are not fully understood. In this work we studied whether endothelin receptor signaling can activate EGFR and ERK signaling in Müller cells. Endothelin expression is robustly upregulated at retinal injury and endothelin receptors have been shown to transactivate EGFRs in other cell types. We analyzed the endothelin signaling system in chicken retina and cultured primary chicken Müller cells as well as the human Müller cell line MIO-M1. The Müller cells were stimulated with receptor agonists and treated with specific blockers to key enzymes in the signaling pathway or with siRNAs. We focused on endothelin receptor mediated transactivation of EGFRs by using western blot analysis, quantitative reverse transcriptase PCR and immunocytochemistry. The results showed that chicken Müller cells and the human Müller cell line MIO-M1 express endothelin receptor B. Stimulation by the endothelin receptor B agonist IRL1620 triggered phosphorylation of ERK1/2 and autophosphorylation of (Y1173 EGFR. The effects could be blocked by Src-kinase inhibitors (PP1, PP2, EGFR-inhibitor (AG1478, EGFR-siRNA and by inhibitors to extracellular matrix metalloproteinases (GM6001, consistent with a Src-kinase mediated endothelin receptor response that engage ligand-dependent and ligand-independent EGFR activation. Our data suggest a mechanism for how injury-induced endothelins, produced in the retina, may modulate the Müller cell responses by Src-mediated transactivation of EGFRs. The data give support to a view in

  16. Higher Spins & Strings

    CERN Multimedia

    CERN. Geneva

    2014-01-01

    The conjectured relation between higher spin theories on anti de-Sitter (AdS) spaces and weakly coupled conformal field theories is reviewed. I shall then outline the evidence in favour of a concrete duality of this kind, relating a specific higher spin theory on AdS3 to a family of 2d minimal model CFTs. Finally, I shall explain how this relation fits into the framework of the familiar stringy AdS/CFT correspondence.

  17. Female white-collar workers remain at higher risk of breast cancer after adjustments for individual risk factors related to reproduction and lifestyle.

    Science.gov (United States)

    Kullberg, Cecilia; Selander, Jenny; Albin, Maria; Borgquist, Signe; Manjer, Jonas; Gustavsson, Per

    2017-09-01

    The aim was to investigate the variation in risk of breast cancer between occupational groups with a focus on white-collar and blue-collar workers and to investigate to what extent the differences were explained by risk factors related to reproduction and lifestyle. Between 1991 and 1996, 14 119 women born between 1923 and 1950 and residents of Malmö, Sweden, were included in this cohort study. Individual data on risk factors (eg, age, parity, age at first child, months of breast feeding per child, hormonal replacement therapy, physical activity, alcohol consumption, smoking, height and body mass index) and occupational history were assessed using a questionnaire. First-time diagnoses of invasive breast cancer were identified through the Swedish Cancer Registry up until 31 December 2013. A total of 897 women were diagnosed with breast cancer. Analyses adjusted for age showed an increased risk for white-collar workers compared with blue-collar workers and indicated higher risks in the occupational categories: professionals, administrative and bookkeeping than among women in sales, transportation, production and service work. This difference was only marginally attenuated after adjustment for an extensive set of risk factors related to reproduction and lifestyle. Reproductive and lifestyle factors explain only a minor part of the increased risk of breast cancer in white-collar workers. Further studies are needed to investigate the remaining factors for the difference in risk between occupational groups. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Population-based estimate of trauma-related deaths for law enforcement personnel: Risks for death are higher and increasing over time.

    Science.gov (United States)

    Eastman, Alexander L; Cripps, Michael W; Abdelfattah, Kareem R; Inaba, Kenji; Weiser, Thomas G; Spain, David A; Staudenmayer, Kristan L

    2017-08-01

    Trauma-related deaths remain an important public health problem. One group susceptible to death due to traumatic mechanisms is US law enforcement (LE). We hypothesized that LE officers experienced a higher chance of violent death compared with the general US population and that risks have increased over time. The National Institute on Occupational Safety and Health National Occupational Mortality Surveillance is a population-based survey of occupational deaths. It includes data for workers who died during 1985 to 1998 in one of 30 US states (EARLY period). Additional deaths were added from 23 US states in 1999, 2003 to 2004, 2007 to 2010 (LATE period). Mortality rates are estimated by calculating proportionate mortality ratios (PMR). A PMR above 100 is considered to exceed the average background risk for all occupations. All adults older than 18 years whose primary occupation was listed as "law enforcement worker" were included in the analysis. Law enforcement personnel were more likely to die from an injury compared with the general population (Fig. 1). The overall PMR for injury in EARLY was 111 (95% confidence interval [CI], 108-114; p increasing over time, suggesting an at-risk population that requires further interventions. Targeted efforts based on risk factors, such as sex and race, may assist with the development of prevention programs for this population. Epidemiologic study, level II.

  19. In Iranian female and male adolescents, romantic love is related to hypomania and low depressive symptoms, but also to higher state anxiety.

    Science.gov (United States)

    Bajoghli, Hafez; Joshaghani, Narges; Gerber, Markus; Mohammadi, Mohammad-Reza; Holsboer-Trachsler, Edith; Brand, Serge

    2013-06-01

    Experiencing romantic love is important in individual development. Little is known about romantic love among adolescents in non-Western countries. The aim of the present study was to explore romantic love among Iranian male and female adolescents. A total of 201 adolescents (mean age: 17.73 years) took part in the study; of these, 81 indicated they were experiencing romantic love at the time of survey, and 120 indicated they were not in love. Participants answered questionnaires related to affective states (hypomania, depressive symptoms, state and trait anxiety) and exercise, and completed a sleep log for seven consecutive nights. Compared to controls, participants in love displayed favourable hypomania scores, fewer depressive symptoms and increased concentration during the day. However, participants in love also had higher state anxiety scores. Moreover, hypomanic-like stages increased with duration of relationship in female, but not in male participants. The pattern of results suggests a favourable association between being currently in love and emotional and cognitive processes. Sleep, however, seemed unrelated to this specific state.

  20. Influence of pupil diameter on the relation between ocular higher-order aberration and contrast sensitivity after laser in situ keratomileusis.

    Science.gov (United States)

    Oshika, Tetsuro; Tokunaga, Tadatoshi; Samejima, Tomokazu; Miyata, Kazunori; Kawana, Keisuke; Kaji, Yuichi

    2006-04-01

    To investigate the influence of pupil diameter on the relation between induced changes in ocular higher-order wavefront aberrations and changes in contrast sensitivity by conventional laser in situ keratomileusis (LASIK) for myopia. In 215 eyes of 117 patients (age, 33.2 +/- 8.3 years) undergoing LASIK for myopia of -1.25 to -13.5 D (-5.28 +/- 2.55 D), ocular wavefront aberrations and contrast sensitivity function were determined before and 1 month after surgery. Preoperative photopic pupil diameter was measured with a digital camera. Ocular higher-order aberrations were measured for a 4-mm pupil with a Hartmann-Shack wavefront analyzer. The root-mean-square (RMS) of the third- and fourth-order Zernike coefficients was used to represent coma- and spherical-like aberration, respectively. From the contrast-sensitivity data, the area under the log contrast sensitivity function (AULCSF) was calculated. One hundred five eyes had a photopic pupil diameter of 4 mm or larger, and the remaining 110 had a photopic pupil diameter smaller than 4 mm. There were no statistically significant differences in the background clinical data between these two groups. In the eyes with a photopic pupil diameter of 4 mm or larger, the changes in third-order comalike aberrations did not correlate with the changes in AULCSF (Pearson correlation coefficient, r = -0.037, P = 0.723) and 10% low-contrast visual acuity (r = 0.125, P = 0.224), but fourth-order spherical-like aberrations correlated significantly with the changes in AULCSF (r = -0.229, P = 0.024) and 10% low-contrast visual acuity (r = 0.221, P = 0.038). In the eyes with photopic pupil size smaller than 4 mm, there were significant correlations between the changes in comalike aberrations and the changes in AULCSF (r = -0.487, P pupil diameter, increases in spherical-like aberration dominantly affect contrast sensitivity, whereas in eyes with smaller pupil size, changes in coma-like aberration exert greater influence on visual

  1. Timing is everything: neural response dynamics during syllable processing and its relation to higher-order cognition in schizophrenia and healthy comparison subjects.

    Science.gov (United States)

    Dale, Corby L; Findlay, Anne M; Adcock, R Alison; Vertinski, Mary; Fisher, Melissa; Genevsky, Alexander; Aldebot, Stephanie; Subramaniam, Karuna; Luks, Tracy L; Simpson, Gregory V; Nagarajan, Srikantan S; Vinogradov, Sophia

    2010-02-01

    Successful linguistic processing requires efficient encoding of successively-occurring auditory input in a time-constrained manner, especially under noisy conditions. In this study we examined the early neural response dynamics to rapidly-presented successive syllables in schizophrenia participants and healthy comparison subjects, and investigated the effects of noise on these responses. We used magnetoencephalography (MEG) to reveal the time-course of stimulus-locked activity over bilateral auditory cortices during discrimination of syllable pairs that differed either in voice onset time (VOT) or place of articulation (POA), in the presence or absence of noise. We also examined the association of these early neural response patterns to higher-order cognitive functions. The M100 response, arising from auditory cortex and its immediate environs, showed less attenuation to the second syllable in patients with schizophrenia than healthy comparison subjects during VOT-based discrimination in noise. M100 response amplitudes were similar between groups for the first syllable during all three discrimination conditions, and for the second syllable during VOT-based discrimination in quiet and POA-based discrimination in noise. Across subjects, the lack of M100 attenuation to the second syllable during VOT-based discrimination in noise was associated with poorer task accuracy, lower education and IQ, and lower scores on measures of Verbal Learning and Memory and Global Cognition. Because the neural response to the first syllable was not significantly different between groups, nor was a schizophrenia-related difference obtained in all discrimination tasks, early linguistic processing dysfunction in schizophrenia does not appear to be due to general sensory input problems. Rather, data suggest that faulty temporal integration occurs during successive syllable processing when the signal-to-noise ratio is low. Further, the neural mechanism by which the second syllable is

  2. Celecoxib offsets the negative renal influences of cyclosporine via modulation of the TGF-β1/IL-2/COX-2/endothelin ET{sub B} receptor cascade

    Energy Technology Data Exchange (ETDEWEB)

    El-Gowelli, Hanan M. [Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria (Egypt); Helmy, Maged W.; Ali, Rabab M. [Pharmacology and Toxicology, Faculty of Pharmacy, Pharos University, Alexandria (Egypt); El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com [Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria (Egypt)

    2014-03-01

    Endothelin (ET) signaling provokes nephrotoxicity induced by the immunosuppressant drug cyclosporine A (CSA). We tested the hypotheses that (i): celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, counterbalances renal derangements caused by CSA in rats and (ii) the COX-2/endothelin ET{sub B} receptor signaling mediates the CSA-celecoxib interaction. Ten-day treatment with CSA (20 mg/kg/day) significantly increased biochemical indices of renal function (serum urea, creatinine), inflammation (interleukin-2, IL-2) and fibrosis (transforming growth factor-β{sub 1}, TGF-β{sub 1}). Histologically, CSA caused renal tubular atrophy along with interstitial fibrosis. These detrimental renal effects of CSA were largely reduced in rats treated concurrently with celecoxib (10 mg/kg/day). We also report that cortical glomerular and medullary tubular protein expressions of COX-2 and ET{sub B} receptors were reduced by CSA and restored to near-control values in rats treated simultaneously with celecoxib. The importance of ET{sub B} receptors in renal control and in the CSA-celecoxib interaction was further verified by the findings (i) most of the adverse biochemical, inflammatory, and histopathological profiles of CSA were replicated in rats treated with the endothelin ET{sub B} receptor antagonist BQ788 (0.1 mg/kg/day, 10 days), and (ii) the BQ788 effects, like those of CSA, were alleviated in rats treated concurrently with celecoxib. Together, the data suggest that the facilitation of the interplay between the TGF-β1/IL-2/COX-2 pathway and the endothelin ET{sub B} receptors constitutes the cellular mechanism by which celecoxib ameliorates the nephrotoxic manifestations of CSA in rats. - Highlights: • Celecoxib abolishes nephrotoxic manifestations of CSA in rats. • Blockade of ETB receptors by BQ788 mimicked the nephrotoxic effects of CSA. • CSA or BQ788 reduces renal protein expression of COX-2 and endothelin ETB receptors. • Enhanced TGFβ1/IL-2/COX2/ETB

  3. Pilot Study of Endothelin Receptor Blockade in Heart Failure with Diastolic Dysfunction and Pulmonary Hypertension (BADDHY-Trial).

    Science.gov (United States)

    Koller, B; Steringer-Mascherbauer, R; Ebner, C H; Weber, Th; Ammer, M; Eichinger, J; Pretsch, I; Herold, M; Schwaiger, J; Ulmer, H; Grander, W

    2017-05-01

    In this multi-centre, randomised, placebo-controlled pilot trial, we investigated the clinical and haemodynamic effects of the endothelin-receptor blocker Bosentan in patients with heart failure, preserved ejection fraction and pulmonary hypertension (PH-HFpEF). Eligible patients received either 12 weeks of Bosentan therapy, or a placebo drug. Patients were thereafter followed for a further period of 12 weeks without the study medication. At three points during the study (study Commencement, Week 12 and Week 24), a six-minute walk test (6MWT), echocardiographic and laboratory assessments were performed, as well as a quality of life survey. Right heart catheterisation (RHC) was undertaken at commencement only. The study was aborted early, after an interim analysis favoured the placebo. Six-minute walk distance (6MWD) did not change in the Bosentan group (309.7±96.3m (Commencement), 317.0±126.1m (Week 12), 307.0±84.4m (Week 24); p=0.86), but almost reached statistical significance in the placebo group from 328.8±79.6m, to 361.6±98.2m and 384.0±74.9m (Week 24); p=0.075. In the placebo group, estimated systolic pulmonary artery pressure (measured via echocardiography) significantly decreased (from 62.3±16.7mmHg [Commencement], 45.3±13.9mmHg [Week 12], to 44.6±14.5mmHg [Week 24]; p=0.014) as did right atrial pressure (13.1±5.3 [Commencement], 10.0±3.8 [Week 12], to 9.4±3.2 [Week 24]; p=0.046). Despite this study's limited sample size and premature cessation, it nevertheless suggests that endothelin receptor blockade in patients with PH-HFpEF may have no beneficial effects and could even be detrimental in comparison to a placebo. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  4. Higher Spin Matrix Models

    Directory of Open Access Journals (Sweden)

    Mauricio Valenzuela

    2017-10-01

    Full Text Available We propose a hybrid class of theories for higher spin gravity and matrix models, i.e., which handle simultaneously higher spin gravity fields and matrix models. The construction is similar to Vasiliev’s higher spin gravity, but part of the equations of motion are provided by the action principle of a matrix model. In particular, we construct a higher spin (gravity matrix model related to type IIB matrix models/string theory that have a well defined classical limit, and which is compatible with higher spin gravity in A d S space. As it has been suggested that higher spin gravity should be related to string theory in a high energy (tensionless regime, and, therefore to M-Theory, we expect that our construction will be useful to explore concrete connections.

  5. Matrix metalloproteinase-9 expression in retinal ganglion cell layer and effect of topically applied brimonidine tartrate 0.2% therapy on this expression in an endothelin-1-induced optic nerve ischemia model.

    Science.gov (United States)

    Aktas, Zeynep; Gurelik, Gokhan; Göçün, Pinar Uyar; Akyürek, Nalan; Onol, Merih; Hasanreisoğlu, Berati

    2010-06-01

    The purpose of this research is to investigate the expression of matrix metalloproteinase-9 (MMP-9) in retinal ganglion cells (RGC) and the impact of topically applied brimonidine tartrate 0.2% (BMD) on this expression in an endothelin-1 (ET-1)-induced chronic optic nerve (ON) ischemia model of rabbit. Osmotically driven minipumps were implanted in one eye of 16 New Zealand albino rabbits to deliver ET-1 at the constant rate of 0.5 microl/h for 2 weeks. ET-1 was given with (group 3) and without topical BMD therapy (group 1). Groups 2 and 4 were taken as controls. MMP-9 expression by immunohistochemically and proportion of cells undergoing apoptosis in RGC layer were investigated. The correlation between the MMP-9 immunopositivity and the proportion of cells undergoing apoptosis in the RGC layer was evaluated. MMP-9 immunopositivity was found to be significantly higher in both groups 1 and 3 compared to that of the controls. There was no difference between groups 1 and 3 regarding MMP-9 expression (p = 0.495). A positive correlation was found between the proportion of cells undergoing apoptosis and MMP-9 expressions in the RGC layer in group 1 (p = 0.031, r = 0.754). MMP-9 expression in the RGC layer seems to significantly increase in the ET-1-induced chronic ON ischemia model. Topical BMD therapy does not seem to affect this MMP-9 expression.

  6. Homocysteine up-regulates endothelin type A receptor in vascular smooth muscle cells through Sirt1/ERK1/2 signaling pathway.

    Science.gov (United States)

    Chen, Yulong; Liu, Huanhuan; Wang, Xinhong; Zhang, Hongmei; Liu, Enqi; Su, Xingli

    2017-11-01

    Sirtuin 1 (Sirt1) is a longevity gene that has protective effects in cardiovascular diseases (CVDs). The endothelin type A (ETA) receptor is involved in pathogenesis of CVDs. The extracellular signal related kinases 1 and 2 (ERK1/2) signaling pathway is involved in regulation of the ETA receptor induced by some CVD risk factors in vascular smooth muscle cells (VSMCs). Hyperhomocysteinemia (HHcy) is an independent risk factor for CVDs. The present study was designed to investigate the hypothesis that homocysteine up-regulates ETA receptor through the Sirt1/ERK1/2 signaling pathway. In vitro experiments were performed in the rat superior mesenteric artery. The rat superior mesenteric artery was cultured with or without homocysteine (Hcy) in the presence and absence of Resveratrol (Res, a Sirt1 agonist), SRT1720 (a specific Sirt1 agonist) or U0126 (an ERK1/2 signaling pathway inhibitor) in serum-free medium for 24h. In vivo, the rats received subcutaneous injections of Hcy in the presence of or absence of Res or U0126 for 3weeks. The contractile response to ET-1 was studied using a sensitive myograph. In addition, the level of protein expression was determined using western blotting. Hcy significantly increased the expression of ETA receptor and also increased the ETA receptor-mediated contractile response induced by ET-1 in vitro. These effects were inhibited by Res, SRT1720 and U0126 treatment. In addition, Hcy down-regulated the level of Sirt1, and up-regulated the level of phosphorylated ERK1/2, which was reversed upon Res or SRT1720 treatment. In vivo results showed that HHcy results in the up-regulation of ETA receptor expression, and elevated blood pressure in rats. However, Res and U0126 could block these effects, respectively. In conclusion, these results suggest that Hcy regulates ETA receptor expression via the Sirt1/ERK1/2 signaling pathway in VSMCs. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Evaluation of deafness in American Paint Horses by phenotype, brainstem auditory-evoked responses, and endothelin receptor B genotype.

    Science.gov (United States)

    Magdesian, K Gary; Williams, D Colette; Aleman, Monica; Lecouteur, Richard A; Madigan, John E

    2009-11-15

    To evaluate deafness in American Paint Horses by phenotype, clinical findings, brainstem auditory-evoked responses (BAERs), and endothelin B receptor (EDNBR) genotype. Case series and case-control studies. 14 deaf American Paint Horses, 20 suspected-deaf American Paint Horses, and 13 nondeaf American Paint Horses and Pintos. Horses were categorized on the basis of coat color pattern and eye color. Testing for the EDNBR gene mutation (associated with overo lethal white foal syndrome) and BAERs was performed. Additional clinical findings were obtained from medical records. All 14 deaf horses had loss of all BAER waveforms consistent with complete deafness. Most horses had the splashed white or splashed white-frame blend coat pattern. Other patterns included frame overo and tovero. All of the deaf horses had extensive head and limb white markings, although the amount of white on the neck and trunk varied widely. All horses had at least 1 partially heterochromic iris, and most had 2 blue eyes. Ninety-one percent (31/34) of deaf and suspected-deaf horses had the EDNBR gene mutation. Deaf and suspected-deaf horses were used successfully for various performance events. All nondeaf horses had unremarkable BAER results. Veterinarians should be aware of deafness among American Paint Horses, particularly those with a splashed white or frame overo coat color pattern, blend of these patterns, or tovero pattern. Horses with extensive head and limb markings and those with blue eyes appeared to be at particular risk.

  8. The Lipid Moiety of Haemozoin (Malaria Pigment and P. falciparum Parasitised Red Blood Cells Bind Synthetic and Native Endothelin-1

    Directory of Open Access Journals (Sweden)

    Nicoletta Basilico

    2010-01-01

    Full Text Available Endothelin1 (ET-1 is a 21-amino acid peptide produced by the vascular endothelium under hypoxia, that acts locally as regulator of vascular tone and inflammation. The role of ET-1 in Plasmodium falciparum malaria is unknown, although tissue hypoxia is frequent as a result of the cytoadherence of parasitized red blood cell (pRBC to the microvasculature. Here, we show that both synthetic and endothelial-derived ET-1 are removed by parasitized RBC (D10 and W2 strains, chloroquine sensitive, and resistant, resp. and native haemozoin (HZ, malaria pigment, but not by normal RBC, delipidized HZ, or synthetic beta-haematin (BH. The effect is dose dependent, selective for ET-1, but not for its precursor, big ET-1, and not due to the proteolysis of ET-1. The results indicate that ET-1 binds to the lipids moiety of HZ and membranes of infected RBCs. These findings may help understanding the consequences of parasite sequestration in severe malaria.

  9. Effect of endothelin receptor antagonists on clinically relevant outcomes after experimental subarachnoid hemorrhage: a systematic review and meta-analysis.

    Science.gov (United States)

    Laban, Kamil G; Vergouwen, Mervyn D I; Dijkhuizen, Rick M; Sena, Emily S; Macleod, Malcolm R; Rinkel, Gabriel J E; van der Worp, H Bart

    2015-07-01

    In clinical trials, endothelin receptor antagonists (ETRAs) reduced vasospasm but did not improve functional outcome after subarachnoid hemorrhage (SAH). We assessed the effects of treatment with ETRAs on clinically relevant outcomes in animal studies modelling SAH by performing a systematic review of the literature for controlled animal studies of ETRAs for the treatment of SAH. Primary outcomes were neurobehavioral outcomes and case fatality. Secondary outcomes were cerebral vasospasm and cerebral blood flow. Summary estimates were calculated using normalized mean difference random effects meta-analysis. We included 27 studies (55 experiments, 639 animals). Neurobehavioral scores were reported in none of the experiments, and case fatality in 8 (15%). Treatment with ETRAs was associated with a pooled odds ratio for case fatality of 0.61 (95% confidence interval (CI), 0.27 to 1.39); a 54% increase (95% CI, 39 to 69) in cerebral arterial diameter; and a 93% increase (95% CI, 58 to 129) in cerebral blood flow. We conclude that there is no evidence from animal studies that treatment with an ETRA improves clinically relevant outcomes after SAH. The reduction in cerebral vasospasm observed in animal studies is consistent with that observed in clinical trials, an effect that is not associated with better functional outcome in patients.

  10. Endothelin-1 enhances corneal fibronectin deposition and promotes corneal epithelial wound healing after photorefractive keratectomy in rabbits.

    Science.gov (United States)

    Lai, Yu-Hung; Wang, Hwei-Zu; Lin, Chang-Ping; Hong, Show-Jen; Chang, Shun-Jen

    2008-05-01

    The objective was to study the effects of endothelin-1 (ET1) on corneal wound healing after photorefractive keratectomy (PRK) in rabbit corneas. Following PRK, 18 New Zealand white rabbits were treated with ET1 in the right eyes and with phosphate-buffered salt solution (PBS) in the left eyes. Corneal epithelial wound size, corneal haze and corneal thickness were recorded. Corneal extracellular matrixes, including collagen types 3, 4 and 7, chondroitin sulfate and fibronectin, were investigated using immunohistochemistry study. ET1 increased the rate of healing of corneal epithelial wounds in rabbits. Anti-fibronectin fluorescence was present at week 12 and week 24 in ET1-treated eyes but not in the control eyes. There were no significant differences in corneal haze, corneal thickness and changes in other extracellular matrixes between ET1- and PBS-treated eyes. ET1 can enhance the deposition of fibronectin in corneal stroma and promote corneal epithelial wound healing after PRK. The increase in fibronectin probably explains the increased healing rate of corneal epithelial wounds.

  11. Endothelin-1 Enhances Corneal Fibronectin Deposition and Promotes Corneal Epithelial Wound Healing after Photorefractive Keratectomy in Rabbits

    Directory of Open Access Journals (Sweden)

    Yu-Hung Lai

    2008-05-01

    Full Text Available The objective was to study the effects of endothelin-1 (ET1 on corneal wound healing after photorefractive keratectomy (PRK in rabbit corneas. Following PRK, 18 New Zealand white rabbits were treated with ET1 in the right eyes and with phosphate-buffered salt solution (PBS in the left eyes. Corneal epithelial wound size, corneal haze and corneal thickness were recorded. Corneal extracellular matrixes, including collagen types 3, 4 and 7, chondroitin sulfate and fibronectin, were investigated using immunohistochemistry study. ET1 increased the rate of healing of corneal epithelial wounds in rabbits. Anti-fibronectin fluorescence was present at week 12 and week 24 in ET1-treated eyes but not in the control eyes. There were no significant differences in corneal haze, corneal thickness and changes in other extracellular matrixes between ET1- and PBS-treated eyes. ET1 can enhance the deposition of fibronectin in corneal stroma and promote corneal epithelial wound healing after PRK. The increase in fibronectin probably explains the increased healing rate of corneal epithelial wounds.

  12. Hydrostatic pressure and shear stress affect endothelin-1 and nitric oxide release by endothelial cells in bioreactors.

    Science.gov (United States)

    Vozzi, Federico; Bianchi, Francesca; Ahluwalia, Arti; Domenici, Claudio

    2014-01-01

    Abundant experimental evidence demonstrates that endothelial cells are sensitive to flow; however, the effect of fluid pressure or pressure gradients that are used to drive viscous flow is not well understood. There are two principal physical forces exerted on the blood vessel wall by the passage of intra-luminal blood: pressure and shear. To analyze the effects of pressure and shear independently, these two stresses were applied to cultured cells in two different types of bioreactors: a pressure-controlled bioreactor and a laminar flow bioreactor, in which controlled levels of pressure or shear stress, respectively, can be generated. Using these bioreactor systems, endothelin-1 (ET-1) and nitric oxide (NO) release from human umbilical vein endothelial cells were measured under various shear stress and pressure conditions. Compared to the controls, a decrease of ET-1 production by the cells cultured in both bioreactors was observed, whereas NO synthesis was up-regulated in cells under shear stress, but was not modulated by hydrostatic pressure. These results show that the two hemodynamic forces acting on blood vessels affect endothelial cell function in different ways, and that both should be considered when planning in vitro experiments in the presence of flow. Understanding the individual and synergic effects of the two forces could provide important insights into physiological and pathological processes involved in vascular remodeling and adaptation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Guidelines for the Design of Developmental Education Programs. Part 4 of the Research Program on Problems Relating to the Desegregation of Higher Education.

    Science.gov (United States)

    Adolphus, Stephen; And Others

    This paper addresses developmental education programs as mechanisms for enhancing the survival rates of disadvantaged populations in higher education. Specifically, the paper identifies and discusses the critical dimensions of effective developmental education programs, including recruitment, admissions, diagnosis and prescription, orientation,…

  14. Empirical Investigation of Moderating and Mediating Variables in between Transformational Leadership and Related Outcomes: A Study of Higher Education Sector in North India

    Science.gov (United States)

    Jyoti, Jeevan; Bhau, Sonia

    2016-01-01

    Purpose: The purpose of this paper is to evaluate the multi-layer effect of transformational leadership (TL) on employee-related outcomes, i.e. relational identification (RI) and satisfaction with leader (SWL). Further, role of leader member exchange (LMX) and the association period in between TL and RI as well as SWL shall also be examined. So,…

  15. Sharply higher rates of iron deficiency in obese Mexican women and children are predicted by obesity-related inflammation rather than by differences in dietary iron intake

    NARCIS (Netherlands)

    Cepeda-Lopez, A.C.; Osendarp, S.J.M.; Boonstra, A.; Aeberli, I.; Gonzalez-Salazar, F.; Feskens, E.J.M.; Villalpando, S.; Zimmermann, M.B.

    2011-01-01

    Background: Obese individuals may be at increased risk of iron deficiency (ID), but it is unclear whether this is due to poor dietary iron intakes or to adiposity-related inflammation. Objective: The aim of this study was to examine the relations between body mass index (BMI), dietary iron, and

  16. Endothelin receptor B2 (EDNRB2 is responsible for the tyrosinase-independent recessive white (mo(w and mottled (mo plumage phenotypes in the chicken.

    Directory of Open Access Journals (Sweden)

    Keiji Kinoshita

    Full Text Available A mutation that confers white plumage with black eyes was identified in the Minohiki breed of Japanese native chicken (Gallus gallus domesticus. The white plumage, with a few partially pigmented feathers, was not associated with the tyrosinase gene, and displayed an autosomal recessive mode of inheritance against the pigmented phenotype. All F1 offspring derived from crosses with mottled chickens (mo/mo, which show characteristic pigmented feathers with white tips, had plumage with a mottled-like pattern. This result indicates that the white plumage mutation is a novel allele at the mo locus; we propose the gene symbol mo(w for this mutant allele. Furthermore, the F1 hybrid between the mo(w /mo(w chicken and the panda (s/s mutant of Japanese quail (Coturnix japonica, whose causative gene is the endothelin receptor B2 (EDNRB2 gene, showed a mo(w/mo(w chicken-like plumage, suggesting the possibility that the mutations in parental species are alleles of the same gene, EDNRB2. Nucleotide sequencing of the entire coding region of EDNRB2 revealed a non-synonymous G1008T substitution, which causes Cys244Phe amino acid substitution in exon 5 (which is part of the extracellular loop between the putative fourth and fifth transmembrane domains of EDNRB2 in the mutant chicken. This Cys244Phe mutation was also present in individuals of four Japanese breeds with white plumage. We also identified a non-synonymous substitution leading to Arg332His substitution that was responsible for the mottled (mo/mo plumage phenotype. These results suggest that the EDN3 (endothelin 3-EDNRB2 signaling is essential for normal pigmentation in birds, and that the mutations of EDNRB2 may cause defective binding of the protein with endothelins, which interferes with melanocyte differentiation, proliferation, and migration.

  17. The inhibitory effect of an extract of Sanguisorba officinalis L. on ultraviolet B-induced pigmentation via the suppression of endothelin-converting enzyme-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Hachiya, Akira; Kobayashi, Akemi; Ohuchi, Atsushi; Kitahara, Takashi; Takema, Yoshinori [Kao Biological Science Lab., Ichikai, Tochigi (Japan)

    2001-06-01

    Endothelin-1 (ET-1) has been reported to be expressed in human epidermis at both the gene and protein levels. ET-1 plays a pivotal role in ultraviolet B (UVB)-induced pigmentation due to its accentuated secretion after UVB irradiation and its function as a mitogen and as a melanogen for human melanocytes. We have recently found that endothelin-converting enzyme (ECE)-1{alpha} plays a constitutive role in the secretion of ET-1 by human keratinocytes and that an extract of Sanguisorba officinalis L. inhibits ECE activity in human endothelial cells, which predominantly express ECE-1{alpha}. In this report, to clarify the potential use of this botanical extract as a whitening agent, we examined whether this extract inhibits UVB-induced pigmentation in vivo. When this extract was applied to human keratinocytes after UVB irradiation, secretion of ET-1 by those cells was reduced, and this was accompanied by a concomitant increase in the secretion of inactive precursor Big endothelin-1. When hairless mice were exposed to UVB light and were treated with the extract, it suppressed the induction of ET-1 in the UVB-irradiated epidermis. In the course of UVB-induced pigmentation of brownish guinea pig skin, this extract significantly diminished pigmentation in UVB-exposed areas. These findings indicate that ECE-1{alpha} in keratinocytes plays a pivotal role in the induction of pigmentation following UVB irradiation and that an extract of S. officinalis, which inhibits ET-1 production in human keratinocytes, is a good ingredient for a whitening agent. (author)

  18. Endothelin Receptor B2 (EDNRB2) Is Responsible for the Tyrosinase-Independent Recessive White (mow) and Mottled (mo) Plumage Phenotypes in the Chicken

    Science.gov (United States)

    Kinoshita, Keiji; Akiyama, Toyoko; Mizutani, Makoto; Shinomiya, Ai; Ishikawa, Akira; Younis, Hassan Hassan; Tsudzuki, Masaoki; Namikawa, Takao; Matsuda, Yoichi

    2014-01-01

    A mutation that confers white plumage with black eyes was identified in the Minohiki breed of Japanese native chicken (Gallus gallus domesticus). The white plumage, with a few partially pigmented feathers, was not associated with the tyrosinase gene, and displayed an autosomal recessive mode of inheritance against the pigmented phenotype. All F1 offspring derived from crosses with mottled chickens (mo/mo), which show characteristic pigmented feathers with white tips, had plumage with a mottled-like pattern. This result indicates that the white plumage mutation is a novel allele at the mo locus; we propose the gene symbol mow for this mutant allele. Furthermore, the F1 hybrid between the mow/mow chicken and the panda (s/s) mutant of Japanese quail (Coturnix japonica), whose causative gene is the endothelin receptor B2 (EDNRB2) gene, showed a mow/mow chicken-like plumage, suggesting the possibility that the mutations in parental species are alleles of the same gene, EDNRB2. Nucleotide sequencing of the entire coding region of EDNRB2 revealed a non-synonymous G1008T substitution, which causes Cys244Phe amino acid substitution in exon 5 (which is part of the extracellular loop between the putative fourth and fifth transmembrane domains of EDNRB2) in the mutant chicken. This Cys244Phe mutation was also present in individuals of four Japanese breeds with white plumage. We also identified a non-synonymous substitution leading to Arg332His substitution that was responsible for the mottled (mo/mo) plumage phenotype. These results suggest that the EDN3 (endothelin 3)–EDNRB2 signaling is essential for normal pigmentation in birds, and that the mutations of EDNRB2 may cause defective binding of the protein with endothelins, which interferes with melanocyte differentiation, proliferation, and migration. PMID:24466053

  19. Report on the results of gender equality analysisof belarusian legislation regulating relations in the field of higher education / V.V. Saskevich

    OpenAIRE

    Saskevich, Veronika

    2015-01-01

    Preparation and publication of this report were arranged by the Raoul Wallenberg Institute of Human Rights and Humanitarian Law as a part of academic cooperation with the Belarus State University and other institutions of higher education in Belarus. The views expressed in this publication are the thoughts and opinions of the author and do not necessarily reflect the views of the Institute. The distribution is free of charge. This publication is the result of gender equality analy...

  20. Quality of Higher Education

    DEFF Research Database (Denmark)

    Zou, Yihuan

    is about constructing a more inclusive understanding of quality in higher education through combining the macro, meso and micro levels, i.e. from the perspectives of national policy, higher education institutions as organizations in society, individual teaching staff and students. It covers both......Quality in higher education was not invented in recent decades – universities have always possessed mechanisms for assuring the quality of their work. The rising concern over quality is closely related to the changes in higher education and its social context. Among others, the most conspicuous...... changes are the massive expansion, diversification and increased cost in higher education, and new mechanisms of accountability initiated by the state. With these changes the traditional internally enacted academic quality-keeping has been given an important external dimension – quality assurance, which...

  1. A feed-forward regulation of endothelin receptors by c-Jun in human non-pigmented ciliary epithelial cells and retinal ganglion cells.

    Science.gov (United States)

    Wang, Junming; Ma, Hai-Ying; Krishnamoorthy, Raghu R; Yorio, Thomas; He, Shaoqing

    2017-01-01

    c-Jun, c-Jun N-terminal kinase(JNK) and endothelin B (ETB) receptor have been shown to contribute to the pathogenesis of glaucoma. Previously, we reported that an increase of c-Jun and CCAAT/enhancer binding protein β (C/EBPβ) immunohistostaining is associated with upregulation of the ETB receptor within the ganglion cell layer of rats with elevated intraocular pressure (IOP). In addition, both transcription factors regulate the expression of the ETB receptor in human non-pigmented ciliary epithelial cells (HNPE). The current study addressed the mechanisms by which ET-1 produced upregulation of ET receptors in primary rat retinal ganglion cells (RGCs) and HNPE cells. Treatment of ET-1 and ET-3 increased the immunocytochemical staining of c-Jun and C/EBPβ in primary rat RGCs and co-localization of both transcription factors was observed. A marked increase in DNA binding activity of AP-1 and C/EBPβ as well as elevated protein levels of c-Jun and c-Jun-N-terminal kinase (JNK) were detected following ET-1 treatment in HNPE cells. Overexpression of ETA or ETB receptor promoted the upregulation of c-Jun and also elevated its promoter activity. In addition, upregulation of C/EBPβ augmented DNA binding and mRNA expression of c-Jun, and furthermore, the interaction of c-Jun and C/EBPβ was confirmed using co-immunoprecipitation. Apoptosis of HNPE cells was identified following ET-1 treatment, and overexpression of the ETA or ETB receptor produced enhanced apoptosis. ET-1 mediated upregulation of c-Jun and C/EBPβ and their interaction may represent a novel mechanism contributing to the regulation of endothelin receptor expression. Reciprocally, c-Jun was also found to regulate the ET receptors and C/EBPβ appeared to play a regulatory role in promoting expression of c-Jun. Taken together, the data suggests that ET-1 triggers the upregulation of c-Jun through both ETA and ETB receptors, and conversely c-Jun also upregulates endothelin receptor expression, thereby

  2. Upregulation of contractile endothelin type B receptors by lipid-soluble cigarette smoking particles in rat cerebral arteries via activation of MAPK

    DEFF Research Database (Denmark)

    Sandhu, Hardip; Xu, Cang Bao; Edvinsson, Lars

    2010-01-01

    Cigarette smoke exposure increases the risk of stroke. However, the underlying molecular mechanisms are poorly understood. Endothelin system plays key roles in the pathogenesis of stroke. The present study was designed to examine if lipid-soluble (dimethyl sulfoxide-soluble) cigarette smoke...... or water-soluble cigarette smoke particles to the organ culture. The increased upregulation of contractile ET(B) receptors by DSP was abrogated by U0126, SP600125, actinomycin D, and cycloheximide, suggesting that the underlying molecular mechanisms involved in this process include activation of MEK...

  3. A feed-forward regulation of endothelin receptors by c-Jun in human non-pigmented ciliary epithelial cells and retinal ganglion cells.

    Directory of Open Access Journals (Sweden)

    Junming Wang

    Full Text Available c-Jun, c-Jun N-terminal kinase(JNK and endothelin B (ETB receptor have been shown to contribute to the pathogenesis of glaucoma. Previously, we reported that an increase of c-Jun and CCAAT/enhancer binding protein β (C/EBPβ immunohistostaining is associated with upregulation of the ETB receptor within the ganglion cell layer of rats with elevated intraocular pressure (IOP. In addition, both transcription factors regulate the expression of the ETB receptor in human non-pigmented ciliary epithelial cells (HNPE. The current study addressed the mechanisms by which ET-1 produced upregulation of ET receptors in primary rat retinal ganglion cells (RGCs and HNPE cells. Treatment of ET-1 and ET-3 increased the immunocytochemical staining of c-Jun and C/EBPβ in primary rat RGCs and co-localization of both transcription factors was observed. A marked increase in DNA binding activity of AP-1 and C/EBPβ as well as elevated protein levels of c-Jun and c-Jun-N-terminal kinase (JNK were detected following ET-1 treatment in HNPE cells. Overexpression of ETA or ETB receptor promoted the upregulation of c-Jun and also elevated its promoter activity. In addition, upregulation of C/EBPβ augmented DNA binding and mRNA expression of c-Jun, and furthermore, the interaction of c-Jun and C/EBPβ was confirmed using co-immunoprecipitation. Apoptosis of HNPE cells was identified following ET-1 treatment, and overexpression of the ETA or ETB receptor produced enhanced apoptosis. ET-1 mediated upregulation of c-Jun and C/EBPβ and their interaction may represent a novel mechanism contributing to the regulation of endothelin receptor expression. Reciprocally, c-Jun was also found to regulate the ET receptors and C/EBPβ appeared to play a regulatory role in promoting expression of c-Jun. Taken together, the data suggests that ET-1 triggers the upregulation of c-Jun through both ETA and ETB receptors, and conversely c-Jun also upregulates endothelin receptor expression

  4. Role of mitogen-activated protein kinases in endothelin ETB receptor up-regulation after organ culture of rat mesenteric artery

    DEFF Research Database (Denmark)

    Uddman, Erik; Henriksson, Marie; Eskesen, Karen

    2003-01-01

    after organ culture of rat mesenteric arteries. Western blot and selective antibodies towards constitutional and phosphorylated MAPKs revealed the appearance of phosphorylated MAPK of the extracellular signal-regulated kinases (ERK) 1/2 type at 3 h of organ culture. The functional ET(B) receptor and its...... Western blot nor myograph or mRNA analysis showed involvement of the other MAPKs studied. Our results suggest that the ERK1/2 MAPKs are involved in the endothelin ET(B) receptor up-regulation following organ culture....

  5. The role of motivation in the development of the idea of pedagogical mutual relations of participants of educational process in higher education.

    Directory of Open Access Journals (Sweden)

    Gonchar E.V.

    2010-12-01

    Full Text Available The essence of specific motivation, mechanism and its particular structure formation through the prism of the basic pedagogical categories of mutual relations of educational process agents are exposed. It is also proved that the functional characteristic of the motif gives a teacher the possibility of selecting the most witty arguments both to motivate the purpose of the activity, and to predict the thoughts, feelings and actions of students, effectively organize pedagogical mutual relations of educational process subjects.

  6. Effect of endothelin receptor antagonist on parathyroid gland growth, PTH values and cell proliferation in azotemic rats.

    Science.gov (United States)

    Jara, Aquiles; von Höveling, Andrea; Jara, Ximena; Burgos, M Eugenia; Valdivieso, Andres; Mezzano, Sergio; Felsenfeld, Arnold J

    2006-04-01

    A variety of stimuli are involved in the pathogenesis of parathyroid gland hyperplasia in renal failure. Recently, it was shown that blocking the signal from the endothelin-1 (ET-1) receptor (ET(A)R/ET(B)R) by a non-selective receptor antagonist, bosentan, reduced parathyroid cell proliferation, parathyroid gland hyperplasia and parathyroid hormone (PTH) levels in normal rats on a calcium deficient diet. Our goal was to determine whether in 5/6 nephrectomized (NPX) rats with developing or established hyperparathyroidism, the endothelin receptor blocker, bosentan, reduced the increase in parathyroid cell proliferation, parathyroid gland hyperplasia and PTH values. High (HPD, 1.2%) or normal phosphorus diets (PD) (NPD, 0.6%) were given to 5/6 NPX rats for 15 days (NPX(15)). In each dietary group, one-half the rats were given bosentan (B) i.p. 100 mg/kg/day. The four groups of rats were: (1) NPX(15)-1.2% P; (2) NPX(15)-1.2% P+B; (3) NPX(15)-0.6% P; and (4) NPX(15)-0.6% P+B. In a second study in which hyperparathyroidism was already established in 5/6 NPX rats fed a HPD for 15 days, rats were divided into two groups in which one group was maintained on a HPD and the other group was changed to very low PD (VLPD, rats were given bosentan i.p. 100 mg/kg-day. The four groups of rats were: (1) NPX(30)-1.2% P; (2) NPX(30)-1.2% P+B; (3) NPX(30)-0.05% P and (4) NPX(30)-0.05% P+B. Parathyroid cell proliferation was measured by proliferating cell nuclear antigen (PCNA) staining and ET-1 expression by immunohistochemical techniques. In the study of developing hyperparathyroidism, bosentan reduced ET-1 expression in the parathyroid glands of rats on the NPD and HPD (Prats on the NPD did bosentan result in a reduced increase in parathyroid gland weight (Phyperparathyroidism, in which 5/6 NPX rats were given a HPD for 15 days, bosentan started on day 15 reduced (Prats maintained for 15 additional days on the HPD or the VLPD. On the VLPD, parathyroid gland weight was less (Prats on

  7. Glucose-Dependent Insulinotropic Polypeptide Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB

    DEFF Research Database (Denmark)

    Berglund, Lisa M; Lyssenko, Valeriya; Ladenvall, Claes

    2016-01-01

    in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients...

  8. Incidence of the endothelin receptor B mutation that causes lethal white foal syndrome in white-patterned horses.

    Science.gov (United States)

    Santschi, E M; Vrotsos, P D; Purdy, A K; Mickelson, J R

    2001-01-01

    To determine incidence of the Ile118Lys endothelin receptor B (EDNRB) mutation responsible for overo lethal white syndrome (OLWS) and its association with specific types of white patterning. 945 horses of white-patterned bloodlines and 55 solid-colored horses of other breeds. Horses were genotyped by use of allele-specific polymerase chain reaction to determine incidence of the Ile118Lys EDNRB mutation. Genotypes detected were homozygous Ile118, homozygous Lys118, and heterozygous. All foals with OLWS were homozygous for the Ile118Lys EDNRB mutation, and adults that were homozygous were not found. White patterning was strongly associated with EDNRB genotype. Color patterns with highest incidence (> 94%) of heterozygotes were frame overo, highly white calico overo, and frame blend overo. White-patterned bloodlines with lowest incidence of heterozygotes (white calico overo, splashed white overo, nonframe blend overo, and breeding-stock solid. The mutation was not detected in solid-colored horses from breeds without white patterning. In homozygotes, the Ile118Lys EDNRB mutation causes OLWS. In heterozygotes, the mutation is usually responsible for a frame overo phenotype. The frame pattern can be combined with other white patterns, making accurate estimation of EDNRB genotype by visual inspection difficult. Wide range of incidence of heterozygotes in various subtypes of white-patterned horses indicates different genetic control of these color patterns. Determination of EDNRB genotype by use of a DNA-based test is the only way to determine with certainty whether white-patterned horses can produce a foal affected with OLWS.

  9. Plasma big endothelin-1 and stent thrombosis: An observational study in patients undergoing percutaneous coronary intervention in China.

    Science.gov (United States)

    Chen, Yan; Li, Jian-Xin; Song, Ying; Xu, Jing-Jing; Tang, Xiao-Fang; Jiang, Lin; Jiang, Ping; Liu, Ru; Wang, Huan-Huan; Zhao, Xue-Yan; Chen, Jue; Gao, Zhan; Qiao, Shu-Bin; Gao, Run-Lin; Yang, Yue-Jin; Xu, Bo; Yuan, Jin-Qing

    2017-11-01

    Stent thrombosis (ST) is a rare but catastrophic complication of percutaneous coronary intervention, leading to poor prognosis. Endothelin-1 (ET-1) plays an important role in endothelial dysfunction and thrombogenesis. However, the impact of big ET-1 level on ST in patients with coronary stenting is unknown. We aimed to evaluate big ET-1 level as a potential predictor of ST in patients undergoing percutaneous coronary intervention. From January 2013 to December 2013, 8106 consecutive patients underwent successful coronary stent implantation and were prospectively enrolled in this study. Patients were stratified into three groups based on plasma big ET-1 level at admission. The incidence of definite and probable ST at 2years postoperatively was 0.84%; ST incidence was lowest in the low big ET-1 group (0.56%), highest in the high big ET-1 group (1.48%), and intermediate in the medium big ET-1 group (0.74%, log-rank p=0.001). Compared with the low big ET-1 group, the multivariate-adjusted hazard ratio (HR) for ST in the high big ET-1 group was 2.06 (95% confidence interval (CI) 1.14-3.73, p=0.017). In subgroup analyses, high big ET-1 level was independently associated with ST in patients with acute coronary syndrome (HR 2.29, 95% CI 1.03-5.06, p=0.041), but not in those with stable coronary artery disease (p=0.331), and tended to be associated with older age. Plasma big ET-1 level is a valuable independent predictor of ST in patients with coronary stents, especially in the acute coronary syndrome population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Correlation of endothelin-1 concentration in aqueous humor with intraocular pressure in primary open angle and pseudoexfoliation glaucoma.

    Science.gov (United States)

    Choritz, Lars; Machert, Maren; Thieme, Hagen

    2012-10-23

    Endothelin-1 (ET-1) has been found in elevated concentrations in the aqueous humor of glaucoma patients. Indirect evidence from animal studies suggests that ET-1 might directly influence intraocular pressure (IOP). The aim of this study was to determine whether ET-1 concentrations in aqueous humor of cataract and glaucoma patients correlate with IOP. Aqueous humor and blood samples from patients with either cataract (control, n = 38), primary open angle glaucoma (POAG, n = 35), or pseudoexfoliation glaucoma (PEXG, n = 21), without other ocular or systemic disease, were collected during routine cataract surgery or trabeculectomy. ET-1 concentration was determined by an ET-1 ELISA kit. IOP was measured preoperatively by standard Goldmann applanation tonometry. All statistical analysis was performed using commercial predictive analytics software. Both IOP and ET-1 concentration in aqueous humor were significantly increased in POAG (23.4 ± 6.8 mm Hg, 5.9 ± 2.9 pg/mL) and PEXG (24.3 ± 8.8 mm Hg, 7.7 ± 2.1 pg/mL) compared with control (15.0 ± 2.9 mm Hg, 4.3 ± 2.4 pg/mL). No difference was detected for plasma ET-1 concentrations. IOP and ET-1 in the aqueous humor were significantly correlated (R = 0.394, R² = 0.155, P < 0.001), although no correlation was found between IOP and ET-1 in blood plasma or between ET-1 in aqueous humor and ET-1 in plasma. In this study, a small but highly significant correlation between IOP and the ET-1 concentration in the aqueous humor was found. Although no causative relationship can be deduced from this, ocular ET-1 effects on IOP control may merit further investigation.

  11. Highly Selective Endothelin-1 Receptor A Inhibition Prevents Bleomycin-Induced Pulmonary Inflammation and Fibrosis in Mice.

    Science.gov (United States)

    Manitsopoulos, Nikolaos; Nikitopoulou, Ioanna; Maniatis, Nikolaos A; Magkou, Christina; Kotanidou, Anastasia; Orfanos, Stylianos E

    2017-11-09

    Pulmonary fibrosis is a chronic disease, which progressively leads to respiratory failure and ultimately death. Endothelin-1 (ET-1), a vasoconstrictor secreted by endothelial cells, promotes vasoconstriction by activation of its receptors A and B. We addressed the role of highly selective ET-1 receptor A (ETA) inhibition in the pathogenesis of experimental pulmonary fibrosis by bleomycin (BLM). BLM sulfate (2 U/mL) or saline was intratracheally administered to C57/Bl6 mice (4 groups; n = 5-11/group). Pretreatment with the highly selective ETA receptor inhibitor sitaxentan (15 mg/kg/day) was started 1 day prior to BLM injection and continued for the duration of the experiment. Lung mechanics were assessed prior to sacrifice at days 7, 14, and 21 after BLM, followed by procurement of bronchoalveolar lavage fluid (BALF), blood, and lung tissue samples. Time-dependent effects of BLM exposure included decreased static compliance and increased lung elastance, airspace inflammation and microvascular permeability, histological acute lung injury and fibrosis, and lung collagen deposition. Pretreatment with highly selective ETA receptor inhibitor had no adverse effect on control mice but improved lung mechanics and lung injury score in addition to decreasing BALF pleocytosis, protein content, and collagen deposition in BLM-treated mice. Mortality from BLM reached 40% and occurred primarily during the inflammatory stage of the model but was abrogated by sitaxentan pretreatment. We conclude that in our BLM-induced pulmonary fibrosis model, prophylactic highly selective ETA inhibition improves survival, preserves lung function, attenuates lung injury, and reduces collagen deposition. © 2017 S. Karger AG, Basel.

  12. Effects of selenium supplementation on expression of endothelin-1 and its receptors in pulmonary microvascular endothelial cells from chick embryos.

    Science.gov (United States)

    Gao, Jianfeng; Zhang, Ding; Zhang, Kerong; Liu, Mengyuan; Han, Zhaoqing; Li, Jiakui

    2012-12-01

    The objective of this study was to evaluate the effects of supplemental selenium (Se) on expression of endothelin-1 (ET-1) and its receptors in cultured chick embryos pulmonary microvascular endothelial cells (PMVECs). To accomplish this, PMVECs were treated in Se-deficient or Se-supplement (12, 24, 50, 100 ng/ml) culture medium for 48 h. Low Se medium was achieved by reducing serum concentrations and the essential growth factors were added. After the incubation, the effects of supplemental Se on ET-1 and its receptors gene expression were assessed by quantitative real-time PCR (qRT-PCR). Compared with the control group, our results showed that among the different concentrations of Se supplement, the levels of ET-1 gene expression treated with both the moderate Se doses (24, 50 ng/ml, P doses (100 ng/ml, P dose group (12 ng/ml), which showed no changes. Meanwhile, Se supplement (24, 50, 100 ng/ml) was found to be effective in reducing the expression levels of ETA (P  0.05) in ETB mRNA levels during the cell proliferation. These observations indicated that Se may play both direct and indirect role in the regulation of ET-1 and its receptors gene expression and their production in avian PMVECs. Se supplement decreases in ET-1 and ETA production in Se-deficient PMVECs may partly explain the mechanism of the protective effects of the Se on the cardiovascular system.

  13. Reduced contribution of endothelin to the regulation of systemic and pulmonary vascular tone in severe familial hypercholesterolaemia

    Science.gov (United States)

    Bender, Shawn B; de Beer, Vincent J; Tharp, Darla L; van Deel, Elza D; Bowles, Douglas K; Duncker, Dirk J; Laughlin, M Harold; Merkus, Daphne

    2014-01-01

    Vascular dysfunction has been associated with familial hypercholesterolaemia (FH), a severe form of hyperlipidaemia. We recently demonstrated that swine with FH exhibit reduced exercise-induced systemic, but not pulmonary, vasodilatation involving reduced nitric oxide (NO) bioavailability. Since NO normally limits endothelin (ET) action, we examined the hypothesis that reduced systemic vasodilatation during exercise in FH swine results from increased ET-mediated vasoconstriction. Systemic and pulmonary vascular responses to exercise were examined in chronically instrumented normal and FH swine in the absence and presence of the ETA/B receptor antagonist tezosentan. Intrinsic reactivity to ET was further assessed in skeletal muscle arterioles. FH swine exhibited ∼9-fold elevation in total plasma cholesterol versus normal swine. Similar to our recent findings, systemic, not pulmonary, vasodilatation during exercise was reduced in FH swine. Blockade of ET receptors caused marked systemic vasodilatation at rest and during exercise in normal swine that was significantly reduced in FH swine. The reduced role of ET in FH swine in vivo was not the result of decreased arteriolar ET responsiveness, as responsiveness was increased in isolated arterioles. Smooth muscle ET receptor protein content was unaltered by FH. However, circulating plasma ET levels were reduced in FH swine. ET receptor antagonism caused pulmonary vasodilatation at rest and during exercise in normal, but not FH, swine. Therefore, contrary to our hypothesis, FH swine exhibit a generalised reduction in the role of ET in regulating vascular tone in vivo probably resulting from reduced ET production. This may represent a unique vascular consequence of severe familial hypercholesterolaemia. PMID:24421352

  14. [Effects of obstructive sleep apnea style intermittent hypoxia on endothelin-1, nitric oxide, and nitric oxide synthase in endothelium: experiment with human umbilical vein endothelial cells].

    Science.gov (United States)

    Zhao, Hai-yan; Chen, Bao-yuan; Cao, Jie; Feng, Jing; Guo, Mei-nan

    2007-08-21

    To investigate the effects of intermittent hypoxia (IH) on the expression of endothelin-1 (ET-1), nitric oxide (NO), and nitric oxide synthase (NOS) in endothelium, and to evaluate the role of functional disorder of endothelium in the mechanism of obstructive sleep apnea syndrome (OSAS) induced hypertension. Human umbilical vein endothelial cells (HUVECs) of the line ECV304 were cultured and divided into 4 groups: IH group (exposed to 1.5% O(2) for 15 s and 21% O(2) for 1 min 15 s, 3 min 45 s, 5 min 15 s, or 8 min 15 s respectively alternatively with 60 episodes), intermittent normal oxygen group (exposed to 21% O(2) for 15 s and 225 s alternatively with 60 episodes), continuous hypoxia group (exposed to 1.5% for 15 min), and blank control group. Then the culture fluid was collected. The levels of activity of ET-1 (EIA) NO, and NOS were detected by enzyme immune assay, nitric acid reductase method, and chemical colorimetric analysis respectively. RT-PCR was used to detect the mRNA expression of endothelial NOS (eNOS). Compared with those of the intermittent normal oxygen group and blank control groups the ET-1 levels of the 4 IH sub groups were significantly higher (F = 28.453, P = 0.000), the NO levels ere significantly lower F = 65.252, P = 0.000), the NOS activity levels were significantly lower (F = 5.969, P = 0.008), and eNOS mRNA was significantly down-regulated (F = 16.630, P = 0.000). Compared with continuous hypoxia group with the exposure time equivalent to the accumulated hypoxia time (15 s with 60 episodes) of the IH group, the ET-1 level was significantly higher (t = 2.742, P = 0.024), the NO level was significantly lower (t = 3.347, P = 0.004), the NOS activity level was significantly lower (t = 3.989, P = 0.004), and the eNOS mRNA expression was down-regulated (t = 5.045, P = 0.000). In the different IH group along with the prolongation of the re-oxygenation time from 105 s to 495 s, while maintaining the duration of hypoxic episodes at 15 s, the ET

  15. Mexico City normal weight children exposed to high concentrations of ambient PM2.5 show high blood leptin and endothelin-1, vitamin D deficiency, and food reward hormone dysregulation versus low pollution controls. Relevance for obesity and Alzheimer disease.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; D'Angiulli, Amedeo; Rodríguez-Díaz, Joel; Blaurock-Busch, Eleonore; Busch, Yvette; Chao, Chih-kai; Thompson, Charles; Mukherjee, Partha S; Torres-Jardón, Ricardo; Perry, George

    2015-07-01

    Millions of Mexico, US and across the world children are overweight and obese. Exposure to fossil-fuel combustion sources increases the risk for obesity and diabetes, while long-term exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with increased risk of Alzheimer's disease (AD). Mexico City Metropolitan Area children are chronically exposed to PM2.5 and O3 concentrations above the standards and exhibit systemic, brain and intrathecal inflammation, cognitive deficits, and Alzheimer disease neuropathology. We investigated adipokines, food reward hormones, endothelial dysfunction, vitamin D and apolipoprotein E (APOE) relationships in 80 healthy, normal weight 11.1±3.2 year olds matched by age, gender, BMI and SES, low (n: 26) versus high (n:54) PM2.5 exposures. Mexico City children had higher leptin and endothelin-1 (pMexico City APOE 4 versus 3 children had higher glucose (p=0.009). Serum 25-hydroxyvitamin DMexico City children. Leptin is strongly positively associated to PM 2.5 cumulative exposures. Residing in a high PM2.5 and O3 environment is associated with 12h fasting hyperleptinemia, altered appetite-regulating peptides, vitamin D deficiency, and increases in ET-1 in clinically healthy children. These changes could signal the future trajectory of urban children towards the development of insulin resistance, obesity, type II diabetes, premature cardiovascular disease, addiction-like behavior, cognitive impairment and Alzheimer's disease. Increased efforts should be made to decrease pediatric PM2.5 exposures, to deliver health interventions prior to the development of obesity and to identify and mitigate environmental factors influencing obesity and Alzheimer disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Requirements of blue, UV-A, and UV-B light for normal growth of higher plants, as assessed by actions spectra for growth and related phenomena

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, T. [Kobe Women`s Univ., Higashisuma (Japan)

    1994-12-31

    It is very important for experimental purposes, as well as for the practical use of plants when not enough sunlight is available. To grow green higher plants in their normal forms under artificial lighting constructing efficient and economically reasonable lighting systems is not an easy task. One possible approach would be to simulate sunlight in intensity and the radiation spectrum, but its high construction and running costs are not likely to allow its use in practice. Sunlight may be excessive in irradiance in some or all portions of the spectrum. Reducing irradiance and removing unnecessary wavebands might lead to an economically feasible light source. However, removing or reducing a particular waveband from sunlight for testing is not easy. Another approach might be to find the wavebands required for respective aspects of plant growth and to combine them in a proper ratio and intensity. The latter approach seems more practical and economical, and the aim of this Workshop lies in advancing this approach. I summarize our present knowledge on the waveband requirements of higher plants for the regions of blue, UV-A and UV-B.

  17. Why Faster, Higher, Stronger Isn't Necessarily Better--The Relations of Paralympian and Women's Soccer Teams' Performance to National Well-Being

    Science.gov (United States)

    Downie, Michelle; Koestner, Richard

    2008-01-01

    The present study considers how the athletic performance of minority groups relates to national subjective well-being (SWB) and life expectancy. Based on the argument that sports represent a microcosm of society and the reliable finding that national inequality is associated with reduced SWB, we hypothesized that greater opportunities for…

  18. Similar or Different?: A Comparative Analysis of Higher Education Research in Political Science and International Relations between the United States of America and the United Kingdom

    Science.gov (United States)

    Blair, Alasdair

    2015-01-01

    This article focuses on the nature of the writing in 73 articles published in six U.S. and U.K. political science and international relations journals that focus on teaching and learning. A comparative analysis is made of the articles through a review of the characteristics of the authors, the themes researched, the analytical focus, the research…

  19. A novel bioinformatics pipeline to discover genes related to arbuscular mycorrhizal symbiosis based on their evolutionary conservation pattern among higher plants.

    Science.gov (United States)

    Favre, Patrick; Bapaume, Laure; Bossolini, Eligio; Delorenzi, Mauro; Falquet, Laurent; Reinhardt, Didier

    2014-12-03

    Genes involved in arbuscular mycorrhizal (AM) symbiosis have been identified primarily by mutant screens, followed by identification of the mutated genes (forward genetics). In addition, a number of AM-related genes has been identified by their AM-related expression patterns, and their function has subsequently been elucidated by knock-down or knock-out approaches (reverse genetics). However, genes that are members of functionally redundant gene families, or genes that have a vital function and therefore result in lethal mutant phenotypes, are difficult to identify. If such genes are constitutively expressed and therefore escape differential expression analyses, they remain elusive. The goal of this study was to systematically search for AM-related genes with a bioinformatics strategy that is insensitive to these problems. The central element of our approach is based on the fact that many AM-related genes are conserved only among AM-competent species. Our approach involves genome-wide comparisons at the proteome level of AM-competent host species with non-mycorrhizal species. Using a clustering method we first established orthologous/paralogous relationships and subsequently identified protein clusters that contain members only of the AM-competent species. Proteins of these clusters were then analyzed in an extended set of 16 plant species and ranked based on their relatedness among AM-competent monocot and dicot species, relative to non-mycorrhizal species. In addition, we combined the information on the protein-coding sequence with gene expression data and with promoter analysis. As a result we present a list of yet uncharacterized proteins that show a strongly AM-related pattern of sequence conservation, indicating that the respective genes may have been under selection for a function in AM. Among the top candidates are three genes that encode a small family of similar receptor-like kinases that are related to the S-locus receptor kinases involved in sporophytic

  20. Modelling exposure of oceanic higher trophic-level consumers to polychlorinated biphenyls: pollution 'hotspots' in relation to mass mortality events of marine mammals.

    Science.gov (United States)

    Handoh, Itsuki C; Kawai, Toru

    2014-08-30

    Marine mammals in the past mass mortality events may have been susceptible to infection because their immune systems were suppressed through the bioaccumulation of environmental pollutants such as polychlorinated biphenyls (PCBs). We compiled mortality event data sets of 33 marine mammal species, and employed a Finely-Advanced Transboundary Environmental model (FATE) to model the exposure of the global fish community to PCB congeners, in order to define critical exposure levels (CELs) of PCBs above which mass mortality events are likely to occur. Our modelling approach enabled us to describe the mass mortality events in the context of exposure of higher-trophic consumers to PCBs and to identify marine pollution 'hotspots' such as the Mediterranean Sea and north-western European coasts. We demonstrated that the CELs can be applied to quantify a chemical pollution Planetary Boundary, under which a safe operating space for marine mammals and humanity can exist. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Serum vaspin concentrations are closely related to insulin resistance, and rs77060950 at SERPINA12 genetically defines distinct group with higher serum levels in Japanese population.

    Science.gov (United States)

    Teshigawara, Sanae; Wada, Jun; Hida, Kazuyuki; Nakatsuka, Atsuko; Eguchi, Jun; Murakami, Kazutoshi; Kanzaki, Motoko; Inoue, Kentaro; Terami, Takahiro; Katayama, Akihiro; Iseda, Izumi; Matsushita, Yuichi; Miyatake, Nobuyuki; McDonald, John F; Hotta, Kikuko; Makino, Hirofumi

    2012-07-01

    Vaspin is an adipokine with insulin-sensitizing effects identified from visceral adipose tissues of genetically obese rats. We investigated genetic and nongenetic factors that define serum concentrations of vaspin. Vaspin levels were measured with RIA in Japanese subjects with normal fasting plasma glucose (NFG; n = 259) and type 2 diabetes patients (T2D; n = 275). Single nucleotide polymorphisms (SNP) at SERPINA12 (vaspin) gene locus were discovered, and five SNP were genotyped in the subjects with varied body mass index (n = 1138). The level of serum vaspin in 93% of the samples was found to vary from 0.2 to nearly 2 ng/ml in NFG subjects (n = 259) and from 0.2 to nearly 3 ng/ml in T2D patients (n = 275) (Vaspin(Low) group), whereas a significant subpopulation (7%) in both groups displayed much higher levels of 10-40 ng/ml (Vaspin(High) group). In the Vaspin(Low) group, serum vaspin levels in T2D were significantly higher than healthy subjects (0.99 ± 0.04 vs. 0.86 ± 0.02 ng/ml; P population, serum vaspin levels closely correlated with homeostasis model of assessment for insulin resistance rather than anthropometric parameters. By genotyping, rs77060950 tightly linked to serum vaspin levels, i.e. CC (0.6 ± 0.4 ng/ml), CA (18.4 ± 9.6 ng/ml), and AA (30.5 ± 5.1 ng/ml) (P population are closely linked to minor allele sequence (A) of rs77060950.

  2. Methylphenidate-Related Improvements in Math Performance Cannot Be Explained by Better Cognitive Functioning or Higher Academic Motivation: Evidence From a Randomized Controlled Trial.

    Science.gov (United States)

    Kortekaas-Rijlaarsdam, Anne Fleur; Luman, Marjolein; Sonuga-Barke, Edmund; Bet, Pierre; Oosterlaan, Jaap

    2017-06-01

    This study investigated whether improvements in working memory, reaction time, lapses of attention, interference control, academic motivation, and perceived competence mediated effects of methylphenidate on math performance. Sixty-three children (ADHD diagnosis; methylphenidate treatment; age 8-13; IQ > 70) were randomly allocated to a 7-day methylphenidate or placebo treatment in this double-blind placebo-controlled crossover study and compared with 67 controls. Data were collected at schools and analyzed using mixed-model analysis. Methylphenidate was hypothesized to improve all measures; all measures were evaluated as potential mediators of methylphenidate-related math improvements. Controls mostly outperformed the ADHD group. Methylphenidate did not affect measures of cognitive functioning ( p = .082-.641) or academic motivation ( p = .199-.865). Methylphenidate improved parent ratings of their child's self-perceived competence ( p motivational deficits associated with ADHD for medication-related academic improvement. They also stimulate further study of perceived competence as a mediator.

  3. Lower prevalence of mild hyperthyroidism related to a higher iodine intake in the population: prospective study of a mandatory iodization programme

    DEFF Research Database (Denmark)

    Vejbjerg, Pernille; Knudsen, Nils; Perrild, Hans

    2009-01-01

    -2 center dot 66) before iodization. The difference was found in both regions and across age groups. There was a lower prevalence of mild hyperthyroidism and a tendency towards a lower prevalence of overt hyperthyroidism. The prevalence of mild hypothyroidism increased, most pronounced among young women...... of thyroid dysfunction was seen in relation to mandatory iodization of salt. There was no rise in the prevalence of hyperthyroidism and the prevalence of mild hyperthyroidism was halved. Conversely, prevalence of hypothyroidism increased....

  4. Countries with Higher Levels of Gender Equality Show Larger National Sex Differences in Mathematics Anxiety and Relatively Lower Parental Mathematics Valuation for Girls.

    Science.gov (United States)

    Stoet, Gijsbert; Bailey, Drew H; Moore, Alex M; Geary, David C

    2016-01-01

    Despite international advancements in gender equality across a variety of societal domains, the underrepresentation of girls and women in Science, Technology, Engineering, and Mathematics (STEM) related fields persists. In this study, we explored the possibility that the sex difference in mathematics anxiety contributes to this disparity. More specifically, we tested a number of predictions from the prominent gender stratification model, which is the leading psychological theory of cross-national patterns of sex differences in mathematics anxiety and performance. To this end, we analyzed data from 761,655 15-year old students across 68 nations who participated in the Programme for International Student Assessment (PISA). Most importantly and contra predictions, we showed that economically developed and more gender equal countries have a lower overall level of mathematics anxiety, and yet a larger national sex difference in mathematics anxiety relative to less developed countries. Further, although relatively more mothers work in STEM fields in more developed countries, these parents valued, on average, mathematical competence more in their sons than their daughters. The proportion of mothers working in STEM was unrelated to sex differences in mathematics anxiety or performance. We propose that the gender stratification model fails to account for these national patterns and that an alternative model is needed. In the discussion, we suggest how an interaction between socio-cultural values and sex-specific psychological traits can better explain these patterns. We also discuss implications for policies aiming to increase girls' STEM participation.

  5. Countries with Higher Levels of Gender Equality Show Larger National Sex Differences in Mathematics Anxiety and Relatively Lower Parental Mathematics Valuation for Girls

    Science.gov (United States)

    2016-01-01

    Despite international advancements in gender equality across a variety of societal domains, the underrepresentation of girls and women in Science, Technology, Engineering, and Mathematics (STEM) related fields persists. In this study, we explored the possibility that the sex difference in mathematics anxiety contributes to this disparity. More specifically, we tested a number of predictions from the prominent gender stratification model, which is the leading psychological theory of cross-national patterns of sex differences in mathematics anxiety and performance. To this end, we analyzed data from 761,655 15-year old students across 68 nations who participated in the Programme for International Student Assessment (PISA). Most importantly and contra predictions, we showed that economically developed and more gender equal countries have a lower overall level of mathematics anxiety, and yet a larger national sex difference in mathematics anxiety relative to less developed countries. Further, although relatively more mothers work in STEM fields in more developed countries, these parents valued, on average, mathematical competence more in their sons than their daughters. The proportion of mothers working in STEM was unrelated to sex differences in mathematics anxiety or performance. We propose that the gender stratification model fails to account for these national patterns and that an alternative model is needed. In the discussion, we suggest how an interaction between socio-cultural values and sex-specific psychological traits can better explain these patterns. We also discuss implications for policies aiming to increase girls’ STEM participation. PMID:27100631

  6. Creativity in Higher Education

    Science.gov (United States)

    Gaspar, Drazena; Mabic, Mirela

    2015-01-01

    The paper presents results of research related to perception of creativity in higher education made by the authors at the University of Mostar from Bosnia and Herzegovina. This research was based on a survey conducted among teachers and students at the University. The authors developed two types of questionnaires, one for teachers and the other…

  7. Reputation in Higher Education

    DEFF Research Database (Denmark)

    Martensen, Anne; Grønholdt, Lars

    2005-01-01

    The purpose of this paper is to develop a reputation model for higher education programmes, provide empirical evidence for the model and illustrate its application by using Copenhagen Business School (CBS) as the recurrent case. The developed model is a cause-and-effect model linking image...... for higher education reputation and which relations exist between the included determinants from a theoretical perspective. It is demonstrated how the model and measurement system may be a useful management tool for the improvement of the reputation of a higher education. In this way, the model can help...... leaders of higher education institutions to set strategic directions and support their decisions in an effort to create even better study programmes with a better reputation. Finally, managerial implications and directions for future research are discussed.Keywords: Reputation, image, corporate identity...

  8. Higher Education in Scandinavia

    DEFF Research Database (Denmark)

    Nielsen, Jørgen Lerche; Birch Andreasen, Lars

    2015-01-01

    Higher education systems around the world have been undergoing fundamental changes through the last 50 years from more narrow self-sustaining universities for the elite and into mass universities, where new groups of students have been recruited and the number of students enrolled has increased....... In this chapter we will examine how higher education systems in Scandinavia are developing in relation to these challenges. To what extent has the democratic tradition had an impact on the educational systems, and what possible futures can be envisioned? In the development of higher education in Scandinavia......, there are different perspectives on education at play. One perspective sees education as a “public good” that benefits society and therefore should be free and accessible for all students who qualify to be admitted. According to this perspective, one of the main purposes of higher education is to add value to all...

  9. [Effect of hypoxia-inducible factor-1α, endothelin-1 and inducible nitric oxide synthase in the pathogenesis of hypoxia-induced pulmonary hypertension of the neonatal rats].

    Science.gov (United States)

    Sang, Kui; Zhou, Ying; Li, Ming-xia

    2012-12-01

    To study the effect of hypoxia-inducible factor-1α (HIF-1α) in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH) of the neonatal rats through the study on the expression level of HIF-1α and its regulation factors: endothelin-1 (ET-1) and inducible nitric oxide synthase (iNOS) in blood serum and lung tissue. To make an HPH model of neonatal rats, 120 newborn Wistar rats were divided at random into two groups: HPH group and the regular oxygen controlled group with the same birthday. The rats of the two groups were put in the condition of hypoxia for 3, 5, 7, 10, 14, 21 days and then 10 rats of HPH group and control group were picked up, their mean pulmonary arterial pressure (mPAP), serum HIF-1α, and iNOS, and ET-1 content were tested, and finally their lung tissue was taken after they were sacrificed and the expression level of the gene mRNA of HIF-1α, iNOS and ET-1. (1) The rats experienced hypoxia for 3, 5, 7, 10, 14 or 21 days had an increasing mPAP: [8.47 ± 1.45, 10.04 ± 1.69, 10.89 ± 2.97, 16.96 ± 1.97, 13.01 ± 1.93, 21.04 ± 2.13 (mm Hg)], which had a significant differences compared with control groups [5.11 ± 1.06, 8.12 ± 1.11, 8.77 ± 0.92, 12.23 ± 1.78, 8.89 ± 0.89, 11.09 ± 1.64 (mm Hg)] (P rats in hypoxia group had a higher serum HIF-1α [0.83 ± 0.07, 0.84 ± 0.17, 0.97 ± 0.13, 1.10 ± 0.30, 0.92 ± 0.19 (pg/nmol)] than the control group [0.26 ± 0.20, 0.37 ± 0.16, 0.44 ± 0.18, 0.41 ± 0.23, 0.66 ± 0.18 (pg/nmol)] as they experienced hypoxia for 3, 5, 7, 10, and 14 days (P 0.05), and the content of serum iNOS after hypoxia for 14 or 21 days (4.56 ± 0.96, 5.86 ± 1.76) µmol/L was lower than that of the control group (10.35 ± 1.99, 8.44 ± 2.76) µmol/L (P rats and causedn a imbalance of ET-1 and NO. HIF-1α, ET-1 and iNOS altogether contributed to the occurrence and development of HPH in neonatal rats.

  10. A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease.

    Science.gov (United States)

    Yang, G C; Croaker, D; Zhang, A L; Manglick, P; Cartmill, T; Cass, D

    1998-06-01

    Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification-created restriction site (ACRS) technique, revealed a dinucleotide TC-->AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.

  11. Pentaerythritol Tetranitrate In Vivo Treatment Improves Oxidative Stress and Vascular Dysfunction by Suppression of Endothelin-1 Signaling in Monocrotaline-Induced Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Sebastian Steven

    2017-01-01

    Full Text Available Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH. The role of the nitrovasodilator pentaerythritol tetranitrate (PETN on endothelial function and oxidative stress in PAH has not yet been defined. Methods and Results. PAH was induced by monocrotaline (MCT, i.v. in Wistar rats. Low (30 mg/kg; MCT30, middle (40 mg/kg; MCT40, or high (60 mg/kg; MCT60 dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d and reduced by oral PETN (10 mg/kg, 24 d therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin-1 signaling was increased in MCT40-treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase-1 (HO-1. PETN therapy improved endothelium-dependent relaxation in pulmonary arteries and inhibited endothelin-1-induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM-1 in endothelial cells. Conclusion. MCT-induced PAH impairs endothelial function (aorta and pulmonary arteries and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.

  12. Efficacy of bosentan, a dual ETA and ETB endothelin receptor antagonist, in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats.

    Science.gov (United States)

    Singh, Gurpreet; Sharma, Bhupesh; Jaggi, Amteshwar Singh; Singh, Nirmal

    2014-09-01

    The study was designed to investigate the efficacy of bosentan a dual endothelin (ETA and ETB) receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia. Diabetes was induced in rats by administration of a single dose (50mg/kg, i.p.) of streptozotocin (STZ). Drug treatment was started after 1 month of STZ administration and treatment was continued until the end of the study. Morris water maze (MWM) test was employed for testing spatial learning and memory. Endothelial function was measured on isolated aortic rings using student physiograph. Serum glucose, body weight, serum nitrite/nitrate, brain thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH) levels, and brain acetylcholinesterase activity were also tested. STZ treatment resulted in significant development of cognitive and vascular endothelial deficits, manifested in the terms of endothelial dysfunction, impairment of learning and memory, reduction in body weight and serum nitrite/nitrate levels along with increase in serum glucose, brain acetylcholinesterase activity, TBARS, and decreased GSH levels. Treatment of bosentan attenuated diabetes induced impairment of learning, memory, endothelial function, and various biochemical parameters. It may be concluded that bosentan has shown efficacy in STZ induced cognitive and vascular endothelial deficits. Thus, endothelin receptors can be considered as a potential pharmacological target for the management of experimental diabetes induced vascular endothelial dysfunction and associated dementia. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Higher vascular endothelial growth factor-C concentration in plasma is associated with increased forearm capillary filtration capacity in breast cancer-related lymphedema

    DEFF Research Database (Denmark)

    Jensen, Mads Radmer; Simonsen, Lene; Karlsmark, Tonny

    2015-01-01

    shown that the forearm capillary filtration coefficient (CFC) is increased bilaterally in BCRL. In this study, we aimed to elucidate if increased CFC is associated with low-grade inflammation and/or vascular endothelial growth factor-c (VEGF-C) signaling. Fourteen patients with unilateral BCRL and nine......Breast cancer-related lymphedema (BCRL) is a frequent, chronic and debilitating swelling that mainly affects the ipsilateral arm and develops as a complication to breast cancer treatment. The pathophysiology is elusive opposing development of means for prediction and treatment. We have earlier...... increased forearm CFC in BCRL subjects. Interstitially increased MCP-1 levels may augment local microvascular protein permeability in BCRL....

  14. Higher spins and holography

    Science.gov (United States)

    Kraus, Per; Ross, Simon F.

    2013-05-01

    The principles of quantum mechanics and relativity impose rigid constraints on theories of massless particles with nonzero spin. Indeed, Yang-Mills theory and General Relativity are the unique solution in the case of spin-1 and spin-2. In asymptotically flat spacetime, there are fundamental obstacles to formulating fully consistent interacting theories of particles of spin greater than 2. However, indications are that such theories are just barely possible in asymptotically anti-de Sitter or de Sitter spacetimes, where the non-existence of an S-matrix provides an escape from the theorems restricting theories in Minkowski spacetime. These higher spin gravity theories are therefore of great intrinsic interest, since they, along with supergravity, provide the only known field theories generalizing the local invariance principles of Yang-Mills theory and General Relativity. While work on higher spin gravity goes back several decades, the subject has gained broader appeal in recent years due to its appearance in the AdS/CFT correspondence. In three and four spacetime dimensions, there exist duality proposals linking higher spin gravity theories to specific conformal field theories living in two and three dimensions respectively. The enlarged symmetry algebra of the conformal field theories renders them exactly soluble, which makes them excellent laboratories for understanding in detail the holographic mechanism behind AdS/CFT duality. Steady progress is also being made on better understanding the space of possible higher spin gravity theories and their physical content. This work includes classifying the possible field multiplets and their interactions, constructing exact solutions of the nonlinear field equations, and relating higher spin theories to string theory. A full understanding of these theories will involve coming to grips with the novel symmetry principles that enlarge those of General Relativity and Yang-Mills theory, and one can hope that this will provide

  15. Accumulation of DOC in Low Phosphate Low Chlorophyll (LPLC area: is it related to higher production under high N:P ratio?

    Directory of Open Access Journals (Sweden)

    R. Mauriac

    2011-04-01

    Full Text Available The biogeochemistry of carbon and nutrients (N,P in the surface layer of the ocean strongly depends on the complex interactions between primary producers (phytoplankton and remineralizers (heterotrophic bacteria. To understand how these interactions impact the overall DOC dynamics in the surface layer of the Mediterranean Sea, we implemented, using Eco3M (Ecological Mechanistic Modular Modelling tool, a multi-element model with a mechanistic description of primary production. We studied the model steady state results under various nutrient conditions and fixed cell abundances. By doing so, we show how the bottom up control of osmotrophs growth can impact the overall DOC dynamics in the system. Based on our set of parameters, the biogeochemical characteristics displayed by the model appear realistic when compared to literature data for the Mediterranean basin. Differences in DOC dynamics between N and P limited systems in the model, lead to the conclusion that the unusually high N:P ratio of the Mediterranean Sea may favour the uncoupling between growth and carbon production leading to higher DOC accumulation compared to systems with lower N:P ratio.

  16. Effect of the energy-environment simulator on achievement, attitudes, and behavior relative to energy-education concepts systematically replicated in higher education

    Energy Technology Data Exchange (ETDEWEB)

    Lees, J.R.

    1983-01-01

    This study was a systematic replication of a study by Stagliano (1981). Additional hypotheses concerning pretest, student major, and student section variance were tested. Achievement in energy knowledge and conservation attitudes attained by (a) lecture-discussion enriched with the Energy-Environment Simulator and (b) lecture-discussion methods of instruction were measured. Energy knowledge was measured on the Energy Knowledge Assessment Test (EKAT), and attitudes were measured on the Youth Energy Survey (YES), the Lecture-discussion simulation (LDS) used a two hour out-of-class activity in debriefing. The population consisted of 142 college student volunteers randomly selected, and assigned to one of two groups of 71 students for each treatment. Stagliano used three groups (n = 35), one group receiving an energy-game treatment. Both studies used the pretest-posttest true experimental design. The present study included 28 hypotheses, eight of which were found to be significant. Stagliano used 12 hypotheses, all of which were rejected. The present study hypothesized that students who received the LDS treatment would obtain significantly higher scores on the EKAT and the YES instruments. Results showed that significance was found (alpha level .05) on the EKAT and also found on the YES total subscale when covaried for effects of pretest, student major, and student section. When covarying the effects of pretest scores only, significance was found on the EKAT. All YES hypotheses were rejected.

  17. Illegitimate tasks associated with higher cortisol levels among male employees when subjective health is relatively low: an intra-individual analysis.

    Science.gov (United States)

    Kottwitz, Maria U; Meier, Laurenz L; Jacobshagen, Nicola; Kälin, Wolfgang; Elfering, Achim; Hennig, Jürgen; Semmer, Norbert K

    2013-05-01

    Illegitimate tasks refer to tasks that do not conform to what can appropriately be expected from an employee. Violating role expectations, they constitute "identity-stressors", as one's professional role tends to become part of one's identity. The current study investigated the impact of illegitimate tasks on salivary cortisol. We analyzed data on an intra-individual level, that is, by examining fluctuations in illegitimate tasks and cortisol within individuals. Furthermore, we investigated the moderating role of perceived health, expecting that illegitimate tasks evoke stronger reactions when perceived health is relatively poor. Illegitimate tasks, salivary cortisol, and perceived health were assessed in each of three waves (time lag: 6 months) in a sample of 104 male employees. Data were analyzed by multilevel analysis using group mean centering. Controlling for social stressors, work interruptions, and emotional stability, the experience of more illegitimate tasks was associated with increased cortisol release if personal health resources were low compared to one's mean value of perceived health. Results cannot be explained by inter-individual differences. This is the first study showing that illegitimate tasks predict a biological indicator of stress, thus confirming and extending previous research on illegitimate tasks. The moderating role of perceived health confirms its importance as a personal resource, implying augmented vulnerability when perceived health is below its usual value. It is plausible to assume that increased stress reactions due to relatively poor health may further weaken available personal resources. Both avoiding illegitimate tasks and restoring personal health seem to be crucial.

  18. Anhedonia in prolonged schizophrenia spectrum patients with relatively lower vs. higher levels of depression disorders: associations with deficits in social cognition and metacognition.

    Science.gov (United States)

    Buck, Kelly D; McLeod, Hamish J; Gumley, Andrew; Dimaggio, Giancarlo; Buck, Benjamin E; Minor, Kyle S; James, Alison V; Lysaker, Paul H

    2014-10-01

    This study has sought to explore whether there are at least two subtypes of anhedonia in schizophrenia: one closely linked with depression and another that occurs in the absence of depression which is related to a general paucity of internal experience. Participants were 163 adults with schizophrenia who completed assessments of depression, anhedonia, executive functioning, positive and negative symptoms, social cognition and metacognition. A cluster analysis based on participants' depression and anhedonia symptom scores produced three groups: High Depression/High Anhedonia (n=52), Low Depression/Low Anhedonia (n=52), and Low Depression/High Anhedonia (n=59). An ANCOVA and post hoc comparisons controlling for positive and negative symptoms found that the Low Depression/High Anhedonia group had poorer metacognition and social cognition than other groups. These findings point to the possibility of a subtype of anhedonia in schizophrenia, one occurring in the relative lesser levels of depression, and tied to deficits in the ability to think about oneself and others. Published by Elsevier Inc.

  19. Analysis of endotoxin and endothelin-1 levels in patients with type 1 hepatorenal syndrome

    Directory of Open Access Journals (Sweden)

    GAO Baoxiu

    2014-01-01

    Full Text Available ObjectiveTo analyze the clinical data, laboratory parameters, infection rate, and serum procalcitonin (PCT and ET-1 levels of patients with cirrhotic ascites and type 1 hepatorenal syndrome (HRS and to investigate the roles of endotoxin and ET-1 in the development of HRS. MethodsBetween January 2009 and October 2012, 56 inpatients with cirrhotic ascites and type 1 HRS (HRS group and 60 inpatients with cirrhotic ascites who had normal renal function (non-HRS group were included in the study. Their general data, causes of liver cirrhosis, infection rates and types, Child-Pugh classification, systemic inflammatory response syndrome (SIRS score, and mean arterial pressure (MAP were recorded; blood samples were collected to evaluate liver and renal function and measure serum electrolyte, PCT, and ET-1 levels. The clinical data and laboratory parameters were compared between the two groups. Categorical data were analyzed by chi-square test; comparison of normally distributed continuous data between the two groups was made by independent-samples t test, and comparison of non-normally distributed continuous data between the two groups was made by Wilcoxon rank sum test. ResultsThe infection rate of HRS group (75.0% was significantly higher than that of non-HRS group (28.4% (χ2=11.91, P<0.05. The PCT and ET-1 levels and SIRS score of HRS group [8.72 (3.14, 31.68 ng/L, 13.04±2.82 pg/ml, and 2.1±1.1] were significantly higher than those of non-HRS group [0.11 (0.04, 0.45 ng/L, 5.76±1.68 pg/ml, and 0.6±0.6] (P<0.05. In addition, the HRS group had significantly higher serum urea, creatine, cystatin C, and K levels than the non-HRS group (P<0.05, while the HRS group had significantly lower Na and Cl levels than the non-HRS group (P<0.05. There were no significant differences in ALT and AST levels between the two groups (P>005. ConclusionEndotoxin causes elevated expression of ET-1, and ET-1 induces renal perfusion deficiency by

  20. Microbial relatives of the seed storage proteins of higher plants: conservation of structure and diversification of function during evolution of the cupin superfamily.

    Science.gov (United States)

    Dunwell, J M; Khuri, S; Gane, P J

    2000-03-01

    This review summarizes the recent discovery of the cupin superfamily (from the Latin term "cupa," a small barrel) of functionally diverse proteins that initially were limited to several higher plant proteins such as seed storage proteins, germin (an oxalate oxidase), germin-like proteins, and auxin-binding protein. Knowledge of the three-dimensional structure of two vicilins, seed proteins with a characteristic beta-barrel core, led to the identification of a small number of conserved residues and thence to the discovery of several microbial proteins which share these key amino acids. In particular, there is a highly conserved pattern of two histidine-containing motifs with a varied intermotif spacing. This cupin signature is found as a central component of many microbial proteins including certain types of phosphomannose isomerase, polyketide synthase, epimerase, and dioxygenase. In addition, the signature has been identified within the N-terminal effector domain in a subgroup of bacterial AraC transcription factors. As well as these single-domain cupins, this survey has identified other classes of two-domain bicupins including bacterial gentisate 1, 2-dioxygenases and 1-hydroxy-2-naphthoate dioxygenases, fungal oxalate decarboxylases, and legume sucrose-binding proteins. Cupin evolution is discussed from the perspective of the structure-function relationships, using data from the genomes of several prokaryotes, especially Bacillus subtilis. Many of these functions involve aspects of sugar metabolism and cell wall synthesis and are concerned with responses to abiotic stress such as heat, desiccation, or starvation. Particular emphasis is also given to the oxalate-degrading enzymes from microbes, their biological significance, and their value in a range of medical and other applications.

  1. Comparing two levels of closed system suction pressure in ICU patients: Evaluating the relative safety of higher values of suction pressure

    Science.gov (United States)

    Yazdannik, Ahmad R.; Haghighat, Somayeh; Saghaei, Mahmoud; Eghbali, Maryam

    2013-01-01

    Background: Endotracheal suctioning (ETS) is one of the most common supportive measures in intensive care units (ICU). ETS may be associated with complications including hypoxia and tachycardia. Closed system suctioning (CSS) decreases the rate of cardiorespiratory complication mainly due to continuation of ventilatory support and oxygenation during procedure. CSS has questionable efficacy, therefore higher values of negative pressure has been recommended to enhance the efficacy of CSS. This study was designed to evaluate the effects on gas exchange of 200 mmHg suctioning pressure compared with 100 mmHg in CSS. Materials and Methods: Fifty mechanically ventilated (MV) ICU patients were selected for the study. Two consecutive ten seconds CSS using suction pressures of 100 and 200 mmHg, in random order applied in each subject with the two hours wash out period. Effects of two levels of suction pressure on gas exchange were measured by recording the SPo2 values at 4 times. Results: Repeated measure analysis of variance didn't show any significant difference between two levels of pressure (P = 0.315), but within each groups (100 and 200 mmHg) SPO2 changes was significant (P = 0.000). There was a mild but significant and transient increase in heart rate following both suction pressures, but no significant difference between two groups. Conclusion: The results show that CSS with suction pressure 200 mmHg has no detrimental effect on cardiorespiratory function of MV ICU patients. Since the safety of 200 mmHg suctioning pressure was approved, using 200 mmHg suction pressures is recommended for ETS of MV patients. PMID:23983740

  2. Infusion-related febrile reaction after haploidentical stem cell transplantation in children is associated with higher rates of engraftment syndrome and acute graft-versus-host disease.

    Science.gov (United States)

    Chen, Yao; Huang, Xiao-Jun; Liu, Kai-Yan; Chen, Huan; Chen, Yu-Hong; Zhang, Xiao-Hui; Wang, Feng-Rong; Han, Wei; Wang, Jing-Zhi; Wang, Yu; Yan, Chen-Hua; Zhang, Yuan-Yuan; Sun, Yu-Qian; Xu, Lan-Ping

    2015-12-01

    The clinical significance and prognostic impact of IRFR in pediatric recipients of haploidentical SCT are not clearly understood. Therefore, we attempted to determine how IRFR affects clinical outcomes in children. Clinical data from 100 consecutive pediatric patients (60 boys and 40 girls; median age, 12 yr [range, 2-18 yr] after haploidentical SCT between January 2010 and December 2012 were collected retrospectively. IRFR was described as unexplained fever (>38 °C) within 24 h after the infusion of haploidentical PBSCs. Thirty-eight (38.0%) cases met the criteria for IRFR. ES was found in 24 (63.2%) of the 38 children with IRFR, with the median time of developing ES of +9 (7-16) days, while only 15 (25.4%) of the 59 children without IRFR were found with ES (p rates of grade II-IV aGVHD were 50.0% in the IRFR group and 29.3% (p = 0.012) in the non-febrile group. Multivariate analysis identified IRFR as the risk factor for ES and aGVHD. In the haploidentical setting, IRFR is associated with the development of ES and aGVHD. We attempted to determine how IRFR affects clinical outcomes in children after haploidentical SCT. Thirty-eight children comprised the IRFR group, and 59 were in the control (non-IRFR) group. High incidence of ES was observed in children with the occurrence of IRFR. Similarly, the incidence of stage I-IV and II-IV aGVHD was significantly higher in the febrile group. Multivariate analysis showed IRFR to be the risk factor for ES and aGVHD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Improvement in neurological outcome and abolition of cerebrovascular endothelin B and 5-hydroxytryptamine 1B receptor upregulation through mitogen-activated protein kinase kinase 1/2 inhibition after subarachnoid hemorrhage in rats

    DEFF Research Database (Denmark)

    Larsen, Carl Christian; Povlsen, Gro Klitgaard; Rasmussen, Marianne Nelly Paola

    2011-01-01

    Delayed cerebral ischemia after subarachnoid hemorrhage (SAH) remains a major cause of death and disability. It has been hypothesized that cerebrovascular upregulation of vasoconstrictor receptors is a key step in the development of delayed cerebral ischemia. Upregulation of endothelin-B (ET(B)) ...

  4. Up-regulation of endothelin type B receptors in the human internal mammary artery in culture is dependent on protein kinase C and mitogen-activated kinase signaling pathways

    DEFF Research Database (Denmark)

    Nilsson, David; Gustafsson, Lotta; Wackenfors, Angelica

    2008-01-01

    Up-regulation of vascular endothelin type B (ETB) receptors is implicated in the pathogenesis of cardiovascular disease. Culture of intact arteries has been shown to induce similar receptor alterations and has therefore been suggested as a suitable method for, ex vivo, in detail delineation of th...

  5. Organized Sport Participation Is Associated with Higher Levels of Overall Health-Related Physical Activity in Children (CHAMPS Study-DK)

    DEFF Research Database (Denmark)

    Hebert, Jeffrey J.; Møller, Niels C.; Andersen, Lars Bo

    2015-01-01

    Introduction Many children fail to meet international guideline recommendations for health-related activity (>= 60 minutes/day of moderate-to-vigorous physical activity [MVPA]), and intervention studies to date have reported negligible effects. Objective Explore the associations of organized...... of 1124 primary school students. Organized leisure-time sport participation was reported via text messaging and physical activity was objectively measured over seven days with accelerometry. Associations between sport participation and physical activity level were explored with multilevel mixed......-effects regression models and reported with beta coefficients (b) and adjusted odds ratios (aOR). Results Participants were 53% female, with mean(SD) age = 8.4(1.4) years. Boys were more active than girls (p...

  6. Higher incidence of bone stress injuries with increasing female athlete triad-related risk factors: a prospective multisite study of exercising girls and women.

    Science.gov (United States)

    Barrack, Michelle T; Gibbs, Jenna C; De Souza, Mary Jane; Williams, Nancy I; Nichols, Jeanne F; Rauh, Mitchell J; Nattiv, Aurelia

    2014-04-01

    Identifying the risk factors associated with a bone stress injury (BSI), including stress reactions and stress fractures, may aid in targeting those at increased risk and in formulating prevention guidelines for exercising girls and women. To evaluate the effect of single or combined risk factors as defined by the female athlete triad-a syndrome involving 3 interrelated spectrums consisting of energy availability, menstrual function, and bone mass-with the incidence of BSIs in a multicenter prospective sample of 4 cohorts of physically active girls and women. Cohort study; Level of evidence, 3. At baseline, participants' (N = 259; mean age, 18.1 ± 0.3 years) anthropometric characteristics, eating attitudes and behaviors, menstrual function, sports participation or exercise activity, and pathological weight control behaviors were assessed. Dual-energy x-ray absorptiometry (DXA) measured the bone mass of the whole body, total hip, femoral neck, lumbar spine, and body composition. Participants were followed prospectively for the occurrence of injuries; those injuries confirmed by a physician were recorded. Twenty-eight participants (10.8%) incurred a BSI. Forty-six percent of those who had ≥12 h/wk of purposeful exercise, a bone mineral density (BMD) Z score sport exercise/activity at baseline, incurred a BSI during the prospective study period. Single factors significantly (P exercise (14.7%), BMI exercise, with 29.7% incurring a BSI (odds ratio [OR], 5.1; 95% CI, 2.2-12.1), and ≥12 h/wk of exercise + leanness sport/activity + dietary restraint, with 46.2% incurring a BSI (OR, 8.7; 95% CI, 2.7-28.3). In the sample, which included female adolescents and young adults participating in competitive or recreational exercise activities, the risk of BSIs increased from approximately 15% to 20% for significant single risk factors to 30% to 50% for significant combined female athlete triad-related risk factor variables. These data support the notion that the cumulative

  7. Higher Anti-Liver Fibrosis Effect of Cordyceps militaris-Fermented Product Cultured with Deep Ocean Water via Inhibiting Proinflammatory Factors and Fibrosis-Related Factors Expressions

    Directory of Open Access Journals (Sweden)

    Yu-Ping Hung

    2017-06-01

    Full Text Available Deep ocean water (DOW has been shown to enhance the functional components of fungi, resulting in increased health benefits. Therefore, using DOW for culturing fungi can enhance the cordycepin and adenosine of Cordyceps militaris (CM and its protective effects on the liver. In this study, the antiliver fibrosis effects and mechanisms of ultrapure water-cultured CM (UCM, DOW-cultured CM (DCM, synthetic water-cultured CM, DOW, cordycepin, and adenosine were compared in the liver fibrosis mice induced by intraperitoneal injections of thioacetamide (TAA. The results indicated that DCM exhibited superior performance in reducing liver collagen accumulation, mitigating liver injuries, inhibiting proinflammatory factors and fibrosis-related factor (TGF-β1, Smad2/3, α-SMA, COL1A1 expression compared with UCM. DOW, cordycepin, and adenosine also performed antiliver fibrosis effect. Therefore, because DCM is rich in DOW and functional components, it can achieve anti-liver fibrosis effects through multiple pathways. These ameliorative effects are considerably superior to those of UCM.

  8. Over-expression of VvWRKY1 in grapevines induces expression of jasmonic acid pathway-related genes and confers higher tolerance to the downy mildew.

    Science.gov (United States)

    Marchive, Chloé; Léon, Céline; Kappel, Christian; Coutos-Thévenot, Pierre; Corio-Costet, Marie-France; Delrot, Serge; Lauvergeat, Virginie

    2013-01-01

    Most WRKY transcription factors activate expression of defence genes in a salicylic acid- and/or jasmonic acid-dependent signalling pathway. We previously identified a WRKY gene, VvWRKY1, which is able to enhance tolerance to fungal pathogens when it is overexpressed in tobacco. The present work analyzes the effects of VvWRKY1 overexpression in grapevine. Microarray analysis showed that genes encoding defence-related proteins were up-regulated in the leaves of transgenic 35S::VvWRKY1 grapevines. Quantitative RT-PCR analysis confirmed that three genes putatively involved in jasmonic acid signalling pathway were overexpressed in the transgenic grapes. The ability of VvWRKY1 to trans-activate the promoters of these genes was demonstrated by transient expression in grape protoplasts. The resistance to the causal agent of downy mildew, Plasmopara viticola, was enhanced in the transgenic plants. These results show that VvWRKY1 can increase resistance of grapevine against the downy mildew through transcriptional reprogramming leading to activation of the jasmonic acid signalling pathway.

  9. Over-expression of VvWRKY1 in grapevines induces expression of jasmonic acid pathway-related genes and confers higher tolerance to the downy mildew.