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Sample records for affect vascular function

  1. Indoor Particles Affect Vascular Function in the Aged

    DEFF Research Database (Denmark)

    Bräuner, Elvira Vaclavik; Forchhammer, Lykke; Møller, Peter;

    2008-01-01

    -4058 and 7718-12988 particles per cm3, respectively) in their homes. Measurements and results. Microvascular function was assessed non-invasively by measuring digital peripheral artery tone following arm ischemia. Secondary endpoints included hemoglobin, red blood cells, platelet count, coagulation factors, P...

  2. [Vascular endothelial Barrier Function].

    Science.gov (United States)

    Ivanov, A N; Puchinyan, D M; Norkin, I A

    2015-01-01

    Endothelium is an important regulator of selective permeability of the vascular wall for different molecules and cells. This review summarizes current data on endothelial barrier function. Endothelial glycocalyx structure, its function and role in the molecular transport and leukocytes migration across the endothelial barrier are discussed. The mechanisms of transcellular transport of macromolecules and cell migration through endothelial cells are reviewed. Special section of this article addresses the structure and function of tight and adherens endothelial junction, as well as their importance for the regulation of paracellular transport across the endothelial barrier. Particular attention is paid to the signaling mechanism of endothelial barrier function regulation and the factors that influence on the vascular permeability.

  3. Vascular function in health, hypertension, and diabetes

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Gliemann, Lasse; Hellsten, Ylva

    2015-01-01

    to the formation of vasodilators such as nitric oxide (NO) and prostacyclin. In essential hypertension and type II diabetes, the endothelial function and regulation of vascular tone is impaired with consequent increases in peripheral vascular resistance and inadequate regulation of oxygen supply to the skeletal...

  4. Regulation of Vascular Function on Posttranscriptional Level

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    Andreas Eisenreich

    2013-01-01

    Full Text Available Posttranscriptional control of gene expression is crucial for regulating plurality of proteins and functional plasticity of the proteome under (pathophysiologic conditions. Alternative splicing as well as micro (miRNA-mediated mechanisms play an important role for the regulation of protein expression on posttranscriptional level. Both alternative splicing and miRNAs were shown to influence cardiovascular functions, such as endothelial thrombogenicity and the vascular tone, by regulating the expression of several vascular proteins and their isoforms, such as Tissue Factor (TF or the endothelial nitric oxide synthase (eNOS. This review will summarize and discuss the latest findings on the (pathophysiologic role of alternative splicing processes as well as of miRNAs on modulation of vascular functions, such as coagulation, thrombosis, and regulation of the vascular tone.

  5. Blood Flow Restricted Exercise and Vascular Function

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    Masahiro Horiuchi

    2012-01-01

    Full Text Available It is established that regular aerobic training improves vascular function, for example, endothelium-dependent vasodilatation and arterial stiffness or compliance and thereby constitutes a preventative measure against cardiovascular disease. In contrast, high-intensity resistance training impairs vascular function, while the influence of moderate-intensity resistance training on vascular function is still controversial. However, aerobic training is insufficient to inhibit loss in muscular strength with advancing age; thus, resistance training is recommended to prevent sarcopenia. Recently, several lines of study have provided compelling data showing that exercise and training with blood flow restriction (BFR leads to muscle hypertrophy and strength increase. As such, BFR training might be a novel means of overcoming the contradiction between aerobic and high-intensity resistance training. Although it is not enough evidence to obtain consensus about impact of BFR training on vascular function, available evidences suggested that BFR training did not change coagulation factors and arterial compliance though with inconsistence results in endothelial function. This paper is a review of the literature on the impact of BFR exercise and training on vascular function, such as endothelial function, arterial compliance, or other potential factors in comparison with those of aerobic and resistance training.

  6. Protein Kinase C Inhibitors as Modulators of Vascular Function and Their Application in Vascular Disease

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    Raouf A. Khalil

    2013-03-01

    Full Text Available Blood pressure (BP is regulated by multiple neuronal, hormonal, renal and vascular control mechanisms. Changes in signaling mechanisms in the endothelium, vascular smooth muscle (VSM and extracellular matrix cause alterations in vascular tone and blood vessel remodeling and may lead to persistent increases in vascular resistance and hypertension (HTN. In VSM, activation of surface receptors by vasoconstrictor stimuli causes an increase in intracellular free Ca2+ concentration ([Ca2+]i, which forms a complex with calmodulin, activates myosin light chain (MLC kinase and leads to MLC phosphorylation, actin-myosin interaction and VSM contraction. Vasoconstrictor agonists could also increase the production of diacylglycerol which activates protein kinase C (PKC. PKC is a family of Ca2+-dependent and Ca2+-independent isozymes that have different distributions in various blood vessels, and undergo translocation from the cytosol to the plasma membrane, cytoskeleton or the nucleus during cell activation. In VSM, PKC translocation to the cell surface may trigger a cascade of biochemical events leading to activation of mitogen-activated protein kinase (MAPK and MAPK kinase (MEK, a pathway that ultimately increases the myofilament force sensitivity to [Ca2+]i, and enhances actin-myosin interaction and VSM contraction. PKC translocation to the nucleus may induce transactivation of various genes and promote VSM growth and proliferation. PKC could also affect endothelium-derived relaxing and contracting factors as well as matrix metalloproteinases (MMPs in the extracellular matrix further affecting vascular reactivity and remodeling. In addition to vasoactive factors, reactive oxygen species, inflammatory cytokines and other metabolic factors could affect PKC activity. Increased PKC expression and activity have been observed in vascular disease and in certain forms of experimental and human HTN. Targeting of vascular PKC using PKC inhibitors may function in

  7. Cytoskeleton, cytoskeletal interactions, and vascular endothelial function

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    Wang J

    2012-12-01

    Full Text Available Jingli Wang,1 Michael E Widlansky1,21Department of Medicine, Cardiovascular Medicine Division, 2Department of Pharmacology, Medical College of Wisconsin, Milwaukee, Wisconsin, USAAbstract: Far from being inert, the vascular endothelium is a critical regulator of vascular function. While the endothelium participates in autocrine, paracrine, and endocrine signaling, it also transduces mechanical signals from the cell surface involving key cell structural elements. In this review, we discuss the structure of the vascular endothelium and its relationship to traditional cardiovascular risk factors and clinical cardiovascular events. Further, we review the emerging evidence that cell structural elements, including the glycocalyx, intercellular junctions, and cytoskeleton elements, help the endothelium to communicate with its environment to regulate vascular function, including vessel permeability and signal transduction via nitric oxide bioavailability. Further work is necessary to better delineate the regulatory relationships between known key regulators of vascular function and endothelial cell structural elements.Keywords: endothelium, shear stress, eNOS, cardiovascular risk factors, glycocalyx

  8. The Relationship between Vascular Function and the Autonomic Nervous System.

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    Amiya, Eisuke; Watanabe, Masafumi; Komuro, Issei

    2014-01-01

    Endothelial dysfunction and autonomic nervous system dysfunction are both risk factors for atherosclerosis. There is evidence demonstrating that there is a close interrelationship between these two systems. In hypertension, endothelial dysfunction affects the pathologic process through autonomic nervous pathways, and the pathophysiological process of autonomic neuropathy in diabetes mellitus is closely related with vascular function. However, detailed mechanisms of this interrelationship have not been clearly explained. In this review, we summarize findings concerning the interrelationship between vascular function and the autonomic nervous system from both experimental and clinical studies. The clarification of this interrelationship may provide more comprehensive risk stratification and a new effective therapeutic strategy against atherosclerosis.

  9. Diacylglycerol Kinase Inhibition and Vascular Function.

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    Choi, Hyehun; Allahdadi, Kyan J; Tostes, Rita C A; Webb, R Clinton

    2009-01-01

    Diacylglycerol kinases (DGKs), a family of lipid kinases, convert diacylglycerol (DG) to phosphatidic acid (PA). Acting as a second messenger, DG activates protein kinase C (PKC). PA, a signaling lipid, regulates diverse functions involved in physiological responses. Since DGK modulates two lipid second messengers, DG and PA, regulation of DGK could induce related cellular responses. Currently, there are 10 mammalian isoforms of DGK that are categorized into five groups based on their structural features. These diverse isoforms of DGK are considered to activate distinct cellular functions according to extracellular stimuli. Each DGK isoform is thought to play various roles inside the cell, depending on its subcellular localization (nuclear, ER, Golgi complex or cytoplasm). In vascular smooth muscle, vasoconstrictors such as angiotensin II, endothelin-1 and norepinephrine stimulate contraction by increasing inositol trisphosphate (IP(3)), calcium, DG and PKC activity. Inhibition of DGK could increase DG availability and decrease PA levels, as well as alter intracellular responses, including calcium-mediated and PKC-mediated vascular contraction. The purpose of this review is to demonstrate a role of DGK in vascular function. Selective inhibition of DGK isoforms may represent a novel therapeutic approach in vascular dysfunction.

  10. On conditions of negativity of friction resistance for non-stationary modes of blood flow and possible mechanism of affecting of environmental factors on energy effectiveness of cardio-vascular system functioning

    CERN Document Server

    Chefranov, S G

    2013-01-01

    It is shown that initiated by action of molecular viscosity impulse flow, directed usually from the moving fluid to limiting it solid surface, can, under certain conditions, turn to zero and get negative values in the case of non-stationary flow caused by alternating in time longitudinal (along the pipe axis) pressure gradient. It is noted that this non-equilibrium mechanism of negative friction resistance in the similar case of pulsating blood flow in the blood vessels, in addition to the stable to turbulent disturbances swirled blood flow structure providing, can also constitute hydro-mechanical basis of the observed but not explained yet paradoxically high energy effectiveness of the normal functioning of the cardio-vascular system (CVS). We consider respective mechanism of affecting on the stability of the normal work of CVS by environmental variable factors using shifting of hydro-dynamic mode with negative resistance realization range boundaries and variation of linear hydro-dynamic instability leading ...

  11. NADH/NADPH Oxidase and Vascular Function.

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    Griendling, K K; Ushio-Fukai, M

    1997-11-01

    The vascular NADH/NADPH oxidase has been shown to be the major source of superoxide in the vessel wall. Recent work has provided insight into its structure and activity in vascular cells. This enzyme is involved in both vascular smooth muscle hypertrophy and in some forms of impaired endothelium-dependent relaxation. Because oxidative stress in general participates in the pathogenesis of hypertension and atherosclerosis, the enzymes that produce reactive oxygen species may be important determinants of the course of vascular disease. (Trends Cardiovasc Med 1997;7:301-307). © 1997, Elsevier Science Inc.

  12. Vascular adaptive responses to physical exercise and to stress are affected differently by nandrolone administration

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    T. Bruder-Nascimento

    2011-04-01

    Full Text Available Androgenic anabolic steroid, physical exercise and stress induce cardiovascular adaptations including increased endothelial function. The present study investigated the effects of these conditions alone and in combination on the vascular responses of male Wistar rats. Exercise was started at 8 weeks of life (60-min swimming sessions 5 days per week for 8 weeks, while carrying a 5% body-weight load. One group received nandrolone (5 mg/kg, twice per week for 8 weeks, im. Acute immobilization stress (2 h was induced immediately before the experimental protocol. Curves for noradrenaline were obtained for thoracic aorta, with and without endothelium from sedentary and trained rats, submitted or not to stress, treated or not with nandrolone. None of the procedures altered the vascular reactivity to noradrenaline in denuded aorta. In intact aorta, stress and exercise produced vascular adaptive responses characterized by endothelium-dependent hyporeactivity to noradrenaline. These conditions in combination did not potentiate the vascular adaptive response. Exercise-induced vascular adaptive response was abolished by nandrolone. In contrast, the aortal reactivity to noradrenaline of sedentary rats and the vascular adaptive response to stress of sedentary and trained rats were not affected by nandrolone. Maximum response for 7-10 rats/group (g: sedentary 3.8 ± 0.2 vs trained 3.0 ± 0.2*; sedentary/stress 2.7 ± 0.2 vs trained/stress 3.1 ± 0.1*; sedentary/nandrolone 3.6 ± 0.1 vs trained/nandrolone 3.8 ± 0.1; sedentary/stress/nandrolone 3.2 ± 0.1 vs trained/stress/nandrolone 2.5 ± 0.1*; *P < 0.05 compared to its respective control. Stress and physical exercise determine similar vascular adaptive response involving distinct mechanisms as indicated by the observation that only the physical exercise-induced adaptive response was abolished by nandrolone.

  13. Melamine Impairs Renal and Vascular Function in Rats.

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    Tian, Xiao Yu; Wong, Wing Tak; Lau, Chi Wai; Wang, Yi-Xiang; Cheang, Wai San; Liu, Jian; Lu, Ye; Huang, Huihui; Xia, Yin; Chen, Zhen Yu; Mok, Chuen-Shing; Lau, Chau-Ming; Huang, Yu

    2016-06-21

    Melamine incident, linked to nephrotoxicity and kidney stone in infants previously exposed to melamine-contaminated milk products, was unprecedentedly grave in China in 2008 as little was known about the mechanistic process leading to renal dysfunction in affected children. This study investigates whether neonatal ingestion of melamine leads to renal and vascular dysfunction in adulthood; and whether ingestion of melamine in pregnant rats leads to renal dysfunction in their offspring. A combination of approaches employed includes functional studies in rat renal arteries, renal blood flow measurement by functional magnetic resonance imaging, assay for pro-inflammatory and fibrotic biomarkers, immunohistochemistry, and detection of plasma and renal melamine. We provide mechanistic evidence showing for the first time that melamine reduces renal blood flow and impairs renal and vascular function associated with overexpression of inflammatory markers, transforming growth factor-β1, bone morphogenic protein 4 and cyclooxygenase-2 in kidney and renal vasculature. Melamine also induces renal inflammation and fibrosis. More importantly, melamine causes nephropathies in offsprings from pregnant rat exposed to melamine during pregnancy, as well as in neonatal rat exposed to melamine afterbirth, thus supporting the clinical observations of kidney stone and acute renal failure in infants consuming melamine-contaminated milk products.

  14. Vascular Burden and Cognitive Function in Late-Life Depression

    NARCIS (Netherlands)

    Zuidersma, Marij; Izaks, Gerbrand J.; Naarding, Paul; Comijs, Hannie C.; Oude Voshaar, Richard C.

    2015-01-01

    OBJECTIVE: To evaluate the relation of vascular risk factors, subclinical, and manifest vascular disease with four domains of cognitive functioning in a large sample of clinically depressed older persons. METHODS: A cross-sectional analysis was used, and depressed patients were recruited from genera

  15. Vascular burden and cognitive function in late-life depression

    NARCIS (Netherlands)

    Zuidersma, M.; Izaks, G.J.; Naarding, P.; Comijs, H.C.; Oude Voshaar, R.C.

    2015-01-01

    OBJECTIVE: To evaluate the relation of vascular risk factors, subclinical, and manifest vascular disease with four domains of cognitive functioning in a large sample of clinically depressed older persons. METHODS: A cross-sectional analysis was used, and depressed patients were recruited from genera

  16. Effects of estradiol on uterine perfusion in anesthetized cyclic mares affected with uterine vascular elastosis.

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    Esteller-Vico, A; Liu, I K M; Vaughan, B; Steffey, E P; Brosnan, R J

    2016-01-01

    Uterine vascular elastosis in mares is characterized by degeneration of uterine vasculature through thickening of the elastin layers. Factors commonly associated with this degeneration include age, parity, and chronic uterine endometritis. Affected mares have also been shown to exhibit decreases in uterine blood flow and perfusion of the uterus. Due to the increased thickness of the elastin layers, we hypothesize that vasodilatation of the uterine vasculature is also impaired. To test the functionality of these vessels, we evaluated the vasodilatory effects of estradiol on the uterine vascular bed in mares with normal vasculature and mares with severe elastosis. Both groups were tested in estrus and diestrus. Fluorescent microspheres were used to determine basal blood perfusion, followed by the intravenous administration of 1.0 μg/kg of 17β-estradiol. After 90 min, perfusion was measured once again to determine the vascular response to estradiol. Control mares in estrus displayed a significant increase in total uterine blood flow after the administration of estradiol when compared to baseline levels. No other group had a significant increase in total blood flow and perfusion after estradiol administration. The administration of estradiol in control mares induced regional increases in perfusion in the uterine horns and uterine body during estrus and only in the uterine horns during diestrus. Mares affected by elastosis exhibited no regional differences in perfusion levels post-estradiol administration. The difference in the vasodilatory response induced by estradiol between reproductively healthy mares and mares affected with elastosis indicates that the functionality of the affected vessels is compromised.

  17. Host tree phenology affects vascular epiphytes at the physiological, demographic and community level.

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    Einzmann, Helena J R; Beyschlag, Joachim; Hofhansl, Florian; Wanek, Wolfgang; Zotz, Gerhard

    2014-11-11

    The processes that govern diverse tropical plant communities have rarely been studied in life forms other than trees. Structurally dependent vascular epiphytes, a major part of tropical biodiversity, grow in a three-dimensional matrix defined by their hosts, but trees differ in their architecture, bark structure/chemistry and leaf phenology. We hypothesized that the resulting seasonal differences in microclimatic conditions in evergreen vs. deciduous trees would affect epiphytes at different levels, from organ physiology to community structure. We studied the influence of tree leaf phenology on vascular epiphytes on the Island of Barro Colorado, Panama. Five tree species were selected, which were deciduous, semi-deciduous or evergreen. The crowns of drought-deciduous trees, characterized by sunnier and drier microclimates, hosted fewer individuals and less diverse epiphyte assemblages. Differences were also observed at a functional level, e.g. epiphyte assemblages in deciduous trees had larger proportions of Crassulacean acid metabolism species and individuals. At the population level a drier microclimate was associated with lower individual growth and survival in a xerophytic fern. Some species also showed, as expected, lower specific leaf area and higher δ(13)C values when growing in deciduous trees compared with evergreen trees. As hypothesized, host tree leaf phenology influences vascular epiphytes at different levels. Our results suggest a cascading effect of tree composition and associated differences in tree phenology on the diversity and functioning of epiphyte communities in tropical lowland forests.

  18. Carbon monoxide and bile pigments: surprising mediators of vascular function.

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    Durante, William

    2002-08-01

    Heme oxygenase (HO) catalyzes the degradation of heme to CO, iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although long considered irrelevant byproducts of heme catabolism, recent studies indicate that CO and the bile pigments biliverdin and bilirubin may play an important physiological role in the circulation. The release of CO by vascular cells may modulate blood flow and blood fluidity by inhibiting vasomotor tone, smooth muscle cell proliferation, and platelet aggregation. CO may also maintain the integrity of the vessel wall by directly blocking vascular cell apoptosis and by inhibiting the release of pro-apoptotic inflammatory cytokines from the vessel wall. These effects of CO are mediated via multiple pathways, including activation of soluble guanylate cyclase, potassium channels, p38 mitogen-activated protein kinase, or inhibition of cytochrome P450. In addition, the release of bile pigments may serve to sustain vascular homeostasis by protecting vascular cells from oxidative stress and by inhibiting the adhesion and infiltration of leukocytes into the vessel wall. Induction of HO-1 gene expression and the subsequent release of CO and bile pigments are observed in numerous vascular disorders and may provide an important adaptive mechanism to preserve homeostasis at sites of vascular injury. Thus, the HO-catalyzed formation of CO and bile pigments by vascular cells may function as a critical endogenous vasoprotective system. Moreover, pharmacological or genetic approaches targeting HO-1 to the vessel wall may represent a novel therapeutic approach in treating vascular disease.

  19. Effect of lower limb preference on local muscular and vascular function.

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    Fahs, Christopher A; Thiebaud, Robert S; Rossow, Lindy M; Loenneke, Jeremy P; Kim, Daeyeol; Abe, Takashi; Bemben, Michael G

    2014-01-01

    Unilateral physical training can enhance muscular size and function as well as vascular function in the trained limb. In non-athletes, the preferred arm for use during unilateral tasks may exhibit greater muscular strength compared to the non-preferred arm. It is unclear if lower limb preference affects lower limb vascular function or muscular endurance and power in recreationally active adults. To examine the effect of lower limb preference on quadriceps muscle size and function and on lower limb vascular function in middle-aged adults. Twenty (13 men, 7 women) recreationally-active middle-aged (55 ± 7 yrs) adults underwent measurements of quadriceps muscle thickness, strength, mean power, endurance, and arterial stiffness, calf venous compliance, and calf blood flow in the preferred and non-preferred lower limb. The preferred limb exhibited greater calf vascular conductance (31.6 ± 15.5 versus 25.8 ± 13.0 units flow/mmHg; p = 0.011) compared to the non-preferred limb. The interlimb difference in calf vascular conductance was negatively related to weekly aerobic activity (hrs/week) (r = -0.521; p = 0.019). Lower limb preference affects calf blood flow but not quadriceps muscle size or function. Studies involving unilateral lower limb testing procedures in middle-aged individuals should consider standardizing the testing to either the preferred or non-preferred limb rather than the right or left limb.

  20. Modulation of Vascular Cell Function by Bim Expression

    Directory of Open Access Journals (Sweden)

    Margaret E. Morrison

    2013-01-01

    Full Text Available Apoptosis of vascular cells, including pericytes and endothelial cells, contributes to disease pathogenesis in which vascular rarefaction plays a central role. Bim is a proapoptotic protein that modulates not only apoptosis but also cellular functions such as migration and extracellular matrix (ECM protein expression. Endothelial cells and pericytes each make a unique contribution to vascular formation and function although the details require further delineation. Here we set out to determine the cell autonomous impact of Bim expression on retinal endothelial cell and pericyte function using cells prepared from Bim deficient (Bim−/− mice. Bim−/− endothelial cells displayed an increased production of ECM proteins, proliferation, migration, adhesion, and VEGF expression but, a decreased eNOS expression and nitric oxide production. In contrast, pericyte proliferation decreased in the absence of Bim while migration, adhesion, and VEGF expression were increased. In addition, we demonstrated that the coculturing of either wild-type or Bim−/− endothelial cells with Bim−/− pericytes diminished their capillary morphogenesis. Thus, our data further emphasizes the importance of vascular cell autonomous regulatory mechanisms in modulation of vascular function.

  1. Modulation of vascular cell function by bim expression.

    Science.gov (United States)

    Morrison, Margaret E; Palenski, Tammy L; Jamali, Nasim; Sheibani, Nader; Sorenson, Christine M

    2013-01-01

    Apoptosis of vascular cells, including pericytes and endothelial cells, contributes to disease pathogenesis in which vascular rarefaction plays a central role. Bim is a proapoptotic protein that modulates not only apoptosis but also cellular functions such as migration and extracellular matrix (ECM) protein expression. Endothelial cells and pericytes each make a unique contribution to vascular formation and function although the details require further delineation. Here we set out to determine the cell autonomous impact of Bim expression on retinal endothelial cell and pericyte function using cells prepared from Bim deficient (Bim(-/-)) mice. Bim(-/-) endothelial cells displayed an increased production of ECM proteins, proliferation, migration, adhesion, and VEGF expression but, a decreased eNOS expression and nitric oxide production. In contrast, pericyte proliferation decreased in the absence of Bim while migration, adhesion, and VEGF expression were increased. In addition, we demonstrated that the coculturing of either wild-type or Bim(-/-) endothelial cells with Bim(-/-) pericytes diminished their capillary morphogenesis. Thus, our data further emphasizes the importance of vascular cell autonomous regulatory mechanisms in modulation of vascular function.

  2. Pioglitazone does not affect vascular or inflammatory responses after endotoxemia in humans.

    Science.gov (United States)

    Schaller, G; Kolodjaschna, J; Pleiner, J; Mittermayer, F; Kapiotis, S; Schmetterer, L; Wolzt, M

    2008-08-01

    PPARgamma agonists have been proposed to exert more than metabolic benefits, particularly by anti-inflammatory mechanisms. We hypothesized that pioglitazone might modulate inflammatory and vascular responses to lipopolysaccharide (LPS). In a placebo-controlled parallel-group study in 18 healthy male subjects, the E. coli endotoxin model of inflammation (20 IU/kg i. v.) was employed to test the effect of 60 mg pioglitazone over nine days on inflammatory cytokines. Macrovascular function and microvascular blood flow were assessed by brachial artery ultrasound and retinal blood flow parameters, respectively. Pioglitazone increased brachial artery diameter by 5.6% but had no effect on other outcome parameters under resting conditions. LPS increased cytokine levels to peak concentrations of 91.3+/-22.5 ng/ml (IL-6), 261.4+/-60.0 ng/ml (TNFalpha), and 524.5+/-15.3 ng/ml (VCAM-1). The endotoxin caused microvascular vasodilation and increased retinal white blood cell flux, while baseline brachial artery diameter remained unchanged. Pioglitazone had no effect on inflammatory cytokine or adhesion molecule release but mitigated LPS-induced hypotension (p<0.05). Neither brachial artery function nor microvascular blood flow was altered by pioglitazone. In conclusion, acute immune reactions to LPS are not affected by pioglitazone, which exerts subtle vascular effects alone and during endotoxemia. The anti-inflammatory properties of short-term pioglitazone to endotoxins in healthy subjects are therefore limited.

  3. Biomarkers of vascular function in pre- and recent post-menopausal women of similar age

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Seidelin, Kåre; Rostgaard Andersen, Thomas;

    2014-01-01

    Menopause is associated with an accelerated decline in vascular function, however, whether this is an effect of age and/or menopause and how exercise training may affect this decline remains unclear. We examined a range of molecular measures related to vascular function in matched pre- and post-menopausal...... women before and after 12 weeks of exercise training. Thirteen pre-menopausal and ten recently post-menopausal (1.6±0.3 (mean±SEM) years after final menstrual period) women only separated by three years (48±1 vs. 51±1 years) were included. Before training, diastolic blood pressure, soluble intercellular...... adhesion molecule-1 (sICAM-1) and skeletal muscle expression of thromboxane A synthase were higher in the post-menopausal women compared to the pre-menopausal women, all indicative of impaired vascular function. In both groups, exercise training lowered diastolic blood pressure, the levels of sICAM-1...

  4. Role of Mitochondria in Cerebral Vascular Function: Energy Production, Cellular Protection, and Regulation of Vascular Tone.

    Science.gov (United States)

    Busija, David W; Rutkai, Ibolya; Dutta, Somhrita; Katakam, Prasad V

    2016-06-13

    Mitochondria not only produce energy in the form of ATP to support the activities of cells comprising the neurovascular unit, but mitochondrial events, such as depolarization and/or ROS release, also initiate signaling events which protect the endothelium and neurons against lethal stresses via pre-/postconditioning as well as promote changes in cerebral vascular tone. Mitochondrial depolarization in vascular smooth muscle (VSM), via pharmacological activation of the ATP-dependent potassium channels on the inner mitochondrial membrane (mitoKATP channels), leads to vasorelaxation through generation of calcium sparks by the sarcoplasmic reticulum and subsequent downstream signaling mechanisms. Increased release of ROS by mitochondria has similar effects. Relaxation of VSM can also be indirectly achieved via actions of nitric oxide (NO) and other vasoactive agents produced by endothelium, perivascular and parenchymal nerves, and astroglia following mitochondrial activation. Additionally, NO production following mitochondrial activation is involved in neuronal preconditioning. Cerebral arteries from female rats have greater mitochondrial mass and respiration and enhanced cerebral arterial dilation to mitochondrial activators. Preexisting chronic conditions such as insulin resistance and/or diabetes impair mitoKATP channel relaxation of cerebral arteries and preconditioning. Surprisingly, mitoKATP channel function after transient ischemia appears to be retained in the endothelium of large cerebral arteries despite generalized cerebral vascular dysfunction. Thus, mitochondrial mechanisms may represent the elusive signaling link between metabolic rate and blood flow as well as mediators of vascular change according to physiological status. Mitochondrial mechanisms are an important, but underutilized target for improving vascular function and decreasing brain injury in stroke patients. © 2016 American Physiological Society. Compr Physiol 6:1529-1548, 2016.

  5. Green tea (Camellia sinensis) catechins and vascular function.

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    Moore, Rosalind J; Jackson, Kim G; Minihane, Anne M

    2009-12-01

    The health benefits of green tea (Camellia sinensis) catechins are becoming increasingly recognised. Amongst the proposed benefits are the maintenance of endothelial function and vascular homeostasis and an associated reduction in atherogenesis and CVD risk. The mounting evidence for the influential effect of green tea catechins on vascular function from epidemiological, human intervention and animal studies is subject to review together with exploration of the potential mechanistic pathways involved. Epigallocatechin-3-gallate, one of the most abundant and widely studied catechin found in green tea, will be prominent in the present review. Since there is a substantial inconsistency in the published data with regards to the impact of green tea catechins on vascular function, evaluation and interpretation of the inter- and intra-study variability is included. In conclusion, a positive effect of green tea catechins on vascular function is becoming apparent. Further studies in animal and cell models using physiological concentrations of catechins and their metabolites are warranted in order to gain some insight into the physiology and molecular basis of the observed beneficial effects.

  6. Potential benefits of exercise on blood pressure and vascular function.

    Science.gov (United States)

    Pal, Sebely; Radavelli-Bagatini, Simone; Ho, Suleen

    2013-01-01

    Physical activity seems to enhance cardiovascular fitness during the course of the lifecycle, improve blood pressure, and is associated with decreased prevalence of hypertension and coronary heart disease. It may also delay or prevent age-related increases in arterial stiffness. It is unclear if specific exercise types (aerobic, resistance, or combination) have a better effect on blood pressure and vascular function. This review was written based on previous original articles, systematic reviews, and meta-analyses indexed on PubMed from years 1975 to 2012 to identify studies on different types of exercise and the associations or effects on blood pressure and vascular function. In summary, aerobic exercise (30 to 40 minutes of training at 60% to 85% of predicted maximal heart rate, most days of the week) appears to significantly improve blood pressure and reduce augmentation index. Resistance training (three to four sets of eight to 12 repetitions at 10 repetition maximum, 3 days a week) appears to significantly improve blood pressure, whereas combination exercise training (15 minutes of aerobic and 15 minutes of resistance, 5 days a week) is beneficial to vascular function, but at a lower scale. Aerobic exercise seems to better benefit blood pressure and vascular function.

  7. Clinical implications of disturbances of uterine vascular morphology and function.

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    Hickey, M; Fraser, I S

    2000-12-01

    Menstrual disturbances are one of the most common problems presenting to the gynaecologist. In order for the endometrium to bleed, vessels must break down. Disruption in the regulation of endometrial vascular growth and function has been found in association with spontaneous and sex steroid-induced disturbances of menstrual bleeding. Although circulating oestrogens and progestogens influence the endometrial vessels, this effect appears to be indirect, and regulation is primarily via local factors. Deficient vasoconstriction and haemostasis with excessive fibrinolysis is seen in menorrhagia. Breakthrough bleeding in users of progestogen-only contraceptives is associated with increased superficial vascular fragility and disruptions in the supporting basement membrane. Blood vessels in uterine fibroids are abnormal in distribution and appearance. Adenomyosis is also commonly associated with menstrual disturbance, and alterations in vascular distribution suggest altered angiogenesis. Successful human embryo implantation requires endometrial vascular breakdown. Excessive thrombosis associated with the antiphospholipid syndrome may interfere with this re-modelling and compromise implantation. Arteriovenous malformations are a rare but important cause of excessive or irregular vaginal bleeding. Abundant vessels with abnormal morphology, associated with aberrant angiogenesis can be seen, and embolization of these vessels may be an effective conservative treatment. Improved understanding of the regulation of the uterine vasculature is likely to lead to targeted therapies to prevent unscheduled vascular breakdown and to control menstrual disturbance at an endometrial level.

  8. The Plant Vascular System: Evolution, Development and Functions

    Institute of Scientific and Technical Information of China (English)

    William J.Lucas; Andrew Groover; Raffael Lichtenberger; Kaori Furuta; Shri-Ram Yadav; Yk(a) Helariutta; Xin-Qiang He

    2013-01-01

    The emergence of the tracheophyte-based vascular system of land plants had major impacts on the evolution of terrestrial biology,in general,through its role in facilitating the development of plants with increased stature,photosynthetic output,and ability to colonize a greatly expanded range of environmental habitats.Recently,considerable progress has been made in terms of our understanding of the developmental and physiological programs involved in the formation and function of the plant vascular system.In this review,we first examine the evolutionary events that gave rise to the tracheophytes,followed by analysis of the genetic and hormonal networks that cooperate to orchestrate vascular development in the gymnosperms and angiosperms.The two essential functions performed by the vascular system,namely the delivery of resources (water,essential mineral nutrients,sugars and amino acids) to the various plant organs and provision of mechanical support are next discussed.Here,we focus on critical questions relating to structural and physiological properties controlling the delivery of material through the xylem and phloem.Recent discoveries into the role of the vascular system as an effective long-distance communication system are next assessed in terms of the coordination of developmental,physiological and defense-related processes,at the whole-plant level.A concerted effort has been made to integrate all these new findings into a comprehensive picture of the state-of-the-art in the area of plant vascular biology.Finally,areas important for future research are highlighted in terms of their likely contribution both to basic knowledge and applications to primary industry.

  9. Serial assessment of local peripheral vascular function after eccentric exercise.

    Science.gov (United States)

    Stacy, Mitchel R; Bladon, Kallie J; Lawrence, Jennifer L; McGlinchy, Sarah A; Scheuermann, Barry W

    2013-12-01

    Muscle damage is a common response to unaccustomed eccentric exercise; however, the effects of skeletal muscle damage on local vascular function and blood flow are poorly understood. This study examined serial local vascular responses to flow-mediated (endothelial-dependent) and nitroglycerin-mediated (endothelial-independent) dilation in the brachial artery after strenuous eccentric exercise and serially assessed resting blood flow. Ten healthy males performed 50 maximal eccentric unilateral arm contractions to induce muscle damage to the biceps brachii. Changes in maximal isometric strength and vascular responses were assessed 1, 24, 48, and 96 h after exercise. Mean blood velocities and arterial diameters, measured with Doppler ultrasound, were used to calculate blood flow and shear stress (expressed as area under the curve). Eccentric exercise resulted in impaired maximal isometric strength for up to 96 h (p exercise, 9.4% ± 2.6%; 1 h after exercise, 5.1% ± 2.2%) and nitroglycerin responses (before exercise, 26.3% ± 6.5%; 1 h after exercise, 20.7% ± 4.7%) were observed in the 1 h after exercise and remained lower for 96 h (p exercise and remained impaired for 48 h (p eccentric exercise leads to impaired local endothelial and vascular smooth muscle function. Lower shear stress after exercise might contribute to the observed reduction in flow-mediated dilation responses, but the mechanism responsible for the attenuated endothelial-independent vasodilation remains unclear.

  10. Maternal Hyperleptinemia Is Associated with Male Offspring's Altered Vascular Function and Structure in Mice.

    Directory of Open Access Journals (Sweden)

    Kathleen A Pennington

    Full Text Available Children of mothers with gestational diabetes have greater risk of developing hypertension but little is known about the mechanisms by which this occurs. The objective of this study was to test the hypothesis that high maternal concentrations of leptin during pregnancy, which are present in mothers with gestational diabetes and/or obesity, alter blood pressure, vascular structure and vascular function in offspring. Wildtype (WT offspring of hyperleptinemic, normoglycemic, Leprdb/+ dams were compared to genotype matched offspring of WT-control dams. Vascular function was assessed in male offspring at 6, and at 31 weeks of age after half the offspring had been fed a high fat, high sucrose diet (HFD for 6 weeks. Blood pressure was increased by HFD but not affected by maternal hyperleptinemia. On a standard diet, offspring of hyperleptinemic dams had outwardly remodeled mesenteric arteries and an enhanced vasodilatory response to insulin. In offspring of WT but not Leprdb/+ dams, HFD induced vessel hypertrophy and enhanced vasodilatory responses to acetylcholine, while HFD reduced insulin responsiveness in offspring of hyperleptinemic dams. Offspring of hyperleptinemic dams had stiffer arteries regardless of diet. Therefore, while maternal hyperleptinemia was largely beneficial to offspring vascular health under a standard diet, it had detrimental effects in offspring fed HFD. These results suggest that circulating maternal leptin concentrations may interact with other factors in the pre- and post -natal environments to contribute to altered vascular function in offspring of diabetic pregnancies.

  11. Enzymatic regulation of functional vascular networks using gelatin hydrogels.

    Science.gov (United States)

    Chuang, Chia-Hui; Lin, Ruei-Zeng; Tien, Han-Wen; Chu, Ya-Chun; Li, Yen-Cheng; Melero-Martin, Juan M; Chen, Ying-Chieh

    2015-06-01

    To manufacture tissue engineering-based functional tissues, scaffold materials that can be sufficiently vascularized to mimic the functionality and complexity of native tissues are needed. Currently, vascular network bioengineering is largely carried out using natural hydrogels as embedding scaffolds, but most natural hydrogels have poor mechanical stability and durability, factors that critically limit their widespread use. In this study, we examined the suitability of gelatin-phenolic hydroxyl (gelatin-Ph) hydrogels that can be enzymatically crosslinked, allowing tuning of the storage modulus and the proteolytic degradation rate, for use as injectable hydrogels to support the human progenitor cell-based formation of a stable and mature vascular network. Porcine gelatin-Ph hydrogels were found to be cytocompatible with human blood-derived endothelial colony-forming cells and white adipose tissue-derived mesenchymal stem cells, resulting in >87% viability, and cell proliferation and spreading could be modulated by using hydrogels with different proteolytic degradability and stiffness. In addition, gelatin was extracted from mouse dermis and murine gelatin-Ph hydrogels were prepared. Importantly, implantation of human cell-laden porcine or murine gelatin-Ph hydrogels into immunodeficient mice resulted in the rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, the degree of enzymatic crosslinking of the gelatin-Ph hydrogels could be used to modulate cell behavior and the extent of vascular network formation in vivo. Our report details a technique for the synthesis of gelatin-Ph hydrogels from allogeneic or xenogeneic dermal skin and suggests that these hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.

  12. Vascular dilatory functions of ovo-lactovegetarians compared with omnivores.

    Science.gov (United States)

    Lin, C L; Fang, T C; Gueng, M K

    2001-09-01

    Vegetarians have lower blood pressure and lower cardiovascular mortality. Vegetarian diets may have lower cardiovascular risks through positive influence on endothelium-dependent relaxation and related functions. The objectives of this study were to assess the differences of vascular dilatory functions between middle-aged vegetarians and sex and age-matched omnivores before they develop any clinical manifestations of atherosclerosis. Twenty healthy vegetarians over the age of 50 and 20 healthy omnivores over the age of 50 were recruited for this study. Subjects with known risk factors for atherosclerosis such as hypertension, diabetes, obesity, hypercholesteremia, cigarette smoking, family history of vascular diseases, or taking any regular medication were excluded. Medical history, body weight, height, and duration of vegetarian diet were recorded. Baseline CBC, urinalysis and biochemical data such as fasting blood glucose, thyroid function, blood urea nitrogen, creatinine, serum electrolytes (sodium, potassium, chloride, calcium and magnesium), lipid profiles [total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol] were obtained after a 14 h fast. Blood pressures and heart rate were recorded in supine position. Vascular dilatory functions, both flow-mediated (endothelium-dependent) and nitroglycerin-induced (endothelium-independent), were evaluated by using a non-invasive ultrasonographic method. The results show that there were no significant differences in the baseline characteristic between the vegetarians and the omnivores. There were also no significant differences in serum glucose, lipid profiles and thyroid function between these two groups. However, vasodilatation responses (both flow-mediated and nitroglycerin-induced) were significantly better in the vegetarian group and the degree of vasodilatation appeared to be correlated with years on vegetarian diets. Our findings suggest that

  13. Role of endothelin in uteroplacental circulation and fetal vascular function.

    Science.gov (United States)

    Paradis, Alexandra; Zhang, Lubo

    2013-09-01

    Endothelins are 21-amino acid peptides involved in vascular homeostasis. Three types of peptide have been identified, with endothelin-1 (ET-1) being the most potent vasoconstrictor currently known. Two endothelin receptor subtypes are found in various tissues, including the brain, heart, blood vessel, lung, and placenta. The ETA-receptor is associated with vasoconstriction in vascular smooth muscle. Conversely, the ETB-receptor can elicit a vasoconstrictor effect in vascular smooth muscle and a vasodilator effect via its action in endothelial cells. Both receptors play a key role in maintaining circulatory homeostasis and vascular function. Changes in ET-1 expression are found in various disease states, and overexpression of ET-1 is observed in hypertension and preeclampsia in pregnancy. Placental localization of ET-1 implies a key role in regulating the uteroplacental circulation. Additionally, ET-1 is important in the fetal circulation and is involved in the pulmonary circulation and closure of the ductus arteriosus after birth, as well as fetal growth constriction in utero. ET receptor antagonists and nitric oxide donors may provide therapeutic potential in treating conditions associated with overexpression of ET and hypertension.

  14. Functional vascular diseases: Raynaud's syndrome, acrocyanosis and erythromelalgia.

    Science.gov (United States)

    Heidrich, H

    2010-02-01

    Raynauds syndrome, acrocyanosis and erythromelalgia are functional vascular diseases that differ with respect to prevalence, clinical picture, therapy, prognosis, and impairment of quality of life. Raynauds syndrome occurs in 5 to 20 % of the population in Europe, is observed four times more often in women than in men and appears first at the age of 40 (3 to 80), on the average. Raynauds attacks are characterized by a paroxysmal white-blue-red or just white and blue discoloration of the fingers and toes; the attacks are induced by cold or stress, usually, cease after no more than some minutes (average 23 min.), but can also persist for hours. A distinction must be made between primary (aetiology unknown), secondary (aetiology known) and suspected secondary Raynauds syndromes (causal underlying disease suspected). There are several different therapy options, but not all of them have been substantiated by evidence. Acrocyanosis is rarer than Raynauds syndrome, and contrary to the latter, is characterized by nonparoxysmal, in most cases persistent, painless bluish-red symmetrical discolorations of the hands, feet and knees. It is more frequent in women than in men and becomes manifest before the 25th year of age, on the average (15th to 70th year of age). A distinction is made between primary acrocyanosis without detectable underlying disease and secondary acrocyanosis with a specific underlying disease. No effective therapy for primary acrocyanosis is known, but secondary forms can sometimes be treated. Patients with primary and secondary erythromelalgia, a very rare condition, sustain paroxysmal burning pain with marked reddening of the legs, feet and less often the hands. The attacks are triggered by warmth. Women are affected more often than men. The age of first manifestation is 40 to 55 years, but the first attacks may just as well occur during childhood. There are different therapeutic approaches with occasional success, but no general recommendations.

  15. Gender Differences in Bed Rest: Preliminary Analysis of Vascular Function

    Science.gov (United States)

    Platts, Steven H.; Stenger, Michael B.; Martin, David S.; Freeman-Perez, Sondra A.; Phillips, Tiffany; Ribeiro, L. Christine

    2008-01-01

    Orthostatic intolerance is a recognized consequence of spaceflight. Numerous studies have shown that women are more susceptible to orthostatic intolerance following spaceflight as well as bed rest, the most commonly used ground-based analog for spaceflight. One of the possible mechanisms proposed to account for this is a difference in vascular responsiveness between genders. We hypothesized that women and men would have differing vascular responses to 90 days of 6-degree head down tilt bed rest. Additionally, we hypothesized that vessels in the upper and lower body would respond differently, as has been shown in the animal literature. Thirteen subjects were placed in bedrest for 90 days (8 men, 5 women) at the Flight Analogs Unit, UTMB. Direct arterial and venous measurements were made with ultrasound to evaluate changes in vascular structure and function. Arterial function was assessed, in the arm and leg, during a reactive hyperemia protocol and during sublingual nitroglycerin administration to gauge the contributions of endothelial dependent and independent dilator function respectively. Venous function was assessed in dorsal hand and foot veins during the administration of pharmaceuticals to assess constrictor and dilator function. Both gender and day effects are seen in arterial dilator function to reactive hyperemia, but none are seen with nitroglycerin. There are also differences in the wall thickness in the arm vs the leg during bed rest, which return toward pre-bed rest levels by day 90. More subjects are required, especially females as there is not sufficient power to properly analyze venous function. Day 90 data are most underpowered.

  16. Uteroplacental circulation and fetal vascular function and development.

    Science.gov (United States)

    Thornburg, Kent L; Louey, Samantha

    2013-09-01

    Although blood flow in the placental vasculature is governed by the same physiological forces of shear, pressure and resistance as in other organs, it is also uniquely specialized on the maternal and fetal sides. At the materno-fetal interface, the independent uteroplacental and umbilicoplacental circulations must coordinate sufficiently to supply the fetus with the nutrients and substrates it needs to grow and develop. Uterine arterial flow must increase dramatically to accommodate the growing fetus. Recent evidence delineates the hormonal and endothelial mechanisms by which maternal vessels dilate and remodel during pregnancy. The umbilical circulation is established de novo during embryonic development but blood does not flow through the placenta until late in the first trimester. The umbilical circulation operates in the interest of maintaining fetal oxygenation over the course of pregnancy, and is affected differently by mechanical and chemical regulators of vascular tone compared to other organs. The processes that match placental vascular growth and fetal tissue growth are not understood, but studies of compromised pregnancies provide clues. The subtle changes that cause the failure of the normally regulated vascular processes during pregnancy have not been thoroughly identified. Likewise, practical and effective therapeutic strategies to reverse detrimental placental perfusion patterns have yet to be investigated.

  17. Flat affect and social functioning

    DEFF Research Database (Denmark)

    Simonsen, Erik; Evensen, Julie; Røsberg, Jan Ivar;

    2012-01-01

    , predictors and outcome factors including social functioning. Methods: Three-hundred-and-one patients with FEP were included at baseline, 186 participated in the 10 year follow-up. These were followed on PANSS item N1 (FA) from baseline through 5 follow-up assessments over 10 years. Patients were grouped...... as having never-present, improving, deteriorating, fluctuating or enduring FA. The groups were compared on baseline variables, variables at 10 year follow-up, and social functioning throughout the follow-up period. Results: Twenty nine percent never displayed FA, 66% had improving, deteriorating...... or fluctuating FA, while 5% of patients had enduring FA. Premorbid social function predicted enduring FA. The patients with enduring, fluctuating and deteriorating FA did poorer on all outcome variables, including remission and recovery rates. The enduring FA group did significantly poorer in social functioning...

  18. Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function.

    Science.gov (United States)

    Hall, Wendy L

    2009-06-01

    The amount and type of dietary fat have long been associated with the risk of CVD. Arterial stiffness and endothelial dysfunction are important risk factors in the aetiology of CHD. A range of methods exists to assess vascular function that may be used in nutritional science, including clinic and ambulatory blood pressure monitoring, pulse wave analysis, pulse wave velocity, flow-mediated dilatation and venous occlusion plethysmography. The present review focuses on the quantity and type of dietary fat and effects on blood pressure, arterial compliance and endothelial function. Concerning fat quantity, the amount of dietary fat consumed habitually appears to have little influence on vascular function independent of fatty acid composition, although single high-fat meals postprandially impair endothelial function compared with low-fat meals. The mechanism is related to increased circulating lipoproteins and NEFA which may induce pro-inflammatory pathways and increase oxidative stress. Regarding the type of fat, cross-sectional data suggest that saturated fat adversely affects vascular function whereas polyunsaturated fat (mainly linoleic acid (18 : 2n-6) and n-3 PUFA) are beneficial. EPA (20 : 5n-3) and DHA (22 : 6n-3) can reduce blood pressure, improve arterial compliance in type 2 diabetics and dyslipidaemics, and augment endothelium-dependent vasodilation. The mechanisms for this vascular protection, and the nature of the separate physiological effects induced by EPA and DHA, are priorities for future research. Since good-quality observational or interventional data on dietary fatty acid composition and vascular function are scarce, no further recommendations can be suggested in addition to current guidelines at the present time.

  19. Placebo Sleep Affects Cognitive Functioning

    Science.gov (United States)

    Draganich, Christina; Erdal, Kristi

    2014-01-01

    The placebo effect is any outcome that is not attributed to a specific treatment but rather to an individual's mindset (Benson & Friedman, 1996). This phenomenon can extend beyond its typical use in pharmaceutical drugs to involve aspects of everyday life, such as the effect of sleep on cognitive functioning. In 2 studies examining whether…

  20. Nitric oxide and reactive oxygen species in limb vascular function

    DEFF Research Database (Denmark)

    Gliemann, Lasse; Nyberg, Michael Permin; Hellsten, Ylva

    2014-01-01

    Abstract Nitric oxide (NO) is known to be one of the most important regulatory compounds within the cardiovascular system where it is central for functions such as regulation of blood pressure, blood flow and vascular growth. The bioavailability of NO is determined by a balance between, on one hand......, the extent of enzymatic and non-enzymatic formation of NO and on the other hand, removal of NO, which in part is dependent on the reaction of NO with reactive oxygen species (ROS). The presence of ROS is dependent on the extent of ROS formation via mitochondria and/or enzymes such as NAD(P)H oxidase...

  1. Impaired vascular function during short-term poor glycaemic control in Type 1 diabetic patients

    DEFF Research Database (Denmark)

    Sørensen, V R; Mathiesen, E R; Clausen, P

    2005-01-01

    in Type 1 diabetic patients may disturb vascular function, possibly mediated through smooth muscle cell dysfunction as well as endothelial dysfunction. We suggest that prolonged and repeated episodes of hyperglycaemia could possibly lead to permanent vascular dysfunction and thereby development...

  2. Activation tagging of the two closely linked genes LEP and VAS independently affects vascular cell number

    DEFF Research Database (Denmark)

    van der Graaff, Eric; Hooykaas, Paul J J; Keller, Beat

    2002-01-01

    The complex dominant Arabidopsis thaliana mutant lettuce (let) shows the conversion of the leaf petiole into a leaf blade caused by an ectopic leaf blade formation. This is the result of the activation tagging of the LEAFY PETIOLE (LEP) gene encoding an AP2/EREBP-like transcription factor. Here, we...... report that in addition to this leafy petiole phenotype, the size of the vascular bundles is increased in all aerial organs in let as a result of an increase in the number of xylem, phloem (pro)cambial and pericycle cells. This vascular phenotype is caused by activation tagging of the two genes VASCULAR...... TISSUE SIZE (VAS) and LEP. These genes are closely linked and arranged in tandem. Activation tagging of LEP only caused a specific increase in the number of xylem cells. This increased xylem cell number, together with the ectopic leaf blade formation, indicates that LEP functions as a cell division...

  3. Regulation of Vascular and Renal Function by Metabolite Receptors*

    Science.gov (United States)

    Peti-Peterdi, János; Kishore, Bellamkonda K.; Pluznick, Jennifer L.

    2016-01-01

    To maintain metabolic homeostasis, the body must be able to monitor the concentration of a large number of substances, including metabolites, in real time and to use that information to regulate the activities of different metabolic pathways. Such regulation is achieved by the presence of sensors, termed metabolite receptors, in various tissues and cells of the body, which in turn convey the information to appropriate regulatory or positive or negative feedback systems. In this review, we cover the unique roles of metabolite receptors in renal and vascular function. These receptors play a wide variety of important roles in maintaining various aspects of homeostasis—from salt and water balance to metabolism—by sensing metabolites from a wide variety of sources. We discuss the role of metabolite sensors in sensing metabolites generated locally, metabolites generated at distant tissues or organs, or even metabolites generated by resident microbes. Metabolite receptors are also involved in various pathophysiological conditions and are being recognized as potential targets for new drugs. By highlighting three receptor families—(a) citric acid cycle intermediate receptors, (b) purinergic receptors, and (c) short-chain fatty acid receptors—we emphasize the unique and important roles that these receptors play in renal and vascular physiology and pathophysiology. PMID:26667077

  4. Vascular function and mild renal impairment in stable coronary artery disease

    NARCIS (Netherlands)

    van der Harst, P; Smilde, TDJ; Buikema, H; Voors, AA; Navis, G; van Veldhuisen, DJ; van Gilst, WH

    2006-01-01

    Objective - In patients with coronary artery disease, the concomitant presence of renal function impairment is associated with decreased survival. We aimed to assess whether in coronary artery diseased patients renal function impairment is associated with systemic vascular function, functional param

  5. Plasma inflammatory and vascular homeostasis biomarkers increase during human pregnancy but are not affected by oily fish intake.

    Science.gov (United States)

    García-Rodríguez, Cruz E; Olza, Josune; Aguilera, Concepción M; Mesa, María D; Miles, Elizabeth A; Noakes, Paul S; Vlachava, Maria; Kremmyda, Lefkothea-Stella; Diaper, Norma D; Godfrey, Keith M; Calder, Philip C; Gil, Angel

    2012-07-01

    The Salmon in Pregnancy Study investigated whether the increased consumption of (n-3) long-chain PUFA (LC-PUFA) from farmed Atlantic salmon affects immune function during pregnancy and atopic disease in neonates compared with a habitual diet low in oily fish. In this context, because the ingestion of (n-3) LC-PUFA may lower the concentrations of inflammatory biomarkers, we investigated whether the consumption of oily fish affects the levels of inflammatory cytokines and vascular adhesion factors during pregnancy. Pregnant women (n = 123) were randomly assigned to continue their habitual diet (control group, n = 61), which was low in oily fish, or to consume two 150-g salmon portions/wk (salmon group, n = 62; providing 3.45 g EPA plus DHA) from 20 wk of gestation until delivery. Plasma inflammatory cytokines and vascular adhesion factors were measured in maternal plasma samples. Inflammatory biomarkers, including IL-8, hepatocyte growth factor, and monocyte chemotactic protein, increased over the course of pregnancy (P pregnancy progressed (P pregnancy, they are not affected by the increased intake of farmed salmon.

  6. Blood flow controls bone vascular function and osteogenesis

    Science.gov (United States)

    Ramasamy, Saravana K.; Kusumbe, Anjali P.; Schiller, Maria; Zeuschner, Dagmar; Bixel, M. Gabriele; Milia, Carlo; Gamrekelashvili, Jaba; Limbourg, Anne; Medvinsky, Alexander; Santoro, Massimo M.; Limbourg, Florian P.; Adams, Ralf H.

    2016-01-01

    While blood vessels play important roles in bone homeostasis and repair, fundamental aspects of vascular function in the skeletal system remain poorly understood. Here we show that the long bone vasculature generates a peculiar flow pattern, which is important for proper angiogenesis. Intravital imaging reveals that vessel growth in murine long bone involves the extension and anastomotic fusion of endothelial buds. Impaired blood flow leads to defective angiogenesis and osteogenesis, and downregulation of Notch signalling in endothelial cells. In aged mice, skeletal blood flow and endothelial Notch activity are also reduced leading to decreased angiogenesis and osteogenesis, which is reverted by genetic reactivation of Notch. Blood flow and angiogenesis in aged mice are also enhanced on administration of bisphosphonate, a class of drugs frequently used for the treatment of osteoporosis. We propose that blood flow and endothelial Notch signalling are key factors controlling ageing processes in the skeletal system. PMID:27922003

  7. Regulation of ROS Production and Vascular Function by Carbon Monoxide

    Directory of Open Access Journals (Sweden)

    Yoon Kyung Choi

    2012-01-01

    Full Text Available Carbon monoxide (CO is a gaseous molecule produced from heme by heme oxygenase (HO. CO interacts with reduced iron of heme-containing proteins, leading to its involvement in various cellular events via its production of mitochondrial reactive oxygen species (ROS. CO-mediated ROS production initiates intracellular signal events, which regulate the expression of adaptive genes implicated in oxidative stress and functions as signaling molecule for promoting vascular functions, including angiogenesis and mitochondrial biogenesis. Therefore, CO generated either by exogenous delivery or by HO activity can be fundamentally involved in regulating mitochondria-mediated redox cascades for adaptive gene expression and improving blood circulation (i.e., O2 delivery via neovascularization, leading to the regulation of mitochondrial energy metabolism. This paper will highlight the biological effects of CO on ROS generation and cellular redox changes involved in mitochondrial metabolism and angiogenesis. Moreover, cellular mechanisms by which CO is exploited for disease prevention and therapeutic applications will also be discussed.

  8. Alcohol and cardiovascular disease--modulation of vascular cell function.

    Science.gov (United States)

    Cahill, Paul A; Redmond, Eileen M

    2012-04-01

    Alcohol is a commonly used drug worldwide. Epidemiological studies have identified alcohol consumption as a factor that may either positively or negatively influence many diseases including cardiovascular disease, certain cancers and dementia. Often there seems to be a differential effect of various drinking patterns, with frequent moderate consumption of alcohol being salutary and binge drinking or chronic abuse being deleterious to one's health. A better understanding of the cellular and molecular mechanisms mediating the many effects of alcohol consumption is beginning to emerge, as well as a clearer picture as to whether these effects are due to the direct actions of alcohol itself, or caused in part by its metabolites, e.g., acetaldehyde, or by incidental components present in the alcoholic beverage (e.g., polyphenols in red wine). This review will discuss evidence to date as to how alcohol (ethanol) might affect atherosclerosis that underlies cardiovascular and cerebrovascular disease, and the putative mechanisms involved, focusing on vascular endothelial and smooth muscle cell effects.

  9. Cognitive function following stroke and vascular cognitive impairment

    NARCIS (Netherlands)

    de Haan, Edward H.; Nys, Gudrun M.; Van Zandvoort, Martine J.

    2006-01-01

    Purpose of review This review of the cognitive status following stroke and vascular cognitive impairment starts by questioning the concept of vascular dementia and related concepts. Our position is that in many cases these labels promote a superficial conceptualization of an inherently complex and h

  10. Effects of Estrogen Level on the Function of Vascular Endothelial Cells and Expression of Vascular Cell Adhesion Molecule - 1φ

    Institute of Scientific and Technical Information of China (English)

    WU Saizhu(吴赛珠); LIU Jiangguo(刘建国); TAN Jiayu(谭家余); ZHoU Kexiang(周可祥); Gorge D Webb; WEI Heming(隗和明); GUO Zhiguang(郭志刚)

    2002-01-01

    Objectives To ob- serve the effect of different estrogen levels on the se- cretory function of vascular endothelial cells of female rats, and study the effect of modulation of estrogen level on the expression of vascular cell adhesion molecule - 1 and the concentration of estrogen receptorin vascular endothelial cells. Methods Radioim-munology was used to measure the serum concentrationof endothelin and PGI2, and copper-cadmium re-duction was employed to measure the serum content ofnitrogen monoxide. Radioligand binding and flowcy-tometry were used to measure the expression of estrogenreceptor and vascular cell adhesion molecule (VCAM-1 ) of vascular endothelial cells respectively. Re-sults 1. The serum concentration of nitric oxide andPGI2 decreased when the ovaries of female rats wereremoved. In ovariectomized rats, given estrogen, theconcentration rose ( P < 0.05), but the plasma con-centration of endothelin was adverse to it. 2. Theconcentration of estrogen receptor of vascular endothe-lial cells decreased remarkably when the ovaries of fe-male rats were removed. When given estrogen, it in-creased. 3. The percent of expressed VCAM - 1 in-creased siguificantly after interleukin- lβoperated onthe cells, but 17 - βestradiol at 3 × 10-8 ~ 10-6 mol/lall decreased the percent. Conclusions Estrogenlevel can influence the secretion of nitrogen monoxide,PGI2 and endothlin of vascular endothelial cells, andalso influence the concentration of estrogen receptor ofvascular endothelial cells. 17 -β Estradiol at 3 × 10-8~ 10-6 M can decrease the elevation of VCAM - 1 ofvascular endothelial cells induced by interleukin - 1 β.

  11. Review of gestational diabetes mellitus effects on vascular structure and function.

    Science.gov (United States)

    Jensen, Louise A; Chik, Constance L; Ryan, Edmond A

    2016-05-01

    Vascular dysfunction has been described in women with a history of gestational diabetes mellitus. Furthermore, previous gestational diabetes mellitus increases the risk of developing Type 2 diabetes mellitus, a risk factor for cardiovascular disease. Factors contributing to vascular changes remain uncertain. The aim of this review was to summarize vascular structure and function changes found to occur in women with previous gestational diabetes mellitus and to identify factors that contribute to vascular dysfunction. A systematic search of electronic databases yielded 15 publications from 1998 to March 2014 that met the inclusion criteria. Our review confirmed that previous gestational diabetes mellitus contributes to vascular dysfunction, and the most consistent risk factor associated with previous gestational diabetes mellitus and vascular dysfunction was elevated body mass index. Heterogeneity existed across studies in determining the relationship of glycaemic levels and insulin resistance to vascular dysfunction.

  12. Regulation of Vascular and Renal Function by Metabolite Receptors.

    Science.gov (United States)

    Peti-Peterdi, János; Kishore, Bellamkonda K; Pluznick, Jennifer L

    2016-01-01

    To maintain metabolic homeostasis, the body must be able to monitor the concentration of a large number of substances, including metabolites, in real time and to use that information to regulate the activities of different metabolic pathways. Such regulation is achieved by the presence of sensors, termed metabolite receptors, in various tissues and cells of the body, which in turn convey the information to appropriate regulatory or positive or negative feedback systems. In this review, we cover the unique roles of metabolite receptors in renal and vascular function. These receptors play a wide variety of important roles in maintaining various aspects of homeostasis-from salt and water balance to metabolism-by sensing metabolites from a wide variety of sources. We discuss the role of metabolite sensors in sensing metabolites generated locally, metabolites generated at distant tissues or organs, or even metabolites generated by resident microbes. Metabolite receptors are also involved in various pathophysiological conditions and are being recognized as potential targets for new drugs. By highlighting three receptor families-(a) citric acid cycle intermediate receptors, (b) purinergic receptors, and

  13. Endothelium-Derived Hyperpolarizing Factor and Vascular Function

    Directory of Open Access Journals (Sweden)

    Muhiddin A. Ozkor

    2011-01-01

    Full Text Available Endothelial function refers to a multitude of physiological processes that maintain healthy homeostasis of the vascular wall. Exposure of the endothelium to cardiac risk factors results in endothelial dysfunction and is associated with an alteration in the balance of vasoactive substances produced by endothelial cells. These include a reduction in nitric oxide (NO, an increase in generation of potential vasoconstrictor substances and a potential compensatory increase in other mediators of vasodilation. The latter has been surmised from data demonstrating persistent endothelium-dependent vasodilatation despite complete inhibition of NO and prostaglandins. This remaining non-NO, non-prostaglandin mediated endothelium-dependent vasodilator response has been attributed to endothelium-derived hyperpolarizing factor/s (EDHF. Endothelial hyperpolarization is likely due to several factors that appear to be site and species specific. Experimental studies suggest that the contribution of the EDHFs increase as the vessel size decreases, with a predominance of EDHF activity in the resistance vessels, and a compensatory up-regulation of hyperpolarization in states characterized by reduced NO availability. Since endothelial dysfunction is a precursor for atherosclerosis development and its magnitude is a reflection of future risk, then the mechanisms underlying endothelial dysfunction need to be fully understood, so that adequate therapeutic interventions can be designed.

  14. The effects of ionizing radiation on the function and vascular structure of the rat submandibular gland

    Energy Technology Data Exchange (ETDEWEB)

    Kawamata, Fumio (Nippon Dental Univ., Tokyo (Japan))

    1991-06-01

    In radiotherapy for the jaw and face, the irradiation field frequently affects the salivary gland, in an aduerse way. In the present study, I assessed the functional influence of radiation on the submandibular gland by RI, with inspection of both the vascular distribution of the submandibular gland by India ink and resin molding methods, and of the histological changes by HE and PAS staining. Each experimental group consisted of 9 male Wistar strain rats aged 8 weeks. Single irradiation was performed at 10 Gy and 50 Gy doses by {sup 60}Co-{gamma} ray. The changes at 6 hours, 3, 7, 14, and 28 days after irradiation were determined and compared with those in the control group. Function tests for uptake and clearance were performed using {sup 99m}TcO{sub 4}{sup -}. Results showed the uptake and clearance value in the irradiation group was higher than that in the control group. With respect to the effect of irradiation on blood vessels, vasodilation, flexion, and destruction of the blood wall were observed. In addition, various histological changes appeared. In each examination, the irradiation effects in the 50 Gy group were greater than those in the 10 Gy group. In conclusion, the decline in submandibular function after 10 Gy and 50 Gy irradiation is related to histological changes in the vascular system and glandular tissues. (author) 63 refs.

  15. Hypothyroidism Affects Vascularization and Promotes Immune Cells Infiltration into Pancreatic Islets of Female Rabbits

    Science.gov (United States)

    Rodríguez-Castelán, Julia; Martínez-Gómez, Margarita; Castelán, Francisco; Cuevas, Estela

    2015-01-01

    Thyroidectomy induces pancreatic edema and immune cells infiltration similarly to that observed in pancreatitis. In spite of the controverted effects of hypothyroidism on serum glucose and insulin concentrations, the number and proliferation of Langerhans islet cells as well as the presence of extracellular matrix are affected depending on the islet size. In this study, we evaluated the effect of methimazole-induced hypothyroidism on the vascularization and immune cells infiltration into islets. A general observation of pancreas was also done. Twelve Chinchilla-breed female adult rabbits were divided into control (n = 6) and hypothyroid groups (n = 6, methimazole, 0.02% in drinking water for 30 days). After the treatment, rabbits were sacrificed and their pancreas was excised, histologically processed, and stained with Periodic Acid-Schiff (PAS) or Masson's Trichrome techniques. Islets were arbitrarily classified into large, medium, and small ones. The external and internal portions of each islet were also identified. Student-t-test and Mann-Whitney-U test or two-way ANOVAs were used to compare variables between groups. In comparison with control rabbits, hypothyroidism induced a strong infiltration of immune cells and a major presence of collagen and proteoglycans in the interlobular septa. Large islets showed a high vascularization and immune cells infiltration. The present results show that hypothyroidism induces pancreatitis and insulitis. PMID:26175757

  16. Hypothyroidism Affects Vascularization and Promotes Immune Cells Infiltration into Pancreatic Islets of Female Rabbits

    Directory of Open Access Journals (Sweden)

    Julia Rodríguez-Castelán

    2015-01-01

    Full Text Available Thyroidectomy induces pancreatic edema and immune cells infiltration similarly to that observed in pancreatitis. In spite of the controverted effects of hypothyroidism on serum glucose and insulin concentrations, the number and proliferation of Langerhans islet cells as well as the presence of extracellular matrix are affected depending on the islet size. In this study, we evaluated the effect of methimazole-induced hypothyroidism on the vascularization and immune cells infiltration into islets. A general observation of pancreas was also done. Twelve Chinchilla-breed female adult rabbits were divided into control n=6 and hypothyroid groups (n=6, methimazole, 0.02% in drinking water for 30 days. After the treatment, rabbits were sacrificed and their pancreas was excised, histologically processed, and stained with Periodic Acid-Schiff (PAS or Masson’s Trichrome techniques. Islets were arbitrarily classified into large, medium, and small ones. The external and internal portions of each islet were also identified. Student-t-test and Mann-Whitney-U test or two-way ANOVAs were used to compare variables between groups. In comparison with control rabbits, hypothyroidism induced a strong infiltration of immune cells and a major presence of collagen and proteoglycans in the interlobular septa. Large islets showed a high vascularization and immune cells infiltration. The present results show that hypothyroidism induces pancreatitis and insulitis.

  17. Peripheral vascular insufficiency impairs functional capacity in patients with heart failure

    Directory of Open Access Journals (Sweden)

    Renato Murayama

    2014-04-01

    Full Text Available INTRODUCTION: Heart failure (HF is a complex syndrome in which effort limitation is associated with deterioration of peripheral musculature. Improving survival rates among these patients have led to the appearance of cases in which other pathologies are associated with HF, such as peripheral vascular insufficiency (PVI. The combination of these two pathologies is common, with significant repercussions for affected patients. OBJECTIVE: To compare functional limitations and quality of life between patients with HF in isolation or HF + PVI. METHOD: Twelve patients with HF+PVI were paired to 12 patients with HF in isolation. All had ejection fraction 0.05. CONCLUSIONS: The study participants who had mixed disease exhibited a greater degree of functional impairment than the group with HF, without reporting worsened quality of life.

  18. Local vascular CO2 reactivity in the infant brain assessed by functional MRI

    DEFF Research Database (Denmark)

    Toft, P.B.; Leth, H; Lou, H.C.

    1995-01-01

    hyperventilated voluntarily, the vascular reactivity was homogeneously distributed predominantly over the grey matter. The experiments demonstrate that local impairment of vascular CO2 reactivity in the distressed infant brain can be detected by T2 sensitive gradient-echo MRI, which is also known as functional...

  19. Omega-3 Polyunsaturated Fatty Acids: Structural and Functional Effects on the Vascular Wall.

    Science.gov (United States)

    Zanetti, Michela; Grillo, Andrea; Losurdo, Pasquale; Panizon, Emiliano; Mearelli, Filippo; Cattin, Luigi; Barazzoni, Rocco; Carretta, Renzo

    2015-01-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFA) consumption is associated with reduced cardiovascular disease risk. Increasing evidence demonstrating a beneficial effect of n-3 PUFA on arterial wall properties is progressively emerging. We reviewed the recent available evidence for the cardiovascular effects of n-3 PUFA focusing on structural and functional properties of the vascular wall. In experimental studies and clinical trials n-3 PUFA have shown the ability to improve arterial hemodynamics by reducing arterial stiffness, thus explaining some of its cardioprotective properties. Recent studies suggest beneficial effects of n-3 PUFA on endothelial activation, which are likely to improve vascular function. Several molecular, cellular, and physiological pathways influenced by n-3 PUFA can affect arterial wall properties and therefore interfere with the atherosclerotic process. Although the relative weight of different physiological and molecular mechanisms and the dose-response on arterial wall properties have yet to be determined, n-3 PUFA have the potential to beneficially impact arterial wall remodeling and cardiovascular outcomes by targeting arterial wall stiffening and endothelial dysfunction.

  20. Omega-3 Polyunsaturated Fatty Acids: Structural and Functional Effects on the Vascular Wall

    Directory of Open Access Journals (Sweden)

    Michela Zanetti

    2015-01-01

    Full Text Available Omega-3 polyunsaturated fatty acids (n-3 PUFA consumption is associated with reduced cardiovascular disease risk. Increasing evidence demonstrating a beneficial effect of n-3 PUFA on arterial wall properties is progressively emerging. We reviewed the recent available evidence for the cardiovascular effects of n-3 PUFA focusing on structural and functional properties of the vascular wall. In experimental studies and clinical trials n-3 PUFA have shown the ability to improve arterial hemodynamics by reducing arterial stiffness, thus explaining some of its cardioprotective properties. Recent studies suggest beneficial effects of n-3 PUFA on endothelial activation, which are likely to improve vascular function. Several molecular, cellular, and physiological pathways influenced by n-3 PUFA can affect arterial wall properties and therefore interfere with the atherosclerotic process. Although the relative weight of different physiological and molecular mechanisms and the dose-response on arterial wall properties have yet to be determined, n-3 PUFA have the potential to beneficially impact arterial wall remodeling and cardiovascular outcomes by targeting arterial wall stiffening and endothelial dysfunction.

  1. Systemic Vascular Function Is Associated with Muscular Power in Older Adults

    Directory of Open Access Journals (Sweden)

    Kevin S. Heffernan

    2012-01-01

    Full Text Available Age-associated loss of muscular strength and muscular power is a critical determinant of loss of physical function and progression to disability in older adults. In this study, we examined the association of systemic vascular function and measures of muscle strength and power in older adults. Measures of vascular endothelial function included brachial artery flow-mediated dilation (FMD and the pulse wave amplitude reactive hyperemia index (PWA-RHI. Augmentation index (AIx was taken as a measure of systemic vascular function related to arterial stiffness and wave reflection. Measures of muscular strength included one repetition maximum (1RM for a bilateral leg press. Peak muscular power was measured during 5 repetitions performed as fast as possible for bilateral leg press at 40% 1RM. Muscular power was associated with brachial FMD (r=0.43, P<0.05, PWA-RHI (r=0.42, P<0.05, and AIx (r=−0.54, P<0.05. Muscular strength was not associated with any measure of vascular function. In conclusion, systemic vascular function is associated with lower-limb muscular power but not muscular strength in older adults. Whether loss of muscular power with aging contributes to systemic vascular deconditioning or vascular dysfunction contributes to decrements in muscular power remains to be determined.

  2. Does selenium supplementation affect thyroid function?

    DEFF Research Database (Denmark)

    Winther, Kristian Hillert; Bonnema, Steen Joop; Cold, Frederik

    2015-01-01

    OBJECTIVE: Selenium is present in the active site of proteins important for thyroid hormone synthesis and metabolism. The objective of this study is to investigate the effect of selenium supplementation in different doses on thyroid function, under conditions of suboptimal dietary selenium intake....... DESIGN: The Danish PREvention of Cancer by Intervention with SElenium pilot study (DK-PRECISE) is a randomized, double-blinded, placebo-controlled trial. A total of 491 males and females aged 60-74 years were randomized to 100 μg (n=124), 200 μg (n=122), or 300 μg (n=119) selenium-enriched yeast......=0.015), respectively, per 100 μg/day increase, with insignificant differences between 6 months and 5 years. No significant effects were found for FT3 and FT3:FT4 ratio. CONCLUSIONS: In euthyroid subjects, selenium supplementation minutely and dose-dependently affects thyroid function, when compared...

  3. Relationship between vascular endothelial function and pulse wave velocity in prehypertension

    Institute of Scientific and Technical Information of China (English)

    杨娉婷

    2014-01-01

    Objective To investigate the association between vascular endothelial function and arteriosclerosis in prehypertensive,hypertensive and healthy subjects.Methods 810 consecutive subjects were divided into three groups:hypertension group,prehypertension group and control group.Brachial-ankle pulse wave velocity(ba PWV)and flow-mediated brachial artery dilation(FMD)were used to evaluate the artery vascular stiffness and endothelial function respectively.Results Prehypertension

  4. The genetic background affects the vascular response in T-type calcium channels 3.2 deficient mice

    DEFF Research Database (Denmark)

    Svenningsen, Per; Hansen, Pernille B L

    2016-01-01

    Voltage-gated calcium channels (Cav ) are important regulators of vascular tone and are attractive targets for pharmacological treatment of hypertension. The clinical used calcium blockers are often not selective for one channel but affect several types of calcium channels (Hansen 2015). L...

  5. Pre-Analytical Parameters Affecting Vascular Endothelial Growth Factor Measurement in Plasma: Identifying Confounders.

    Directory of Open Access Journals (Sweden)

    Johanna M Walz

    Full Text Available Vascular endothelial growth factor-A (VEGF-A is intensively investigated in various medical fields. However, comparing VEGF-A measurements is difficult because sample acquisition and pre-analytic procedures differ between studies. We therefore investigated which variables act as confounders of VEGF-A measurements.Following a standardized protocol, blood was taken at three clinical sites from six healthy participants (one male and one female participant at each center twice one week apart. The following pre-analytical parameters were varied in order to analyze their impact on VEGF-A measurements: analyzing center, anticoagulant (EDTA vs. PECT / CTAD, cannula (butterfly vs. neonatal, type of centrifuge (swing-out vs. fixed-angle, time before and after centrifugation, filling level (completely filled vs. half-filled tubes and analyzing method (ELISA vs. multiplex bead array. Additionally, intrapersonal variations over time and sex differences were explored. Statistical analysis was performed using a linear regression model.The following parameters were identified as statistically significant independent confounders of VEGF-A measurements: analyzing center, anticoagulant, centrifuge, analyzing method and sex of the proband. The following parameters were no significant confounders in our data set: intrapersonal variation over one week, cannula, time before and after centrifugation and filling level of collection tubes.VEGF-A measurement results can be affected significantly by the identified pre-analytical parameters. We recommend the use of CTAD anticoagulant, a standardized type of centrifuge and one central laboratory using the same analyzing method for all samples.

  6. The interrelations between malfunctioning DNA damage response (DDR) and the functionality of the neuro-glio-vascular unit.

    Science.gov (United States)

    Barzilai, Ari

    2013-08-01

    A hallmark of neurodegenerative diseases is impairment of certain aspects of "brain functionality". Brain functionality is defined as the total input and output of the brain's neural circuits and networks. A given brain degenerative disorder does not deregulate total brain functionality but rather the activity of specific circuits in a given network, affecting their organization and topology, their cell numbers, their cellular functionality, and the interactions between neural circuits. Similarly, our concept of neurodegenerative diseases, which for many years revolved around neural survival or death, has now been extended to emphasize the role of glia. In particular, the role of glial cells in neuro-vascular communication is now known to be central to the effect of insults to the nervous system. In addition, a malfunctioning vascular system likely plays a role in the etiology of certain neurodegenerative diseases. Thus, the symptoms of neurodegenerative or more correctly brain degenerative disease are, to a very large extent, a result of impairment in glial cells that lead to pathological neuro-vascular interactions that, in turn, generate a rather "hostile" environment in which the neurons fail to function. These events lead to systematic neural cell death on a scale that appears to be proportional to the severity of the neurological deficit.

  7. Vascular Function and Handgrip Strength in Rheumatoid Arthritis Patients

    Directory of Open Access Journals (Sweden)

    Mahmoud A. Alomari

    2012-01-01

    Full Text Available Objective. To examine the relationship of handgrip strength with forearm blood flow (BF and vascular resistance (VR in rheumatoid arthritis (RA patients. Methods. Forearm BF at rest (RBF and after upper arm occlusion (RHBF, and handgrip strength were examined in 78 individuals (RA=42 and controls (CT=36. Subsequently, VR at rest (RVR and after occlusion (RHVR were calculated. Results. The patients’ RBF (P=0.02 and RHBF (P=0.0001 were less, whereas RVR (P=0.002 and RHVR (P=0.0001 were greater as compared to the CTs. Similarly, handgrip strength was lower in the RAs (P=0.0001. Finally, handgrip strength was directly associated with RBF (r=0.43; P=0.0001, and RHBF (r=0.5; P=0.0001, and inversely related to RVR (r=-0.3; P=0.009 and RHVR (r=-0.3; P=0.007. Conclusion. The present study uniquely identifies an association between regional measures of forearm blood flow and handgrip strength in patients and healthy control. In addition, this study confirms the presence of vascular and muscle dysfunction in patients with rheumatoid arthritis, as evidenced by lower forearm blood flow indices, at rest and following occlusion, and lower handgrip strength as compared to healthy individuals.

  8. Pulmonary Function Affects Language Performance in Aging

    Directory of Open Access Journals (Sweden)

    Lewina O Lee

    2014-04-01

    associated with better ES performance (B = 6.64, SE = 2.43, p = .01. Higher FVC and FEV1 were related to better MN performance, but this did not reach statistical significance (FVC: B = 3.68, SE = 2.16, p = .09; FEV1: B = 4.92, SE = 2.64, p = .06. Higher FVC (B = 3.98, SE = 1.44, p = .01 and FEV1 (B = 4.79, SE = 1.75, p = .01 were associated with better ANT performance. The positive association between PF and BNT performance was marginally significant (FVC: B = 4.19, SE = 2.18, p = .06; FEV1: B = 3.51, SE = 2.66, p = .10. Discussion and Conclusion Better PF was associated with higher accuracy on sentence processing and naming-based lexical retrieval tasks, consistent with the conclusion that pulmonary function affects older adults’ language performance. Our findings support the emerging thesis that language changes in aging are influenced by health-related physiological and neural mechanisms (e.g., Albert et al., 2009; Cahana-Amitay et al., 2013. From a clinical perspective, these findings highlight the promise of targeting PF as an intervention for improving language abilities among the elderly.

  9. Modular Small Diameter Vascular Grafts with Bioactive Functionalities.

    Directory of Open Access Journals (Sweden)

    Meik Neufurth

    Full Text Available We report the fabrication of a novel type of artificial small diameter blood vessels, termed biomimetic tissue-engineered blood vessels (bTEBV, with a modular composition. They are composed of a hydrogel scaffold consisting of two negatively charged natural polymers, alginate and a modified chitosan, N,O-carboxymethyl chitosan (N,O-CMC. Into this biologically inert scaffold two biofunctionally active biopolymers are embedded, inorganic polyphosphate (polyP and silica, as well as gelatin which exposes the cell recognition signal, Arg-Gly-Asp (RGD. These materials can be hardened by exposure to Ca(2+ through formation of Ca(2+ bridges between the polyanions, alginate, N,O-CMC, and polyP (alginate-Ca(2+-N,O-CMC-polyP. The bTEBV are formed by pressing the hydrogel through an extruder into a hardening solution, containing Ca(2+. In this universal scaffold of the bTEBV biomaterial, polycations such as poly(L-Lys, poly(D-Lys or a His/Gly-tagged RGD peptide (three RGD units were incorporated, which promote the adhesion of endothelial cells to the vessel surface. The mechanical properties of the biopolymer material (alginate-Ca(2+-N,O-CMC-polyP-silica revealed a hardness (elastic modulus of 475 kPa even after a short incubation period in CaCl2 solution. The material of the artificial vascular grafts (bTEBVs with an outer size 6 mm and 1.8 mm, and an inner diameter 4 mm and 0.8 mm, respectively turned out to be durable in 4-week pulsatile flow experiments at an alternating pressure between 25 and 100 mbar (18.7 and 75.0 mm Hg. The burst pressure of the larger (smaller vessels was 850 mbar (145 mbar. Incorporation of polycationic poly(L-Lys, poly(D-Lys, and especially the His/Gly-tagged RGD peptide, markedly increased the adhesion of human, umbilical vein/vascular endothelial cells, EA.HY926 cells, to the surface of the hydrogel. No significant effect of the polyP samples on the clotting of human plasma is measured. We propose that the metabolically

  10. Distribution and functional traits of charophytes and vascular plants

    DEFF Research Database (Denmark)

    Båstrup-Spohr, Lars

    rare species are specialists in particular environments, while the abundant species have traits such as broad salinity tolerance, tall shoots, vegetative reproduction and variable life form. Vascular plants, in contrast to charophytes, occupy the entire gradient from submerged to drained conditions...... environmental filtering also proved to be the most important in predicting the species composition under local conditions. The results stress the importance of environmental filtering as mechanism determining community assembly in plant communities. The zone from submerged to drained conditions along...... if sediment desiccation leads to high mineralization without stressing the plants. The sediment mineralization increased following desiccation and plants continued to grow well under drained, fluctuating and submerged conditions stressing the potential use of desiccation as a sediment restoration tool...

  11. Prevention of vascular calcification with bisphosphonates without affecting bone mineralization: a new challenge?

    Science.gov (United States)

    Neven, Ellen G; De Broe, Marc E; D'Haese, Patrick C

    2009-03-01

    Arterial calcification has been found to coexist with bone loss. Bisphosphonates, used as standard therapy for osteoporosis, inhibit experimentally induced vascular calcification, offering perspectives for the treatment of vascular calcification in renal failure patients. However, Lomashvili et al. report that the doses of etidronate and pamidronate that are effective in attenuating aortic calcification also decrease bone formation and mineralization in uremic rats, limiting their therapeutic use as anticalcifying agents.

  12. Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function After Hemorrhagic Shock.

    Science.gov (United States)

    Deng, Xiyun; Cao, Yanna; Huby, Maria P; Duan, Chaojun; Baer, Lisa; Peng, Zhanglong; Kozar, Rosemary A; Doursout, Marie-Francoise; Holcomb, John B; Wade, Charles E; Ko, Tien C

    2016-01-01

    Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use of fresh frozen plasma (FFP) in patients requiring massive transfusion is associated with improved outcomes. FFP contains significant amounts of adiponectin, which is known to have vascular protective function. We hypothesize that FFP improves vascular barrier function largely via adiponectin. Plasma adiponectin levels were measured in 19 severely injured patients in hemorrhagic shock (HS). Compared with normal individuals, plasma adiponectin levels decreased to 49% in HS patients before resuscitation (P < 0.05) and increased to 64% post-resuscitation (but not significant). In a HS mouse model, we demonstrated a similar decrease in plasma adiponectin to 54% but a significant increase to 79% by FFP resuscitation compared with baseline (P < 0.05). HS disrupted lung vascular barrier function, leading to an increase in permeability. FFP resuscitation reversed these HS-induced effects. Immunodepletion of adiponectin from FFP abolished FFP's effects on blocking endothelial hyperpermeability in vitro, and on improving lung vascular barrier function in HS mice. Replenishment with adiponectin rescued FFP's effects. These findings suggest that adiponectin is an important component in FFP resuscitation contributing to the beneficial effects on vascular barrier function after HS.

  13. Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men.

    Science.gov (United States)

    Esser, Diederik; Mars, Monica; Oosterink, Els; Stalmach, Angelique; Müller, Michael; Afman, Lydia A

    2014-03-01

    Flavanol-enriched chocolate consumption increases endothelium-dependent vasodilation. Most research so far has focused on flow-mediated dilation (FMD) only; the effects on other factors relevant to endothelial health, such as inflammation and leukocyte adhesion, have hardly been addressed. We investigated whether consumption of regular dark chocolate also affects other markers of endothelial health, and whether chocolate enrichment with flavanols has additional benefits. In a randomized double-blind crossover study, the effects of acute and of 4 wk daily consumption of high flavanol chocolate (HFC) and normal flavanol chocolate (NFC) on FMD, augmentation index (AIX), leukocyte count, plasma cytokines, and leukocyte cell surface molecules in overweight men (age 45-70 yr) were investigated. Sensory profiles and motivation scores to eat chocolate were also collected. Findings showed that a 4 wk chocolate intake increased FMD by 1%, which was paralleled by a decreased AIX of 1%, decreased leukocyte cell count, decreased plasma sICAM1 and sICAM3, and decreased leukocyte adhesion marker expression (Pchocolate. This study provides new insights on how chocolate affects endothelial health by demonstrating that chocolate consumption, besides improving vascular function, also lowers the adherence capacity of leukocytes in the circulation.

  14. Flow-dependent regulation of vascular function and gene expression in rat superior mesenteric artery

    Institute of Scientific and Technical Information of China (English)

    XIA Shang; DENG Chang-sheng

    2009-01-01

    Background Mesenteric artery thrombosis is prone to occur at specific arterial regions with different fluid flow patterns,yet mechanistic links between blood flow and vascular function remain unclear. This study aired to investigate the role of blood flow in regulation of vascular function and gene expression in rats.Methods Isometric tension was recorded in wire myograph to examine vascular function of specific regions (trunk parts and proximal parts from the origin) with different blood flow in superior mesenteric artery (SMA). Endothelial nitric oxide syntheses (eNOS), phosphorylated-eNOS (p-eNOS), serine-threonine kinase Akt and phosphorylated-Akt (p-Akt) protein expressions in SMA were examined by Western blotting. Significance was analyzed using a Student's ttest or analysis of variance (ANOVA) followed by a Dunnett's multiple-comparison post hoc test.Results Compared with trunks, proximal parts exhibited severely impaired relaxant responses to acetylcholine (Ach) (1 nmol/L to 10 pmol/L) (P 0.05).Conclusion Critical components that drive the vascular function and influence the localization of mesenteric artery thrombosis are flow-responsive elements within the vascular endothelium.

  15. Luminal epithelium in endometrial fragments affects their vascularization, growth and morphological development into endometriosis-like lesions in mice

    Directory of Open Access Journals (Sweden)

    Dilu Feng

    2014-02-01

    Full Text Available In endometriosis research, endometriosis-like lesions are usually induced in rodents by transplantation of isolated endometrial tissue fragments to ectopic sites. In the present study, we investigated whether this approach is affected by the cellular composition of the grafts. For this purpose, endometrial tissue fragments covered with luminal epithelium (LE+ and without luminal epithelium (LE− were transplanted from transgenic green-fluorescent-protein-positive (GFP+ donor mice into the dorsal skinfold chamber of GFP− wild-type recipient animals to analyze their vascularization, growth and morphology by means of repetitive intravital fluorescence microscopy, histology and immunohistochemistry during a 14-day observation period. LE− fragments developed into typical endometriosis-like lesions with cyst-like dilated endometrial glands and a well-vascularized endometrial stroma. In contrast, LE+ fragments exhibited a polypoid morphology and a significantly reduced blood perfusion after engraftment, because the luminal epithelium prevented the vascular interconnection with the microvasculature of the surrounding host tissue. This was associated with a markedly decreased growth rate of LE+ lesions compared with LE− lesions. In addition, we found that many GFP+ microvessels grew outside the LE− lesions and developed interconnections to the host microvasculature, indicating that inosculation is an important mechanism in the vascularization process of endometriosis-like lesions. Our findings demonstrate that the luminal epithelium crucially affects the vascularization, growth and morphology of endometriosis-like lesions. Therefore, it is of major importance to standardize the cellular composition of endometrial grafts in order to increase the validity and reliability of pre-clinical rodent studies in endometriosis research.

  16. Luminal epithelium in endometrial fragments affects their vascularization, growth and morphological development into endometriosis-like lesions in mice.

    Science.gov (United States)

    Feng, Dilu; Menger, Michael D; Wang, Hongbo; Laschke, Matthias W

    2014-02-01

    In endometriosis research, endometriosis-like lesions are usually induced in rodents by transplantation of isolated endometrial tissue fragments to ectopic sites. In the present study, we investigated whether this approach is affected by the cellular composition of the grafts. For this purpose, endometrial tissue fragments covered with luminal epithelium (LE(+)) and without luminal epithelium (LE(-)) were transplanted from transgenic green-fluorescent-protein-positive (GFP(+)) donor mice into the dorsal skinfold chamber of GFP(-) wild-type recipient animals to analyze their vascularization, growth and morphology by means of repetitive intravital fluorescence microscopy, histology and immunohistochemistry during a 14-day observation period. LE(-) fragments developed into typical endometriosis-like lesions with cyst-like dilated endometrial glands and a well-vascularized endometrial stroma. In contrast, LE(+) fragments exhibited a polypoid morphology and a significantly reduced blood perfusion after engraftment, because the luminal epithelium prevented the vascular interconnection with the microvasculature of the surrounding host tissue. This was associated with a markedly decreased growth rate of LE(+) lesions compared with LE(-) lesions. In addition, we found that many GFP(+) microvessels grew outside the LE(-) lesions and developed interconnections to the host microvasculature, indicating that inosculation is an important mechanism in the vascularization process of endometriosis-like lesions. Our findings demonstrate that the luminal epithelium crucially affects the vascularization, growth and morphology of endometriosis-like lesions. Therefore, it is of major importance to standardize the cellular composition of endometrial grafts in order to increase the validity and reliability of pre-clinical rodent studies in endometriosis research.

  17. Vascular Cognitive Impairment.

    Science.gov (United States)

    Dichgans, Martin; Leys, Didier

    2017-02-03

    Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts.

  18. Blood flow interplays with elastin: collagen and MMP: TIMP ratios to maintain healthy vascular structure and function

    Directory of Open Access Journals (Sweden)

    Poulami Basu

    2010-03-01

    thickness and elastin:collagen ratios had a threshold in blood flow in the range 0.6–2.5 mL/min, which increased robustly if blood flow increased to 2.7 mL/min. This pattern was inverted by the total MMP:TIMP ratio. We conclude that vascular remodeling is a function of rate of blood flow, which would in turn be determined by the amounts of MMPs and their inhibitors present. The study combined the endothelial and dynamic (blood flow/pressure components that affect medial thickness and elastin: collagen ratios.Keywords: vascular remodeling, atherosclerosis, passive stretch-tension relationship

  19. Beta-lactam antibiotic-mediated changes in platelet reactivity and vascular endothelial functions.

    Science.gov (United States)

    Togna, G I; Togna, A R; Caprino, L

    2001-05-01

    To evaluate vascular and platelet compatibility of intravenous administration of beta-lactam antibiotics, we assessed the effects of therapeutic concentrations of ceftriaxone, aztreonam, and ceftazidime on platelet reactivity to different agonists (sodium arachidonate, collagen and adenosine diphosphate) and on selected vascular endothelial functions (adenosine diphosphatase activity, prostacyclin production and t-PA release). Ceftriaxone and, to a lesser degree, aztreonam, enhanced platelet reactivity, evaluated as onset of platelet aggregating response, and increased thromboxane production to subthreshold concentrations of arachidonate. There was no modification in platelet reactivity after ceftazidime treatment. Ceftriaxone and ceftazidime, but not aztreonam, inhibited endothelial adenosine diphosphatase activity. Prostacyclin production and t-PA release were inhibited only by ceftriaxone at high concentrations. While it is difficult to establish which marker (platelet or endothelial functions) has more clinical reference in human vascular compatibility, it seems feasible to consider aztreonam the most compatible of the beta-lactams studied.

  20. A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct

    Science.gov (United States)

    Valarmathi, Mani T.; Fuseler, John W.; Davis, Jeffrey M.; Price, Robert L.

    2017-01-01

    Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty. PMID:28194397

  1. Construction of a fucoidan/laminin functional multilayer to direction vascular cell fate and promotion hemocompatibility

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Changrong; Wang, Yan; Su, Hong; Yang, Ping; Huang, Nan [Key Laboratory of Advanced Materials Technology of Ministry of Education, Department of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Maitz, Manfred F. [Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Dresden 01069 (Germany); Zhao, Anshan [Key Laboratory of Advanced Materials Technology of Ministry of Education, Department of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China)

    2016-07-01

    Surface biofunctional modification of cardiovascular stents is a versatile approach to reduce the adverse effects after implantation. In this work, a novel multifunctional coating was fabricated by coimmobilization of the sulfated polysaccharide of brown algae fucoidan and laminin to biomimic the vascular intimal conditions in order to support rapid endothelialization, prevent restenosis and improve hemocompatibility. The surface properties of the coating such as hydrophilicity, bonding density of biomolecules and stability were evaluated and optimized. According to the biocompatibility tests, the fucoidan/laminin multilayer coated surface displayed less platelet adhesion with favorable anticoagulant property. In addition, the fucoidan/laminin complex showed function to selectively regulate vascular cells growth behavior. The proliferation of endothelial cells (ECs) on the fucoidan/laminin biofunctional coating was significantly promoted. For the smooth muscle cells (SMCs), inhibitory effects on cell adhesion and proliferation were observed. In conclusion, the fucoidan/laminin biofunctional coating was successfully fabricated with desirable anticoagulant and endothelialization properties which show a promising application in the vascular devices such as vascular stents or grafts surface modification. - Highlights: • Construction of fucoidan/laminin functional multilayer to biomimic the basement membrane of vascular • The fucoidan/laminin complex demonstrates anti-coagulation property. • The fucoidan/laminin complex can selectively regulate EC and SMC growth behavior to prevent restenosis.

  2. Relationship between dyslipidemia and vascular endothelial function in patients with coronary artery spasm

    Institute of Scientific and Technical Information of China (English)

    向定成

    2006-01-01

    Objectives To investigate the effects of dyslipidemia on vascular endothelial function in patients with coronary artery spasm. Methods Sixty-four patients with chest pain but without significant angiographic stenosis were divided into coronary spasm group (n=46 with coronary spasm) and control group (n=18 without coronary spasm) according to acetylcholine provoking test. Endothelin-1 (ET-1), nitric oxide (NO) and lipids were

  3. Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomized, crossover study

    NARCIS (Netherlands)

    Dower, James I.; Geleijnse, Marianne; Kroon, Paul A.; Philo, Mark; Mensink, Marco; Kromhout, Daan; Hollman, Peter C.H.

    2016-01-01

    Scope: Cocoa, rich in flavan-3-ols, improves vascular function, but the contribution of specific flavan-3-ols is unknown. We compared the effects of pure epicatechin, a major cocoa flavan-3-ol, and chocolate. Methods and results: In a randomized crossover study, twenty healthy men (40-80 years) w

  4. Exercise training improves physical fitness and vascular function in children with type 1 diabetes

    NARCIS (Netherlands)

    Seeger, J.P.H.; Thijssen, D.H.J.; Noordam, K.; Cranen, M.E.; Hopman, M.T.E.; Nijhuis-Van der Sanden, M.W.G.

    2011-01-01

    Children with type 1 diabetes mellitus (DM1) show endothelial dysfunction and mild artery wall thickening compared to their age-matched healthy peers. In this study, we examined the effect of 18-week exercise training on physical fitness and vascular function and structure in children with DM1. We e

  5. Nitinol-based Nanotubular and Nanowell Coatings for the Modulation of Human Vascular Cell Functions

    Science.gov (United States)

    Lee, Phin Peng

    Current approaches to reducing restenosis do not balance the reduction of vascular smooth muscle cell proliferation with the increase in the healing of the endothelium. Here, I present my study on the synthesis and characterization of a nanotubular coating on Nitinol substrates. I found that the coating demonstrated 'pro-healing' properties by increasing primary human aortic endothelial cell spreading, migration and collagen and elastin production. Certain cellular functions such as collagen and elastin production were also found to be affected by changes in nanotube diameter. The coating also reduced the proliferation and mRNA expression of collagen I and MMP2 for primary human aortic smooth muscle cells. I will also demonstrate the synthesis of a nanowell coating on Nitinol stents as well as an additional poly(lactic-co-glycolic acid) coating on top of the nanowells that has the potential for controlling drug release. These findings demonstrate the potential for the coatings to aid in the prevention of restenosis and sets up future explorations of ex vivo and in vivo studies.

  6. Impact of AT2-receptor stimulation on vascular biology, kidney function, and blood pressure

    DEFF Research Database (Denmark)

    Danyel, L.A.; Schmerler, P.; Paulis, L.;

    2013-01-01

    angiotensin II) and with relevance for blood pressure (BP) regulation or hypertensive end-organ damage. These data will include studies on vasodilation/vasoconstriction in isolated resistance arteries ex vivo, studies on kidney function, studies on vascular remodeling, and studies that measured the net effect...... to attenuate hypertension-induced vascular remodeling and reduce arterial stiffening, which in more chronic settings and together with the natriuretic effect may result in modest lowering of BP. We conclude from these preclinical data that AT2R agonists are not suitable for antihypertensive monotherapy...

  7. An analysis of vascular surgery in elderly patients to determine whether age affects treatment strategy.

    LENUS (Irish Health Repository)

    O'Brien, G

    2012-03-01

    The incidence of arterial disease increases with age. Increasing life expectancy in the western world will intensify demands on vascular surgeons with regard to increasing caseload, expanding patient selection criteria, and more complex and minimally-invasive treatment options. We analysed our arterial cases over the past 31 years (n = 6,144) and compared our methods of intervention and complication rates in the elderly population (>75) with the younger cohort, in order to determine whether age should influence our management strategies.

  8. Novel Vascular Malformation in an Affected Newborn with Deletion Del(4)(q31.3)

    OpenAIRE

    Norma Elena de León Ojeda; Michel Soriano-Torres; Cabrera, Mercedes J.; Dunia Bárbara Benítez Ramos

    2012-01-01

    We report on a newborn male patient with a terminal deletion in the long arm of the chromosome 4 with a congenital heart defect unreported before in association with this syndrome. The patient had multiple congenital anomalies including a pointed duplicated fingernail, low set posteriorly rotated ears, large anterior fontanel, micrognathia, glabellar capillary vascular malformation, and Interrupted Aortic Arch type C. The patient died due to multiple congenital malformations; a peripheral chr...

  9. A novel approach to the assessment of vascular endothelial function

    Energy Technology Data Exchange (ETDEWEB)

    Sathasivam, S; Siddiqui, Z; Greenwald, S [Pathology Group, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (United Kingdom); Phababpha, S; Sengmeuan, P; Detchaporn, P; Kukongviriyapan, U, E-mail: s.e.greenwald@qmul.ac.uk [Department of Physiology, Khon Kaen University, Khon Kaen (Thailand)

    2011-08-17

    Impaired endothelial function (EF) is associated with atherogenesis, and its quantitative assessment has prognostic value. Currently, methods based on assessing flow-mediated dilation (FMD) are technically difficult and expensive. We tested a novel way of assessing EF by measuring the time difference between pulses arriving at the middle fingers of each hand (f-f{Delta}T), whilst FMD is induced in one arm. We compared f-f{Delta}T with standard methods in healthy and diseased subjects. Our findings suggest that the proposed simple and inexpensive technique gives comparable results and has the potential to qualitatively assess EF in the clinical setting, although further work is required.

  10. Loss-of-function mutations in APOC3 and risk of ischemic vascular disease

    DEFF Research Database (Denmark)

    Jørgensen, Anders Berg; Frikke-Schmidt, Ruth; Nordestgaard, Børge G;

    2014-01-01

    BACKGROUND: High plasma levels of nonfasting triglycerides are associated with an increased risk of ischemic cardiovascular disease. Whether lifelong low levels of nonfasting triglycerides owing to mutations in the gene encoding apolipoprotein C3 (APOC3) are associated with a reduced risk...... of ischemic cardiovascular disease in the general population is unknown. METHODS: Using data from 75,725 participants in two general-population studies, we first tested whether low levels of nonfasting triglycerides were associated with reduced risks of ischemic vascular disease and ischemic heart disease....... Second, we tested whether loss-of-function mutations in APOC3, which were associated with reduced levels of nonfasting triglycerides, were also associated with reduced risks of ischemic vascular disease and ischemic heart disease. During follow-up, ischemic vascular disease developed in 10...

  11. Vascular Function and Angiogenesis in Aging and Essential Hypertension

    DEFF Research Database (Denmark)

    Gliemann, Lasse

    markers of basal oxidative stress and inflammation in skeletal muscle. The effect of training on markers of oxidative stress was likely, at least in part, due to a increase in skeletal muscle levels of SOD2, as the potential for ROS formation actually increased as evidenced by an increase...... age and inactivity, muscle capillarization is decreased, which may contribute to decreased muscle function and physical capacity. In agreement with previous observations, the present work shows that exercise training induces a marked angiogenic response and increases capillarization in skeletal muscle...... capillary lumen area and a tendency for increased basement membrane thickness in the skeletal muscle. The physiological consequences of these alterations are unknown but may constitute a limitation for diffusion of oxygen and nutrients. Increased basement membrane thickness has also been associated...

  12. Clinical Correlates of Hachinski Ischemic Score and Vascular Factors in Cognitive Function of Elderly

    Directory of Open Access Journals (Sweden)

    Youn Ho Kim

    2014-01-01

    Full Text Available The aim of this study is to investigate the relationship between Hachinski ischemic score (HIS and vascular factors as well as between HIS and the cognitive function in elderly community. Demographic characteristics, such as sex, age, education, history of drinking and smoking, family history of dementia and stroke, diabetes mellitus, hypertension, hyperlipidemia, cardiovascular disease, stroke, and dementia, were surveyed. Neurological examination was administered to every subject and HIS was checked by a neurologist. From a total of 392 participants aged 65 and over in a rural community, 348 completed the survey and were finally enrolled. Among the vascular factors, history of hypertension (P=0.008, history of stroke (P<0.001, family history of dementia (P=0.01, and history of cardiac diseases (P=0.012 showed a significant relationship with HIS. In the cognitive function tests, both Korean version of the Mini-Mental State Examination and the Clinical Dementia Rating (Global and Sum of Boxes had a significant relationship with HIS. Our study suggested HIS may have an association with some vascular factors and cognitive scales in community dwelling elderly. In this study, the HIS seemed to contribute to the evaluation of the quantity of vascular factors and to the prediction of status of cognitive function.

  13. Alterations in vascular function in primary aldosteronism: a cardiovascular magnetic resonance imaging study.

    Science.gov (United States)

    Mark, P B; Boyle, S; Zimmerli, L U; McQuarrie, E P; Delles, C; Freel, E M

    2014-02-01

    Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV). We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass. Subjects with PA had significantly lower aortic distensibility and higher PWV compared with EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including ageing. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular ageing. As expected, aortic distensibility and PWV were closely correlated. These results demonstrate that PA patients display increased arterial stiffness compared with EH, independent of vascular ageing. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.

  14. Vascular function assessed with cardiovascular magnetic resonance predicts survival in patients with advanced chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Steedman Tracey

    2008-08-01

    Full Text Available Abstract Background Increased arterial stiffness is associated with mortality in patients with chronic kidney disease. Cardiovascular magnetic resonance (CMR permits assessment of the central arteries to measure aortic function. Methods We studied the relationship between central haemodynamics and outcome using CMR in 144 chronic kidney disease patients with estimated glomerular filtration rate Results Median follow up after the scan was 24 months. There were no significant differences in aortic distensibilty or aortic volumetric arterial strain between pre-dialysis and dialysis patients. Aortic distensibilty and volumetric arterial strain negatively correlated with age. Aortic distensibilty and volumetric arterial strain were lower in diabetics, patients with ischaemic heart disease and peripheral vascular disease. During follow up there were 20 deaths. Patients who died had lower aortic distensibilty than survivors. In a survival analysis, diabetes, systolic blood pressure and aortic distensibilty were independent predictors of mortality. There were 12 non-fatal cardiovascular events during follow up. Analysing the combined end point of death or a vascular event, diabetes, aortic distensibilty and volumetric arterial strain were predictors of events. Conclusion Deranged vascular function measured with CMR correlates with cardiovascular risk factors and predicts outcome. CMR measures of vascular function are potential targets for interventions to reduce cardiovascular risk.

  15. Discovery and functional assessment of gene variants in the vascular endothelial growth factor pathway

    OpenAIRE

    Paré-Brunet, Laia; Glubb, Dylan; Evans, Patrick; Berenguer-Llergo, Antoni; Etheridge, Amy S.; Skol, Andrew D.; Di Rienzo, Anna; Duan, Shiwei; Gamazon, Eric R.; Innocenti, Federico

    2013-01-01

    Angiogenesis is a host-mediated mechanism in disease pathophysiology. The vascular endothelial growth factor (VEGF) pathway is a major determinant of angiogenesis, and a comprehensive annotation of the functional variation in this pathway is essential to understand the genetic basis of angiogenesis-related diseases. We assessed the allelic heterogeneity of gene expression, population specificity of cis expression quantitative trait loci (eQTLs), and eQTL function in luciferase assays in CEU a...

  16. Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder.

    Science.gov (United States)

    Moises, H W; Wollschläger, D; Binder, H

    2015-08-11

    In search for the elusive schizophrenia pathway, candidate genes for the disorder from a discovery sample were localized within the energy-delivering and ischemia protection pathway. To test the adult vascular-ischemic (AVIH) and the competing neurodevelopmental hypothesis (NDH), functional genomic analyses of practically all available schizophrenia-associated genes from candidate gene, genome-wide association and postmortem expression studies were performed. Our results indicate a significant overrepresentation of genes involved in vascular function (P schizophrenia-associated genes from genetic association studies. These findings support both the NDH and the AVIH. The genes from postmortem studies showed an upregulation of vascular-ischemic genes (P = 0.020) combined with downregulated synaptic (P = 0.005) genes, and ND/repair (P = 0.003) genes. Evidence for the AVIH and the NDH is critically discussed. We conclude that schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder. Adult postischemic repair involves ND genes for adult neurogenesis, synaptic plasticity, glutamate and increased long-term potentiation of excitatory neurotransmission (i-LTP). Schizophrenia might be caused by the cerebral analog of microvascular angina.

  17. Smoking as a confounding factor on the influence of cold therapy on the vascular endothelium function of young men.

    Science.gov (United States)

    Noguchi, Masahiro; Fujikawa, Ryoya; Kimura, Akira

    2013-10-01

    [Purpose] This study was designed to determine whether smoking affects endothelium function after cold therapy in young men. [Subjects] The final cohort included 27 healthy men (age, 20-21 years). Because an impact on vascular endothelium function was anticipated to be caused by smoking, the study enrolled 14 participants in a smoking group and 13 in a non-smoking group. [Methods] Vascular endothelial function was assessed by determining the reactive hyperemia index (RHI), using finger-tonometry. RHI was measured twice, at rest (baseline) and after a cold stimulus. The forearm was cooled with an ice bag for 10 min as the cold stimulus. Comparisons between the RHI at baseline and after cold treatment, and between the smoking and non-smoking groups, were performed using the paired and unpaired t-tests, respectively. [Results] There was a significant difference in baseline RHI values between the smoking and non-smoking groups, but there was no significant difference between the baseline and post-treatment RHI values in either group. [Conclusion] These results suggest that cigarette smoking damages the endothelial cells in young men with a short history of smoking. However, cold therapy did not have a significant impact on the RHI in either group.

  18. Exercise training improves vascular endothelial function in patients with type 1 diabetes.

    Science.gov (United States)

    Fuchsjäger-Mayrl, Gabriele; Pleiner, Johannes; Wiesinger, Günther F; Sieder, Anna E; Quittan, Michael; Nuhr, Martin J; Francesconi, Claudia; Seit, Hans-Peter; Francesconi, Mario; Schmetterer, Leopold; Wolzt, Michael

    2002-10-01

    OBJECTIVE-Impaired endothelial function of resistance and conduit arteries can be detected in patients with type 1 diabetes. We studied whether a persistent improvement of endothelial function can be achieved by regular physical training. RESEARCH DESIGN AND METHODS-The study included 26 patients with type 1 diabetes of 20 +/- 10 years' duration and no overt angiopathy; 18 patients (42 +/- 10 years old) participated in a bicycle exercise training program, and 8 patients with type 1 diabetes (33 +/- 11 years old) served as control subjects. Vascular function of conduit arteries was assessed by flow-mediated and endothelium-independent dilation of the brachial artery and of resistance vessels by the response of ocular fundus pulsation amplitudes to intravenous N(G)-monomethyl-L-arginine (L-NMMA) at baseline, after 2 and 4 months of training, and 8 months after cessation of regular exercise. RESULTS-Training increased peak oxygen uptake (VO(2max)) by 13% after 2 months and by 27% after 4 months (P = 0.04). Flow-mediated dilation (FMD) of the brachial artery increased from 6.5 +/- 1.1 to 9.8 +/- 1.1% (P = 0.04) by training. L-NMMA administration decreased fundus pulsation amplitude (FPA) by 9.1 +/- 0.9% before training and by 13.4 +/- 1.5% after 4 months of training (P = 0.02). VO(2max), FMD, and FPA were unchanged in the control group. Vascular effects from training were abrogated 8 months after cessation of exercise. CONCLUSIONS-Our study demonstrates that aerobic exercise training can improve endothelial function in different vascular beds in patients with long-standing type 1 diabetes, who are at considerable risk for diabetic angiopathy. However, the beneficial effect on vascular function is not maintained in the absence of exercise.

  19. Does Acquired Hypothyroidism Affect the Hearing Functions?

    Directory of Open Access Journals (Sweden)

    Ayşe Arduç

    2015-12-01

    Full Text Available Purpose: It is well known that congenital hypothyroidism can cause hearing loss. However, conflicting results were found in studies investigating hearing functions in acquired hypothyroidism. Therefore, we evaluated the audiometric findings in patients with acquired hypothyroidism. Material and Method: The study included 58 patients with hypothyroidism and age- and gender-matched 34 healthy controls. Twenty eight (48.27% patients had subclinical hypothyroidism, and 30 (51.73% had obvious hypothyroidism. All subjects had a normal otoscopic examination and tympanometry. Pure tone audiometry at 250, 500, 1000, 2000, 4000, 6000, and 8000 Hertz (Hz was performed in both groups. Blood pressure measurements and the levels of plasma electrolytes, lipids and vitamin B12 were available in all subjects. Results: Hypothyroidism group and control group were similar with respect to systolic and diastolic blood pressures and plasma glucose, lipid, vitamin B12, calcium, sodium, potassium, and chloride levels. Significantly higher audiometric thresholds (dB at 250 (10 (0-45 vs. 5 (0-15, p<0.001 and 500 Hz (10 (0-40 vs. 10 (-5-15, p=0.003 were recorded in hypothyroid patients compared to that in healthy controls. Hearing thresholds at 250 and 500 Hz correlated positively with thyroid-stimulating hormone (TSH, and negatively with free triiodothyronine and free thyroxine. Subclinical hypothyroid patients had a higher hearing threshold at 250 Hz than healthy controls (p=0.001. Discussion: Our study demonstrated that hearing ability decreases in hypothyroidism, even in subclinical hypothyroidism. The changes in TSH and thyroid hormone levels seem to be directly related to the hearing loss in this population of patients.

  20. Construction of a fucoidan/laminin functional multilayer to direction vascular cell fate and promotion hemocompatibility.

    Science.gov (United States)

    Ye, Changrong; Wang, Yan; Su, Hong; Yang, Ping; Huang, Nan; F Maitz, Manfred; Zhao, Anshan

    2016-07-01

    Surface biofunctional modification of cardiovascular stents is a versatile approach to reduce the adverse effects after implantation. In this work, a novel multifunctional coating was fabricated by coimmobilization of the sulfated polysaccharide of brown algae fucoidan and laminin to biomimic the vascular intimal conditions in order to support rapid endothelialization, prevent restenosis and improve hemocompatibility. The surface properties of the coating such as hydrophilicity, bonding density of biomolecules and stability were evaluated and optimized. According to the biocompatibility tests, the fucoidan/laminin multilayer coated surface displayed less platelet adhesion with favorable anticoagulant property. In addition, the fucoidan/laminin complex showed function to selectively regulate vascular cells growth behavior. The proliferation of endothelial cells (ECs) on the fucoidan/laminin biofunctional coating was significantly promoted. For the smooth muscle cells (SMCs), inhibitory effects on cell adhesion and proliferation were observed. In conclusion, the fucoidan/laminin biofunctional coating was successfully fabricated with desirable anticoagulant and endothelialization properties which show a promising application in the vascular devices such as vascular stents or grafts surface modification.

  1. Fetal Growth Restriction Induces Heterogeneous Effects on Vascular Biomechanical and Functional Properties in Guinea Pigs (Cavia porcellus)

    Science.gov (United States)

    Cañas, Daniel; Herrera, Emilio A.; García-Herrera, Claudio; Celentano, Diego; Krause, Bernardo J.

    2017-01-01

    Aim: Fetal growth restriction (FGR) is associated with a variety of cardiometabolic diseases in adulthood which could involve remodeling processes of the vascular walls that could start in the fetal period. However, there is no consensus whether this remodeling affects in a similar way the whole vascular system. We aimed to determine the effects of FGR on the vasoactive and biomechanical properties of umbilical and systemic vessels in fetal guinea pigs. Methods: FGR was induced by implanting ameroid occluders at mid-gestation in uterine arteries of pregnant guinea pigs, whilst the control group was exposed to simulated surgery. At the term of gestation, systemic arteries (aorta, carotid and femoral) and umbilical vessels were isolated to determine ex vivo contractile and biomechanical responses (stretch-stress until rupture) on a wire myograph, as well as opening angle and residual stresses. Histological characteristics in tissue samples were measured by van Gieson staining. Results: Aorta and femoral arteries from FGR showed an increased in biomechanical markers of stiffness (p < 0.01), contractile capacity (p < 0.05) and relative media thickness (p < 0.01), but a reduced internal diameter (p < 0.001), compared with controls. There were no differences in the biomechanical properties of carotid and umbilical from control and FGR fetuses, but FGR umbilical arteries had a decreased contractile response to KCl (p < 0.05) along with a reduced relative media thickness (p < 0.05). Conclusion: Altogether, these changes in functional, mechanical and morphological properties suggest that FGR is associated with a heterogeneous pro-constrictive vascular remodeling affecting mainly the lower body fetal arteries. These effects would be set during a pathologic pregnancy in order to sustain the fetal blood redistribution in the FGR and may persist up to adulthood increasing the risk of a cardiovascular disease. PMID:28344561

  2. Impaired cardiac response to exercise in post-menopausal women: relationship with peripheral vascular function.

    Science.gov (United States)

    Yoshioka, J; Node, K; Hasegawa, S; Paul, A K; Mu, X; Maruyama, K; Nakatani, D; Kitakaze, M; Hori, M; Nishimura, T

    2003-04-01

    Endothelial dysfunction has been demonstrated in post-menopausal women. To assess the relationship between peripheral vascular reserve and cardiac function during exercise in post-menopausal women, 91 subjects, who had no ischaemic findings on myocardial SPECT, were assigned to four groups: pre-menopausal women (n=13), post-menopausal women (n=33), younger men aged 50 years (n=35). First-pass radionuclide angiography was performed before and during bicycle exercise to calculate ejection fraction (EF) and peripheral vascular resistance (VR). There were no differences in haemodynamic variables among the groups at baseline. The per cent increase in EF=(exercise EF - resting EF)x100/resting EF, and the per cent decrease in VR=(resting VR - exercise VR)x100/resting VR were depressed in the post-menopausal women (0.4+/-2% and 35+/-3%, respectively) compared to the pre-menopausal women (10+/-3% and 47+/-3%, respectively; PPost-menopausal women exhibited depressed cardiac function during exercise, which may be related to the impairment of peripheral vascular function after menopause.

  3. Assessment of vascular function in Mexican women exposed to polycyclic aromatic hydrocarbons from wood smoke.

    Science.gov (United States)

    Ruiz-Vera, Tania; Pruneda-Álvarez, Lucia G; Ochoa-Martínez, Ángeles C; Ramírez-GarcíaLuna, José L; Pierdant-Pérez, Mauricio; Gordillo-Moscoso, Antonio A; Pérez-Vázquez, Francisco J; Pérez-Maldonado, Iván N

    2015-09-01

    The use of solid fuels for cooking and heating is likely to be the largest source of indoor air pollution on a global scale; these fuels emit substantial amounts of toxic pollutants such as polycyclic aromatic hydrocarbons (PAHs) when used in simple cooking stoves (such as open "three-stone" fires). Moreover, indoor air pollution from biomass fuels is considered an important risk factor for human health. The aim of this study was to evaluate the relationship between exposure to PAHs from wood smoke and vascular dysfunction; in a group of Mexican women that use biomass combustion as their main energy source inside their homes. We used 1-hydroxypyrene (1-OHP) as an exposure biomarker to PAHs and it was assessed using high performance liquid chromatography. The endothelium-dependent vasodilation was assessed through a vascular reactivity compression test performed with a pneumatic cuff under visualization of the brachial artery using high resolution ultrasonography (HRU). Assessment of the carotid intima-media thickness (CIMT) was used as an atherosclerosis biomarker (also assessed using HRU); and clinical parameters such as anthropometry, blood pressure, glucose, triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, among others were also evaluated. The mean concentration of urinary 1-OHP found in exposed women was 0.46±0.32μmol/mol Cr (range: 0.086-1.23μmol/mol Cr). Moreover, vascular dysfunction (diminished endothelium dependent vasodilation) was found in 45% of the women participating in the study. Association between vascular function and 1-OHP levels was found to be significant through a logistic regression analysis (p=0.034; r(2)=0.1329). Furthermore, no association between CIMT and clinical parameters, urinary 1-OHP levels or vascular dysfunction was found. Therefore, with the information obtained in this study, we advocate for the need to implement programs to reduce the risk of exposure to PAHs in communities that use biomass fuels as a main

  4. Vascular wall function in insulin-resistant JCR:LA-cp rats: role of male and female sex.

    Science.gov (United States)

    O'Brien, S F; Russell, J C; Dolphin, P J; Davidge, S T

    2000-08-01

    Vascular wall function was assessed in obese insulin-resistant (cp/cp) and lean normal (+/?), male and female, JCR:LA-cp rats. Both male and female cp/cp rats showed enhanced maximum contractility in response to norepinephrine; impaired smooth muscle in response to sodium nitroprusside, a nitric oxide (NO) donor; and impaired relaxation in response to acetylcholine (ACh), compared with their lean counterparts. The abnormalities were similar in male and female cp/cp rats. The NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), inhibited ACh-mediated relaxation significantly in male rats, both cp/cp and +/?. The inhibition of ACh-mediated relaxation by L-NAME in +/? females was less, with no reduction in maximal relaxation, and was absent in cp/cp females. These effects suggest that the relative importance of NO in the endothelial modulation of smooth muscle contractility is greater in male rats. The results are consistent with a decreased role for endothelial NO in the cp/cp rats of both sexes and a reduction in NO-independent cholinergic relaxation in the male cp/cp rat. This NO-independent mechanism is not affected in the female cp/cp rats. The relatively small differences between males and females in smooth muscle cell and vascular function may contribute to sex-related differences in the atherogenesis, vasospasm, and ischemic damage associated with the obese insulin-resistant state.

  5. Effect of recombinant human growth hormone administration on body composition and vascular function and structure in old male Wistar rats.

    Science.gov (United States)

    Castillo, Carmen; Cruzado, Mar; Ariznavarreta, Carmen; Gil-Loyzaga, Pablo; Lahera, Vicente; Cachofeiro, Victoria; Tresguerres, Jesús A F

    2005-01-01

    The process of ageing affects negatively both cardiovascular system and body composition. On the other hand, the hormones of the somatotrophic axis, growth hormone (GH) and insulin-like growth factor-I (IGF-I), whose production is reduced by age, are involved in the regulation of the cardiovascular system. The aim of this study was to investigate the effect of GH on body composition, vascular function and structure in old male rats. Old (20 months) and adult (4 months) male Wistar rats were used. One group of old animals was treated with GH for 4 weeks. Periepididimary fat weight, Specific Gravity Index (SGI), dose responses to Acetylcholine (ACh), Isoproterenol (Iso), Phenylephrine (Phe) and ACh in the presence of NG-nitro-L: -arginine metylester (L-NAME; ACh + L-NAME), as well as vascular morphology in aortic rings, were studied. Old rats showed increased fat weight and decreased SGI as compared to adult animals. GH increased SGI and tended to reduce fat weight. Old rats showed an impairment in the vasodilator response to ACh and Iso; GH significantly improved the vasodilatation induced by Iso, whereas the response to ACh was not significantly enhanced by GH treatment. There were no significant differences between adult and old rats in the contractile response to Phe, and GH did not show any effect. Contraction induced by ACh + L-NAME was higher in old rats as compared to adults, and treatment with GH significantly reduced this response. Aortic media area was increased in old rats, and GH administration reduced this parameter. In conclusion, GH shows beneficial effects on body composition, as well as on vascular function and morphology in old male rats.

  6. SIFT: predicting amino acid changes that affect protein function

    OpenAIRE

    Ng, Pauline C.; Henikoff, Steven

    2003-01-01

    Single nucleotide polymorphism (SNP) studies and random mutagenesis projects identify amino acid substitutions in protein-coding regions. Each substitution has the potential to affect protein function. SIFT (Sorting Intolerant From Tolerant) is a program that predicts whether an amino acid substitution affects protein function so that users can prioritize substitutions for further study. We have shown that SIFT can distinguish between functionally neutral and deleterious amino acid changes in...

  7. Smooth Muscle Endothelin B Receptors Regulate Blood Pressure but Not Vascular Function or Neointimal Remodeling.

    Science.gov (United States)

    Miller, Eileen; Czopek, Alicja; Duthie, Karolina M; Kirkby, Nicholas S; van de Putte, Elisabeth E Fransen; Christen, Sibylle; Kimmitt, Robert A; Moorhouse, Rebecca; Castellan, Raphael F P; Kotelevtsev, Yuri V; Kuc, Rhoda E; Davenport, Anthony P; Dhaun, Neeraj; Webb, David J; Hadoke, Patrick W F

    2017-02-01

    The role of smooth muscle endothelinB (ETB) receptors in regulating vascular function, blood pressure (BP), and neointimal remodeling has not been established. Selective knockout mice were generated to address the hypothesis that loss of smooth muscle ETB receptors would reduce BP, alter vascular contractility, and inhibit neointimal remodeling. ETB receptors were selectively deleted from smooth muscle by crossing floxed ETB mice with those expressing cre-recombinase controlled by the transgelin promoter. Functional consequences of ETB deletion were assessed using myography. BP was measured by telemetry, and neointimal lesion formation induced by femoral artery injury. Lesion size and composition (day 28) were analyzed using optical projection tomography, histology, and immunohistochemistry. Selective deletion of ETB was confirmed by genotyping, autoradiography, polymerase chain reaction, and immunohistochemistry. ETB-mediated contraction was reduced in trachea, but abolished from mesenteric veins, of knockout mice. Induction of ETB-mediated contraction in mesenteric arteries was also abolished in these mice. Femoral artery function was unaltered, and baseline BP modestly elevated in smooth muscle ETB knockout compared with controls (+4.2±0.2 mm Hg; P<0.0001), but salt-induced and ETB blockade-mediated hypertension were unaltered. Circulating endothelin-1 was not altered in knockout mice. ETB-mediated contraction was not induced in femoral arteries by incubation in culture medium or lesion formation, and lesion size was not altered in smooth muscle ETB knockout mice. In the absence of other pathology, ETB receptors in vascular smooth muscle make a small but significant contribution to ETB-dependent regulation of BP. These ETB receptors have no effect on vascular contraction or neointimal remodeling.

  8. Single passive leg movement-induced hyperemia: a simple vascular function assessment without a chronotropic response.

    Science.gov (United States)

    Venturelli, Massimo; Layec, Gwenael; Trinity, Joel; Hart, Corey R; Broxterman, Ryan M; Richardson, Russell S

    2017-01-01

    Passive leg movement (PLM)-induced hyperemia is a novel approach to assess vascular function, with a potential clinical role. However, in some instances, the varying chronotropic response induced by PLM has been proposed to be a potentially confounding factor. Therefore, we simplified and modified the PLM model to require just a single PLM (sPLM), an approach that may evoke a peripheral hemodynamic response, allowing a vascular function assessment, but at the same time minimizing central responses. To both characterize and assess the utility of sPLM, in 12 healthy subjects, we measured heart rate (HR), stroke volume, cardiac output (CO), mean arterial pressure (MAP), leg blood flow (LBF), and calculated leg vascular conductance (LVC) during both standard PLM, consisting of passive knee flexion and extension performed at 1 Hz for 60 s, and sPLM, consisting of only a single passive knee flexion and extension over 1 s. During PLM, MAP transiently decreased (5 ± 1 mmHg), whereas both HR and CO increased from baseline (6.0 ± 1.1 beats/min, and 0.8 ± 0.01 l/min, respectively). Following sPLM, MAP fell similarly (5 ± 2 mmHg; P = 0.8), but neither HR nor CO responses were identifiable. The peak LBF and LVC response was similar for PLM (993 ± 189 ml/min; 11.9 ± 1.5 ml·min(-1)·mmHg(-1), respectively) and sPLM (878 ± 119 ml/min; 10.9 ± 1.6 ml·min(-1)·mmHg(-1), respectively). Thus sPLM represents a variant of the PLM approach to assess vascular function that is more easily performed and evokes a peripheral stimulus that induces a significant hyperemia, but does not generate a potentially confounding, chronotropic response, which may make sPLM more useful clinically.

  9. Effects of swimming training on blood pressure and vascular function in adults >50 years of age.

    Science.gov (United States)

    Nualnim, Nantinee; Parkhurst, Kristin; Dhindsa, Mandeep; Tarumi, Takashi; Vavrek, Jackie; Tanaka, Hirofumi

    2012-04-01

    Swimming is ideal for older adults because it includes minimum weight-bearing stress and decreased heat load. However, there is very little information available concerning the effects of regular swimming exercise on vascular risks. We determined if regular swimming exercise would decrease arterial blood pressure (BP) and improve vascular function. Forty-three otherwise healthy adults >50 years old (60 ± 2) with prehypertension or stage 1 hypertension and not on any medication were randomly assigned to 12 weeks of swimming exercise or attention time controls. Before the intervention period there were no significant differences in any of the variables between groups. Body mass, adiposity, and plasma concentrations of glucose and cholesterol did not change in either group throughout the intervention period. Casual systolic BP decreased significantly from 131 ± 3 to 122 ± 4 mm Hg in the swimming training group. Significant decreases in systolic BP were also observed in ambulatory (daytime) and central (carotid) BP measurements. Swimming exercise produced a 21% increase in carotid artery compliance (p improved after the swim training program (p improvements in vascular function in previously sedentary older adults.

  10. A review about biomarkers for the investigation of vascular function and impairment in diabetes mellitus.

    Science.gov (United States)

    Derosa, Giuseppe; Maffioli, Pamela

    2016-01-01

    The aim of this review was to analyze the main biomarkers of vascular function and impairment in patients with type 2 diabetes. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched. We concluded that proatherogenic adhesion molecules (soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and soluble E selectin) and inflammatory cytokines (high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α) were elevated in type 2 diabetes mellitus. Their increased expression and release contribute to the accelerated atherogenesis typical of these patients. For these reasons, the early identification of high levels of these biomarkers will help to establish new strategies to reduce cardiovascular complications.

  11. Segmental analysis of indocyanine green pharmacokinetics for the reliable diagnosis of functional vascular insufficiency

    Science.gov (United States)

    Kang, Yujung; Lee, Jungsul; An, Yuri; Jeon, Jongwook; Choi, Chulhee

    2011-03-01

    Accurate and reliable diagnosis of functional insufficiency of peripheral vasculature is essential since Raynaud phenomenon (RP), most common form of peripheral vascular insufficiency, is commonly associated with systemic vascular disorders. We have previously demonstrated that dynamic imaging of near-infrared fluorophore indocyanine green (ICG) can be a noninvasive and sensitive tool to measure tissue perfusion. In the present study, we demonstrated that combined analysis of multiple parameters, especially onset time and modified Tmax which means the time from onset of ICG fluorescence to Tmax, can be used as a reliable diagnostic tool for RP. To validate the method, we performed the conventional thermographic analysis combined with cold challenge and rewarming along with ICG dynamic imaging and segmental analysis. A case-control analysis demonstrated that segmental pattern of ICG dynamics in both hands was significantly different between normal and RP case, suggesting the possibility of clinical application of this novel method for the convenient and reliable diagnosis of RP.

  12. Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess.

    Science.gov (United States)

    Wyrwoll, Caitlin S; Noble, June; Thomson, Adrian; Tesic, Dijana; Miller, Mark R; Rog-Zielinska, Eva A; Moran, Carmel M; Seckl, Jonathan R; Chapman, Karen E; Holmes, Megan C

    2016-05-31

    Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a key role. We previously discovered that Hsd11b2(-/-) mice, lacking 11β-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2(+/+), Hsd11b2(+/-), and Hsd11b2(-/-) littermates from heterozygous (Hsd11b(+/-)) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2(-/-) fetuses did not undergo the normal gestational increase seen in Hsd11b2(+/+) littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11β-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2(-/-) fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2(-/-) fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2(-/-) fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction.

  13. Acute Effect of High-Intensity Eccentric Exercise on Vascular Endothelial Function in Young Men.

    Science.gov (United States)

    Choi, Youngju; Akazawa, Nobuhiko; Zempo-Miyaki, Asako; Ra, Song-Gyu; Shiraki, Hitoshi; Ajisaka, Ryuichi; Maeda, Seiji

    2016-08-01

    Choi, Y, Akazawa, N, Zempo-Miyaki, A, Ra, S-G, Shiraki, H, Ajisaka, R, and Maeda, S. Acute effect of high-intensity eccentric exercise on vascular endothelial function in young men. J Strength Cond Res 30(8): 2279-2285, 2016-Increased central arterial stiffness is as an independent risk factor for cardiovascular disease. Evidence regarding the effects of high-intensity resistance exercise on vascular endothelial function and central arterial stiffness is conflicting. The purpose of this study was to examine the effects of acute high-intensity eccentric exercise on vascular endothelial function and central arterial stiffness. We evaluated the acute changes in endothelium-dependent flow-mediated dilation (FMD), low-flow-mediated constriction (L-FMC), and arterial stiffness after high-intensity eccentric exercise. Seven healthy, sedentary men (age, 24 ± 1 year) performed maximal eccentric elbow flexor exercise using their nondominant arm. Before and 45 minutes after eccentric exercise, carotid arterial compliance and brachial artery FMD and L-FMC in the nonexercised arm were measured. Carotid arterial compliance was significantly decreased, and β-stiffness index significantly increased after eccentric exercise. Brachial FMD was significantly reduced after eccentric exercise, whereas there was no significant difference in brachial L-FMC before and after eccentric exercise. A positive correlation was detected between change in arterial compliance and change in FMD (r = 0.779; p ≤ 0.05), and a negative correlation was detected between change in β-stiffness index and change in FMD (r = -0.891; p eccentric exercise. In this study, acute high-intensity eccentric exercise increased central arterial stiffness; this increase was accompanied by a decrease in endothelial function caused by reduced endothelium-dependent vasodilation but not by a change in endothelium-dependent vasoconstriction.

  14. Experimental studies of mitochondrial function in CADASIL vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Viitanen, Matti [Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm (Sweden); Department of Geriatrics, Turku City Hospital and University of Turku, Turku (Finland); Sundström, Erik [Division of Neurodegeneration, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm (Sweden); Baumann, Marc [Protein Chemistry Unit, Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki (Finland); Poyhonen, Minna [Department of Clinical Genetics, Helsinki University Hospital, HUSLAB, Helsinki (Finland); Tikka, Saara [Protein Chemistry Unit, Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki (Finland); Behbahani, Homira, E-mail: homira.behbahani@ki.se [Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm (Sweden); Karolinska Institutet Alzheimer' s Disease Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm (Sweden)

    2013-02-01

    Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a familiar fatal progressive degenerative disorder characterized by cognitive decline, and recurrent stroke in young adults. Pathological features include a dramatic reduction of brain vascular smooth muscle cells and severe arteriopathy with the presence of granular osmophilic material in the arterial walls. Here we have investigated the cellular and mitochondrial function in vascular smooth muscle cell lines (VSMCs) established from CADASIL mutation carriers (R133C) and healthy controls. We found significantly lower proliferation rates in CADASIL VSMC as compared to VSMC from controls. Cultured CADASIL VSMCs were not more vulnerable than control cells to a number of toxic substances. Morphological studies showed reduced mitochondrial connectivity and increased number of mitochondria in CADASIL VSMCs. Transmission electron microscopy analysis demonstrated increased irregular and abnormal mitochondria in CADASIL VSMCs. Measurements of mitochondrial membrane potential (Δψ{sub m}) showed a lower percentage of fully functional mitochondria in CADASIL VSMCs. For a number of genes previously reported to be changed in CADASIL VSMCs, immunoblotting analysis demonstrated a significantly reduced SOD1 expression. These findings suggest that alteration of proliferation and mitochondrial function in CADASIL VSMCs might have an effect on vital cellular functions important for CADASIL pathology. -- Highlights: ► CADASIL is an inherited disease of cerebral vascular cells. ► Mitochondrial dysfunction has been implicated in the pathogenesis of CADASIL. ► Lower proliferation rates in CADASIL VSMC. ► Increased irregular and abnormal mitochondria and lower mitochondrial membrane potential in CADASIL VSMCs. ► Reduced mitochondrial connectivity and increased number of mitochondria in CADASIL VSMCs.

  15. Physical Activity and Vascular Dilation Function in Healthy Middle-aged Individuals

    Institute of Scientific and Technical Information of China (English)

    LIANG Qi; LIU Donghong; WANG Yuling; SUN Bing; LIN Fengqiao; GAN Hanjing; WU Guifu; WANG Lichun; MA Hong

    2009-01-01

    Objective: Vascular dilation dysfunction has been linked with risk of cardiovascular disease. This study was undertaken to investigate the relationship between physical activity and vascular dilation function in healthy middle-aged adults to help explaining the effect of physical activity on preventing cardiovascular disease. Method: We recruited 91 healthy middle-aged adults to complete a serf-report 7-day physical activity recall questionnaire and an exam of brachial artery flow-mediated dilation(FMD) and Nitroglycerin-mediated dilation (NMD) detected by ultrasound. The relationship between physical activity level (PAL) and FMD and NMD were explored. Result: Physical activity showed a significant and positive relationship with the brachial artery FMD, even after adjustment for possible confounding factors (r=0.363, P 0.05) and there was no significant difference among three groups. There was no positive relation between PAL and FMD in premenopausal females but in men and postmenopausal females. Although individuals of high PAL have the best FMD, the moderate PAL can also retard FMD decrease with ageing. Conclusion: Maintaining high physical activity level can enhance endothelial-dependent vascular dilation, and moderate or high physical activity level can prevent endothelial-dependent vaseular dilation declining with aging, which may contribute to decrease risk of cardiovascular disease in healthy middle-aged adults.

  16. Maintenance of vascular integrity by pericytes is essential for normal kidney function.

    Science.gov (United States)

    Lemos, Dario R; Marsh, Graham; Huang, Angela; Campanholle, Gabriela; Aburatani, Takahide; Dang, Lan; Gomez, Ivan; Fisher, Ken; Ligresti, Giovanni; Peti-Peterdi, Janos; Duffield, Jeremy S

    2016-12-01

    Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature that have been shown to participate in tissue regeneration. Here, we tested the hypothesis that kidney pericytes, derived from FoxD1(+) mesodermal progenitors during embryogenesis, are necessary for postnatal kidney homeostasis. Diphtheria toxin delivery to FoxD1Cre::RsDTR transgenic mice resulted in selective ablation of >90% of kidney pericytes but not other cell lineages. Abrupt increases in plasma creatinine, blood urea nitrogen, and albuminuria within 96 h indicated acute kidney injury in pericyte-ablated mice. Loss of pericytes led to a rapid accumulation of neutral lipid vacuoles, swollen mitochondria, and apoptosis in tubular epithelial cells. Pericyte ablation led to endothelial cell swelling, reduced expression of vascular homeostasis markers, and peritubular capillary loss. Despite the observed injury, no signs of the acute inflammatory response were observed. Pathway enrichment analysis of genes expressed in kidney pericytes in vivo identified basement membrane proteins, angiogenic factors, and factors regulating vascular tone as major regulators of vascular function. Using novel microphysiological devices, we recapitulated human kidney peritubular capillaries coated with pericytes and showed that pericytes regulate permeability, basement membrane deposition, and microvascular tone. These findings suggest that through the active support of the microvasculature, pericytes are essential to adult kidney homeostasis.

  17. Exercise training improves vascular function in adolescents with type 2 diabetes.

    Science.gov (United States)

    Naylor, Louise H; Davis, Elizabeth A; Kalic, Rachelle J; Paramalingam, Niru; Abraham, Mary B; Jones, Timothy W; Green, Daniel J

    2016-02-01

    The impact of exercise training on vascular health in adolescents with type 2 diabetes has not been previously studied. We hypothesized that exercise training would improve micro- and macrovascular health in adolescents with type 2 diabetes. Thirteen adolescents (13-21 years, 10F) with type 2 diabetes were recruited from Princess Margaret Hospital. Participants were randomized to receive either an exercise program along with standard clinical care (n = 8) or standard care alone (n = 5). Those in the intervention group received 12 weeks of gym-based, personalized, and supervised exercise training. Those in the control group were instructed to maintain usual activity levels. Assessments were conducted at baseline and following week 12. The exercise group was also studied 12 weeks following the conclusion of their program. Assessments consisted of conduit artery endothelial function (flow-mediated dilation, FMD) and microvascular function (cutaneous laser Doppler). Secondary outcomes included body composition (dual-energy X-ray absorptiometry, DXA), glycemic control (whole body insulin sensitivity, M) assessed using the euglycemic-hyperinsulinemic clamp protocol, cardiorespiratory fitness (V˙O2peak), and muscular strength (1RM). Exercise training increased FMD (P improvements in vascular function were reversed. This study indicates that exercise training can improve both conduit and microvascular endothelial function and health, independent of changes in insulin sensitivity in adolescents with type 2 diabetes.

  18. Comparative assessment of vascular function in autoimmune rheumatic diseases: considerations of prevention and treatment.

    Science.gov (United States)

    Soltész, Pál; Kerekes, György; Dér, Henriett; Szücs, Gabriella; Szántó, Sándor; Kiss, Emese; Bodolay, Edit; Zeher, Margit; Timár, Orsolya; Szodoray, Péter; Szegedi, Gyula; Szekanecz, Zoltán

    2011-05-01

    Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to increased cardio- and cerebrovascular disease risk. Traditional risk factors, as well as the role of systemic inflammation including cytokines, chemokines, proteases, autoantibodies, adhesion receptors and others have been implicated in the development of these vascular pathologies. The characteristics of vasculopathies may significantly differ depending on the underlying disease. While classical accelerated atherosclerosis has been associated with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or spondyloarthropathies (SpA), obliterative vasculopathy may rather be characteristic for systemic sclerosis (SSc) or mixed connective tissue disease (MCTD). Antiphospholipid antibodies have been implicated in vasculopathies underlying SLE, antiphospholipid syndrome (APS), RA and MCTD. There is also heterogeneity with respect to inflammatory risk factors. Cytokines, such as tumor necrosis factor-α (TNF-α) or interleukin 6 (IL-6) and immune complexes are primarily involved in arthritides, such as RA, SpA, as well as in SLE. On the other hand, autoantibodies including anti-oxLDL anti-cardiolipin and anti-β2GPI are rather involved in SLE- and APS-associated vasculopathies. Regarding the non-invasive assessment of vascular function, endothelial dysfunction, overt atherosclerosis and vascular stiffness may be indicated by brachial artery flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and aortic pulse-wave velocity (PWV), respectively. These abnormalities have been described in most inflammatory rheumatic diseases. While ccIMT and stiffness are relatively stable, FMD may be influenced by many confounding factors. In addition to traditional vasculoprotection, immunosuppressive agents including corticosteroids, traditional and biologic DMARDs may have significant vascular and metabolic

  19. Diverse Functional Roles of Monosaccharide Transporters and their Homologs in Vascular Plants: A Physiological Perspective

    Institute of Scientific and Technical Information of China (English)

    Thomas L. Slewinski

    2011-01-01

    Vascular plants contain two gene families that encode monosaccharide transporter proteins. The classical monosaccharide transporter(-like)gene superfamily is large and functionally diverse, while the recently identified SWEET transporter family is smaller and, thus far, only found to transport glucose. These transporters play essential roles at many levels, ranging from organelles to the whole plant. Many family members are essential for cellular homeostasis and re-productive success. Although most transporters do not directly participate in long-distance transport, their indirect roles greatly impact carbon allocation and transport flux to the heterotrophic tissues of the plant. Functional characterization of some members from both gene families has revealed their diverse roles in carbohydrate partitioning, phloem function,resource allocation, plant defense, and sugar signaling. This review highlights the broad impacts and implications of monosaccharide transport by describing some of the functional roles of the monosaccharide transporter(-like)superfamily and the SWEET transporter family.

  20. Affect integration and reflective function: clarification of central conceptual issues.

    Science.gov (United States)

    Solbakken, Ole André; Hansen, Roger Sandvik; Monsen, Jon Trygve

    2011-07-01

    The importance of affect regulation, modulation or integration for higher-order reflection and adequate functioning is increasingly emphasized across different therapeutic approaches and theories of change. These processes are probably central to any psychotherapeutic endeavor, whether explicitly conceptualized or not, and in recent years a number of therapeutic approaches have been developed that explicitly target them as a primary area of change. However, there still is important lack of clarity in the field regarding the understanding and operationalization of affect integration, particularly when it comes to specifying underlying mechanisms, the significance of different affect states, and the establishment of operational criteria for measurement. The conceptual relationship between affect integration and reflective function thus remains ambiguous. The present article addresses these topics, indicating ways in which a more complex and exhaustive understanding of integration of affect, cognition and behavior can be attained.

  1. Identification of Chemical Vascular Disruptors During Development Using An Integrative Predictive Toxicity Model and Zebrafish and in Vitro Functional Angiogenesis Assays.

    Science.gov (United States)

    Identification of chemical vascular disruptors during development using an integrative predictive toxicity model and zebrafish and in vitro functional angiogenesis assays Chemically-induced vascular toxicity during embryonic development can result in a wide range of adverse pre...

  2. Effect of Ginkgo Leaf Extract on Vascular Endothelial Function in Patients with Early Stage Diabetic Nephropathy

    Institute of Scientific and Technical Information of China (English)

    LI Xu-sheng; ZHENG Wei-ying; LOU Shi-xian; LU Xiao-wen; YE Shang-he

    2009-01-01

    Objective: To explore the effect of ginkgo leaf extract (GLE) on vascular endothelial function (VEF) in patients with early stage diabetic nephropathy (DN). Methods: Sixty-four patients were randomized equally by a randomzing digital table into two groups, the treated group and the control group. They were all treated for 8 weeks with conventional therapy for diabetes, but GLE tablets were given to the treated group additionally. Changes in VEF were estimated before and after treatment by ultrasonic examination of the brachial artery. In the meantime, changes in plasma levels of the von Willebrand factor (vWF), nitric oxide (NO) and endothelin-1 (ET-1) were observed as well. Results: The brachial arterial endothelium dependent dilating function in the treated group increased from 4.91±2.31% before treatment to 6.78±3.89% after treatment (P0.05). Conclusion: GLE could decrease the plasma level of vWF, raise the plasma NO level and improve the endothelium dependent vascular dilating function in DN patients.

  3. SIFT: Predicting amino acid changes that affect protein function.

    Science.gov (United States)

    Ng, Pauline C; Henikoff, Steven

    2003-07-01

    Single nucleotide polymorphism (SNP) studies and random mutagenesis projects identify amino acid substitutions in protein-coding regions. Each substitution has the potential to affect protein function. SIFT (Sorting Intolerant From Tolerant) is a program that predicts whether an amino acid substitution affects protein function so that users can prioritize substitutions for further study. We have shown that SIFT can distinguish between functionally neutral and deleterious amino acid changes in mutagenesis studies and on human polymorphisms. SIFT is available at http://blocks.fhcrc.org/sift/SIFT.html.

  4. Affecting of aquatic vascular plant Lemna minor by cisplatin revealed by voltammetry.

    Science.gov (United States)

    Supalkova, Veronika; Beklova, Miroslava; Baloun, Jiri; Singer, Christoph; Sures, Bernd; Adam, Vojtech; Huska, Dalibor; Pikula, Jiri; Rauscherova, Libuse; Havel, Ladislav; Zehnalek, Josef; Kizek, Rene

    2008-02-01

    Within the context of application of platinum derivates based effective cytostatics, we can suppose that these risk metals can get into aquatic ecosystems where they can show biologic availability for food chain. In the present work we report on investigation of affecting of duckweed (Lemna minor) by various doses of cisplatin (0, 5, 10, 20, 40, 80 and 160 microM) for 4 days. The toxic influence of cisplatin was evaluated on the basis of growth inhibition expressed as number of leaves, growth rate, and total amount of biomass. The result value of 96hEC50, calculated from growth inhibition with comparison of growth rates, was 6.93 microM. Moreover we aimed on determination of cisplatin content using differential pulse voltammetry. The highest content of cisplatin (320 ng g(-1) of fresh weight) was determined in plants treated by 80 microM at the second day of treatment. Plants protect themselves against heavy metals by means of synthesis of cysteine-rich peptides such as glutathione and phytochelatins. Thus thiol determination in the treated plants by means of Brdicka reaction followed. The marked increase in thiol concentration detected is associated with defence reaction of the plant against stress caused by cisplatin.

  5. Hatha yoga and vascular function: results from cross-sectional and interventional studies.

    Science.gov (United States)

    Hunter, Stacy D; Tarumi, Takashi; Dhindsa, Mandeep S; Nualnim, Nantinee; Tanaka, Hirofumi

    2013-07-01

    The aim of this study was to determine the effect of hatha yoga on arterial elasticity and endothelial function. First, a cross-sectional study was performed to determine whether yoga practitioners would demonstrate greater arterial compliance and endothelium-dependent vasodilation than their sedentary peers. Second, an intervention study involving 13 sedentary middle-aged and older adults (51 ± 7 years) was performed to determine whether 12 weeks of hatha yoga would elicit increases in arterial compliance and endothelial function. In the cross-sectional study involving a total of 34 subjects, there were no group differences in body fatness, blood lipid and lipoprotein concentrations, carotid artery compliance or brachial artery flow-mediated dilation (FMD). Hemoglobin A1c was lower in yoga practitioners than in sedentary adults (P hatha yoga is not associated with improvements in vascular functions.

  6. Arterial structure and function in vascular ageing: are you as old as your arteries?

    Science.gov (United States)

    Thijssen, Dick H J; Carter, Sophie E; Green, Daniel J

    2016-04-15

    Advancing age may be the most potent independent predictor of future cardiovascular events, a relationship that is not fully explained by time-related changes in traditional cardiovascular risk factors. Since some arteries exhibit differential susceptibility to atherosclerosis, generalisations regarding the impact of ageing in humans may be overly simplistic, whereas in vivo assessment of arterial function and health provide direct insight. Coronary and peripheral (conduit, resistance and skin) arteries demonstrate a gradual, age-related impairment in vascular function that is likely to be related to a reduction in endothelium-derived nitric oxide bioavailability and/or increased production of vasoconstrictors (e.g. endothelin-1). Increased exposure and impaired ability for defence mechanisms to resist oxidative stress and inflammation, but also cellular senescence processes, may contribute to age-related changes in vascular function and health. Arteries also undergo structural changes as they age. Gradual thickening of the arterial wall, changes in wall content (i.e. less elastin, advanced glycation end-products) and increase in conduit artery diameter are observed with older age and occur similarly in central and peripheral arteries. These changes in structure have important interactive effects on artery function, with increases in small and large arterial stiffness representing a characteristic change with older age. Importantly, direct measures of arterial function and structure predict future cardiovascular events, independent of age or other cardiovascular risk factors. Taken together, and given the differential susceptibility of arteries to atherosclerosis in humans, direct measurement of arterial function and health may help to distinguish between biological and chronological age-related change in arterial health in humans.

  7. Effect of Carvedilol on the Coronary Vascular Endothelial Function after Percutaneous Transluminal Coronary Angioplasty

    Institute of Scientific and Technical Information of China (English)

    苏显明; 马奕; 崔长琮

    2003-01-01

    Objectives To understand the effect of carvedilol on the coronary vascular endothelial function of the patients with coronary heart disease after percutaneous transluminal coronary angioplasty (PTCA). Methods 51cases, having one or more than two branches narrow ( ≥ 70% ) , were diagnosed by coronary angiography. These patients were divided randomly into carvedilol group (n = 28 ) and control group (n = 23) who did not take carvedilol.Endothelin (ET) and nitro dioxide (NO) levels of peripheral blood were measured before and after PTCA,before and after two weeks by taking carvedilol. Results Compared with the ET and NO levels before PTCA, ET were markedly increased and NO were decreased after PTCA (p < 0.05); compared with the ET and NO levels before taking carvedilol, ET were decreased and NO were increased after two week (p <0.05) , but the ET and NO levels of the control group did not change in the period of two weeks observation (p > 0.05). Conclusions Carvedilol may improve the coronary vascular endothelial function after PTCA.

  8. Molecular Mechanisms for Exercise Training-Induced Changes in Vascular Structure and Function: Skeletal Muscle, Cardiac Muscle, and the Brain.

    Science.gov (United States)

    Olver, T Dylan; Ferguson, Brian S; Laughlin, M Harold

    2015-01-01

    Compared with resting conditions, during incremental exercise, cardiac output in humans is elevated from ~5 to 25 L min(-1). In conjunction with this increase, the proportion of cardiac output directed toward skeletal muscle increases from ~20% to 85%, while blood flow to cardiac muscle increases 500% and blood flow to specific brain structures increases nearly 200%. Based on existing evidence, researchers believe that blood flow in these tissues is matched to the increases in metabolic rate during exercise. This phenomenon, the matching of blood flow to metabolic requirement, is often referred to as functional hyperemia. This chapter summarizes mechanical and metabolic factors that regulate functional hyperemia as well as other exercise-induced signals, which are also potent stimuli for chronic adaptations in vascular biology. Repeated exposure to exercise-induced increases in shear stress and the induction of angiogenic factors alter vascular cell gene expression and mediate changes in vascular volume and blood flow control. The magnitude and regulation of this coordinated response appear to be tissue specific and coupled to other factors such as hypertrophy and hyperplasia. The cumulative effects of these adaptations contribute to increased exercise capacity, reduced relative challenge of a given submaximal exercise bout and ameliorated vascular outcomes in patient populations with pathological conditions. In the subsequent discussion, this chapter explores exercise as a regulator of vascular biology and summarizes the molecular mechanisms responsible for exercise training-induced changes in vascular structure and function in skeletal and cardiac muscle as well as the brain.

  9. Morphological, functional and metabolic imaging biomarkers: assessment of vascular-disrupting effect on rodent liver tumours

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Huaijun; Li, Junjie; Keyzer, Frederik De; Yu, Jie; Feng, Yuanbo; Marchal, Guy; Ni, Yicheng [University Hospitals, University of Leuven, Department of Radiology, Leuven (Belgium); Chen, Feng [University Hospitals, University of Leuven, Department of Radiology, Leuven (Belgium); Southeast University, Department of Radiology, Zhongda Hospital, Nanjing (China); Nuyts, Johan [University Hospitals, University of Leuven, Department of Nuclear Medicine, Leuven (Belgium)

    2010-08-15

    To evaluate effects of a vascular-disrupting agent on rodent tumour models. Twenty rats with liver rhabdomyosarcomas received ZD6126 intravenously at 20 mg/kg, and 10 vehicle-treated rats were used as controls. Multiple sequences, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI) with the microvascular permeability constant (K), were acquired at baseline, 1 h, 24 h and 48 h post-treatment by using 1.5-T MRI. [{sup 18}F]fluorodeoxyglucose micro-positron emission tomography ({sup 18}F-FDG {mu}PET) was acquired pre- and post-treatment. The imaging biomarkers including tumour volume, enhancement ratio, necrosis ratio, apparent diffusion coefficient (ADC) and K from MRI, and maximal standardised uptake value (SUV{sub max}) from FDG {mu}PET were quantified and correlated with postmortem microangiography and histopathology. In the ZD6126-treated group, tumours grew slower with higher necrosis ratio at 48 h (P < 0.05), corresponding well to histopathology; tumour K decreased from 1 h until 24 h, and partially recovered at 48 h (P < 0.05), parallel to the evolving enhancement ratios (P < 0.05); ADCs varied with tumour viability and perfusion; and SUV{sub max} dropped at 24 h (P < 0.01). Relative K of tumour versus liver at 48 h correlated with relative vascular density on microangiography (r = 0.93, P < 0.05). The imaging biomarkers allowed morphological, functional and metabolic quantifications of vascular shutdown, necrosis formation and tumour relapse shortly after treatment. A single dose of ZD6126 significantly diminished tumour blood supply and growth until 48 h post-treatment. (orig.)

  10. Functional Vascular Study in Hypertensive Subjects with Type 2 Diabetes Using Losartan or Amlodipine

    Directory of Open Access Journals (Sweden)

    Cesar Romaro Pozzobon

    2014-07-01

    Full Text Available Background: Antihypertensive drugs are used to control blood pressure (BP and reduce macro- and microvascular complications in hypertensive patients with diabetes. Objectives: The present study aimed to compare the functional vascular changes in hypertensive patients with type 2 diabetes mellitus after 6 weeks of treatment with amlodipine or losartan. Methods: Patients with a previous diagnosis of hypertension and type 2 diabetes mellitus were randomly divided into 2 groups and evaluated after 6 weeks of treatment with amlodipine (5 mg/day or losartan (100 mg/day. Patient evaluation included BP measurement, ambulatory BP monitoring, and assessment of vascular parameters using applanation tonometry, pulse wave velocity (PWV, and flow-mediated dilation (FMD of the brachial artery. Results: A total of 42 patients were evaluated (21 in each group, with a predominance of women (71% in both groups. The mean age of the patients in both groups was similar (amlodipine group: 54.9 ± 4.5 years; losartan group: 54.0 ± 6.9 years, with no significant difference in the mean BP [amlodipine group: 145 ± 14 mmHg (systolic and 84 ± 8 mmHg (diastolic; losartan group: 153 ± 19 mmHg (systolic and 90 ± 9 mmHg (diastolic]. The augmentation index (30% ± 9% and 36% ± 8%, p = 0.025 and augmentation pressure (16 ± 6 mmHg and 20 ± 8 mmHg, p = 0.045 were lower in the amlodipine group when compared with the losartan group. PWV and FMD were similar in both groups. Conclusions: Hypertensive patients with type 2 diabetes mellitus treated with amlodipine exhibited an improved pattern of pulse wave reflection in comparison with those treated with losartan. However, the use of losartan may be associated with independent vascular reactivity to the pressor effect.

  11. Hypotension Due to Kir6.1 Gain‐of‐Function in Vascular Smooth Muscle

    Science.gov (United States)

    Li, Anlong; Knutsen, Russell H.; Zhang, Haixia; Osei‐Owusu, Patrick; Moreno‐Dominguez, Alex; Harter, Theresa M.; Uchida, Keita; Remedi, Maria S.; Dietrich, Hans H.; Bernal‐Mizrachi, Carlos; Blumer, Kendall J.; Mecham, Robert P.; Koster, Joseph C.; Nichols, Colin G.

    2013-01-01

    Background KATP channels, assembled from pore‐forming (Kir6.1 or Kir6.2) and regulatory (SUR1 or SUR2) subunits, link metabolism to excitability. Loss of Kir6.2 results in hypoglycemia and hyperinsulinemia, whereas loss of Kir6.1 causes Prinzmetal angina–like symptoms in mice. Conversely, overactivity of Kir6.2 induces neonatal diabetes in mice and humans, but consequences of Kir6.1 overactivity are unknown. Methods and Results We generated transgenic mice expressing wild‐type (WT), ATP‐insensitive Kir6.1 [Gly343Asp] (GD), and ATP‐insensitive Kir6.1 [Gly343Asp,Gln53Arg] (GD‐QR) subunits, under Cre‐recombinase control. Expression was induced in smooth muscle cells by crossing with smooth muscle myosin heavy chain promoter–driven tamoxifen‐inducible Cre‐recombinase (SMMHC‐Cre‐ER) mice. Three weeks after tamoxifen induction, we assessed blood pressure in anesthetized and conscious animals, as well as contractility of mesenteric artery smooth muscle and KATP currents in isolated mesenteric artery myocytes. Both systolic and diastolic blood pressures were significantly reduced in GD and GD‐QR mice but normal in mice expressing the WT transgene and elevated in Kir6.1 knockout mice as well as in mice expressing dominant‐negative Kir6.1 [AAA] in smooth muscle. Contractile response of isolated GD‐QR mesenteric arteries was blunted relative to WT controls, but nitroprusside relaxation was unaffected. Basal KATP conductance and pinacidil‐activated conductance were elevated in GD but not in WT myocytes. Conclusions KATP overactivity in vascular muscle can lead directly to reduced vascular contractility and lower blood pressure. We predict that gain of vascular KATP function in humans would lead to a chronic vasodilatory phenotype, as indeed has recently been demonstrated in Cantu syndrome. PMID:23974906

  12. Functional analysis of zebrafish microfibril-associated glycoprotein-1 (Magp1) in vivo reveals roles for microfibrils in vascular development and function.

    Science.gov (United States)

    Chen, Eleanor; Larson, Jon D; Ekker, Stephen C

    2006-06-01

    Mutations in fibrillin-1 (FBN1) result in Marfan syndrome, demonstrating a critical requirement for microfibrils in vessel structure and function. However, the identity and function of many microfibril-associated molecules essential for vascular development and function have yet to be characterized. In our morpholino-based screen for members of the secretome required for vascular development, we identified a key player in microfibril formation in zebrafish embryogenesis. Microfibril-associated glycoprotein-1 (MAGP1) is a conserved protein found in mammalian and zebrafish microfibrils. Expression of magp1 mRNA is detected in microfibril-producing cells. Analysis of a functional Magp1-mRFP fusion protein reveals localization along the midline and in the vasculature during embryogenesis. Underexpression and overexpression analyses demonstrate that specific Magp1 protein levels are critical for vascular development. Integrin function is compromised in magp1 morphant embryos, suggesting that reduced integrin-matrix interaction is the main mechanism for the vascular defects in magp1 morphants. We further show that Magp1 and fibrillin-1 interact in vivo. This study implicates MAGP1 as a key player in microfibril formation and integrity during development. The essential role for MAGP1 in vascular morphogenesis and function also supports a wide range of clinical applications, including therapeutic targets in vascular disease and cardiovascular tissue engineering.

  13. Functions of Müller cell-derived vascular endothelial growthfactor in diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Müller cells are macroglia and play many essentialroles as supporting cells in the retina. To respond topathological changes in diabetic retinopathy (DR), amajor complication in the eye of diabetic patients,retinal Müller glia produce a high level of vascularendothelial growth factor (VEGF or VEGF-A). As VEGFis expressed by multiple retinal cell-types and Müllerglia comprise only a small portion of cells in the retina,it has been a great challenge to reveal the function ofVEGF or other globally expressed proteins produced byMüller cells. With the development of conditional genetargeting tools, it is now possible to dissect the functionof Müller cell-derived VEGF in vivo . By using conditionalgene targeting approach, we demonstrate that Müllerglia are a major source of retinal VEGF in diabetic miceand Müller cell-derived VEGF plays a significant role inthe alteration of protein expression and peroxynitration,which leads to retinal inflammation, neovascularization,vascular leakage, and vascular lesion, key pathologicalchanges in DR. Therefore, Müller glia are a potentialcellular target for the treatment of DR, a leading causeof blindness.

  14. White matter hyperintensities, executive function and global cognitive performance in vascular mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Felipe Kenji Sudo

    2013-07-01

    Full Text Available Vascular mild cognitive impairment (VaMCI represents an early symptomatic stage of vascular cognitive impairment and might be associated to fronto-executive dysfunction. Methods Twenty-six individuals (age: 73.11±7.90 years; 65.4% female; schooling: 9.84±3.61 years were selected through neuropsychological assessment and neuroimaging. Clinical and neuroimaging data of VaMCI individuals (n=15 were compared to normal controls (NC, n=11 and correlated with Fazekas scale. Results VaMCI performed significantly worse than NC in Trail-Making Test (TMT B, errors in TMT B, difference TMT B-A and Cambridge Cognitive Examination (CAMCOG final scores. Correlations were found among scores in modified Fazekas scale and performances in TMT B (time to complete and errors, difference TMT B-A and CAMCOG total score. Conclusion Extension of white matter hyperintensities might be correlated to poorer global cognition and impairments in a set of fronto-executive functions, such as cognitive speed, set shifting and inhibitory control in VaMCI.

  15. Short-term exposure to air pollution and digital vascular function.

    Science.gov (United States)

    Ljungman, Petter L; Wilker, Elissa H; Rice, Mary B; Schwartz, Joel; Gold, Diane R; Koutrakis, Petros; Vita, Joseph A; Mitchell, Gary F; Vasan, Ramachandran S; Benjamin, Emelia J; Mittleman, Murray A; Hamburg, Naomi M

    2014-09-01

    We investigated associations between ambient air pollution and microvessel function measured by peripheral arterial tonometry between 2003 and 2008 in the Framingham Heart Study Offspring and Third Generation Cohorts. We measured particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), black carbon, sulfates, particle number, nitrogen oxides, and ozone by using fixed monitors, and we determined moving averages for 1-7 days preceding vascular testing. We examined associations between these exposures and hyperemic response to ischemia and baseline pulse amplitude, a measure of arterial tone (n = 2,369). Higher short-term exposure to air pollutants, including PM2.5, black carbon, and particle number was associated with higher baseline pulse amplitude. For example, higher 3-day average PM2.5 exposure was associated with 6.3% higher baseline pulse amplitude (95% confidence interval: 2.0, 10.9). However, there were no consistent associations between the air pollution exposures assessed and hyperemic response. Our findings in a community-based sample exposed to relatively low pollution levels suggest that short-term exposure to ambient particulate pollution is not associated with vasodilator response, but that particulate air pollution is associated with baseline pulse amplitude, suggesting potentially adverse alterations in baseline vascular tone or compliance.

  16. Function if Cooperative Learning in Developing Positive Affect

    Institute of Scientific and Technical Information of China (English)

    佟玉平

    2008-01-01

    This paper focus on the function of cooperative learning in developing positive affect, Including reducing anxiety, increasing motivation, facilitating the development of positive attitudes toward learning and language learning, promoting serf- esteem, as well as supporting different learning styles and encouraging perseverance in the difficult and confusing process of learning a foreign language.

  17. Effect of Danshen injection on the vascular endothelial function and renal function in patients with pregnancy induced hypertension syndrome

    Institute of Scientific and Technical Information of China (English)

    Jun-Qing Zhang; Wei Gao

    2016-01-01

    Objective:To explore the effect of Danshen injection on the vascular endothelial function and renal function in patients with pregnancy induced hypertension syndrome (PIH). Methods:A total of 100 patients with PIH who were admitted in our hospital from May, 2015 to May, 2016 were included in the study and randomized into the observation group and the control group. The patients in the control group were given blood pressure reduction, diuresis, spasmolysis, sedation, magnesium sulfate, and comprehensive nursing intervention. On this basis, the patients in the observation group were given additional Danshen injection (20 mL) + 5% glucose (250 mL), ivdrip, 1 time/d. After 10 d treatment, the efficacy was evaluated. The peripheral venous blood before and after treatment in the two groups was collected. The radioimmunoassay was used to detect ET-1. ELISA was used to detect Hcy. The immunoturbidimetry was used to detect vWF. The radioimmunoassay was used to detect BUN, Scr, UA, andβ2-MG. The standard sphygmomanometer was used to monitor the blood pressure and MAP was calculated. The biuret colorimetry was used to determine 24 h Upro. Results:The reduced degree of ET-1, Hcy, and vWF after treatment in the observation group was significantly superior to that in the control group. The reduced degree of BUN, Scr, UA, andβ2-MG after treatment in the observation group was significantly superior to that in the control group. The reduced degree of MPA and 24 h Upro after treatment in the observation group was significantly superior to that in the control group.Conclusions:Routine treatments, comprehensive nursing intervention, and Danshen injection in the treatment of PIH can effectively improve the vascular endothelial function and renal function in order to reduce the blood pressure and alleviate the urine protein.

  18. Vascular Function and Regulation of Blood Flow in Resting and Contracting Skeletal Muscle

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin

    in the regulation of exercise hyperemia. Furthermore, blood flow to contracting leg skeletal muscles is reduced both in essential hypertension and with aging. The potential difference in vasoactive system(s) responsible for the reduction in blood flow in the two conditions is in agreement with the suggestion......The precise matching of blood flow, oxygen delivery and metabolism is essential as it ensures that any increase in muscle work is precisely matched by increases in oxygen delivery. Therefore, understanding the control mechanisms of skeletal muscle blood flow regulation is of great biological...... importance. The present work provides new insight in to vasodilator interactions important for exercise hyperemia and sheds light on mechanisms important for vascular function and regulation of skeletal muscle blood flow in essential hypertension (high blood pressure) and aging and identifies mechanisms...

  19. [Monitoring by non-flowmeter vascular function tests following lumbar sympathectomy].

    Science.gov (United States)

    Becker, F; Davinroy, M

    1985-01-01

    Postoperative follow up examinations were conducted using vascular functional explorations (V.F.E.) including thermometry, Doppler, irrigraphy, digital plethysmography and tread mill. Immediate and long-term effects of lumbar sympathectomy have to be distinguished: the majority of hemodynamic variations noted are not due exclusively to lumbar sympathectomy, except for the iatrogenic development of vasomotor inertia (R.H.T. indifferent or negative) and perhaps values with time of the digital flow curve. Results of V.F.E. after lumbar sympathectomy are discussed in relation to three modalities and taking into account the efficacy and extent of the sympathetic chain resection. The question is raised as to the usefulness of lumbar sympathectomy when the pretreatment V.F.E. findings show hemodynamic elements of the type that would be expected after lumbar sympathectomy.

  20. Acute exercise improves endothelial function despite increasing vascular resistance during stress in smokers and nonsmokers.

    Science.gov (United States)

    Rooks, Cherie R; McCully, Kevin K; Dishman, Rod K

    2011-09-01

    The present study examined the effect of acute exercise on flow mediated dilation (FMD) and reactivity to neurovascular challenges among female smokers and nonsmokers. FMD was determined by arterial diameter, velocity, and blood flow measured by Doppler ultrasonography after forearm occlusion. Those measures and blood pressure and heart rate were also assessed in response to forehead cold and the Stroop Color-Word Conflict Test (CWT) before and after 30 min of rest or an acute bout of cycling exercise (∼50% VO₂ peak). Baseline FMD and stress responses were not different between smokers and nonsmokers. Compared to passive rest, exercise increased FMD and decreased arterial velocity and blood flow responses during the Stroop CWT and forehead cold in both groups. Overall, acute exercise improved endothelial function among smokers and nonsmokers despite increasing vascular resistance and reducing limb blood flow during neurovascular stress.

  1. Effects of Salvia miltiorrhiza on Hemorheology and vascular endothelial function in patients with unstable angina pectoris

    Institute of Scientific and Technical Information of China (English)

    Shi-Lian Chen; Sheng-Bing Huang

    2016-01-01

    Objective:To investigate the effect of Salvia miltiorrhiza (SM) on vascular endothelial function and hemorheology in patients with unstable angina pectoris (UAP).Methods: A total of 60 cases of UAP patients from October 2014 to October 2015 as the research object, randomly divided into treatment group and control group; the two groups were treated with conventional bed rest, ECG monitoring, oxygen inhalation, application of nitroglycerin, beta blockers, aspirin and antiplatelet, statin therapy, the treatment group based on the use of salvianolate 200 mg+5% glucose 250 mL (neutralization amount of 0.9% sodium chloride was used in patients with diabetes or glucose insulin) intravenous drip, 1 times/d, two groups were treated for 2 weeks; the two groups before and after treatment and take venous blood in the morning fasting peripheral blood viscosity, plasma viscosity, measured by automatic blood rheometer (low and middle shear and high shear rate), hematocrit and erythrocyte aggregation index, serum endothelin (ET) and nitric oxide (NO) level was measured by nitrate reductase Set.Results:after the treatment, the treatment group, the plasma viscosity, whole blood viscosity (low shear, cut and high shear rate), red blood cell hematocrit and red blood cell aggregation index decreased than the control group, there is statistical significance; after treatment, in treatment group, the serum NO level, et reduce degree is significantly better than the contrast group, there is statistical significance.Conclusion: Salvia miltiorrhiza can effectively improve blood rheology, improve microcirculation, regulate vascular endothelial function, effectively reduce the risk of cardiovascular events in UAP patients, it is worthy of clinical application.

  2. Effects of black raspberry on lipid profiles and vascular endothelial function in patients with metabolic syndrome.

    Science.gov (United States)

    Jeong, Han Saem; Hong, Soon Jun; Lee, Tae-Bum; Kwon, Ji-Wung; Jeong, Jong Tae; Joo, Hyung Joon; Park, Jae Hyoung; Ahn, Chul-Min; Yu, Cheol Woong; Lim, Do-Sun

    2014-10-01

    Black raspberry (Rubus occidentalis) has been known for its anti-inflammatory and anti-oxidant effects. However, short-term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12-week follow-up. Lipid profiles, brachial artery flow-mediated dilatation (baFMD), and inflammatory cytokines such as IL-6, TNF-α, C-reactive protein, adiponectin, sICAM-1, and sVCAM-1 were measured at the baseline and at the 12-week follow-up. Decreases from the baseline in the total cholesterol level (-22.8 ± 30.4 mg/dL vs. -1.9 ± 31.8 mg/dL, p raspberry than in the placebo group. Increases in baFMD at the 12-week follow-up were significantly greater in the group with black raspberry than in the placebo group (0.33 ± 0.44 mm vs. 0.10 ± 0.35 mm, p raspberry. The use of black raspberry significantly decreased serum total cholesterol level and inflammatory cytokines, thereby improving vascular endothelial function in patients with metabolic syndrome during the 12-week follow-up.

  3. Coffee polyphenol consumption improves postprandial hyperglycemia associated with impaired vascular endothelial function in healthy male adults.

    Science.gov (United States)

    Jokura, Hiroko; Watanabe, Isamu; Umeda, Mika; Hase, Tadashi; Shimotoyodome, Akira

    2015-10-01

    Epidemiological studies indicate that habitual coffee consumption lowers the risk of diabetes and cardiovascular diseases. Postprandial hyperglycemia is a direct and independent risk factor for cardiovascular diseases. We previously demonstrated that coffee polyphenol ingestion increased secretion of Glucagon-like peptide 1 (GLP-1), which has been shown to exhibit anti-diabetic and cardiovascular effects. We hypothesized coffee polyphenol consumption may improve postprandial hyperglycemia and vascular endothelial function by increasing GLP-1 release and/or reducing oxidative stress. To examine this hypothesis, we conducted a randomized, acute, crossover, intervention study in healthy male adults, measuring blood parameters and flow-mediated dilation (FMD) after ingestion of a meal with or without coffee polyphenol extract (CPE). Nineteen subjects consumed a test meal with either a placebo- or CPE-containing beverage. Blood biomarkers and FMD were measured at fasting and up to 180 minutes postprandially. The CPE beverage led to a significantly lower peak postprandial increase in blood glucose and diacron-reactive oxygen metabolite, and significantly higher postprandial FMD than the placebo beverage. Postprandial blood GLP-1 increase tended to be higher after ingestion of the CPE beverage, compared with placebo. Subclass analysis revealed that the CPE beverage significantly improved postprandial blood GLP-1 response and reduced blood glucose increase in the subjects with a lower insulinogenic index. Correlation analysis showed postprandial FMD was negatively associated with blood glucose increase after ingestion of the CPE beverage. In conclusion, these results suggest that coffee polyphenol consumption improves postprandial hyperglycemia and vascular endothelial function, which is associated with increased GLP-1 secretion and decreased oxidative stress in healthy humans.

  4. vascular hemiplegia

    OpenAIRE

    Voto Bernales, Jorge; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    The vascular hemiplegia is the functional disorder of a lateral half of the body produced by alterations of cerebral vessels. Should review the concepts of this common condition, with the dual aim of expanding its nosographic value and considering the hemiplegic patient as worthy of the highest professional care La hemiplejia vascular, es el trastorno funcional de una mitad lateral del cuerpo producido por alteraciones de los vasos cerebrales. Conviene revisar los conceptos sobre esta frec...

  5. Experimental Study of 103Pd Stent Affecting Dynamic Equilibrium Between Proliferation and Apoptosis of Vascular Smooth Muscle Cells

    Institute of Scientific and Technical Information of China (English)

    Liu Yingmei; Fu Yuewu; Wei Yulin; Wu Wei

    2006-01-01

    Objectives By observing γ radioactive 103Pd stent affecting the proliferation and apoptosis of vascular smooth muscle cells (VSMCs) to explore the mechanism of radioactive stent preventing in-stent restenosis. Methods Fifty male New Zealand rabbits were randomized into stent group and 103Pd stent group. Control group was set up. The materials were harvested on 3, 7, 14, 28, 56 days after operation and the following investigations were carried out, including pathomorphology, immunohistochemistry, apoptosis (TUNEL) and in situs hybridization studies. Results ①The severity of the stenosis in 103Pd stent group was less than that of stent group.It was the most obvious on 56th day (P < 0.01).②The expression of PCNA of 103Pd stent group was lower than that of stent group on 3 to 28 days. It was the most obvious on 7th day, 16.35%±0.79% vs 24.36%±0.55% (P< 0.01 ). ③TUNEL method showed that the 103Pd stent group had much more apoptosis of VSMCs than that of stent group. The highest rate of apoptosis appeared on day 7, 14.72%±0.53% vs 12.42%±1.13% (P<0.01). ④ By calculating the ratio of PCNA/apoptosis (P:A), a much lower ratio was seen in 103Pd-stent group than that of stent group at 3 to 28 days. There was significant statistic difference between two groups (P<0.05). ⑤For bcl-2/bax ratio, the result in 103Pd-stent group was lower than that of stent group at 3 to 28 days. It had significant statistic difference (P < 0.05). Conclusions γ radioactive stent can inhibit the proliferation and accelerate apoptosis of injured media VSMCs. Also it can decrease the ratio of proliferation to apoptosis and relieve the severity of restenosis.

  6. Childhood trauma and cognitive function in first-episode affective and non-affective psychosis.

    LENUS (Irish Health Repository)

    Aas, Monica

    2011-06-01

    A history of childhood trauma is reportedly more prevalent in people suffering from psychosis than in the general population. Childhood trauma has also been linked to cognitive abnormalities in adulthood, and cognitive abnormalities, in turn, are one of the key clinical features of psychosis. Therefore, this study investigated whether there was a relationship between childhood trauma and cognitive function in patients with first-episode psychosis. The potential impact of diagnosis (schizophrenia or affective psychosis) and gender on this association was also examined.

  7. Cognitive function in the affective disorders: a prospective study.

    Science.gov (United States)

    Bulbena, A; Berrios, G E

    1993-01-01

    A prospective, controlled study of 50 subjects confirmed claims that major depression or mania may cause temporary disorders of attention, memory, visuo-spatial function, and choice reaction time, and cause-independently of medication-the appearance of glabellar tap, positive hand-face test, nuchocephalic reflex, and graphesthesia. On follow-up, all these phenomena either disappeared or markedly improved. Age and age of onset, but not pre-morbid intelligence or history of ECT, seemed to modulate the severity of the cognitive impairment. Presence of delusions predicted poor (but reversible) visuo-spatial function. Cognitive impairment accompanied by reversible soft neurological signs was more marked but patients thus affected surprisingly showed lower depressive scores; this was interpreted as representing a secondary, 'organic' form of affective disorder (i.e. a behavioural phenocopy of depression) characterised by a reduced capacity to experience depressive symptoms and by little improvement at follow-up.

  8. Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease

    Institute of Scientific and Technical Information of China (English)

    Jin-Ping Li; De-Li Zhao; Hui-Jie Jiang; Ya-Hua Huang; Da-Qing Li; Yong Wan; Xin-Ding Liu; Jin-E Wang

    2011-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhoticliverdiseasebythisfastimagingmethod. METHODS: CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. RESULTS: In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The

  9. Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks

    Science.gov (United States)

    Kang, Tae-Yun; Hong, Jung Min; Jung, Jin Woo; Kang, Hyun-Wook; Cho, Dong-Woo

    2016-01-01

    We used indirect stereolithography (SL) to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture. PMID:27228079

  10. Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks.

    Directory of Open Access Journals (Sweden)

    Tae-Yun Kang

    Full Text Available We used indirect stereolithography (SL to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture.

  11. Association Between Peripheral Vascular Endothelial Function and Progression of Open-Angle Glaucoma.

    Science.gov (United States)

    Liu, Chun-Hsiu; Su, Wei-Wen; Shie, Shian-Sen; Cheng, Shih-Tsung; Su, Cheng-Wen; Ho, Wang-Jing

    2016-03-01

    The aim of the study is to evaluate the relationship between Humphrey visual field progression and peripheral vascular endothelial function in patients with open-angle glaucoma (OAG), assessed by noninvasive endothelium-dependent flow-mediated vasodilation (FMD).Forty OAG patients, among which 22 had normal-tension glaucoma (NTG) and 18 had primary open-angle glaucoma (POAG) were enrolled. Each enrolled patient underwent a thorough ophthalmological examination including the Humphrey visual field test and measurement of FMD via high-resolution 2-dimensional ultrasonographic imaging of the brachial artery. Blood samples were evaluated for biochemistry and lipid profiles as well as levels of high-sensitivity C-reactive protein (hsCRP). The annual change of threshold sensitivity of the visual field in each test location were analyzed with pointwise linear regression. The correlation between long-term visual field progression and FMD was evaluated.A mean follow-up of 7.47 ± 1.84 years revealed a faster progression rate over the superior visual field in all 40 OAG patients (superior field -0.24 ± 0.67 dB/y, inferior field -0.10 ± 0.59 dB/y, P = 0.37). However, only the annual sensitivity change of the inferior peripheral field showed correlation with baseline FMD. There was no significant difference in the change slope of visual field between NTG and POAG patients.A correlation between baseline brachial artery FMD and visual field progression was observed in the inferior peripheral field in patients with NTG and POAG. This result suggests that peripheral vascular endothelial dysfunction may be related to glaucoma progression.

  12. Clinical Study of Respiratory Function and Difference in Pneumonia History between Alzheimer’s Disease and Vascular Dementia Groups

    OpenAIRE

    2014-01-01

    [Purpose] This study compared respiratory function and differences in pneumonia history between Alzheimer’s disease and vascular dementia groups. [Subjects] Fifty-eight inpatients in the dementia treatment ward in a psychiatric facility were enrolled. [Methods] Patients underwent respiratory function testing twice using an 80-cm party horn. The Mini-Mental State Examination was also performed and motor functions were evaluated. Patient characteristics were obtained from medical records. [Resu...

  13. Effects of increased physical activity on body composition, physical functions, vascular functions, HR-QOL, and self-efficacy in community-dwelling elderly people

    Science.gov (United States)

    Morisawa, Tomoyuki; Tamaki, Akira; Nagai, Kotatsu; Tsukagoshi, Rui; Nozaki, Sonoko; Miyamoto, Toshiaki; Mori, Akiko; Kaya, Mitsumasa; Fujioka, Hiroyuki

    2017-01-01

    [Purpose] The objective of this study was to clarify the effects of increased number of steps on body composition, physical functions, vascular functions, health-related quality of life (HR-QOL) and self-efficacy in elderly people. [Subjects and Methods] The subjects were 47 elderly persons who resided in Port Island in the Chuo Ward of Kobe City in Hyogo Prefecture, Japan. After the calculation of the mean preintervention physical activity (PA), the subjects were instructed to increase their PA to a target baseline + 1,300 steps/day. Body composition, physical functions, vascular functions, HR-QOL, and self-efficacy were measured at baseline, after 3 and 6 months. These items were compared between a group that increased their PA and a group that did not. [Results] After 6 months, 26.1% of the subjects achieved the PA target. No significant improvements were observed in body composition, physical functions, vascular functions, or self-efficacy for either group after 3 and 6 months. However, the HR-QOL improved significantly after 6 months in the achievement group. [Conclusion] Although the intervention to increase PA did not produce significant improvements after 6 months in body composition, physical functions, vascular functions, or self-efficacy, the HR-QOL improved significantly during this relatively short period. PMID:28210063

  14. Effects of increased physical activity on body composition, physical functions, vascular functions, HR-QOL, and self-efficacy in community-dwelling elderly people.

    Science.gov (United States)

    Morisawa, Tomoyuki; Tamaki, Akira; Nagai, Kotatsu; Tsukagoshi, Rui; Nozaki, Sonoko; Miyamoto, Toshiaki; Mori, Akiko; Kaya, Mitsumasa; Fujioka, Hiroyuki

    2017-01-01

    [Purpose] The objective of this study was to clarify the effects of increased number of steps on body composition, physical functions, vascular functions, health-related quality of life (HR-QOL) and self-efficacy in elderly people. [Subjects and Methods] The subjects were 47 elderly persons who resided in Port Island in the Chuo Ward of Kobe City in Hyogo Prefecture, Japan. After the calculation of the mean preintervention physical activity (PA), the subjects were instructed to increase their PA to a target baseline + 1,300 steps/day. Body composition, physical functions, vascular functions, HR-QOL, and self-efficacy were measured at baseline, after 3 and 6 months. These items were compared between a group that increased their PA and a group that did not. [Results] After 6 months, 26.1% of the subjects achieved the PA target. No significant improvements were observed in body composition, physical functions, vascular functions, or self-efficacy for either group after 3 and 6 months. However, the HR-QOL improved significantly after 6 months in the achievement group. [Conclusion] Although the intervention to increase PA did not produce significant improvements after 6 months in body composition, physical functions, vascular functions, or self-efficacy, the HR-QOL improved significantly during this relatively short period.

  15. Observation on the changes of vascular functional status and RAAS indexes of senium patients with hypertension complicated with diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Song-Geng Du; De-Jun Chen; Zun-Fa Chen

    2015-01-01

    Objective: To observe the change situation of vascular function state and RAAS indexes of elderly patients with hypertension complicated with diabetes mellitus. Methods: 50 elderly patients with hypertension complicated with diabetes mellitus in our hospital from September 2013 to October 2014 were selected as group A, 50 patients with only hypertension at the same time were selected as group B, 50 patients with only diabetes mellitus were selected as group C, 50 health elderly patients were the group D, then the vascular function related indexes and RAAS indexes of four groups were compared, and the detection results of group A with different grades of hypertension were compared too. Results: The vascular function state related indexes and RAAS indexes of group A were all worse than those of group B, group C and group D, the detection results of group B and group C were worse than those of group D, and the detection results of group A with different grades of hypertension all had significant differences too, all P<0.05. Conclusion: The change of vascular function state and RAAS indexes of elderly patients with hypertension complicated with diabetes mellitus are great, and the influence of the disease for the detection levels are all great.

  16. Bone marrow-derived macrophages incorporate into the endothelium and influence vascular and renal function after irradiation

    NARCIS (Netherlands)

    de Cortie, Karin; Russell, Nicola S.; Coppes, Rob P.; Stewart, Fiona A.; Scharpfenecker, Marion

    2014-01-01

    Purpose: We recently demonstrated that endoglin, an ancillary transforming growth factor beta (TGF-beta) receptor, modulates vascular damage and fibrosis formation and influences renal function after kidney irradiation. We also suggested that this was partially accomplished by endoglin-mediated regu

  17. Systemic vascular function, measured with forearm flow mediated dilatation, in acute and stable cerebrovascular disease: a case-control study

    Directory of Open Access Journals (Sweden)

    Blacker David

    2010-10-01

    Full Text Available Abstract Background Acute ischaemic stroke is associated with alteration in systemic markers of vascular function. We measured forearm vascular function (using forearm flow mediated dilatation to clarify whether recent acute ischaemic stroke/TIA is associated with impaired systemic vascular function. Methods Prospective case control study enrolling 17 patients with recent acute ischaemic stroke/TIA and 17 sex matched controls with stroke more than two years previously. Forearm vascular function was measured using flow medicated dilatation (FMD. Results Flow mediated dilatation was 6.0 ± 1.1% in acute stroke/TIA patients and 4.7 ± 1.0% among control subjects (p = 0.18. The mean paired difference in FMD between subjects with recent acute stroke and controls was 1.25% (95% CI -0.65, 3.14; p = 0.18. Endothelium independent dilatation was measured in six pairs of participants and was similar in acute stroke/TIA patients (22.6 ± 4.3% and control subjects (19.1 ± 2.6%; p = 0.43. Conclusions Despite the small size of this study, these data indicate that recent acute stroke is not necessarily associated with a clinically important reduction in FMD.

  18. Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects.

    Science.gov (United States)

    García, José R; Clark, Amy Y; García, Andrés J

    2016-04-01

    Vascularization of bone defects is considered a crucial component to the successful regeneration of large bone defects. Although vascular endothelial growth factor (VEGF) has been delivered to critical-size bone defect models to augment blood vessel infiltration into the defect area, its potential to increase bone repair remains ambiguous. In this study, we investigated whether integrin-specific biomaterials modulate the effects of VEGF on bone regeneration. We engineered protease-degradable, VEGF-loaded poly(ethylene glycol) (PEG) hydrogels functionalized with either a triple-helical, α2 β1 integrin-specific peptide GGYGGGP(GPP)5 GFOGER(GPP)5 GPC (GFOGER) or an αv β3 integrin-targeting peptide GRGDSPC (RGD). Covalent incorporation of VEGF into the PEG hydrogel allowed for protease degradation-dependent release of the protein while maintaining VEGF bioactivity. When applied to critical-size segmental defects in the murine radius, GFOGER-functionalized VEGF-free hydrogels exhibited significantly increased vascular volume and density and resulted in a larger number of thicker blood vessels compared to RGD-functionalized VEGF-free hydrogels. VEGF-loaded RGD hydrogels increased vascularization compared to VEGF-free RGD hydrogels, but the levels of vascularization for these VEGF-containing RGD hydrogels were similar to those of VEGF-free GFOGER hydrogels. VEGF transiently increased bone regeneration in RGD hydrogels but had no effect at later time points. In GFOGER hydrogels, VEGF did not show an effect on bone regeneration. However, VEGF-free GFOGER hydrogels resulted in increased bone regeneration compared to VEGF-free RGD hydrogels. These findings demonstrate the importance of integrin-specificity in engineering constructs for vascularization and associated bone regeneration.

  19. Localization and function of KLF4 in cytoplasm of vascular smooth muscle cell

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yan [Department of Biochemistry and Molecular Biology, The Key Laboratory of Neurobiology and Vascular Biology (China); The Third Hospital of Hebei Medical University, Shijazhuang (China); Zheng, Bin; Zhang, Xin-hua; Nie, Chan-juan; Li, Yong-hui [Department of Biochemistry and Molecular Biology, The Key Laboratory of Neurobiology and Vascular Biology (China); Wen, Jin-kun, E-mail: wjk@hebmu.edu.cn [Department of Biochemistry and Molecular Biology, The Key Laboratory of Neurobiology and Vascular Biology (China)

    2013-06-28

    Highlights: •PDGF-BB prompts the translocation of KLF4 to the cytoplasm. •PDGF-BB promotes interaction between KLF4 and actin in the cytoplasm. •Phosphorylation and SUMOylation of KLF4 participates in regulation of cytoskeletal organization. •KLF4 regulates cytoskeleton by promoting the expression of contraction-associated genes. -- Abstract: The Krüppel-like factor 4 is a DNA-binding transcriptional regulator that regulates a diverse array of cellular processes, including development, differentiation, proliferation, and apoptosis. The previous studies about KLF4 functions mainly focused on its role as a transcription factor, its functions in the cytoplasm are still unknown. In this study, we found that PDGF-BB could prompt the translocation of KLF4 to the cytoplasm through CRM1-mediated nuclear export pathway in vascular smooth muscle cells (VSMCs) and increased the interaction of KLF4 with actin in the cytoplasm. Further study showed that both KLF4 phosphorylation and SUMOylation induced by PDGF-BB participates in regulation of cytoskeletal organization by stabilizing the actin cytoskeleton in VSMCs. In conclusion, these results identify that KLF4 participates in the cytoskeletal organization by stabilizing cytoskeleton in the cytoplasm of VSMCs.

  20. Factors potentially affecting the function of kidney grafts

    Institute of Scientific and Technical Information of China (English)

    LIN Jun; ZHENG Xin; XIE Ze-lin; SUN Wen; ZHANG Lei; TIAN Ye; GUO Yu-wen

    2013-01-01

    Background Donor and recipient risk factors on graft function have been well characterized.The contribution of demographic factors,such as age,gender,and other potential factors of donor and recipient at the time of transplantation on the function of a graft is much less well understood.In this study,we analyzed the effects of factors such as age,gender,etc.,on the short-term and long-term graft function in kidney transplant recipients from living donor.Methods A total of 335 living donors and their recipients,who had kidney transplantation in our center from May 2004 to December 2009,were included.Serum creatinine level was used as the assessment criterion (serum creatinine level lower than 115 mmol/L is normal).Factors related to graft function such as age,gender,blood relation by consanguinity,human leukocyte antigen (HLA) mismatch,ABO type,etc.,were analyzed separately.Results Donor age is the key factor affecting both the short-term and long-term function of a grafted kidney from a living donor.The group with donors younger than 48 years showed the best kidney function post transplantation.Match of gender and age is another important factor that influences the function of grafted kidney from a living donor.The older donor to younger recipient group had the worst outcome after kidney transplantation.After 36 months post transplantation,female donor to male recipient group had worse kidney function compared to other groups.We also found that calcinerin inhibitor used in the maintenance period may influence the function of a grafted kidney.No significant statistical differences were found in consanguinity,blood type,and mismatch of HLA.Conclusions Donor age is an important factor affecting the function of a grafted kidney from a living donor.We also recommend taking nephron,immunology factor,infection,and demographic information all into consideration when assessing the outcome of kidney transplantation.

  1. [The specific features of the vestibular function in the patients presenting with sensorineural hearing loss of vascular genesis].

    Science.gov (United States)

    Kirichenko, I M; Popadyuk, V I; Tuzhilina, K V

    2016-01-01

    The authors consider the specific features of the vestibular function in the patients with sensorineural hearing loss of vascular genesis. The study included 60 patients at the age from 28 to 75 years presenting with sensorineural impairment of hearing of vascular genesis. All of them were examined with the use of the extended otoneurological method. The data obtained were compared with the structural changes and hemodynamic characteristics of vertebral arteries (VA) and internal carotid arteries (ICA) and with the results of magnetic resonance imaging (MRI) of the brain.

  2. Montmorency Tart cherries (Prunus cerasus L.) modulate vascular function acutely, in the absence of improvement in cognitive performance.

    Science.gov (United States)

    Keane, K M; Haskell-Ramsay, C F; Veasey, R C; Howatson, G

    2016-12-01

    Cerebral blood volume and metabolism of oxygen decline as part of human ageing, and this has been previously shown to be related to cognitive decline. There is some evidence to suggest that polyphenol-rich foods can play an important role in delaying the onset or halting the progression of age-related health disorders such as CVD and Alzheimer's disease and to improve cognitive function. In the present study, an acute, placebo-controlled, double-blinded, cross-over, randomised Latin-square design study with a washout period of at least 14 d was conducted on twenty-seven, middle-aged (defined as 45-60 years) volunteers. Participants received either a 60 ml dose of Montmorency tart cherry concentrate (MC), which contained 68·0 (sd 0·26) mg cyanidin-3-glucoside/l, 160·75 (sd 0·55) mean gallic acid equivalent/l and 0·59 (sd 0·02) mean Trolox equivalent/l, respectively, or a placebo. Cerebrovascular responses, cognitive performance and blood pressure were assessed at baseline and 1, 2, 3 and 5 h following consumption. There were significant differences in concentrations of total Hb and oxygenated Hb during the task period 1 h after MC consumption (P≤0·05). Furthermore, MC consumption significantly lowered systolic blood pressure (P≤0·05) over a period of 3 h, with peak reductions of 6±2 mmHg at 1 h after MC consumption relative to the placebo. Cognitive function and mood were not affected. These results show that a single dose of MC concentrate can modulate certain variables of vascular function; however, this does not translate to improvements in cognition or mood.

  3. Neurovascular Recovery via Cotransplanted Neural and Vascular Progenitors Leads to Improved Functional Restoration after Ischemic Stroke in Rats

    Directory of Open Access Journals (Sweden)

    Jia Li

    2014-07-01

    Full Text Available The concept of the “neurovascular unit,” emphasizing the interactions between neural and vascular components in the brain, raised the notion that neural progenitor cell (NPC transplantation therapy aimed at neural repair may be insufficient for the treatment of ischemic stroke. Here, we demonstrate that enhanced neurovascular recovery via cotransplantation of NPCs and embryonic stem cell-derived vascular progenitor cells (VPCs in a rat stroke model is correlated with improved functional recovery after stroke. We found that cotransplantation promoted the survival, migration, differentiation, and maturation of neuronal and vascular cells derived from the cotransplanted progenitors. Furthermore, it triggered an increased generation of VEGF-, BDNF-, and IGF1-expressing neural cells derived from the grafted NPCs. Consistently, compared with transplantation of NPCs alone, cotransplantation more effectively improved the neurobehavioral deficits and attenuated the infarct volume. Thus, cotransplantation of NPCs and VPCs represents a more effective therapeutic strategy for the treatment of stroke than transplantation of NPCs alone.

  4. New Indices of Endothelial Function Measured by Digital Thermal Monitoring of Vascular Reactivity: Data from 6084 Patients Registry

    Directory of Open Access Journals (Sweden)

    Morteza Naghavi

    2016-01-01

    Full Text Available Background. Endothelial function is viewed as a barometer of cardiovascular health and plays a central role in vascular reactivity. Several studies showed digital thermal monitoring (DTM as a simple noninvasive method to measure vascular reactivity that is correlated with atherosclerosis risk factors and coronary artery disease. Objectives. To further evaluate the relations between patient characteristics and DTM indices in a large patient registry. Methods. DTM measures were correlated with age, sex, heart rate, and systolic and diastolic blood pressure in 6084 patients from 18 clinics. Results. DTM vascular reactivity index (VRI was normally distributed and inversely correlated with age (r=-0.21, p<0.0001. Thirteen percent of VRI tests were categorized as poor vascular reactivity (VRI < 1.0, 70 percent as intermediate (1.0 ≤ VRI < 2.0, and 17 percent as good (VRI ≥ 2.0. Poor VRI (<1.0 was noted in 6% of <50 y, 10% of 50–70 y, and 18% of ≥70 y. In multiple linear regression analyses, age, sex, and diastolic blood pressure were significant but weak predictors of VRI. Conclusions. As the largest database of finger-based vascular reactivity measurement, this report adds to prior findings that VRI is a meaningful physiological marker and reflects a high level of residual risk found in patients currently under care.

  5. No adverse affect after harvesting of free fibula osteoseptocutaneous flaps on gait function.

    Science.gov (United States)

    Maurer-Ertl, Werner; Glehr, Mathias; Friesenbichler, Joerg; Sadoghi, Patrick; Wiedner, Maria; Haas, Franz; Leithner, Andreas; Windhager, Reinhard; Zwick, Ernst B

    2012-07-01

    The aim of this study was to analyze gait function and muscular strength on donor site after harvesting of a vascularized fibula osteoseptocutaneous flap. Nine patients with a mean follow-up of 33 months (range, 7-59) and a mean resection length of the middle portion of the fibula of 18.0 cm (range, 14.0-23.0) underwent an instrumented three-dimensional gait analysis to evaluate gait function. Furthermore, CYBEX II extremity system was used for muscular strength measurements. Subjective muscle strength measurements were performed according to Kendall et al. and were classified according to the British Medical Research Council. Intraindividual comparison between the operated and the nonoperated leg revealed no significant differences for gait function parameters (cadence, velocity, and stride length, P > 1.00) and for muscular strength measurements for flexion (knee: P = 0.93, ankle: P = 0.54) and extension (knee: P = 0.97, ankle: P= 0.21), respectively. In conclusion, intraindividual comparison of the operated and nonoperated sides after harvesting of the middle portion of the fibula for gaining a free fibula osteoseptocutaneous flap has no adverse affect on gait function or muscular flexion and extension strength on donor site at a mean follow-up of 33 months.

  6. No effect of unfractioned or low molecular weight heparin treatment on markers of vascular wall and hemostatic function in incipient diabetic nephropathy

    NARCIS (Netherlands)

    Myrup, B.; Jensen, T.; Gram, J.; Kluft, C.; Jespersen, J.; Deckert, T.

    1997-01-01

    OBJECTIVE - The high risk for cardiovascular disease in IDDM patients with nephropathy may be mediated by abnormal function of the vascular wall. We investigated whether heparin was able to modulate markers of vascular wall and hemostatic function in patients with incipient nephropathy. RESEARCH DES

  7. Cognitive function in unaffected twins discordant for affective disorder

    DEFF Research Database (Denmark)

    Christensen, Maj Vinberg; Kyvik, Kirsten Ohm; Kessing, Lars Vedel

    2006-01-01

    is associated with cognitive impairment. METHOD: In a cross-sectional high-risk case-control study, healthy monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers....... Cognitive performance of 203 High-Risk and Low-Risk twins was compared. RESULTS: Healthy twins discordant for unipolar disorder showed lower performance on almost all measures of cognitive function: selective and sustained attention, executive function, language processing and working and declarative memory......, and also after adjustment for demographic variables, subclinical symptoms and minor psychopathology. Healthy twins discordant for bipolar disorder showed lower performance on tests measuring episodic and working memory, also after adjustment for the above-mentioned covariables. The discrete cognitive...

  8. Role of olmesartan in combination therapy in blood pressure control and vascular function

    Directory of Open Access Journals (Sweden)

    Carlos M Ferrario

    2010-08-01

    Full Text Available Carlos M Ferrario, Ronald D SmithWake Forest University School of Medicine, Winston-Salem, North Carolina, USAAbstract: Angiotensin receptor blockers have emerged as a first-line therapy in the management of hypertension and hypertension-related comorbidities. Since national and international guidelines have stressed the need to control blood pressure to <140/90 mmHg in uncomplicated hypertension and <130/80 mmHg in those with associated comorbidities such as diabetes or chronic kidney disease, these goal blood pressures can only be achieved through combination therapy. Of several drugs that can be effectively combined to attain the recommended blood pressure goals, fixed-dose combinations of angiotensin receptor blockers and the calcium channel blocker amlodipine provide additive antihypertensive effects associated with a safe profile and increased adherence to therapy. In this article, we review the evidence regarding the beneficial effects of renin–angiotensin system blockade with olmesartan medoxomil and amlodipine in terms of blood pressure control and improvement of vascular function and target organ damage.Keywords: amlodipine, angiotensin receptor blockers, angiotensin-converting enzyme 2, hypertension, renin–angiotensin system

  9. Synergistic effects of matrix nanotopography and stiffness on vascular smooth muscle cell function.

    Science.gov (United States)

    Chaterji, Somali; Kim, Peter; Choe, Seung H; Tsui, Jonathan H; Lam, Christoffer H; Ho, Derek S; Baker, Aaron B; Kim, Deok-Ho

    2014-08-01

    Vascular smooth muscle cells (vSMCs) retain the ability to undergo modulation in their phenotypic continuum, ranging from a mature contractile state to a proliferative, secretory state. vSMC differentiation is modulated by a complex array of microenvironmental cues, which include the biochemical milieu of the cells and the architecture and stiffness of the extracellular matrix. In this study, we demonstrate that by using UV-assisted capillary force lithography (CFL) to engineer a polyurethane substratum of defined nanotopography and stiffness, we can facilitate the differentiation of cultured vSMCs, reduce their inflammatory signature, and potentially promote the optimal functioning of the vSMC contractile and cytoskeletal machinery. Specifically, we found that the combination of medial tissue-like stiffness (11 MPa) and anisotropic nanotopography (ridge width_groove width_ridge height of 800_800_600 nm) resulted in significant upregulation of calponin, desmin, and smoothelin, in addition to the downregulation of intercellular adhesion molecule-1, tissue factor, interleukin-6, and monocyte chemoattractant protein-1. Further, our results allude to the mechanistic role of the RhoA/ROCK pathway and caveolin-1 in altered cellular mechanotransduction pathways via differential matrix nanotopography and stiffness. Notably, the nanopatterning of the stiffer substrata (1.1 GPa) resulted in the significant upregulation of RhoA, ROCK1, and ROCK2. This indicates that nanopatterning an 800_800_600 nm pattern on a stiff substratum may trigger the mechanical plasticity of vSMCs resulting in a hypercontractile vSMC phenotype, as observed in diabetes or hypertension. Given that matrix stiffness is an independent risk factor for cardiovascular disease and that CFL can create different matrix nanotopographic patterns with high pattern fidelity, we are poised to create a combinatorial library of arterial test beds, whether they are healthy, diseased, injured, or aged. Such

  10. Dehydration affects brain structure and function in healthy adolescents.

    Science.gov (United States)

    Kempton, Matthew J; Ettinger, Ulrich; Foster, Russell; Williams, Steven C R; Calvert, Gemma A; Hampshire, Adam; Zelaya, Fernando O; O'Gorman, Ruth L; McMorris, Terry; Owen, Adrian M; Smith, Marcus S

    2011-01-01

    It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing.

  11. Can the hydrophilicity of functional monomers affect chemical interaction?

    Science.gov (United States)

    Feitosa, V P; Ogliari, F A; Van Meerbeek, B; Watson, T F; Yoshihara, K; Ogliari, A O; Sinhoreti, M A; Correr, A B; Cama, G; Sauro, S

    2014-02-01

    The number of carbon atoms and/or ester/polyether groups in spacer chains may influence the interaction of functional monomers with calcium and dentin. The present study assessed the chemical interaction and bond strength of 5 standard-synthesized phosphoric-acid ester functional monomers with different spacer chain characteristics, by atomic absorption spectroscopy (AAS), ATR-FTIR, thin-film x-ray diffraction (TF-XRD), scanning electron microscopy (SEM), and microtensile bond strength (μTBS). The tested functional monomers were 2-MEP (two-carbon spacer chain), 10-MDP (10-carbon), 12-MDDP (12-carbon), MTEP (more hydrophilic polyether spacer chain), and CAP-P (intermediate hydrophilicity ester spacer). The intensity of monomer-calcium salt formation measured by AAS differed in the order of 12-MDDP=10-MDP>CAP-P>MTEP>2-MEP. FTIR and SEM analyses of monomer-treated dentin surfaces showed resistance to rinsing for all monomer-dentin bonds, except with 2-MEP. TF-XRD confirmed the weaker interaction of 2-MEP. Highest µTBS was observed for 12-MDDP and 10-MDP. A shorter spacer chain (2-MEP) of phosphate functional monomers induced formation of unstable monomer-calcium salts, and lower chemical interaction and dentin bond strength. The presence of ester or ether groups within longer spacer carbon chains (CAP-P and MTEP) may affect the hydrophilicity, μTBS, and also the formation of monomer-calcium salts.

  12. How does temperature affect the function of tissue macrophages?

    Science.gov (United States)

    Lee, Chen-Ting; Repasky, Elizabeth A.

    2011-03-01

    Macrophages create a major danger signal following injury or infection and upon activation release pro-inflammatory cytokines, which in turn help to generate febrile conditions. Thus, like other cells of the body, tissue macrophages are often exposed to naturally occurring elevations in tissue temperature during inflammation and fever. However, whether macrophages sense and respond to temperature changes in a specific manner which modulates their function is still not clear. In this brief review, we highlight recent studies which have analyzed the effects of temperatures on macrophage function, and summarize the possible underlying molecular mechanisms which have been identified. Mild, physiological range hyperthermia has been shown to have both pro- and anti-inflammatory roles in regulating macrophage inflammatory cytokine production and at the meeting presentation, we will show new data demonstrating that hyperthermia can indeed exert both positive and negative signals to macrophages. While some thermal effects are correlated with the induction of heat shock factors/heat shock proteins, overall it is not clear how mild hyperthermia can exert both pro- and anti-inflammatory functions. We also summarize data which shows that hyperthermia can affect other macrophage effector functions, including the anti-tumor cytotoxicity. Overall, these studies may help us to better understand the immunological role of tissue temperature and may provide important information needed to maximize the application of heat in the treatment of various diseases including cancer.

  13. Subfailure overstretch injury leads to reversible functional impairment and purinergic P2X7 receptor activation in intact vascular tissue

    Directory of Open Access Journals (Sweden)

    Weifeng Luo

    2016-09-01

    Full Text Available Vascular stretch injury is associated with blunt trauma, vascular surgical procedures, and harvest of human saphenous vein for use in vascular bypass grafting. A model of subfailure overstretch in rat abdominal aorta was developed to characterize surgical vascular stretch injury. Longitudinal stretch of rat aorta was characterized ex vivo. Stretch to the haptic endpoint where the tissues would no longer lengthen, occurred at twice the resting length. The stress produced at this length was greater than physiologic mechanical forces but well below the level of mechanical disruption. Functional responses were determined in a muscle bath and this subfailure overstretch injury led to impaired smooth muscle function that was partially reversed by treatment with purinergic receptor (P2X7R antagonists. These data suggest that vasomotor dysfunction caused by subfailure overstretch injury may be due to activation of P2X7R. These studies have implications for our understanding of mechanical stretch injury of blood vessels and offer novel therapeutic opportunities.

  14. Reduced cyclooxygenase involvement in vascular endothelial function in rat renal transplantation

    NARCIS (Netherlands)

    Smit-Van Oosten, Annemieke; Boonstra, Arnold H.; Navis, Gerjan; Van Goor, Harry; Buikema, Hendrik

    2005-01-01

    Background: Cardiovascular disease is a major cause of death following renal transplantation. Mechanisms leading to vascular dysfunction outside the transplanted organ involve common risk factors such as hypertension, hypercholesterolemia, proteinuria, but immune-mediated factors may also be involve

  15. Tropomyosin variants describe distinct functional subcellular domains in differentiated vascular smooth muscle cells.

    Science.gov (United States)

    Gallant, Cynthia; Appel, Sarah; Graceffa, Philip; Leavis, Paul; Lin, Jim Jung-Ching; Gunning, Peter W; Schevzov, Galina; Chaponnier, Christine; DeGnore, Jon; Lehman, William; Morgan, Kathleen G

    2011-06-01

    Tropomyosin (Tm) is known to be an important gatekeeper of actin function. Tm isoforms are encoded by four genes, and each gene produces several variants by alternative splicing, which have been proposed to play roles in motility, proliferation, and apoptosis. Smooth muscle studies have focused on gizzard smooth muscle, where a heterodimer of Tm from the α-gene (Tmsm-α) and from the β-gene (Tmsm-β) is associated with contractile filaments. In this study we examined Tm in differentiated mammalian vascular smooth muscle (dVSM). Liquid chromatography-tandem mass spectrometry (LC MS/MS) analysis and Western blot screening with variant-specific antibodies revealed that at least five different Tm proteins are expressed in this tissue: Tm6 (Tmsm-α) and Tm2 from the α-gene, Tm1 (Tmsm-β) from the β-gene, Tm5NM1 from the γ-gene, and Tm4 from the δ-gene. Tm6 is by far most abundant in dVSM followed by Tm1, Tm2, Tm5NM1, and Tm4. Coimmunoprecipitation and coimmunofluorescence studies demonstrate that Tm1 and Tm6 coassociate with different actin isoforms and display different intracellular localizations. Using an antibody specific for cytoplasmic γ-actin, we report here the presence of a γ-actin cortical cytoskeleton in dVSM cells. Tm1 colocalizes with cortical cytoplasmic γ-actin and coprecipitates with γ-actin. Tm6, on the other hand, is located on contractile bundles. These data indicate that Tm1 and Tm6 do not form a classical heterodimer in dVSM but rather describe different functional cellular compartments.

  16. Bisphenol A affects androgen receptor function via multiple mechanisms.

    Science.gov (United States)

    Teng, Christina; Goodwin, Bonnie; Shockley, Keith; Xia, Menghang; Huang, Ruili; Norris, John; Merrick, B Alex; Jetten, Anton M; Austin, Christopher P; Tice, Raymond R

    2013-05-25

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR.

  17. Vascular Cures

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  18. Vascular Risk Factors in Patients with Different Subtypes of Ischemic Stroke May Affect Their Outcome after Intravenous tPA.

    Directory of Open Access Journals (Sweden)

    Yi Dong

    Full Text Available Intravenous (i.v. tissue-type plasminogen activator (tPA is the only approved noninvasive therapy for acute ischemic stroke (AIS. However, after tPA treatment, the outcome of patients with different subtypes of stroke according to their vascular risk factors remains to be elucidated. We aim to explore the relationship between the outcome and different risk factors in patients with different subtype of acute strokes treated with i.v. tPA. Records of patients in this cohort were reviewed. Data collected and analysed included the demographics, vascular risk factors, baseline National Institutes of Health Stroke Scale (NIHSS scores, 90-day modified Rankin Scores (mRS, and subtypes of stroke. By using the 90-day mRS, patients were dichotomized into favorable versus unfavorable outcome in each subtype of stroke. We identified the vascular risk factors that are likely associated with the poor outcome in each subtype. Among 570 AIS patients received i.v. tPA, 217 were in the large artery atherosclerosis (LAA group, 146 in the small vessel occlusion (SVO group, and 140 in the cardioaortic embolism (CE group. Lower NIHSS score on admission was related to favorable outcome in patients in all subtypes. Patients with history of dyslipidemia were likely on statin treatment before their admission and hence less likely to have elevated cholesterol level on admission. Therefore, there was a possible paradoxical effect on the outcome in patients with LAA and SVO subtypes of strokes. SVO patients with history of diabetes had higher risk of unfavorable outcome. SVO patients had favorable outcome if their time from onset to treatment was short. In conclusion, the outcome of patients treated with i.v. tPA may be related to different vascular risk factors associated with different subtypes of stroke.

  19. Vascular Risk Factors in Patients with Different Subtypes of Ischemic Stroke May Affect Their Outcome after Intravenous tPA

    Science.gov (United States)

    Ren, Jinma; Nair, Deepak S.; Parker, Sarah; Jahnel, Jan L.; Swanson-Devlin, Teresa G.; Beck, Judith M.; Mathews, Maureen; McNeil, Clayton J.; Upadhyaya, Manas; Gao, Yuan; Dong, Qiang; Wang, David Z.

    2015-01-01

    Intravenous (IV) tissue-type plasminogen activator (tPA) is the only approved noninvasive therapy for acute ischemic stroke (AIS). However, after tPA treatment, the outcome of patients with different subtypes of stroke according to their vascular risk factors remains to be elucidated. We aim to explore the relationship between the outcome and different risk factors in patients with different subtype of acute strokes treated with IV tPA. Records of patients in this cohort were reviewed. Data collected and analysed included the demographics, vascular risk factors, baseline National Institutes of Health Stroke Scale (NIHSS) scores, 90-day modified Rankin Scores (mRS), and subtypes of stroke. By using the 90-day mRS, patients were dichotomized into favorable versus unfavorable outcome in each subtype of stroke. We identified the vascular risk factors that are likely associated with the poor outcome in each subtype. Among 570 AIS patients received IV tPA, 217 were in the large artery atherosclerosis (LAA) group, 146 in the small vessel occlusion(SVO) group, and 140 in the cardioaortic embolism(CE) group. Lower NIHSS score on admission was related to favorable outcome in patients in all subtypes. Patients with history of dyslipidemia were likely on statin treatment before their admission and hence less likely to have elevated cholesterol level on admission. Therefore, there was a possible paradoxical effect on the outcome in patients with LAA and SVO subtypes of strokes. SVO patients with history of diabetes had higher risk of unfavorable outcome. SVO patients had favorable outcome if their time from onset to treatment was short. In conclusion, the outcome of patients treated with IV tPA may be related to different vascular risk factors associated with different subtypes of stroke. PMID:26247772

  20. Indoor particles affect vascular function in the aged - An air filtration-based intervention study

    DEFF Research Database (Denmark)

    Brauner, E.V.; Forchhammer, L.; Moller, P.;

    2008-01-01

    -filtered or nonfiltered air (2,533-4,058 and 7,718-12,988 particles/cm(3), respectively) in their homes. Measurements and Main Results: MVF was assessed noninvasively by measuring digital peripheral artery tone after arm ischemia. Secondary endpoints included hemoglobin, red blood cells, platelet count, coagulation...... of cardiovascular disease....

  1. Altered Functional Connectivity in Patients with Subcortical Vascular Cognitive Impairment--A Resting-State Functional Magnetic Resonance Imaging Study.

    Directory of Open Access Journals (Sweden)

    Weina Ding

    Full Text Available Recent neuroimaging studies have shown that people with subcortical vascular cognitive impairment (sVCI have structural and functional abnormalities in the frontal lobe and subcortical brain sites. In this study, we used seed-based resting-state functional connectivity (rsFC analysis and voxel-mirrored homotopic connectivity (VMHC techniques to investigate the alteration of rsFC in patients with sVCI. rsFC and structural magnetic resonance images were acquired for 51 patients with subcortical cerebrovascular disease. All patients were subdivided based on cognitive status into 29 with sVCI and 22 controls; patient characteristics were matched. rsFC of the posterior cingulate cortex (PCC and VMHC were calculated separately, and rsFC of the PCC and VMHC between the two groups were compared. The regions showing abnormal rsFC of the PCC or VMHC in sVCI patients were adopted as regions of interest for correlation analyses. Our results are as follows: The patients with sVCI exhibited increases in rsFC in the left middle temporal lobe, right inferior temporal lobe and left superior frontal gyrus, and significant decreases in rsFC of the left thalamus with the PCC. sVCI patients showed a significant deficit in VMHC between the bilateral lingual gyrus, putamen, and precentral gyrus. Additionally, the z-memory score was significantly positively associated with connectivity between the left thalamus and the PCC (r = 0.41, p = 0.03, uncorrected in the sVCI group. Our findings suggest that the frontal lobe and subcortical brain sites play an important role in the pathogenesis of sVCI. Furthermore, rsFC between the left thalamus and the PCC might indicate the severity of sVCI.

  2. Evaluation of the relationship between renal function and renal volume-vascular indices using 3D power Doppler ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Cansu, Aysegul, E-mail: drcansu@gmail.com; Kupeli, Ali; Kul, Sibel; Eyuboglu, Ilker; Oguz, Sukru; Ozturk, Mehmet Halil; Dinc, Hasan

    2014-07-15

    Purpose: To investigate the relationship between renal function and total renal volume-vascular indices using 3D power Doppler ultrasound (3DPDUS). Materials and methods: One hundred six patients with hypertensive proteinuric nephropathy (HPN) (49 male, 57 female) and 65 healthy controls (32 male, 33 female) were evaluated prospectively using 3DPDUS. Total renal volume (RV), vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were calculated using Virtual Organ Computer-aided Analysis (VOCAL). The estimated glomerular filtration rates (GFRs) of the patients with HPN and the control group were calculated. The patients with HPN were divided into two groups on the basis of GFR, normal (≥90) or reduced (<90). Differences between groups were compared using ANOVA. Correlations between GFR, renal volume and vascular indices were analyzed using Pearson's correlation analysis. Significance was set at p < 0.05. Results: The mean total RV, VI, FI and VFI values in the reduced GFR, normal GFR and control groups were RV (ml): 234.7, 280.7 and 294.6; VI: 17.6, 27.6 and 46.8; FI: 79.1, 88.7 and 93.9 and VFI: 7.1, 12.7 and 23.8. There were statistically significant differences between the groups (p < 0.001). Total RVs and vascular indices exhibited significant correlations with estimated GFR (r = 0.53–0.59, p < 0.001) Conclusion: Three-dimensional power Doppler ultrasound is a reliable predictive technique in renal function analysis.

  3. Functional roles affect diversity-succession relationships for boreal beetles.

    Directory of Open Access Journals (Sweden)

    Heloise Gibb

    Full Text Available Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of "functional" groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species. We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies. Species associated with microhabitats that accumulate with succession (fungi and dead wood thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience.

  4. Prevention of Hippocampal Neuronal Damage and Cognitive Function Deficits in Vascular Dementia by Dextromethorphan.

    Science.gov (United States)

    Xu, Xiaofeng; Zhang, Bin; Lu, Kaili; Deng, Jiangshan; Zhao, Fei; Zhao, Bing-Qiao; Zhao, Yuwu

    2016-07-01

    Dextromethorphan (DM) is a non-competitive antagonist of NMDA receptors and a widely used component of cough medicine. Recently, its indication has been extended experimentally to a wide range of disorders including inflammation-mediated central nervous system disorders such as Parkinson disease (PD) and multiple sclerosis (MS). In this study, we investigate whether DM treatment has protective effects on the hippocampal neuron damage induced by bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]), an animal model of vascular dementia (VaD). Sprague-Dawley (SD) (10 weeks of age) rats were subjected to the 2VO, and DM was injected intraperitoneally once per day for 37 days. Neuron death, glial activation, and cognitive function were assessed at 37 days after 2VO (0.2 mg/kg, i.p., "DM-0.2" and 2 mg/kg, i.p., "DM-2"). DM-2 treatment provided protection against neuronal death and glial activation in the hippocampal CA1 subfield and reduced cognitive impairment induced by 2VO in rats. The study also demonstrates that activation of the Nrf2-HO-1 pathway and upregulation of superoxide dismutase (SOD) play important roles in these effects. These results suggest that DM is effective in treating VaD and protecting against oxidative stress, which is strongly implicated in the pathogenesis of VaD. Therefore, the present study suggests that DM treatment may represent a new and promising protective strategy for treating VaD.

  5. LRP1 functions as an atheroprotective integrator of TGFbeta and PDFG signals in the vascular wall: implications for Marfan syndrome.

    Directory of Open Access Journals (Sweden)

    Philippe Boucher

    Full Text Available BACKGROUND: The multifunctional receptor LRP1 controls expression, activity and trafficking of the PDGF receptor-beta in vascular smooth muscle cells (VSMC. LRP1 is also a receptor for TGFbeta1 and is required for TGFbeta mediated inhibition of cell proliferation. METHODS AND PRINCIPAL FINDINGS: We show that loss of LRP1 in VSMC (smLRP(- in vivo results in a Marfan-like syndrome with nuclear accumulation of phosphorylated Smad2/3, disruption of elastic layers, tortuous aorta, and increased expression of the TGFbeta target genes thrombospondin-1 (TSP1 and PDGFRbeta in the vascular wall. Treatment of smLRP1(- animals with the PPARgamma agonist rosiglitazone abolished nuclear pSmad accumulation, reversed the Marfan-like phenotype, and markedly reduced smooth muscle proliferation, fibrosis and atherosclerosis independent of plasma cholesterol levels. CONCLUSIONS AND SIGNIFICANCE: Our findings are consistent with an activation of TGFbeta signals in the LRP1-deficient vascular wall. LRP1 may function as an integrator of proliferative and anti-proliferative signals that control physiological mechanisms common to the pathogenesis of Marfan syndrome and atherosclerosis, and this is essential for maintaining vascular wall integrity.

  6. In vitro modeling of endothelial interaction with macrophages and pericytes demonstrates Notch signaling function in the vascular microenvironment.

    Science.gov (United States)

    Tattersall, Ian W; Du, Jing; Cong, Zhuangzhuang; Cho, Bennet S; Klein, Alyssa M; Dieck, Chelsea L; Chaudhri, Reyhaan A; Cuervo, Henar; Herts, James H; Kitajewski, Jan

    2016-04-01

    Angiogenesis is regulated by complex interactions between endothelial cells and support cells of the vascular microenvironment, such as tissue myeloid cells and vascular mural cells. Multicellular interactions during angiogenesis are difficult to study in animals and challenging in a reductive setting. We incorporated stromal cells into an established bead-based capillary sprouting assay to develop assays that faithfully reproduce major steps of vessel sprouting and maturation. We observed that macrophages enhance angiogenesis, increasing the number and length of endothelial sprouts, a property we have dubbed "angiotrophism." We found that polarizing macrophages toward a pro-inflammatory profile further increased their angiotrophic stimulation of vessel sprouting, and this increase was dependent on macrophage Notch signaling. To study endothelial/pericyte interactions, we added vascular pericytes directly to the bead-bound endothelial monolayer. These pericytes formed close associations with the endothelial sprouts, causing increased sprout number and vessel caliber. We found that Jagged1 expression and Notch signaling are essential for the growth of both endothelial cells and pericytes and may function in their interaction. We observed that combining endothelial cells with both macrophages and pericytes in the same sprouting assay has multiplicative effects on sprouting. These results significantly improve bead-capillary sprouting assays and provide an enhanced method for modeling interactions between the endothelium and the vascular microenvironment. Achieving this in a reductive in vitro setting represents a significant step toward a better understanding of the cellular elements that contribute to the formation of mature vasculature.

  7. Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study

    Directory of Open Access Journals (Sweden)

    Thiago Bruder-Nascimento

    2015-03-01

    Full Text Available Background: Stress is associated with cardiovascular diseases. Objective: This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO and Ca2+ dependent. Methods: Wistar rats, 30 days of age, were separated into 2 groups: control (C and Stress (St. Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca2+ flux was also evaluated. Results: Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca2+ was decreased in the aorta of stressed rats. Conclusion: Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca2+-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0

  8. Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study

    Energy Technology Data Exchange (ETDEWEB)

    Bruder-Nascimento, Thiago, E-mail: bruderthiago@usp.br [Departamento de Farmacologia - Instituto de Biociências de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil); Departamento de Clínica Médica - Faculdade de Medicina de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil); Campos, Dijon Henrique Salome [Departamento de Clínica Médica - Faculdade de Medicina de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil)

    2015-03-15

    Stress is associated with cardiovascular diseases. This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca{sup 2+} flux was also evaluated. Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca{sup 2+} was decreased in the aorta of stressed rats. Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca{sup 2+}-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)

  9. Ultrasound -- Vascular

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Ultrasound - Vascular Vascular ultrasound uses sound waves to evaluate ... the limitations of Vascular Ultrasound? What is Vascular Ultrasound? Ultrasound is safe and painless, and produces pictures ...

  10. Are left ventricular mass, geometry and function related to vascular changes and/or insulin resistance in long-standing hypertension? ICARUS: a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, M H; Hjerkinn, E; Wachtell, K;

    2003-01-01

    Vascular hypertrophy and insulin resistance have been associated with abnormal left ventricular (LV) geometry in population studies. We wanted to investigate the influence of vascular hypertrophy and insulin resistance on LV hypertrophy and its function in patients with hypertension. In 89 patients...

  11. Are left ventricular mass, geometry and function related to vascular changes and/or insulin resistance in long-standing hypertension? ICARUS: a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, M H; Hjerkinn, E; Wachtell, K;

    2003-01-01

    Vascular hypertrophy and insulin resistance have been associated with abnormal left ventricular (LV) geometry in population studies. We wanted to investigate the influence of vascular hypertrophy and insulin resistance on LV hypertrophy and its function in patients with hypertension. In 89 patien...

  12. The Peroxisome Proliferator Activated Receptor‐γ Pioglitazone Improves Vascular Function and Decreases Disease Activity in Patients With Rheumatoid Arthritis

    Science.gov (United States)

    Marder, Wendy; Khalatbari, Shokoufeh; Myles, James D.; Hench, Rita; Lustig, Susan; Yalavarthi, Srilakshmi; Parameswaran, Aishwarya; Brook, Robert D.; Kaplan, Mariana J.

    2013-01-01

    Background Rheumatoid arthritis (RA) is associated with heightened mortality due to atherosclerotic cardiovascular disease (CVD). Inflammatory pathways in RA negatively affect vascular physiology and promote metabolic disturbances that contribute to CVD. We hypothesized that the peroxisome proliferator activated receptor‐γ (PPAR‐γ) pioglitazone could promote potent vasculoprotective and anti‐inflammatory effects in RA. Methods and Results One hundred forty‐three non‐diabetic adult RA patients (76.2% female, age 55.2±12.1 [mean±SD]) on stable RA standard of care treatment were enrolled in a randomized, double‐blind placebo controlled crossover trial of 45 mg daily pioglitazone versus placebo, with a 3‐month duration/arm and a 2‐month washout period. Pulse wave velocity of the aorta (PWV), brachial artery flow mediated dilatation (FMD), nitroglycerin mediated dilatation (NMD), microvascular endothelial function (reactive hyperemia index [RHI]), and circulating biomarkers of inflammation, insulin resistance, and atherosclerosis risk all were quantified. RA disease activity was assessed with the 28‐Joint Count Disease Activity Score (DAS‐28) C‐reactive protein (CRP) and the Short Form (36) Health Survey quality of life questionnaire. When added to standard of care RA treatment, pioglitazone significantly decreased pulse wave velocity (ie, aortic stiffness) (P=0.01), while FMD and RHI remained unchanged when compared to treatment with placebo. Further, pioglitazone significantly reduced RA disease activity (P=0.02) and CRP levels (P=0.001), while improving lipid profiles. The drug was well tolerated. Conclusions Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues. The clinical implications of these findings remain to be established. Clinical Trial Registration URL: ClinicalTrials.gov Unique Identifier: NCT00554853. PMID:24252844

  13. The Soluble Epoxide Hydrolase Inhibitor AR9281 Decreases Blood Pressure, Ameliorates Renal Injury and Improves Vascular Function in Hypertension

    Directory of Open Access Journals (Sweden)

    Sean Shaw

    2009-12-01

    Full Text Available Soluble epoxide hydrolase inhibitors (sEHIs are demonstrating promise as potential pharmaceutical agents for the treatment of cardiovascular disease, diabetes, inflammation, and kidney disease. The present study determined the ability of a first-inclass sEHI, AR9281, to decrease blood pressure, improve vascular function, and decrease renal inflammation and injury in angiotensin hypertension. Rats were infused with angiotensin and AR9281 was given orally during the 14-day infusion period. Systolic blood pressure averaged 180 ± 5 mmHg in vehicle treated and AR9281 treatment significantly lowered blood pressure to 142 ± 7 mmHg in angiotensin hypertension. Histological analysis demonstrated decreased injury to the juxtamedullary glomeruli. Renal expression of inflammatory genes was increased in angiotensin hypertension and two weeks of AR9281 treatment decreased this index of renal inflammation. Vascular function in angiotensin hypertension was also improved by AR9281 treatment. Decreased afferent arteriolar and mesenteric resistance endothelial dependent dilator responses were ameliorated by AR9281 treatment of angiotensin hypertensive rats. These data demonstrate that the first-in-class sEHI, AR9281, lowers blood pressure, improves vascular function and reduces renal damage in angiotensin hypertension.

  14. Vascular function assessed by passive leg movement and flow-mediated dilation: initial evidence of construct validity.

    Science.gov (United States)

    Rossman, Matthew J; Groot, H Jonathan; Garten, Ryan S; Witman, Melissa A H; Richardson, Russell S

    2016-11-01

    The vasodilatory response to passive leg movement (PLM) appears to provide a novel, noninvasive assessment of vascular function. However, PLM has yet to be compared with the established noninvasive assessment of vascular health, flow-mediated dilation (FMD). Therefore, as an initial evaluation of the construct validity of PLM and upright seated and supine PLM as well as brachial (BA) and superficial femoral (SFA) artery FMDs were performed in 10 young (22 ± 1) and 30 old (73 ± 2) subjects. During upright seated PLM, the peak change in leg blood flow (ΔLBF) and leg vascular conductance (ΔLVC) was significantly correlated with BA (r = 0.57 and r = 0.66) and SFA (r = 0.44 and r = 0.41, ΔLBF and ΔLVC, respectively) FMD. Furthermore, although the relationships were not as strong, the supine PLM response was also significantly correlated with BA (r = 0.38 and r = 0.35) and SFA (r = 0.39 and r = 0.35, ΔLBF and ΔLVC, respectively) FMD. Examination of the young and old separately, however, revealed that significant relationships persisted in both groups only for the upright seated PLM response and BA FMD (young: r = 0.73 and r = 0.77; old: r = 0.35 and r = 0.45, ΔLBF and ΔLVC, respectively). Normalizing FMD for shear rate during PLM abrogated all significant relationships between the PLM and FMD response, suggesting a role for nitric oxide (NO) in these associations. Collectively, these data indicate that PLM, particularly upright seated PLM, likely provides an index of vascular health analogous to the traditional FMD test. Given the relative ease of PLM implementation, these data have important positive implications for PLM as a clinical vascular health assessment.

  15. Acute impact of intermittent pneumatic leg compression frequency on limb hemodynamics, vascular function, and skeletal muscle gene expression in humans.

    Science.gov (United States)

    Sheldon, Ryan D; Roseguini, Bruno T; Thyfault, John P; Crist, Brett D; Laughlin, M H; Newcomer, Sean C

    2012-06-01

    The mechanisms by which intermittent pneumatic leg compression (IPC) treatment effectively treats symptoms associated with peripheral artery disease remain speculative. With the aim of gaining mechanistic insight into IPC treatment, the purpose of this study was to investigate the effect of IPC frequency on limb hemodynamics, vascular function, and skeletal muscle gene expression. In this two study investigation, healthy male subjects underwent an hour of either high-frequency (HF; 2-s inflation/3-s deflation) or low-frequency (LF; 4-s inflation/16-s deflation) IPC treatment of the foot and calf. In study 1 (n = 11; 23.5 ± 4.7 yr), subjects underwent both HF and LF treatment on separate days. Doppler/ultrasonography was used to measure popliteal artery diameter and blood velocity at baseline and during IPC treatment. Flow-mediated dilation (FMD) and peak reactive hyperemia blood flow (RHBF) were determined before and after IPC treatment. In study 2 (n = 19; 22.0 ± 4.6 yr), skeletal muscle biopsies were taken from the lateral gastrocnemius of the treated and control limb at baseline and at 30- and 150-min posttreatment. Quantitative PCR was used to assess mRNA concentrations of genes associated with inflammation and vascular remodeling. No treatment effect on vascular function was observed. Cuff deflation resulted in increased blood flow (BF) and shear rate (SR) in both treatments at the onset of treatment compared with baseline (P inflation. IPC decreased the mRNA expression of cysteine-rich protein 61 from baseline and controls (P <0 .01) and connective tissue growth factor from baseline (P < 0.05) in a frequency-dependent manner. In conclusion, a single session of IPC acutely impacts limb hemodynamics and skeletal muscle gene expression in a frequency-dependent manner but does not impact vascular function.

  16. Salvianolic acid B improves vascular endothelial function in diabetic rats with blood glucose fluctuations via suppression of endothelial cell apoptosis.

    Science.gov (United States)

    Ren, Younan; Tao, Shanjun; Zheng, Shuguo; Zhao, Mengqiu; Zhu, Yuanmei; Yang, Jieren; Wu, Yuanjie

    2016-11-15

    Vascular endothelial cell injury is an initial event in atherosclerosis. Salvianolic acid B (Sal B), a main bioactive component in the root of Salvia miltiorrhiza, has vascular protective effect in diabetes, but the underlying mechanisms remain unclear. The present study investigated the effect of Sal B on vascular endothelial function in diabetic rats with blood glucose fluctuations and the possible mechanisms implicated. The results showed that diabetic rats developed marked endothelial dysfunction as exhibited by impaired acetylcholine induced vasodilation. Supplementation with Sal B resulted in an evident improvement of endothelial function. Phosphorylation (Ser 1177) of endothelial nitric oxide synthase (eNOS) was significantly restored in Sal B treated diabetic rats, accompanied by an evident recovery of NO metabolites. Sal B effectively reduced vascular endothelial cell apoptosis, with Bcl-2 protein up-regulated and Bax protein down-regulated markedly. Treatment with Sal B led to an evident amelioration of oxidative stress in diabetic rats as manifested by enhanced antioxidant capacity and decreased contents of malondialdehyde in aortas. Protein levels of NOX2 and NOX4, two main isoforms of NADPH oxidase known as the major source of reactive oxygen species in the vasculature, were markedly decreased in Sal B treated groups. In addition, treatment with Sal B led to an evident decrease of serum lipids. Taken together, this study indicates that Sal B is capable of improving endothelial function in diabetic rats with blood glucose fluctuations, of which the underlying mechanisms might be related to suppression of endothelial cell apoptosis and stimulation of eNOS phosphorylation (Ser 1177).

  17. Preservation of endothelial integrity and function in experimental vascular anastomosis with non-penetrating clips

    NARCIS (Netherlands)

    Zeebregts, C; van den Dungen, J; Buikema, H; Tiebosch, A; van der Want, J; van Schilfgaarde, R

    2001-01-01

    Background: Vascular repair with sutures is associated with disruption of the endothelial lining and subsequent thrombus formation on the intraluminal lesions. This experimental study was designed to determine whether the use of non-penetrating clips improved endothelial preservation. Methods: In te

  18. Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study.

    Science.gov (United States)

    Bruder-Nascimento, Thiago; Campos, Dijon Henrique Salome

    2015-01-23

    Background: Stress is associated with cardiovascular diseases. Objective: This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Methods: Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca2+ flux was also evaluated. Results: Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca2+ was decreased in the aorta of stressed rats. Conclusion: Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca2+-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)Fundamento: Estresse está associado com complicações cardiovasculares. Objetivos: O objetivo do presente estudo foi avaliar se o estresse crônico induz alterações vasculares, e se essas alterações são dependentes de óxido nítrico (NO) e Ca2+. Métodos: Ratos machos Wistar com 30 dias de idade foram separados em 2 grupos: controle (C) e Estresse (St). Utilizou-se estresse crônico de imobilização por 1 hora/dia, 5 dias/semana, 15 semanas. Pressão arterial sistólica foi avaliada. A função vascular foi

  19. Sertoli Cells Modulate Testicular Vascular Network Development, Structure, and Function to Influence Circulating Testosterone Concentrations in Adult Male Mice.

    Science.gov (United States)

    Rebourcet, Diane; Wu, Junxi; Cruickshanks, Lyndsey; Smith, Sarah E; Milne, Laura; Fernando, Anuruddika; Wallace, Robert J; Gray, Calum D; Hadoke, Patrick W F; Mitchell, Rod T; O'Shaughnessy, Peter J; Smith, Lee B

    2016-06-01

    The testicular vasculature forms a complex network, providing oxygenation, micronutrients, and waste clearance from the testis. The vasculature is also instrumental to testis function because it is both the route by which gonadotropins are delivered to the testis and by which T is transported away to target organs. Whether Sertoli cells play a role in regulating the testicular vasculature in postnatal life has never been unequivocally demonstrated. In this study we used models of acute Sertoli cell ablation and acute germ cell ablation to address whether Sertoli cells actively influence vascular structure and function in the adult testis. Our findings suggest that Sertoli cells play a key role in supporting the structure of the testicular vasculature. Ablating Sertoli cells (and germ cells) or germ cells alone results in a similar reduction in testis size, yet only the specific loss of Sertoli cells leads to a reduction in total intratesticular vascular volume, the number of vascular branches, and the numbers of small microvessels; loss of germ cells alone has no effect on the testicular vasculature. These perturbations to the testicular vasculature leads to a reduction in fluid exchange between the vasculature and testicular interstitium, which reduces gonadotropin-stimulated circulating T concentrations, indicative of reduced Leydig cell stimulation and/or reduced secretion of T into the vasculature. These findings describe a new paradigm by which the transport of hormones and other factors into and out of the testis may be influenced by Sertoli cells and highlights these cells as potential targets for enhancing this endocrine relationship.

  20. Thigh muscle size and vascular function after blood flow-restricted elastic band training in older women

    Science.gov (United States)

    Yasuda, Tomohiro; Fukumura, Kazuya; Tomaru, Takanobu; Nakajima, Toshiaki

    2016-01-01

    We examined the effect of elastic band training with blood flow restriction (BFR) on thigh muscle size and vascular function in older women. Older women were divided into three groups: low-intensity elastic band BFR training (BFR-Tr, n = 10), middleto high-intensity elastic band training (MH-Tr, n = 10), and no training (Ctrl, n = 10) groups. BFR-Tr and MH-Tr groups performed squat and knee extension exercises using elastic band, 2 days/week for 12 weeks. During BFR-Tr exercise session, subjects wore pressure cuffs around the most proximal region of both thighs. The following measurements were taken before (pre) and 3-5 days after (post) the final training session: MRI-measured muscle cross-sectional area (CSA) at mid-thigh, maximum voluntary isometric contraction (MVIC) of knee extension, central systolic blood pressure (c-SBP), central-augmentation index (c-AIx), cardio-ankle vascular index testing (CAVI), ankle-brachial pressure index (ABI). Quadriceps muscle CSA (6.9%) and knee extension MVIC (13.7%) were increased (p muscle CSA as well as maximal muscle strength, but does not decrease vascular function in older women. PMID:27244884

  1. Effects of Acute Exposure to Moderate Altitude on Vascular Function, Metabolism and Systemic Inflammation

    Science.gov (United States)

    Stöwhas, Anne-Christin; Latshang, Tsogyal D.; Lo Cascio, Christian M.; Lautwein, Sina; Stadelmann, Katrin; Tesler, Noemi; Ayers, Lisa; Berneis, Kaspar; Gerber, Philipp A.; Huber, Reto; Achermann, Peter; Bloch, Konrad E.; Kohler, Malcolm

    2013-01-01

    Background Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown. Objectives To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation. Methods In 51 healthy male subjects with a mean (SD) age of 26.9 (9.3) years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL) particle size, insulin resistance (HOMA-index), highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich) and during two days at 2590 m, (Davos Jakobshorn, Switzerland) in randomized order. The largest differences in outcomes between the two altitudes are reported. Results Mean (SD) oxygen saturation was significantly lower at 2590 m, 91.0 (2.0)%, compared to 490 m, 96.0 (1.0)%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001) and heart rate (mean difference +3.3 bpm, p<0.001) were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides −0.14 mmol/l, p = 0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio −0.25, p = 0.001), LDL particle size increased (median difference +0.45 nm, p = 0.048) and hsCRP decreased (median difference −0.18 mg/l, p = 0.024) compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m. Conclusions Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism. Trial Registration ClinicalTrials.gov NCT01130948 PMID:23936377

  2. Effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Anne-Christin Stöwhas

    Full Text Available BACKGROUND: Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown. OBJECTIVES: To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation. METHODS: In 51 healthy male subjects with a mean (SD age of 26.9 (9.3 years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL particle size, insulin resistance (HOMA-index, highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich and during two days at 2590 m, (Davos Jakobshorn, Switzerland in randomized order. The largest differences in outcomes between the two altitudes are reported. RESULTS: Mean (SD oxygen saturation was significantly lower at 2590 m, 91.0 (2.0%, compared to 490 m, 96.0 (1.0%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001 and heart rate (mean difference +3.3 bpm, p<0.001 were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides -0.14 mmol/l, p=0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio -0.25, p=0.001, LDL particle size increased (median difference +0.45 nm, p=0.048 and hsCRP decreased (median difference -0.18 mg/l, p=0.024 compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m. CONCLUSIONS: Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism. TRIAL REGISTRATION: ClinicalTrials.gov NCT01130948.

  3. Di-peptidyl peptidase-4 inhibitor sitagliptin protects vascular function in metabolic syndrome: possible role of epigenetic regulation.

    Science.gov (United States)

    Cicek, Figen Amber; Amber, Cicek Figen; Tokcaer-Keskin, Zeynep; Zeynep, Tokcaer-Keskin; Ozcinar, Evren; Evren, Ozcinar; Bozkus, Yosuf; Yusuf, Bozkus; Akcali, Kamil Can; Can, Akcali Kamil; Turan, Belma; Belma, Turan

    2014-08-01

    Metabolic syndrome (MetS) is a complex medical disorder characterized by insulin resistance, hypertension, and high risk of coronary disease and stroke. Microvascular rarefaction and endothelial dysfunction have also been linked with MetS, and recent evidence from clinical studies supports the efficacy of incretin-based antidiabetic therapies for vascular protection in diabetes. Previous studies pointed out the importance of dipeptidyl peptidase-4 (DPP-4) inhibition in endothelial cells due to getting protection against metabolic pathologies. We therefore aimed to investigate the acute effects of a DPP-4 inhibitor, sitagliptin, on vascular function in rats with high-sucrose diet-induced MetS. In order to elucidate the mechanisms implicated in the effects of DPP-4 inhibition, we tested the involvement of NO pathway and epigenetic regulation in the MetS. Acute use of sitagliptin protects the vascular function in the rats with MetS in part due to NO pathway via restoring the depressed aortic relaxation responses mediated by receptors. Application of sitagliptin enhanced the depressed phosphorylation levels of both the endothelial NO synthase and the apoptotic status of protein kinase B, known as Akt, in endothelium-intact thoracic aorta from rats with MetS. One-hour application of sitagliptin on aortic rings from rats with MetS also induced remarkable histon posttranslational modifications such as increased expression of H3K27Me3, but not of H3K27Me2, resulting in an accumulation of the H3K27Me3. Our findings suggest that, in addition to its well-known hypoglycemic action, sitagliptin may also have beneficial effects on hyperglycemia-induced vascular changes in an endotheium-dependent manner. These present results with sitagliptin aside from the glycaemic control, may demonstrate its important role in the treatment of patients with MetS.

  4. Functional characteristics of coronary vasomotor function following intramyocardial gene therapy with naked DNA encoding for vascular endothelial growth factor 165

    NARCIS (Netherlands)

    Tio, RA; Wijpkema, JS; Tan, ES; Asselbergs, FW; Hospers, GAP; Jessurun, GAJ; Zijlstra, F

    2005-01-01

    Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. VEGF gene therapy improves perfusion of ischemic myocardium in experimental models and possibly in patients with end-stage coronary artery disease. In addition to its proliferative and migratory effect on endothelial cells, it

  5. Reprint of "The role of cytoskeleton in the regulation of vascular endothelial barrier function" [Microvascular Research 76 (2008) 202-207].

    Science.gov (United States)

    Bogatcheva, Natalia V; Verin, Alexander D

    2009-01-01

    The cytoskeleton is vital to the function of virtually all cell types in the organism as it is required for cell division, cell motility, endo- or exocytosis and the maintenance of cell shape. Endothelial cells, lining the inner surface of the blood vessels, exploit cytoskeletal elements to ensure the integrity of cell monolayer in quiescent endothelium, and to enable the disintegration of the formed barrier in response to various agonists. Vascular permeability is defined by the combination of transcellular and paracellular pathways, with the latter being a major contributor to the inflammation-induced barrier dysfunction. This review will analyze the cytoskeletal elements, which reorganization affects endothelial permeability, and emphasize signaling mechanisms with barrier-protective or barrier-disruptive potential.

  6. Dietary flavonoids and nitrate: effects on nitric oxide and vascular function.

    Science.gov (United States)

    Bondonno, Catherine P; Croft, Kevin D; Ward, Natalie; Considine, Michael J; Hodgson, Jonathan M

    2015-04-01

    Emerging evidence highlights dietary flavonoids and nitrate as candidates that may explain at least part of the cardioprotective effect of a fruit and vegetable diet. Nitric oxide plays a pivotal role in cardiovascular health. Components of a fruit and vegetable diet that are cardioprotective, in part through effects on nitric oxide status, could substantially reduce the cardiovascular risk profile of the general population with increased intake of such a diet. Epidemiological evidence suggests that dietary flavonoids and nitrate have a cardioprotective effect. Clinical trials with flavonoid- and nitrate-rich foods have shown benefits on measures of vascular health. While the molecular mechanisms by which flavonoids and nitrate are cardioprotective are not completely understood, recent evidence suggests both nonspecific and specific effects through nitric oxide pathways. This review presents an overview of nitric oxide and its key role in cardiovascular health and discusses the possible vascular benefits of flavonoids and nitrate, individually and in combination, through effects on nitric oxide status.

  7. Coaxial electrospinning multicomponent functional controlled-release vascular graft: Optimization of graft properties.

    Science.gov (United States)

    Yin, Anlin; Luo, Rifang; Li, Jiukai; Mo, Xiumei; Wang, Yunbing; Zhang, Xingdong

    2017-04-01

    Small diameter vascular grafts possessing desirable biocompatibility and suitable mechanical properties have become an urgent clinic demand. Herein, heparin loaded fibrous grafts of collagen/chitosan/poly(l-lactic acid-co-ε-caprolactone) (PLCL) were successfully fabricated via coaxial electrospinning. By controlling the concentration of heparin and the ratio of collagen/chitosan/PLCL, most grafts had the heparin encapsulation efficiency higher than 70%, and the heparin presented sustained release for more than 45 days. Particularly, such multicomponent grafts had relative low initial burst release, and after heparin releasing for 3 weeks, the grafts still showed good anti-platelet adhesion ability. In addition, along with the excellent cell biocompatibility, the fabricated grafts possessed suitable mechanical properties including good tensile strength, suture retention strength, burst pressure and compliance which could well match the native blood vessels. Thus, the optimized graft properties could be properly addressed for vascular tissue application via coaxial electrospinning.

  8. Lipid lowering and HDL raising gene transfer increase endothelial progenitor cells, enhance myocardial vascularity, and improve diastolic function.

    Directory of Open Access Journals (Sweden)

    Stephanie C Gordts

    Full Text Available BACKGROUND: Hypercholesterolemia and low high density lipoprotein (HDL cholesterol contribute to coronary heart disease but little is known about their direct effects on myocardial function. Low HDL and raised non-HDL cholesterol levels carried increased risk for heart failure development in the Framingham study, independent of any association with myocardial infarction. The objective of this study was to test the hypothesis that increased endothelial progenitor cell (EPC number and function after lipid lowering or HDL raising gene transfer in C57BL/6 low density lipoprotein receptor deficient (LDLr(-/- mice may be associated with an enhanced relative vascularity in the myocardium and an improved cardiac function. METHODOLOGY/PRINCIPAL FINDINGS: Lipid lowering and HDL raising gene transfer were performed using the E1E3E4-deleted LDLr expressing adenoviral vector AdLDLr and the human apolipoprotein A-I expressing vector AdA-I, respectively. AdLDLr transfer in C57BL/6 LDLr(-/- mice resulted in a 2.0-fold (p<0.05 increase of the circulating number of EPCs and in an improvement of EPC function as assessed by ex vivo EPC migration and EPC adhesion. Capillary density and relative vascularity in the myocardium were 28% (p<0.01 and 22% (p<0.05 higher, respectively, in AdLDLr mice compared to control mice. The peak rate of isovolumetric relaxation was increased by 12% (p<0.05 and the time constant of isovolumetric relaxation was decreased by 14% (p<0.05 after AdLDLr transfer. Similarly, HDL raising gene transfer increased EPC number and function and raised both capillary density and relative vascularity in the myocardium by 24% (p<0.05. The peak rate of isovolumetric relaxation was increased by 16% (p<0.05 in AdA-I mice compared to control mice. CONCLUSIONS/SIGNIFICANCE: Both lipid lowering and HDL raising gene transfer have beneficial effects on EPC biology, relative myocardial vascularity, and diastolic function. These findings raise concerns over the

  9. Age related vascular endothelial function following lifelong sedentariness: positive impact of cardiovascular conditioning without further improvement following low frequency high intensity interval training

    OpenAIRE

    Grace, Fergal M.; Herbert, Peter; Ratcliffe, John W.; New, Karl J; Baker, Julien S; Sculthorpe, Nicholas F.

    2015-01-01

    Abstract Aging is associated with diffuse impairments in vascular endothelial function and traditional aerobic exercise is known to ameliorate these changes. High intensity interval training (HIIT) is effective at improving vascular function in aging men with existing disease, but its effectiveness remains to be demonstrated in otherwise healthy sedentary aging. However, the frequency of commonly used HIIT protocols may be poorly tolerated in older cohorts. Therefore, the present study invest...

  10. Notch2 and Notch3 Function Together to Regulate Vascular Smooth Muscle Development

    OpenAIRE

    Qingqing Wang; Ning Zhao; Simone Kennard; Brenda Lilly

    2012-01-01

    Notch signaling has been implicated in the regulation of smooth muscle differentiation, but the precise role of Notch receptors is ill defined. Although Notch3 receptor expression is high in smooth muscle, Notch3 mutant mice are viable and display only mild defects in vascular patterning and smooth muscle differentiation. Notch2 is also expressed in smooth muscle and Notch2 mutant mice show cardiovascular abnormalities indicative of smooth muscle defects. Together, these findings infer that N...

  11. TGF-beta is required for vascular barrier function, endothelial survival and homeostasis of the adult microvasculature.

    Directory of Open Access Journals (Sweden)

    Tony E Walshe

    Full Text Available Pericyte-endothelial cell (EC interactions are critical to both vascular development and vessel stability. We have previously shown that TGF-beta signaling between EC and mural cells participates in vessel stabilization in vitro. We therefore investigated the role of TGF-beta signaling in maintaining microvessel structure and function in the adult mouse retinal microvasculature. TGF-beta signaling was inhibited by systemic expression of soluble endoglin (sEng and inhibition was demonstrated by reduced phospho-smad2 in the adult retina. Blockade of TGF-beta signaling led to increased vascular and neural cell apoptosis in the retina, which was associated with decreased retinal function, as measured by electroretinogram (ERG. Perfusion of the inner retinal vasculature was impaired and was accompanied by defective autoregulation and loss of capillary integrity. Fundus angiography and Evans blue permeability assay revealed a breakdown of the blood-retinal-barrier that was characterized by decreased association between the tight junction proteins zo-1 and occludin. Inhibition of TGF-beta signaling in cocultures of EC and 10T1/2 cells corroborated the in vivo findings, with impaired EC barrier function, dissociation of EC from 10T1/2 cells, and endothelial cell death, supporting the role of EC-mesenchymal interactions in TGF-beta signaling. These results implicate constitutive TGF-beta signaling in maintaining the integrity and function of the adult microvasculature and shed light on the potential role of TGF-beta signaling in vasoproliferative and vascular degenerative retinal diseases.

  12. Arterial wall mechanics as a function of heart rate: role of vascular smooth muscle

    Energy Technology Data Exchange (ETDEWEB)

    Salvucci, Fernando Pablo; Schiavone, Jonathan; Craiem, Damian; Barra, Juan Gabriel [Facultad de Ingenieria y Ciencias Exactas y Naturales, Universidad Favaloro Av. Belgrano 1723 - Buenos Aires (Argentina)

    2007-11-15

    Vascular wall viscoelasticity can be evaluated using a first-order lumped model. This model consists of a spring with elastic constant E and a dashpot with viscous constant {eta}. More importantly, this viscoelastic model can be fitted in-vivo measuring arterial pressure and diameter. The aim of this work is to analyze the influence of heart rate over E and {eta}. In two anesthetized sheep, diameter in thoracic aorta and intravascular pressure has been registered. The right atrium was connected to a programmable stimulator through a pair of pace-maker wires to produce changes in stimulation heart rate (HR) from 80 to 160 bpm. Additionally, local activation of vascular smooth muscle was induced with phenylephrine. After converting pressure and diameter signals into stress and strain respectively, E y {eta} were calculated in control state and during muscle activation. The elastic modulus E did not present significant changes with heart rate. The viscous modulus {eta} decreased 49% with a two-fold acceleration in heart rate from 80 to 160 bpm. However, the product {eta} HR remained stable. The viscous modulus {eta} increased 39% with smooth muscle activation. No significant pressure changes were registered during the experiment. The contractile action of vascular smooth muscle could contribute to increasing arterial wall viscosity. The decrease of {eta} when HR increased might be related to smooth muscle relaxation mediated by endothelium activity, which was stimulated by flow increase. We conclude that HR can modulate arterial wall viscoelasticity through endothelium-dependent mechanisms.

  13. Human apolipoprotein E ɛ4 expression impairs cerebral vascularization and blood-brain barrier function in mice.

    Science.gov (United States)

    Alata, Wael; Ye, Yue; St-Amour, Isabelle; Vandal, Milène; Calon, Frédéric

    2015-01-01

    Human apolipoprotein E (APOE) exists in three isoforms ɛ2, ɛ3, and ɛ4, of which APOE4 is the main genetic risk factor of Alzheimer's disease (AD). As cerebrovascular defects are associated with AD, we tested whether APOE genotype has an impact on the integrity and function of the blood-brain barrier (BBB) in human APOE-targeted replacement mice. Using the quantitative in situ brain perfusion technique, we first found lower (13.0% and 17.0%) brain transport coefficient (Clup) of [(3)H]-diazepam in APOE4 mice at 4 and 12 months, compared with APOE2 and APOE3 mice, reflecting a decrease in cerebral vascularization. Accordingly, results from immunohistofluorescence experiments revealed a structurally reduced cerebral vascularization (26% and 38%) and thinner basement membranes (30% and 35%) in 12-month-old APOE4 mice compared with APOE2 and APOE3 mice, suggesting vascular atrophy. In addition, APOE4 mice displayed a 29% reduction in [(3)H]-d-glucose transport through the BBB compared with APOE2 mice without significant changes in the expression of its transporter GLUT1 in brain capillaries. However, an increase of 41.3% of receptor for advanced glycation end products (RAGE) was found in brain capillaries of 12-month-old APOE4 mice. In conclusion, profound divergences were observed between APOE genotypes at the cerebrovascular interface, suggesting that APOE4-induced BBB anomalies may contribute to AD development.

  14. Human apolipoprotein E ɛ4 expression impairs cerebral vascularization and blood–brain barrier function in mice

    Science.gov (United States)

    Alata, Wael; Ye, Yue; St-Amour, Isabelle; Vandal, Milène; Calon, Frédéric

    2015-01-01

    Human apolipoprotein E (APOE) exists in three isoforms ɛ2, ɛ3, and ɛ4, of which APOE4 is the main genetic risk factor of Alzheimer's disease (AD). As cerebrovascular defects are associated with AD, we tested whether APOE genotype has an impact on the integrity and function of the blood–brain barrier (BBB) in human APOE-targeted replacement mice. Using the quantitative in situ brain perfusion technique, we first found lower (13.0% and 17.0%) brain transport coefficient (Clup) of [3H]-diazepam in APOE4 mice at 4 and 12 months, compared with APOE2 and APOE3 mice, reflecting a decrease in cerebral vascularization. Accordingly, results from immunohistofluorescence experiments revealed a structurally reduced cerebral vascularization (26% and 38%) and thinner basement membranes (30% and 35%) in 12-month-old APOE4 mice compared with APOE2 and APOE3 mice, suggesting vascular atrophy. In addition, APOE4 mice displayed a 29% reduction in [3H]-d-glucose transport through the BBB compared with APOE2 mice without significant changes in the expression of its transporter GLUT1 in brain capillaries. However, an increase of 41.3% of receptor for advanced glycation end products (RAGE) was found in brain capillaries of 12-month-old APOE4 mice. In conclusion, profound divergences were observed between APOE genotypes at the cerebrovascular interface, suggesting that APOE4-induced BBB anomalies may contribute to AD development. PMID:25335802

  15. Comparison of blood pool and extracellular gadolinium chelate for functional MR evaluation of vascular thoracic outlet syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Ruth P., E-mail: ruthplim74@gmail.com [New York University School of Medicine, Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, 660 1st Avenue, New York, NY 10016 (United States); Austin Health, Department of Radiology, Heidelberg, Victoria 3084 (Australia); The University of Melbourne, School of Medicine, Parkville, Victoria 3010 (Australia); Bruno, Mary, E-mail: mary.bruno@nyumc.org [New York University School of Medicine, Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, 660 1st Avenue, New York, NY 10016 (United States); Rosenkrantz, Andrew B., E-mail: Andrew.rosenkrantz@nyumc.org [New York University School of Medicine, Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, 660 1st Avenue, New York, NY 10016 (United States); Kim, Danny C., E-mail: danny.kim@nyumc.org [New York University School of Medicine, Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, 660 1st Avenue, New York, NY 10016 (United States); Mulholland, Thomas, E-mail: Thomas.mulholland@nyumc.org [New York University School of Medicine, Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, 660 1st Avenue, New York, NY 10016 (United States); Kwon, Jane, E-mail: jane.kwon@nyumc.org [New York University School of Medicine, Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, 660 1st Avenue, New York, NY 10016 (United States); Palfrey, Amy P., E-mail: amy.pastva10@stjohns.edu [St John' s University, Department of Psychology, 8000 Utopia Parkway, Jamaica-Queens, NY 11439 (United States); Ogedegbe, Olugbenga, E-mail: Olugbenga.Ogedegbe@nyumc.org [New York University School of Medicine, Clinical and Translational Science Institute, 227 E30th St, 8th Floor, New York, NY 10016 (United States)

    2014-07-15

    Objective: To compare performance of single-injection blood pool agent (gadofosveset trisodium, BPA) against dual-injection extracellular contrast (gadopentetate dimeglumine, ECA) for MRA/MRV in assessment of suspected vascular TOS. Materials and methods: Thirty-one patients referred for vascular TOS evaluation were assessed with BPA (n = 18) or ECA (n = 13) MRA/MRV in arm abduction and adduction. Images were retrospectively assessed for: image quality (1 = non-diagnostic, 5 = excellent), vessel contrast (1 = same signal as muscle, 4 = much brighter than muscle) and vascular pathology by two independent readers, with a separate experienced reader providing reference assessment of vascular pathology. Results: Median image quality was diagnostic or better (score ≥3) for ECA and BPA at all time points, with BPA image quality superior at abduction late (BPA 4.5, ECA 4, p = 0.042) and ECA image quality superior at adduction-early (BPA 4.5; ECA 4.0, p = 0.018). High qualitative vessel contrast (mean score ≥3) was observed at all time points with both BPA and ECA, with superior BPA vessel contrast at abduction-late (BPA 3.97 ± 0.12; ECA 3.73 ± 0.26, p = 0.007) and ECA at adduction-early (BPA 3.42 ± 0.52; ECA 3.96 ± 0.14, p < 0.001). Readers readily identified arterial and venous pathology with BPA, similar to ECA examinations. Conclusion: Single-injection BPA MRA/MRV for TOS evaluation demonstrated diagnostic image quality and high vessel contrast, similar to dual-injection ECA imaging, enabling identification of fixed and functional arterial and venous pathology.

  16. Admixture mapping scans identify a locus affecting retinal vascular caliber in hypertensive African Americans: the Atherosclerosis Risk in Communities (ARIC study.

    Directory of Open Access Journals (Sweden)

    Ching-Yu Cheng

    2010-04-01

    Full Text Available Retinal vascular caliber provides information about the structure and health of the microvascular system and is associated with cardiovascular and cerebrovascular diseases. Compared to European Americans, African Americans tend to have wider retinal arteriolar and venular caliber, even after controlling for cardiovascular risk factors. This has suggested the hypothesis that differences in genetic background may contribute to racial/ethnic differences in retinal vascular caliber. Using 1,365 ancestry-informative SNPs, we estimated the percentage of African ancestry (PAA and conducted genome-wide admixture mapping scans in 1,737 African Americans from the Atherosclerosis Risk in Communities (ARIC study. Central retinal artery equivalent (CRAE and central retinal vein equivalent (CRVE representing summary measures of retinal arteriolar and venular caliber, respectively, were measured from retinal photographs. PAA was significantly correlated with CRVE (rho = 0.071, P = 0.003, but not CRAE (rho = 0.032, P = 0.182. Using admixture mapping, we did not detect significant admixture association with either CRAE (genome-wide score = -0.73 or CRVE (genome-wide score = -0.69. An a priori subgroup analysis among hypertensive individuals detected a genome-wide significant association of CRVE with greater African ancestry at chromosome 6p21.1 (genome-wide score = 2.31, locus-specific LOD = 5.47. Each additional copy of an African ancestral allele at the 6p21.1 peak was associated with an average increase in CRVE of 6.14 microm in the hypertensives, but had no significant effects in the non-hypertensives (P for heterogeneity <0.001. Further mapping in the 6p21.1 region may uncover novel genetic variants affecting retinal vascular caliber and further insights into the interaction between genetic effects of the microvascular system and hypertension.

  17. Markers of T cell infiltration and function associate with favorable outcome in vascularized high-grade serous ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Katelin N Townsend

    Full Text Available BACKGROUND: When T cells infiltrate the tumor environment they encounter a myriad of metabolic stressors including hypoxia. Overcoming the limitations imposed by an inadequate tumor vasculature that contributes to these stressors may be a crucial step to immune cells mounting an effective anti-tumor response. We sought to determine whether the functional capacity of tumor infiltrating lymphocytes (TIL could be influenced by the tumor vasculature and correlated this with survival in patients with ovarian cancer. METHODOLOGY AND PRINCIPAL FINDINGS: In 196 high-grade serous ovarian tumors, we confirmed that the tumor vascularity as measured by the marker CD31 was associated with improved patient disease-specific survival. We also found that tumors positive for markers of TIL (CD8, CD4 and forkhead box P3 (FoxP3 and T cell function (granzyme B and T-cell restricted intracellular antigen-1 (TIA-1 correlated significantly with elevated vascularity. In vitro, hypoxic CD8 T cells showed reduced cytolytic activity, secreted less effector cytokines and upregulated autophagy. Survival analysis revealed that patients had a significant improvement in disease-specific survival when FoxP3 expressing cells were present in CD31-high tumors compared to patients with FoxP3 expressing cells in CD31-low tumors [HR: 2.314 (95% CI 1.049-5.106; p = 0.0377]. Patients with high vascular endothelial growth factor (VEGF expressing tumors containing granzyme B positive cells had improved survival compared to patients with granzyme B positive cells in VEGF-low tumors [HR: 2.522 (95% CI 1.097-5.799; p = 0.0294]. SIGNIFICANCE: Overall, this data provides a rationale for developing strategies aimed at improving the adaptability and function of TIL to hypoxic tumor conditions.

  18. Effect of Solitaire AB stent thrombectomy on vascular endothelial function and inflammatory cytokines in patients with progressive cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Zhi-Bao Wu; Xue-Juan Han; Zi-Hao Zhang; Wen-Liang Zhang; Liang Liu

    2016-01-01

    Objective:To observe the effect of Solitaire AB stent thrombectomy on the vascular endothelial function and inflammatory cytokines in patients with progressive cerebral infarction.Methods:A total of 58 patients with progressive cerebral infarction who were admitted in our hospital were included in the study and divided into the observation group and the control group according to different treatment protocols with 29 cases in each group. The patients in the control group were given the conservation treatment. On this basis, the patients in the observation group were given Solitaire AB stent thrombectomy. The changes of vascular endothelial function and inflammatory cytokines before and after treatment in the two groups were compared.Results:ET-1 after treatment in the two groups was significantly reduced, while NO and CGRP were significantly elevated when compared with before treatment (P<0.05). ET-1 after treatment in the observation group was significantly lower than that in the control group (P<0.05), while NO and CGRP were significantly higher than those in the control group (P<0.05). S100β protein, IL-6, TNF-α, hs-CRP, and MMP-9 levels after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05). The above indicators after treatment in the observation group were significantly lower than those in the control group (P<0.05). MCA and ACA blood flow velocity after treatment in the two groups were significantly elevated when compared with before treatment (P<0.05). MCA and ACA blood flow velocity after treatment in the observation group were significantly higher than those in the control group (P<0.05).Conclusions:Solitaire AB stent thrombectomy can effectively reduce the inflammatory reaction in patients with progressive cerebral infarction, and improve the vascular endothelial function and blood supply for brain tissues.

  19. Influence of amlodipine combined with valsartan to the vascular elasticity function and myocardial cells apoptosis of elderly patients with hypertension

    Institute of Scientific and Technical Information of China (English)

    Xing-Bin Zou; He Huang

    2015-01-01

    Objective: To discuss the influence of amlodipine combined with valsartan to the vascular elasticity function and myocardial cells apoptosis of elderly patients with hypertension. Methods: Selected 70 cases of elderly patients with hypertension treated in our hospital as the research object, using the random number table method to divide them into study group and control group (n=35), and control group was given valsartan treatment, while study group was given amlodipine combined with valsartan treatment, course of treatment of both groups was 2 weeks, to compare the vascular elasticity function, plasma sDR4, sDR5 levels and blood pressure changes before and after treatment of both groups. Results: (1)Vascular elasticity function: C1, C2, ankle brachial index in study group was obviously higher than that in control group [(13.48±3.79) vs (9.18±2.84) mL/mmHg×10, (4.69±1.88 vs 3.71±1.85) mL/mmHg×10, (1.24±0.05 vs 1.14±0.12)] (P<0.05), but PWV was obviously lower than that in control group (10.35±2.5 vs 12.01±2.68) m/s (P<0.05); (2)Myocardial cells: sDR4, sDR5 levels in study group was obviously lower than that in control group (3.63±0.69 vs 5.57±0.15, 39.09±5.18 vs 49.43±6.17)(P<0.05); (3)Blood pressure control: 24 h SBP, 24 h DBP in studygroup was obviously lower than that in control group (122.23±8.42 vs 140.57±9.65, 80.56±8.78 vs 97.54±8.35)(P<0.05). Conclusion: Amlodipine combined with valsartan was helpful to improve vascular elasticity function,slow down myocardial cells apoptosis and control blood pressure levels.

  20. INFLUENCE OF ELECTROACUPUNCTURE ON HYPERTENSION VASCULAR DEMENTIA AND ITS RED CELL IMMUNE-FUNCTION IN THE RAT

    Institute of Scientific and Technical Information of China (English)

    莫飞智; 李坚强; 雷立屏; 赖新生; 刘颂豪

    2000-01-01

    Objective: To probe into the effect of electroacupuncture (EA)on vascular dementia and red cell immune function in the rat. Methods: 30 SD rats were made into renal hypertension rats (RHR) by clamping the kidney arteries with silver clip. 42 days later, their bilateral common carotid arteries were blocked repeatedly to cause cerebral ischemia. The Hypertension vascular dementia model was then set up. Then they were randomly divided into VD model group, EA groupand medication group (Dihydroergotoxine, DHET), with 10 cases in each group. The therapeutic course was 28 days. The ability of learning and memory was using an obs erved by water maze, and the function of red blood cell immune was detected after treatment. Results: the latecy Of the EA group and medication group was shorter than that of model group (P<0.05, P<0. 005), and that of EA group was shorter than medication group (P<0.05, P<0.005). EA and medication could increase the RBC C3b receptor flower circle rate and reduce the RBC-IC flower circle rate significantly(P<0.05,P<0.01). Conclusion: The results indicated that EA therapy could raise the ability of learning and memory and improve the function of red cell immune in VD rats, while the therapeutic effect of EAis better than DHET.

  1. Matrix metalloproteinases limit functional recovery after spinal cord injury by modulation of early vascular events.

    Science.gov (United States)

    Noble, Linda J; Donovan, Frances; Igarashi, Takuji; Goussev, Staci; Werb, Zena

    2002-09-01

    Inflammation in general and proteinases generated as a result are likely mediators of early secondary pathogenesis after spinal cord injury. We report that matrix metalloproteinase-9 (MMP-9) plays an important role in blood-spinal cord barrier dysfunction, inflammation, and locomotor recovery. MMP-9 was present in the meninges and neurons of the uninjured cord. MMP-9 increased rapidly after a moderate contusion spinal cord injury, reaching a maximum at 24 hr, becoming markedly reduced by 72 hr, and not detectable at 7 d after injury. It was seen in glia, macrophages, neutrophils, and vascular elements in the injured spinal cord at 24 hr after injury. The natural tissue inhibitors of MMPs were unchanged over this time course. MMP-9-null mice exhibited significantly less disruption of the blood-spinal cord barrier, attenuation of neutrophil infiltration, and significant locomotor recovery compared with wild-type mice. Similar findings were observed in mice treated with a hydroxamic acid MMP inhibitor from 3 hr to 3 d after injury, compared with the vehicle controls. Moreover, the area of residual white matter at the lesion epicenter was significantly greater in the inhibitor-treated group. This study provides evidence that MMP-9 plays a key role in abnormal vascular permeability and inflammation within the first 3 d after spinal cord injury, and that blockade of MMPs during this critical period attenuates these vascular events and leads to improved locomotor recovery. Our findings suggest that early inhibition of MMPs may be an efficacious strategy for the spinal cord-injured patient.

  2. Penile vascular evaluation and sexual function before and after radical retropubic prostatectomy: 5-year follow-up.

    Science.gov (United States)

    Dubbelman, Yvette D; Wildhagen, Mark F; Dohle, Gert R

    2008-09-01

    Sexual dysfunction is common after surgery for prostate cancer. The aetiology of changes in sexual potency after radical prostatectomy is probably multifactorial, including neurogenic, vascular and psychosexual factors. A prospective study was designed to investigate haemodynamic and psychosexual changes before and after radical retropubic prostatectomy (RRP) for organ-confined prostate cancer. Penile haemodynamic evaluation and an assessment of sexual excitement were performed preoperatively and 3 months after RRP by colour Doppler ultrasonography (CDU) with visual erotic stimulation combined with a single intracavernous injection of a mixture of papaverine/phentolamine. Questionnaires on sexual function [International Index of Erectile Function (IIEF)], general health and quality of life were sent to the patients preoperative, 3 months and 5 years after operation. Forty-eight men participated in the study. Mean age was 62.6 years (range 55-69). CDU did not show any significant reduction in mean peak systolic flow velocity and mean resistance index. From the men who preoperatively had normal arterial inflow 18% developed arteriogenic insufficiency. Some form of veno-occlusive insufficiency and low resistance indices were already present in the majority of normal potent men preoperatively. Surgical technique did not influence penile arterial blood flow after the operation. Three months and 5 years postoperatively, there was a highly significant reduction in erectile function, intercourse satisfaction, overall satisfaction, orgasmic function and sexual desire. However, with respect to the outcome at 3 months there was a significant improvement of orgasmic function 5 years after operation, especially after a bilateral nerve sparing procedure. Erections sufficient for vaginal penetration (questions 3 and 4 of the IIEF, score >or=8) improved from 2% to 11% 3 months and 5 years after RRP respectively. Total IIEF score was significantly better after a bilateral nerve

  3. Trans, and n-3 polyunsaturated fatty acids and vascular function-a yin yang situation?

    Science.gov (United States)

    Dyerberg, Jørn; Christensen, Jeppe H; Eskesen, Dorte; Astrup, Arne; Stender, Steen

    2006-05-01

    Trans fatty acids (TFA) and n-3 polyunsaturated fatty acids (n-3 PUFA) have opposite effects on several biological functions. We report a study on the effects on risk markers for cardiovascular disease. Eighty-seven healthy males were randomly assigned to 8 weeks of daily intake of either 20 g of industrially produced TFA (IP-TFA), 4 g n-3 PUFA, or control fat, incorporated in bakery products as part of the daily food. High-density lipoprotein cholesterol decreased in the TFA-group, triglycerides and mean arterial blood pressure decreased in the n-3 group. Heart rate variability (HRV), arterial dilatory capacity, flow mediated vasodilation, compliance, and distensibility were unchanged. Post hoc, we did a subgroup analysis of the results from the subjects with normal initial HRV. In these, 24-h heart rate (HR) was significantly increased by approximately three beats/min in the TFA group, with a decrease of the same magnitude in the n-3 group. A high HR is associated to an increased mortality and vice versa. Our results thus support the notion that IP-TFA and n-3 PUFA affect risk for cardiovascular mortality via mechanisms not only related to changes in plasma concentrations of lipids and lipoproteins.

  4. Vascular endothelial growth inhibitor affects the invasion, apoptosis and vascularisation in breast cancer cell line MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    Gao Yinguang; Ge Zhicheng; Zhang Zhongtao; Bai Zhigang; Ma Xuemei; Wang Yu

    2014-01-01

    Background Breast cancer is one of the most common malignant female diseases worldwide.It is a significant threat to every woman's health.Vascular endothelial growth inhibitor (VEGI) is known to be abundant in endothelial cells.According to previous literature,overexpression of VEGI has been shown to inhibit tumor neovascularisation and progression in cellular and animal models,but there has been limited research on the significance of VEGI in the breast cancer.Methods In our study,cell lines MDA-MB-231 were first constructed in which VEGI mediated by lentivirus over-expressed.The effects of VEGI over-expression on MDA-MB-231 cells were investigated both in vitro and in vivo.The expression of VEGI in the MDA-MB-231 cells after infection of lentivirus was analyzed using real-time PCR and Western blotting.The effect of the biological characteristics of MDA-MB-231 cells was assessed by growth,invasion,adhesion,and migration assay with subcutaneous tumor-bearing nude mice models.Then the growth curves of the subcutaneous tumors were studied.Expressions of VEGI,CD31 and CD34 in the tumors were analyzed by immunohistochemistry and apoptosis was detected by flow cytometry and immunohistochemistry.Results Infection of MDA-MB-231 cells within the lentivirus resulted in approximately a 1 000-fold increase in the expression of VEGI.As can be seen in the invasion,adhesion and migration assay,the over-expression of VEGI can inhibit the ability of MDA-MB-231 cells during migration,adhesion and invasion.The volume of the subcutaneous tumor in the over-expression group was distinctly and significantly less than that of the control groups.Immunohistochemistry analysis of the tumor biopsies cleady showed the expression of VEGI in the over-expression group increased while CD31 and CD34 decreased significantly.In vitro and in vivo,the early apoptosis rate and the apoptosis index were increased within the VEGI over-expression group as compared with the control group.Conclusions Taken

  5. Circulating vascular endothelial growth factor and its soluble receptors in patients with liver cirrhosis: possible association with hepatic function impairment.

    Science.gov (United States)

    Jaroszewicz, Jerzy; Januszkiewicz, Marcin; Flisiak, Robert; Rogalska, Magdalena; Kalinowska, Alicja; Wierzbicka, Iwona

    2008-10-01

    Recent studies provided in vivo evidences of an increased angiogenesis in animal model of portal hypertension and cirrhosis which was linked to increased expression of vascular endothelial growth factor. The aim of study was to evaluate the plasma concentration of VEGF and its receptors in liver cirrhosis and the possible association with the degree of liver insufficiency. Methods. Vascular endothelial growth factor (VEGF) and its soluble receptors: sVEGF-R1, sVEGF-R2 were measured in plasma of 78 patients with liver cirrhosis by ELISA. Results. The significant increase of plasma VEGF and sVEGF-R1 was observed in liver cirrhosis compared to healthy individuals (153.1+/-51.9 vs. 46.8+/-4.1pg/mL, P<0.05; 279.8+/-34.3 vs. 105.1+/-5.9pg/mL, P<0.001, respectively). Plasma VEGF and foremost sVEGF R1 showed significant associations with biochemical indices of liver function. Among clinical parameters, only ascites revealed significant association with plasma VEGR and sVEGF-R1. VEGF and sVEGF-R1 were increased respectively to the degree of liver insufficiency. It was demonstrated through a significant positive correlation with Child-Pugh score and MELD classification. In conclusion, our study suggests that serum VEGF and VEGF-R1 may reflect the hepatic function impairment in liver cirrhosis and seems to be associated with portal hypertension symptoms.

  6. Effect of mitiglinide combined laser photocoagulation on blood glucose, blood lipid and vascular endothelial function in diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Yun-Yan Fan; Gui-Jun Luo

    2016-01-01

    Objective:To observe the effect of mitiglinide combined laser photocoagulation on blood glucose, blood lipid and vascular endothelial function in diabetic retinopathy.Methods:A total of 106 patients with diabetic retinopathy treated in our hospital from January 2014 to January 2015 were selected and assigned into the separate group and combined group. Fifty-three patients in the separate group only received oral mitiginide, while other 53 patients in the combined group received oral mitiglinide and laster photocoagulation surgery. Before and after treatment, the FBG, 2hPBG, HbA1c, TC, TG, HDL-C, LDL-C, ET-1, VEGF, PEDF, ICAM-1, FMD of patients in the two groups were analyzed.Results: After treatment, the blood glucose and blood lipid indexes of patients in the two groups were improved significantly, and there was no statistical difference between the two groups. The ET-1, ICAM-1 and VEGF of patients in the two groups decreased, and the decrease of the combined group was more distinctly. The PEDF and FMD in the two groups all increased, and the combined group changed more obviously. The regression of the blood vessel and the recovery of visual acuity in the combined group were better than the separate group.Conclusions:Mitiglinide combined with laser photocoagulation can effectively improve the level of blood glucose and blood lipid, promote vascular endothelial function and inhibit the formation of retinal neovascularization so as to improve the visual acuity level.

  7. Biomimetic control of vascular smooth muscle cell morphology and phenotype for functional tissue-engineered small-diameter blood vessels.

    Science.gov (United States)

    Chan-Park, Mary B; Shen, Jin Ye; Cao, Ye; Xiong, Yun; Liu, Yunxiao; Rayatpisheh, Shahrzad; Kang, Gavin Chun-Wei; Greisler, Howard P

    2009-03-15

    Small-diameter blood vessel substitutes are urgently needed for patients requiring replacements of their coronary and below-the-knee vessels and for better arteriovenous dialysis shunts. Circulatory diseases, especially those arising from atherosclerosis, are the predominant cause of mortality and morbidity in the developed world. Current therapies include the use of autologous vessels or synthetic materials as vessel replacements. The limited availability of healthy vessels for use as bypass grafts and the failure of purely synthetic materials in small-diameter sites necessitate the development of a biological substitute. Tissue engineering is such an approach and has achieved promising results, but reconstruction of a functional vascular tunica media, with circumferentially oriented contractile smooth muscle cells (SMCs) and extracellular matrix, appropriate mechanical properties, and vasoactivity has yet to be demonstrated. This review focuses on strategies to effect the switch of SMC phenotype from synthetic to contractile, which is regarded as crucial for the engineering of a functional vascular media. The synthetic SMC phenotype is desired initially for cell proliferation and tissue remodeling, but the contractile phenotype is then necessary for sufficient vasoactivity and inhibition of neointima formation. The factors governing the switch to a more contractile phenotype with in vitro culture are reviewed.

  8. Effect of computerized cognitive training with virtual spatial navigation task during bed rest immobilization and recovery on vascular function: A pilot study

    Directory of Open Access Journals (Sweden)

    Goswami N

    2015-02-01

    Full Text Available Nandu Goswami,1 Voyko Kavcic,2 Uros Marusic,3 Bostjan Simunic,3 Andreas Rössler,1 Helmut Hinghofer-Szalkay,1 Rado Pisot3 1Institute of Physiology, Medical University of Graz, Graz, Austria; 2Institute of Gerontology, Wayne State University, Detroit, MI, USA; 3Institute for Kinesiology Research, University of Primorska, Ankaran, Slovenia Abstract: We investigated the effects of bed rest (BR immobilization, with and without computerized cognitive training with virtual spatial navigation task (CCT, on vascular endothelium on older subjects. The effects of 14-day BR immobilization in healthy older males (n=16 of ages 53–65 years on endothelial function were studied using EndoPAT®, a noninvasive and user-independent method. From the group of 16 older men, 8 randomly received CCT during the BR, using virtual navigation tasks in a virtual environment with joystick device. In all the cases, EndoPAT assessments were done at pre- and post-BR immobilization as well as following 28 days of ambulatory recovery. The EndoPAT index increased from 1.53±0.09 (mean ± standard error of the mean at baseline to 1.61±0.16 following immobilization (P=0.62 in the group with CCT. The EndoPAT index decreased from 2.06±0.13 (mean ± standard error of the mean at baseline to 1.70±0.09 at the last day of BR study, day 14 (BR14 (P=0.09 in the control group. Additionally, there were no statistically significant differences between BR14 and at 28 days of follow-up (rehabilitation program (R28. Our results show a trend of immobilization in older persons affecting the vasoconstrictory endothelial response. As the control subjects had a greater increase in EndoPAT index after R28 (+0.018 compared to subjects who had cognitive training (+0.11 (calculated from the first day of BR study, it is possible that cognitive training during BR does not improve endothelial function but rather contributes to slowing down the impairment of endothelial function. Finally, our results

  9. Bem-estar subjetivo e senso de ajustamento psicológico em idosos que sofreram acidente vascular cerebral: uma revisão Subjective well being and perceived psychological adjustment among old people affected by stroke: a review

    Directory of Open Access Journals (Sweden)

    Dóris Firmino Rabelo

    2006-08-01

    Full Text Available Foi feito um levantamento dos estudos brasileiros e estrangeiros publicados entre 1996 e 2005 que relacionavam bem-estar subjetivo, senso de ajustamento psicológico e acidente vascular cerebral, com o objetivo de identificar variáveis mediadoras dessa relação em idosos. Estudos transversais e prospectivos indicaram que os afetados por acidente vascular cerebral apresentam menor bem-estar subjetivo quando comparados com a população geral. Boa capacidade cognitiva, suporte social efetivo, continuidade de uma ocupação produtiva, manutenção da competência em atividades instrumentais de vida diária e humor positivo são fatores que podem melhorar o bem-estar subjetivo e psicológico. Variáveis que podem piorar o bem-estar subjetivo e psicológico são incapacidade funcional, déficits cognitivos, depressão, dificuldade em restabelecer a identidade e restrição à possibilidade de desempenhar atividades e papéis que contribuem para a auto-definição. O conhecimento das implicações psicológicas de sofrer acidente vascular cerebral pode beneficiar pacientes, familiares e profissionais no gerenciamento do evento.We gathered data from Brazilian and foreign studies published between 1996 and 2005 which related subjective well-being, sense of psychological adjustment and stroke. The objective was identifying mediator variables of this relation among old people. Prospective and cross-sectional studies indicated that those affected by stroke showed less subjective well-being than the general population. Good cognitive capacity, effective social support, continuity of a productive occupation, keeping the competence in instrumental activities of daily living and good mood are factors which can affect positively the subjective and psychological well-being. Variables which can affect negatively the subjective and psychological well-being are functional incapacity, cognitive deficits, depression, difficulty in re-establishing the identity and

  10. Effect of Shengmai Injection on Vascular Endothelial and Heart Functions in Patients with Coronary Heart Disease Complicated with Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ya-chen; LU Bao-jing; ZHAO Mei-hua; RONG Ye-zhi; CHEN Rui-ming

    2008-01-01

    Objective: To study the effect of Shengrnai injection (生脉注射液, SMI) on vascular endothelial and heart functions in coronary heart disease patients complicated with diabetes mellitus (CHD-DM). Methods: One hundred and twenty patients with CHD-DM, their diagnosis confirmed by coronary arteriography, were equally randomized into a control group treated with conventional treatment and a treated group treated with conventional treatment plus SMI. The changes in blood levels of nitric oxide (NO), endothelin-1 (ET-1) and angiotensin Ⅱ (Ang Ⅱ ), as well as endothelium-dependent vascular dilating function and heart function in the patients were observed before treatment and after the 3-week treatment. Results: After being treated with SMI for 3 weeks, in the treated group, blood level of NO was raised significantly from 69.8 ± 33.1 μ mol/L to 120.1 ± 50.8 μ mol/L, and ET-1 was lowered from 70.1 ± 32.1 ng/L to 46.2±21.3 ng/L, respectively (P<0.01); that of Ang Ⅱ was lowered from 81.3 ± 24.3 ng/L to 50.2 ± 27.3 ng/L (P<0.01); brachial arterial post-congestion blood flow increasing rate was raised from 389.4 ± 26.3% to 459.3 ± 27.8% (P<0.01); and the improvement in heart function as seen through the ejection fraction (EF) was increased from 44 ± 5% to 68 ± 6% (P<0.01), all the changes being more significant than those in the control group (all P<0.01). Conclusion: SMI can improve not only the endothelial function in CHD-DM patients, but also heart contraction significantly.

  11. Porphyromonas gingivalis infection modifies oral microcirculation and aortic vascular function in the stroke-prone spontaneously hypertensive rat (SHRSP).

    Science.gov (United States)

    Funaki, Seiko; Tokutomi, Fumiaki; Wada-Takahashi, Satoko; Yoshino, Fumihiko; Yoshida, Ayaka; Maehata, Yojiro; Miyamoto, Chihiro; Toyama, Toshizo; Sato, Takenori; Hamada, Nobushiro; Lee, Masaichi Chang-il; Takahashi, Shun-suke

    2016-03-01

    The functional modulation of vascular endothelial cells associated with stroke and periodontal disease has not yet been clarified. The objective of this study is to analyze the vascular endothelial function of periodontitis and stroke animal models. We examined endothelial function and gingival blood flow in oral microcirculation in vivo and measured the isometric tension in vitro of the aorta in animal models for lifestyle-related diseases, such as periodontitis and stroke. Gingival reactive hyperemia (GRH) was measured using laser Doppler flowmetry. Wistar Kyoto rats (WKY) were used as control animals; Porphyromonas gingivalis (P. gingivalis) infected WKY (WKY + Pg) as the periodontitis model; stroke-prone spontaneously hypertensive rat (SHRSP) as the stroke model; and a final group consisting of P. gingivalis infected SHRSP (SHRSP + Pg). Furthermore, for each group, the relaxation of descending aortic ring preparations was measured using a force transducer. The GRH was estimated by maximum response (peak), time taken for the maximum response to fall to one half (T1/2), and increased total amount of blood flow (mass). The relative change in T1/2 and mass increased in SHRSP + Pg compared to WKY. However, mass significantly increased in WKY (758.59 ± 88.21 ml/min/100 g s to 1755.55 ± 226.10 ml/min/100 g s) and SHRSP (1214.87 ± 141.61 ml/min/100 g s to 2674.32 ± 675.48 ml/min/100 g s) after treatment with acetylcholine. In addition, T1/2 and mass significantly increased in WKY + Pg (624.18 ± 96.36 ml/min/100 g s to 2629.90 ± 612.01 ml/min/100 g s) and SHRSP + Pg (1116.36 ± 206.24 ml/min/100 g s to 1952.76 ± 217.39 ml/min/100 g s) after treatment with nitroglycerin. Furthermore, the endothelium-dependent relaxation of ring preparations, evoked by acetylcholine, was attenuated in SHRSP compared with WKY, but not in SHRSP + Pg. This attenuation effect in SHRSP could be prevented by superoxide dismutase pretreatment. Our results suggest altered endothelial

  12. Effects of aerobic exercise training on cognitive function and cortical vascularity in monkeys.

    Science.gov (United States)

    Rhyu, I J; Bytheway, J A; Kohler, S J; Lange, H; Lee, K J; Boklewski, J; McCormick, K; Williams, N I; Stanton, G B; Greenough, W T; Cameron, J L

    2010-06-02

    This study examined whether regular exercise training, at a level that would be recommended for middle-aged people interested in improving fitness could lead to improved cognitive performance and increased blood flow to the brain in another primate species. Adult female cynomolgus monkeys were trained to run on treadmills for 1 h a day, 5 days a week, for a 5 month period (n=16; 1.9+/-0.4 miles/day). A sedentary control group sat daily on immobile treadmills (n=8). Half of the runners had an additional sedentary period for 3 months at the end of the exercise period (n=8). In all groups, half of the monkeys were middle-aged (10-12 years old) and half were more mature (15-17 years old). Starting the fifth week of exercise training, monkeys underwent cognitive testing using the Wisconsin General Testing Apparatus (WGTA). Regardless of age, the exercising group learned to use the WGTA significantly faster (4.6+/-3.4 days) compared to controls (8.3+/-4.8 days; P=0.05). At the end of 5 months of running monkeys showed increased fitness, and the vascular volume fraction in the motor cortex in mature adult running monkeys was increased significantly compared to controls (P=0.029). However, increased vascular volume did not remain apparent after a 3-month sedentary period. These findings indicate that the level of exercise associated with improved fitness in middle-aged humans is sufficient to increase both the rate of learning and blood flow to the cerebral cortex, at least during the period of regular exercise.

  13. Genotype-related effect of crowding stress on blood pressure and vascular function in young female rats.

    Science.gov (United States)

    Slezak, Peter; Puzserova, Angelika; Balis, Peter; Sestakova, Natalia; Majzunova, Miroslava; Dovinova, Ima; Kluknavsky, Michal; Bernatova, Iveta

    2014-01-01

    This study investigated the influence of chronic crowding stress on nitric oxide (NO) production, vascular function and oxidative status in young Wistar-Kyoto (WKY), borderline hypertensive (BHR) and spontaneously hypertensive (SHR) female rats. Five-week old rats were exposed to crowding for two weeks. Crowding elevated plasma corticosterone (PCrowding elevated NO production in all strains investigated but superoxide concentration was increased only in WKY, which resulted in reduced NO-dependent relaxation in WKY. In crowded BHR and SHR, superoxide concentration was either unchanged or reduced, respectively, but NO-dependent relaxation was unchanged in both BHR and SHR versus their respective control group. This study points to genotype-related differences in stress vulnerability in young female rats. The most pronounced negative influence of stress was observed in BHR despite preserved endothelial function.

  14. Interaction between maternal and offspring diet to impair vascular function and oxidative balance in high fat fed male mice.

    Directory of Open Access Journals (Sweden)

    Christopher Torrens

    Full Text Available AIMS: To determine the impact of maternal and post-weaning consumption of a high fat diet on endothelium-dependent vasorelaxation and redox regulation in adult male mouse offspring. METHODS: Female C57BL6J mice were fed an obesogenic high fat diet (HF, 45% kcal fat or standard chow (C, 21% kcal fat pre-conception and throughout pregnancy and lactation. Post-weaning, male offspring were continued on the same diet as their mothers or placed on the alternative diet to give 4 dietary groups (C/C, HF/C, C/HF and HF/HF which were studied at 15 or 30 weeks of age. RESULTS: There were significant effects of maternal diet on offspring body weight (p<0.004, systolic blood pressure (p = 0.026 and endothelium-dependent relaxation to ACh (p = 0.004 and NO production (p = 0.005 measured in the femoral artery. With control for maternal diet there was also an effect of offspring post-weaning dietary fat to increase systolic blood pressure (p<0.0001 and reduce endothelium-dependent relaxation (p = 0.022 and ACh-mediated NO production (p = 0.007. There was also a significant impact of age (p<0.005. Redox balance was perturbed, with altered regulation of vascular enzymes involved in ROS/NO signalling. CONCLUSIONS: Maternal consumption of a HF diet is associated with changes in vascular function and oxidative balance in the offspring of similar magnitude to those seen with consumption of a high fat diet post-weaning. Further, this disadvantageous vascular phenotype is exacerbated by age to influence the risk of developing obesity, raised blood pressure and endothelial dysfunction in adult life.

  15. Continuous theta burst transcranial magnetic stimulation affects brain functional connectivity.

    Science.gov (United States)

    Dan Cao; Yingjie Li; Ling Wei; Yingying Tang

    2016-08-01

    Prefrontal cortex (PFC) plays an important role in the emotional processing as well as in the functional brain network. Hyperactivity in the right dorsolateral prefrontal cortex (DLPFC) would be found in anxious participants. However, it is still unclear what the role of PFC played in a resting functional network. Continuous theta burst transcranial magnetic stimulation (cTBS) is an effective tool to create virtual lesions on brain regions. In this paper, we applied cTBS over right prefrontal area, and investigated the effects of cTBS on the brain activity for functional connectivity by the method of graph theory. We recorded 64-channels EEG on thirteen healthy participants in the resting condition and emotional tasks before and after 40 s of cTBS. This work focused on the effect of cTBS on cortical activities in the resting condition by calculating the coherence between EEG channels and building functional networks before and after cTBS in the delta, theta, alpha and beta bands. Results revealed that 1) The functional connectivity after cTBS was significantly increased compared with that before cTBS in delta, theta, alpha and beta bands in the resting condition; 2) The efficiency-cost reached the maximum before and after cTBS both with the cost about 0.3 in the bands above, which meant that the information transmission of functional brain network with this cost was highly efficient; 3) the clustering coefficient and path length after cTBS was significantly increased in delta, theta and beta bands. In conclusion, cTBS over PFC indeed enhanced the functional connectivity in the resting condition. In addition, the information transmission in the resting brain network was highly efficient with the cost about 0.3.

  16. Experimental Benefits of Sex Hormones on Vascular Function and the Outcome of Hormone Therapy in Cardiovascular Disease

    OpenAIRE

    Ross, Reagan L.; Serock, Michelle R; Khalil, Raouf A.

    2008-01-01

    Cardiovascular disease (CVD) is more common in men and postmenopausal women than premenopausal women, suggesting vascular benefits of female sex hormones. Experimental data have shown beneficial vascular effects of estrogen including stimulation of endothelium-dependent nitric oxide, prostacyclin and hyperpolarizing factor-mediated vascular relaxation. However, the experimental evidence did not translate into vascular benefits of hormone replacement therapy (HRT) in postmenopausal women, and ...

  17. Factors affecting functional prognosis of patients with hip fracture

    DEFF Research Database (Denmark)

    Kristensen, M T

    2011-01-01

    Having a hip fracture is considered one of the most fatal fractures for elderly people, resulting in impaired function, and increased morbidity and mortality. This challenges clinicians in identifying patients at risk of worse outcome, in order to optimise and intensify treatment in these patient...

  18. Seed treatments affect functional and antinutritional properties of amaranth flours

    NARCIS (Netherlands)

    Gamel, T.H.; Linssen, J.P.H.; Mesallam, A.S.; Damir, A.A.; Shekib, L.A.

    2006-01-01

    The effects of seed treatments, including cooking, popping germination and flour air classification, on the functional properties and antinutritional factors of Amaranthus caudatus and Amaranthus cruentus seeds were studied. Thermal treatments increased the water absorption with a maximum value of 5

  19. Ectomycorrhizal symbiosis affects functional diversity of rhizosphere fluorescent pseudomonads

    NARCIS (Netherlands)

    Frey-Klett, P.; Chavatte, M.; Clausse, M.L.; Courrier, S.; Roux, Le C.; Raaijmakers, J.M.; Giovanna Martinotti, M.; Pierrat, J.C.; Garbaye, J.

    2005-01-01

    Here we characterized the effect of the ectomycorrhizal symbiosis on the genotypic and functional diversity of soil Pseudomonas fluorescens populations and analysed its possible consequences in terms of plant nutrition, development and health. ¿ Sixty strains of P. fluorescens were isolated from the

  20. Does vitamin C deficiency affect cognitive development and function?

    DEFF Research Database (Denmark)

    Hansen, Stine Normann; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-01-01

    Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(-/-) mi...

  1. Lipid Bilayer Composition Affects Transmembrane Protein Orientation and Function

    Directory of Open Access Journals (Sweden)

    Katie D. Hickey

    2011-01-01

    Full Text Available Sperm membranes change in structure and composition upon ejaculation to undergo capacitation, a molecular transformation which enables spermatozoa to undergo the acrosome reaction and be capable of fertilization. Changes to the membrane environment including lipid composition, specifically lipid microdomains, may be responsible for enabling capacitation. To study the effect of lipid environment on proteins, liposomes were created using lipids extracted from bull sperm membranes, with or without a protein (Na+ K+-ATPase or -amylase. Protein incorporation, function, and orientation were determined. Fluorescence resonance energy transfer (FRET confirmed protein inclusion in the lipid bilayer, and protein function was confirmed using a colourometric assay of phosphate production from ATP cleavage. In the native lipid liposomes, ATPase was oriented with the subunit facing the outer leaflet, while changing the lipid composition to 50% native lipids and 50% exogenous lipids significantly altered this orientation of Na+ K+-ATPase within the membranes.

  2. Experimental conditions affecting functional comparison of highly active glutathione transferases.

    Science.gov (United States)

    Fedulova, Natalia; Mannervik, Bengt

    2011-06-01

    Glutathione transferases (GSTs, EC 2.5.1.18) possess multiple functions and have potential applications in biotechnology. Direct evidence of underestimation of activity of human GST A3-3 and porcine GST A2-2 measured at submicromolar enzyme concentrations is reported here for the first time. The combination of time-dependent and enzyme concentration-dependent loss of activity and the choice of the organic solvent for substrates were found to cause irreproducibility of activity measurements of GSTs. These effects contribute to high variability of activity values of porcine GST A2-2 and human Alpha-class GSTs reported in the literature. Adsorption of GSTs to surfaces was found to be the main explanation of the observed phenomena. Several approaches to improved functional comparison of highly active GSTs are proposed.

  3. Insulin resistance impairs endothelial function but not adrenergic reactivity or vascular structure in fructose-fed rats.

    Science.gov (United States)

    Romanko, Olga P; Ali, M Irfan; Mintz, James D; Stepp, David W

    2009-07-01

    Obesity and diabetes are major risk factors for the development of vascular disease in the lower limbs. Previous studies have demonstrated reduced nitric oxide (NO)-mediated vasodilation, increased adrenergic constriction, and inward, atrophic remodeling in the limb circulation of obese Zucker rats, but the component of the "metabolic syndrome" driving these changes is unclear. Because insulin resistance precedes the state of frank diabetes, the current study hypothesized that insulin resistance independent of obesity induced by fructose feeding would impair microvascular function in the skeletal muscle circulation in lean Zucker rats (LZR). A 66% fructose diet impaired glucose tolerance and induced moderate insulin resistance with no changes in whole-body hemodynamics of anesthetized rats (FF-LZR), compared to control LZR. NO-mediated vasodilation of isolated gracilis arteries, assessed in vitro with acetylcholine and sodium nitroprusside, was reduced approximately 20% in FF-LZR vs. LZR. NO-independent cGMP-mediated vasodilation was unimpaired. Pretreatment of isolated vessels with the superoxide scavenger, tempol, improved responses to both vasodilators. Reactivity to adrenergic stimulation was unaltered in FF-LZR vs. LZR, although constriction to endothelin was increased. Structural and passive mechanical characteristics of isolated gracilis arteries were similar in both LZR and FF-LZR. Taken together, these findings indicate that moderate insulin resistance is sufficient to impair endothelial function in an oxidant-dependent manner in the rat hindlimb circulation. Other aspects of skeletal muscle vascular function documented in obese models, specifically adrenergic tone and inward remodeling, must reflect either severe insulin resistance or other aspects of obesity. The factors accounting for nonendothelial vasculopathies remain unknown.

  4. Alginate overproduction affects Pseudomonas aeruginosa biofilm structure and function

    DEFF Research Database (Denmark)

    Hentzer, Morten; Teitzel, G.M.; Balzer, G.J.;

    2001-01-01

    During the course of chronic cystic fibrosis (CF) infections, Pseudomonas aeruginosa undergoes a conversion to a mucoid phenotype, which is characterized by overproduction of the exopolysaccharide alginate. Chronic P. aeruginosa infections involve surface-attached, highly antibiotic-resistant com......During the course of chronic cystic fibrosis (CF) infections, Pseudomonas aeruginosa undergoes a conversion to a mucoid phenotype, which is characterized by overproduction of the exopolysaccharide alginate. Chronic P. aeruginosa infections involve surface-attached, highly antibiotic......-resistant communities of microorganisms organized in biofilms. Although biofilm formation and the conversion to mucoidy are both important aspects of CF pathogenesis, the relationship between them is at the present unclear. In this study, we report that the overproduction of alginate affects biofilm development...

  5. Genes affecting β-cell function in type 1 diabetes

    DEFF Research Database (Denmark)

    Fløyel, Tina; Kaur, Simranjeet; Pociot, Flemming

    2015-01-01

    Type 1 diabetes (T1D) is a multifactorial disease resulting from an immune-mediated destruction of the insulin-producing pancreatic β cells. Several environmental and genetic risk factors predispose to the disease. Genome-wide association studies (GWAS) have identified around 50 genetic regions...... that affect the risk of developing T1D, but the disease-causing variants and genes are still largely unknown. In this review, we discuss the current status of T1D susceptibility loci and candidate genes with focus on the β cell. At least 40 % of the genes in the T1D susceptibility loci are expressed in human...... islets and β cells, where they according to recent studies modulate the β-cell response to the immune system. As most of the risk variants map to noncoding regions of the genome, i.e., promoters, enhancers, intergenic regions, and noncoding genes, their possible involvement in T1D pathogenesis as gene...

  6. Risk factors affecting somatosensory function after sagittal split osteotomy

    DEFF Research Database (Denmark)

    Thygesen, Torben Henrik; Jensen, Allan Bardow; Helleberg, M;

    2008-01-01

    Purpose The aim of this study was to evaluate potential individual and intraoperative risk factors associated with bilateral sagittal split osteotomy (BSSO) and to correlate the findings with postoperative changes in somatosensory function. Patients and Methods A total of 18 men and 29 women (mean...... and free dissection of the inferior alveolar nerve during BSSO increased self-reported changes in lower lip sensation and lower lip tactile threshold after BSSO (P discrimination (P

  7. Does caregiving stress affect cognitive function in older women?

    Science.gov (United States)

    Lee, Sunmin; Kawachi, Ichiro; Grodstein, Francine

    2004-01-01

    Increasing numbers of women provide care to their ill spouses; however, no studies have examined possible effects of caregiving stress on cognitive function. We administered 6 tests of cognitive function to 13740 Nurses' Health Study participants aged 70-79 years. We collected information on caregiving and numerous potential confounding variables via biennial mailed questionnaires. After adjustment for potential confounders (age, education, mental health index, vitality index, use of antidepressants, and history of high blood pressure, diabetes, and heart disease), we found modest but significantly increased risks of low cognitive function on three of the cognitive tests among women who provided care to a disabled or ill spouse compared with women who did not provide any care. For example, on the TICS, a test of general cognition, the risk of a low score was 31% higher in women who provided care compared with women who did not (RR = 1.31, 95% CI 1.10, 1.56). We found a moderately increased risk of poor performance on several cognitive tests among women who provided care to their disabled or ill husbands.

  8. Prenatal drug exposure affects neonatal brain functional connectivity.

    Science.gov (United States)

    Salzwedel, Andrew P; Grewen, Karen M; Vachet, Clement; Gerig, Guido; Lin, Weili; Gao, Wei

    2015-04-01

    Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala-frontal, insula-frontal, and insula-sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala-frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention.

  9. Role of 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids in the regulation of vascular function in a model of hypertension and endothelial dysfunction.

    Science.gov (United States)

    Yousif, Mariam H M; Benter, Ibrahim F

    2010-01-01

    The objective of this study was to determine if acute inhibition of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis or reduced inactivation of epoxyeicosatrienoic acids (EETs) can correct L-N(G)-nitro-arginine-methyl-ester (L-NAME)-induced abnormal vascular reactivity in the perfused mesenteric bed and the carotid artery of spontaneously hypertensive rats (SHR). Administration of L-NAME in drinking water (80 mg/l) to SHR for 3 weeks resulted in abnormal vascular reactivity to norepinephrine and carbachol in the perfused mesenteric vascular bed and carotid artery, and significantly elevated mean arterial blood pressure (244 +/- 9 mm Hg) as compared to SHR controls drinking regular water (176 +/- 3 mm Hg). In the perfused mesenteric vascular bed, the impaired vascular responsiveness to norepinephrine was corrected by acute treatment with N-hydroxy-N'-(4-butyl-2-methylphenyl)formamidine (HET0016), an inhibitor of 20-HETE formation, but not by 1-cyclohexyl-3-dodecyl urea (CDU), an inhibitor of soluble epoxide hydrolase. Treatment with either HET0016 or CDU did not improve impaired carbachol-induced vasodilation in the perfused mesenteric vascular bed. In the isolated carotid artery, treatment with HET0016 corrected the L-NAME-induced increase in norepinephrine-induced vasoconstriction, whereas only CDU treatment could improve impaired carbachol-induced vasodilation. Results of this study indicate that vascular function in a state of compromised nitric oxide formation is differentially modulated by 20-HETE and EETs, and that treatment with HET0016 or CDU may improve vascular function in a state of high blood pressure and endothelial dysfunction.

  10. Structure and vascular function of MEKK3–cerebral cavernous malformations 2 complex

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, Oriana S. [Yale Univ., New Haven, CT (United States); Deng, Hanqiang [Shanghai Jiao Tong Univ. School of Medicine (SJTU-SM), Shanghai (China); Liu, Dou [Yale Univ. School of Medicine, New Haven, CT (United States); Zhang, Ya [Yale Univ. School of Medicine, New Haven, CT (United States); Wei, Rong [Shanghai Jiao Tong Univ. School of Medicine (SJTU-SM), Shanghai (China); Deng, Yong [Yale Univ. School of Medicine, New Haven, CT (United States); Zhang, Fan [Yale Univ. School of Medicine, New Haven, CT (United States); Louvi, Angeliki [Yale Univ. School of Medicine, New Haven, CT (United States); Turk, Benjamin E. [Yale Univ., New Haven, CT (United States); Boggon, Titus J. [Yale Univ., New Haven, CT (United States); Su, Bing [Shanghai Jiao Tong Univ. School of Medicine (SJTU-SM), Shanghai (China)

    2015-08-03

    Cerebral cavernous malformations 2 (CCM2) loss is associated with the familial form of CCM disease. The protein kinase MEKK3 (MAP3K3) is essential for embryonic angiogenesis in mice and interacts physically with CCM2, but how this interaction is mediated and its relevance to cerebral vasculature are unknown. Here we report that Mekk3 plays an intrinsic role in embryonic vascular development. Inducible endothelial Mekk3 knockout in neonatal mice is lethal due to multiple intracranial haemorrhages and brain blood vessels leakage. We discover direct interaction between CCM2 harmonin homology domain (HHD) and the N terminus of MEKK3, and determine a 2.35 Å cocrystal structure. We find Mekk3 deficiency impairs neurovascular integrity, which is partially dependent on Rho–ROCK signalling, and that disruption of MEKK3:CCM2 interaction leads to similar neurovascular leakage. We conclude that CCM2:MEKK3-mediated regulation of Rho signalling is required for maintenance of neurovascular integrity, unravelling a mechanism by which CCM2 loss leads to disease.

  11. Endothelial Microparticle-Derived Reactive Oxygen Species: Role in Endothelial Signaling and Vascular Function

    Directory of Open Access Journals (Sweden)

    Dylan Burger

    2016-01-01

    Full Text Available Endothelial microparticles are effectors of endothelial damage; however mechanisms involved are unclear. We examined the effects of eMPs on cultured endothelial cells (ECs and isolated vessels and investigated the role of eMP-derived reactive oxygen species (ROS and redox signaling in these processes. eMPs were isolated from EC media and their ability to directly produce ROS was assessed by lucigenin and liquid chromatography. Nicotinamide adenine dinucleotide phosphate oxidase (Nox subunits were probed by Western blot. ECs were treated with eMPs and effects on kinase signaling, superoxide anion (O2∙- generation, and nitric oxide (NO production were examined. Acetylcholine-mediated vasorelaxation was assessed by myography in eMP-treated mesenteric arteries. eMPs contained Nox1, Nox2, Nox4, p47phox, p67phox, and p22phox and they produced ROS which was inhibited by the Nox inhibitor, apocynin. eMPs increased phosphorylation of ERK1/2 and Src, increased O2∙- production, and decreased A23187-induced NO production in ECs. Pretreatment of eMPs with apocynin diminished eMP-mediated effects on ROS and NO production but had no effect on eMP-mediated kinase activation or impairment in vasorelaxation. Our findings identify a novel mechanism whereby eMP-derived ROS contributes to MP bioactivity. These interactions may be important in conditions associated with vascular injury and increased eMP formation.

  12. The Electroretinogram in Patients with Retinal Vascular Occlusion

    Institute of Scientific and Technical Information of China (English)

    Shizhou Huang; Lezheng Wu; Taiqing Luo; De-Zheng Wu; Futian Jiang; Guangwei Luo; Juanmei Ma

    2001-01-01

    Purpose: to measure and analyze the electroretinogram (ERG) in patients with retinal vascular occlusion. Method: fifty-eight cases (59 eyes) of retinal vascular occlusion and the fellow eyes of 47 cases were tested with Ganzfeld ERG. The scotopic and photopic ERG, and oscillatory potentials were tested according to the ERG standard of ISCEV. Results: The abnormal rates of Ops and b wave were higher in retinal vascular occlusion. The abnormal ERG appeared mostly in CRVO among four types of retinal vascular occlusion. The comparisons of some amplitudes and latencies between the fellow eyes and the affected eyes showed statistically significant difference. Conclusion: The oscillatory potentials and b waves have important roles in evaluating the retinal function of patients with retinal vascular occlusions. There are some clinical significance for comparing ERG between the affected eye and the fellow eye. Eye Science 2001; 17: 50 ~ 53.

  13. Visual function affects prosocial behaviors in older adults.

    Science.gov (United States)

    Teoli, Dac A; Smith, Merideth D; Leys, Monique J; Jain, Priyanka; Odom, J Vernon

    2016-02-01

    Eye-related pathological conditions such as glaucoma, diabetic retinopathy, and age-related macular degeneration commonly lead to decreased peripheral/central field, decreased visual acuity, and increased functional disability. We sought to answer if relationships exist between measures of visual function and reported prosocial behaviors in an older adult population with eye-related diagnoses. The sample consisted of adults, aged ≥ 60 years old, at an academic hospital's eye institute. Vision ranged from normal to severe impairment. Medical charts determined the visual acuities, ocular disease, duration of disease (DD), and visual fields (VF). Measures of giving help were via validated questionnaires on giving formal support (GFS) and giving informal support; measures of help received were perceived support (PS) and informal support received (ISR). ISR had subscales: tangible support (ISR-T), emotional support (ISR-E), and composite (ISR-C). Visual acuities of the better and worse seeing eyes were converted to LogMAR values. VF information converted to a 4-point rating scale of binocular field loss severity. DD was in years. Among 96 participants (mean age 73.28; range 60-94), stepwise regression indicated a relationship of visual variables to GFS (p < 0.05; Multiple R (2) = 0.1679 with acuity-better eye, VF rating, and DD), PS (p < 0.05; Multiple R (2) = 0.2254 with acuity-better eye), ISR-C (p < 0.05; Multiple R (2) = 0.041 with acuity-better eye), and ISR-T (p < 0.05; Multiple R (2) = 0.1421 with acuity-better eye). The findings suggest eye-related conditions can impact levels and perceptions of support exchanges. Our data reinforces the importance of visual function as an influence on prosocial behavior in older adults.

  14. Effects of Replenishing Qi, Promoting Blood Circulation and Resolving Phlegm on Vascular Endothelial Function and Blood Coagulation System in Senile Patients with Hyperlipemia

    Institute of Scientific and Technical Information of China (English)

    Yang Huimin; Han Libei; Sheng Tong; He Qiong; Liang Jinpu

    2006-01-01

    Objective: To observe the curative effect of the method of replenishing qi, promoting blood circulation and resolving phlegm on senile hyperlipemia and its effects on vascular endothelial function and blood coagulation system. Method: 96 patients with senile hyperlipemia were randomly divided into a treatment group and a of blood lipid, vascular endothelial function, blood coagulation system and safety. Results: After treatment,the treatment group was obviously superior to the control group (P<0.05) in reducing plasma total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) as well as in the ratio of thromboxane B2 (TXB2) to 6-keto-prostaglandin F1α (6-keto-PGF1α), D-dimer (D-D) and fibrinogen (FIB). Conclusion: Danshen Jueming Granules have the effect of regulating metabolism of blood lipid, and improving vascular endothelial function and blood coagulation system in senile patients with hyperlipemia.

  15. Affected functional networks associated with sentence production in classic galactosemia.

    Science.gov (United States)

    Timmers, Inge; van den Hurk, Job; Hofman, Paul Am; Zimmermann, Luc Ji; Uludağ, Kâmil; Jansma, Bernadette M; Rubio-Gozalbo, M Estela

    2015-08-07

    Patients with the inherited metabolic disorder classic galactosemia have language production impairments in several planning stages. Here, we assessed potential deviations in recruitment and connectivity across brain areas responsible for language production that may explain these deficits. We used functional magnetic resonance imaging (fMRI) to study neural activity and connectivity while participants carried out a language production task. This study included 13 adolescent patients and 13 age- and gender-matched healthy controls. Participants passively watched or actively described an animated visual scene using two conditions, varying in syntactic complexity (single words versus a sentence). Results showed that patients recruited additional and more extensive brain regions during sentence production. Both groups showed modulations with syntactic complexity in left inferior frontal gyrus (IFG), a region associated with syntactic planning, and in right insula. In addition, patients showed a modulation with syntax in left superior temporal gyrus (STG), whereas the controls did not. Further, patients showed increased activity in right STG and right supplementary motor area (SMA). The functional connectivity data showed similar patterns, with more extensive connectivity with frontal and motor regions, and restricted and weaker connectivity with superior temporal regions. Patients also showed higher baseline cerebral blood flow (CBF) in right IFG and trends towards higher CBF in bilateral STG, SMA and the insula. Taken together, the data demonstrate that language abnormalities in classic galactosemia are associated with specific changes within the language network. These changes point towards impairments related to both syntactic planning and speech motor planning in these patients.

  16. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    Science.gov (United States)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-02-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  17. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    Science.gov (United States)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-01-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  18. Low level methylmercury exposure affects neuropsychological function in adults

    Directory of Open Access Journals (Sweden)

    Platt Illeane

    2003-06-01

    , consistent with a dose-dependent effect. Conclusions This study suggests that adults exposed to MeHg may be at risk for deficits in neurocognitive function. The functions disrupted in adults, namely attention, fine-motor function and verbal memory, are similar to some of those previously reported in children with prenatal exposures.

  19. Osmotic stress affects functional properties of human melanoma cell lines

    CERN Document Server

    La Porta, Caterina A M; Pasini, Maria; Laurson, Lasse; Alava, Mikko J; Zapperi, Stefano; Amar, Martine Ben

    2015-01-01

    Understanding the role of microenvironment in cancer growth and metastasis is a key issue for cancer research. Here, we study the effect of osmotic pressure on the functional properties of primary and metastatic melanoma cell lines. In particular, we experimentally quantify individual cell motility and transmigration capability. We then perform a circular scratch assay to study how a cancer cell front invades an empty space. Our results show that primary melanoma cells are sensitive to a low osmotic pressure, while metastatic cells are less. To better understand the experimental results, we introduce and study a continuous model for the dynamics of a cell layer and a stochastic discrete model for cell proliferation and diffusion. The two models capture essential features of the experimental results and allow to make predictions for a wide range of experimentally measurable parameters.

  20. Cardiac and Vascular Function in Bedrested Volunteers: Effects of Artificial Gravity Training

    Science.gov (United States)

    Meng, M.; Platts, S.; Stenger, M.; Diedrich, A.; Schlegel, T.; Natapoff, A.; Knapp, C.; Evans, J.

    2007-01-01

    Cardiovascular effects of an artificial gravity (AG) countermeasure on deconditioned male volunteers were studied. In two groups of men we measured cardiovascular parameters at rest and in response to 30 minutes of 80 deg. head up tilt (HUT) before, at the end of, and four days following 21 days of 6 deg. head down bed rest (HDBR). One group (N=7) underwent no countermeasure while the other (N=8) received a daily, one hour, dose (2.5 gz at the foot, decreasing to 1.0 gz at the heart) of AG training on the Johnson Space Center short radius centrifuge. Cardiovascular parameters measured included heart rate, blood pressure, stroke volume, cardiac output, peripheral vascular resistance, plasma volume shifts, and vasoactive hormones. Untrained subjects exhibited shorter tilt survival (on average 8 minutes shorter) compared to trained subjects. By the end of bed rest, mean heart rate (MHR) was elevated in both groups (both supine and during tilt). In addition, treated subjects demonstrated lower, tilt-induced, increases in MHR four days following HDBR, indicating a more rapid return to pre bed rest conditions. Results from an index of autonomic balance (percentage of MHR spectral power in the respiratory frequency range) in control of heart rate are consistent with the interpretation that parasympathetic nervous system withdrawal was responsible for both tilt- and bed rest-induced increases in MHR. Our data support our pre-study hypothesis that AG treatment would lessen cardiovascular effects of deconditioning in bed rested men and suggest that AG should be further pursued as a space flight countermeasure.

  1. Functionally graded electrospun scaffolds with tunable mechanical properties for vascular tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Vinoy [Center for Nanoscale Materials and Biointegration (CNMB), Department of Physics, University of Alabama at Birmingham (UAB), AL 35294 (United States); Zhang Xing [Department of Biomedical Engineering, School of Engineering, University of Alabama at Birmingham (UAB), AL 35294 (United States); Catledge, Shane A [Center for Nanoscale Materials and Biointegration (CNMB), Department of Physics, University of Alabama at Birmingham (UAB), AL 35294 (United States); Vohra, Yogesh K [Center for Nanoscale Materials and Biointegration (CNMB), Department of Physics, University of Alabama at Birmingham (UAB), AL 35294 (United States)

    2007-12-15

    Electrospun tubular scaffolds (4 mm inner diameter) based on bio-artificial blends of polyglyconate (Maxon (registered) ) and proteins such as gelatin and elastin having a spatially designed multilayer structure were prepared for use as vascular tissue scaffolds. Scanning electron microscopy analysis of scaffolds showed a random nanofibrous morphology with fiber diameter in the range of 200-400 nm for protein-blended Maxon, which mimics the nanoscale dimensions of collagen (50-500 nm). The scaffolds have a well interconnected pore structure and porosity up to 82%, with protein blending and multi-layering in contrast to electrospun Maxon (registered) scaffolds (67%). Fourier-transform infrared spectroscopy, x-ray diffraction and differential scanning calorimetry results confirmed the blended composition and crystallinity of fibers. Uniaxial tensile testing revealed a strength of 14.46 {+-} 0.42 MPa and a modulus of 15.44 {+-} 2.53 MPa with a failure strain of 322.5 {+-} 10% for a pure Maxon (registered) scaffold. The blending of polyglyconate with biopolymers decreased the tensile properties in general, with an exception of the tensile modulus (48.38 {+-} 2 MPa) of gelatin/Maxon mesh, which was higher than that of the pure Maxon (registered) scaffold. Trilayered tubular scaffolds of gelatin/elastin, gelatin/elastin/Maxon and gelatin/Maxon (GE-GEM-GM) that mimic the complex trilayer matrix structure of natural artery have been prepared by sequential electrospinning. Tensile testing under dry conditions revealed a tensile strength of 2.71 {+-} 0.2 MPa and a modulus of 20.4 {+-} 3 MPa with a failure strain of 140 {+-} 10%. However, GE-GEM-GM scaffolds tested under wet conditions after soaking in a phosphate buffered saline medium at 37 {sup 0}C for 24 h exhibited mechanical properties (2.5 MPa tensile strength and 9 MPa tensile modulus) comparable to those of native femoral artery.

  2. Functionally graded electrospun scaffolds with tunable mechanical properties for vascular tissue regeneration.

    Science.gov (United States)

    Thomas, Vinoy; Zhang, Xing; Catledge, Shane A; Vohra, Yogesh K

    2007-12-01

    Electrospun tubular scaffolds (4 mm inner diameter) based on bio-artificial blends of polyglyconate (Maxon) and proteins such as gelatin and elastin having a spatially designed multilayer structure were prepared for use as vascular tissue scaffolds. Scanning electron microscopy analysis of scaffolds showed a random nanofibrous morphology with fiber diameter in the range of 200-400 nm for protein-blended Maxon, which mimics the nanoscale dimensions of collagen (50-500 nm). The scaffolds have a well interconnected pore structure and porosity up to 82%, with protein blending and multi-layering in contrast to electrospun Maxon scaffolds (67%). Fourier-transform infrared spectroscopy, x-ray diffraction and differential scanning calorimetry results confirmed the blended composition and crystallinity of fibers. Uniaxial tensile testing revealed a strength of 14.46 +/- 0.42 MPa and a modulus of 15.44 +/- 2.53 MPa with a failure strain of 322.5 +/- 10% for a pure Maxon scaffold. The blending of polyglyconate with biopolymers decreased the tensile properties in general, with an exception of the tensile modulus (48.38 +/- 2 MPa) of gelatin/Maxon mesh, which was higher than that of the pure Maxon scaffold. Trilayered tubular scaffolds of gelatin/elastin, gelatin/elastin/Maxon and gelatin/Maxon (GE-GEM-GM) that mimic the complex trilayer matrix structure of natural artery have been prepared by sequential electrospinning. Tensile testing under dry conditions revealed a tensile strength of 2.71 +/- 0.2 MPa and a modulus of 20.4 +/- 3 MPa with a failure strain of 140 +/- 10%. However, GE-GEM-GM scaffolds tested under wet conditions after soaking in a phosphate buffered saline medium at 37 degrees C for 24 h exhibited mechanical properties (2.5 MPa tensile strength and 9 MPa tensile modulus) comparable to those of native femoral artery.

  3. Dark chocolate and vascular function in patients with peripheral artery disease: a randomized, controlled cross-over trial.

    Science.gov (United States)

    Hammer, Alexandra; Koppensteiner, Renate; Steiner, Sabine; Niessner, Alexander; Goliasch, Georg; Gschwandtner, Michael; Hoke, Matthias

    2015-01-01

    Flavonoid-rich dark chocolate has positive effects on vascular function in healthy subjects and in patients at risk of atherosclerosis. The impact of dark chocolate on endothelial and microvascular function in patients with symptomatic peripheral artery disease (PAD) has not been investigated so far. In an investigator blinded, randomized, controlled, cross-over trial we assessed the effect of flavonoid-rich dark chocolate and cocoa-free control chocolate on flow-mediated dilatation (FMD) of the brachial artery and on microvascular function (assessed by Laser Doppler fluxmetry) in 21 patients with symptomatic (Fontaine stage II) PAD. Measurements were done in each patient on 2 single days, with an interval of 7 days, at baseline and at 2 hours after ingestion of 50 g dark chocolate or 50 g white chocolate, respectively. FMD remained unchanged after intake of dark chocolate (baseline and 2 hours after ingestion, %: 5.1 [IQR 4.4 to 7.3] and 5.5 [IQR 3.9 to 10.4]; p = 0.57, and after intake of white chocolate (baseline and 2 hours after ingestion, %: 6.4 [IQR 4.5 to 11.4] and 4.4 [IQR 2.6 to 8.7]; p = 0.14. Similarly, microcirculatory parameters were not significantly altered after intake of any chocolate compared with the respective baseline values. In conclusion, a single consumption of 50 g dark chocolate has no effect on endothelial and microvascular function in patients with symptomatic PAD.

  4. Vascular Endothelial Growth Factor Is Associated with the Morphologic and Functional Parameters in Patients with Hypertrophic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Radek Pudil

    2015-01-01

    Full Text Available Background. Hypertrophic cardiomyopathy (HCM is mostly autosomal dominant disease of the myocardium, which is characterized by myocardial hypertrophy. Vascular endothelial growth factor (VEGF is involved in myocyte function, growth, and survival. The aim of study was to analyze the clinical significance of VEGF in structural and functional changes in patient with HCM. Methods. In a group of 21 patients with nonobstructive HCM, we assessed serum VEGF and analyzed its association with morphological and functional parameters. Compared to healthy controls, serum VEGF was increased: 199 (IQR: 120.4–260.8 ng/L versus 20 (IQR: 14.8–37.7 ng/L, P<0.001. VEGF levels were associated with left atrium diameter (r=0.51, P=0.01, left ventricle ejection fraction (r=-0.56, P=0.01, fractional shortening (r=-0.54, P=0.02, left ventricular mass (r=0.61, P=0.03, LV mass index (r=0.46, P=0.04, vena cava inferior diameter (r=0.65, P=0.01, and peak gradient of tricuspid regurgitation (r=0.46, P=0.03. Conclusions. Increased VEGF level is associated with structural and functional parameters in patients with HCM and serves as a potential tool for diagnostic process of these patients.

  5. Short- and long-term functional effects of percutaneous transluminal angioplasty in hemodialysis vascular access

    NARCIS (Netherlands)

    J. van der Linden (Joke); J.H. Smits (Johannes); J.H. Assink (Jan Hendrik); D.W. Wolterbeek (Derk); J.J. Zijlstra (Jan); G.H.T. de Jong (Gijs); M.A. van den Dorpel; P.J. Blankestijn (Peter)

    2002-01-01

    textabstractThe efficacy of percutaneous transluminal angioplasty (PTA) is usually expressed as the angiographic result. Access flow (Qa) measurements offer a means to quantify the functional effects. This study was performed to evaluate the short-term functional and angiographic e

  6. Short- and long-term functional effects of percutaneous transluminal angioplasty in hemodialysis vascular access

    NARCIS (Netherlands)

    Van der Linden, J; Smits, JHM; Wolterbeek, DW; Zijlstra, JJ; De Jong, GHT; Van den Dorpel, MA; Blankestijn, PJ

    2002-01-01

    The efficacy of percutaneous transluminal angioplasty (PTA) is usually expressed as the angiographic result. Access flow (Qa) measurements offer a means to quantify the functional effects. This study was performed to evaluate the short-term functional and angiographic effects of PTA and to determine

  7. Endocannabinoids affect the reproductive functions in teleosts and amphibians.

    Science.gov (United States)

    Cottone, E; Guastalla, A; Mackie, K; Franzoni, M F

    2008-04-16

    Following the discovery in the brain of the bonyfish Fugu rubripes of two genes encoding for type 1 cannabinoid receptors (CB1A and CB1B), investigations on the phylogeny of these receptors have indicated that the cannabinergic system is highly conserved. Among the multiple functions modulated by cannabinoids/endocannabinoids through the CB1 receptors one of the more investigated is the mammalian reproduction. Therefore, since studies performed in animal models other than mammals might provide further insight into the biology of these signalling molecules, the major aim of the present paper was to review the comparative data pointing toward the endocannabinoid involvement in the reproductive control of non-mammalian vertebrates, namely bonyfish and amphibians. The expression and distribution of CB1 receptors were investigated in the CNS and gonads of two teleosts, Pelvicachromis pulcher and Carassius auratus as well as in the anuran amphibians Xenopus laevis and Rana esculenta. In general the large diffusion of neurons targeted by cannabinoids in both fish and amphibian forebrain indicate endocannabinoids as pivotal local messengers in several neural circuits involved in either sensory integrative activities, like the olfactory processes (in amphibians) and food response (in bonyfish), or neuroendocrine machinery (in both). By using immunohistochemistry for CB1 and GnRH-I, the codistribution of the two signalling molecules was found in the fish basal telencephalon and preoptic area, which are key centers for gonadotropic regulation in all vertebrates. A similar topographical codistribution was observed also in the septum of the telencephalon in Rana esculenta and Xenopus laevis. Interestingly, the double standard immunofluorescence on the same brain section, aided with a laser confocal microscope, showed that in anurans a subset of GnRH-I neurons exhibited also the CB1 immunostaining. The fact that CB1-LI-IR was found indeed in the FSH gonadotrophs of the Xenopus

  8. Neurology of Affective Prosody and Its Functional-Anatomic Organization in Right Hemisphere

    Science.gov (United States)

    Ross, Elliott D.; Monnot, Marilee

    2008-01-01

    Unlike the aphasic syndromes, the organization of affective prosody in brain has remained controversial because affective-prosodic deficits may occur after left or right brain damage. However, different patterns of deficits are observed following left and right brain damage that suggest affective prosody is a dominant and lateralized function of…

  9. 67. Do prenatal intracardiac echogenic foci affect postnatal cardiac function?

    Directory of Open Access Journals (Sweden)

    R. Bader

    2016-07-01

    Full Text Available Echogenic foci in the prenatal hear is not an uncommon finding. To determine whether prenatally diagnosed intracardiac echogenic foci are associated with neonatal cardiac dysfunction and persistence. Fetuses in which intracardiac echogenic foci were shown on prenatal sonography at 1 perinatal center from (September 2009 to December 2013 underwent postnatal echocardiography at ages 1 month to1 year. A single pediatric cardiologist assessed cardiac function by measuring the left ventricular shortening fraction and myocardial performance index. The presence of tricuspid valve regurgitation was also sought. Prenatally 60 fetuses had intracardiac echogenic foci mean age ± SD at diagnosis (23 ± 3.1. 53 (88.3% had left ventricular intracardiac echogenic foci, and 7 (11.6% had right ventricular intracardiac echogenic foci. 12 preganant ladies were lost for follow up (2 fetuses of 7 (28.5% with right ventricular intracardiac echogenic foci., and 10 fetuses of 53 (18.8% with LV intracardiac echogenic foci %. Post natally, those infants, 32 (66.6% males and 16 (33.3% females were examined. At a mean age ± SD of 7.4 ± 3.1 months. Prenatally, all infants had a normal left ventricular shortening fraction. The overall mean left ventricular myocardial performance index (reference value, 0.36 ± 0.06, was normal for both infants with left ventricular intracardiac echogenic foci (0.32 ± 0.01 and those with right ventricular intracardiac echogenic foci (0.33 ± 0.05. Trace tricuspid valve regurgitation were noted in 15 (31% of the infants. Left ventricular intracardiac echogenic foci persisted in 15 infants (34.8%, whereas right ventricular intracardiac echogenic foci persisted in 1 infant (20%. Prenatally diagnosed intracardiac echogenic foci can be persistent but is not associated with myocardial dysfunction in the first year of life.

  10. Molecular defects in the ABCA1 pathway affect platelet function.

    Science.gov (United States)

    Schmitz, Gerd; Schambeck, Christian M

    2006-01-01

    Platelet function is sensitive to alterations in cholesterol metabolism, and hypercholesterolemia is associated with enhanced platelet reagibility. Atherogenic low-density lipoproteins (LDL), in particular oxidized LDL, activate src-kinase-family-dependent signalling. In contrast, antiatherogenic high-density lipoproteins(HDL) inhibit platelet aggregation and target the phosphatidylinositol phospholipase C (PI-PLC) pathway. Sphingosine 1-phosphate is a major HDL component and may be crucial for downstream reactions of collagen-induced glycoprotein VI signalling and phosphoinositide 3-kinase. The ATP-binding cassette transporter A1 (ABCA1) regulates cell membrane phospholipid and cholesterol homeostasis and their release to lipid-poor apolipoprotein AI to generate prebeta-HDL precursor particles. ABCA1 also interacts with modulators of vesicular trafficking and number and impaired release of dense bodies from platelets. The ABCA1-NH2-terminus-associated Syntaxin-13, a SNARE complex protein, interacts with syntaxin 13-interacting protein (pallidin) whose deficiency leads to impaired platelet granule release from the dense granule Adapter Protein-3 (AP-3)-related pathway. Interestingly, the cholesterol transporter ABCG1 in addition to ABCA1 is another constituent of the AP-3 pathway, and disorders of lysosome-related organelles such as the Hermansky-Pudlack syndrome complex, Chediak-Higashi syndrome and the ceroid lipofuscinoses provide new opportunities to understand AP-3 pathway-related disorders and the irrelation to membrane phospholipid processing. ABCA1 mutations are involved in dysregulated vesicular trafficking from the trans golgi compartment to the plasma membrane, and ABCA1 R1925Q was shown to contribute to Scott syndrome, a phospholipid-processing disorder of missing surface exposure of phosphatidlyserine. The P2Y12 receptor triggers dense granule secretion by downstream effectors including the G-protein-coupled inward rectifier K+ channel-4 (GIRK-4), and

  11. Familial clustering of executive functioning in affected sibling pair families with ADHD.

    NARCIS (Netherlands)

    Slaats-Willemse, D.I.; Swaab-Barneveld, H.J.; Sonneville, L.

    2005-01-01

    OBJECTIVE: To investigate familial clustering of executive functioning (i.e., response inhibition, fine visuomotor functioning, and attentional control) in attention-deficit/hyperactivity disorder (ADHD)-affected sibling pairs. METHOD: Fifty-two affected sibling pairs aged 6 to 18 years and diagnose

  12. Cloning and functional studies of a splice variant of CYP26B1 expressed in vascular cells.

    Directory of Open Access Journals (Sweden)

    Ali Ateia Elmabsout

    Full Text Available BACKGROUND: All-trans retinoic acid (atRA plays an essential role in the regulation of gene expression, cell growth and differentiation and is also important for normal cardiovascular development but may in turn be involved in cardiovascular diseases, i.e. atherosclerosis and restenosis. The cellular atRA levels are under strict control involving several cytochromes P450 isoforms (CYPs. CYP26 may be the most important regulator of atRA catabolism in vascular cells. The present study describes the molecular cloning, characterization and function of atRA-induced expression of a spliced variant of the CYP26B1 gene. METHODOLOGY/PRINCIPAL FINDINGS: The coding region of the spliced CYP26B1 lacking exon 2 was amplified from cDNA synthesized from atRA-treated human aortic smooth muscle cells and sequenced. Both the spliced variant and full length CYP26B1 was found to be expressed in cultured human endothelial and smooth muscle cells, and in normal and atherosclerotic vessel. atRA induced both variants of CYP26B1 in cultured vascular cells. Furthermore, the levels of spliced mRNA transcript were 4.5 times higher in the atherosclerotic lesion compared to normal arteries and the expression in the lesions was increased 20-fold upon atRA treatment. The spliced CYP26B1 still has the capability to degrade atRA, but at an initial rate one-third that of the corresponding full length enzyme. Transfection of COS-1 and THP-1 cells with the CYP26B1 spliced variant indicated either an increase or a decrease in the catabolism of atRA, probably depending on the expression of other atRA catabolizing enzymes in the cells. CONCLUSIONS/SIGNIFICANCE: Vascular cells express the spliced variant of CYP26B1 lacking exon 2 and it is also increased in atherosclerotic lesions. The spliced variant displays a slower and reduced degradation of atRA as compared to the full-length enzyme. Further studies are needed, however, to clarify the substrate specificity and role of the CYP26B1

  13. High dietary sodium blunts affects of angiotensin-converting enzyme inhibition on vascular angiotensin I-to-angiotensin II conversion in rats

    NARCIS (Netherlands)

    Kocks, Menno J A; Buikema, Hendrik; Gschwend, Simone; Boomsma, Frans; de Zeeuw, Dick; Navis, Gerjan

    2003-01-01

    High sodium intake blunts the efficacy of angiotensin (Ang)-converting enzyme (ACE) inhibition (ACEi), but the underlying mechanism is incompletely characterized. High sodium has been reported to increase vascular expression and vascular activity of ACE. To investigate whether high-dietary sodium-in

  14. The functional outcome of lower-extremity fractures with vascular injury.

    Science.gov (United States)

    Lin, C H; Wei, F C; Levin, L S; Su, J I; Yeh, W L

    1997-09-01

    Salvage of lower-extremity Gustilo type IIIC fractures is difficult, time-consuming for the patients and physicians, and not universally successful because of poor functional outcomes. Even if successful with limb salvage, the functional result may be unsatisfactory because of mutilating injuries to muscle and nerve, bone loss, and the presence of chronic infection. From July 1991 until July 1994, revascularizations of open IIIC fractures were attempted for wounds with Mangled Extremity Severity Score (MESS) MESS was able to predict the secondary amputation rate and the functional result. Sixteen of the 17 limb-salvaged patients with MESS MESS = 8 to 10 failed to achieve minimal functional requirements at the 2-year follow-up. Using statistical analysis, we found that the salvaged limbs with MESS MESS > 9. Using our protocol for treatment for IIIC fractures, the threshold for immediate amputation can be raised from MESS = 7 to MESS = 9. Our conclusions are (1) more severely injured limbs have poor functional results, (2) every patient needs subsequent reconstructive surgery, and (3) the MESS may be helpful in decision-making.

  15. The relation of red blood cell fatty acids with vascular stiffness, cardiac structure and left ventricular function: the Framingham Heart Study.

    Science.gov (United States)

    Kaess, Bernhard M; Harris, William S; Lacey, Sean; Larson, Martin G; Hamburg, Naomi M; Vita, Joseph A; Robins, Sander J; Benjamin, Emelia J; Mitchell, Gary F; Vasan, Ramachandran S

    2015-02-01

    Polyunsaturated fatty acids have been associated with beneficial influences on cardiovascular health. However, the underlying mechanisms are not clear, and data on the relations of polyunsaturated fatty acids to subclinical disease measures such as vascular stiffness and cardiac function are sparse and inconclusive. In a large community-based cohort, we examined the relations of omega-3 and other fatty acids to a comprehensive panel of vascular function measures (assessing microvascular function and large artery stiffness), cardiac structure and left ventricular function. Red blood cell (RBC) membrane fatty acid composition, a measure of long-term fatty acid intake, was assessed in participants of the Framingham Offspring Study and Omni cohorts and related to tonometry-derived measures of vascular stiffness and to a panel of echocardiographic traits using partial correlations. Up to n=3055 individuals (56% women, mean age 66 years) were available for analyses. In age- and sex-adjusted models, higher RBC omega-3 content was moderately associated (p≤0.002) with several measures of vascular stiffness and function in a protective direction. However, after multivariable adjustment, only an association of higher RBC omega-3 content with lower carotid-femoral pulse wave velocity (a measure of aortic stiffness) remained significant (r = -0.06, p=0.002). In secondary analyses, higher linoleic acid, the major nutritional omega-6 fatty acid, was associated with smaller left atrial size, even after multivariable adjustment (r = -0.064, pacid. The clinical significance of these modest associations remains to be elucidated.

  16. Effect of treadmill exercise and Ferula gummosa on myocardial HSP72, vascular function, and antioxidant defenses in spontaneously hypertensive rats.

    Science.gov (United States)

    Gholitabar, Samira; Roshan, Valiollah Dabidi

    2013-01-01

    This study evaluates the effect of treadmill exercise and Ferula gummosa (FG) on heat shock protein (HSP72), biomarkers related to vascular function, and oxidant/antioxidant system in the heart tissue of spontaneously hypertensive rats treated with N(ω)-nitro-L-arginine-methyl ester (L-NAME). Fifty adult male Wistar rats are randomly classified into five groups: treadmill exercise, FG, combination of treadmill exercise + FG, L-NAME, and saline. Treadmill exercise was performed between 25 and 64 minutes at the speed of 15-22 m per minute for 8 weeks and five sessions a week. The FG will be fed through gavage with 90 mg/kg dosage. Hypertension was induced by l-NAME (10 mg/kg) for 8 weeks and six sessions a week. Administration of L-NAME for 8 weeks caused significant increase in HSP72, angiotensin-converting enzyme (ACE), and protein carbonyl (PC), and significant decrease in glutathione peroxidase (GPx) and nitric oxide (NO) level, when compared with the saline group. In contrast, both treadmill exercise and/or FG protocols, in particular, the combined protocol, led to the improvement in HSP72 and balance in oxidant/antioxidant process and inhibited vascular dysfunction, when compared with the L-NAME group. Moreover, no significant differences were detected in the HSP72 level between rats in the treadmill exercise and FG groups. These results provide a rationale for an inhibitory role and a cardioprotective effect of lifestyle related to the health in the attenuation of hypertension-induced cardiotoxicity.

  17. Angiotensin II impairs endothelial progenitor cell number and function in vitro and in vivo: implications for vascular regeneration.

    Science.gov (United States)

    Endtmann, Cathleen; Ebrahimian, Talin; Czech, Thomas; Arfa, Omar; Laufs, Ulrich; Fritz, Mathias; Wassmann, Kerstin; Werner, Nikos; Petoumenos, Vasileios; Nickenig, Georg; Wassmann, Sven

    2011-09-01

    Endothelial progenitor cells (EPCs) contribute to endothelial regeneration. Angiotensin II (Ang II) through Ang II type 1 receptor (AT(1)-R) activation plays an important role in vascular damage. The effect of Ang II on EPCs and the involved molecular mechanisms are incompletely understood. Stimulation with Ang II decreased the number of cultured human early outgrowth EPCs, which express both AT(1)-R and Ang II type 2 receptor, mediated through AT(1)-R activation and induction of oxidative stress. Ang II redox-dependently induced EPC apoptosis through increased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase phosphorylation; decreased Bcl-2 and increased Bax expression; and activation of caspase 3 but had no effect on the low cell proliferation. In addition, Ang II impaired colony-forming and migratory capacities of early outgrowth EPCs. Ang II infusion diminished numbers and functional capacities of EPCs in wild-type (WT) but not AT(1)a-R knockout mice (AT(1)a(-/-)). Reendothelialization after focal carotid endothelial injury was decreased during Ang II infusion. Salvage of reendothelialization by intravenous application of spleen-derived progenitor cells into Ang II-treated WT mice was pronounced with AT(1)a(-/-) cells compared with WT cells, and transfusion of Ang II-pretreated WT cells into WT mice without Ang II infusion was associated with less reendothelialization. Transplantation of AT(1)a(-/-) bone marrow reduced atherosclerosis development in cholesterol-fed apolipoprotein E-deficient mice compared with transplantation of apolipoprotein E-deficient or WT bone marrow. Randomized treatment of patients with stable coronary artery disease with the AT(1)-R blocker telmisartan significantly increased the number of circulating CD34/KDR-positive EPCs. Ang II through AT(1)-R activation, oxidative stress, and redox-sensitive apoptosis signal-regulating kinase 1-dependent proapoptotic pathways impairs EPCs in

  18. Improvement of vascular function by acute and chronic treatment with the GPR30 agonist G1 in experimental diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Zi-lin Li

    Full Text Available The G-protein coupled estrogen receptor 30 (GPR30 is a seven-transmembrane domain receptor that mediates rapid estrogen responses in a wide variety of cell types. This receptor is highly expressed in the cardiovascular system, and exerts vasodilatory effects. The objective of the present study was to investigate the effects of GPR30 on vascular responsiveness in diabetic ovariectomized (OVX rats and elucidate the possible mechanism involved. The roles of GPR30 were evaluated in the thoracic aorta and cultured endothelial cells. The GPR30 agonist G1 induced a dose-dependent vasodilation in the thoracic aorta of the diabetic OVX rats, which was partially attenuated by the nitric oxide synthase (NOS inhibitor, nitro-L-arginine methylester (L-NAME and the GPR30-selective antagonist G15. Dose-dependent vasoconstrictive responses to phenylephrine were attenuated significantly in the rings of the thoracic aorta following the acute G1 administration in the diabetic OVX rats. This effect of G1 was abolished partially by L-NAME and G15. The acute administration of G1 increased significantly the eNOS activity and the concentration of NO in the endothelial cells exposed to high glucose. G1 treatment induced an enhanced endothelium-dependent relaxation to acetylcholine (Ach in the diabetic OVX rats. Further examination revealed that G1 induced vasodilation in the diabetic OVX rats by increasing the phosphorylation of eNOS. These findings provide preliminary evidence that GPR30 activation leads to eNOS activation, as well as vasodilation, to a certain degree and has beneficial effects on vascular function in diabetic OVX rats.

  19. Radiological functional analysis of the vascular system contrast media, methods, results

    CERN Document Server

    1983-01-01

    Scientists and engineers have been involved in medical radiology from the very beginning. At times advances in this field occur at a tremen­ dously fast pace. Developments in radiological diagnostics have - technologically and medically speaking - focused on morphology. At present, computer-aided tomography (CAT) is at a high point in deve1opment, medical application, and validation. The preconditions for this success were rapid advances in electronics and computer technology - in hardware and in software - and an unexpected cost reduction in these fields; the co operation of various scientific disci­ plines was also essential. Functional radiological diagnosis has been neglected in part, owing to the emphasis on morphology, but alone the synthesis of morphology and function prornises further advances. Apart from the limited capabilities ofuItrasonic techniques there is no way other than using X-rays to carry out functional studies of organs and their systems through an intact body surface. It is frequently...

  20. Electrospun aligned nanofibrous composite of MWCNT/polyurethane to enhance vascular endothelium cells proliferation and function.

    Science.gov (United States)

    Meng, Jie; Han, Zhaozhao; Kong, Hua; Qi, Xiaojin; Wang, Chaoying; Xie, Sishen; Xu, Haiyan

    2010-10-01

    Aligned or random nanofibrous meshes of multiwalled carbon nanotubes/polyurethane composite (MWCNT/PU) were fabricated by electrospinning and characterized by scanning electron microscopy (SEM). The regulatory effects of nanofibrous structure and MWCNT on the growth and anticoagulant function of human umbilical vein endothelial cells (HUVECs) were investigated by examining proliferation, type IV collagen secretion, tissue factor and plasminogen activator inhibitor-1 (PAI-1) release, and cytoskeleton arrangement, as well as via pull-down analysis. We show that aligned nanofibrous structure and MWCNT can function as extracellular signals to stimulate cell growth, proliferation, and extracellular collagen secretion, in addition to preserving anticoagulant function. The nanofibrous structures played important roles in the activation of Rac and Cdc42, while CNT regulated the activation of Rho. These two features synergistically activated Rho GTPases that transmitted cell-substrate signals to the cytoplasm. These signals were then relayed to the nucleus by the MAP kinase pathway to direct cytoskeletal arrangement and cell orientation.

  1. Vascular Functions and Brain Integrity in Midlife: Effects of Obesity and Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Andreana P. Haley

    2014-01-01

    Full Text Available Intact cognitive function is the best predictor of quality of life and functional ability in older age. Thus, preventing cognitive decline is central to any effort to guarantee successful aging for our growing population of elderly. The purpose of the work discussed in this outlook paper is to bridge knowledge from basic and clinical neuroscience with the aim of improving how we understand, predict, and treat age- and disease-related cognitive impairment. Over the past six years, our research team has focused on intermediate neuroimaging phenotypes of brain vulnerability in midlife and isolating the underlying physiological mechanisms. The ultimate goal of this work was to pave the road for the development of early interventions to enhance cognitive function and preserve brain integrity throughout the lifespan.

  2. Vascular endothelial cell function and cardiovascular risk factors in patients with chronic renal failure

    DEFF Research Database (Denmark)

    Haaber, A B; Eidemak, I; Jensen, T

    1995-01-01

    Cardiovascular risk factors and markers of endothelial cell function were studied in nondiabetic patients with mild to moderate chronic renal failure. The transcapillary escape rate of albumin and the plasma concentrations of von Willebrand factor, fibrinogen, and plasma lipids were measured in 29...

  3. Functional activities of receptors for tumor necrosis factor-alpha on human vascular endothelial cells.

    NARCIS (Netherlands)

    Paleolog, E.M.; Delasalle, S.A.; Buurman, W.A.; Feldmann, M.

    1994-01-01

    Tumor necrosis factor-alpha (TNF-alpha) plays a critical role in the control of endothelial cell function and hence in regulating traffic of circulating cells into tissues in vivo. Stimulation of endothelial cells in vitro by TNF-alpha increases the surface expression of leukocyte adhesion molecules

  4. Exercise-induced changes in venous vascular function in nonpregnant formerly preeclamptic women.

    NARCIS (Netherlands)

    Krabbendam, I.; Maas, M.L.; Thijssen, D.H.J.; Oyen, W.J.G.; Lotgering, F.K.; Hopman, M.T.E.; Spaanderman, M.E.A.

    2009-01-01

    OBJECTIVE: Formerly preeclamptic women with low plasma volume are at increased risk of recurrent gestational hypertensive disease. We hypothesized that a 4-week cycling training in formerly preeclamptic women improves (venous) hemodynamic function. METHODS: In 9 formerly preeclamptic women, we exami

  5. Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization

    NARCIS (Netherlands)

    Westenbrink, B. Daan; Lipsic, Erik; van der Meer, Peter; van der Harst, Pirn; Oeseburg, Hisko; Sarvaas, Gideon J. Du Marchie; Koster, Johan; Voors, Adriaan A.; van Veldhuisen, Dirk J.; van Gilst, Wiek H.; Schoemaker, Regien G.

    2007-01-01

    Aims Erythropoietin (EPO) improves cardiac function and induces neovascutarization in chronic heart failure (CHF), although the exact mechanism has not been elucidated. We studied the effects of EPO on homing and incorporation of endothelial progenitor cells (EPC) into the myocardial microvasculatur

  6. Diagnosing vascular causes of renal failure.

    Science.gov (United States)

    Abuelo, J G

    1995-10-15

    The incidence of renal failure due to vascular diseases is increasing. Two reasons for this are the epidemic of atherosclerotic vascular disease in the aging population and the widespread use of vasoactive drugs that can adversely affect renal function. These vascular causes of renal failure include vasomotor disorders such as that associated with nonsteroidal antiinflammatory drugs, small-vessel diseases such as cholesterol crystal embolization, and large-vessel diseases such as renal artery stenosis. These causes of azotemia are less familiar to physicians than more classic causes, such as acute tubular necrosis, and are less likely to be recognized in their early stages. This article describes the various vascular diseases that impair renal function and outlines the steps necessary to identify them. Although some of these conditions, such as renal artery stenosis, can gradually impair function, the vascular causes of acute renal failure are emphasized in this article. Because the vasculitides primarily cause renal failure through secondary glomerulonephritis, they are mentioned only briefly. Extensive testing is rarely necessary because the cause is usually suspected through syndrome recognition. The diagnosis can then be confirmed by the results of one or two additional tests or by improved renal function after treatment.

  7. Imaging vascular function for early stage clinical trials using dynamic contrast-enhanced magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Leach, M.O.; Orton, M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Research UK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom); Morgan, B. [Univ. of Leicester, College of Medicine, Biological Sciences and Psychology, Leicester (United Kingdom); Tofts, P.S. [Brighton and Sussex Medical School, Univ. of Sussex, Clinical Imaging Sciences Centre, Sussex (United Kingdom); Buckley, D.L. [University of Leeds, Division of Medical Physics, Leeds (United Kingdom); Huang, W. [Oregon Health and Science Univ., Advanced Imaging Research Centre, Portland, OR (United States); Horsfield, M.A. [Medical Physics Section, Leicester Royal Infirmary, Dept. of Cardiovascular Sciences, Leicester (United Kingdom); Chenevert, T.L. [Univ. of Michigan Health System, Ann Arbor, MI (United States); Collins, D.J. [Royal Marsden Hospital NHS Foundation Trust, Cancer Research UK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom); Jackson, A. [Univ. of Manchester, Wolfson Molecular Imaging Centre, Withington, Manchester, M20 3LJ (United Kingdom); Lomas, D. [Univ. of Cambridge, Dept. of Radiology, Cambridge (United Kingdom); Whitcher, B. [Unit 2 Greenways Business Park, Mango Solutions, Chippenham (United Kingdom); Clarke, L. [Cancer Imaging Program, Imaging Technology Development Branch, Rockville, MD (United States); Plummer, R. [Univ. of Newcastle Upon Tyne, The Medical School, Medical Oncology, Northern Inst. for Cancer Research, Newcastle Upon Tyne (United Kingdom); Judson, I. [Royal Marsden Hospital, Sutton, Surrey (United Kingdom); Jones, R. [Beatson West of Scotland Cancer Centre, Glasgow (United Kingdom); Alonzi, R. [Mount Vernon Cancer Centre, Northwood (United Kingdom); Brunner, T. [Gray Inst. for Radiation, Oncology and Biology, Oxford (United Kingdom); Koh, D.M. [Royal Marsden NHS Foundation Trust, Diagnostic Radiology, Sutton, Surrey (United Kingdom)] [and others

    2012-07-15

    Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process (i.e. image acquisition and analysis) can be performed effectively and with consistency among contributing centres. As the technique continues to develop in order to provide potential improvements in sensitivity and physiological relevance, there is considerable scope for between-centre variation in techniques. A workshop was convened by the Imaging Committee of the Experimental Cancer Medicine Centres (ECMC) to review the current status of DCE-MRI and to provide recommendations on how the technique can best be used for early stage trials. This review and the consequent recommendations are summarised here. (orig.)

  8. Role of leptin signaling in hemato-vascular development and niche function: Leptin receptor-mediated signaling regulates LT-HSC homeostasis in vivo

    Science.gov (United States)

    Homeostatic functioning of the cardiovascular and hematopoietic systems is known to be interdependent and strongly influenced by the microenvironment in which hemato-vascular cells develop and reside. The role of nutrition and metabolism as regulable and dynamic extracellular cues however, remains a...

  9. Increasing functional modularity with residence time in the co-distribution of native and introduced vascular plants

    Science.gov (United States)

    Hui, Cang; Richardson, David M.; Pyšek, Petr; Le Roux, Johannes J.; Kučera, Tomáš; Jarošík, Vojtěch

    2013-01-01

    Species gain membership of regional assemblages by passing through multiple ecological and environmental filters. To capture the potential trajectory of structural changes in regional meta-communities driven by biological invasions, one can categorize species pools into assemblages of different residence times. Older assemblages, having passed through more environmental filters, should become more functionally ordered and structured. Here we calculate the level of compartmentalization (modularity) for three different-aged assemblages (neophytes, introduced after 1500 AD; archaeophytes, introduced before 1500 AD, and natives), including 2,054 species of vascular plants in 302 reserves in central Europe. Older assemblages are more compartmentalized than younger ones, with species composition, phylogenetic structure and habitat characteristics of the modules becoming increasingly distinctive. This sheds light on two mechanisms of how alien species are functionally incorporated into regional species pools: the settling-down hypothesis of diminishing stochasticity with residence time, and the niche-mosaic hypothesis of inlaid neutral modules in regional meta-communities. PMID:24045305

  10. Physical activity measured by accelerometry and its associations with cardiac structure and vascular function in young and middle-aged adults

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Lyass, Asya; Larson, Martin G

    2015-01-01

    BACKGROUND: Physical activity is associated with several health benefits, including lower cardiovascular disease risk. The independent influence of physical activity on cardiac and vascular function in the community, however, has been sparsely investigated. MEASURES AND RESULTS: We related...... relations of usual levels of physical activity and cardiovascular remodeling....... objective measures of moderate- to vigorous-intensity physical activity (MVPA, assessed by accelerometry) to cardiac and vascular indices in 2376 participants of the Framingham Heart Study third generation cohort (54% women, mean age 47 years). Using multivariable regression models, we related MVPA...

  11. Engineering a growth factor embedded nanofiber matrix niche to promote vascularization for functional cardiac regeneration.

    Science.gov (United States)

    Lakshmanan, Rajesh; Kumaraswamy, Priyadharshini; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2016-08-01

    The major loss of tissue extracellular matrix (ECM) after myocardial ischemia is a serious burden that gradually leads to heart failure. Due to lack of available treatment methods to restore the cardiac function, various research strategies have come up to treat the ischemic myocardium. However these have met with limited success due to the complexity of the cardiac tissue, which exhibits a nanofibrous collagenous matrix with spatio-temporal localization of a combination of growth factors. To mimic the topographical and chemical cues of the natural cardiac tissue, we have fabricated a growth factor embedded nanofibrous scaffold through electrospinning. In our previous work, we have reported a nanofibrous matrix made of PLCL and PEOz with an average diameter of 500 nm. The scaffold properties were specifically characterized in vitro for cardio-compatibility. In the present study, we have loaded dual growth factors VEGF and bFGF in the nanofiber matrix and investigated its suitability for cardiac tissue engineering. The encapsulation and release of dual growth factors from the matrix were studied using XPS and ELISA. Bioactivity of the loaded growth factors towards proliferation and migration of endothelial cells (HUVECs) was evaluated through MTS and Boyden chamber assays respectively. The efficiency of growth factors on the nanofibrous matrix to activate signaling molecules was studied in HUVECs through gene expression analysis. Preclinical evaluation of the growth factor embedded nanofibrous patch in a rabbit acute myocardial infarction (AMI) model was studied and cardiac function assessment was made through ECG and echocardiography. The evidence for angiogenesis in the patch secured regions was analyzed through histopathology and immunohistochemistry. Our results confirm the effectiveness of growth factor embedded nanofiber matrix in restoration of cardiac function after ischemia when compared to conventional patch material thereby exhibiting promise as a

  12. Plasma-polyplumbagin-modified microfiber probes: a functional material approach to monitoring vascular access line contamination.

    Science.gov (United States)

    Davis, James; Molina, María Teresa; Leach, Christopher P; Cardosi, Marco F

    2013-10-01

    Atmospheric plasma treated carbon fiber filaments (10 micrometer) were used as the base substrate in the design of a probe intended for use within intravascular access devices. The microfiber probe was further functionalized with a polyplumbagin layer through which the line pH could be determined voltammetrically and therein provide the potential for obtaining diagnostic information relating to bacterial colonization of the line. The redox processes attributed to the immobilized polymer are characterized and a methodology developed to enable the acquisition of a redox signal that is selective and sensitive to pH. The applicability of the composite probe was demonstrated through examining the direct response in whole blood.

  13. Mechanisms of oxidative stress and vascular dysfunction

    Science.gov (United States)

    Nedeljkovic, Z; Gokce, N; Loscalzo, J

    2003-01-01

    The endothelium regulates vascular homoeostasis through local elaboration of mediators that modulate vascular tone, platelet adhesion, inflammation, fibrinolysis, and vascular growth. Impaired vascular function contributes to the pathogenesis of atherosclerosis and acute coronary syndromes. There is growing pathophysiological evidence that increased generation of reactive oxygen species and oxidative stress participates in proatherogenic mechanisms of vascular dysfunction and atherothrombosis. In this review, the role of oxidative stress in mechanisms of vascular dysfunction is discussed, and potential antioxidant strategies are reviewed. PMID:12743334

  14. Functional proteomics reveal the effect of Salvia miltiorrhiza aqueous extract against vascular atherosclerotic lesions.

    Science.gov (United States)

    Hung, Yu-Chiang; Wang, Pei-Wen; Pan, Tai-Long

    2010-06-01

    Salvia miltiorrhiza is a Chinese herb widely used for cardiovascular disorder regimens, yet little is known about the cellular mechanisms that contribute to attenuated growth of smooth muscle cells (SMCs) under oxidative stress such as homocysteine (Hcy) treatment. As anticipated, a low dose (0.015 mg/mL) of S.miltiorrhiza aqueous extract (SMAE) significantly inhibited (>60%) the growth of a rat smooth muscle cell line (A10) under Hcy stimulation and the intracellular reactive oxygen species (ROS) concentration obviously decreased after SMAE treatment in terms of reducing p47(phox) translocation and increasing catalase activity. Signaling profile suggests that SMAE inhibited Hcy-induced A10 cell growth via the PKC/MAPK-dependent pathway. Two-dimensional electrophoresis (2-DE) coupled with mass spectrometry revealed statistically significant changes in the intensity of 14 proteins in response to Hcy and Hcy/SMAE. Meanwhile, SMAE attenuated carbonyl-modification of specific cytoskeleton and chaperone proteins leading to cell type transformation. Moreover, a network analysis using MetaCore shed more light on the molecular basis associated with SMAE efficacy. SMAE exerts its protective effect through the scavenging of ROS and subsequent modulation of protein carbonylation to inhibit cell proliferation. These signature networks and functional proteomics highlighted herein may facilitate the evaluation of potential therapeutic targets and elucidate novel mechanisms through which protein functions can be regulated by the redox status.

  15. Role of Cell-Cell bond for the viability and the function of vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    M. Mura

    2010-01-01

    Full Text Available Vascular smooth muscle cell (VSMC viability and homeostasis is regulated by cell-matrix and cell-cell contact: disruption of these interactions are responsible of a switch from a mature to a high proliferative phenotype. VSMCs migration, rate of growth and apoptosis, and the extent of their extracellular matrix (ECM deposition can be also modulated by proatherogenic peptides. Among them, ATII induces the transactivation of IGF I R, which, together with the binding protein IGFBP3, represents a determinant of cell survival, growth and proliferation. Aim of our in vitro study was to verify the role of elective cell-cell bond in moulating the response to ATII. Thus, we evaluated viability, proliferation, IGFIR, IGFBP3 expression and the long term survival and production of ECM in a provisional tissue. A7r5 cell-line was used in adherent cultures or incubated in agarose-coated culture plates to inhibit cell-matrix interactions. Cells, treated or not with ATII 100 nM, were evaluated for apoptosis rate, cell cycle, IGFIR and IGFBP3 protei expression. Fibrin provisional tissue was developed polymerizing a fibrin solution. cantaining A7r5 cells with thrombin. Histological stainings for ECM components were performed on sections of prvisional tissue. An exclusive cell-cell contact resulted to monolayer cell cultures. ATII did not affect the cell survival in both culture conditions, but promoted a 10% decrease in "S" phase and an increases IGFIR expression only in adherent cells. while suspended cell aggregates were resistant to ATII administration; IGFBP3 was reduced both in ATII treated adherent cells and in floating clustered cells, irrespective of the treatmentn. VSMC conditioning in agarose-coated plates before seeding in fibrin provisional matrix reduced, but not abolished, the cell ability to colonize the clot and to produce ECM. This study demonstrates that the elective cell-cell contact induces a quiescent status in cells lacking of cell

  16. Nitric oxide-mediated vascular function in sepsis using passive leg movement as a novel assessment: a cross-sectional study.

    Science.gov (United States)

    Nelson, Ashley D; Rossman, Matthew J; Witman, Melissa A; Barrett-O'Keefe, Zachary; Groot, H Jonathan; Garten, Ryan S; Richardson, Russell S

    2016-05-01

    Post-cuff occlusion flow-mediated dilation (FMD) is a proposed indicator of nitric oxide (NO) bioavailability and vascular function. FMD is reduced in patients with sepsis and may be a marker of end organ damage and mortality. However, FMD likely does not solely reflect NO-mediated vasodilation, is technically challenging, and often demonstrates poor reproducibility. In contrast, passive leg movement (PLM), a novel methodology to assess vascular function, yields a hyperemic response that is predominately NO-dependent, reproducible, and easily measured. This study evaluated PLM as an approach to assess NO-mediated vascular function in patients with sepsis. We hypothesized that PLM-induced hyperemia, quantified by the increase in leg blood flow (LBF), would be attenuated in sepsis. In a cross-sectional study, 17 subjects in severe sepsis or septic shock were compared with 16 matched healthy controls. Doppler ultrasound was used to assess brachial artery FMD and the hyperemic response to PLM in the femoral artery. FMD was attenuated in septic compared with control subjects (1.1 ± 1.7% vs. 6.8 ± 1.3%; values are means ± SD). In terms of PLM, baseline LBF (196 ± 33 ml/min vs. 328 ± 20 ml/min), peak change in LBF from baseline (133 ± 28 ml/min vs. 483 ± 86 ml/min), and the LBF area under the curve (16 ± 8.3 vs. 143 ± 33) were all significantly attenuated in septic subjects. Vascular function, as assessed by both FMD and PLM, is attenuated in septic subjects compared with controls. These data support the concept that NO bioavailability is attenuated in septic subjects, and PLM appears to be a novel and feasible approach to assess NO-mediated vascular function in sepsis.

  17. Vascular dysfunction in preeclampsia.

    Science.gov (United States)

    Brennan, Lesley J; Morton, Jude S; Davidge, Sandra T

    2014-01-01

    Preeclampsia is a complex disorder which affects an estimated 5% of all pregnancies worldwide. It is diagnosed by hypertension in the presence of proteinuria after the 20th week of pregnancy and is a prominent cause of maternal morbidity and mortality. As delivery is currently the only known treatment, preeclampsia is also a leading cause of preterm delivery. Preeclampsia is associated with maternal vascular dysfunction, leading to serious cardiovascular risk both during and following pregnancy. Endothelial dysfunction, resulting in increased peripheral resistance, is an integral part of the maternal syndrome. While the cause of preeclampsia remains unknown, placental ischemia resulting from aberrant placentation is a fundamental characteristic of the disorder. Poor placentation is believed to stimulate the release of a number of factors including pro- and antiangiogenic factors and inflammatory activators into the maternal systemic circulation. These factors are critical mediators of vascular function and impact the endothelium in distinctive ways, including enhanced endothelial oxidative stress. The mechanisms of action and the consequences on the maternal vasculature will be discussed in this review.

  18. Is there any association of personality traits with vascular endothelial function or systemic inflammation?

    Directory of Open Access Journals (Sweden)

    Reza Bagherian Sararoudi

    2014-01-01

    Full Text Available Background: Evidences showed association of some personality traits with increased risk of cardiovascular diseases, but mediated mechanisms are not entirely described. In this study, we investigated the association of different personality traits with systemic inflammation and endothelial function as probable mediators. Methods: This cross-sectional study was conducted in 2011 on 40-60 years old employees of an industrial company located in Isfahan city (central Iran. Participants were selected through simple random sampling. Personality types were evaluated using the neuroticism-extroversion-openness personality inventory and systemic inflammatory status was determined with high sensitive C-reactive protein (hs-CRP level. To evaluate endothelial function flow mediated dilation (FMD were measured. The obtained data were analyzed with univariate correlation and multiple linear regression tests. Results: A total of 254 cases with mean age of 51.4 ± 6.1 years were evaluated. There was no significant relationship between hs-CRP level and FMD with the personality traits in univariate analysis. In multivariate analysis, no association was found between the scores of personality traits and FMD with controlling the factors such as age, body mass index dyslipidemia, hypertension and diabetes. Only there was an inverse association between conscientiousness score and hs-CRP (β = −0.241, P = 0.013. Conclusions: In our population who were the employees of an industrial company, no relationship was found between specific personality trait and endothelial dysfunction. However, we found that the personality trait of responsibility (conscientiousness is negatively associated with inflammation. Further multi-center studies and also cohort studies are recommended in this regard.

  19. Admixture Mapping Scans Identify a Locus Affecting Retinal Vascular Caliber in Hypertensive African Americans: The Atherosclerosis Risk in Communities (ARIC) Study

    OpenAIRE

    Ching-Yu Cheng; David Reich; Wong, Tien Y.; Ronald Klein; Klein, Barbara E K; Nick Patterson; Arti Tandon; Man Li; Eric Boerwinkle; A Richey Sharrett; W H Linda Kao

    2010-01-01

    Retinal vascular caliber provides information about the structure and health of the microvascular system and is associated with cardiovascular and cerebrovascular diseases. Compared to European Americans, African Americans tend to have wider retinal arteriolar and venular caliber, even after controlling for cardiovascular risk factors. This has suggested the hypothesis that differences in genetic background may contribute to racial/ethnic differences in retinal vascular caliber. Using 1,365 a...

  20. Effects of Quyu Xiaoban Capsule(祛瘀消斑胶囊) on Vascular Endothelial Function in Patients with Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    LIU Yun-fang; ZHAO Yu-xia; Yu Hui-ming

    2006-01-01

    Objective: To evaluate the therapeutic effects of Quyu Xiaoban Capsule (祛瘀消斑胶囊 ,QYXBC) on endothelial dependent vascular relaxation (EDVR) function in patients with atherosclerosis (AS)with ultrasonic technique. Methods: Tested were the endothelial function and blood lipids of 42 patients with AS in the treated group and 30 healthy volunteers in the control group. And re-examination of these parameters was carried out on the AS patients after they had been treated with QYXBC for 10 months. Results: Before treatment, the reactive hyperemia induced changes in artery diameter in the treated group was significantly lower than that in the control group (P<0.01), while insignificant difference was found between the two groups in response to nitroglycerin. In the treated group after treatment, with D%-R improved significantly (P<0.01), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C)decreased by 16.3%, 5.6%, 10.2% respectively and high-density lipoprotein cholesterol (HDL-C) increased by 7.5%. EDVR was correlated negatively with the serum TC, LDL-C concentrations and the baseline brachial diameter (D0) (r = -0.41, -0.66, -0.59, respectively, all P<0.01), but correlated positively with HDL-C (r = 0.62, P<0.05). The ameliorative extent of EDVR was correlated positively to the decreased magnitude of TC and LDL-C concentrations ( r = 0.67,0.59, both P<0.01 ). Conclusion: QYXBC can lower the level of blood lipids and improve significantly EDVR function.

  1. [Vascular depression in the elderly. Does inflammation play a role?].

    Science.gov (United States)

    Viscogliosi, Giovanni; Andreozzi, Paola; Chiriac, Iulia Maria; Ettorre, Evaristo; Vulcano, Achiropita; Servello, Adriana; Marigliano, Benedetta; Marigliano, Vincenzo

    2011-06-01

    Vascular depression in the elderly. Does inflammation play a role?Depression is the most common comorbidity in the elderly, and it is a major determinant of disability. The late-onset depression in highly associated to cardiovascular disease. Depressive symptoms may follow vascular brain damage, especially when mood regulating areas are affected. However depression is strongly associated to vascular disease even when there is no manifest brain damage. Recently great attention has been given to chronic inflammation, both related to depression and vascular disease. Both experimental and clinical evidence shows that a rise in the concentrations of proinflammatory cytokines and glucocorticoids in depressed patients is associated with defect in serotonergic function. Chronic inflammation may underlie many forms of depression associated with vascular disease and metabolic syndrome. The importance of the inflammation hypothesis of depression lies is that psychotropic drugs may have central anti-inflammatory action, and that new generation of central anti-inflammatory drugs may be useful in depression treatment.

  2. Effects of Digoxin and Tongxinluo capsule combination treatment on oxidative stress, cytokines and vascular endothelial function in patients with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    Zhi Wang; Zhong-Dao Zhang; Si-Hong Zhao; Zhi-Juan Chen

    2017-01-01

    Objective:To explore the effect of digoxin and Tongxin capsule combined therapy on oxidative stress, cytokines and vascular endothelial function in patients with chronic heart failure, and provide help for clinical treatment of patients with chronic heart failure.Methods:95 cases of chronic heart failure in our hospital were randomly divided into observation group (47 cases) and control group (48 cases). Control group patients were given basic treatment, and observation group received combination therapy of digoxin and Tongxinluo capsule, to detect and to investigate the changes of oxidative stress, cytokines and vascular endothelial function in two groups of patients before and after treatment.Results:There was no significant difference in oxidative stress, cytokines and vascular endothelial function between the two groups of chronic heart failure patients before treatment (P>0.05). Compared with before treatment, the malondialdehyde (MDA) and cytokines [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-6 (IL-6) and brain natriuretic peptide (BNP)] in two groups of patients with chronic heart failure after treatment decreased significantly (P<0.05), while indexes related to endothelial function [hyperemic brachial artery diameter after reactive hyperemia, brachial artery diameter change rate, brachial artery endothelial dependent diastolic function (FMD), and brachial artery endothelium dependent diastolic function (NMD)] and related indexes of oxidative stress [glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT)] were significantly increased (P<0.05). The related indexes and oxidative stress indexes (GSH-Px, CAT and SOD) of observation group after the combined treatment in patients with endothelial function were significantly higher than the control group after treatment (P<0.05). After treatment, cytokines and MDA levels were significantly lower than the control group (P<0.05).Conclusions:Tongxinluo capsule

  3. Exercise and postprandial lipaemia: effects on peripheral vascular function, oxidative stress and gastrointestinal transit

    Directory of Open Access Journals (Sweden)

    McLaughlin Jim

    2007-10-01

    Full Text Available Abstract Postprandial lipaemia may lead to an increase in oxidative stress, inducing endothelial dysfunction. Exercise can slow gastric emptying rates, moderating postprandial lipaemia. The purpose of this study was to determine if moderate exercise, prior to fat ingestion, influences gastrointestinal transit, lipaemia, oxidative stress and arterial wall function. Eight apparently healthy males (age 23.6 ± 2.8 yrs; height 181.4 ± 8.1 cm; weight 83.4 ± 16.2 kg; all data mean ± SD participated in the randomised, crossover design, where (i subjects ingested a high-fat meal alone (control, and (ii ingested a high-fat meal, preceded by 1 h of moderate exercise. Pulse Wave Velocity (PWV was examined at baseline, post-exercise, and in the postprandial period. Gastric emptying was measured using the 13C-octanoic acid breath test. Measures of venous blood were obtained prior to and following exercise and at 2, 4 and 6 hours post-ingestion. PWV increased (6.5 ± 1.9 m/sec at 2 (8.9 ± 1.7 m/sec and 4 hrs (9.0 ± 1.6 m/sec post-ingestion in the control group (time × group interaction, P

  4. Functional and splicing defect analysis of 23 ACVRL1 mutations in a cohort of patients affected by Hereditary Hemorrhagic Telangiectasia.

    Directory of Open Access Journals (Sweden)

    Ferdos Alaa El Din

    Full Text Available Hereditary Hemorrhagic Telangiectasia syndrome (HHT or Rendu-Osler-Weber (ROW syndrome is an autosomal dominant vascular disorder. Two most common forms of HHT, HHT1 and HHT2, have been linked to mutations in the endoglin (ENG and activin receptor-like kinase 1 (ACVRL1or ALK1 genes respectively. This work was designed to examine the pathogenicity of 23 nucleotide variations in ACVRL1 gene detected in more than 400 patients. Among them, 14 missense mutations and one intronic variant were novels, and 8 missense mutations were previously identified with questionable implication in HHT2. The functionality of missense mutations was analyzed in response to BMP9 (specific ligand of ALK1, the maturation of the protein products and their localization were analyzed by western blot and fluorescence microscopy. The splicing impairment of the intronic and of two missense mutations was examined by minigene assay. Functional analysis showed that 18 out of 22 missense mutations were defective. Splicing analysis revealed that one missense mutation (c.733A>G, p.Ile245Val affects the splicing of the harboring exon 6. Similarly, the intronic mutation outside the consensus splicing sites (c.1048+5G>A in intron 7 was seen pathogenic by splicing study. Both mutations induce a frame shift creating a premature stop codon likely resulting in mRNA degradation by NMD surveillance mechanism. Our results confirm the haploinsufficiency model proposed for HHT2. The affected allele of ACVRL1 induces mRNA degradation or the synthesis of a protein lacking the receptor activity. Furthermore, our data demonstrate that functional and splicing analyses together, represent two robust diagnostic tools to be used by geneticists confronted with novel or conflicted ACVRL1 mutations.

  5. Advanced glycation end product associated skin autofluorescence: a mirror of vascular function?

    Science.gov (United States)

    Hofmann, Britt; Adam, Anne-Catrin; Jacobs, Kathleen; Riemer, Marcus; Erbs, Christian; Bushnaq, Hasan; Simm, Andreas; Silber, Rolf-Edgar; Santos, Alexander Navarrete

    2013-01-01

    Advanced glycation end products (AGEs) seem to be involved in aging as well as in the development of cardiovascular diseases. During aging, AGEs accumulate in extracellular matrix proteins like collagen and contribute to vessel stiffness. Whether non-invasive measurement of AGE accumulation in the skin may reflect vessel function and vessel protein modification is unknown. Herein we set out to analyze the AGE-modifications in the collagens extracted from residual bypass graft material, the skin autofluorescence reflecting the accumulation of AGEs in the body as well as the pulse wave velocity reflecting vessel stiffness. Collagen types I and III (pepsin digestible collagen fraction) were isolated from the veins of 52 patients by proteolysis. The residual collagen fraction was further extracted by collagenase digestion. Collagen was quantified by hydroxyproline assay and AGEs by the AGE intrinsic fluorescence. Skin autofluorescence was measured with an autofluorescence reader; pulse wave velocity with the VICORDER. The collagen AGE autofluorescence in patient vein graft material increased with patient age. The pepsin digestible collagen fraction was significantly less modified in comparison to the collagenase digestible fraction. Decreasing amounts of extracted collagenase digestible collagen correspond with increasing AGE autofluorescence. Skin autofluorescence and vessel stiffness were significantly linked to the AGE autofluorescence of the collagenase digestible collagen fraction from graft material. In conclusion we have found that skin autofluorescence and pulse wave velocity as non-invasive parameters significantly correlate with the AGE contained in graft material and therefore are strong predictors of vessel AGE modifications in patients with coronary heart disease. Whether the analysis of the skin autofluorescence leads to an improvement of the risk stratification in patients suffering from cardiovascular disease has to be further tested.

  6. Vascular endothelial function is improved by oral glycine treatment in aged rats.

    Science.gov (United States)

    Gómez-Zamudio, Jaime H; García-Macedo, Rebeca; Lázaro-Suárez, Martha; Ibarra-Barajas, Maximiliano; Kumate, Jesús; Cruz, Miguel

    2015-06-01

    Glycine has been used to reduce oxidative stress and proinflammatory mediators in some metabolic disorders; however, its effect on the vasculature has been poorly studied. The aim of this work was to explore the effect of glycine on endothelial dysfunction in aged rats. Aortic rings with intact or denuded endothelium were obtained from untreated or glycine-treated male Sprague-Dawley rats at 5 and 15 months of age. Concentration-response curves to phenylephrine (PHE) were obtained from aortic rings incubated with N(G)-nitro-l-arginine methyl ester (l-NAME), superoxide dismutase (SOD), indomethacin, SC-560, and NS-398. Aortic mRNA expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase 4 (NOX-4), cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2), tumour necrosis factor (TNF)-α, and interleukin-1 β was measured by real time RT-PCR. The endothelial modulation of the contraction by PHE was decreased in aortic rings from aged rats. Glycine treatment improved this modulator effect and increased relaxation to acetylcholine. Glycine augmented the sensitivity for PHE in the presence of l-NAME and SOD. It also reduced the contraction by incubation with indomethacin, SC-560, and NS-398. Glycine increased the mRNA expression of eNOS and decreased the expression of COX-2 and TNF-α. Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability.

  7. Improving Functional Outcomes for Vascular Amputees Through Use of Mirror Therapy and Elimination of the Effects of Electromagnetic Fields.

    Science.gov (United States)

    Houston, Helen; Dickerson, Anne E

    2016-01-01

    The objective of this pilot study was to investigate the effectiveness of combining an amputee limb cover to eliminate the effects of electromagnetic fields (i.e., pain) and a Mirror Therapy exercise program to improve functional outcomes for vascular amputees. A cross-sectional repeated-measures design was used with 14 participants with either acute amputations or surgery at least 8 to 24 months previously. The 4-week intervention included the use of an amputee limb cover and mirror therapy exercises each day. The outcome measures were activities of daily living interference (e.g., self-care, walking, car transfer, low chair transfer, sleep), and well-being (e.g., satisfaction, mood, quality of life) at three times (pre- and posttreatment and maintenance). Participants with acute amputations made significant improvements in the areas of self-care, walking, car transfer, sleep, mood, and quality of life, while the subacute participants improved significantly in sleep and satisfaction. A reduction in the time required before prosthetic fitting decreased from 12 weeks to 8 weeks for acute amputees and an improvement in wearing tolerance from 0-2 to 8-12 hours for the subacute amputees were unexpected results suggesting the combined intervention may improves the extent to which amputees can increase participation in their activities of everyday living.

  8. Oxygen as a regulator of MA-10 cell functions: effect of cobalt chloride on vascular endothelial growth factor production.

    Science.gov (United States)

    Kumar, A; Rani, L; Dhole, B; Chaturvedi, P K

    2012-05-01

    Mammalian testis functions at a temperature and oxygen tension (pO(2)) lower than the core body. Hypoxia-inducible factor-1α (HIF-1α) mediates the adaptive responses to hypoxia such as production of angiogenic vascular endothelial growth factor (VEGF) in a variety of cells and tissues. VEGF production in Leydig cells is stimulated by luteinising hormone (LH)/cAMP. We have conducted experiments to find out whether HIF-1α is involved in LH/cAMP-induced secretion of VEGF by Leydig cell-derived MA-10 cells. Both cobalt chloride (CoCl(2)), an inducer of hypoxia, and 8-Br-cAMP enhanced HIF-1α activity followed by an increase in VEGF secretion. However, there was no change in mRNA levels of HIF-1α. Inhibition of HIF-1α activity by cyclosporine A (CsA) inhibited a rise in VEGF production in response to CoCl(2) as well as 8-Br-cAMP. Inhibitors of protein kinase A (PKA), extracellular regulated kinase 1/2 (ERK1/2) and phosphatidyl inositol-3 kinase/Akt (PI3-K/Akt) inhibited the increase in VEGF levels in response to both CoCl(2) and 8-Br-cAMP. The data suggest that HIF-1α is a mediator of hypoxia- as well as 8-Br-cAMP-stimulated production of VEGF in MA-10 cells; both the stimuli act through a common signalling cascade.

  9. THE USE OF A NOVEL ALDEHYDE-FUNCTIONALIZED CHITOSAN HYDROGEL TO PREPARE POROUS TUBULAR SCAFFOLDS FOR VASCULAR TISSUE ENGINEERING APPLICATIONS

    Directory of Open Access Journals (Sweden)

    Eduardo P. Azevedo

    Full Text Available In this work, porous tubular scaffolds were prepared from a novel water soluble aldehyde-functionalized chitosan (ALDCHIT hydrogel, which was obtained by dissolving this chitosan derivative in water and using oxidized dextrose (OXDEXT as the crosslinking agent at different ALDCHIT:OXDEXT mole ratios (10:1, 10:2 and 10:4. By increasing the amount of OXDEXT in respect to ALDCHIT the hydrogels became more rigid and could absorb more than 200% of its weight in water. Since the ALDCHIT:OXDEXT 10:4 was the most stable hydrogel, its ability to form porous tubular scaffolds was investigated. The tubular scaffolds were prepared by the lyophilization method, where the orientation of the pores was controlled by exposing either the internal or the external surface of the frozen hydrogel during the sublimation step. When only the inner surface of the frozen hydrogel was exposed, tubular scaffolds with a highly porous lumen and a sealed outer surface were obtained, where the orientation of the pores, their sizes and interconnectivity seem to be optimum for vascular tissue engineering application.

  10. Single Low-Density Lipoprotein Apheresis Does Not Improve Vascular Endothelial Function in Chronically Treated Hypercholesterolemic Patients

    Directory of Open Access Journals (Sweden)

    Kevin D. Ballard

    2016-01-01

    Full Text Available Objective. To investigate vascular endothelial function (VEF responses to a single low-density lipoprotein (LDL apheresis session in hypercholesterolemic patients undergoing chronic treatment. Methods. We measured brachial artery flow-mediated dilation (FMD, plasma lipids, vitamin E (α- and γ-tocopherol, markers of oxidative/nitrative stress (malondialdehyde (MDA and nitro-γ-tocopherol (NGT, and regulators of NO metabolism (arginine (ARG and asymmetric dimethylarginine (ADMA prior to (Pre and immediately following (Post LDL apheresis and at 1, 3, 7, and 14 d Post in 5 hypercholesterolemic patients (52 ± 11 y. Results. Relative to Pre, total cholesterol (7.8±1.5 mmol/L and LDL-cholesterol (6.2±1.2 mmol/L were 61% and 70% lower (P<0.01, respectively, at Post and returned to Pre levels at 14 d. Brachial FMD responses (6.9 ± 3.6% and plasma MDA, ARG, and ADMA concentrations were unaffected by LDL apheresis. Plasma α-tocopherol, γ-tocopherol, and NGT concentrations were 52–69% lower at Post (P<0.01, and α-tocopherol remained 36% lower at 1 d whereas NGT remained 41% lower at d 3. Conclusions. Acute cholesterol reduction by LDL apheresis does not alter VEF, oxidative stress, or NO homeostasis in patients treated chronically for hypercholesterolemia.

  11. Deviations in upper limb function of the less-affected side in congenital hemiparesis

    NARCIS (Netherlands)

    Steenbergen, B.; Meulenbroek, R.G.J.

    2006-01-01

    In the present study we examined upper-limb function of the less-affected side in young adolescents with congenital hemiparesis (cerebral palsy: CP). Five participants with hemiparetic CP and five control participants performed a cyclical reach-and-grasp task with the less-affected hand towards targ

  12. Development of Affective Theory of Mind Across Adolescence: Disentangling the Role of Executive Functions

    NARCIS (Netherlands)

    Vetter, N.C.; Altgassen, A.M.; Phillips, L.H.; Mahy, C.E.V.; Kliegel, M.

    2013-01-01

    Theory of mind, the ability to understand mental states, involves inferences about others' cognitive (cognitive theory of mind) and emotional (affective theory of mind) mental states. The current study explored the role of executive functions in developing affective theory of mind across adolescence

  13. The Role of Acute Intermittent Hypoxia in Neutrophil-Generated Superoxide, Sympathovagal Balance, and Vascular Function in Healthy Subjects

    Science.gov (United States)

    Almeida, Germana P. L.; Trombetta, Ivani C.; Cepeda, Felipe X.; Hatanaka, Elaine; Curi, Rui; Mostarda, Cristiano; Irigoyen, Maria C.; Barreto-Filho, José A. S.; Krieger, Eduardo M.; Consolim-Colombo, Fernanda M.

    2017-01-01

    Introduction: Recurrent hypoxia (HPX), a hallmark of the obstructive sleep apnea (OSA), impairs autonomic balance, and increases arterial blood pressure (BP). Oxidative stress is one of the mechanisms involved in these alterations. The cumulative effect of acute intermittent HPX and the chronicity may determine whether the response crosses the threshold from having protective value to pathology. However, the impact of acute intermittent HPX–reoxygenation on markers of oxidative stress in healthy individuals remains to be fully understood. Objective: To analyze the effects of the acute intermittent HPX on the generation of neutrophil-derived superoxide, sympathovagal balance, and vascular function in healthy subjects. Methods: We applied six cycles of intermittent HPX (10% O2 and 90% N2) for 5 min followed by 2 min of room-air in 15 healthy volunteers (34 ± 2 years; 22.3 ± 0.46 kg/m2), without OSA (polysomnography), during wakefulness. During the experimental protocol, we recorded O2 saturation, end-tidal CO2, heart rate (HR), systolic, and diastolic BP, cardiac output (CO) and peripheral resistance (PR). Cardiac sympathovagal balance was determined by HR variability analysis (low frequency and high frequency bands, LF/HF). Superoxide generation in polymorphonuclear neutrophil cells were established using relative luminescence units (PMNs RLU) at baseline (pre-HPX) and immediately after hypoxia induction (post-HPX6). Results: The studied subjects had normal levels of BP, plasma glucose, lipid profile, and inflammatory marker (C-reactive protein). Acute intermittent HPX increased HR, systolic BP, CO, and decreased PR. Additionally, acute intermittent HPX increased PMNs RLU, measured post-HPX6 (470 ± 50 vs. 741 ± 135, P < 0.05). We found a similar increase in LF/HF post-HPX6 (0.91 ± 0.11 vs. 2.85 ± 0.40, P < 0.05). PR was diminished from pre-HPX to post-HPX6 (1.0 ± 0.03 vs. 0.85 ± 0.06, P < 0.05). Further analysis showed significant association between O2

  14. Vascular quality of care pilot study: how admission to a vascular surgery service affects evidence-based pharmacologic risk factor modification in patients with lower extremity peripheral arterial disease

    Directory of Open Access Journals (Sweden)

    Steenhof N

    2014-06-01

    Full Text Available Naomi Steenhof,1,2 Francesca Le Piane,1 Kori Leblanc,1–3 Naomi R Eisenberg,4 Yvonne Kwan,1 Christine Malmberg,1,6 Alexandra Papadopoulos,5,7 Graham Roche-Nagle4,7,8 1Department of Pharmacy, University Health Network, 2Leslie Dan Faculty of Pharmacy, University of Toronto, 3Centre for Innovation in Complex Care, University Health Network, 4Division of Vascular Surgery, University Health Network, 5Faculty of Nursing, University of Toronto, Toronto, ON, 6Victoria General Hospital, Vancouver Island Health Authority, Victoria, BC, 7Peter Munk Cardiac Centre, University Health Network, 8Faculty of Medicine, University of Toronto, Toronto, ON, Canada Background: Peripheral arterial disease (PAD guidelines recommend aggressive risk factor modification to improve cardiovascular outcomes. Recommended pharmacologic therapies include antiplatelets, angiotensin converting enzyme (ACE inhibitors, and HMG-CoA-reductase inhibitors (statins. Purpose: We studied the degree to which patient admission to a vascular surgery service increased the use of these therapies. Patients and methods: The authors conducted a retrospective chart review of 150 patients with PAD admitted to the vascular surgery service at a large Canadian tertiary care hospital. The use of recommended pharmacologic therapies at the time of admission and discharge were compared. A multidisciplinary clinical team established criteria by which patients were deemed ineligible to receive any of the recommended therapies. Angiotensin receptor blockers (ARBs were considered an alternative to ACE inhibitors. Results: Prior to hospital admission, 64% of patients were on antiplatelet therapy, 67% were on an ACE inhibitor or ARB, and 71% were on a statin. At the time of discharge, 91% of patients were on an antiplatelet (or not, with an acceptable reason, 77% were on an ACE inhibitor or an ARB (or not, with an acceptable reason, and 85% were on a statin (or not, with an acceptable reason. While new

  15. Gallic acid tailoring surface functionalities of plasma-polymerized allylamine-coated 316L SS to selectively direct vascular endothelial and smooth muscle cell fate for enhanced endothelialization.

    Science.gov (United States)

    Yang, Zhilu; Xiong, Kaiqin; Qi, Pengkai; Yang, Ying; Tu, Qiufen; Wang, Jin; Huang, Nan

    2014-02-26

    The creation of a platform for enhanced vascular endothelia cell (VEC) growth while suppressing vascular smooth muscle cell (VSMC) proliferation offers possibility for advanced coatings of vascular stents. Gallic acid (GA), a chemically unique phenolic acid with important biological functions, presents benefits to the cardiovascular disease therapy because of its superior antioxidant effect and a selectivity to support the growth of ECs more than SMCs. In this study, GA was explored to tailor such a multifunctional stent surface combined with plasma polymerization technique. On the basis of the chemical coupling reaction, GA was bound to an amine-group-rich plasma-polymerized allylamine (PPAam) coating. The GA-functionalized PPAam (GA-PPAam) surface created a favorable microenvironment to obtain high ECs and SMCs selectivity. The GA-PPAam coating showed remarkable enhancement in the adhesion, viability, proliferation, migration, and release of nitric oxide (NO) of human umbilical vein endothelial cells (HUVECs). The GA-PPAam coating also resulted in remarkable inhibition effect on human umbilical artery smooth muscle cell (HUASMC) adhesion and proliferation. These striking findings may provide a guide for designing the new generation of multifunctional vascular devices.

  16. 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.

  17. The survival condition and immunoregulatory function of adipose stromal vascular fraction (SVF in the early stage of nonvascularized adipose transplantation.

    Directory of Open Access Journals (Sweden)

    Ziqing Dong

    Full Text Available INTRODUCTION: Adipose tissue transplantation is one of the standard procedures for soft-tissue augmentation, reconstruction, and rejuvenation. However, it is unknown as to how the graft survives after transplantation. We thus seek out to investigate the roles of different cellular components in the survival of graft. MATERIALS & METHODS: The ratios of stromal vascular fraction (SVF cellular components from human adipose tissue were evaluated using flow cytometry. Human liposuction aspirates that were either mixed with marked SVF cells or PBS were transplanted into nude mice. The graft was harvested and stained on days 1,4,7 and 14. The inflammation level of both SVF group and Fat-only group were also evaluated. RESULTS: Flow cytometric analysis showed SVF cells mainly contained blood-derived cells, adipose-derived stromal cells (ASCs, and endothelial cells. Our study revealed that most cells are susceptible to death after transplantation, although CD34+ ASCs can remain viable for 14 days. Notably, we found that ASCs migrated to the peripheral edge of the graft. Moreover, the RT-PCR and the immuno-fluorescence examination revealed that although the SVF did not reduce the number of infiltrating immune cells (macrophages in the transplant, it does have an immunoregulatory function of up-regulating the expression of CD163 and CD206 and down-regulating that of IL-1β, IL-6. CONCLUSIONS: Our study suggests that the survival of adipose tissue after nonvascularized adipose transplantation may be due to the ASCs in SVF cells. Additionally, the immunoregulatory function of SVF cells may be indirectly contributing to the remolding of adipose transplant, which may lead to SVF-enriched adipose transplantation.

  18. Effects of oral lycopene supplementation on vascular function in patients with cardiovascular disease and healthy volunteers: a randomised controlled trial.

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    Parag R Gajendragadkar

    Full Text Available AIMS: The mechanisms by which a 'Mediterranean diet' reduces cardiovascular disease (CVD burden remain poorly understood. Lycopene is a potent antioxidant found in such diets with evidence suggesting beneficial effects. We wished to investigate the effects of lycopene on the vasculature in CVD patients and separately, in healthy volunteers (HV. METHODS AND RESULTS: We randomised 36 statin treated CVD patients and 36 healthy volunteers in a 2∶1 treatment allocation ratio to either 7 mg lycopene or placebo daily for 2 months in a double-blind trial. Forearm responses to intra-arterial infusions of acetylcholine (endothelium-dependent vasodilatation; EDV, sodium nitroprusside (endothelium-independent vasodilatation; EIDV, and NG-monomethyl-L-arginine (basal nitric oxide (NO synthase activity were measured using venous plethysmography. A range of vascular and biochemical secondary endpoints were also explored. EDV in CVD patients post-lycopene improved by 53% (95% CI: +9% to +93%, P = 0.03 vs. placebo without changes to EIDV, or basal NO responses. HVs did not show changes in EDV after lycopene treatment. Blood pressure, arterial stiffness, lipids and hsCRP levels were unchanged for lycopene vs. placebo treatment groups in the CVD arm as well as the HV arm. At baseline, CVD patients had impaired EDV compared with HV (30% lower; 95% CI: -45% to -10%, P = 0.008, despite lower LDL cholesterol (1.2 mmol/L lower, 95% CI: -1.6 to -0.9 mmol/L, P<0.001. Post-therapy EDV responses for lycopene-treated CVD patients were similar to HVs at baseline (2% lower, 95% CI: -30% to +30%, P = 0.85, also suggesting lycopene improved endothelial function. CONCLUSIONS: Lycopene supplementation improves endothelial function in CVD patients on optimal secondary prevention, but not in HVs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01100385.

  19. The effects of Δ9-Tetrahydrocannabinole treatment on gonadal micro-vascularization and affected fertility examined by SEM and 3D-morphometry

    Science.gov (United States)

    Erlbacher, K. M. T.; Minnich, B.

    2015-10-01

    The present study focuses on the effects of Δ9-tetrahydrocannabinol (THC) on the reproductive system in nude rats with special emphasis on how Δ9-THC impacts the vascularization of testes which in turn indirectly influences fertility. Basically, Δ9-tetrahydrocannabinol (THC) causes not only negative (psychoactive) effects in the human body as cannabinole administration in medical use (dose-dependent) offers multiple new treatment opportunities such as pain relief or containment of various cancers. Concerning the reproductive system it strongly influences CB-receptors along the hypothalamic-pituitary-gonadal axis resulting in reduced plasma testosterone levels. There is also altered sperm quality parameters reported such as sperm motility or sperm count. On the other hand Δ9-THC effects endothelial growth factors (VEGF, Ang-1 etc.) respectively acts on their specific receptors which in turn modify angiogenesis and vascularization of tissues and organs (e.g. tumorous tissues). This leads to new therapeutical strategies in the suppression of various cancers by inhibiting (neo-)vascularization and in turn famishment of tumorous tissues (lack of nutrition supply). Here we studied the micro-vascularization of gonads in a long-term THC-treated nude rat model by vascular corrosion casting, SEM and 3D-morphometry.

  20. Perception of affective prosody in major depression: a link to executive functions?

    Science.gov (United States)

    Uekermann, Jennifer; Abdel-Hamid, Mona; Lehmkämper, Caroline; Vollmoeller, Wolfgang; Daum, Irene

    2008-07-01

    Major depression is associated with impairments of executive functions and affect perception deficits, both being linked to dysfunction of fronto-subcortical networks. So far, little is known about the relationship between cognitive and affective deficits in major depression. In the present investigation, affect perception and executive functions were assessed in 29 patients with a diagnosis of major depression (Dep) and 29 healthy controls (HC). Both groups were comparable on IQ, age, and gender distribution. Depressed patients showed deficits of perception of affective prosody, which were significantly related to inhibition, set shifting, and working memory. Our findings suggest a significant association between cognitive deficits and affect perception impairments in major depression, which may be of considerable clinical relevance and might be addressed in treatment approaches. Future studies are desirable to investigate the nature of the association in more detail.

  1. Negative affect predicts social functioning across schizophrenia and bipolar disorder: Findings from an integrated data analysis.

    Science.gov (United States)

    Grove, Tyler B; Tso, Ivy F; Chun, Jinsoo; Mueller, Savanna A; Taylor, Stephan F; Ellingrod, Vicki L; McInnis, Melvin G; Deldin, Patricia J

    2016-09-30

    Most people with a serious mental illness experience significant functional impairment despite ongoing pharmacological treatment. Thus, in order to improve outcomes, a better understanding of functional predictors is needed. This study examined negative affect, a construct comprised of negative emotional experience, as a predictor of social functioning across serious mental illnesses. One hundred twenty-seven participants with schizophrenia, 113 with schizoaffective disorder, 22 with psychosis not otherwise specified, 58 with bipolar disorder, and 84 healthy controls (N=404) completed self-report negative affect measures. Elevated levels of negative affect were observed in clinical participants compared with healthy controls. For both clinical and healthy control participants, negative affect measures were significantly correlated with social functioning, and consistently explained significant amounts of variance in functioning. For clinical participants, this relationship persisted even after accounting for cognition and positive/negative symptoms. The findings suggest that negative affect is a strong predictor of outcome across these populations and treatment of serious mental illnesses should target elevated negative affect in addition to cognition and positive/negative symptoms.

  2. Earthworm functional traits and interspecific interactions affect plant nitrogen acquisition and primary production

    NARCIS (Netherlands)

    Andriuzzi, Walter; Schmidt, Olaf; Brussaard, L.; Faber, J.H.; Bolger, T.

    2016-01-01

    We performed a greenhouse experiment to test how the functional diversity of earthworms, the dominant group of soil macro-invertebrates in many terrestrial ecosystems, affects nitrogen cycling and plant growth. Three species were chosen to represent a range of functional traits: Lumbricus terrestris

  3. [Sex steroids and vascular risk].

    Science.gov (United States)

    Rozenbaum, H

    1983-01-01

    The chemical diversity of estrogen and progestogen components of oral contraceptive (OC) products, their use alone or in combination, and the diversity of treatment regimens and doses account for the majority of contradictions in the immense literature on vascular and metabolic side effects of these hormones. OCs are exclusively composed of synthetic hormones. All OCs impose metabolic modifications on the organism and especially on the hepatic parenchyma due to delayed hepatic degradation. Certain factors increase the risk of vascular accidents associated with OC use: metabolic changes affecting coagulation, lipids, glucides, and arterial hypertension, immunologic phenomena, smoking, and obesity. As a whole, OCs affect coagulation by elevating factors 7 and 10, decreasing antithrombin iii (in high doses), and decreasing plasma fibrinolytic activity. synthetic estrogens cause an elevation of HDL cholesterol, a slight elevation of phospholipids, and a dose-dependent elevation of triglycerides and their VLDL fraction. As a group, progestogens tend to decrease the HDL fraction of cholesterol. Norethindrone is incapable of opposing the hypertriglyceridemic action of synthtic estrogens, while norgestrel partially opposes it. Lipid modifications provoked by combined OCs are a function of the nature and dosage of the components. Among hemodynamic modifications, synthetic estrogens cause elevations in renin substrate, plasma renin activity, angiotensin 2 and aldosterone. Synthetic progestogens may have various effects depending on type and dose, but they do not appear sufficient to cause hypertension unless other factors linked to individual predispositions are present. Microdoses of progestogens alone do not affect the renin-angiotensin-aldosterone system. Studies have also been conducted on the effect of OCs on cardiac function and on the vascular walls. Prospective studies suggest a relative risk of 3 for venous thromboembolic accidents among OC users, while

  4. The role of affect in attentional functioning for younger and older adults

    Directory of Open Access Journals (Sweden)

    Soo Rim eNoh

    2012-08-01

    Full Text Available Although previous research has shown that positive affect (PA and negative affect (NA modulate attentional functioning in distinct ways, few studies have considered whether the links between affect and attentional functioning may vary as a function of age. Using the Attention Network Test (Fan, McCandliss, Sommer, Raz, & Posner, 2002, we tested whether participants’ current state of PA and NA influenced distinct attentional functions (i.e., alerting, orienting, and executive attention and how the relationships between affective states and attentional functioning differ in younger (18-25 yrs and older (60-85 yrs age groups. The results revealed that higher PA was associated with lower alerting efficiency; however, this pattern did not vary by age group. While there were age differences in alerting efficiency, these age differences were mediated by PA, indicating that the higher state PA found in older adults may contribute to age differences in alerting. Furthermore, age group moderated the relationship between PA and orienting as well as NA and orienting. That is, higher levels of PA and lower levels of NA were associated with enhanced orienting efficiency in older adults. Neither PA nor NA had any influence on executive attention. The current results suggest that positive and negative affect may influence attentional functioning in distinct ways, but that these patterns may depend on age groups.

  5. [Vascular dementia

    NARCIS (Netherlands)

    Leeuw, H.F. de; Gijn, J. van

    2004-01-01

    Vascular dementia is one of the most frequently occurring dementia syndromes. Its prevalence is about 5% among subjects above 85 years of age. Elevated blood pressure and atherosclerosis are the most important risk factors. According to international criteria, vascular dementia usually occurs within

  6. Preoperative liver functional volumetry performed by 3D-99mTc-GSA scintigraphy/vascular fusion imaging using SYNAPSE VINCENT:a preliminary study

    Institute of Scientific and Technical Information of China (English)

    Hiroshi Yoshida; Hiroshi Makino; Tadashi Yokoyama; Hiroshi Maruyama; Atsushi Hirakata; Junji Ueda; Yasuhiro Mamada; Nobuhiko Taniai; Eiji Uchida

    2016-01-01

    Aim: The present study was designed to evaluate the feasibility of preoperative liver functional volumetry performed by 3D-technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) scintigraphy/vascular fusion imaging using SYNAPSE VINCENT and to examine the discrepancy between conventional and functional volumetry.Methods: The study group comprised 15 patients who underwent preoperative 3-dimensional (3D)-99mTc-GSA scintigraphy/vascular fusion imaging using SYNAPSE VINCENT software before hepatectomy between July 2014 and August 2015. The diagnosis was hepatocelular carcinoma (n = 4), metastatic liver tumor (n = 10), or intrahepatic cholangiocarcinoma (n = 1). Right hepatectomy was performed in 2 patients, left hepatectomy in 3 patients, right posterior sectionectomy in 3 patients, segmentectomy in 2 patients, and partial hepatectomy in 4 patients. 99mTc-GSA scintigraphy and computed tomography (CT) were performed to construct 3D-99mTc-GSA scintigraphy/vascular fused images. The conventional volume ratio of the planned resection region without tumor (% CT), and the functional volume ratio of the planned resection region without tumor (% GSA) were calculated. The discrepancy ratio was calculated as folows: discrepancy ratio = 100 - % GSA/ % CT × 100 (%).Results: The % GSA (17.9 ± 16.7%) was signiifcantly lower than the % CT (21.5 ± 17.6%) (P < 0.036). In al except 2 patients, the % GSA was lower than the % CT. The discrepancy ratio ranged from -4% to 75% (median, 20.7%).Conclusion: 3D-99mTc-GSA scintigraphy/vascular fused images constructed using SYNAPSE VINCENT were useful for noninvasively performing functional liver volumetry in patients scheduled to undergo various patterns of hepatectomy. In planned resection regions without tumor, the functional volume ratio was about 20% lower than the conventional volume ratio.

  7. Antibodies against AT1 receptors are associated with vascular endothelial and smooth muscle function impairment: protective effects of hydroxysafflor yellow A.

    Directory of Open Access Journals (Sweden)

    Zhu Jin

    Full Text Available Ample evidence has shown that autoantibodies against AT1 receptors (AT1-AA are closely associated with human cardiovascular disease. The aim of this study was to investigate mechanisms underlying AT1-AA-induced vascular structural and functional impairments in the formation of hypertension, and explore ways for preventive treatment. We used synthetic peptide corresponding to the sequence of the second extracellular loop of the AT1 receptor (165-191 to immunize rats and establish an active immunization model. Part of the model received preventive therapy by losartan (20 mg/kg/day and hyroxysafflor yellow A (HSYA (10 mg/kg/day. The result show that systolic blood pressure (SBP and heart rate (HR of immunized rats was significantly higher, and closely correlated with the plasma AT1-Ab titer. The systolic response of thoracic aortic was increased, but diastolic effects were attenuated markedly. Histological observation showed that the thoracic aortic endothelium of the immunized rats became thinner or ruptured, inflammatory cell infiltration, medial smooth muscle cell proliferation and migration, the vascular wall became thicker. There was no significant difference in serum antibody titer between losartan and HSYA groups and the immunized group. The vascular structure and function were reversed, and plasma biochemical parameters were also improved significantly in the two treatment groups. These results suggest that AT1-Ab could induce injury to vascular endothelial cells, and proliferation of smooth muscle cells. These changes were involved in the formation of hypertension. Treatment with AT1 receptor antagonists and anti oxidative therapy could block the pathogenic effect of AT1-Ab on vascular endothelial and smooth muscle cells.

  8. DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

    Directory of Open Access Journals (Sweden)

    Xavier eLópez-Gil

    2014-07-01

    Full Text Available The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm3 isometric resolution at 10, 14, 18, 22, 26 and 40 weeks after birth. Diffusion weighted imaging was analyzed in 2 different ways, by regional characterization of diffusion tensor imaging indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, diffusion tensor imaging scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and grey matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional 3-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.

  9. DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

    Science.gov (United States)

    López-Gil, Xavier; Amat-Roldan, Iván; Tudela, Raúl; Castañé, Anna; Prats-Galino, Alberto; Planas, Anna M.; Farr, Tracy D.; Soria, Guadalupe

    2014-01-01

    The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging (MRI) to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory, and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm3 isometric resolution at 10, 14, 18, 22, 26, and 40 weeks after birth. Diffusion weighted imaging was analyzed in two different ways, by regional characterization of diffusion tensor imaging (DTI) indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, DTI scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and gray matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional three-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent. PMID:25100993

  10. Low dietary protein intake during pregnancy differentially affects mitochondrial copy number in stromal vascular cells from subcutaneous versus visceral adipose tissue in the offspring

    Science.gov (United States)

    The present study examined the influence of protein intake during pregnancy on mitochondrial metabolism in stromal vascular cells from subcutaneous (SVSu) and visceral (SVVi) adipose tissue of offspring fed a high fat diet. Obese-prone Sprague-Dawley rats were fed diets containing either 8% or 20% p...

  11. Impairment of executive function and attention predicts onset of affective disorder in healthy high-risk twins

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla W; Kessing, Lars Vedel

    2013-01-01

    To investigate whether measures of cognitive function can predict onset of affective disorder in individuals at heritable risk.......To investigate whether measures of cognitive function can predict onset of affective disorder in individuals at heritable risk....

  12. Carbohydrates and endothelial function: is a low-carbohydrate diet or a low-glycemic index diet favourable for vascular health?

    Science.gov (United States)

    Jovanovski, Elena; Zurbau, Andreea; Vuksan, Vladimir

    2015-04-01

    Low-carbohydrate diets have become increasingly popular in both media and clinical research settings. Although they may improve some metabolic markers, their effects on arterial function remain unclear. Endothelial dysfunction is the well-established response to cardiovascular risk factors and a pivotal feature that precedes atherosclerotic diseases. It has been demonstrated that a high carbohydrate-induced hyperglycemia and subsequent oxidative stress acutely worsen the efficacy of the endothelial vasodilatory system. Thus, in theory, a carbohydrate restricted diet may preserve the integrity of the arterial system. This review attempts to provide insight on whether low-carbohydrate diets have a favorable or detrimental impact on vascular function, or it is perhaps the quality of carbohydrate that should direct dietary recommendations. Research to date suggests that diets low in carbohydrate amount may negatively impact vascular endothelial function. Conversely, it appears that maintaining recommended carbohydrate intake with utilization of low glycemic index foods generates a more favorable vascular profile. Understanding these relationships will aid in deciphering the diverging role of modulating quantity and quality of carbohydrates on cardiovascular risk.

  13. Functional hepatocyte heterogeneity. Vascular 2-oxoglutarate is almost exclusively taken up by perivenous, glutamine-synthetase-containing hepatocytes.

    Science.gov (United States)

    Stoll, B; Hüssinger, D

    1989-05-15

    about 100% utilization of the [14C]oxoglutarate taken up by the liver for glutamine synthesis. This was again true for both the antegrade and the retrograde perfusion directions. On the other hand, addition of ammonia did not affect 14CO2 production from labeled oxoglutarate, when glutamine synthetase was inhibited by methionine sulfoximine. 4. The data suggest that vascular oxoglutarate is almost exclusively taken up by the small perivenous hepatocyte population containing glutamine synthetase, i.e. a cell population comprising only 6-7% of all hepatocytes. Thus, the findings demonstrate the existence of a, to date, uniquely zonally distributed oxoglutarate transport system which is probably Na+-dependent in the plasma membrane.(ABSTRACT TRUNCATED AT 400 WORDS)

  14. Affect and the brain's functional organization: a resting-state connectivity approach.

    Directory of Open Access Journals (Sweden)

    Christiane S Rohr

    Full Text Available The question of how affective processing is organized in the brain is still a matter of controversial discussions. Based on previous initial evidence, several suggestions have been put forward regarding the involved brain areas: (a right-lateralized dominance in emotional processing, (b hemispheric dominance according to positive or negative valence, (c one network for all emotional processing and (d region-specific discrete emotion matching. We examined these hypotheses by investigating intrinsic functional connectivity patterns that covary with results of the Positive and Negative Affective Schedule (PANAS from 65 participants. This approach has the advantage of being able to test connectivity rather than activation, and not requiring a potentially confounding task. Voxelwise functional connectivity from 200 regions-of-interest covering the whole brain was assessed. Positive and negative affect covaried with functional connectivity involving a shared set of regions, including the medial prefrontal cortex, the anterior cingulate, the visual cortex and the cerebellum. In addition, each affective domain had unique connectivity patterns, and the lateralization index showed a right hemispheric dominance for negative affect. Therefore, our results suggest a predominantly right-hemispheric network with affect-specific elements as the underlying organization of emotional processes.

  15. Vascular compression syndromes.

    Science.gov (United States)

    Czihal, Michael; Banafsche, Ramin; Hoffmann, Ulrich; Koeppel, Thomas

    2015-11-01

    Dealing with vascular compression syndromes is one of the most challenging tasks in Vascular Medicine practice. This heterogeneous group of disorders is characterised by external compression of primarily healthy arteries and/or veins as well as accompanying nerval structures, carrying the risk of subsequent structural vessel wall and nerve damage. Vascular compression syndromes may severely impair health-related quality of life in affected individuals who are typically young and otherwise healthy. The diagnostic approach has not been standardised for any of the vascular compression syndromes. Moreover, some degree of positional external compression of blood vessels such as the subclavian and popliteal vessels or the celiac trunk can be found in a significant proportion of healthy individuals. This implies important difficulties in differentiating physiological from pathological findings of clinical examination and diagnostic imaging with provocative manoeuvres. The level of evidence on which treatment decisions regarding surgical decompression with or without revascularisation can be relied on is generally poor, mostly coming from retrospective single centre studies. Proper patient selection is critical in order to avoid overtreatment in patients without a clear association between vascular compression and clinical symptoms. With a focus on the thoracic outlet-syndrome, the median arcuate ligament syndrome and the popliteal entrapment syndrome, the present article gives a selective literature review on compression syndromes from an interdisciplinary vascular point of view.

  16. Plant species and functional group combinations affect green roof ecosystem functions.

    Directory of Open Access Journals (Sweden)

    Jeremy Lundholm

    Full Text Available BACKGROUND: Green roofs perform ecosystem services such as summer roof temperature reduction and stormwater capture that directly contribute to lower building energy use and potential economic savings. These services are in turn related to ecosystem functions performed by the vegetation layer such as radiation reflection and transpiration, but little work has examined the role of plant species composition and diversity in improving these functions. METHODOLOGY/PRINCIPAL FINDINGS: We used a replicated modular extensive (shallow growing- medium green roof system planted with monocultures or mixtures containing one, three or five life-forms, to quantify two ecosystem services: summer roof cooling and water capture. We also measured the related ecosystem properties/processes of albedo, evapotranspiration, and the mean and temporal variability of aboveground biomass over four months. Mixtures containing three or five life-form groups, simultaneously optimized several green roof ecosystem functions, outperforming monocultures and single life-form groups, but there was much variation in performance depending on which life-forms were present in the three life-form mixtures. Some mixtures outperformed the best monocultures for water capture, evapotranspiration, and an index combining both water capture and temperature reductions. Combinations of tall forbs, grasses and succulents simultaneously optimized a range of ecosystem performance measures, thus the main benefit of including all three groups was not to maximize any single process but to perform a variety of functions well. CONCLUSIONS/SIGNIFICANCE: Ecosystem services from green roofs can be improved by planting certain life-form groups in combination, directly contributing to climate change mitigation and adaptation strategies. The strong performance by certain mixtures of life-forms, especially tall forbs, grasses and succulents, warrants further investigation into niche complementarity or

  17. Skin barrier function in healthy volunteers as assessed by transepidermal water loss and vascular response to hexyl nicotinate: intra- and inter-individual variability.

    Science.gov (United States)

    Oestmann, E; Lavrijsen, A P; Hermans, J; Ponec, M

    1993-02-01

    This study assesses the variability of two non-invasive methods of measuring stratum corneum barrier function in vivo. Transepidermal water loss (TEWL), and the vascular response to hexyl nicotinate (HN) penetration as determined by laser-Doppler flowmetry, were measured in a group of 21 healthy volunteers. Each time profile of the vascular response to HN penetration was analysed using the following parameters: the baseline cutaneous blood flow, the lag-time between application and initial response (t0), the time between application and maximum response (tmax), the maximum response, and the slope of the curve. TEWL measured on the left volar forearm showed a normal range of 3.9-7.6 g/m2h and a small inter-individual variability [coefficient of variation (CV) 19.4%]. TEWL values at three other forearm sites did not show differences of clinical importance compared with the left volar forearm. The parameters of the vascular response to HN penetration spanned a wider normal range than the TEWL values (CV between 33 and 52%). Repeat measurements after a 1-2 month interval showed highly reproducible individual TEWL values. The mean difference between first and second measurements was only 0.03 g/m2h; the relative difference 0.6%. The intra-individual reproducibility of t0 and tmax. for HN penetration was also high (relative differences of 2.8 and 3.1%, respectively). The other vascular response parameters were less reproducible (relative differences of 6.9-18.6%). We conclude that TEWL and selected parameters of HN penetration, as non-invasive tests of the stratum corneum barrier function, yield reproducible results and are hence useful for investigations assessing the skin barrier function in various disorders.

  18. Vascular endothelial growth factor is crucial for erythropoietin-induced improvement of cardiac function in heart failure

    NARCIS (Netherlands)

    Westenbrink, B. Daan; Ruifrok, Willem-Peter T.; Voors, Adriaan A.; Tilton, Ronald G.; van Veldhuisen, Dirk J.; Schoemaker, Regien G.; van Gilst, Wiek H.; de Boer, Rudolf A.

    2010-01-01

    We intended to delineate the mechanisms of erythropoietin (EPO)-induced cardiac vascular endothelial growth factor (VEGF) production and to establish if VEGF is crucial for EPO-induced improvement of cardiac performance. The effects of EPO on VEGF expression were studied in cultured cardiac cells an

  19. Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

    Science.gov (United States)

    Lee, Stuart M. C.; Rana, Brinda K.; Stenger, Michael B.; Sears, Dorothy D.; Smith, Scott M.; Zwart, Sara R.; Macias, Brandon R.; Hargans, Alan R.; Sharma, Kumar; De Vivo, Immaculata

    2017-01-01

    that is associated with elevated atherosclerosis risk factors. METHODS: In the space-flown twin, a panel of biomarkers of oxidative and inflammatory stress were measured in venous blood samples and in 24-h (in-flight) and 48-h (pre- and post-flight) urine pools collected twice before flight, six times during the mission (FD15, 75, 180, 240, 300, 335), and early in the post-flight recovery phase (3-5 days after landing). We also measured metabolomic (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) in these samples. Arterial structure, assessed from measures of intima-media thickness, also were measured using standard clinical ultrasound at the same time points. Arterial function was assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. All of the same measures were obtained in the ground-based twin, but less frequently. DISCUSSION: All data collection has been completed for both the space-flown twin and the ground-based twin. Vascular structure and function measures have been analyzed, blood and urine samples have been batch-processed. Results from these individuals will be compared to each other, to data from other Twin Study investigations, and to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

  20. Multimodal cardiovascular magnetic resonance quantifies regional variation in vascular structure and function in patients with coronary artery disease: Relationships with coronary disease severity

    Directory of Open Access Journals (Sweden)

    Kylintireas Ilias

    2011-10-01

    Full Text Available Abstract Background Cardiovascular magnetic resonance (CMR of the vessel wall is highly reproducible and can evaluate both changes in plaque burden and composition. It can also measure aortic compliance and endothelial function in a single integrated examination. Previous studies have focused on patients with pre-identified carotid atheroma. We define these vascular parameters in patients presenting with coronary artery disease and test their relations to its extent and severity. Methods and Results 100 patients with CAD [single-vessel (16%; two-vessel (39%; and three-vessel (42% non-obstructed coronary arteries (3%] were studied. CAD severity and extent was expressed as modified Gensini score (mean modified score 12.38 ± 5.3. A majority of carotid plaque was located in the carotid bulb (CB. Atherosclerosis in this most diseased segment correlated modestly with the severity and extent of CAD, as expressed by the modified Gensini score (R = 0.251, P Conclusions Multimodal vascular CMR shows regional abnormalities of vascular structure and function that correlate modestly with the degree and extent of CAD.

  1. Obesity, inflammation, and exercise training: relative contribution of iNOS and eNOS in the modulation of vascular function in the mouse aorta

    Directory of Open Access Journals (Sweden)

    Josiane Fernandes da Silva

    2016-09-01

    Full Text Available Background - The understanding of obsesity-related vascular dysfunction remains controversial mainly because of the diseases associated with vascular injury. Exercise training is known to prevent vascular dysfunction. Using an obesity model without comorbidities, we aimed at investigating the underlying mechanism of vascular dysfunction and how exercise interferes with this process.Methods - High-sugar diet was used to induce obesity in mice. Exercise training was performed 5 days/week. Body weight, energy intake, and adipose tissues were assessed; blood metabolic and hormonal parameters were determined; and serum TNFα was measured. Blood pressure and heart rate were assessed by plethysmography. Changes in aortic isometric tension were recorded on myograph. Western blot was used to analyze protein expression. Nitric oxide (NO was evaluated using fluorescence microscopy. Antisense oligodeoxynucleotides were used for inducible nitric oxide synthase isoform (iNOS knockdown.Results - Body weight, fat mass, total cholesterol, low-density lipoprotein cholesterol fraction, insulin, and leptin were higher in the sedentary obese group (SD than in the sedentary control animals (SS. Exercise training prevented these changes. No difference in glucose tolerance, insulin sensitivity, blood pressure, and heart rate was found. Decreased vascular relaxation and reduced endothelial nitric oxide synthase (eNOS functioning in the SD group were prevented by exercise. Contractile response to phenylephrine was decreased in the aortas of the wild SD mice, compared with that of the SS group; however, no alteration was noted in the SD iNOS-/- animals. The decreased contractility was endothelium-dependent, and was reverted by iNOS inhibition or iNOS silencing. The aortas from the SD group showed increased basal NO production, serum TNFα, TNF receptor-1, and phospho-IκB. Exercise training attenuated iNOS-dependent reduction in contractile response in high-sugar diet

  2. Obesity, Inflammation, and Exercise Training: Relative Contribution of iNOS and eNOS in the Modulation of Vascular Function in the Mouse Aorta

    Science.gov (United States)

    Silva, Josiane F.; Correa, Izabella C.; Diniz, Thiago F.; Lima, Paulo M.; Santos, Roger L.; Cortes, Steyner F.; Coimbra, Cândido C.; Lemos, Virginia S.

    2016-01-01

    Background: The understanding of obsesity-related vascular dysfunction remains controversial mainly because of the diseases associated with vascular injury. Exercise training is known to prevent vascular dysfunction. Using an obesity model without comorbidities, we aimed at investigating the underlying mechanism of vascular dysfunction and how exercise interferes with this process. Methods: High-sugar diet was used to induce obesity in mice. Exercise training was performed 5 days/week. Body weight, energy intake, and adipose tissues were assessed; blood metabolic and hormonal parameters were determined; and serum TNFα was measured. Blood pressure and heart rate were assessed by plethysmography. Changes in aortic isometric tension were recorded on myograph. Western blot was used to analyze protein expression. Nitric oxide (NO) was evaluated using fluorescence microscopy. Antisense oligodeoxynucleotides were used for inducible nitric oxide synthase isoform (iNOS) knockdown. Results: Body weight, fat mass, total cholesterol, low-density lipoprotein cholesterol fraction, insulin, and leptin were higher in the sedentary obese group (SD) than in the sedentary control animals (SS). Exercise training prevented these changes. No difference in glucose tolerance, insulin sensitivity, blood pressure, and heart rate was found. Decreased vascular relaxation and reduced endothelial nitric oxide synthase (eNOS) functioning in the SD group were prevented by exercise. Contractile response to phenylephrine was decreased in the aortas of the wild SD mice, compared with that of the SS group; however, no alteration was noted in the SD iNOS−/− animals. The decreased contractility was endothelium-dependent, and was reverted by iNOS inhibition or iNOS silencing. The aortas from the SD group showed increased basal NO production, serum TNFα, TNF receptor-1, and phospho-IκB. Exercise training attenuated iNOS-dependent reduction in contractile response in high-sugar diet–fed animals

  3. Loss-of-Function Mutations in YY1AP1 Lead to Grange Syndrome and a Fibromuscular Dysplasia-Like Vascular Disease.

    Science.gov (United States)

    Guo, Dong-Chuan; Duan, Xue-Yan; Regalado, Ellen S; Mellor-Crummey, Lauren; Kwartler, Callie S; Kim, Dong; Lieberman, Kenneth; de Vries, Bert B A; Pfundt, Rolph; Schinzel, Albert; Kotzot, Dieter; Shen, Xuetong; Yang, Min-Lee; Bamshad, Michael J; Nickerson, Deborah A; Gornik, Heather L; Ganesh, Santhi K; Braverman, Alan C; Grange, Dorothy K; Milewicz, Dianna M

    2017-01-05

    Fibromuscular dysplasia (FMD) is a heterogeneous group of non-atherosclerotic and non-inflammatory arterial diseases that primarily involves the renal and cerebrovascular arteries. Grange syndrome is an autosomal-recessive condition characterized by severe and early-onset vascular disease similar to FMD and variable penetrance of brachydactyly, syndactyly, bone fragility, and learning disabilities. Exome-sequencing analysis of DNA from three affected siblings with Grange syndrome identified compound heterozygous nonsense variants in YY1AP1, and homozygous nonsense or frameshift YY1AP1 variants were subsequently identified in additional unrelated probands with Grange syndrome. YY1AP1 encodes yin yang 1 (YY1)-associated protein 1 and is an activator of the YY1 transcription factor. We determined that YY1AP1 localizes to the nucleus and is a component of the INO80 chromatin remodeling complex, which is responsible for transcriptional regulation, DNA repair, and replication. Molecular studies revealed that loss of YY1AP1 in vascular smooth muscle cells leads to cell cycle arrest with decreased proliferation and increased levels of the cell cycle regulator p21/WAF/CDKN1A and disrupts TGF-β-driven differentiation of smooth muscle cells. Identification of YY1AP1 mutations as a cause of FMD indicates that this condition can result from underlying genetic variants that significantly alter the phenotype of vascular smooth muscle cells.

  4. Effect of low-energy extracorporeal shock wave on vascular regeneration after spinal cord injury and the recovery of motor function [Retraction

    Directory of Open Access Journals (Sweden)

    Wang L

    2016-10-01

    Full Text Available Wang L, Jiang Y, Jiang Z, Han L. Effect of low-energy extracorporeal shock wave on vascular regeneration after spinal cord injury and the recovery of motor function. Neuropsychiatr Dis Treat. 2016 Aug 31;12:2189–2198. doi: 10.2147/NDT.S82864.This article was found to have plagiarized the content of:Low-energy extracorporeal shock wave therapy promotes vascular endothelial growth factor expression and improves locomotor recovery after spinal injury published in the Journal of Neurosurgery in 2014 (J Neurosurg. 121: 1514–1525, 2014.Accordingly, Dr Pinder, Editor-in-Chief of Neuropsychiatric Disease and Treatment has decided to issue a Retraction notice and advise the academic supervisors of Dr Wang et al of this matter. This Retraction relates to

  5. A single portion of blueberry (Vaccinium corymbosum L) improves protection against DNA damage but not vascular function in healthy male volunteers

    DEFF Research Database (Denmark)

    Del Bo, Cristian; Riso, Patrizia; Campolo, Jonica;

    2013-01-01

    It has been suggested that anthocyanin-rich foods may exert antioxidant effects and improve vascular function as demonstrated mainly in vitro and in the animal model. Blueberries are rich sources of anthocyanins and we hypothesized that their intake could improve cell protection against oxidative...... were collected and used to evaluate anthocyanin absorption (through mass spectrometry), endogenous and H(2)O(2)-induced DNA damage in blood mononuclear cells (through the comet assay), and plasma nitric oxide concentrations (through a fluorometric assay). Peripheral arterial function was assessed...

  6. DISC1 gene and affective psychopathology: a combined structural and functional MRI study.

    Science.gov (United States)

    Opmeer, Esther M; van Tol, Marie-José; Kortekaas, Rudie; van der Wee, Nic J A; Woudstra, Saskia; van Buchem, Mark A; Penninx, Brenda W; Veltman, Dick J; Aleman, André

    2015-02-01

    The gene Disrupted-In-Schizophrenia-1 (DISC1) has been indicated as a determinant of psychopathology, including affective disorders, and shown to influence prefrontal cortex (PFC) and hippocampus functioning, regions of major interest for affective disorders. We aimed to investigate whether DISC1 differentially modulates brain function during executive and memory processing, and morphology in regions relevant for depression and anxiety disorders (affective disorders). 128 participants, with (n = 103) and without (controls; n = 25) affective disorders underwent genotyping for Ser704Cys (with Cys-allele considered as risk-allele) and structural and functional (f) Magnetic Resonance Imaging (MRI) during visuospatial planning and emotional episodic memory tasks. For both voxel-based morphometry and fMRI analyses, we investigated the effect of genotype in controls and explored genotypeXdiagnosis interactions. Results are reported at p < 0.05 FWE small volume corrected. In controls, Cys-carriers showed smaller bilateral (para)hippocampal volumes compared with Ser-homozygotes, and lower activation in the anterior cingulate cortex (ACC) and dorsolateral PFC during visuospatial planning. In anxiety patients, Cys-carriers showed larger (para)hippocampal volumes and more ACC activation during visuospatial planning. In depressive patients, no effect of genotype was observed and overall, no effect of genotype on episodic memory processing was detected. We demonstrated that Ser704Cys-genotype influences (para)hippocampal structure and functioning the dorsal PFC during executive planning, most prominently in unaffected controls. Results suggest that presence of psychopathology moderates Ser704Cys effects.

  7. Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells

    NARCIS (Netherlands)

    M.J. Crop (Meindert); C.C. Baan (Carla); S.S. Korevaar (Sander); J.N.M. IJzermans (Jan); M. Pescatori (Mario); A. Stubbs (Andrew); W.F.J. van IJcken (Wilfred); M.H. Dahlke (Marc); E. Eggenhofer (Elke); W. Weimar (Willem); M.J. Hoogduijn (Martin)

    2010-01-01

    textabstractThere is emerging interest in the application of mesenchymal stem cells (MSC) for the prevention and treatment of autoimmune diseases, graft-versus-host disease and allograft rejection. It is, however, unknown how inflammatory conditions affect phenotype and function of MSC. Adipose tiss

  8. Automatic Processing of Emotional Faces in High-Functioning Pervasive Developmental Disorders: An Affective Priming Study

    Science.gov (United States)

    Kamio, Yoko; Wolf, Julie; Fein, Deborah

    2006-01-01

    This study examined automatic processing of emotional faces in individuals with high-functioning Pervasive Developmental Disorders (HFPDD) using an affective priming paradigm. Sixteen participants (HFPDD and matched controls) were presented with happy faces, fearful faces or objects in both subliminal and supraliminal exposure conditions, followed…

  9. The role of cellular senescence during vascular calcification: a key paradigm in aging research.

    Science.gov (United States)

    Mackenzie, N C W; MacRae, V E

    2011-07-01

    Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events. Vascular calcification refers to the deposition of calcium phosphate mineral, most often hydroxyapatite, in arteries. Extensive calcification of the vascular system is a key characteristic of aging. In this article, we outline the mechanisms governing vascular calcification and highlight its association with cellular senescence. This review discusses the molecular mechanisms of cellular senescence and its affect on calcification of vascular cells, the relevance of phosphate regulation and the function of FGF23 and Klotho proteins. The association of vascular calcification and cellular senescence with the rare human aging disorder Hutchison-Gilford Progeria Syndrome (HGPS) is highlighted and the mouse models used to try to determine the underlying pathways are discussed. By understanding the pathways involved in these processes novel drug targets may be elucidated in an effort to reduce the effects of cellular aging as a risk factor in cardiovascular disease.

  10. The effect of affective bibliotherapy on clients' functioning in group therapy.

    Science.gov (United States)

    Shechtman, Zipora; Nir-Shfrir, Rivka

    2008-01-01

    Abstract The effect of affective group bibliotherapy (GB) was compared to affective group therapy (GT) on patients' functioning in therapy and their session impression. Three small groups totaling twenty-five in-patients in a hospital in Israel participated in the study. Clients concurrently participated in both group types, undergoing three sessions in each condition. In-therapy behaviors were assessed through the Client Behavior System (CBS; Hill & O'Brien, 1999). Results indicated that in the GB condition compared to the GT condition, clients showed less resistance, used simple responses less frequently, and expressed greater affective exploration. The Session Evaluation Questionnaire (SEQ; Stiles et al., 1994) was used to measure clients' impressions of the sessions. Results indicated that patients evaluated the two treatment conditions equally. Overall, the results support earlier findings, suggesting that affective bibliotherapy can be an effective method of treatment.

  11. The performance of single- and multi-proxy transfer functions (testate amoebae, bryophytes, vascular plants) for reconstructing mire surface wetness and pH

    Science.gov (United States)

    Mitchell, Edward A. D.; Payne, Richard J.; van der Knaap, Willem O.; Lamentowicz, Łukasz; Gąbka, Maciej; Lamentowicz, Mariusz

    2013-01-01

    Peatlands are widely exploited archives of paleoenvironmental change. We developed and compared multiple transfer functions to infer peatland depth to the water table (DWT) and pH based on testate amoeba (percentages, or presence/absence), bryophyte presence/absence, and vascular plant presence/absence data from sub-alpine peatlands in the SE Swiss Alps in order to 1) compare the performance of single-proxy vs. multi-proxy models and 2) assess the performance of presence/absence models. Bootstrapping cross-validation showing the best performing single-proxy transfer functions for both DWT and pH were those based on bryophytes. The best performing transfer functions overall for DWT were those based on combined testate amoebae percentages, bryophytes and vascular plants; and, for pH, those based on testate amoebae and bryophytes. The comparison of DWT and pH inferred from testate amoeba percentages and presence/absence data showed similar general patterns but differences in the magnitude and timing of some shifts. These results show new directions for paleoenvironmental research, 1) suggesting that it is possible to build good-performing transfer functions using presence/absence data, although with some loss of accuracy, and 2) supporting the idea that multi-proxy inference models may improve paleoecological reconstruction. The performance of multi-proxy and single-proxy transfer functions should be further compared in paleoecological data.

  12. A novel tumor-promoting function residing in the 5' non-coding region of vascular endothelial growth factor mRNA.

    Directory of Open Access Journals (Sweden)

    Kiyoshi Masuda

    2008-05-01

    Full Text Available BACKGROUND: Vascular endothelial growth factor-A (VEGF is one of the key regulators of tumor development, hence it is considered to be an important therapeutic target for cancer treatment. However, clinical trials have suggested that anti-VEGF monotherapy was less effective than standard chemotherapy. On the basis of the evidence, we hypothesized that vegf mRNA may have unrecognized function(s in cancer cells. METHODS AND FINDINGS: Knockdown of VEGF with vegf-targeting small-interfering (si RNAs increased susceptibility of human colon cancer cell line (HCT116 to apoptosis caused with 5-fluorouracil, etoposide, or doxorubicin. Recombinant human VEGF165 did not completely inhibit this apoptosis. Conversely, overexpression of VEGF165 increased resistance to anti-cancer drug-induced apoptosis, while an anti-VEGF165-neutralizing antibody did not completely block the resistance. We prepared plasmids encoding full-length vegf mRNA with mutation of signal sequence, vegf mRNAs lacking untranslated regions (UTRs, or mutated 5'UTRs. Using these plasmids, we revealed that the 5'UTR of vegf mRNA possessed anti-apoptotic activity. The 5'UTR-mediated activity was not affected by a protein synthesis inhibitor, cycloheximide. We established HCT116 clones stably expressing either the vegf 5'UTR or the mutated 5'UTR. The clones expressing the 5'UTR, but not the mutated one, showed increased anchorage-independent growth in vitro and formed progressive tumors when implanted in athymic nude mice. Microarray and quantitative real-time PCR analyses indicated that the vegf 5'UTR-expressing tumors had up-regulated anti-apoptotic genes, multidrug-resistant genes, and growth-promoting genes, while pro-apoptotic genes were down-regulated. Notably, expression of signal transducers and activators of transcription 1 (STAT1 was markedly repressed in the 5'UTR-expressing tumors, resulting in down-regulation of a STAT1-responsive cluster of genes (43 genes. As a result, the

  13. Subclinical hypothyroidism after vascular complicated pregnancy

    NARCIS (Netherlands)

    Zanden, M. van der; Hop-de Groot, R.J.; Sweep, F.C.; Ross, H.A.; Heijer, M. den; Spaanderman, M.E.A.

    2013-01-01

    OBJECTIVE: Women with a history of vascular complicated pregnancy are at risk for developing remote cardiovascular disease. It is associated with underlying cardiovascular risk factors both jeopardizing trophoblast and vascular function. Subclinical hypothyroidism may relate to both conditions. METH

  14. Time course of fibronectin in the peri-implant tissue and neointima formation after functional implantation of polyester-based vascular prostheses with different porosity in pigs.

    Science.gov (United States)

    Patrzyk, Maciej; Hoene, Andreas; Jarchow, Raymond; Wilhelm, Lutz; Walschus, Uwe; Zippel, Roland; Schlosser, Michael

    2010-10-01

    Intima hyperplasia, resulting from extracellular matrix (ECM) secretion, can lead to vascular prosthesis occlusion and is a major problem in vascular surgery. Fibronectin might contribute to ongoing ECM secretion. However, the exact role of fibronectin and its influence on neointima formation remains unclear. This study was aimed at investigating the time course of the fibronectin area fraction and neointima formation following the functional implantation of three different polyester vascular prostheses into pigs. The infrarenal aorta from 15 animals (n = 5/group) was replaced by prosthesis segments with low, medium and high primary porosity. After 7, 14, 21, 28 and 116 days, the prostheses were morphometrically examined. Overall, the fibronectin area fraction was inversely correlated with the neointima thickness, demonstrating high fibronectin levels in the early phase (days 7 and 14) and low levels in the later phase with almost complete neointima formation (days 21-116). Throughout the study, fibronectin levels were highest at the proximal anastomosis region. The low porosity prosthesis had the highest fibronectin area fraction and a delayed neointima formation in the middle phase (days 21 and 28) but the highest neointima lining on day 116. The results indicate a relationship between fibronectin and neointima formation with the prosthesis porosity, demonstrating the importance of the textile design for tissue reactions following implantation.

  15. Time course of fibronectin in the peri-implant tissue and neointima formation after functional implantation of polyester-based vascular prostheses with different porosity in pigs

    Energy Technology Data Exchange (ETDEWEB)

    Patrzyk, Maciej; Hoene, Andreas [Department of Surgery, Ernst Moritz Arndt University Greifswald, Friedrich-Loeffler-Str. 23, D-17489 Greifswald (Germany); Jarchow, Raymond [Computation Centre, Ernst Moritz Arndt University Greifswald, Felix-Hausdorff-Str. 12, D-17489 Greifswald (Germany); Wilhelm, Lutz [Department of Surgery, Hospital Demmin, Loitzer Str. 1, D-17109 Demmin (Germany); Walschus, Uwe; Schlosser, Michael [Research Group of Predictive Diagnostics of the Department of Medical Biochemistry and Molecular Biology and Institute of Pathophysiology, Ernst Moritz Arndt University Greifswald, Greifswalder Str. 11c, D-17495 Karlsburg (Germany); Zippel, Roland, E-mail: schlosse@uni-greifswald.d [Department of Surgery, Elbland Hospital Center, Weinbergstr. 8, D-01589 Riesa (Germany)

    2010-10-01

    Intima hyperplasia, resulting from extracellular matrix (ECM) secretion, can lead to vascular prosthesis occlusion and is a major problem in vascular surgery. Fibronectin might contribute to ongoing ECM secretion. However, the exact role of fibronectin and its influence on neointima formation remains unclear. This study was aimed at investigating the time course of the fibronectin area fraction and neointima formation following the functional implantation of three different polyester vascular prostheses into pigs. The infrarenal aorta from 15 animals (n = 5/group) was replaced by prosthesis segments with low, medium and high primary porosity. After 7, 14, 21, 28 and 116 days, the prostheses were morphometrically examined. Overall, the fibronectin area fraction was inversely correlated with the neointima thickness, demonstrating high fibronectin levels in the early phase (days 7 and 14) and low levels in the later phase with almost complete neointima formation (days 21-116). Throughout the study, fibronectin levels were highest at the proximal anastomosis region. The low porosity prosthesis had the highest fibronectin area fraction and a delayed neointima formation in the middle phase (days 21 and 28) but the highest neointima lining on day 116. The results indicate a relationship between fibronectin and neointima formation with the prosthesis porosity, demonstrating the importance of the textile design for tissue reactions following implantation.

  16. A content analysis of cognitive and affective uses of patient support groups for rare and uncommon vascular diseases: comparisons of may thurner, thoracic outlet, and superior mesenteric artery syndrome.

    Science.gov (United States)

    Walker, Kimberly K

    2015-01-01

    Rare disease patients are the predominant group of patients who are now connecting online to patient support groups, yet research on their uses of support groups has received little attention. This is a content analysis of three vascular diseases of differing degrees of rarity. Wall posts from Facebook patient support groups for May Thurner syndrome, thoracic outlet syndrome, and superior mesenteric artery syndrome were analyzed over a period of two years. Using Uses and Gratifications as the theoretical framework, the study purpose was to assess how variations in health condition and rarity of condition affect online support group user needs. Results indicated common main cognitive and affective uses across conditions, indicating a consistent pattern of needs communicated by all patients. However, there were nuanced differences in subcategories of cognitive and affective uses between the most and least rare disorders, which inform areas for tailored support mechanisms. Additionally, these vascular patients used their respective support groups primarily for cognitive reasons, especially for the rarest conditions, which informs of basic medical informational needs these patients face related to tests, treatment, surgery, and diagnoses.

  17. Admixture mapping scans identify a locus affecting retinal vascular caliber in hypertensive African Americans: the Atherosclerosis Risk in Communities (ARIC) study.

    Science.gov (United States)

    Cheng, Ching-Yu; Reich, David; Wong, Tien Y; Klein, Ronald; Klein, Barbara E K; Patterson, Nick; Tandon, Arti; Li, Man; Boerwinkle, Eric; Sharrett, A Richey; Kao, W H Linda

    2010-04-15

    Retinal vascular caliber provides information about the structure and health of the microvascular system and is associated with cardiovascular and cerebrovascular diseases. Compared to European Americans, African Americans tend to have wider retinal arteriolar and venular caliber, even after controlling for cardiovascular risk factors. This has suggested the hypothesis that differences in genetic background may contribute to racial/ethnic differences in retinal vascular caliber. Using 1,365 ancestry-informative SNPs, we estimated the percentage of African ancestry (PAA) and conducted genome-wide admixture mapping scans in 1,737 African Americans from the Atherosclerosis Risk in Communities (ARIC) study. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) representing summary measures of retinal arteriolar and venular caliber, respectively, were measured from retinal photographs. PAA was significantly correlated with CRVE (rho = 0.071, P = 0.003), but not CRAE (rho = 0.032, P = 0.182). Using admixture mapping, we did not detect significant admixture association with either CRAE (genome-wide score = -0.73) or CRVE (genome-wide score = -0.69). An a priori subgroup analysis among hypertensive individuals detected a genome-wide significant association of CRVE with greater African ancestry at chromosome 6p21.1 (genome-wide score = 2.31, locus-specific LOD = 5.47). Each additional copy of an African ancestral allele at the 6p21.1 peak was associated with an average increase in CRVE of 6.14 microm in the hypertensives, but had no significant effects in the non-hypertensives (P for heterogeneity retinal vascular caliber and further insights into the interaction between genetic effects of the microvascular system and hypertension.

  18. AMP-Activated Protein Kinase α2 in Neutrophils Regulates Vascular Repair via Hypoxia-Inducible Factor-1α and a Network of Proteins Affecting Metabolism and Apoptosis

    Science.gov (United States)

    Abdel Malik, Randa; Zippel, Nina; Frömel, Timo; Heidler, Juliana; Zukunft, Sven; Walzog, Barbara; Ansari, Nariman; Pampaloni, Francesco; Wingert, Susanne; Rieger, Michael A.; Wittig, Ilka; Fisslthaler, Beate

    2017-01-01

    Rationale: The AMP-activated protein kinase (AMPK) is stimulated by hypoxia, and although the AMPKα1 catalytic subunit has been implicated in angiogenesis, little is known about the role played by the AMPKα2 subunit in vascular repair. Objective: To determine the role of the AMPKα2 subunit in vascular repair. Methods and Results: Recovery of blood flow after femoral artery ligation was impaired (>80%) in AMPKα2−/− versus wild-type mice, a phenotype reproduced in mice lacking AMPKα2 in myeloid cells (AMPKα2ΔMC). Three days after ligation, neutrophil infiltration into ischemic limbs of AMPKα2ΔMC mice was lower than that in wild-type mice despite being higher after 24 hours. Neutrophil survival in ischemic tissue is required to attract monocytes that contribute to the angiogenic response. Indeed, apoptosis was increased in hypoxic neutrophils from AMPKα2ΔMC mice, fewer monocytes were recruited, and gene array analysis revealed attenuated expression of proangiogenic proteins in ischemic AMPKα2ΔMC hindlimbs. Many angiogenic growth factors are regulated by hypoxia-inducible factor, and hypoxia-inducible factor-1α induction was attenuated in AMPKα2-deficient cells and accompanied by its enhanced hydroxylation. Also, fewer proteins were regulated by hypoxia in neutrophils from AMPKα2ΔMC mice. Mechanistically, isocitrate dehydrogenase expression and the production of α-ketoglutarate, which negatively regulate hypoxia-inducible factor-1α stability, were attenuated in neutrophils from wild-type mice but remained elevated in cells from AMPKα2ΔMC mice. Conclusions: AMPKα2 regulates α-ketoglutarate generation, hypoxia-inducible factor-1α stability, and neutrophil survival, which in turn determine further myeloid cell recruitment and repair potential. The activation of AMPKα2 in neutrophils is a decisive event in the initiation of vascular repair after ischemia. PMID:27777247

  19. Longer term improvement in neurocognitive functioning and affective distress among methamphetamine users who achieve stable abstinence.

    Science.gov (United States)

    Iudicello, Jennifer E; Woods, Steven P; Vigil, Ofilio; Scott, J Cobb; Cherner, Mariana; Heaton, Robert K; Atkinson, J Hampton; Grant, Igor

    2010-08-01

    Chronic use of methamphetamine (MA) is associated with neuropsychological dysfunction and affective distress. Some normalization of function has been reported after abstinence, but little in the way of data is available on the possible added benefits of long-term sobriety. To address this, we performed detailed neuropsychological and affective evaluations in 83 MA-dependent individuals at a baseline visit and following an average one-year interval period. Among the 83 MA-dependent participants, 25 remained abstinent, and 58 used MA at least once during the interval period. A total of 38 non-MA-addicted, demographically matched healthy comparison (i.e., HC) participants were also examined. At baseline, both MA-dependent participants who were able to maintain abstinence and those who were not performed significantly worse than the healthy comparison subjects on global neuropsychological functioning and were significantly more distressed. At the one-year follow-up, both the long-term abstainers and healthy comparison groups showed comparable global neuropsychological performance and affective distress levels, whereas the MA-dependent group who continued to use MA were worse than the comparison participants in terms of global neuropsychological functioning and affective distress. An interaction was observed between neuropsychological impairment at baseline, MA abstinence, and cognitive improvement, with abstinent MA-dependent participants who were neuropsychologically impaired at baseline demonstrating significantly and disproportionately greater improvement in processing speed and slightly greater improvement in motor abilities than the other participants. These results suggest partial recovery of neuropsychological functioning and improvement in affective distress upon sustained abstinence from MA that may extend beyond a year or more.

  20. An investigation on pharmacy functions and services affecting satisfaction of patients with prescriptions in community pharmacies.

    Science.gov (United States)

    Sakurai, Hidehiko; Nakajima, Fumio; Tada, Yuichirou; Yoshikawa, Emi; Iwahashi, Yoshiki; Fujita, Kenji; Hayase, Yukitoshi

    2009-05-01

    Various functions expected by patient expects are needed with progress in the system for separation of dispensing and prescribing functions. In this investigation, the relationship between patient satisfaction and pharmacy function were analyzed quantitatively. A questionnaire survey was conducted in 178 community pharmacies. Questions on pharmacy functions and services totaled 87 items concerning information service, amenities, safety, personnel training, etc. The questionnaires for patients had five-grade scales and composed 11 items (observed variables). Based on the results, "the percentage of satisfied patients" was determined. Multivariate analysis was performed to investigate the relationship between patient satisfaction and pharmacy functions or services provided, to confirm patient's evaluation of the pharmacy, and how factors affected comprehensive satisfaction. In correlation analysis, "the number of pharmacists" and "comprehensive satisfaction" had a negative correlation. Other interesting results were obtained. As a results of factor analysis, three latent factors were obtained: the "human factor," "patients' convenience," and "environmental factor," Multiple regression analysis showed that the "human factor" affected "comprehensive satisfaction" the most. Various pharmacy functions and services influence patient satisfaction, and improvement in their quality increases patient satisfaction. This will result in the practice of patient-centered medicine.

  1. Decellularized aortic conduits: could their cryopreservation affect post-implantation outcomes? A morpho-functional study on porcine homografts.

    Science.gov (United States)

    Gallo, Michele; Bonetti, Antonella; Poser, Helen; Naso, Filippo; Bottio, Tomaso; Bianco, Roberto; Paolin, Adolfo; Franci, Paolo; Busetto, Roberto; Frigo, Anna Chiara; Buratto, Edward; Spina, Michele; Marchini, Maurizio; Ortolani, Fulvia; Iop, Laura; Gerosa, Gino

    2016-11-01

    Decellularized porcine aortic valve conduits (AVCs) implanted in a Vietnamese Pig (VP) experimental animal model were matched against decellularized and then cryopreserved AVCs to assess the effect of cryopreservation on graft hemodynamic performance and propensity to in vivo repopulation by host's cells. VPs (n = 12) underwent right ventricular outflow tract substitution using AVC allografts and were studied for 15-month follow-up. VPs were randomized into two groups, receiving AVCs treated with decellularization alone (D; n = 6) or decellularization/cryopreservation (DC; n = 6), respectively. Serial echocardiography was carried out to follow up hemodynamic function. All explanted AVCs were processed for light and electron microscopy. No signs of dilatation, progressive stenosis, regurgitation, and macroscopic calcification were echocardiographically observed in both D and DC groups. Explanted D grafts exhibited near-normal features, whereas the presence of calcification, inflammatory infiltrates, and disarray of elastic lamellae occurred in some DC grafts. In the unaltered regions of AVCs from both groups, almost complete re-endothelialization was observed for both valve cusps and aorta walls. In addition, side-by-side repopulation by recipient's fibroblasts, myofibroblasts, and smooth muscle cells was paralleled by ongoing tissue remodeling, as revealed by the ultrastructural identification of typical canals of collagen fibrillogenesis and elastogenesis-related features. Incipient neo-vascularization and re-innervation of medial and adventitial tunicae of grafted aortic walls were also detected for both D and DC groups. Cryopreservation did not affect post-implantation AVC hemodynamic behavior and was topically propensive to cell repopulation and tissue renewal, although graft deterioration including calcification was present in several areas. Thus, these preliminary data provide essential information on feasibility of decellularization and

  2. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  3. Fish oil affects immune function in 9 to 12 month old infants

    DEFF Research Database (Denmark)

    Damsgaard, Camilla Trab; Lauritzen, Lotte; Kjær, Tanja;

    Background - n-3 Polyunsaturated fatty acids (PUFA) are thought to affect immune function and may affect immune maturation in early life. Objective - To examine if fish oil supplementation in late infancy could modify immune function. Design - A 2×2 intervention with fish oil (3.4 ± 1.1 ml....../day) or no fish oil and cow’s milk or infant formula from 9 to 12 month of age in 64 healthy Danish infants. Before and after the intervention we measured the fatty acid composition of erythrocyte (RBC) membranes, plasma IgE levels, C-reactive protein and soluble IL-2 receptors (sIL-2R) as well as cytokine...... production in whole-blood cultures stimulated with lipopolysaccharide (LPS)/phytohaemaglutinin (PHA) or Lactobacillus paracasei for 22 h. IgA was measured in feces at 10 months of age. Results - Fish oil supplementation effectively raised RBC n-3 PUFA (p...

  4. The relationship between sleep-wake cycle and cognitive functioning in young people with affective disorders.

    Directory of Open Access Journals (Sweden)

    Joanne S Carpenter

    Full Text Available Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disorders and examine associations between these profiles and cognitive performance. Actigraphy monitoring was completed in 152 young people (16-30 years; 66% female with primary diagnoses of affective disorders, and 69 healthy controls (18-30 years; 57% female. Patients also underwent detailed neuropsychological assessment. Actigraphy data were processed to estimate both sleep and circadian parameters. Overall neuropsychological performance in patients was poor on tasks relating to mental flexibility and visual memory. Two hierarchical cluster analyses identified three distinct patient groups based on sleep variables and three based on circadian variables. Sleep clusters included a 'long sleep' cluster, a 'disrupted sleep' cluster, and a 'delayed and disrupted sleep' cluster. Circadian clusters included a 'strong circadian' cluster, a 'weak circadian' cluster, and a 'delayed circadian' cluster. Medication use differed between clusters. The 'long sleep' cluster displayed significantly worse visual memory performance compared to the 'disrupted sleep' cluster. No other cognitive functions differed between clusters. These results highlight the heterogeneity of sleep and circadian profiles in young people with affective disorders, and provide preliminary evidence in support of a relationship between sleep and visual memory, which may be mediated by use of antipsychotic medication. These findings have implications for the personalisation of treatments and improvement

  5. The relationship between sleep-wake cycle and cognitive functioning in young people with affective disorders.

    Science.gov (United States)

    Carpenter, Joanne S; Robillard, Rébecca; Lee, Rico S C; Hermens, Daniel F; Naismith, Sharon L; White, Django; Whitwell, Bradley; Scott, Elizabeth M; Hickie, Ian B

    2015-01-01

    Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disorders and examine associations between these profiles and cognitive performance. Actigraphy monitoring was completed in 152 young people (16-30 years; 66% female) with primary diagnoses of affective disorders, and 69 healthy controls (18-30 years; 57% female). Patients also underwent detailed neuropsychological assessment. Actigraphy data were processed to estimate both sleep and circadian parameters. Overall neuropsychological performance in patients was poor on tasks relating to mental flexibility and visual memory. Two hierarchical cluster analyses identified three distinct patient groups based on sleep variables and three based on circadian variables. Sleep clusters included a 'long sleep' cluster, a 'disrupted sleep' cluster, and a 'delayed and disrupted sleep' cluster. Circadian clusters included a 'strong circadian' cluster, a 'weak circadian' cluster, and a 'delayed circadian' cluster. Medication use differed between clusters. The 'long sleep' cluster displayed significantly worse visual memory performance compared to the 'disrupted sleep' cluster. No other cognitive functions differed between clusters. These results highlight the heterogeneity of sleep and circadian profiles in young people with affective disorders, and provide preliminary evidence in support of a relationship between sleep and visual memory, which may be mediated by use of antipsychotic medication. These findings have implications for the personalisation of treatments and improvement of functioning in

  6. The Relationship between Sleep-Wake Cycle and Cognitive Functioning in Young People with Affective Disorders

    Science.gov (United States)

    Carpenter, Joanne S.; Robillard, Rébecca; Lee, Rico S. C.; Hermens, Daniel F.; Naismith, Sharon L.; White, Django; Whitwell, Bradley; Scott, Elizabeth M.; Hickie, Ian B.

    2015-01-01

    Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disorders and examine associations between these profiles and cognitive performance. Actigraphy monitoring was completed in 152 young people (16–30 years; 66% female) with primary diagnoses of affective disorders, and 69 healthy controls (18–30 years; 57% female). Patients also underwent detailed neuropsychological assessment. Actigraphy data were processed to estimate both sleep and circadian parameters. Overall neuropsychological performance in patients was poor on tasks relating to mental flexibility and visual memory. Two hierarchical cluster analyses identified three distinct patient groups based on sleep variables and three based on circadian variables. Sleep clusters included a ‘long sleep’ cluster, a ‘disrupted sleep’ cluster, and a ‘delayed and disrupted sleep’ cluster. Circadian clusters included a ‘strong circadian’ cluster, a ‘weak circadian’ cluster, and a ‘delayed circadian’ cluster. Medication use differed between clusters. The ‘long sleep’ cluster displayed significantly worse visual memory performance compared to the ‘disrupted sleep’ cluster. No other cognitive functions differed between clusters. These results highlight the heterogeneity of sleep and circadian profiles in young people with affective disorders, and provide preliminary evidence in support of a relationship between sleep and visual memory, which may be mediated by use of antipsychotic medication. These findings have implications for the personalisation of treatments

  7. Vascular Disease Foundation

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  8. What Is Vascular Disease?

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  9. Adaptation gap hypothesis: How differences between users’ expected and perceived agent functions affect their subjective impression

    Directory of Open Access Journals (Sweden)

    Takanori Komatsu

    2011-02-01

    Full Text Available We describe an “adaptation gap” that indicates the differences between the functions of artificial agents that users expect before starting their interactions and the functions they perceive after their interactions. We investigated the effect of this adaptation gap on users’ impressions of artificial agents because any variations in impression before and after the start of an interaction determines whether the user feels that this agent is worth interacting with. The results showed that positive or negative signs of the adaptation gap and subjective impression scores of agents before the experiment significantly affected the users’ final impressions of the agents.

  10. Testing two mechanisms by which rational and irrational beliefs may affect the functionality of inferences.

    Science.gov (United States)

    Bond, F W; Dryden, W; Briscoe, R

    1999-12-01

    This article describes a role playing experiment that examined the sufficiency hypothesis of Rational Emotive Behaviour Therapy (REBT). This proposition states that it is sufficient for rational and irrational beliefs to refer to preferences and musts, respectively, if those beliefs are to affect the functionality of inferences (FI). Consistent with the REBT literature (e.g. Dryden, 1994; Dryden & Ellis, 1988; Palmer, Dryden, Ellis & Yapp, 1995) results from this experiment showed that rational and irrational beliefs, as defined by REBT, do affect FI. Specifically, results showed that people who hold a rational belief form inferences that are significantly more functional than those that are formed by people who hold an irrational belief. Contrary to REBT theory, the sufficiency hypothesis was not supported. Thus, results indicated that it is not sufficient for rational and irrational beliefs to refer to preferences and musts, respectively, if those beliefs are to affect the FI. It appears, then, that preferences and musts are not sufficient mechanisms by which rational and irrational beliefs, respectively, affect the FI. Psychotherapeutic implications of these findings are considered.

  11. Vascularization and restoration of heart function in rat myocardial infarction using transplantation of human cbMSC/HUVEC core-shell bodies.

    Science.gov (United States)

    Lee, Wen-Yu; Wei, Hao-Ji; Wang, Jiun-Jie; Lin, Kun-Ju; Lin, Wei-Wen; Chen, Ding-Yuan; Huang, Chieh-Cheng; Lee, Ting-Yin; Ma, Hsiang-Yang; Hwang, Shiaw-Min; Chang, Yen; Sung, Hsing-Wen

    2012-03-01

    Cell transplantation is a promising strategy for therapeutic treatment of ischemic heart diseases. In this study, cord blood mesenchymal stem cells (cbMSCs) and human umbilical vein endothelial cells (HUVECs) in the form of core-shell bodies (cbMSC/HUVEC bodies) were prepared to promote vascularization and restore heart functions in an experimentally-created myocardial infarction (MI) rat model. Saline, cbMSC bodies and HUVEC bodies were used as controls. In vitro results indicated that cbMSC/HUVEC bodies possessed the capability of heterotypic assembly of cbMSCs and HUVECs into robust and durable tubular networks on Matrigel. The up-regulated gene expressions of VEGF and IGF-1 reflected the robust expansion of tubular networks; in addition, the augmented levels of SMA and SM22 suggested smooth muscle differentiation of cbMSCs, possibly helping to improve the durability of networks. Moreover, according to the in vivo echocardiographic, magnetic resonance and computed-tomographic results, transplantation of cbMSC/HUVEC bodies benefited post-MI dysfunction. Furthermore, the vascularization analyses demonstrated the robust vasculogenic potential of cbMSC/HUVEC bodies in vivo, thus contributing to the greater viable myocardium and the less scar region, and ultimately restoring the cardiac function. The concept of core-shell bodies composed of perivascular cells and endothelial cells may serve as an attractive cell delivery vehicle for vasculogenesis, thus improving the cardiac function significantly.

  12. Amygdala perfusion is predicted by its functional connectivity with the ventromedial prefrontal cortex and negative affect.

    Directory of Open Access Journals (Sweden)

    Garth Coombs

    Full Text Available BACKGROUND: Previous studies have shown that the activity of the amygdala is elevated in people experiencing clinical and subclinical levels of anxiety and depression (negative affect. It has been proposed that a reduction in inhibitory input to the amygdala from the prefrontal cortex and resultant over-activity of the amygdala underlies this association. Prior studies have found relationships between negative affect and 1 amygdala over-activity and 2 reduced amygdala-prefrontal connectivity. However, it is not known whether elevated amygdala activity is associated with decreased amygdala-prefrontal connectivity during negative affect states. METHODS: Here we used resting-state arterial spin labeling (ASL and blood oxygenation level dependent (BOLD functional magnetic resonance imaging (fMRI in combination to test this model, measuring the activity (regional cerebral blood flow, rCBF and functional connectivity (correlated fluctuations in the BOLD signal of one subregion of the amygdala with strong connections with the prefrontal cortex, the basolateral nucleus (BLA, and subsyndromal anxiety levels in 38 healthy subjects. RESULTS: BLA rCBF was strongly correlated with anxiety levels. Moreover, both BLA rCBF and anxiety were inversely correlated with the strength of the functional coupling of the BLA with the caudal ventromedial prefrontal cortex. Lastly, BLA perfusion was found to be a mediator of the relationship between BLA-prefrontal connectivity and anxiety. CONCLUSIONS: These results show that both perfusion of the BLA and a measure of its functional coupling with the prefrontal cortex directly index anxiety levels in healthy subjects, and that low BLA-prefrontal connectivity may lead to increased BLA activity and resulting anxiety. Thus, these data provide key evidence for an often-cited circuitry model of negative affect, using a novel, multi-modal imaging approach.

  13. Vascular emergencies.

    Science.gov (United States)

    Semashko, D C

    1997-01-01

    This article reviews the initial assessment and emergent management of several common as well as uncommon vascular emergencies. Aortic dissection, aneurysms, and arterial occlusive disease are familiar but challenging clinical entities. Less frequently encountered conditions are also discussed including an aortic enteric fistula, mesenteric venous thrombosis, phlegmasia alba dolens, and subclavian vein thrombosis.

  14. Affective response to a loved one's pain: insula activity as a function of individual differences.

    Directory of Open Access Journals (Sweden)

    Viridiana Mazzola

    Full Text Available Individual variability in emotion processing may be associated with genetic variation as well as with psychological predispositions such as dispositional affect styles. Our previous fMRI study demonstrated that amygdala reactivity was independently predicted by affective-cognitive styles (phobic prone or eating disorders prone and genotype of the serotonin transporter in a discrimination task of fearful facial expressions. Since the insula is associated with the subjective evaluation of bodily states and is involved in human feelings, we explored whether its activity could also vary in function of individual differences. In the present fMRI study, the association between dispositional affects and insula reactivity has been examined in two groups of healthy participants categorized according to affective-cognitive styles (phobic prone or eating disorders prone. Images of the faces of partners and strangers, in both painful and neutral situations, were used as visual stimuli. Interaction analyses indicate significantly different activations in the two groups in reaction to a loved one's pain: the phobic prone group exhibited greater activation in the left posterior insula. These results demonstrate that affective-cognitive style is associated with insula activity in pain empathy processing, suggesting a greater involvement of the insula in feelings for a certain cohort of people. In the mapping of individual differences, these results shed new light on variability in neural networks of emotion.

  15. Verbal marking of affect by children with Asperger Syndrome and high functioning autism during spontaneous interactions with family members.

    Science.gov (United States)

    Müller, Eve; Schuler, Adriana

    2006-11-01

    Verbal marking of affect by older children with Asperger Syndrome (AS) and high functioning autism (HFA) during spontaneous interactions is described. Discourse analysis of AS and HFA and typically developing children included frequency of affective utterances, affective initiations, affective labels and affective explanations, attribution of affective responses to self and others, and positive and negative markers of affect. Findings indicate that children with AS and HFA engaged in a higher proportion of affect marking and provided a higher proportion of affective explanations than typically developing children, yet were less likely to initiate affect marking sequences or talk about the affective responses of others. No significant differences were found between groups in terms of the marking of positive and negative affect.

  16. Vascular and lung function related to ultrafine and fine particles exposure assessed by personal and indoor monitoring: a cross-sectional study

    DEFF Research Database (Denmark)

    Olsen, Yulia; Karottki, Dorina Gabriela; Jensen, Ditte Marie

    2014-01-01

    -related effects. Methods: Associations between vascular and lung function, inflammation markers and exposure in terms of particle number concentration (PNC; d = 10-300 nm) were studied in a cross-sectional design with personal and home indoor monitoring in the Western Copenhagen Area, Denmark. During 48-h, PNC...... and PM2.5 were monitored in living rooms of 60 homes with 81 non-smoking subjects (30-75 years old), 59 of whom carried personal monitors both when at home and away from home. We measured lung function in terms of the FEV1/FVC ratio, microvascular function (MVF) and pulse amplitude by digital artery...... tonometry, blood pressure and biomarkers of inflammation including C-reactive protein, and leukocyte counts with subdivision in neutrophils, eosinophils, monocytes, and lymphocytes in blood. Results: PNC from personal and stationary home monitoring showed weak correlation (r = 0.15, p = 0.24). Personal UFP...

  17. New aspects of vascular remodelling: the involvement of all vascular cell types.

    Science.gov (United States)

    McGrath, John C; Deighan, Clare; Briones, Ana M; Shafaroudi, Majid Malekzadeh; McBride, Melissa; Adler, Jeremy; Arribas, Silvia M; Vila, Elisabet; Daly, Craig J

    2005-07-01

    Conventionally, the architecture of arteries is based around the close-packed smooth muscle cells and extracellular matrix. However, the adventitia and endothelium are now viewed as key players in vascular growth and repair. A new dynamic picture has emerged of blood vessels in a constant state of self-maintenance. Recent work raises fundamental questions about the cellular heterogeneity of arteries and the time course and triggering of normal and pathological remodelling. A common denominator emerging in hypertensive remodelling is an early increase in adventitial cell density suggesting that adventitial cells drive remodelling and may initiate subsequent changes such as re-arrangement of smooth muscle cells and extracellular matrix. The organization of vascular smooth muscle cells follows regular arrangements that can be modelled mathematically. In hypertension, new patterns can be quantified in these terms and give insights to how structure affects function. As with smooth muscle, little is known about the organization of the vascular endothelium, or its role in vascular remodelling. Current observations suggest that there may be a close relationship between the helical organization of smooth muscle cells and the underlying pattern of endothelial cells. The function of myoendothelial connections is a topic of great current interest and may relate to the structure of the internal elastic lamina through which the connections must pass. In hypertensive remodelling this must present an organizational challenge. The objective of this paper is to show how the functions of blood vessels depend on their architecture and a continuous interaction of different cell types and extracellular proteins.

  18. Psychosocial Functioning in Depressive Patients: A Comparative Study between Major Depressive Disorder and Bipolar Affective Disorder

    Directory of Open Access Journals (Sweden)

    Shubham Mehta

    2014-01-01

    Full Text Available Introduction. Major depressive disorder (MDD and bipolar affective disorder (BAD are among the leading causes of disability. These are often associated with widespread impairments in all domains of functioning including relational, occupational, and social. The main aim of the study was to examine and compare nature and extent of psychosocial impairment of patients with MDD and BAD during depressive phase. Methodology. 96 patients (48 in MDD group and 48 in BAD group were included in the study. Patients were recruited in depressive phase (moderate to severe depression. Patients having age outside 18–45 years, psychotic symptoms, mental retardation, and current comorbid medical or axis-1 psychiatric disorder were excluded. Psychosocial functioning was assessed using Range of Impaired Functioning Tool (LIFE-RIFT. Results. Domains of work, interpersonal relationship, life satisfaction, and recreation were all affected in both groups, but the groups showed significant difference in global psychosocial functioning score only (P=0.031 with BAD group showing more severe impairment. Conclusion. Bipolar depression causes higher global psychosocial impairment than unipolar depression.

  19. The protective function of personal growth initiative among a genocide-affected population in Rwanda.

    Science.gov (United States)

    Blackie, Laura E R; Jayawickreme, Eranda; Forgeard, Marie J C; Jayawickreme, Nuwan

    2015-07-01

    The aim of the current study was to investigate the extent to which individual differences in personal growth initiative (PGI) were associated with lower reports of functional impairment of daily activities among a genocide-affected population in Rwanda. PGI measures an individual's motivation to develop as a person and the extent to which he or she is active in setting goals that work toward achieving self-improvement. We found that PGI was negatively associated with functional impairment when controlling for depression, posttraumatic stress disorder, and other demographic factors. Our results suggest that PGI may constitute an important mindset for facilitating adaptive functioning in the aftermath of adversity and in the midst of psychological distress, and as such they might have practical applications for the development of intervention programs.

  20. MRI evaluation of vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Yicheng Liu; Hongxing Zhang; Wei Huang; Wenjun Wan; Hongfen Peng

    2006-01-01

    OBJECTTVE: To explain the association between vascular dementia and the cranial MRI manifestations, and recognize the value of cranial MRI in the early diagnosis of vascular dementia and the assessment of disease conditions.DATA SOURCES: Pubmed database was searched to identify articles about the cranial MRI manifestations of patients with vascular dementia published in English from January 1992 to June 2006 by using the key words of "MRI, vascular dementia". Others were collected by searching the name of journals and title of articles in the Chinese full-text journal database.STUDY SELECTTON: The collected articles were primarily checked, those correlated with the cranial MRI manifestations of patients with vascular dementia were selected, while the obviously irrelative ones were excluded, and the rest were retrieved manually, the full-texts were searched.DATA EXTRACTION: Totally 255 articles were collected, 41 of them were involved, and the other 214 were excluded.DATA SYNTHESIS: MRI can be taken as one of the effective methods for the early diagnosis and disease evaluation of vascular dementia. White matter lesions are the important risk factors of vascular dementia.Vascular dementia is accompanied by the atrophy of related brain sites, but further confirmation is needed to investigate whether there is significant difference. MRI can be used to quantitatively investigate the infarcted sites and sizes of patients with vascular dementia after infarction, but there is still lack of systematic investigation on the association of the infarcted sites and sizes with the cognitive function of patients with vascular dementia.CONCLUSTON: Cranial MRI can detect the symptoms of vascular dementia at early period, so that corresponding measures can be adopted to prevent and treat vascular dementia in time.

  1. Effect of Xiongshao Capsule(芎芍胶囊)on the Function of Vascular Endothelium of Patients with Cervical Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    徐凤芹; 李立志; 徐浩; 姚立芳; 陈可冀; 邵念方

    2004-01-01

    Objective: To study the effect of Xiongshao Capsule (芎芍胶囊, XSC), a TCM herb that can promote blood circulation to remove blood stasis, on the endothelial dependent relaxation function, serum nitric oxide (NO), and plasma endothelin-1 (ET-1) of the patients with cervical atherosclerosis. Methods: Forty patients were randomly divided into two groups: XSC group and Probucol group (western medicine control).In addition, 20 healthy people were set as a normal control group. Plasma ET-1, serum NO, the internal diameter of basal brachial artery, endothelial dependent flow mediated dilation (FMD) and non-endothelial dependent nitroglycerin induced dilation (NID) to the trial group before and after therapy and to the healthy control group were determined respectively. Results: Compared to the healthy control group, FMD of patients with atherosclerosis was damaged obviously, the serum NO level decreased, plasma ET-1 increased (P<0.01), NID also decreased (P<0.05), the internal diameter of basal brachial artery has no obvious difference (P>0.05). After the patients with atherosclerosis were treated with Xiongshao Capsule for 12 weeks,FMD increased evidently, plasma ET-1 decreased, serum NO and the ratio of NO/ET-1 increased, compared with the level before therapy and Probucol group, the difference was significant (P<0.05, P<0.01), NIDdidn′t change obviously (P>0.05). Conclusion: XSC could regulate vascular activity factor and improve the function of endothelial dependent vascular dilation of patients with atherosclerosis.

  2. Effect of Xiongshao Capsule (芎芍胶囊) on the Function of Vascular Endothelium of Patients with Cervical Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    徐凤芹; 李立志; 徐浩; 姚立芳; 陈可冀; 邵念方

    2004-01-01

    Objective: To study the effect of Xiongshao Capsule (芎芍胶囊, XSC), a TCM herb that can promote blood circulation to remove blood stasis, on the endothelial dependent relaxation function, serum nitric oxide (NO), and plasma endothelin-1(ET-1) of the patients with cervical atherosclerosis. Methods. Forty patients were randomly divided into two groups: XSC group and Probucol group (western medicine control). In addition, 20 healthy people were set as a normal control group. Plasma ET-1, serum NO, the internal diameter of basal brachial artery, endothelial dependent flow mediated dilation (FMD) and non-endothelial dependent nitroglycerin induced dilation (NID) to the trial group before and after therapy and to the healthy control group were determined respectively. Results: Compared to the healthy control group, FMD of patients with atherosclerosis was damaged obviously, the serum NO level decreased, plasma ET-1 increased (P0.05). After the patients with atherosclerosis were treated with Xiongshao Capsule for 12 weeks, FMD increased evidently, plasma ET-1 decreased, serum NO and the ratio of NO/ET-1 increased, compared with the level before therapy and Probucol group, the difference was significant (P0.05). Conclusion: XSC could regulate vascular activity factor and improve the function of endothelial dependent vascular dilation of patients with atherosclerosis.

  3. Plant diversity and functional groups affect Si and Ca pools in aboveground biomass of grassland systems.

    Science.gov (United States)

    Schaller, Jörg; Roscher, Christiane; Hillebrand, Helmut; Weigelt, Alexandra; Oelmann, Yvonne; Wilcke, Wolfgang; Ebeling, Anne; Weisser, Wolfgang W

    2016-09-01

    Plant diversity is an important driver of nitrogen and phosphorus stocks in aboveground plant biomass of grassland ecosystems, but plant diversity effects on other elements also important for plant growth are less understood. We tested whether plant species richness, functional group richness or the presence/absence of particular plant functional groups influences the Si and Ca concentrations (mmol g(-1)) and stocks (mmol m(-2)) in aboveground plant biomass in a large grassland biodiversity experiment (Jena Experiment). In the experiment including 60 temperate grassland species, plant diversity was manipulated as sown species richness (1, 2, 4, 8, 16) and richness and identity of plant functional groups (1-4; grasses, small herbs, tall herbs, legumes). We found positive species richness effects on Si as well as Ca stocks that were attributable to increased biomass production. The presence of particular functional groups was the most important factor explaining variation in aboveground Si and Ca stocks (mmol m(-2)). Grass presence increased the Si stocks by 140 % and legume presence increased the Ca stock by 230 %. Both the presence of specific plant functional groups and species diversity altered Si and Ca stocks, whereas Si and Ca concentration were affected mostly by the presence of specific plant functional groups. However, we found a negative effect of species diversity on Si and Ca accumulation, by calculating the deviation between mixtures and mixture biomass proportions, but in monoculture concentrations. These changes may in turn affect ecosystem processes such as plant litter decomposition and nutrient cycling in grasslands.

  4. Arrival order among native plant functional groups does not affect invasibility of constructed dune communities.

    Science.gov (United States)

    Mason, T J; French, K; Jolley, D

    2013-10-01

    Different arrival order scenarios of native functional groups to a site may influence both resource use during development and final community structure. Arrival order may then indirectly influence community resistance to invasion. We present a mesocosm experiment of constructed coastal dune communities that monitored biotic and abiotic responses to different arrival orders of native functional groups. Constructed communities were compared with unplanted mesocosms. We then simulated a single invasion event by bitou (Chrysanthemoides monilifera ssp. rotundata), a dominant exotic shrub of coastal communities. We evaluated the hypothesis that plantings with simultaneous representation of grass, herb and shrub functional groups at the beginning of the experiment would more completely sequester resources and limit invasion than staggered plantings. Staggered plantings in turn would offer greater resource use and invasion resistance than unplanted mesocosms. Contrary to our expectations, there were few effects of arrival order on abiotic variables for the duration of the experiment and arrival order was unimportant in final community invasibility. All planted mesocosms supported significantly more invader germinants and significantly less invader abundance than unplanted mesocosms. Native functional group plantings may have a nurse effect during the invader germination and establishment phase and a competitive function during the invader juvenile and adult phase. Arrival order per se did not affect resource use and community invasibility in our mesocosm experiment. While grass, herb and shrub functional group plantings will not prevent invasion success in restored communities, they may limit final invader biomass.

  5. Functional connectivity of pain-mediated affect regulation in Borderline Personality Disorder.

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    Inga Niedtfeld

    Full Text Available Affective instability and self-injurious behavior are important features of Borderline Personality Disorder. Whereas affective instability may be caused by a pattern of limbic hyperreactivity paired with dysfunctional prefrontal regulation mechanisms, painful stimulation was found to reduce affective arousal at the neural level, possibly underlying the soothing effect of pain in BPD.We used psychophysiological interactions to analyze functional connectivity of (para- limbic brain structures (i.e. amygdala, insula, anterior cingulate cortex in Borderline Personality Disorder in response to painful stimulation. Therefore, we re-analyzed a dataset from 20 patients with Borderline Personality Disorder and 23 healthy controls who took part in an fMRI-task inducing negative (versus neutral affect and subsequently applying heat pain (versus warmth perception.Results suggest an enhanced negative coupling between limbic as well as paralimbic regions and prefrontal regions, specifically with the medial and dorsolateral prefrontal cortex, when patients experienced pain in addition to emotional arousing pictures. When neutral pictures were combined with painful heat sensation, we found positive connectivity in Borderline Personality Disorder between (para-limbic brain areas and parts of the basal ganglia (lentiform nucleus, putamen, as well areas involved in self-referential processing (precuneus and posterior cingulate.We found further evidence for alterations in the emotion regulation process in Borderline Personality Disorder, in the way that pain improves the inhibition of limbic activity by prefrontal areas. This study provides new insights in pain processing in BPD, including enhanced coupling of limbic structures and basal ganglia.

  6. Modulation of α power and functional connectivity during facial affect recognition.

    Science.gov (United States)

    Popov, Tzvetan; Miller, Gregory A; Rockstroh, Brigitte; Weisz, Nathan

    2013-04-03

    Research has linked oscillatory activity in the α frequency range, particularly in sensorimotor cortex, to processing of social actions. Results further suggest involvement of sensorimotor α in the processing of facial expressions, including affect. The sensorimotor face area may be critical for perception of emotional face expression, but the role it plays is unclear. The present study sought to clarify how oscillatory brain activity contributes to or reflects processing of facial affect during changes in facial expression. Neuromagnetic oscillatory brain activity was monitored while 30 volunteers viewed videos of human faces that changed their expression from neutral to fearful, neutral, or happy expressions. Induced changes in α power during the different morphs, source analysis, and graph-theoretic metrics served to identify the role of α power modulation and cross-regional coupling by means of phase synchrony during facial affect recognition. Changes from neutral to emotional faces were associated with a 10-15 Hz power increase localized in bilateral sensorimotor areas, together with occipital power decrease, preceding reported emotional expression recognition. Graph-theoretic analysis revealed that, in the course of a trial, the balance between sensorimotor power increase and decrease was associated with decreased and increased transregional connectedness as measured by node degree. Results suggest that modulations in α power facilitate early registration, with sensorimotor cortex including the sensorimotor face area largely functionally decoupled and thereby protected from additional, disruptive input and that subsequent α power decrease together with increased connectedness of sensorimotor areas facilitates successful facial affect recognition.

  7. Analgesic nephropathy selectively affecting a unilateral non-functioning hypoplastic kidney.

    Science.gov (United States)

    Granese, J; Brightbill, K; Osborne, P; Cox, C E; Gaber, L W

    2007-08-01

    Analgesic nephropathy results from chronic abuse of non-narcotic analgesics, most frequently with the use of phenacetin and mixed analgesic preparations. Renal papillary necrosis and chronic interstitial nephritis with progressive scarring are characteristic of the histopathology of analgesic nephropathy. Typically, papillary necrosis in these patients is bilateral and affects almost all renal papillae. This report describes a case of severe analgesic nephropathy that discriminantly affected a unilateral non-functioning kidney and spared the contralateral normally developed kidney. The patient herein consumed therapeutic doses of acetaminophen and naproxen daily and for several years. We estimated the cumulative doses of acetaminophen and naproxen used by the patient during that period to be approximately 1.0 and 0.4 kg, respectively. The cumulative dose of acetaminophen is at the threshold of doses that were traditionally associated with an increased risk for end-stage kidney failure. Simultaneous intake of both analgesics could have had a synergetic adverse effect on renal function. This case also demonstrates that preexisting renal insufficiency is prerequisite to the development of analgesic nephropathy. Conversely, kidneys with normal function are resistant to the chronic nephrotoxicity associated with habitual analgesic use.

  8. Diagnosis advances in vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    Hua Zhou; Zhong Zhao

    2009-01-01

    Vascular cognitive impairment(VCI) encompasses the entire range of cognitive deficits associated with cerebrovascular disease(CVD), from mild deficits with little or no functional impairment, such as vascular cognitive impairment-no dementia(VCIND), to full-blown vascular dementia(VaD). Accurate diagnosis of vascular cognitive impairment is important but may be difficult. In this review we report advances in VCI in the following areas: etiology, subtypes, neuropsychology, biomarkers, neuroimaging, and diagnostic criteria.

  9. The Ketogenic Diet Alters the Hypoxic Response and Affects Expression of Proteins Associated with Angiogenesis, Invasive Potential and Vascular Permeability in a Mouse Glioma Model.

    Directory of Open Access Journals (Sweden)

    Eric C Woolf

    Full Text Available The successful treatment of malignant gliomas remains a challenge despite the current standard of care, which consists of surgery, radiation and temozolomide. Advances in the survival of brain cancer patients require the design of new therapeutic approaches that take advantage of common phenotypes such as the altered metabolism found in cancer cells. It has therefore been postulated that the high-fat, low-carbohydrate, adequate protein ketogenic diet (KD may be useful in the treatment of brain tumors. We have demonstrated that the KD enhances survival and potentiates standard therapy in a mouse model of malignant glioma, yet the mechanisms are not fully understood.To explore the effects of the KD on various aspects of tumor growth and progression, we used the immunocompetent, syngeneic GL261-Luc2 mouse model of malignant glioma.Tumors from animals maintained on KD showed reduced expression of the hypoxia marker carbonic anhydrase 9, hypoxia inducible factor 1-alpha, and decreased activation of nuclear factor kappa B. Additionally, tumors from animals maintained on KD had reduced tumor microvasculature and decreased expression of vascular endothelial growth factor receptor 2, matrix metalloproteinase-2 and vimentin. Peritumoral edema was significantly reduced in animals fed the KD and protein analyses showed altered expression of zona occludens-1 and aquaporin-4.The KD directly or indirectly alters the expression of several proteins involved in malignant progression and may be a useful tool for the treatment of gliomas.

  10. Social-adaptive and psychological functioning of patients affected by Fabry disease.

    Science.gov (United States)

    Laney, Dawn Alyssia; Gruskin, Daniel J; Fernhoff, Paul M; Cubells, Joseph F; Ousley, Opal Y; Hipp, Heather; Mehta, Ami J

    2010-12-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of alpha-galactosidase A. In addition to the debilitating physical symptoms of FD, there are also under-recognized and poorly characterized psychiatric features. As a first step toward characterizing psychiatric features of FD, we administered the Achenbach adult self report questionnaire to 30 FD patients and the Achenbach adult behavior checklist questionnaire to 28 partners/parents/friends of FD patients. Data from at least one of the questionnaires were available on 33 subjects. Analysis focused on social-adaptive functioning in various aspects of daily life and on criteria related to the Diagnostic and statistical manual of mental disorders IV (DSM-IV). Adaptive functioning scale values, which primarily measure social and relationship functioning and occupational success, showed that eight FD patients (six female and two male) had mean adaptive functioning deficits as compared to population norms. Greater rates of depression (P personality (P Individuals affected by Fabry disease exhibited social-adaptive functioning deficits that were significantly correlated with anxiety, depression, antisocial behavior, and AD/H problems in a sampling of our male and female patients aged between 18 years and 59 years.

  11. Cure Kinetics of Epoxy Nanocomposites Affected by MWCNTs Functionalization: A Review

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Saeb

    2013-01-01

    Full Text Available The current paper provides an overview to emphasize the role of functionalization of multiwalled carbon nanotubes (MWCNTs in manipulating cure kinetics of epoxy nanocomposites, which itself determines ultimate properties of the resulting compound. In this regard, the most commonly used functionalization schemes, that is, carboxylation and amidation, are thoroughly surveyed to highlight the role of functionalized nanotubes in controlling the rate of autocatalytic and vitrification kinetics. The current literature elucidates that the mechanism of curing in epoxy/MWCNTs nanocomposites remains almost unaffected by the functionalization of carbon nanotubes. On the other hand, early stage facilitation of autocatalytic reactions in the presence of MWCNTs bearing amine groups has been addressed by several researchers. When carboxylated nanotubes were used to modify MWCNTs, the rate of such reactions diminished as a consequence of heterogeneous dispersion within the epoxy matrix. At later stages of curing, however, the prolonged vitrification was seen to be dominant. Thus, the type of functional groups covalently located on the surface of MWCNTs directly affects the degree of polymer-nanotube interaction followed by enhancement of curing reaction. Our survey demonstrated that most widespread efforts ever made to represent multifarious surface-treated MWCNTs have not been directed towards preparation of epoxy nanocomposites, but they could result in property synergism.

  12. Função endotelial vascular em pacientes com fluxo coronário lento e os efeitos do nebivolol Vascular endothelial function in patients with coronary slow flow and the effects of nebivolol

    Directory of Open Access Journals (Sweden)

    Yilmaz Gunes

    2011-10-01

    Full Text Available FUNDAMENTO: A função endotelial braquial tem sido associada ao fluxo lento coronário (FLC. O aumento do fluxo sanguíneo para a artéria braquial faz com que o endotélio libere óxido nítrico (ON, com subsequente vasodilatação. Além de sua atividade com betabloqueador, o nebivolol provoca vasodilatação, aumentando a liberação endotelial de ON. OBJETIVO: Avaliar os efeitos do nebivolol na função endotelial vascular em pacientes com FLC. MÉTODOS: 46 pacientes com FLC e 23 indivíduos com artérias coronárias epicárdicas normais foram examinados com ecocardiografia transtorácica e ultrassonografia da artéria braquial. Os pacientes foram reavaliados dois meses após o tratamento com aspirina ou aspirina e nebivolol. RESULTADOS: Os pacientes com FLC apresentaram maior índice de massa corporal (26,5 ± 3,3 vs. 23,8 ± 2,8, p BACKGROUND: Brachial endothelial function has been associated with coronary slow flow (CSF. Increasing blood flow to brachial artery provokes endothelium to release nitric oxide (NO with subsequent vasodilatation. Besides its β1-blocker activity, nebivolol causes vasodilatation by increasing endothelial NO release. OBJECTIVE: To assess the effects of nebivolol on vascular endothelial function in patients with CSF. METHODS: Forty-six patients with CSF and 23 individuals with normal epicardial coronary arteries were examined with transthoracic echocardiography and brachial artery ultrasonography. The patients were reevaluated two months after treatment with aspirin or aspirin plus nebivolol. RESULTS: Patients with CSF had higher body mass index (26.5 ± 3.3 vs. 23.8 ± 2.8, p < 0.001, mitral inflow isovolumetric relaxation time (IVRT (114.9 ± 18.0 vs. 95.0 ± 22.0 msec, p < 0.001 and lower left ventricular ejection fraction (LVEF (63.5 ± 3.1% vs. 65.4 ± 2.2, p = 0.009, HDL-cholesterol (39.4 ± 8.5 vs. 45.8 ± 7.7 mg/dL, p = 0.003 and brachial flow-mediated dilatation (FMD (6.1 ± 3.9% vs. 17.6 ± 4.5%, p < 0

  13. S1P(1) Receptor Modulation Preserves Vascular Function in Mesenteric and Coronary Arteries after CPB in the Rat Independent of Depletion of Lymphocytes

    NARCIS (Netherlands)

    Samarska, Iryna V.; Bouma, Hjalmar R.; Buikema, Hendrik; Mungroop, Hubert E.; Houwertjes, Martin C.; Absalom, Anthony R.; Epema, Anne H.; Henning, Robert H.

    2014-01-01

    Background: Cardiopulmonary bypass (CPB) may induce systemic inflammation and vascular dysfunction. Sphingosine 1-phosphate (S1P) modulates various vascular and immune responses. Here we explored whether agonists of the S1P receptors, FTY720 and SEW2871 improve vascular reactivity after CPB in the r

  14. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function.

    Science.gov (United States)

    Baruch, Kuti; Deczkowska, Aleksandra; David, Eyal; Castellano, Joseph M; Miller, Omer; Kertser, Alexander; Berkutzki, Tamara; Barnett-Itzhaki, Zohar; Bezalel, Dana; Wyss-Coray, Tony; Amit, Ido; Schwartz, Michal

    2014-10-03

    Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent gene expression profile that was also found in aged human brains. In aged mice, this response was induced by brain-derived signals, present in the cerebrospinal fluid. Blocking IFN-I signaling within the aged brain partially restored cognitive function and hippocampal neurogenesis and reestablished IFN-II-dependent choroid plexus activity, which is lost in aging. Our data identify a chronic aging-induced IFN-I signature, often associated with antiviral response, at the brain's choroid plexus and demonstrate its negative influence on brain function, thereby suggesting a target for ameliorating cognitive decline in aging.

  15. Developing fragility functions for the areas affected by the 2009 Samoa earthquake and tsunami

    Directory of Open Access Journals (Sweden)

    H. Gokon

    2014-01-01

    Full Text Available Fragility functions in terms of flow depth, flow velocity and hydrodynamic force are developed to evaluate structural vulnerability in the areas affected by the 2009 Samoa earthquake and tsunami. First, numerical simulations of tsunami propagation and inundation are conducted to reproduce the features of tsunami inundation. To validate the results, flow depths measured in field surveys and waveforms measured by Deep-ocean Assessment and Reporting of Tsunamis (DART gauges are utilized. Next, building damage is investigated by manually detecting changes between pre- and post-tsunami high-resolution satellite images. Finally, the data related to tsunami features and building damage are integrated using GIS, and tsunami fragility functions are developed based on the statistical analyses.

  16. Structural and functional changes in subcortical vascular mild cognitive impairment: a combined voxel-based morphometry and resting-state fMRI study.

    Directory of Open Access Journals (Sweden)

    Liye Yi

    Full Text Available The present study aimed to investigate changes in structural gray matter (GM volume and functional amplitude of spontaneous low-frequency oscillations (LFO and functional connectivity density in patients with subcortical vascular mild cognitive impairment (svMCI. Structural MRI and resting-sate functional MRI data were collected from 26 svMCI patients and 28 age- and gender-matched healthy controls. Structurally, widespread GM atrophy was found in the svMCI patients that resided primarily in frontal (e.g., the superior and middle frontal gyri and medial prefrontal cortex and temporal (the superior and inferior temporal gyri brain regions as well as several subcortical brain sites (e.g., the thalamus and the caudate. Functionally, svMCI-related changes were predominantly found in the default mode network (DMN. Compared with the healthy controls, the svMCI patients exhibited decreased LFO amplitudes in the anterior part of the DMN (e.g., the medial prefrontal cortex, whereas increased LFO amplitudes in the posterior part of the DMN (e.g., the posterior cingulate/precuneus. As for functional connectivity density, the DMN regions (e.g., the posterior cingulate/precuneus, the medial prefrontal cortex and the middle temporal gyrus consistently exhibited decreased functional connectivity. Finally, the overall patterns of functional alterations in LFO amplitudes and functional connectivity density remained little changed after controlling for structural GM volume losses, which suggests that functional abnormalities can be only partly explained by morphological GM volume changes. Together, our results indicate that svMCI patients exhibit widespread abnormalities in both structural GM volume and functional intrinsic brain activity, which have important implications in understanding the pathophysiological mechanism of svMCI.

  17. Thyroid, brain and mood modulation in affective disorder: insights from molecular research and functional brain imaging.

    Science.gov (United States)

    Bauer, M; London, E D; Silverman, D H; Rasgon, N; Kirchheiner, J; Whybrow, P C

    2003-11-01

    The efficacy resulting from adjunctive use of supraphysiological doses of levothyroxine has emerged as a promising approach to therapy and prophylaxis for refractory mood disorders. Most patients with mood disorders who receive treatment with supraphysiological doses of levothyroxine have normal peripheral thyroid hormone levels, and also respond differently to the hormone and tolerate it better than healthy individuals and patients with primary thyroid diseases. Progress in molecular and functional brain imaging techniques has provided a new understanding of these phenomena, illuminating the relationship between thyroid function, mood modulation and behavior. Thyroid hormones are widely distributed in the brain and have a multitude of effects on the central nervous system. Notably many of the limbic system structures where thyroid hormone receptors are prevalent have been implicated in the pathogenesis of mood disorders. The influence of the thyroid system on neurotransmitters (particularly serotonin and norepinephrine), which putatively play a major role in the regulation of mood and behavior, may contribute to the mechanisms of mood modulation. Recent functional brain imaging studies using positron emission tomography (PET) with [ (18)F]-fluorodeoxyglucose demonstrated that thyroid hormone treatment with levothyroxine affects regional brain metabolism in patients with hypothyroidism and bipolar disorder. Theses studies confirm that thyroid hormones are active in modulating metabolic function in the mature adult brain, and provide intriging neuroanatomic clues that may guide future research.

  18. The modulation of vascular ATP-sensitive K+ channel function via the phosphatidylinositol 3-kinase-Akt pathway activated by phenylephrine.

    Science.gov (United States)

    Haba, Masanori; Hatakeyama, Noboru; Kinoshita, Hiroyuki; Teramae, Hiroki; Azma, Toshiharu; Hatano, Yoshio; Matsuda, Naoyuki

    2010-08-01

    The present study examined the modulator role of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway activated by the alpha-1 adrenoceptor agonist phenylephrine in ATP-sensitive K(+) channel function in intact vascular smooth muscle. We evaluated the ATP-sensitive K(+) channel function and the activity of the PI3K-Akt pathway in the rat thoracic aorta without endothelium. The PI3K inhibitor 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) (10(-5) M) augmented relaxation in response to the ATP-sensitive K(+) channel opener levcromakalim (10(-8) to 3 x 10(-6) M) in aortic rings contracted with phenylephrine (3 x 10(-7) M) but not with 9,11-dideoxy-11alpha,9alpha-epoxy-methanoprostaglandin F(2alpha) (U46619; 3 x 10(-8) M), although those agents induced similar contraction. ATP-sensitive K(+) channel currents induced by levcromakalim (10(-6) M) in the presence of phenylephrine (3 x 10(-7) M) were enhanced by the nonselective alpha-adrenoceptor antagonist phentolamine (10(-7) M) and LY294002 (10(-5) M). Levels of the regulatory subunits of PI3K p85-alpha and p55-gamma increased in the membrane fraction from aortas without endothelium treated with phenylephrine (3 x 10(-7) M) but not with U46619 (3 x 10(-8) M). Phenylephrine simultaneously augmented Akt phosphorylation at Ser473 and Thr308. Therefore, activation of the PI3K-Akt pathway seems to play a role in the impairment of ATP-sensitive K(+) channel function in vascular smooth muscle exposed to alpha-1 adrenergic stimuli.

  19. Arabidopsis AtADF1 is Functionally Affected by Mutations on Actin Binding Sites

    Institute of Scientific and Technical Information of China (English)

    Chun-Hai Dong; Wei-Ping Tang; Jia-Yao Liu

    2013-01-01

    The plant actin depolymerizing factor (ADF) binds to both monomeric and filamentous actin,and is directly involved in the depolymerization of actin filaments.To better understand the actin binding sites of the Arabidopsis thaliana L.AtADF1,we generated mutants of AtADF1 and investigated their functions in vitro and in vivo.Analysis of mutants harboring amino acid substitutions revealed that charged residues (Arg98 and Lys100) located at the α-helix 3 and forming an actin binding site together with the N-terminus are essential for both G-and F-actin binding.The basic residues on the β-strand 5 (K82/A) and the α-helix 4 (R135/A,R137/A) form another actin binding site that is important for F-actin binding.Using transient expression of CFP-tagged AtADF1 mutant proteins in onion (Allium cepa) peel epidermal cells and transgenic Arabidopsis thaliana L.plants overexpressing these mutants,we analyzed how these mutant proteins regulate actin organization and affect seedling growth.Our results show that the ADF mutants with a lower affinity for actin filament binding can still be functional,unless the affinity foractin monomers is also affected.The G-actin binding activity of the ADF plays an essential role in actin binding,depolymerization of actin polymers,and therefore in the control of actin organization.

  20. Attachment style predicts affect, cognitive appraisals, and social functioning in daily life.

    Science.gov (United States)

    Sheinbaum, Tamara; Kwapil, Thomas R; Ballespí, Sergi; Mitjavila, Mercè; Chun, Charlotte A; Silvia, Paul J; Barrantes-Vidal, Neus

    2015-01-01

    The way in which attachment styles are expressed in the moment as individuals navigate their real-life settings has remained an area largely untapped by attachment research. The present study examined how adult attachment styles are expressed in daily life using experience sampling methodology (ESM) in a sample of 206 Spanish young adults. Participants were administered the Attachment Style Interview (ASI) and received personal digital assistants that signaled them randomly eight times per day for 1 week to complete questionnaires about their current experiences and social context. As hypothesized, participants' momentary affective states, cognitive appraisals, and social functioning varied in meaningful ways as a function of their attachment style. Individuals with an anxious attachment, as compared with securely attached individuals, endorsed experiences that were congruent with hyperactivating tendencies, such as higher negative affect, stress, and perceived social rejection. By contrast, individuals with an avoidant attachment, relative to individuals with a secure attachment, endorsed experiences that were consistent with deactivating tendencies, such as decreased positive states and a decreased desire to be with others when alone. Furthermore, the expression of attachment styles in social contexts was shown to be dependent upon the subjective appraisal of the closeness of social contacts, and not merely upon the presence of social interactions. The findings support the ecological validity of the ASI and the person-by-situation character of attachment theory. Moreover, they highlight the utility of ESM for investigating how the predictions derived from attachment theory play out in the natural flow of real life.

  1. Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function

    Directory of Open Access Journals (Sweden)

    Ville Y. P. Väre

    2017-03-01

    Full Text Available RNAs are central to all gene expression through the control of protein synthesis. Four major nucleosides, adenosine, guanosine, cytidine and uridine, compose RNAs and provide sequence variation, but are limited in contributions to structural variation as well as distinct chemical properties. The ability of RNAs to play multiple roles in cellular metabolism is made possible by extensive variation in length, conformational dynamics, and the over 100 post-transcriptional modifications. There are several reviews of the biochemical pathways leading to RNA modification, but the physicochemical nature of modified nucleosides and how they facilitate RNA function is of keen interest, particularly with regard to the contributions of modified nucleosides. Transfer RNAs (tRNAs are the most extensively modified RNAs. The diversity of modifications provide versatility to the chemical and structural environments. The added chemistry, conformation and dynamics of modified nucleosides occurring at the termini of stems in tRNA’s cloverleaf secondary structure affect the global three-dimensional conformation, produce unique recognition determinants for macromolecules to recognize tRNAs, and affect the accurate and efficient decoding ability of tRNAs. This review will discuss the impact of specific chemical moieties on the structure, stability, electrochemical properties, and function of tRNAs.

  2. STN1 OB Fold Mutation Alters DNA Binding and Affects Selective Aspects of CST Function

    Science.gov (United States)

    Bhattacharjee, Anukana; Stewart, Jason; Chaiken, Mary; Price, Carolyn M.

    2016-01-01

    Mammalian CST (CTC1-STN1-TEN1) participates in multiple aspects of telomere replication and genome-wide recovery from replication stress. CST resembles Replication Protein A (RPA) in that it binds ssDNA and STN1 and TEN1 are structurally similar to RPA2 and RPA3. Conservation between CTC1 and RPA1 is less apparent. Currently the mechanism underlying CST action is largely unknown. Here we address CST mechanism by using a DNA-binding mutant, (STN1 OB-fold mutant, STN1-OBM) to examine the relationship between DNA binding and CST function. In vivo, STN1-OBM affects resolution of endogenous replication stress and telomere duplex replication but telomeric C-strand fill-in and new origin firing after exogenous replication stress are unaffected. These selective effects indicate mechanistic differences in CST action during resolution of different replication problems. In vitro binding studies show that STN1 directly engages both short and long ssDNA oligonucleotides, however STN1-OBM preferentially destabilizes binding to short substrates. The finding that STN1-OBM affects binding to only certain substrates starts to explain the in vivo separation of function observed in STN1-OBM expressing cells. CST is expected to engage DNA substrates of varied length and structure as it acts to resolve different replication problems. Since STN1-OBM will alter CST binding to only some of these substrates, the mutant should affect resolution of only a subset of replication problems, as was observed in the STN1-OBM cells. The in vitro studies also provide insight into CST binding mechanism. Like RPA, CST likely contacts DNA via multiple OB folds. However, the importance of STN1 for binding short substrates indicates differences in the architecture of CST and RPA DNA-protein complexes. Based on our results, we propose a dynamic DNA binding model that provides a general mechanism for CST action at diverse forms of replication stress. PMID:27690379

  3. Relationship of mercury to cognitive, affective and perceptual motor functioning in a normal sample in Hawaii

    Energy Technology Data Exchange (ETDEWEB)

    Sine, L.F.

    1983-01-01

    Although the effects of toxic levels of mercury have been well documented, the effects of subclinical levels of mercury on normal populations have generally not been studied. The purpose of this investigation was to assess the impact of mercury risk factors on cognition, affect, psychopathology, and known mercury-related symptoms in a normal sample in Hawaii exposed to subclinical although elevated levels of elemental mercury through inhalation associated with volcanic activity and of methylmercury mostly through ingestion of large ocean species fish. The following summarizes the findings and conclusions of the study: 1) a four week test-retest reliability using 41 of the subjects showed that the 41 measures used in the study exhibited an average correlation of .78. Using all 413 subjects, the average internal consistency measured by Cronbach's ..cap alpha.. was .82 for the 17 affect, psychopathology, and symptom measures; 2) nine mercury source variables were used to predict the amount of total mercury in hair. Interestingly, none of the source variables predicted hair total mercury; 3) the source variables in addition to hair total mercury and statistical control variables were used to predict the twenty-two functioning variables in the four domains cited above with a relative absence of relationships noted. This finding indicates that the normal population in Hawaii appears not to be at risk; and 4) one historical mercury source variable, reported fish intake when young, related to six functioning variables - the psychopathology measures of Somatization, Obsessive-Compulsive and Anxiety as well as the Sensory, Affect and Mental symptoms - with Beta weights in the .15 to .20 range. The implications of the findings were discussed and suggestions offered for future research especially with respect to specific high risk subgroups.

  4. Sydnone SYD-1 affects the metabolic functions of isolated rat hepatocytes.

    Science.gov (United States)

    Brandt, Anna Paula; Pires, Amanda do Rocio Andrade; Rocha, Maria Eliane Merlin; Noleto, Guilhermina Rodrigues; Acco, Alexandra; de Souza, Carlos Eduardo Alves; Echevarria, Aurea; Canuto, André Vinícius dos Santos; Cadena, Sílvia Maria Suter Correia

    2014-07-25

    Previously, we demonstrated that sydnone SYD-1 (3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate) impairs the mitochondrial functions linked to energy provision and suggested that this effect could be associated with its antitumor activity. Herein, we evaluated the effects of SYD-1 (25 and 50 μM) on rat hepatocytes to determine its cytotoxicity on non-tumor cells. SYD-1 (25 and 50 μM) did not affect the viability of hepatocytes in suspension after 1-40 min of incubation. However, the viability of the cultured hepatocytes was decreased by ∼66% as a consequence of treatment with SYD-1 (50 μM) for 18 h. Under the same conditions, SYD-1 promoted an increase in the release of LDH by ∼19%. The morphological changes in the cultured cells treated with SYD-1 (50 μM) were suggestive of cell distress, which was demonstrated by the presence of rounded hepatocytes, cell fragments and monolayer impairment. Furthermore, fluorescence microscopy showed an increase in the annexin label after treatment with SYD-1 (50 μM), suggesting that apoptosis had been induced in these cells. SYD-1 did not affect the states of respiration in the suspended hepatocytes, but the pyruvate levels were decreased by ∼36%, whereas the lactate levels were increased by ∼22% (for the 50 μM treatment). The basal and uncoupled states of respiration of the cultured hepatocytes were inhibited by ∼79% and ∼51%, respectively, by SYD-1 (50 μM). In these cells, SYD-1 (50 μM) increased the pyruvate and lactate levels by ∼84% and ∼16%, respectively. These results show that SYD-1 affects important metabolic functions related to energy provision in hepatocytes and that this effect was more pronounced on cells in culture than those in suspension.

  5. Breakfast staple types affect brain gray matter volume and cognitive function in healthy children.

    Science.gov (United States)

    Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Takeuchi, Hikaru; Asano, Michiko; Asano, Kohei; Kawashima, Ryuta

    2010-12-08

    Childhood diet is important for brain development. Furthermore, the quality of breakfast is thought to affect the cognitive functioning of well-nourished children. To analyze the relationship among breakfast staple type, gray matter volume, and intelligence quotient (IQ) in 290 healthy children, we used magnetic resonance images and applied voxel-based morphometry. We divided subjects into rice, bread, and both groups according to their breakfast staple. We showed that the rice group had a significantly larger gray matter ratio (gray matter volume percentage divided by intracranial volume) and significantly larger regional gray matter volumes of several regions, including the left superior temporal gyrus. The bread group had significantly larger regional gray and white matter volumes of several regions, including the right frontoparietal region. The perceptual organization index (POI; IQ subcomponent) of the rice group was significantly higher than that of the bread group. All analyses were adjusted for age, gender, intracranial volume, socioeconomic status, average weekly frequency of having breakfast, and number of side dishes eaten for breakfast. Although several factors may have affected the results, one possible mechanism underlying the difference between the bread and the rice groups may be the difference in the glycemic index (GI) of these two substances; foods with a low GI are associated with less blood-glucose fluctuation than are those with a high GI. Our study suggests that breakfast staple type affects brain gray and white matter volumes and cognitive function in healthy children; therefore, a diet of optimal nutrition is important for brain maturation during childhood and adolescence.

  6. Breakfast staple types affect brain gray matter volume and cognitive function in healthy children.

    Directory of Open Access Journals (Sweden)

    Yasuyuki Taki

    Full Text Available Childhood diet is important for brain development. Furthermore, the quality of breakfast is thought to affect the cognitive functioning of well-nourished children. To analyze the relationship among breakfast staple type, gray matter volume, and intelligence quotient (IQ in 290 healthy children, we used magnetic resonance images and applied voxel-based morphometry. We divided subjects into rice, bread, and both groups according to their breakfast staple. We showed that the rice group had a significantly larger gray matter ratio (gray matter volume percentage divided by intracranial volume and significantly larger regional gray matter volumes of several regions, including the left superior temporal gyrus. The bread group had significantly larger regional gray and white matter volumes of several regions, including the right frontoparietal region. The perceptual organization index (POI; IQ subcomponent of the rice group was significantly higher than that of the bread group. All analyses were adjusted for age, gender, intracranial volume, socioeconomic status, average weekly frequency of having breakfast, and number of side dishes eaten for breakfast. Although several factors may have affected the results, one possible mechanism underlying the difference between the bread and the rice groups may be the difference in the glycemic index (GI of these two substances; foods with a low GI are associated with less blood-glucose fluctuation than are those with a high GI. Our study suggests that breakfast staple type affects brain gray and white matter volumes and cognitive function in healthy children; therefore, a diet of optimal nutrition is important for brain maturation during childhood and adolescence.

  7. Effect of exercise-induced neurogenesis on cognitive function deficit in a rat model of vascular dementia.

    Science.gov (United States)

    Choi, Dong-Hee; Lee, Kyoung-Hee; Lee, Jongmin

    2016-04-01

    Chronic cerebral hypoperfusion (CCH) is strongly correlated with progressive cognitive decline in neurological diseases, such as vascular dementia (VaD) and Alzheimer's disease. Exercise can enhance learning and memory, and delay age-related cognitive decline. However, exercise-induced hippocampal neurogenesis in experimental animals submitted to CCH has not been investigated. The present study aimed to investigate whether hippocampal neurogenesis induced by exercise can improve cognitive deficit in a rat model of VaD. Male Wistar rats (age, 8 weeks; weight, 292±3.05 g; n=12-13/group) were subjected to bilateral common carotid artery occlusion (2VO) or sham‑surgery and each group was then subdivided randomly into no exercise and treadmill exercise groups. Exercise groups performed treadmill exercise daily at 15 m/min for 30 min for 4 weeks from the third to the seventh week after 2VO. It was demonstrated that the number of neural progenitor cells and mature neurons in the subgranular zone of 2VO rats was increased by exercise, and cognitive impairment in 2VO rats was attenuated by treadmill exercise. In addition, mature brain‑derived neurotrophic factor (BDNF) levels in the hippocampus were increased in the exercise groups. Thus the present study suggests that exercise delays cognitive decline by the enhancing neurogenesis and increasing BDNF expression in the context of VaD.

  8. Bmx tyrosine kinase has a redundant function downstream of angiopoietin and vascular endothelial growth factor receptors in arterial endothelium.

    Science.gov (United States)

    Rajantie, I; Ekman, N; Iljin, K; Arighi, E; Gunji, Y; Kaukonen, J; Palotie, A; Dewerchin, M; Carmeliet, P; Alitalo, K

    2001-07-01

    The Bmx gene, a member of the Tec tyrosine kinase gene family, is known to be expressed in subsets of hematopoietic and endothelial cells. In this study, mice were generated in which the first coding exon of the Bmx gene was replaced with the lacZ reporter gene by a knock-in strategy. The homozygous mice lacking Bmx activity were fertile and had a normal life span without an obvious phenotype. Staining of their tissues using beta-galactosidase substrate to assess the sites of Bmx expression revealed strong signals in the endothelial cells of large arteries and in the endocardium starting between days 10.5 and 12.5 of embryogenesis and continuing in adult mice, while the venular endothelium showed a weak signal only in the superior and inferior venae cavae. Of the five known endothelial receptor tyrosine kinases tested, activated Tie-2 induced tyrosyl phosphorylation of the Bmx protein and both Tie-2 and vascular endothelial growth factor receptor 1 (VEGFR-1) stimulated Bmx tyrosine kinase activity. Thus, the Bmx tyrosine kinase has a redundant role in arterial endothelial signal transduction downstream of the Tie-2 and VEGFR-1 growth factor receptors.

  9. Expression and Purification of Functional Human Vascular Endothelial Growth Factor-A121; the Most Important Angiogenesis Factor

    Directory of Open Access Journals (Sweden)

    Fatemeh Kazemi-Lomedasht

    2014-12-01

    Full Text Available Purpose: Angiogenesis or formation of new blood vessels is an essential process for tumor growth, invasion and metastasis. Vascular Endothelial Growth Factor (VEGF and its receptors play an important role in angiogenesis-dependent tumors. VEGF-A is the most important factor in angiogenesis process. Human VEGF-A gene consists of eight exons that undergoes alternative exon splicing and produce five different proteins consisting of 121, 145, 165, 189 and 206 amino acids (named VEGF121, VEGF145, VEGF165, VEGF189, and VEGF206. Methods: In this study, VEGF121 gene synthesized and cloned into the pET-26b plasmid. The recombinant plasmid was transferred into appropriate expression strain of BL-21. Expression of VEGF121 induced by IPTG (Isopropyl β-D-1-thiogalactopyranoside and confirmed by SDS-PAGE and Western-Blotting. Recombinant VEGF121 was purified by nickel affinity chromatography. HUVECs (Human Umbilical Vein Endothelia Cells cells were isolated from umbilical vein and the effect of VEGF121 on tube formation of endothelial cells was investigated. Results: SDS-PAGE and Western-Blotting results verified the purification of VEGF121. The final yield of recombinant protein was about 5mg per liter. Endothelial cell tube formation assay results showed that VEGF121 leads to tube formation of endothelial cell on matrix and induces angiogenesis in vitro. Conclusion: Recombinant VEGF121 is important factor in tube formation of endothelial cell, so it could be used in different cancer researches and angiogenesis assay.

  10. Perturbed lignification impacts tree growth in hybrid poplar--a function of sink strength, vascular integrity, and photosynthetic assimilation.

    Science.gov (United States)

    Coleman, Heather D; Samuels, A Lacey; Guy, Robert D; Mansfield, Shawn D

    2008-11-01

    The effects of reductions in cell wall lignin content, manifested by RNA interference suppression of coumaroyl 3'-hydroxylase, on plant growth, water transport, gas exchange, and photosynthesis were evaluated in hybrid poplar trees (Populus alba x grandidentata). The growth characteristics of the reduced lignin trees were significantly impaired, resulting in smaller stems and reduced root biomass when compared to wild-type trees, as well as altered leaf morphology and architecture. The severe inhibition of cell wall lignification produced trees with a collapsed xylem phenotype, resulting in compromised vascular integrity, and displayed reduced hydraulic conductivity and a greater susceptibility to wall failure and cavitation. In the reduced lignin trees, photosynthetic carbon assimilation and stomatal conductance were also greatly reduced, however, shoot xylem pressure potential and carbon isotope discrimination were higher and water-use efficiency was lower, inconsistent with water stress. Reductions in assimilation rate could not be ascribed to increased stomatal limitation. Starch and soluble sugars analysis of leaves revealed that photosynthate was accumulating to high levels, suggesting that the trees with substantially reduced cell wall lignin were not carbon limited and that reductions in sink strength were, instead, limiting photosynthesis.

  11. Realistic changes in seaweed biodiversity affect multiple ecosystem functions on a rocky shore.

    Science.gov (United States)

    Bracken, Matthew E S; Williams, Susan L

    2013-09-01

    Given current threats to biodiversity, understanding the effects of diversity changes on the functions and services associated with intact ecosystems is of paramount importance. However, limited realism in most biodiversity studies makes it difficult to link the large and growing body of evidence for important functional consequences of biodiversity change to real-world losses of biodiversity. Here, we explored two methods of incorporating realism into biodiversity research: (1) the use of two-, five-, and eight-species assemblages that mimicked those that we observed in surveys of seaweed biodiversity patterns on a northern California (USA) rocky shore and the explicit comparison of those assemblages to random assemblages compiled from the same local species pool; and (2) the measurement of two fundamental ecosystem functions, nitrate uptake and photosynthesis, both of which contribute to growth of primary producers. Specifically, we measured nitrate uptake rates of seaweed assemblages as a function of initial nitrate concentrations and photosynthetic rates as a function of irradiance levels for both realistic and random assemblages of seaweeds. We only observed changes in ecosystem functioning along a richness gradient for realistic assemblages, and both maximum nitrate uptake rates (V(max)) and photosynthetic light use efficiency values (alpha(p) = P(max)/I(K)) were higher in realistic assemblages than in random assemblages. Furthermore, the parameter affected by changes in richness depended on the function being measured. Both V(max) and alpha(p) declined with increasing richness in nonrandom assemblages due to a combination of species identity effects (for V(max) and overyielding effects (for both V(max) and alpha(p)). In contrast, neither nitrate uptake efficiency values (alpha(N) = V(max)/K(s)), nor maximum photosynthetic rates (Pmax) changed along the gradient in seaweed species richness. Furthermore, overyielding was only evident in realistic assemblages

  12. Disturbance gradient shows logging affects plant functional groups more than fire.

    Science.gov (United States)

    Blair, David P; McBurney, Lachlan M; Blanchard, Wade; Banks, Sam C; Lindenmayer, David B

    2016-10-01

    Understanding the impacts of natural and human disturbances on forest biota is critical for improving forest management. Many studies have examined the separate impacts on fauna and flora of wildfire, conventional logging, and salvage logging, but empirical comparisons across a broad gradient of simultaneous disturbances are lacking. We quantified species richness and frequency of occurrence of vascular plants, and functional group responses, across a gradient of disturbances that occurred concurrently in 2009 in the mountain ash forests of southeastern Australia. Our study encompassed replicated sites in undisturbed forest (~70 yr post fire), forest burned at low severity, forest burned at high severity, unburned forest that was clearcut logged, and forest burned at high severity that was clearcut salvage logged post-fire. All sites were sampled 2 and 3 yr post fire. Mean species richness decreased across the disturbance gradient from 30.1 species/site on low-severity burned sites and 28.9 species/site on high-severity burned sites, to 25.1 species/site on clearcut sites and 21.7 species/site on salvage logged sites. Low-severity burned sites were significantly more species-rich than clearcut sites and salvage logged sites; high-severity burned sites supported greater species richness than salvage logged sites. Specific traits influenced species' sensitivity to disturbance. Resprouting species dominated undisturbed mountain ash forests, but declined significantly across the gradient. Fern and midstory trees decreased significantly in frequency of occurrence across the gradient. Ferns (excluding bracken) decreased from 34% of plants in undisturbed forest to 3% on salvage logged sites. High-severity burned sites supported a greater frequency of occurrence and species richness of midstory trees compared to clearcut and salvage logged sites. Salvage logging supported fewer midstory trees than any other disturbance category, and were distinctly different from

  13. Earthworm-Mycorrhiza Interactions Can Affect the Diversity, Structure and Functioning of Establishing Model Grassland Communities

    Science.gov (United States)

    Zaller, Johann G.; Heigl, Florian; Grabmaier, Andrea; Lichtenegger, Claudia; Piller, Katja; Allabashi, Roza; Frank, Thomas; Drapela, Thomas

    2011-01-01

    Both earthworms and arbuscular mycorrhizal fungi (AMF) are important ecosystem engineers co-occurring in temperate grasslands. However, their combined impacts during grassland establishment are poorly understood and have never been studied. We used large mesocosms to study the effects of different functional groups of earthworms (i.e., vertically burrowing anecics vs. horizontally burrowing endogeics) and a mix of four AMF taxa on the establishment, diversity and productivity of plant communities after a simulated seed rain of 18 grassland species comprising grasses, non-leguminous forbs and legumes. Moreover, effects of earthworms and/or AMF on water infiltration and leaching of ammonium, nitrate and phosphate were determined after a simulated extreme rainfall event (40 l m−2). AMF colonisation of all three plant functional groups was altered by earthworms. Seedling emergence and diversity was reduced by anecic earthworms, however only when AMF were present. Plant density was decreased in AMF-free mesocosms when both anecic and endogeic earthworms were active; with AMF also anecics reduced plant density. Plant shoot and root biomass was only affected by earthworms in AMF-free mesocosms: shoot biomass increased due to the activity of either anecics or endogeics; root biomass increased only when anecics were active. Water infiltration increased when earthworms were present in the mesocosms but remained unaffected by AMF. Ammonium leaching was increased only when anecics or a mixed earthworm community was active but was unaffected by AMF; nitrate and phosphate leaching was neither affected by earthworms nor AMF. Ammonium leaching decreased with increasing plant density, nitrate leaching decreased with increasing plant diversity and density. In order to understand the underlying processes of these interactions further investigations possibly under field conditions using more diverse belowground communities are required. Nevertheless, this study demonstrates that

  14. Earthworm-mycorrhiza interactions can affect the diversity, structure and functioning of establishing model grassland communities.

    Directory of Open Access Journals (Sweden)

    Johann G Zaller

    Full Text Available Both earthworms and arbuscular mycorrhizal fungi (AMF are important ecosystem engineers co-occurring in temperate grasslands. However, their combined impacts during grassland establishment are poorly understood and have never been studied. We used large mesocosms to study the effects of different functional groups of earthworms (i.e., vertically burrowing anecics vs. horizontally burrowing endogeics and a mix of four AMF taxa on the establishment, diversity and productivity of plant communities after a simulated seed rain of 18 grassland species comprising grasses, non-leguminous forbs and legumes. Moreover, effects of earthworms and/or AMF on water infiltration and leaching of ammonium, nitrate and phosphate were determined after a simulated extreme rainfall event (40 l m(-2. AMF colonisation of all three plant functional groups was altered by earthworms. Seedling emergence and diversity was reduced by anecic earthworms, however only when AMF were present. Plant density was decreased in AMF-free mesocosms when both anecic and endogeic earthworms were active; with AMF also anecics reduced plant density. Plant shoot and root biomass was only affected by earthworms in AMF-free mesocosms: shoot biomass increased due to the activity of either anecics or endogeics; root biomass increased only when anecics were active. Water infiltration increased when earthworms were present in the mesocosms but remained unaffected by AMF. Ammonium leaching was increased only when anecics or a mixed earthworm community was active but was unaffected by AMF; nitrate and phosphate leaching was neither affected by earthworms nor AMF. Ammonium leaching decreased with increasing plant density, nitrate leaching decreased with increasing plant diversity and density. In order to understand the underlying processes of these interactions further investigations possibly under field conditions using more diverse belowground communities are required. Nevertheless, this study

  15. Analysis of common and specific mechanisms of liver function affected by nitrotoluene compounds.

    Directory of Open Access Journals (Sweden)

    Youping Deng

    Full Text Available BACKGROUND: Nitrotoluenes are widely used chemical manufacturing and munitions applications. This group of chemicals has been shown to cause a range of effects from anemia and hypercholesterolemia to testicular atrophy. We have examined the molecular and functional effects of five different, but structurally related, nitrotoluenes on using an integrative systems biology approach to gain insight into common and disparate mechanisms underlying effects caused by these chemicals. METHODOLOGY/PRINCIPAL FINDINGS: Sprague-Dawley female rats were exposed via gavage to one of five concentrations of one of five nitrotoluenes [2,4,6-trinitrotoluene (TNT, 2-amino-4,6-dinitrotoluene (2ADNT 4-amino-2,6-dinitrotoulene (4ADNT, 2,4-dinitrotoluene (2,4DNT and 2,6-dinitrotoluene (2,6DNT] with necropsy and tissue collection at 24 or 48 h. Gene expression profile results correlated well with clinical data and liver histopathology that lead to the concept that hematotoxicity was followed by hepatotoxicity. Overall, 2,4DNT, 2,6DNT and TNT had stronger effects than 2ADNT and 4ADNT. Common functional terms, gene expression patterns, pathways and networks were regulated across all nitrotoluenes. These pathways included NRF2-mediated oxidative stress response, aryl hydrocarbon receptor signaling, LPS/IL-1 mediated inhibition of RXR function, xenobiotic metabolism signaling and metabolism of xenobiotics by cytochrome P450. One biological process common to all compounds, lipid metabolism, was found to be impacted both at the transcriptional and lipid production level. CONCLUSIONS/SIGNIFICANCE: A systems biology strategy was used to identify biochemical pathways affected by five nitroaromatic compounds and to integrate data that tie biochemical alterations to pathological changes. An integrative graphical network model was constructed by combining genomic, gene pathway, lipidomic, and physiological endpoint results to better understand mechanisms of liver toxicity and

  16. Critical role of nucleotide-binding oligomerization domain-like receptor 3 in vascular repair

    Energy Technology Data Exchange (ETDEWEB)

    Schlaweck, Sebastian; Zimmer, Sebastian; Struck, Rafael [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Bartok, Eva [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Werner, Nikos [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Bauernfeind, Franz [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Latz, Eicke [Institute of Innate Immunity, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Nickenig, Georg [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Hornung, Veit [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Ghanem, Alexander, E-mail: ghanem@uni-bonn.de [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany)

    2011-08-05

    Highlights: {yields} NLRP3 is not required for systemic cardiovascular function in healthy mice. {yields} NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and that it does not alter peripheral differential blood counts. {yields} NLRP3 is critical in neointima formation following vascular injury. -- Abstract: Vascular remodeling characterized by hyperproliferative neointima formation is an unfavorable repair process that is triggered by vascular damage. This process is characterized by an increased local inflammatory and proliferative response that critically involves the pro-inflammatory cytokine interleukin-1{beta} (IL-1{beta}). IL-1{beta} is expressed and cytosolically retained as a procytokine that requires additional processing prior to exerting its pro-inflammatory function. Maturation and release of pro IL-1{beta} is governed by a cytosolic protein scaffold that is known as the inflammasome. Here we show that NLRP3 (NOD-like receptor family, pryin domain containing 3), an important activating component of the inflammasome, is involved in neointima formation after vascular injury. NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and does not alter peripheral differential blood counts. However, neointima development following wire injury of the carotid artery was significantly decreased in NLRP3-deficient mice as compared to wild-type controls. In all, NLRP3 plays a non-redundant role in vascular damage mediated neointima formation. Our data establish NLRP3 as a key player in the response to vascular damage, which could open new avenues to therapeutic intervention.

  17. Functional high-resolution computed tomography of pulmonary vascular and airway reactions. Experimental results. Funktionelle HR-CT der Lunge. Experimentelle Untersuchungen pulmonaler Gefaess- und Atemwegsreaktionen

    Energy Technology Data Exchange (ETDEWEB)

    Herold, C.J. (Universitaetsklinik fuer Radiodiagnostik, Vienna (Austria) Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology); Brown, R.H. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Anesthesiology and Intensive Care Medicine Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Physiology); Wetzel, R.C.; Herold, S.M. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Anesthesiology and Intensive Care Medicine); Zeerhouni, E.A. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology)

    1993-03-01

    We describe the use of high-resolution computed tomography (HRCT) for assessment of the function of pulmonary vessels and airways. With its excellent spatial resolution, HRCT is able to demonstrate pulmonary structures as small as 300 [mu]m and can be used to monitor changes following various stimuli. HRCT also provides information about structures smaller than 300 [mu]m through measurement of parenchymal background density. To date, sequential, spiral and ultrafast HRCT techniques have been used in a variety of challenges to gather information about the anatomical correlates of traditional physiological measurements, thus making anatomical-physiological correlation possible. HRCT of bronchial reactivity can demonstrate the location and time course of aerosol-induced broncho-constriction and may show changes not apparent on spirometry. HRCT of the pulmonary vascular system visualized adaptations of vessels during hypoxia and intravascular volume loading and elucidates cardiorespiratory interactions. Experimental studies provide a basis for potential clinical applications of this method. (orig.).

  18. Effect of continuous positive airway pressure treatment on vascular endothelial function in patients with obstructive sleep apnea hypopnea syndrome and coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    张希龙; 殷凯生; 毛辉; 王虹; 杨玉

    2004-01-01

    Background Continuous positive airway pressure (CPAP) treatment has been proven to be effective in improving the symptoms of coexisting coronary heart disease (CHD) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). However, it is still unclear whether such improvements are linked to changes in vascular endothelial function. This research was carried out to investigate the effects of CPAP treatment on vascular endothelial function in patients with OSAHS and CHD.Methods Thirty-six patients with moderate or severe OSAHS and CHD undergoing three months of CPAP treatment were recruited for this study. The changes in their morning plasma nitric oxide (NO) and endothelin (ET) levels, NO/ET ratio, total ischemic burden (TIB) of the myocardium, apnea hypopnea index (AHI), and minimal and mean pulse oxygen saturation (SpO2) were compared and analyzed before and during CPAP treatment. Results Compared with the plasma levels of ET [(51.39±11.69) ng/L] and NO [(36.67±11.86) μmol/L], NO/ET (0.71±0.14), AHI (32.4±7.9), minimal SpO2 [(68.9±11.4)%], and myocardial TIB [(66.29±16.37) mm*min] before treatment, there were significant decreases in ET [(33.41±10.03) ng/L] (P<0.05), increases in NO [(59.89±10.26) μmol/L] and NO/ET (1.79±0.38) (P<0.01), decreases in AHI (1.9±0.5), and increases in minimal SpO2 [(90.6±1.8) %] (all P<0.01) and myocardial TIB [(36.42±10.87) mm*min] (P<0.05) after three months of CPAP treatment.Conclusion CPAP treatment may play an important role in the improvement and protection of vascular endothelial dysfunction and myocardial ischemia in OSAHS patients with CHD.

  19. Plant species richness and functional traits affect community stability after a flood event.

    Science.gov (United States)

    Fischer, Felícia M; Wright, Alexandra J; Eisenhauer, Nico; Ebeling, Anne; Roscher, Christiane; Wagg, Cameron; Weigelt, Alexandra; Weisser, Wolfgang W; Pillar, Valério D

    2016-05-19

    Climate change is expected to increase the frequency and magnitude of extreme weather events. It is therefore of major importance to identify the community attributes that confer stability in ecological communities during such events. In June 2013, a flood event affected a plant diversity experiment in Central Europe (Jena, Germany). We assessed the effects of plant species richness, functional diversity, flooding intensity and community means of functional traits on different measures of stability (resistance, resilience and raw biomass changes from pre-flood conditions). Surprisingly, plant species richness reduced community resistance in response to the flood. This was mostly because more diverse communities grew more immediately following the flood. Raw biomass increased over the previous year; this resulted in decreased absolute value measures of resistance. There was no clear response pattern for resilience. We found that functional traits drove these changes in raw biomass: communities with a high proportion of late-season, short-statured plants with dense, shallow roots and small leaves grew more following the flood. Late-growing species probably avoided the flood, whereas greater root length density might have allowed species to better access soil resources brought from the flood, thus growing more in the aftermath. We conclude that resource inputs following mild floods may favour the importance of traits related to resource acquisition and be less associated with flooding tolerance.

  20. Aesthetic and Functional Rehabilitation of the Primary Dentition Affected by Amelogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Maria Carolina Salomé Marquezin

    2015-01-01

    Full Text Available The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child’s psychosocial development.

  1. The role of the vascular dendritic cell network in atherosclerosis

    OpenAIRE

    Alberts-Grill, Noah; Denning, Timothy L.; Rezvan, Amir; Jo, Hanjoong

    2013-01-01

    A complex role has been described for dendritic cells (DCs) in the potentiation and control of vascular inflammation and atherosclerosis. Resident vascular DCs are found in the intima of atherosclerosis-prone vascular regions exposed to disturbed blood flow patterns. Several phenotypically and functionally distinct vascular DC subsets have been described. The functional heterogeneity of these cells and their contributions to vascular homeostasis, inflammation, and atherosclerosis are only rec...

  2. 6A3-5/Osa2 is an Early Activated Gene Implicated in the Control of Vascular Smooth Muscle Cell Functions

    Directory of Open Access Journals (Sweden)

    Gwenaele Garin

    2006-01-01

    Full Text Available Vascular smooth muscle cells (VSMC growth plays a key role in the pathophysiology of vascular diseases. However, the molecular mechanisms controlling gene transcription in VSMC remain poorly understood. We previously identified, by differential display, a new gene (6A3-5 overexpressed in proliferating rat VSMC. In this study, we have cloned the full-length cDNA by screening a rat foetal brain cDNA library and investigated its functions. The 6A3-5 protein shows 4 putative conserved functional motifs: a DNA binding domain called ARID (AT-rich interaction domain, two recently described motifs (Osa Homology Domain, and a nuclear localization signal. The deduced protein sequence was observed to be 85% identical to the recently described human Osa2 gene. Immunolabelling, using an anti-6A3-5/Osa2 monoclonal antibody, showed a nuclear localization of the 6A3-5/Osa2 protein. In addition, PDGF upregulated 6A3-5/Osa2 expression at both the transcript and protein levels in a dose and time-dependent fashion. The pattern of upregulation by PDGF was reminiscent of the early responsive gene c-fos. The PDGF-induced upregulation of 6A3-5/Osa2 and proliferation of VSMC were significantly inhibited in a dose and sequence-dependent fashion by an antisense, but not by sense, scrambled or mismatched oligonucleotides directed against 6A3-5/Osa2. In VSMC of aortas derived from hypertensive (LH rats, 6A3-5/Osa2 is overexpressed as compared to that in normotensive (LL rats. The 6A3-5/Osa2-gene expression is downregulated by an ACE inhibitor and upregulated by exogenous AngiotensinII in LH rats. In summary, these results indicate that 6A3-5/Osa2 is an early activated gene that belongs to a new family of proteins involved in the control of VSMC growth.

  3. Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice.

    Science.gov (United States)

    Sartori, Claudio; Dessen, Pierre; Mathieu, Caroline; Monney, Anita; Bloch, Jonathan; Nicod, Pascal; Scherrer, Urs; Duplain, Hervé

    2009-12-01

    Obesity and insulin resistance represent a problem of utmost clinical significance worldwide. Insulin-resistant states are characterized by the inability of insulin to induce proper signal transduction leading to defective glucose uptake in skeletal muscle tissue and impaired insulin-induced vasodilation. In various pathophysiological models, melatonin interacts with crucial molecules of the insulin signaling pathway, but its effects on glucose homeostasis are not known. In a diet-induced mouse model of insulin resistance and normal chow-fed control mice, we sought to assess the effects of an 8-wk oral treatment with melatonin on insulin and glucose tolerance and to understand underlying mechanisms. In high-fat diet-fed mice, but not in normal chow-fed control mice, melatonin significantly improved insulin sensitivity and glucose tolerance, as evidenced by a higher rate of glucose infusion to maintain euglycemia during hyperinsulinemic clamp studies and an attenuated hyperglycemic response to an ip glucose challenge. Regarding underlying mechanisms, we found that melatonin restored insulin-induced vasodilation to skeletal muscle, a major site of glucose utilization. This was due, at least in part, to the improvement of insulin signal transduction in the vasculature, as evidenced by increased insulin-induced phosphorylation of Akt and endoethelial nitric oxide synthase in aortas harvested from melatonin-treated high-fat diet-fed mice. In contrast, melatonin had no effect on the ability of insulin to promote glucose uptake in skeletal muscle tissue in vitro. These data demonstrate for the first time that in a diet-induced rodent model of insulin resistance, melatonin improves glucose homeostasis by restoring the vascular action of insulin.

  4. Cognitive and cognitive-motor interventions affecting physical functioning: A systematic review

    Directory of Open Access Journals (Sweden)

    Murer Kurt

    2011-06-01

    Full Text Available Abstract Background Several types of cognitive or combined cognitive-motor intervention types that might influence physical functions have been proposed in the past: training of dual-tasking abilities, and improving cognitive function through behavioral interventions or the use of computer games. The objective of this systematic review was to examine the literature regarding the use of cognitive and cognitive-motor interventions to improve physical functioning in older adults or people with neurological impairments that are similar to cognitive impairments seen in aging. The aim was to identify potentially promising methods that might be used in future intervention type studies for older adults. Methods A systematic search was conducted for the Medline/Premedline, PsycINFO, CINAHL and EMBASE databases. The search was focused on older adults over the age of 65. To increase the number of articles for review, we also included those discussing adult patients with neurological impairments due to trauma, as these cognitive impairments are similar to those seen in the aging population. The search was restricted to English, German and French language literature without any limitation of publication date or restriction by study design. Cognitive or cognitive-motor interventions were defined as dual-tasking, virtual reality exercise, cognitive exercise, or a combination of these. Results 28 articles met our inclusion criteria. Three articles used an isolated cognitive rehabilitation intervention, seven articles used a dual-task intervention and 19 applied a computerized intervention. There is evidence to suggest that cognitive or motor-cognitive methods positively affects physical functioning, such as postural control, walking abilities and general functions of the upper and lower extremities, respectively. The majority of the included studies resulted in improvements of the assessed functional outcome measures. Conclusions The current evidence on the

  5. Metacognitive Awareness of Facial Affect in Higher-Functioning Children and Adolescents with Autism Spectrum Disorder.

    Science.gov (United States)

    McMahon, Camilla M; Henderson, Heather A; Newell, Lisa; Jaime, Mark; Mundy, Peter

    2016-03-01

    Higher-functioning participants with and without autism spectrum disorder (ASD) viewed a series of face stimuli, made decisions regarding the affect of each face, and indicated their confidence in each decision. Confidence significantly predicted accuracy across all participants, but this relation was stronger for participants with typical development than participants with ASD. In the hierarchical linear modeling analysis, there were no differences in face processing accuracy between participants with and without ASD, but participants with ASD were more confident in their decisions. These results suggest that individuals with ASD have metacognitive impairments and are overconfident in face processing. Additionally, greater metacognitive awareness was predictive of better face processing accuracy, suggesting that metacognition may be a pivotal skill to teach in interventions.

  6. Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model.

    Science.gov (United States)

    Chaillou, Thomas; Koulmann, Nathalie; Simler, Nadine; Meunier, Adélie; Serrurier, Bernard; Chapot, Rachel; Peinnequin, Andre; Beaudry, Michèle; Bigard, Xavier

    2012-03-01

    Hypoxia induces a loss of skeletal muscle mass, but the signaling pathways and molecular mechanisms involved remain poorly understood. We hypothesized that hypoxia could impair skeletal muscle hypertrophy induced by functional overload (Ov). To test this hypothesis, plantaris muscles were overloaded during 5, 12, and 56 days in female rats exposed to hypobaric hypoxia (5,500 m), and then, we examined the responses of specific signaling pathways involved in protein synthesis (Akt/mTOR) and breakdown (atrogenes). Hypoxia minimized the Ov-induced hypertrophy at days 5 and 12 but did not affect the hypertrophic response measured at day 56. Hypoxia early reduced the phosphorylation levels of mTOR and its downstream targets P70(S6K) and rpS6, but it did not affect the phosphorylation levels of Akt and 4E-BP1, in Ov muscles. The role played by specific inhibitors of mTOR, such as AMPK and hypoxia-induced factors (i.e., REDD1 and BNIP-3) was studied. REDD1 protein levels were reduced by overload and were not affected by hypoxia in Ov muscles, whereas AMPK was not activated by hypoxia. Although hypoxia significantly increased BNIP-3 mRNA levels at day 5, protein levels remained unaffected. The mRNA levels of the two atrogenes MURF1 and MAFbx were early increased by hypoxia in Ov muscles. In conclusion, hypoxia induced a transient alteration of muscle growth in this hypertrophic model, at least partly due to a specific impairment of the mTOR/P70(S6K) pathway, independently of Akt, by an undefined mechanism, and increased transcript levels for MURF1 and MAFbx that could contribute to stimulate the proteasomal proteolysis.

  7. Identification and Functional Characterization of GAA Mutations in Colombian Patients Affected by Pompe Disease.

    Science.gov (United States)

    Niño, Mónica Yasmín; Mateus, Heidi Eliana; Fonseca, Dora Janeth; Kroos, Marian A; Ospina, Sandra Yaneth; Mejía, Juan Fernando; Uribe, Jesús Alfredo; Reuser, Arnold J J; Laissue, Paul

    2013-01-01

    Pompe disease (PD) is a recessive metabolic disorder characterized by acid α-glucosidase (GAA) deficiency, which results in lysosomal accumulation of glycogen in all tissues, especially in skeletal muscles. PD clinical course is mainly determined by the nature of the GAA mutations. Although ~400 distinct GAA sequence variations have been described, the genotype-phenotype correlation is not always evident.In this study, we describe the first clinical and genetic analysis of Colombian PD patients performed in 11 affected individuals. GAA open reading frame sequencing revealed eight distinct mutations related to PD etiology including two novel missense mutations, c.1106 T > C (p.Leu369Pro) and c.2236 T > C (p.Trp746Arg). In vitro functional studies showed that the structural changes conferred by both mutations did not inhibit the synthesis of the 110 kD GAA precursor form but affected the processing and intracellular transport of GAA. In addition, analysis of previously described variants located at this position (p.Trp746Gly, p.Trp746Cys, p.Trp746Ser, p.Trp746X) revealed new insights in the molecular basis of PD. Notably, we found that p.Trp746Cys mutation, which was previously described as a polymorphism as well as a causal mutation, displayed a mild deleterious effect. Interestingly and by chance, our study argues in favor of a remarkable Afro-American and European ancestry of the Colombian population. Taken together, our report provides valuable information on the PD genotype-phenotype correlation, which is expected to facilitate and improve genetic counseling of affected individuals and their families.

  8. How measurement artifacts affect cerebral autoregulation outcomes: A technical note on transfer function analysis.

    Science.gov (United States)

    Meel-van den Abeelen, Aisha S S; de Jong, Daan L K; Lagro, Joep; Panerai, Ronney B; Claassen, Jurgen A H R

    2016-05-01

    Cerebral autoregulation (CA) is the mechanism that aims to maintain adequate cerebral perfusion during changes in blood pressure (BP). Transfer function analysis (TFA), the most reported method in literature to quantify CA, shows large between-study variability in outcomes. The aim of this study is to investigate the role of measurement artifacts in this variation. Specifically, the role of distortion in the BP and/or CBFV measurementon TFA outcomes was investigated. The influence of three types of artifacts on TFA outcomes was studied: loss of signal, motion artifacts, and baseline drifts. TFA metrics of signals without the simulated artifacts were compared with those of signals with artifacts. TFA outcomes scattered highly when more than 10% of BP signal or over 8% of the CBFV signal was lost, or when measurements contained one or more artifacts resulting from head movement. Furthermore, baseline drift affected interpretation of TFA outcomes when the power in the BP signal was 5 times the power in the LF band. In conclusion, loss of signal in BP and loss in CBFV, affects interpretation of TFA outcomes. Therefore, it is vital to validate signal quality to the defined standards before interpreting TFA outcomes.

  9. Macrofauna assemblage composition and soil moisture interact to affect soil ecosystem functions

    Science.gov (United States)

    Collison, E. J.; Riutta, T.; Slade, E. M.

    2013-02-01

    Changing climatic conditions and habitat fragmentation are predicted to alter the soil moisture conditions of temperate forests. It is not well understood how the soil macrofauna community will respond to changes in soil moisture, and how changes to species diversity and community composition may affect ecosystem functions, such as litter decomposition and soil fluxes. Moreover, few studies have considered the interactions between the abiotic and biotic factors that regulate soil processes. Here we attempt to disentangle the interactive effects of two of the main factors that regulate soil processes at small scales - moisture and macrofauna assemblage composition. The response of assemblages of three common temperate soil invertebrates (Glomeris marginata Villers, Porcellio scaber Latreille and Philoscia muscorum Scopoli) to two contrasting soil moisture levels was examined in a series of laboratory mesocosm experiments. The contribution of the invertebrates to the leaf litter mass loss of two common temperate tree species of contrasting litter quality (easily decomposing Fraxinus excelsior L. and recalcitrant Quercus robur L.) and to soil CO2 fluxes were measured. Both moisture conditions and litter type influenced the functioning of the invertebrate assemblages, which was greater in high moisture conditions compared with low moisture conditions and on good quality vs. recalcitrant litter. In high moisture conditions, all macrofauna assemblages functioned at equal rates, whereas in low moisture conditions there were pronounced differences in litter mass loss among the assemblages. This indicates that species identity and assemblage composition are more important when moisture is limited. We suggest that complementarity between macrofauna species may mitigate the reduced functioning of some species, highlighting the importance of maintaining macrofauna species richness.

  10. Attachment Style Predicts Affect, Cognitive Appraisals, and Social Functioning in Daily Life

    Directory of Open Access Journals (Sweden)

    Tamara eSheinbaum

    2015-03-01

    Full Text Available The way in which attachment styles are expressed in the moment as individuals navigate their real-life settings has remained an area largely untapped by attachment research. The present study examined how adult attachment styles are expressed in daily life using Experience Sampling Methodology (ESM in a sample of 206 Spanish young adults. Participants were administered the Attachment Style Interview and received personal digital assistants that signaled them randomly eight times per day for one week to complete questionnaires about their current experiences and social context. As hypothesized, participants’ momentary affective states, cognitive appraisals, and social functioning varied in meaningful ways as a function of their attachment style. Individuals with an anxious attachment, as compared with securely attached individuals, endorsed experiences that were congruent with hyperactivating tendencies, such as higher negative affect, stress, and perceived social rejection. By contrast, individuals with an avoidant attachment, relative to individuals with a secure attachment, endorsed experiences that were consistent with deactivating tendencies, such as decreased positive states and a decreased desire to be with others when alone. Furthermore, the expression of attachment styles in social contexts was shown to be dependent upon the subjective appraisal of the closeness of social contacts, and not merely upon the presence of social interactions. The findings support the ecological validity of the Attachment Style Interview and the person-by-situation character of attachment theory. Moreover, they highlight the utility of ESM for investigating how the predictions derived from attachment theory play out in the natural flow of real life.

  11. Behavioral Functions of the Mesolimbic Dopaminergic System: an Affective Neuroethological Perspective

    Science.gov (United States)

    Alcaro, Antonio; Huber, Robert; Panksepp, Jaak

    2008-01-01

    The mesolimbic dopaminergic (ML-DA) system has been recognized for its central role in motivated behaviors, various types of reward, and, more recently, in cognitive processes. Functional theories have emphasized DA's involvement in the orchestration of goal-directed behaviors, and in the promotion and reinforcement of learning. The affective neuroethological perspective presented here, views the ML-DA system in terms of its ability to activate an instinctual emotional appetitive state (SEEKING) evolved to induce organisms to search for all varieties of life-supporting stimuli and to avoid harms. A description of the anatomical framework in which the ML system is embedded is followed by the argument that the SEEKING disposition emerges through functional integration of ventral basal ganglia (BG) into thalamocortical activities. Filtering cortical and limbic input that spread into BG, DA transmission promotes the “release” of neural activity patterns that induce active SEEKING behaviors when expressed at the motor level. Reverberation of these patterns constitutes a neurodynamic process for the inclusion of cognitive and perceptual representations within the extended networks of the SEEKING urge. In this way, the SEEKING disposition influences attention, incentive salience, associative learning, and anticipatory predictions. In our view, the rewarding properties of drugs of abuse are, in part, caused by the activation of the SEEKING disposition, ranging from appetitive drive to persistent craving depending on the intensity of the affect. The implications of such a view for understanding addiction are considered, with particular emphasis on factors predisposing individuals to develop compulsive drug seeking behaviors. PMID:17905440

  12. Citicoline in vascular cognitive impairment and vascular dementia after stroke.

    Science.gov (United States)

    Alvarez-Sabín, Jose; Román, Gustavo C

    2011-01-01

    Cognitive decline after stroke is more common than stroke recurrence. Stroke doubles the risk of dementia and is a major contributor to vascular cognitive impairment and vascular dementia. Neuropathological studies in most cases of dementia in the elderly reveal a large load of vascular ischemic brain lesions mixed with a lesser contribution of neurodegenerative lesions of Alzheimer disease. Nonetheless, few pharmacological studies have addressed vascular cognitive impairment and vascular dementia after stroke. Citicoline has demonstrated neuroprotective effects in acute stroke and has been shown to improve cognition in patients with chronic cerebrovascular disease and in some patients with Alzheimer disease. A recent trial lasting 6 months in patients with first-ever ischemic stroke showed that citicoline prevented cognitive decline after stroke with significant improvement of temporal orientation, attention, and executive function. Experimentally, citicoline exhibits neuroprotective effects and enhances neural repair. Citicoline appears to be a safe and promising alternative to improve stroke recovery and could be indicated in patients with vascular cognitive impairment, vascular dementia, and Alzheimer disease with significant cerebrovascular disease.

  13. Arteriovenous Malformations and Other Vascular Lesions of the Central Nervous System

    Science.gov (United States)

    ... Malformations and Other Vascular Lesions of the Central Nervous System Fact Sheet Table of Contents (click to jump ... other types of vascular lesions affect the central nervous system? What causes vascular lesions? How are AVMs and ...

  14. Arterial stiffness, as monitored by cardio–ankle vascular index, is affected by obstructive sleep apnea, blood glucose control, and body weight – a case with 8 years follow up

    Directory of Open Access Journals (Sweden)

    Shimizu K

    2016-08-01

    Full Text Available Kazuhiro Shimizu,1 Tomoyuki Yamamoto,2,3 Kohji Shirai2,4 1Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan; 2Department of Vascular Function, Toho University Sakura Medical Center, Chiba, Japan; 3Biological Information Analysis Section, Fukuda Denshi Co., Ltd., Tokyo, Japan; 4Department of Internal Medicine, Mihama Hospital, Chiba, Japan Abstract: The cardio–ankle vascular index (CAVI is an indicator of arterial stiffness from the heart to the ankles. The CAVI increases as arteriosclerosis progresses, but it can be decreased by appropriate treatment. There are several risk factors for coronary artery disease, however, the degree of stress caused by each separate risk factor to arteries cannot be assessed. CAVI increases with age and according to the severity of atherosclerosis. We found that CAVI also changes in response to the control of risk factors, which may be associated with the functional stiffness of arteries. CAVI can be a useful indicator of risk control for coronary artery disease. We followed a patient aged 71 years who had diabetes mellitus and obstructive sleep apnea (OSA by measuring CAVI for 8 years from age 63. He underwent coronary artery bypass grafting due to angina pectoris when he was 63 years old. Before coronary artery bypass grafting, CAVI was 11.8 on the right and 11.5 on the left. Three years later he was found to have OSA and received treatment with continuous positive airway pressure. There was a marked improvement in CAVI after continuous positive airway pressure (age 68; right 10.4, left 10.2. However, following a gradual increase in body weight and worsening of diabetes mellitus, CAVI showed an increasing trend. CAVI decreased with biguanides treatment, but increased again with an increase in body weight. In conclusion, CAVI responded to the patient’s conditions including obesity, diabetes mellitus, and OSA. CAVI is not only a marker of arterial stiffness, but can also be a

  15. Recovery of renal function after administration of adipose-tissue-derived stromal vascular fraction in rat model of acute kidney injury induced by ischemia/reperfusion injury.

    Science.gov (United States)

    Lee, Chunwoo; Jang, Myoung Jin; Kim, Bo Hyun; Park, Jin Young; You, Dalsan; Jeong, In Gab; Hong, Jun Hyuk; Kim, Choung-Soo

    2017-03-10

    Acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) injury is a major challenge in critical care medicine. The purpose of this study is to determine the therapeutic effects of the adipose-tissue-derived stromal vascular fraction (SVF) and the optimal route for SVF delivery in a rat model of AKI induced by I/R injury. Fifty male Sprague-Dawley rats were randomly divided into five groups (10 animals per group): sham, nephrectomy control, I/R injury control, renal arterial SVF infusion and subcapsular SVF injection. To induce AKI by I/R injury, the left renal artery was clamped with a nontraumatic vascular clamp for 40 min, and the right kidney was removed. Rats receiving renal arterial infusion of SVF had a significantly reduced increase in serum creatinine compared with the I/R injury control group at 4 days after I/R injury. The glomerular filtration rate of the renal arterial SVF infusion group was maintained at a level similar to that of the sham and nephrectomy control groups at 14 days after I/R injury. Masson's trichrome staining showed significantly less fibrosis in the renal arterial SVF infusion group compared with that in the I/R injury control group in the outer stripe (P renal arterial SVF infusion and subcapsular SVF injection groups compared with the I/R injury control group in the outer stripe (P renal function is effectively rescued from AKI induced by I/R injury through the renal arterial administration of SVF in a rat model.

  16. Acute effect of a single bout of aerobic exercise on vascular and baroreflex function of young males with a family history of hypertension.

    Science.gov (United States)

    Boutcher, Y N; Hopp, J P; Boutcher, S H

    2011-05-01

    The effect of one single bout of aerobic exercise on the vascular and baroreceptor function of individuals with a family history of hypertension was investigated. Forty young males, mean age 21 years, comprising offspring with (FH(+); n=20) and without (FH(-); n=20) a family history of hypertension participated in this study. Acute exercise was performed on a stationary bike for 20 min at 60% of maximal oxygen uptake. Peak forearm blood flow (FBF) was assessed using plethysmography and was determined as the highest blood flow after 5 min of reactive hyperaemia. Cardiopulmonary baroreceptor (CPBR) sensitivity was measured using lower-body negative pressure (LBNP) for 5 min at -20 mm Hg. CPBR was determined by calculating change of stroke volume and forearm vascular resistance (FVR) at baseline and during LBNP. Carotid baroreceptor (CBR) sensitivity was assessed using neck suction at -20, -40, -60 and -80 mm Hg pressures and was determined from RR interval divided by systolic blood pressure. Augmentation index (AIx), a measure of wave reflection, was assessed using applanation tonometry, and was calculated as the ratio of augmented pressure and pulse pressure. The peak FBF at pre-exercise was lower in FH(+) than in FH(-) subjects. Twenty minutes of acute cycle exercise resulted in significantly increased peak FBF by 22% in FH(+) and by 11% in FH(-) subjects, whereas peak FVR of both groups decreased by 17% and 11%, respectively. No change occurred in CPBR, CBR or AIx. It is concluded that 20 min of acute cycle exercise normalised baseline FBF and forearm vasodilation during hyperaemia in FH(+) subjects.

  17. Sensory integration dysfunction affects efficacy of speech therapy on children with functional articulation disorders

    Directory of Open Access Journals (Sweden)

    Tung LC

    2013-01-01

    = 70.393; P > 0.001 and interaction between the pre/post speech therapy treatment and groups (F = 11.119; P = 0.002.Conclusions: Speech therapy can improve the articulation performance of children who have functional articulation disorders whether or not they have SID, but it results in significantly greater improvement in children without SID. SID may affect the treatment efficiency of speech therapy in young children with articulation disorders.Keywords: children, functional articulation disorders, sensory integration dysfunction, speech therapy, efficacy

  18. Plant Vascular Biology 2010

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Biao

    2014-11-17

    This grant supported the Second International Conference on Plant Vascular Biology (PVB 2010) held July 24-28, 2010 on the campus of Ohio State University, Columbus, Ohio. Biao Ding (Ohio State University; OSU) and David Hannapel (Iowa State University; ISU) served as co-chairs of this conference. Biao Ding served as the local organizer. PVB is defined broadly here to include studies on the biogenesis, structure and function of transport systems in plants, under conditions of normal plant growth and development as well as of plant interactions with pathogens. The transport systems cover broadly the xylem, phloem, plasmodesmata and vascular cell membranes. The PVB concept has emerged in recent years to emphasize the integrative nature of the transport systems and approaches to investigate them.

  19. Avaliação da capacidade funcional de idosos com acidente vascular encefálico Evaluación de la capacidad funcional de adultos mayores con accidente vascular encefálico Evaluation of functional capaciy in elders with encephalic vascular accident

    Directory of Open Access Journals (Sweden)

    Keila Cristianne Trindade da Cruz

    2009-10-01

    ó un promedio de 97,0. Los pacientes con acceso al servicio de salud presentaron valores superiores a aquellas personas que no tenían acceso (Test de Mann-Whitney. Fue observada una correlación negativa entre la MIF y sus dominios y la edad (Pearson. CONCLUSIÓN: El AVE causó alteración en la capacidad funcional de los sujetos de la investigación, lo que indica la necesidad de invertir en estrategias de rehabilitación que amenicen las pérdidas funcionales procedentes de la propia edad y, principalmente, de las secuelas del AVE.OBJECTIVE: To evaluate the functional capacity of elders with encephalic vascular accident (EVA and to examine the association between sociodemographic variables and functional capacity. METHODS: Interviews with 44 elders who had EVA were conducted during their assessment and treatment in the data collection settings. The instrument contemplated clinical and social-demographic variables. Functional Independence Measure (FIM was used to measure the subjects' functional capacity. RESULTS: Most subjects were between 60 and 69 years of age. The MIF had good internal consistency reliability estimate. Subjects had a mean score of 97.0 on FIM. Mann-Whitney test indicated that participants who had access to health care services had higher FIM scores than individuals without health care access. Pearson's correlation analysis indicated a significantly negative correlation coefficient between age and FIM score. CONCLUSION: Encephalic vascular accident is associated with alterations in functional capacity of the sample of this study. This finding suggests the need for the use of effective rehabilitation strategies to help individuals who have decreased functional capacity due to normal aging and/or sequela to encephalic vascular accident.

  20. Expression of angiopoietin-2 and vascular endothelial growth factor receptor-3 correlates with lymphangiogenesis and angiogenesis and affects survival of oral squamous cell carcinoma.

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    Chao Li

    Full Text Available BACKGROUND: Both Ang-2 and VEGFR-3 are major regulators of angiogenesis and lymphangiogenesis, respectively, and thus may affect prognosis of OSCC. We sought to determine the associations between Ang-2 and VEGFR-3 expression and survival of OSCC. METHODS: Ang-2 and VEGFR-3 expression was determined immunohistochemically in tumor tissues from 112 patients with OSCC; OSCC-adjacent noncancerous oral tissue from 85 OSCC patients; and normal oral mucosa from 37 cancer-free individuals. A log-rank test and Cox proportional hazard models were used to compare survival among different groups with expression of Ang-2 and VEGFR-3. RESULTS: Ang-2 and VEGFR-3 expression was upregulated in OSCC compared to nontumor tissue (all P<0.05. High Ang-2 expression positively correlated with microvessel density (MVD (P<0.01, and high VEGFR-3 expression positively correlated with lymph node metastasis (P<0.01 and lymphatic vessel density (LVD (P<0.01. The patients with high expression of Ang-2 alone or in combination with VEGFR-3 had a significantly worse survival than in patients with low expression of Ang-2 or any other co-expression status (all P<0.05, respectively. Furthermore, multivariable analysis showed that patients with high expression of Ang-2 alone or in combination with VEGFR-3 had a significantly increased risk of death compared with those with low expression of Ang-2 or any other co-expression status (HR, 2.7, 95% CI, 1.1-6.2 and 5.0, 1.3-15.4, respectively. CONCLUSIONS: These results suggest that increased expression in tumors of Ang-2 may individually, or in combination with VEGFR-3, predict poor prognosis of OSCC.

  1. Effects of pioglitazone and metformin on vascular endothelial function in patients with type 2 diabetes treated with sulfonylureas.

    Science.gov (United States)

    Naka, Katerina K; Papathanassiou, Katerina; Bechlioulis, Aris; Pappas, Konstantinos; Kazakos, Nikolaos; Kanioglou, Chryssanthi; Kostoula, Aggeliki; Vezyraki, Patra; Makriyiannis, Demetrios; Tsatsoulis, Agathocles; Michalis, Lampros K

    2012-01-01

    Pioglitazone and metformin are insulin sensitisers used for the treatment of T2DM. The effects of pioglitazone and metformin on endothelial function, assessed by FMD, in T2DM patients treated with sulfonylureas were compared. Patients were randomised to receive pioglitazone (n = 15) 30 mg once daily or metformin (n = 16) 850 mg twice daily for six months. Pioglitazone significantly decreased fasting insulin, HbA(1C) and HOMA-IR (p pioglitazone, compared with metformin, did not reach significance (p = 0.11). Treatment-induced changes in FMD were not associated with the effects of the two insulin sensitisers on glycaemic control or insulin resistance. The beneficial effects of pioglitazone and metformin on endothelial function in T2DM patients did not differ greatly. Larger studies are needed to explore whether a potentially greater benefit with pioglitazone may exist.

  2. Exposure to ambient concentrations of particulate air pollution does not influence vascular function or inflammatory pathways in young healthy individuals

    DEFF Research Database (Denmark)

    Bräuner, E. V.; Møller, P.; Barregård, L.;

    2008-01-01

    : 11600 +/- 5600 per cm(3), mass concentrations: 13.8 +/- 7.4 mu g/m(3) and 10.5 +/- 4.8 mu g/m(3) for PM10-2.5 and PM2.5, respectively) or particle filtered (NC: 555 +/- 1053 per cm(3)) air collected above a busy street. Microvascular function was assessed non-invasively by measuring digital peripheral......Background: Particulate air pollution is associated with increased risk of cardiovascular events although the involved mechanisms are poorly understood. The objective of the present study was to investigate the effects of controlled exposure to ambient air fine and ultrafine particles...... on microvascular function and biomarkers related to inflammation, haemostasis and lipid and protein oxidation. Methods: Twenty-nine subjects participated in a randomized, two-factor crossover study with or without biking exercise for 180 minutes and with 24 hour exposure to particle rich (number concentrations, NC...

  3. Exposure to ambient concentrations of particulate air pollution does not influence vascular function or inflammatory pathways in young healthy individuals

    Directory of Open Access Journals (Sweden)

    Vinzents Peter

    2008-10-01

    Full Text Available Abstract Background Particulate air pollution is associated with increased risk of cardiovascular events although the involved mechanisms are poorly understood. The objective of the present study was to investigate the effects of controlled exposure to ambient air fine and ultrafine particles on microvascular function and biomarkers related to inflammation, haemostasis and lipid and protein oxidation. Methods Twenty-nine subjects participated in a randomized, two-factor crossover study with or without biking exercise for 180 minutes and with 24 hour exposure to particle rich (number concentrations, NC: 11600 ± 5600 per cm3, mass concentrations: 13.8 ± 7.4 μg/m3 and 10.5 ± 4.8 μg/m3 for PM10-2.5 and PM2.5, respectively or particle filtered (NC: 555 ± 1053 per cm3 air collected above a busy street. Microvascular function was assessed non-invasively by measuring digital peripheral artery tone following arm ischemia. Biomarkers included haemoglobin, red blood cells, platelet count, coagulation factors, C-reactive protein, fibrinogen, interleukin-6, tumour necrosis factor α, lag time to copper-induced oxidation of plasma lipids and protein oxidation measured as 2-aminoadipic semialdehyde in plasma. Results No statistically significant differences were observed on microvascular function or the biomarkers after exposure to particle rich or particle filtered air. Conclusion This study indicates that exposure to air pollution particles at outdoor concentrations is not associated with detectable systemic inflammation, lipid or protein oxidation, altered haemostasis or microvascular function in young healthy participants.

  4. Expression of BMP-2 in Vascular Endothelial Cells of Recipient May Predict Delayed Graft Function After Renal Transplantation

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    Nikolina Basic-Jukic

    2016-11-01

    Full Text Available Background/Aims: Delayed graft function (DGF is associated with adverse outcomes after renal transplantation. Bone morphogenetic protein-2 (BMP-2 is involved in both endothelial function and immunological events. We compared expression of BMP-2 in epigastric artery of renal transplant recipients with immediate graft function (IGF and DGF. Methods: 79 patients were included in this prospective study. Patients were divided in IGF group (64 patients and DGF group (15 patients. BMP-2 expression in intima media (BMP2m and endothelium (BMP2e of epigastric artery was assessed by immunohistochemistry. Results: Lower intensity of BMP2e staining was recorded in DGF compared to IGF. In DGF patients, 93% had no expression of BMP2e and 7% had 1st grade expression, compared to 45% and 41% in IGF group, respectively (P=0.001 (Pst grade expression. Patients who had BMP2e staining positive had lower odds for DGF (OR 0.059 [0.007, 0.477] and this remained significant even after adjustment for donor and recipient variables, cold ischemia time, and immunological matching (OR 0.038 [0.003, 0.492]. Conclusions: Our results demonstrate that BMP-2 expression in endothelial cells of epigastric arteries may predict development of DGF.

  5. Determination of phagocytic functions of macrophages,vascular density and NPY-nerve within autotransplanted splenic tissue in adult rats

    Institute of Scientific and Technical Information of China (English)

    JIANG Deng-jin; GUO Guang-jin; ZHANG Kun; LAN Yang-jun; WANG Lin; ZHANG Tian-fei; ZUO Yan-fang

    2004-01-01

    Abstract Objective: To estimate directly phagocytic functions of the macrophages because of the importance in innate immunity, determine blood vessel density and re-innervation density which are basis of function. Methods: Eighty adult Wistar rats were randomly divided into experimental and control groups. The formers underwent splenotomy and a half splenic slice was transplanted into greater omentum. The latter only moved. After 6 months, examination was made as follows: ① After injection of 0.4% carbon particles by vein, splenic tissues were taken out at different times for estimating phagocytosis by light microscope. ② When splenic tissues had been intubated into left ventricle under total anesthesia, animals were perfused by formalin and India ink mixture suspension. Splenic tissues were taken out for making sections for measurement of area density of blood vessels. ③ Immunohistochemical procedure was used for detecting neuropeptide Y (NPY). Results: Phagocytic functions had no difference between two groups, but the area density of blood vessels and NPY-positive fibers redued ( P < 0.01 ) in experimental group. Conclusion: Autotransplanted splenic tissues show good innate immunity though regeneration of blood vessels and nerves do not reach normal level.

  6. Red blood cells in retinal vascular disorders.

    Science.gov (United States)

    Agrawal, Rupesh; Sherwood, Joseph; Chhablani, Jay; Ricchariya, Ashutosh; Kim, Sangho; Jones, Philip H; Balabani, Stavroula; Shima, David

    2016-01-01

    Microvascular circulation plays a vital role in regulating physiological functions, such as vascular resistance, and maintaining organ health. Pathologies such as hypertension, diabetes, or hematologic diseases affect the microcirculation posing a significant risk to human health. The retinal vasculature provides a unique window for non-invasive visualisation of the human circulation in vivo and retinal vascular image analysis has been established to predict the development of both clinical and subclinical cardiovascular, metabolic, renal and retinal disease in epidemiologic studies. Blood viscosity which was otherwise thought to play a negligible role in determining blood flow based on Poiseuille's law up to the 1970s has now been shown to play an equally if not a more important role in controlling microcirculation and quantifying blood flow. Understanding the hemodynamics/rheology of the microcirculation and its changes in diseased states remains a challenging task; this is due to the particulate nature of blood, the mechanical properties of the cells (such as deformability and aggregability) and the complex architecture of the microvasculature. In our review, we have tried to postulate a possible role of red blood cell (RBC) biomechanical properties and laid down future framework for research related to hemorrheological aspects of blood in patients with retinal vascular disorders.

  7. Research progress of vascular endothelial function in chronic kidney disease%慢性肾脏病与血管内皮细胞功能的研究进展

    Institute of Scientific and Technical Information of China (English)

    张霞; 金惠敏

    2012-01-01

    The changes of vascular endothelial function are closely related to the development of chronic kidney disease (CKD). Cardiovascular diseases caused by vascular endothelial dysfunction are the common complications of CKD, and are important causes of mortality in patients with CKD. Based on the control of primary diseases, antioxidant drugs that ameliorate the vascular endothelial injury are now applied in the treatment of vascular endothelial dysfunction. The improvement of vascular endothelial function brought by dialysis is limited to some extent due to many influencing factors. New strategies such as gene therapy and cell transplantation, together with treatment available, may improve function and regeneration of vascular endothelial cells, reduce cardiovascular events, and decrease the mortality of patients with CKD.%血管内皮细胞的功能改变与慢性肾脏病(CKD)的发生和发展密切相关.由血管内皮细胞功能失调引起的心血管疾病是CKD患者常见的并发症,同时也是患者死亡的重要原因.目前治疗血管内皮功能异常的主要方法是在控制原发疾病的基础上,运用减轻和修复血管内皮损伤的抗氧化药物.由于受多种因素影响,透析对血管内皮细胞功能的改善作用尚有一定局限性.采用基因治疗或细胞移植等新型治疗方法,结合现有治疗策略,改善血管内皮细胞功能或增强其再生能力,可减少CKD患者心血管事件的发生,降低患者病死率.

  8. Cardiopulmonary stress testing using ambulatory radionuclide monitoring system: The relationship between vascular endothelial function and cardiac response in patients with ischemic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Akima, Takashi; Tabata, Hirotsugu [Self-Defense Forces Central Hospital, Tokyo (Japan); Takase, Bonpei [National Defense Medical Coll., Tokorozawa, Saitama (Japan)] [and others

    2002-02-01

    The relationship in the title was studied with a new type ambulatory radionuclide monitoring system. Subjects were 12 male patients with ischemic heart diseases. After cardiac scintigraphy at rest of {sup 99m}Tc-human serum albumin (740 MBq) with GE Mirenium, patients wore the C-VEST jacket (Capintec medset cardiolight), which consisted from 2 radioactivity detectors and Holter ECG recorder, and underwent the cardiopulmonary stress testing with Treadmill Ramp exercise to evaluate the anaerobic threshold (AT), VO{sub 2}, left ventricular ejection flow (EF) and stroke volume (SV). Vascular endothelial function was recorded by ultrasonography of brachial artery by monitoring the flow-mediated dilation (FD). Mean EF at rest was 56% and there was no relationship between VO{sub 2} at rest or exercise and FD. However, the relationship between FD and change of SV or EF from rest to AT was recognized and thus FD was suggested to participate in cardiac function change at exercise of those patients. (K.H.)

  9. Human Chorionic Gonadotropin Protects Vascular Endothelial Cells from Oxidative Stress by Apoptosis Inhibition, Cell Survival Signalling Activation and Mitochondrial Function Protection

    Directory of Open Access Journals (Sweden)

    Daniela Surico

    2015-07-01

    Full Text Available Background/Aim: Previous reports have made it hypothetically possible that human chorionic gonadotropin (hCG could protect against the onset of pregnancy-related pathological conditions by acting as an antioxidant. In the present study we planned to examine the effects of hCG against oxidative stress in human umbilical vein endothelial cells (HUVEC. Methods: HUVEC were subjected to peroxidation by hydrogen peroxide. The modulation of nitric oxide (NO release by hCG and its effects on cell viability, glutathione (GSH levels, mitochondrial membrane potential and mitochondrial transition pore opening (MPTP were examined by specific dyes. Endothelial and inducible NO synthase (eNOS and iNOS, Akt and extracellular -signal-regulated kinases 1/2 (ERK1/2 activation and markers of apoptosis were analyzed by Western Blot. Results: In HUVEC, hCG reduced NO release by modulating eNOS and iNOS. Moreover, hCG protected HUVEC against oxidative stress by preventing GSH reduction and apoptosis, by maintaining Akt and ERK1/2 activation and by keeping mitochondrial function. Conclusion: The present results have for the first time shown protective effects exerted by hCG on vascular endothelial function, which would be achieved by modulation of NO release, antioxidant and antiapoptotic actions and activation of cell survival signalling. These findings could have clinical implications in the management of pregnancy-related disorders.

  10. Functional assessment of human coding mutations affecting skin pigmentation using zebrafish.

    Directory of Open Access Journals (Sweden)

    Zurab R Tsetskhladze

    Full Text Available A major challenge in personalized medicine is the lack of a standard way to define the functional significance of the numerous nonsynonymous, single nucleotide coding variants that are present in each human individual. To begin to address this problem, we have used pigmentation as a model polygenic trait, three common human polymorphisms thought to influence pigmentation, and the zebrafish as a model system. The approach is based on the rescue of embryonic zebrafish mutant phenotypes by "humanized" zebrafish orthologous mRNA. Two hypomorphic polymorphisms, L374F in SLC45A2, and A111T in SLC24A5, have been linked to lighter skin color in Europeans. The phenotypic effect of a second coding polymorphism in SLC45A2, E272K, is unclear. None of these polymorphisms had been tested in the context of a model organism. We have confirmed that zebrafish albino fish are mutant in slc45a2; wild-type slc45a2 mRNA rescued the albino mutant phenotype. Introduction of the L374F polymorphism into albino or the A111T polymorphism into slc24a5 (golden abolished mRNA rescue of the respective mutant phenotypes, consistent with their known contributions to European skin color. In contrast, the E272K polymorphism had no effect on phenotypic rescue. The experimental conclusion that E272K is unlikely to affect pigmentation is consistent with a lack of correlation between this polymorphism and quantitatively measured skin color in 59 East Asian humans. A survey of mutations causing human oculocutaneous albinism yielded 257 missense mutations, 82% of which are theoretically testable in zebrafish. The developed approach may be extended to other model systems and may potentially contribute to our understanding the functional relationships between DNA sequence variation, human biology, and disease.

  11. Role of Affective Self-Regulatory Efficacy in Diverse Spheres of Psychosocial Functioning.

    Science.gov (United States)

    Bandura, Albert; Caprara, Gian Vittorio; Barbaranelli, Claudio; Gerbino, Maria; Pastorelli, Concetta

    2003-01-01

    Examined influence of perceived self-efficacy for affect regulation with older adolescents. Found that self-efficacy to regulate affect related to high efficacy to manage academic development, resist social pressures for antisocial activities, and engage with empathy in others' emotional experiences. Perceived self-efficacy for affect regulation…

  12. Suppression of circulating free fatty acids with acipimox in chronic heart failure patients changes whole body metabolism but does not affect cardiac function.

    Science.gov (United States)

    Halbirk, Mads; Nørrelund, Helene; Møller, Niels; Schmitz, Ole; Gøtzsche, Liv; Nielsen, Roni; Nielsen-Kudsk, Jens Erik; Nielsen, Søren Steen; Nielsen, Torsten Toftegaard; Eiskjær, Hans; Bøtker, Hans Erik; Wiggers, Henrik

    2010-10-01

    Circulating free fatty acids (FFAs) may worsen heart failure (HF) due to myocardial lipotoxicity and impaired energy generation. We studied cardiac and whole body effects of 28 days of suppression of circulating FFAs with acipimox in patients with chronic HF. In a randomized double-blind crossover design, 24 HF patients with ischemic heart disease [left ventricular ejection fraction: 26 ± 2%; New York Heart Association classes II (n = 13) and III (n = 5)] received 28 days of acipimox treatment (250 mg, 4 times/day) and placebo. Left ventricular ejection fraction, diastolic function, tissue-Doppler regional myocardial function, exercise capacity, noninvasive cardiac index, NH(2)-terminal pro-brain natriuretic peptide (NT-pro-BNP), and whole body metabolic parameters were measured. Eighteen patients were included for analysis. FFAs were reduced by 27% in the acipimox-treated group [acipimox vs. placebo (day 28-day 0): -0.10 ± 0.03 vs. +0.01 ± 0.03 mmol/l, P < 0.01]. Glucose and insulin levels did not change. Acipimox tended to increase glucose and decrease lipid utilization rates at the whole body level and significantly changed the effect of insulin on substrate utilization. The hyperinsulinemic euglycemic clamp M value did not differ. Global and regional myocardial function did not differ. Exercise capacity, cardiac index, systemic vascular resistance, and NT-pro-BNP were not affected by treatment. In conclusion, acipimox caused minor changes in whole body metabolism and decreased the FFA supply, but a long-term reduction in circulating FFAs with acipimox did not change systolic or diastolic cardiac function or exercise capacity in patients with HF.

  13. Developing a function impairment measure for children affected by political violence: a mixed methods approach in Indonesia

    NARCIS (Netherlands)

    Tol, W.A.; Komproe, I.H.; Jordans, M.J.D.; Susanty, D.; de Jong, J.T.V.M.

    2011-01-01

    Objective: Practitioners in political violence-affected settings would benefit from rating scales that assess child function impairment in a reliable and valid manner when designing and evaluating interventions. We developed a procedure to construct child function impairment rating scales using reso

  14. Effect of moderate- versus high-intensity exercise on vascular function, biomarkers and quality of life in heart transplant recipients

    DEFF Research Database (Denmark)

    Dall, Christian H; Gustafsson, Finn; Christensen, Stefan B

    2015-01-01

    .001). The physical component score of the 36-item Short Form (SF-36) was increased significantly in HIIT patients (p = 0.02) and borderline increased in CON patients (p = 0.07), whereas there was no significant effect of exercise on the mental component. Depression score decreased significantly in HIIT patients (p...... by a 5-month washout and crossover. Outcomes included endothelial function, arterial stiffness, biomarkers, HRQoL and markers of anxiety and depression. RESULTS: Sixteen HTx recipients (mean age 52 years, 75% male) completed the study. HIIT increased VO2peak more than CON (between-group difference, p

  15. Prospective associations between forms and functions of aggression and social and affective processes during early childhood.

    Science.gov (United States)

    Ostrov, Jamie M; Murray-Close, Dianna; Godleski, Stephanie A; Hart, Emily J

    2013-09-01

    The central goal of this study was to examine the prospective associations between forms (i.e., physical and relational) and functions (i.e., proactive and reactive) of aggressive behavior with social (i.e., peer rejection) and affective (i.e., anger, emotion regulation skills) processes during early childhood (N = 96, mean age = 42.80 months, SD = 7.57). A cross-lagged path analysis revealed that proactive relational aggression was uniquely associated with decreases in peer rejection, whereas reactive relational aggression was associated with increases in peer rejection over time. Proactive relational aggression predicted decreases in anger, whereas reactive relational aggression tended to be associated with increases in anger. Proactive relational aggression uniquely predicted increases in emotion regulation skills, whereas reactive relational aggression tended to be associated with decreases in emotion regulation skills over time. Finally, anger was significantly associated with increases in several subtypes of aggressive behavior. In sum, the findings provide further support for the distinction between subtypes of aggressive behavior in young children.

  16. Novel function of perforin in negatively regulating CD4+T cell activation by affecting calcium signaling

    Institute of Scientific and Technical Information of China (English)

    Enguang Bi; Kairui Mao; Jia Zou; Yuhan Zheng; Bing Sun; Chunjian Huang; Yu Hu; Xiaodong Wu; Weiwen Deng; Guomei Lin; Zhiduo Liu; Lin Tian; Shuhui Sun

    2009-01-01

    Perforin is a pore-forming protein engaged mainly in mediating target T cell death and is employed by cytotoxic Tlymphocytes (CTLs) and natural killer cells. However, whether it also plays a role in conventional CD4+ T cell func-tion remains unclear. Here we report that in perforin-deficient (PKO) mice, CD4+ T cells are hyperproliferative in response to T cell receptor (TCR) stimulation. This feature of hyperproliferation is accompanied by the enhancement both in cell division and in IL-2 secretion. It seems that the perforin deficiency does not influence T cell development in thymus spleen and lymph node. In vivo, perforin deficiency results in increased antigen-specific T cell prolifera-tion and antibody production. Furthermore, PKO mice are more susceptible to experimental autoimmune uveitis. To address the molecular mechanism, we found that after TCR stimulation, CD44 T cells from PKO mice display an increased intracellular calcium flux and subsequently enhance activation of transcription factor NFATI. Our results indicate that perforin plays a negative role in regulating CD4+ T cell activation and immune response by affecting TCR-dependent Ca2+ signaling.

  17. Identification of archaeal proteins that affect the exosome function in vitro

    Directory of Open Access Journals (Sweden)

    Palhano Fernando L

    2010-05-01

    Full Text Available Abstract Background The archaeal exosome is formed by a hexameric RNase PH ring and three RNA binding subunits and has been shown to bind and degrade RNA in vitro. Despite extensive studies on the eukaryotic exosome and on the proteins interacting with this complex, little information is yet available on the identification and function of archaeal exosome regulatory factors. Results Here, we show that the proteins PaSBDS and PaNip7, which bind preferentially to poly-A and AU-rich RNAs, respectively, affect the Pyrococcus abyssi exosome activity in vitro. PaSBDS inhibits slightly degradation of a poly-rA substrate, while PaNip7 strongly inhibits the degradation of poly-A and poly-AU by the exosome. The exosome inhibition by PaNip7 appears to depend at least partially on its interaction with RNA, since mutants of PaNip7 that no longer bind RNA, inhibit the exosome less strongly. We also show that FITC-labeled PaNip7 associates with the exosome in the absence of substrate RNA. Conclusions Given the high structural homology between the archaeal and eukaryotic proteins, the effect of archaeal Nip7 and SBDS on the exosome provides a model for an evolutionarily conserved exosome control mechanism.

  18. Personality, clinical features, and test instructions can affect executive functions in Eating Disorders.

    Science.gov (United States)

    Pignatti, Riccardo; Bernasconi, Valentina

    2013-04-01

    Cognitive deficits in Eating Disorders have been related to the executive function domain. Yet, to date, only few works investigated the relationship between neuropsychological and clinical issues, and these studies were separately conducted either on Anorexia Nervosa (AN) or Bulimia Nervosa (BN). In this study, three groups of AN, BN and matched controls were administered the Trail Making Test, the Wisconsin Card Sorting Test, and the Hayling Sentence Completion Test, in addition to personality and clinical assessments (Temperament and Character Inventory, SCL-90-R, EDI-2). Results from AN indicated a relationship between cognitive rigidity and fixed psychological traits. Conversely, BN showed broader correlations among slowness, inhibition, and psychopathology-state indexes, confirming the clear relation published in the literature. We also hypothesize that task peculiar characteristics can affect high-order attentional activities in Eating Disorders. In fact, these patients do not differ from controls when the examiner provides overt instruction and run-in examples, but they can find serious difficulties when the correct rule is to be derived and modified from feedbacks during the test, as in the Wisconsin Card Sorting Test. Perfectionist stable traits support this hypothesis, especially in AN, as excessive cognitive control can either improve or damage set-shifting and decision-making procedures.

  19. Naloxonazine, an Amastigote-Specific Compound, Affects Leishmania Parasites through Modulation of Host-Encoded Functions

    Science.gov (United States)

    Vanhollebeke, Benoit; Caljon, Guy; Wolfe, Alan R.; McKerrow, James; Dujardin, Jean-Claude

    2016-01-01

    Host-directed therapies (HDTs) constitute promising alternatives to traditional therapy that directly targets the pathogen but is often hampered by pathogen resistance. HDT could represent a new treatment strategy for leishmaniasis, a neglected tropical disease caused by the obligate intracellular parasite Leishmania. This protozoan develops exclusively within phagocytic cells, where infection relies on a complex molecular interplay potentially exploitable for drug targets. We previously identified naloxonazine, a compound specifically active against intracellular but not axenic Leishmania donovani. We evaluated here whether this compound could present a host cell-dependent mechanism of action. Microarray profiling of THP-1 macrophages treated with naloxonazine showed upregulation of vATPases, which was further linked to an increased volume of intracellular acidic vacuoles. Treatment of Leishmania-infected macrophages with the vATPase inhibitor concanamycin A abolished naloxonazine effects, functionally demonstrating that naloxonazine affects Leishmania amastigotes indirectly, through host cell vacuolar remodeling. These results validate amastigote-specific screening approaches as a powerful way to identify alternative host-encoded targets. Although the therapeutic value of naloxonazine itself is unproven, our results further demonstrate the importance of intracellular acidic compartments for host defense against Leishmania, highlighting the possibility of targeting this host cell compartment for anti-leishmanial therapy. PMID:28036391

  20. Initial evidence demonstrating the association between the vascular status in surgically resected renal parenchymal pathology and sexual function.

    Science.gov (United States)

    Sejima, T; Iwamoto, H; Masago, T; Morizane, S; Yao, A; Umekita, Y; Honda, M; Takenaka, A

    2015-01-01

    Our goal is to evaluate the association between histopathology of glomerulosclerosis (GS) and atherosclerosis (AS) in the nephrectomized normal parenchyma together with patients' background, and erectile dysfunction (ED) of patients treated with radical nephrectomy (RN) for renal cell carcinoma (RCC). ED was assessed with the International Index of Erectile Function in 65 patients who were less than age 70 years at the time of questionnaire. Glomeruli status was assessed by the extent of global GS. AS was graded based on lumen occlusion and frequency of involvement. Patients' backgrounds included any comorbidities, post-RN renal insufficiency, tumor pathology, demographics and social status. The presence of diabetes mellitus and lack of a spouse were independent predictors for severe ED, whereas G0/1 AS was an independent predictor for mild/no ED. The extent of global GS was significantly lower in patients with mild/no ED than in other patients. Our study represents the first report identifying healthy arterial status in the renal parenchyma as a significant indicator of favorable erectile function and that the evaluation of AS severity is not a superior indicator of severe ED in the presence of comorbidities or social status among patients treated with RN.

  1. Functional Analysis of Autophagy Genes via Agrobacterium-Mediated Transformation in the Vascular Wilt Fungus Verticillium dahliae

    Institute of Scientific and Technical Information of China (English)

    Lei Zhou; Jun Zhao; Wangzhen Guo; Tianzhen Zhang

    2013-01-01

    Autophagy is a widely conserved intracellular process for degradation and recycling of proteins,organelles and cytoplasm in eukaryotic organisms and is now emerging as an important process in foliar infection by many plant pathogenic fungi.However,the role of autophagy in soil-borne fungal physiology and infection biology is poorly understood.Here,we report the establishment of an Agrobacterium tumefaciens-mediated transformation (ATMT) system and its application to investigate two autophagy genes,VdATG8 and VdATG12,by means of targeted gene replacement and complementadon.Transformation of a cotton-infecting Verticilliun dahliae strain Vd8 with a novel binary vector pCOM led to the production of 384 geneticin-resistant transformants per 1 × 106 conidia.V.dahliae mutants lacking either VdATG8 or VdATG12 exhibited reduced conidiation and impaired aerial hyphae production.Disease development on Arabidopsis plants was slightly delayed when inoculated with VdATG8 or VdATG12 gene deletion mutants,compared with the wildtype and gene complemented strains.Surprisingly,in vitro inoculation with unimpaired roots revealed that the abilities of root invasion were not affected in gene deletion mutants.These results indicate that autophagy is necessary for aerial hyphae development and plant colonization but not for root infection in V.dahliae.

  2. Functional analysis of autophagy genes via Agrobacterium-mediated transformation in the vascular Wilt fungus Verticillium dahliae.

    Science.gov (United States)

    Zhou, Lei; Zhao, Jun; Guo, Wangzhen; Zhang, Tianzhen

    2013-08-20

    Autophagy is a widely conserved intracellular process for degradation and recycling of proteins, organelles and cytoplasm in eukaryotic organisms and is now emerging as an important process in foliar infection by many plant pathogenic fungi. However, the role of autophagy in soil-borne fungal physiology and infection biology is poorly understood. Here, we report the establishment of an Agrobacterium tumefaciens-mediated transformation (ATMT) system and its application to investigate two autophagy genes, VdATG8 and VdATG12, by means of targeted gene replacement and complementation. Transformation of a cotton-infecting Verticillium dahliae strain Vd8 with a novel binary vector pCOM led to the production of 384 geneticin-resistant transformants per 1 × 10(6) conidia. V. dahliae mutants lacking either VdATG8 or VdATG12 exhibited reduced conidiation and impaired aerial hyphae production. Disease development on Arabidopsis plants was slightly delayed when inoculated with VdATG8 or VdATG12 gene deletion mutants, compared with the wild-type and gene complemented strains. Surprisingly, in vitro inoculation with unimpaired roots revealed that the abilities of root invasion were not affected in gene deletion mutants. These results indicate that autophagy is necessary for aerial hyphae development and plant colonization but not for root infection in V. dahliae.

  3. Expression of a ferredoxin-dependent glutamate synthase gene in mesophyll and vascular cells and functions of the enzyme in ammonium assimilation in Nicotiana tabacum (L.).

    Science.gov (United States)

    Feraud, Magali; Masclaux-Daubresse, Céline; Ferrario-Méry, Sylvie; Pageau, Karine; Lelandais, Maud; Ziegler, Chr