WorldWideScience

Sample records for nos stn 50-508

  1. 31 CFR 50.8 - Procedure for requesting determinations of controlling influence.

    Science.gov (United States)

    2010-07-01

    ... determinations of controlling influence. 50.8 Section 50.8 Money and Finance: Treasury Office of the Secretary of... determinations of controlling influence. (a) An insurer or insurers not having control over another insurer under... controlling influence under § 50.5(c)(4)(i) through (iv) or otherwise to request a determination...

  2. 22 CFR 50.8 - Certification of Report of Birth Abroad of a United States Citizen.

    Science.gov (United States)

    2010-04-01

    ... United States Citizen. 50.8 Section 50.8 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS... Certification of Report of Birth Abroad of a United States Citizen. At any time subsequent to the issuance of a Consular Report of Birth Abroad of a Citizen of the United States of America, when requested and upon...

  3. 40 CFR 50.8 - National primary ambient air quality standards for carbon monoxide.

    Science.gov (United States)

    2010-07-01

    ... (CONTINUED) AIR PROGRAMS NATIONAL PRIMARY AND SECONDARY AMBIENT AIR QUALITY STANDARDS § 50.8 National primary ambient air quality standards for carbon monoxide. (a) The national primary ambient air quality standards... 40 Protection of Environment 2 2010-07-01 2010-07-01 false National primary ambient air...

  4. Deformation behavior after stress-induced martensite transformation in a Ti-50.8 at.% Ni alloy

    Directory of Open Access Journals (Sweden)

    Wang Xiebin

    2015-01-01

    Full Text Available In this study, the deformation behavior of a Ti-50.8 at.% Ni thin wire, which was subjected to different heat treatments, was investigated by means of uniaxial tensile tests. Considerable ductility (tensile elongation >50% and a large variation of the stress-strain relations are observed after different heat treatments, especially in the stage after the stress-induced martensite transformation plateau. A possible explanation for the observed phenomenon is discussed in this work.

  5. STN-LCD技术的发展%Progress of STN-LCD Technology

    Institute of Scientific and Technical Information of China (English)

    凌志华

    2002-01-01

    介绍了目前人们对改善STN-LCD特性所取得的一些研究进展,主要包括反射式STN-LCD彩色显示,高分辨率STN-LCD用液晶材料,彩色STN-LCD用彩色滤光膜,以及STN-LCD用光学膜,如偏振片、相位差补偿膜等.

  6. Effect of warm rolling on the martensite transformation temperatures, shape memory effect, and superelasticity in Ti49.2Ni50.8 alloy

    Science.gov (United States)

    Lotkov, Aleksander; Zhapova, Dorzhima; Grishkov, Victor; Cherniavsky, Alexander; Timkin, Victor

    2016-11-01

    The paper presents research data demonstrating the effect of warm caliber rolling on the martensite transformation temperatures, shape memory effect, and superelasticity in Ti49.2Ni50.8 (at %). The experimental values of inelastic strain in coarse-grained and microcrystalline Ti49.2Ni50.8 (at %) specimens exceed the theoretical limit of recoverable strain or maximum lattice strain for TiNi-based alloys.

  7. Reflective color STN-LCD technologies

    Science.gov (United States)

    Fujita, Shingo; Yamaguchi, Hisanori; Mizuno, Hiroaki; Ohtani, Toshiya; Sekime, Tomoaki; Hatanaka, Takayuki; Ogawa, Tetsu

    1998-04-01

    Reflective color STN-LCDs should be one of the most promising devices for mobile business tools (MBT), because the demand such as low cost, low power consumption, light weight and compact size is especially strong for this application. A reflective color STN-LCD with a single polarizer and double retardation films has been investigated. The double retardation films arranged in front of LC-layer enabled the LCD to contain reflective electrodes inside the panel. This configuration achieves the bright image with no parallax. A new construction of a reflective STN-LCD with a single polarizer has been decided by means of our own method in which the color difference (Delta) E* as the optimizing parameter has been used. Further, RGB color filters has been newly designed for our reflective LCD, and the aluminum (Al) layer has been introduced as reflective electrodes. As a result, we have realized 7.8-in.-diagonal refractive color STN-LCD(640 by 480) which has 15% reflectance, 1:14 contrast ratio, 4096 color capability and the sufficient color gamut. It has been confirmed that the single polarizer reflective color STN-LCD has sufficient enough performance for MBT use. We believe that it will be a key device for this application.

  8. Acoustic analysis of aft noise reduction techniques measured on a subsonic tip speed 50.8 cm (twenty inch) diameter fan. [quiet engine program

    Science.gov (United States)

    Stimpert, D. L.; Clemons, A.

    1977-01-01

    Sound data which were obtained during tests of a 50.8 cm diameter, subsonic tip speed, low pressure ratio fan were analyzed. The test matrix was divided into two major investigations: (1) source noise reduction techniques; and (2) aft duct noise reduction with acoustic treatment. Source noise reduction techniques were investigated which include minimizing second harmonic noise by varying vane/blade ratio, variation in spacing, and lowering the Mach number through the vane row to lower fan broadband noise. Treatment in the aft duct which includes flow noise effects, faceplate porosity, rotor OGV treatment, slant cell treatment, and splitter simulation with variable depth on the outer wall and constant thickness treatment on the inner wall was investigated. Variable boundary conditions such as variation in treatment panel thickness and orientation, and mixed porosity combined with variable thickness were examined. Significant results are reported.

  9. High Precision Metrology on the Ultra-Lightweight W 50.8 cm f/1.25 Parabolic SHARPI Primary Mirror using a CGH Null Lens

    Science.gov (United States)

    Antonille, Scott

    2004-01-01

    For potential use on the SHARPI mission, Eastman Kodak has delivered a 50.8cm CA f/1.25 ultra-lightweight UV parabolic mirror with a surface figure error requirement of 6nm RMS. We address the challenges involved in verifying and mapping the surface error of this large lightweight mirror to +/-3nm using a diffractive CGH null lens. Of main concern is removal of large systematic errors resulting from surface deflections of the mirror due to gravity as well as smaller contributions from system misalignment and reference optic errors. We present our efforts to characterize these errors and remove their wavefront error contribution in post-processing as well as minimizing the uncertainty these calculations introduce. Data from Kodak and preliminary measurements from NASA Goddard will be included.

  10. Salmonella enterotoxin (Stn regulates membrane composition and integrity

    Directory of Open Access Journals (Sweden)

    Masayuki Nakano

    2012-07-01

    The mechanism of action of Salmonella enterotoxin (Stn as a virulence factor in disease is controversial. Studies of Stn have indicated both positive and negative effects on Salmonella virulence. In this study, we attempted to evaluate Stn function and its effects on Salmonella virulence. To investigate Stn function, we first performed in vitro and in vivo analysis using mammalian cells and a murine ileal loop model. In these systems, we did not observe differences in virulence phenotypes between wild-type Salmonella and an stn gene-deleted mutant. We next characterized the phenotypes and molecular properties of the mutant strain under various in vitro conditions. The proteomic profiles of the total cell membrane protein fraction differed between wild type and mutant in that there was an absence of a protein in the mutant strain, which was identified as OmpA. By far-western blotting, OmpA was found to interact directly with Stn. To verify this result, the morphology of Salmonella was examined by transmission electron microscopy, with OmpA localization being analyzed by immunogold labeling. Compared with wild-type Salmonella, the mutant strain had a different pole structure and a thin periplasmic space; OmpA was not seen in the mutant. These results indicate that Stn, via regulation of OmpA membrane localization, functions in the maintenance of membrane composition and integrity.

  11. The Student Telescope Network (STN) experiment

    Science.gov (United States)

    Hannahoe, Ryan M.; Stencel, Robert E.; Bisque, Steve; Rice, Mike

    2003-02-01

    support of this effort, and acknowleedge in-kind support from the estate of William Herschel Womble. Details at website www.du.edu/~rstencel/stn.htm.

  12. Comparison of weight changes following unilateral and staged bilateral STN DBS for advanced PD

    OpenAIRE

    Lee, Eric M; Kurundkar, Ashish; Cutter, Gary R.; Huang, He; Guthrie, Barton L.; Watts, Ray L; Walker, Harrison C.

    2011-01-01

    Unilateral and bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson's disease (PD) result in weight gain in the initial postoperative months, but little is known about the changes in weight following unilateral and staged bilateral STN DBS over longer time intervals. A case–control comparison evaluated weight changes over 2 years in 43 consecutive unilateral STN DBS patients, among whom 25 elected to undergo staged bilateral STN DBS, and 21 age-matched and disease sever...

  13. Improved dithering algorithms and circuit implementing for STN-LCD

    Institute of Scientific and Technical Information of China (English)

    FU Xian-cheng; ZOU Xue-cheng; LEI Jian-ming

    2006-01-01

    This article proposes a creative brightness average method to improve the traditional dithering algorithm for super twisted nematic-liquid crystal display (STN-LCD).This method restrains the flicker and crosstalk phenomena by avoiding the simultaneous turning on or turning off between adjacent pixels in the same frame. It costs little hardware to realize the brightness average circuit in the liquid crystal display (LCD) controller, without increasing the complexity of STN-LCD driver circuit. The experimental results show that when the frame frequency is 60 Hz, the monochrome image adds up to 64 gray levels, while the multicolor image adds up to 643= 262 144 colors. Meanwhile, the power consumption of the prototype is only 3 317 mW. In short, the brightness average circuit can restrain the phenomena of flicker in high efficiency, and can remarkedly improve the gray and multicolor effect for STN-LCD without increasing the frame frequency, which leads to an apparent decrease in the power consumption.

  14. Special Features of the Two-Way Shape Memory Effect in Stress-Assisted Aged Ti49.2Ni50.8 Single Crystals Oriented Along the [111] Direction

    Science.gov (United States)

    Panchenko, E. Yu.; Osipovich, K. S.; Chumlyakov, Yu. I.; Eftifeeva, A. S.; Maier, H.

    2017-04-01

    On the example of Ti49.2Ni50.8 (at.%) single crystals oriented along the [111]B2 directions, influence of aging at 673 and 823 K for 1 h under tensile and compressive load of 150 MPa was studied on the magnitude and sign of the two-way shape memory effect (TWSME). It is experimentally shown that the TWSME sign (tension/compression) and magnitude are determined by the size of disperse Ti3Ni4 particles, the character of interaction of the disperse particles with martensitic crystals, and the direction of external load application during aging. For one variant of nanodimensional Ti3Ni4 particles (d stress-assisted aging at 673 K for 1 h), the TWSME makes 1.3-1.7%, and the TWSME sign is independent of the direction (tension/compression) of stress application during aging: the sample size increases upon cooling and is restored upon heating. In the Ti49.2Ni50.8 [111]B2 single crystals (with particle size d = 390 nm) during stressassisted aging at 823 K for 1 h, the TWSME magnitude and sign are determined by the direction of external loading application during aging: aging under compressive loading leads to tensile TWSME with reversible strain ɛTWSME = 2.4%, and aging under tensile loading leads to compressive TWSME (ɛTWSME = -1.2%).

  15. 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

  16. Stn1-Ten1 is an Rpa2-Rpa3-like complex at telomeres

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jia; Yu, Eun Young; Yang, Yuting; Confer, Laura A; Sun, Steven H; Wan, Ke; Lue, Neal F; Lei, Ming; (Weill); (Michigan-Med)

    2010-09-02

    In budding yeast, Cdc13, Stn1, and Ten1 form a heterotrimeric complex (CST) that is essential for telomere protection and maintenance. Previous bioinformatics analysis revealed a putative oligonucleotide/oligosaccharide-binding (OB) fold at the N terminus of Stn1 (Stn1N) that shows limited sequence similarity to the OB fold of Rpa2, a subunit of the eukaryotic ssDNA-binding protein complex replication protein A (RPA). Here we present functional and structural analyses of Stn1 and Ten1 from multiple budding and fission yeast. The crystal structure of the Candida tropicalis Stn1N complexed with Ten1 demonstrates an Rpa2N-Rpa3-like complex. In both structures, the OB folds of the two components pack against each other through interactions between two C-terminal helices. The structure of the C-terminal domain of Saccharomyces cerevisiae Stn1 (Stn1C) was found to comprise two related winged helix-turn-helix (WH) motifs, one of which is most similar to the WH motif at the C terminus of Rpa2, again supporting the notion that Stn1 resembles Rpa2. The crystal structure of the fission yeast Schizosaccharomyces pombe Stn1N-Ten1 complex exhibits a virtually identical architecture as the C. tropicalis Stn1N-Ten1. Functional analyses of the Candida albicans Stn1 and Ten1 proteins revealed critical roles for these proteins in suppressing aberrant telomerase and recombination activities at telomeres. Mutations that disrupt the Stn1-Ten1 interaction induce telomere uncapping and abolish the telomere localization of Ten1. Collectively, our structural and functional studies illustrate that, instead of being confined to budding yeast telomeres, the CST complex may represent an evolutionarily conserved RPA-like telomeric complex at the 3' overhangs that works in parallel with or instead of the well-characterized POT1-TPP1/TEBP{alpha}-{beta} complex.

  17. STN-stimulation in Parkinson's disease restores striatal inhibition of thalamocortical projection

    DEFF Research Database (Denmark)

    Geday, Jacob; Østergaard, Karen; Johnsen, Erik;

    2009-01-01

    To test the hypothesis that deep brain stimulation of the subthalamic nucleus (STN) restores the inhibitory output to the striatothalamocortical loop in Parkinson's disease, we obtained functional brain images of blood flow in 10 STN-stimulated patients with Parkinson's disease. Patients were...

  18. Comparison of weight changes following unilateral and staged bilateral STN DBS for advanced PD.

    Science.gov (United States)

    Lee, Eric M; Kurundkar, Ashish; Cutter, Gary R; Huang, He; Guthrie, Barton L; Watts, Ray L; Walker, Harrison C

    2011-09-01

    Unilateral and bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson's disease (PD) result in weight gain in the initial postoperative months, but little is known about the changes in weight following unilateral and staged bilateral STN DBS over longer time intervals. A case-control comparison evaluated weight changes over 2 years in 43 consecutive unilateral STN DBS patients, among whom 25 elected to undergo staged bilateral STN DBS, and 21 age-matched and disease severity matched PD controls without DBS. Regression analyses incorporating age, gender, and baseline weight in case or control were conducted to assess weight changes 2 years after the initial unilateral surgery. Unilateral STN DBS and staged bilateral STN DBS patients gained 3.9 ± 2.0 kg and 5.6 ± 2.1 kg versus their preoperative baseline weight (P weight gain in staged bilateral STN DBS patients versus unilateral patients, we found no evidence for an equivalent or synergistic increase in body weight following placement of the second DBS electrode.

  19. Stn1 is critical for telomere maintenance and long-term viability of somatic human cells.

    Science.gov (United States)

    Boccardi, Virginia; Razdan, Neetu; Kaplunov, Jessica; Mundra, Jyoti J; Kimura, Masayuki; Aviv, Abraham; Herbig, Utz

    2015-06-01

    Disruption of telomere maintenance pathways leads to accelerated entry into cellular senescence, a stable proliferative arrest that promotes aging-associated disorders in some mammals. The budding yeast CST complex, comprising Cdc13, Stn1, and Ctc1, is critical for telomere replication, length regulation, and end protection. Although mammalian homologues of CST have been identified recently, their role and function for telomere maintenance in normal somatic human cells are still incompletely understood. Here, we characterize the function of human Stn1 in cultured human fibroblasts and demonstrate its critical role in telomere replication, length regulation, and function. In the absence of high telomerase activity, shRNA-mediated knockdown of hStn1 resulted in aberrant and fragile telomeric structures, stochastic telomere attrition, increased telomere erosion rates, telomere dysfunction, and consequently accelerated entry into cellular senescence. Oxidative stress augmented the defects caused by Stn1 knockdown leading to almost immediate cessation of cell proliferation. In contrast, overexpression of hTERT suppressed some of the defects caused by hStn1 knockdown suggesting that telomerase can partially compensate for hStn1 loss. Our findings reveal a critical role for human Stn1 in telomere length maintenance and function, supporting the model that efficient replication of telomeric repeats is critical for long-term viability of normal somatic mammalian cells.

  20. Time-Based Dithering Algorithm and Frame Rate Control Technique for STN LCD Controller

    Institute of Scientific and Technical Information of China (English)

    LEIJianming; ZOUXuechen

    2004-01-01

    Time-based dithering algorithm and Frame rate control (FRC) technique applied to the STN liquid crystal display controller are presented. The dithering unit performs time-based dithering algorithm on pixel data to advantageously increase smoothness of an image displayed. The frame rate control unit is responsive to the dithering unit and performs frame rate controlling to generate more gray-shades, which may reduce flicker and visual artifacts. Results show that the gray shades displayed on images can be up to 256 for monochrome STN LCD panels or 2563 colors for color STN LCD panels respectively by using timebased dithering algorithm and frame rate control technique if each encoded pixel data is 8 bits. The images displayed on the STN liquid crystal display can get desirable grayshades and very little flicker and visual artifacts.

  1. Articulatory Changes in Vowel Production following STN DBS and Levodopa Intake in Parkinson’s Disease

    National Research Council Canada - National Science Library

    Martel Sauvageau, Vincent; Roy, Johanna-Pascale; Cantin, Léo; Prud’Homme, Michel; Langlois, Mélanie; Macoir, Joël

    2015-01-01

    ...) and levodopa intake on vowel articulation in dysarthric speakers with Parkinson’s disease (PD). Methods. Vowel articulation was assessed in seven Quebec French speakers diagnosed with idiopathic PD who underwent STN DBS...

  2. Articulatory Changes in Vowel Production following STN DBS and Levodopa Intake in Parkinson's Disease

    National Research Council Canada - National Science Library

    Martel Sauvageau, Vincent; Roy, Johanna-Pascale; Cantin, Léo; Prud'Homme, Michel; Langlois, Mélanie; Macoir, Joël

    2015-01-01

    ...) and levodopa intake on vowel articulation in dysarthric speakers with Parkinson's disease (PD). Methods. Vowel articulation was assessed in seven Quebec French speakers diagnosed with idiopathic PD who underwent STN DBS...

  3. Articulatory Changes in Vowel Production following STN DBS and Levodopa Intake in Parkinson’s Disease

    OpenAIRE

    Vincent Martel Sauvageau; Johanna-Pascale Roy; Léo Cantin; Michel Prud’Homme; Mélanie Langlois; Joël Macoir

    2015-01-01

    Purpose. To investigate the impact of deep brain stimulation of the subthalamic nucleus (STN DBS) and levodopa intake on vowel articulation in dysarthric speakers with Parkinson's disease (PD). Methods. Vowel articulation was assessed in seven Quebec French speakers diagnosed with idiopathic PD who underwent STN DBS. Assessments were conducted on- and off-medication, first prior to surgery and then 1 year later. All recordings were made on-stimulation. Vowel articulation was measured using ac...

  4. The Application and Development Tendency of Color STN-LCD Both Domestically and Abroad%国内外彩色STN-LCD的应用及发展动态

    Institute of Scientific and Technical Information of China (English)

    孙政民

    2002-01-01

    本文介绍了彩色STN-LCD的性能、特点及与其他显示器件的比较,阐述了彩色STN-LCD的应用、国内外发展的动态以及未来变化的趋势.文中也对国内发展彩色STN-LCD所面临的问题进行了讨论.

  5. Articulatory Changes in Vowel Production following STN DBS and Levodopa Intake in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Vincent Martel Sauvageau

    2015-01-01

    Full Text Available Purpose. To investigate the impact of deep brain stimulation of the subthalamic nucleus (STN DBS and levodopa intake on vowel articulation in dysarthric speakers with Parkinson’s disease (PD. Methods. Vowel articulation was assessed in seven Quebec French speakers diagnosed with idiopathic PD who underwent STN DBS. Assessments were conducted on- and off-medication, first prior to surgery and then 1 year later. All recordings were made on-stimulation. Vowel articulation was measured using acoustic vowel space and formant centralization ratio. Results. Compared to the period before surgery, vowel articulation was reduced after surgery when patients were off-medication, while it was better on-medication. The impact of levodopa intake on vowel articulation changed with STN DBS: before surgery, levodopa impaired articulation, while it no longer had a negative effect after surgery. Conclusions. These results indicate that while STN DBS could lead to a direct deterioration in articulation, it may indirectly improve it by reducing the levodopa dose required to manage motor symptoms. These findings suggest that, with respect to speech production, STN DBS and levodopa intake cannot be investigated separately because the two are intrinsically linked. Along with motor symptoms, speech production should be considered when optimizing therapeutic management of patients with PD.

  6. Articulatory Changes in Vowel Production following STN DBS and Levodopa Intake in Parkinson's Disease.

    Science.gov (United States)

    Martel Sauvageau, Vincent; Roy, Johanna-Pascale; Cantin, Léo; Prud'Homme, Michel; Langlois, Mélanie; Macoir, Joël

    2015-01-01

    Purpose. To investigate the impact of deep brain stimulation of the subthalamic nucleus (STN DBS) and levodopa intake on vowel articulation in dysarthric speakers with Parkinson's disease (PD). Methods. Vowel articulation was assessed in seven Quebec French speakers diagnosed with idiopathic PD who underwent STN DBS. Assessments were conducted on- and off-medication, first prior to surgery and then 1 year later. All recordings were made on-stimulation. Vowel articulation was measured using acoustic vowel space and formant centralization ratio. Results. Compared to the period before surgery, vowel articulation was reduced after surgery when patients were off-medication, while it was better on-medication. The impact of levodopa intake on vowel articulation changed with STN DBS: before surgery, levodopa impaired articulation, while it no longer had a negative effect after surgery. Conclusions. These results indicate that while STN DBS could lead to a direct deterioration in articulation, it may indirectly improve it by reducing the levodopa dose required to manage motor symptoms. These findings suggest that, with respect to speech production, STN DBS and levodopa intake cannot be investigated separately because the two are intrinsically linked. Along with motor symptoms, speech production should be considered when optimizing therapeutic management of patients with PD.

  7. Comparative study of microelectrode recording-based STN location and MRI-based STN location in low to ultra-high field (7.0 T) T2-weighted MRI images

    Science.gov (United States)

    Verhagen, Rens; Schuurman, P. Richard; van den Munckhof, Pepijn; Fiorella Contarino, M.; de Bie, Rob M. A.; Bour, Lo J.

    2016-12-01

    Objective. The correspondence between the anatomical STN and the STN observed in T2-weighted MRI images used for deep brain stimulation (DBS) targeting remains unclear. Using a new method, we compared the STN borders seen on MRI images with those estimated by intraoperative microelectrode recordings (MER). Approach. We developed a method to automatically generate a detailed estimation of STN shape and the location of its borders, based on multiple-channel MER measurements. In 33 STNs of 19 Parkinson patients, we quantitatively compared the dorsal and lateral borders of this MER-based STN model with the STN borders visualized by 1.5 T (n = 14), 3.0 T (n = 10) and 7.0 T (n = 9) T2-weighted MRI. Main results. The dorsal border was identified more dorsally on coronal T2 MRI than by the MER-based STN model, with a significant difference in the 3.0 T (range 0.97-1.19 mm) and 7.0 T (range 1.23-1.25 mm) groups. The lateral border was significantly more medial on 1.5 T (mean: 1.97 mm) and 3.0 T (mean: 2.49 mm) MRI than in the MER-based STN; a difference that was not found in the 7.0 T group. Significance. The STN extends further in the dorsal direction on coronal T2 MRI images than is measured by MER. Increasing MRI field strength to 3.0 T or 7.0 T yields similar discrepancies between MER and MRI at the dorsal STN border. In contrast, increasing MRI field strength to 7.0 T may be useful for identification of the lateral STN border and thereby improve DBS targeting.

  8. Inhibition of Serratia marcescens Smj-11 biofilm formation by Alcaligenes faecalis STN17 crude extract

    Energy Technology Data Exchange (ETDEWEB)

    Lutfi, Zainal; Ahmad, Asmat [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), 43600 Bangi, Selangor (Malaysia); Usup, Gires [School of Environmental and Natural Resources Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), 43600 Bangi, Selangor (Malaysia)

    2014-09-03

    Serratia marcescens biofilms are formed when they are bound to surfaces in aqueous environments. S. marcescens utilizes N-acylhomoserine lactone (AHL) as its quorum sensing signal molecule. The accumulation of AHL indicates the bacteria to produce matrices to form biofilms. Prodigiosin (2-methyl-3-pentyl-6-methoxyprodigiosin), which causes red pigmentation in the colonies, are also produced when the AHL reaches a certain threshold. The Alcaligenes faecalis STN17 crude extract is believed to inhibit quorum sensing in the S. marcescens Smj-11 and, thus, impedes its biofilm formation ability. A. faecalis STN17 was grown in marine broth, and ethyl acetate extraction was carried out. The crude compound of A. faecalis STN17 was diluted at high concentration (0.2-6.4 mg/mL) and was taken to confirm anti-biofilm activity through the crystal violet method in 96-wells plate. Then, the crude extract underwent purification using simple solvents partitioning test to discern the respective compounds that had the anti-biofilm activity under the crystal violet method. The crystal violet test showed that the crude did have anti-biofilm activity on S. marcescens Smj-11, but did not kill the cells. This finding signifies that the suppression of biofilm formation in S. marcescens by A. faecalis STN17 has a strong correlation. The partitioning test showed that A. faecalis STN17 crude extract has several compounds and only the compound(s) in chloroform showed activities. In conclusion, the crude extract of A. faecalis STN17 has the ability to inhibit S. marcescens Smj-11 biofilm formation.

  9. Using STN DBS and medication reduction as a strategy to treat pathological gambling in Parkinson's disease.

    Science.gov (United States)

    Bandini, Fabio; Primavera, Alberto; Pizzorno, Matteo; Cocito, Leonardo

    2007-08-01

    We describe two patients with Parkinson's disease (PD) who developed clinical criteria of pathological gambling addiction in the setting of increased dopamine replacement therapy (levodopa and dopamine agonist medications). The second patient showed also signs of dopamine dysregulation syndrome, with an addiction to dopaminergic medication. Neither patients responded to the standard therapy for gambling behavior, but dramatically improved after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) and early postoperative withdrawal of dopaminergic therapy. The possible therapeutic role of subthalamic nucleus deep brain stimulation (STN-DBS) on such a disabling behavior needs to be investigated prospectively.

  10. STN vs. GPi Deep Brain Stimulation: Translating the Rematch into Clinical Practice.

    Science.gov (United States)

    Williams, Nolan R; Foote, Kelly D; Okun, Michael S

    2014-04-01

    When formulating a deep brain stimulation (DBS) treatment plan for a patient with Parkinson's disease (PD), two critical questions should be addressed: 1- Which brain target should be chosen to optimize this patient's outcome? and 2- Should this patient's DBS operation be unilateral or bilateral? Over the past two decades, two targets have emerged as leading contenders for PD DBS; the subthalamic nucleus (STN) and the globus pallidus internus (GPi). While the GPi target does have a following, most centers have uniformly employed bilateral STN DBS for all Parkinson's disease cases (Figure 1). This bilateral STN "one-size-fits-all" approach was challenged by an editorial entitled "STN vs. GPi: The Rematch," which appeared in the Archives of Neurology in 2005. Since 2005, a series of well designed clinical trials and follow-up studies have addressed the question as to whether a more tailored approach to DBS therapy might improve overall outcomes. Such a tailored approach would include the options of targeting the GPi, or choosing a unilateral operation. The results of the STN vs. GPi 'rematch' studies support the conclusion that bilateral STN DBS may not be the best option for every Parkinson's disease surgical patient. Off period motor symptoms and tremor improve in both targets, and with either unilateral or bilateral stimulation. Advantages of the STN target include more medication reduction, less frequent battery changes, and a more favorable economic profile. Advantages of GPi include more robust dyskinesia suppression, easier programming, and greater flexibility in adjusting medications. In cases where unilateral stimulation is anticipated, the data favor GPi DBS. This review summarizes the accumulated evidence regarding the use of bilateral vs. unilateral DBS and the selection of STN vs. GPi DBS, including definite and possible advantages of different targets and approaches. Based on this evidence, a more patient-tailored, symptom specific approach will be

  11. Predictors of cognitive and psychosocial outcome after STN DBS in Parkinson's Disease

    NARCIS (Netherlands)

    Smeding, H.M.M.; Speelman, J.D.; Huizenga, H.M.; Schuurman, P.R.; Schmand, B.

    2011-01-01

    Objective: To find predictors of cognitive decline and quality of life one year after bilateral subthalamic nucleus stimulation (STN DBS) in Parkinson’s disease (PD). Methods: A total of 105 patients were evaluated with a comprehensive neuropsychological assessment before and 12 months after surgery

  12. Neuropsychological effects of bilateral STN stimulation in Parkinson disease - A controlled study

    NARCIS (Netherlands)

    Smeding, HMM; Koning-Haanstra, M; Schuurman, PR; Nijssen, P; van Laar, T; Schmand, B; Speelman, J.D.

    2006-01-01

    Objective: To evaluate the cognitive and behavioral effects of bilateral subthalamic nucleus (STN) stimulation in patients with Parkinson disease (PD). Methods: The authors included 103 patients; 99 patients were evaluated 6 months after surgery. A control group of 39 patients with PD was formed and

  13. The preliminary assessment of the Social Transition in the North dataset: a comparison of STN survey and enumeration data for selected Northwest Alaskan communities

    OpenAIRE

    Saylor, Brian; Hughes, Gary

    2004-01-01

    Objective. This study compared the results from STN survey data with a mailback health study of the same communities to assess the reliability of the STN data. Study Design. Sample characteristics and respondes to health questions were compared through secondary data analysis. Data from the STN sample was compared to an enumeration study for the same or similar questions, including demographic characteristics and health status indicators, were compared. Methods. The STN study used the sample ...

  14. STN area detection using K-NN classifiers for MER recordings in Parkinson patients during neurostimulator implant surgery

    Science.gov (United States)

    Schiaffino, L.; Rosado Muñoz, A.; Guerrero Martínez, J.; Francés Villora, J.; Gutiérrez, A.; Martínez Torres, I.; Kohan, y. D. R.

    2016-04-01

    Deep Brain Stimulation (DBS) applies electric pulses into the subthalamic nucleus (STN) improving tremor and other symptoms associated to Parkinson’s disease. Accurate STN detection for proper location and implant of the stimulating electrodes is a complex task and surgeons are not always certain about final location. Signals from the STN acquired during DBS surgery are obtained with microelectrodes, having specific characteristics differing from other brain areas. Using supervised learning, a trained model based on previous microelectrode recordings (MER) can be obtained, being able to successfully classify the STN area for new MER signals. The K Nearest Neighbours (K-NN) algorithm has been successfully applied to STN detection. However, the use of the fuzzy form of the K-NN algorithm (KNN-F) has not been reported. This work compares the STN detection algorithm of K-NN and KNN-F. Real MER recordings from eight patients where previously classified by neurophysiologists, defining 15 features. Sensitivity and specificity for the classifiers are obtained, Wilcoxon signed rank non-parametric test is used as statistical hypothesis validation. We conclude that the performance of KNN-F classifier is higher than K-NN with p<0.01 in STN specificity.

  15. Predictors of cognitive and psychosocial outcome after STN DBS in Parkinson's Disease

    OpenAIRE

    Smeding, H M M; Speelman, J D; Huizenga, H.M.; Schuurman, P R; Schmand, B

    2011-01-01

    Objective: To find predictors of cognitive decline and quality of life one year after bilateral subthalamic nucleus stimulation (STN DBS) in Parkinson’s disease (PD). Methods: A total of 105 patients were evaluated with a comprehensive neuropsychological assessment before and 12 months after surgery. A control group of 40 PD patients was included to control for effects of repeated testing and disease progression. We determined individual changes in cognition, mood and quality of life using a ...

  16. Læsning af stnætter

    DEFF Research Database (Denmark)

    Huang, Marianne Ping

    2007-01-01

    Artiklen præsenterer en læsning af tid, rum og bevidsthedsstrøm i Christian Skovs roman, Høstnætter (1994). Antologien Christian Skov. Læsninger i forfatterskabet præsenterer et forfatterskab, der refererer til det jyske landskab, men gør det med afsæt i europæisk avantgarde og dagliglivets reali...

  17. Effects of STN and GPi deep brain stimulation on impulse control disorders and dopamine dysregulation syndrome.

    Directory of Open Access Journals (Sweden)

    Sarah J Moum

    Full Text Available OBJECTIVE: Impulse control disorders (ICDs and dopamine dysregulation syndrome (DDS are important behavioral problems that affect a subpopulation of patients with Parkinson's disease (PD and typically result in markedly diminished quality of life for patients and their caregivers. We aimed to investigate the effects of subthalamic nucleus (STN and internal globus pallidus (GPi deep brain stimulation (DBS on ICD/DDS frequency and dopaminergic medication usage. METHODS: A retrospective chart review was performed on 159 individuals who underwent unilateral or bilateral PD DBS surgery in either STN or GPi. According to published criteria, pre- and post-operative records were reviewed to categorize patients both pre- and post-operatively as having ICD, DDS, both ICD and DDS, or neither ICD nor DDS. Group differences in patient demographics, clinical presentations, levodopa equivalent dose (LED, and change in diagnosis following unilateral/bilateral by brain target (STN or GPi DBS placement were examined. RESULTS: 28 patients met diagnostic criteria for ICD or DDS pre- or post-operatively. ICD or DDS classification did not differ by GPi or STN target stimulation. There was no change in DDS diagnosis after unilateral or bilateral stimulation. For ICD, diagnosis resolved in 2 of 7 individuals after unilateral or bilateral DBS. Post-operative development of these syndromes was significant; 17 patients developed ICD diagnoses post-operatively with 2 patients with pre-operative ICD developing DDS post-operatively. CONCLUSIONS: Unilateral or bilateral DBS did not significantly treat DDS or ICD in our sample, even though a few cases of ICD resolved post-operatively. Rather, our study provides preliminary evidence that DDS and ICD diagnoses may emerge following DBS surgery.

  18. Coordinated reset stimulation in a large-scale model of the STN-GPe circuit

    Directory of Open Access Journals (Sweden)

    Martin eEbert

    2014-11-01

    Full Text Available Synchronization of populations of neurons is a hallmark of several brain diseases. Coordinated reset (CR stimulation is a model-based stimulation technique which specifically counteracts abnormal synchrony by desynchronization. Electrical CR stimulation, e.g. for the treatment of Parkinson’s disease (PD, is administered via depth electrodes. In order to get a deeper understanding of this technique, we extended the top-down approach of previous studies and constructed a large-scale computational model of the respective brain areas. Furthermore, we took into account the spatial anatomical properties of the simulated brain structures and incor- porated a detailed numerical representation of 2·104 simulated neurons. We simulated the subthalamic nucleus (STN and the globus pallidus externus (GPe. Connections within the STN were governed by spike-timing dependent plasticity (STDP. In this way, we modeled the physiological and pathological activity of the considered brain structures. In particular, we investigated how plasticity could be exploited and how the model could be shifted from strongly synchronized (pathological activity to strongly desynchronized (healthy activity of the neuronal populations via CR stimulation of the STN neurons. Furthermore, we investigated the impact of specific stimulation parameters especially the electrode position on the stimulation outcome. Our model provides a step forward towards a biophysically realistic model of the brain areas relevant to the emergence of pathological neuronal activity in PD. Furthermore, our model constitutes a test bench for the optimization of both stimulation parameters and novel electrode geometries for efficient CR stimulation.

  19. Locating the STN-DBS electrodes and resolving their subsequent networks using coherent source analysis on EEG.

    Science.gov (United States)

    Muthuraman, M; Paschen, S; Hellriegel, H; Groppa, S; Deuschl, G; Raethjen, J

    2012-01-01

    The deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the most effective surgical therapy for Parkinson's disease (PD). The first aim of the study was to locate the STN-DBS electrode by applying source analysis on EEG. Secondly, to identify tremor related areas which are associated with the STN. The Dynamic imaging of coherent sources (DICS) was used to find the coherent sources in the brain. The capability of the source analysis to detect deep sources like STN in the brain using EEG data was tested with two model dipole simulations. The simulations were concentrated on two aspects, the angle of the dipole orientation and the disturbance of the cortical areas on locating subcortical regions. In all the DBS treated Parkinsonian tremor patients the power spectrum showed a clear peak at the stimulated frequency and followed by there harmonics. The DBS stimulated frequency constituted a network of primary sensory motor cortex, supplementary motor area, prefrontal cortex, diencephalon, cerebellum and brainstem. Thus the STN was located in the region of the diencephalon. The resolved network may give better understanding to the pathophysiology of the effected tremor network in PD patients with STN-DBS.

  20. Differential modulation of STN-cortical and cortico-muscular coherence by movement and levodopa in Parkinson's disease.

    Science.gov (United States)

    Hirschmann, J; Özkurt, T E; Butz, M; Homburger, M; Elben, S; Hartmann, C J; Vesper, J; Wojtecki, L; Schnitzler, A

    2013-03-01

    Previous research suggests that oscillatory coupling between cortex, basal ganglia and muscles plays an important role in motor behavior. Furthermore, there is evidence that oscillatory coupling is altered in patients with movement disorders such as Parkinson's disease (PD). In this study, we performed simultaneous magnetoencephalography (MEG), local field potential (LFP) and electromyogram (EMG) recordings in PD patients selected for therapeutic subthalamic nucleus (STN) stimulation. Patients were recorded (i) after withdrawal of anti-parkinsonian medication (OFF) and (ii) after levodopa administration (ON). We analyzed STN-cortical and cortico-muscular coherence during static forearm contraction and repetitive hand movement in order to evaluate modulations of coherence by movement and medication. Based on previous results from studies investigating resting state coherence in PD patients, we selected primary motor cortex (M1) and superior temporal gyrus (STG) as regions of interest. We found beta coherence between M1 and STN to be suppressed by administration of levodopa. M1-muscular coherence was strongly reduced in the alpha and beta band during repetitive movement compared to static contraction, but was unaffected by administration of levodopa. Strong STG-STN but not STG-muscular coherence could be observed in the alpha band. Coherence with STG was modulated neither by movement nor by medication. Finally, we found both M1-STN and M1-muscular beta coherence to be negatively correlated with UPDRS akinesia and rigidity sub-scores in the OFF state. The present study provides new insights into the functional roles of STN-cortical and cortico-muscular coherence and their relationship to PD symptoms. The results indicate that STN-cortical and cortico-muscular coupling are correlated, but can be modulated independently. Moreover, they show differences in their frequency-specific topography. We conclude that they represent partly independent sub-loops within the motor

  1. Prediction of STN-DBS Electrode Implantation Track in Parkinson's Disease by Using Local Field Potentials

    Science.gov (United States)

    Telkes, Ilknur; Jimenez-Shahed, Joohi; Viswanathan, Ashwin; Abosch, Aviva; Ince, Nuri F.

    2016-01-01

    Optimal electrophysiological placement of the DBS electrode may lead to better long term clinical outcomes. Inter-subject anatomical variability and limitations in stereotaxic neuroimaging increase the complexity of physiological mapping performed in the operating room. Microelectrode single unit neuronal recording remains the most common intraoperative mapping technique, but requires significant expertise and is fraught by potential technical difficulties including robust measurement of the signal. In contrast, local field potentials (LFPs), owing to their oscillatory and robust nature and being more correlated with the disease symptoms, can overcome these technical issues. Therefore, we hypothesized that multiple spectral features extracted from microelectrode-recorded LFPs could be used to automate the identification of the optimal track and the STN localization. In this regard, we recorded LFPs from microelectrodes in three tracks from 22 patients during DBS electrode implantation surgery at different depths and aimed to predict the track selected by the neurosurgeon based on the interpretation of single unit recordings. A least mean square (LMS) algorithm was used to de-correlate LFPs in each track, in order to remove common activity between channels and increase their spatial specificity. Subband power in the beta band (11–32 Hz) and high frequency range (200–450 Hz) were extracted from the de-correlated LFP data and used as features. A linear discriminant analysis (LDA) method was applied both for the localization of the dorsal border of STN and the prediction of the optimal track. By fusing the information from these low and high frequency bands, the dorsal border of STN was localized with a root mean square (RMS) error of 1.22 mm. The prediction accuracy for the optimal track was 80%. Individual beta band (11–32 Hz) and the range of high frequency oscillations (200–450 Hz) provided prediction accuracies of 72 and 68% respectively. The best

  2. Emotion recognition in Parkinson's disease after subthalamic deep brain stimulation: differential effects of microlesion and STN stimulation.

    Science.gov (United States)

    Aiello, Marilena; Eleopra, Roberto; Lettieri, Christian; Mondani, Massimo; D'Auria, Stanislao; Belgrado, Enrico; Piani, Antonella; De Simone, Luca; Rinaldo, Sara; Rumiati, Raffaella I

    2014-02-01

    Deep brain stimulation of the subthalamic nucleus (STN-DBS) has acquired a relevant role in the treatment of Parkinson's disease (PD). Despite being a safe procedure, it may expose patients to an increased risk to experience cognitive and emotional difficulties. Impairments in emotion recognition, mediated both by facial and prosodic expressions, have been reported in PD patients treated with such procedure. However, it is still unclear whether the STN per se is responsible for such changes or whether others factors like the microlesion produced by the electrode implantation may also play a role. In this study we evaluated facial emotions discrimination and emotions recognition using both facial and prosodic expressions in 12 patients with PD and 13 matched controls. Patients' were tested in four conditions: before surgery, both in on and off medication, and after surgery, respectively few days after STN implantation before turning stimulator on and few months after with stimulation on. We observed that PD patients were impaired in discriminating and recognizing facial emotions, especially disgust, even before DBS implant. Microlesion caused by surgical procedure was found to influence patients' performance on the discrimination task and recognition of sad facial expression while, after a few months of STN stimulation, impaired disgust recognition was again prominent. No impairment in emotional prosody recognition was observed both before and after surgery. Our study confirms that PD patients may experience a deficit in disgust recognition and provides insight into the differential effect of microlesion and stimulation of STN on several tasks assessing emotion recognition.

  3. Distinct effects of dopamine vs STN stimulation therapies in associative learning and retention in Parkinson disease.

    Science.gov (United States)

    Ventre-Dominey, Jocelyne; Mollion, Hélène; Thobois, Stephane; Broussolle, Emmanuel

    2016-04-01

    Evidence has been provided in Parkinson's disease patients of cognitive impairments including visual memory and learning which can be partially compensated by dopamine medication or subthalamic nucleus stimulation. The effects of these two therapies can differ according to the learning processes involving the dorsal vs ventral part of the striatum. Here we aimed to investigate and compare the outcomes of dopamine vs stimulation treatment in Parkinson patient's ability to acquire and maintain over successive days their performance in visual working memory. Parkinson patients performed conditional associative learning embedded in visual (spatial and non spatial) working memory tasks over two consecutive days either ON or OFF dopaminergic drugs or STN stimulation depending on the group of patients studied. While Parkinson patients were more accurate and faster in memory tasks ON vs OFF stimulation independent of the day of testing, performance in medicated patients differed depending on the medication status during the initial task acquisition. Patients who learnt the task ON medication the first day were able to maintain or even improve their memory performance both OFF and ON medication on the second day after consolidation. These effects were observed only in patients with dopamine replacement with or without motor fluctuations. This enhancement in memory performance after having learnt under dopamine medication and not under STN stimulation was mostly significant in visuo-spatial working memory tasks suggesting that dopamine replacement in the depleted dorsal striatum is essential for retention and consolidation of learnt skill.

  4. Human Stn1 protects telomere integrity by promoting efficient lagging-strand synthesis at telomeres and mediating C-strand fill-in

    Institute of Scientific and Technical Information of China (English)

    Chenhui Huang; Xueyu Dai; Weihang Chai

    2012-01-01

    Telomere maintenance is critical for genome stability.The newly-identified Ctc1/Stn1/Ten1 complex is important for telomere maintenance,though its precise role is unclear.We report here that depletion of hStn1 induces catastrophic telomere shortening,DNA damage response,and early senescence in human somatic cells.These phenotypes are likely due to the essential role of hStn1 in promoting efficient replication of lagging-strand telomeric DNA.Downregulation of hStn1 accumulates single-stranded G-rich DNA specifically at lagging-strand telomeres,increases telomere fragility,hinders telomere DNA synthesis,as well as delays and compromises telomeric C-strand synthesis.We further show that hStn1 deficiency leads to persistent and elevated association of DNA polymerase α(polα)to telomeres,suggesting that hStn1 may modulate the DNA synthesis activity of polα rather than controlling the loading of polα to telomeres.Additionally,our data suggest that hStn1 is unlikely to be part of the telomere capping complex.We propose that the hStn1 assists DNA polymerases to efficiently duplicate lagging-strand telomeres in order to achieve complete synthesis of telomeric DNA,therefore preventing rapid telomere loss.

  5. Structural and Resting State Functional Connectivity of the Subthalamic Nucleus: Identification of Motor STN Parts and the Hyperdirect Pathway

    NARCIS (Netherlands)

    Brunenberg, E.J.; Moeskops, P.; Backes, W.H.; Pollo, C.; Cammoun, L.; Vilanova, A.; Janssen, M.L.H.; Visser-Vandewalle, V.E.R.M.; Haar Romeny, Bart M. ter; Thiran, J.-P.; Platel, B.

    2012-01-01

    Deep brain stimulation (DBS) for Parkinson's disease often alleviates the motor symptoms, but causes cognitive and emotional side effects in a substantial number of cases. Identification of the motor part of the subthalamic nucleus (STN) as part of the presurgical workup could minimize these adverse

  6. The role of cancer vaccines following autologous stem cell rescue in breast and ovarian cancer patients: experience with the STn-KLH vaccine (Theratope).

    Science.gov (United States)

    Holmberg, Leona A; Oparin, Dimitri V; Gooley, Ted; Sandmaier, Brenda M

    2003-02-01

    The success of high-dose chemotherapy followed by autologous stem-cell rescue as treatment for breast and ovarian cancer is limited by a high incidence of relapse. After autologous transplantation, patients are likely to have a low tumor burden and thus would be more likely to respond immunologically to a cancer vaccine. Sialyl-Tn (STn) is a carbohydrate associated with the MUC1 mucin on breast and ovarian cancer and is an ideal candidate for vaccine immunotherapy. Sialyl-Tn-keyhole limpet hemocyanin (STn-KLH) vaccine (Theratope) incorporates a synthetic STn antigen that mimics the unique tumor-associated STn carbohydrate and is designed to stimulate tumor antigen-specific immune responses in patients with mucin-expressing tumors. Between 1995 and 2000, 70 patients (16 with stage II/III breast cancer, 17 with stage III/IV ovarian cancer, and 37 with stage IV breast cancer) were treated with 2 different formulations of STn-KLH. Toxicity, outcome, and immune response data are reported. STn-KLH was well-tolerated with minimal toxicity. The most common side effects were indurations and erythema at the sites of injections. Humoral and cellular responses were elicited in the majority of patients. Overall, these data indicate that post-autologous transplant patients are able to mount an effective immune response to vaccine immunotherapy with minimal side effects, and that vaccine immunotherapy may be a useful addition to high-dose chemotherapy regimens.

  7. Influence of silane additive Y9669 on STN liquid crystal alignment agent‘s performance%硅烷添加剂 Y9669对 STN 液晶取向剂性能的影响

    Institute of Scientific and Technical Information of China (English)

    汪映寒; 周于蓝; 刘斌; 龚世铭

    2015-01-01

    When the STN liquid crystal alignment agent is filmed and thermoformed on the surface of glass substrates in industrial production,it is necessary to clean the substrates with solvents.In the process of cleaning,the film often peels off from its substrate.To tackle this problem,an additive is required to improve the adhesive performance of the agent without sacrificing its viscosity,outlook, pretilt angle and hardness.A silane additive N-[3-(trimethoxysilyl)propyl]aniline (Y9669)is intro-duced into the agent.Five solutions were prepared for the agent in mixture with the additive in differ-ent proportions.The viscosity,outlook,pretilt angle,hardness and etc.of the solutions were exam-ined.The STN liquid crystal alignment agent system reaches its best overall performance when the si-lane additive Y9669 is added 0.5% equal to the solid content of the agent.The silane additive Y9669 could improve the adhesive performance to the substrate with almost no impact on the other perfor-mances of the agent.%在工业生产中,STN 液晶取向剂在以薄膜形式涂覆在玻璃基板表面并进行热固化后,需要用溶剂对其进行洗涤。在洗涤中,薄膜从玻璃基板上脱落的现象时有发生。针对这种现象,需要一种添加剂,在不影响 STN 液晶取向剂的粘度、外观、预倾角、硬度等性质的同时,提高其粘接性能。在液晶取向剂中引入了 N-苯基-3-氨基丙基三甲氧基硅烷(Y9669)添加剂,将硅烷添加剂以不同添加比例与取向剂搅拌混合后,得到5份添加剂含量不同的溶液。表征并对比了含有不同含量添加剂的 STN 液晶取向剂的粘度、外观、预倾角、硬度、粘接性等性质。实验结果表明:对于 STN 液晶取向剂体系,硅烷添加剂 Y9669的最佳添加比例为取向剂固含量的0.5%,此时得到的取向剂综合性能更加优异。硅烷添加剂 Y9669基本能够达到在不影响取向剂其他性能的同时,提高其对基板粘接性能的要求。

  8. Návrh IS pro Místní knihovnu města Jevišovice

    OpenAIRE

    2010-01-01

    Bakalářská práce pojednává o návrhu vytvoření databáze pro místní knihovnu města Jevišovice. Práce obsahuje vlastní návrh databáze a její vytvoření v programu Microsoft Access. Dále obsahuje vytvoření pracovního rozhraní pomocí VBA. The thesis deals with the concept of the Jevisovice city Local Library database creating. The thesis contains the concept of the database and its creation in the Microsoft Access software. Further, the work includes the creation of the VBA comunication interfac...

  9. Gait analysis in patients with advanced Parkinson disease: different or additive effects on gait induced by levodopa and chronic STN stimulation.

    Science.gov (United States)

    Lubik, S; Fogel, W; Tronnier, V; Krause, M; König, J; Jost, W H

    2006-02-01

    The aim of our study was to observe the effects on gait parameters induced by STN stimulation and levodopa medication in patients with advanced Parkinson's disease in order to determine different or additive effects. Therefore we examined 12 patients with advanced Parkinson disease after bilateral implantation of DBS into the STN. We assessed the motor score of the UPDRS and quantitative gait analysis under 4 treatment conditions: with and without stimulation as well as with and without levodopa. The mean improvement of the UPDRS motor score was almost the same with levodopa and DBS. Combining both therapies we saw a further improvement of the motor score. Gait parameters of patients with PD treated either with levodopa or STN stimulation were greatly improved. A significant difference between levodopa and STN stimulation could only be shown for the parameters velocity and step length. These parameters improved more with levodopa than with stimulation. The combination of both therapeutic methods showed the best results on the UPDRS motor score and gait parameters.

  10. Comparison of imaging modalities and source-localization algorithms in locating the induced activity during deep brain stimulation of the STN.

    Science.gov (United States)

    Mideksa, K G; Singh, A; Hoogenboom, N; Hellriegel, H; Krause, H; Schnitzler, A; Deuschl, G; Raethjen, J; Schmidt, G; Muthuraman, M

    2016-08-01

    One of the most commonly used therapy to treat patients with Parkinson's disease (PD) is deep brain stimulation (DBS) of the subthalamic nucleus (STN). Identifying the most optimal target area for the placement of the DBS electrodes have become one of the intensive research area. In this study, the first aim is to investigate the capabilities of different source-analysis techniques in detecting deep sources located at the sub-cortical level and validating it using the a-priori information about the location of the source, that is, the STN. Secondly, we aim at an investigation of whether EEG or MEG is best suited in mapping the DBS-induced brain activity. To do this, simultaneous EEG and MEG measurement were used to record the DBS-induced electromagnetic potentials and fields. The boundary-element method (BEM) have been used to solve the forward problem. The position of the DBS electrodes was then estimated using the dipole (moving, rotating, and fixed MUSIC), and current-density-reconstruction (CDR) (minimum-norm and sLORETA) approaches. The source-localization results from the dipole approaches demonstrated that the fixed MUSIC algorithm best localizes deep focal sources, whereas the moving dipole detects not only the region of interest but also neighboring regions that are affected by stimulating the STN. The results from the CDR approaches validated the capability of sLORETA in detecting the STN compared to minimum-norm. Moreover, the source-localization results using the EEG modality outperformed that of the MEG by locating the DBS-induced activity in the STN.

  11. Effect of Ru/CGO versus Ni/CGO Co- Infiltration on the Performance and Stability of STN-Based SOFCs

    DEFF Research Database (Denmark)

    Ramos, Tania; Veltzé, Sune; Sudireddy, Bhaskar Reddy

    2014-01-01

    Electrolyte supported cells (ESC), with Sc2O3-stabilized ZrO2 (ScSZ) electrolytes, Gd-doped ceria (CGO) or M/CGO (M = Ni, Ru) infiltrated Sr0.94Ti0.9Nb0.1O3 (STN94) anodes and LSM/YSZ cathodes, were evaluated for their initial performance and long-term stability. Power density for the Ru/CGO infi......Electrolyte supported cells (ESC), with Sc2O3-stabilized ZrO2 (ScSZ) electrolytes, Gd-doped ceria (CGO) or M/CGO (M = Ni, Ru) infiltrated Sr0.94Ti0.9Nb0.1O3 (STN94) anodes and LSM/YSZ cathodes, were evaluated for their initial performance and long-term stability. Power density for the Ru...

  12. Freestanding rGO-SWNT-STN Composite Film as an Anode for Li Ion Batteries with High Energy and Power Densities

    Directory of Open Access Journals (Sweden)

    Taeseup Song

    2015-12-01

    Full Text Available Freestanding Si-Ti-Ni alloy particles/reduced graphene oxide/single wall carbon nanotube composites have been prepared as an anode for lithium ion batteries via a simple filtration method. This composite electrode showed a 9% increase in reversible capacity, a two-fold higher cycle retention at 50 cycles and a two-fold higher rate capability at 2 C compared to pristine Si-Ti-Ni (STN alloy electrodes. These improvements were attributed to the suppression of the pulverization of the STN active material by the excellent mechanical properties of the reduced graphene oxide-single wall carbon nanotube networks and the enhanced kinetics associated with both electron and Li ion transport.

  13. Freestanding rGO-SWNT-STN Composite Film as an Anode for Li Ion Batteries with High Energy and Power Densities.

    Science.gov (United States)

    Song, Taeseup; Choi, Junghyun; Paik, Ungyu

    2015-12-18

    Freestanding Si-Ti-Ni alloy particles/reduced graphene oxide/single wall carbon nanotube composites have been prepared as an anode for lithium ion batteries via a simple filtration method. This composite electrode showed a 9% increase in reversible capacity, a two-fold higher cycle retention at 50 cycles and a two-fold higher rate capability at 2 C compared to pristine Si-Ti-Ni (STN) alloy electrodes. These improvements were attributed to the suppression of the pulverization of the STN active material by the excellent mechanical properties of the reduced graphene oxide-single wall carbon nanotube networks and the enhanced kinetics associated with both electron and Li ion transport.

  14. Stratifying Parkinson's Patients With STN-DBS Into High-Frequency or 60 Hz-Frequency Modulation Using a Computational Model.

    Science.gov (United States)

    Khojandi, Anahita; Shylo, Oleg; Mannini, Lucia; Kopell, Brian H; Ramdhani, Ritesh A

    2017-07-01

    High frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well-established therapy for Parkinson's disease (PD), particularly the cardinal motor symptoms and levodopa induced motor complications. Recent studies have suggested the possible role of 60 Hz stimulation in STN-deep brain stimulation (DBS) for patients with gait disorder. The objective of this study was to develop a computational model, which stratifies patients a priori based on symptomatology into different frequency settings (i.e., high frequency or 60 Hz). We retrospectively analyzed preoperative MDS-Unified Parkinson's Disease Rating Scale III scores (32 indicators) collected from 20 PD patients implanted with STN-DBS at Mount Sinai Medical Center on either 60 Hz stimulation (ten patients) or HFS (130-185 Hz) (ten patients) for an average of 12 months. Predictive models using the Random Forest classification algorithm were built to associate patient/disease characteristics at surgery to the stimulation frequency. These models were evaluated objectively using leave-one-out cross-validation approach. The computational models produced, stratified patients into 60 Hz or HFS (130-185 Hz) with 95% accuracy. The best models relied on two or three predictors out of the 32 analyzed for classification. Across all predictors, gait and rest tremor of the right hand were consistently the most important. Computational models were developed using preoperative clinical indicators in PD patients treated with STN-DBS. These models were able to accurately stratify PD patients into 60 Hz stimulation or HFS (130-185 Hz) groups a priori, offering a unique potential to enhance the utilization of this therapy based on clinical subtypes. © 2017 International Neuromodulation Society.

  15. Tu nos aposte protege

    DEFF Research Database (Denmark)

    Frederiksen, Britta Olrik

    2007-01-01

    Aspirationen af p, t og k i dansk er stedmoderligt behandlet af den gren af den historiske sprogforskning der bygger på skriftligt kildemateriale. Skrivemåden tu nos aposte protege for tu nos ab hoste protege 'bekyt du os mod fjenden' i en tilskrift fra anden halvdel af 1300-tallet i...

  16. 鼠伤寒沙门菌stn基因突变株的构建与毒力检测%CONSTRUCTION OF SALMONELLA STN-DEFICENT MUTANTS AND DETECTION OF THEIR VIRULENCE

    Institute of Scientific and Technical Information of China (English)

    黄建华; 徐心晶

    2001-01-01

    作者构建了鼠伤寒沙门菌肠毒素(stn)基因插入失活型与缺失型突变的重组自杀载体质粒,通过重组自杀质粒中的突变stn基因与鼠伤寒沙门菌株2000染色体上野生型stn基因发生同源交换,筛选获得stn基因突变的同源突变菌株。在小鼠体内检测菌株stn基因产物生物活性的结果表明,突变菌株诱发小鼠肠液分泌的能力较野生菌株明显减弱,而小鼠口服突变菌株的半致死剂量较野生株明显增高,提示stn基因是鼠伤寒沙门菌致病机制中一个较为重要的毒力因子。%The plasmids of recombinant suicide vector containing the truncated stn gene and the deleted stn gene were constructed. The Salmonella stn-deficient mutant was prepared by homologous recombination between the mutant stn gene in the recombinant suicide vector and the wild-type gene in the chromosome of S. Typhimurium 2000. The detection of biological activity of stn gene production in those mutants indicated that Salmonella stn-deficient mutants evoked significantly less fluid secretion in mouse intestinal loops compared to that seen with wild-type Salmonella. Upon oral challenge of mice, the fifty percent lethal dose of the Salmonella stn-deficient mutants was greater than that for the wild-type bacteria. Those studies showed that the stn gene is very important factor in the pathogenesis of salmonellosis.

  17. EMBASE remains EMBASE--on every host? A comparative analysis of EMBASE on the hosts DATA-STAR, DIALOG, DIMDI, and STN.

    Science.gov (United States)

    Gretz, M; Schmitt, R D; Thomas, M

    1996-12-01

    Differing results of the same search request processed on different hosts led the authors to investigate this issue more thoroughly. Two authors, two journal titles, two drug names, and two topics of a general medical nature were retrieved under identical circumstances and conditions on the hosts DATA-STAR, DIALOG, DIMDI, and STN. Comparing the figures revealed that none of the nine search request produced an identical result on all hosts. Some of the search results differed only slightly, while the searches in the basic index produced considerable discrepancies.

  18. S3C2410A中STN型LCD显示驱动的实现%THE IMPLEMENTATION OF STN- LCD DISPLAY DRIVER IN S3C2410A

    Institute of Scientific and Technical Information of China (English)

    张永安

    2012-01-01

    通过对LCD显示原理的分析和对嵌入式芯片S3C2410A中LCD控制器的研究,设计了STNLCD的硬件驱动电路和软件驱动程序,完成了在S3C2410A中对STN LCD驱动的设计.实验结果显示LCD上图像显示稳定清晰,达到设计要求.该设计可用于大部分嵌入式芯片对STNLCD的驱动,是嵌入式系统中实现LCD驱动的一套较好解决方案.%By analyzing the principles of LCD display and researching embedded chips S3C2410A LCD controller, the STN LCD driver in the S3C2410A is designed ,the driver included a STNLCD hardware driver and software drivers. Experimental results show stable and clear image display on the LCD, meet the design requirements. The design can be used for most of the embedded chip STNLCD drive, it become a better solution way of LCD driver in embedded systems.

  19. Endothelial NOS (NOS3) impairs myocardial function in developing sepsis.

    Science.gov (United States)

    van de Sandt, Annette M; Windler, Rainer; Gödecke, Axel; Ohlig, Jan; Zander, Simone; Reinartz, Michael; Graf, Jürgen; van Faassen, Ernst E; Rassaf, Tienush; Schrader, Jürgen; Kelm, Malte; Merx, Marc W

    2013-03-01

    Endothelial nitric oxide synthase (NOS)3-derived nitric oxide (NO) modulates inotropic response and diastolic interval for optimal cardiac performance under non-inflammatory conditions. In sepsis, excessive NO production plays a key role in severe hypotension and myocardial dysfunction. We aimed to determine the role of NOS3 on myocardial performance, NO production, and time course of sepsis development. NOS3(-/-) and C57BL/6 wildtype mice were rendered septic by cecum ligation and puncture (CLP). Cardiac function was analyzed by serial echocardiography, in vivo pressure and isolated heart measurements. Cardiac output (CO) increased to 160 % of baseline at 10 h after sepsis induction followed by a decline to 63 % of baseline after 18 h in wildtype mice. CO was unaltered in septic NOS3(-/-) mice. Despite the hyperdynamic state, cardiac function and mean arterial pressure were impaired in septic wildtype as early as 6 h post CLP. At 12 h, cardiac function in septic wildtype was refractory to catecholamines in vivo and respective isolated hearts showed impaired pressure development and limited coronary flow reserve. Hemodynamics remained stable in NOS3(-/-) mice leading to significant survival benefit. Unselective NOS inhibition in septic NOS3(-/-) mice diminished this survival benefit. Plasma NO( x )- and local myocardial NO( x )- and NO levels (via NO spin trapping) demonstrated enhanced NO( x )- and bioactive NO levels in septic wildtype as compared to NOS3(-/-) mice. Significant contribution by inducible NOS (NOS2) during this early phase of sepsis was excluded. Our data suggest that NOS3 relevantly contributes to bioactive NO pool in developing sepsis resulting in impaired cardiac contractility.

  20. Offre pour nos membres

    CERN Multimedia

    Staff Association

    2016-01-01

    Walibi Rhône-Alpes accueille son événement Halloween FreakShow le week-end du 15 et 16 octobre puis tous les jours du 20 octobre au 02 novembre 2016 ! ouverture prolongée jusqu’à 19h et feu d’artifices chaque soir 29, 30 et 31 octobre ! Loup-garou show; 1 labyrinthe; jeu de piste sur le parc (et nombreux lots à gagner); animations (sculpture sur citrouilles et maquillage) et d'autres surpises ! Tarifs pour nos membres : Entrée "Zone terrestre": 23 € au lieu de 29 €. Entrée gratuite pour les enfants de moins de 3 ans, avec accès aux attractions limité. Parking gratuit.

  1. Offre pour nos membres

    CERN Multimedia

    Staff Association

    2016-01-01

    Walibi Rhône-Alpes accueille son événement Halloween FreakShow le week-end du 15 et 16 octobre puis tous les jours du 20 octobre au 02 novembre 2016 ! ouverture prolongée jusqu’à 19h et feu d’artifices chaque soir 29, 30 et 31 octobre ! Loup-garou show; 1 labyrinthe; jeu de piste sur le parc (et nombreux lots à gagner); animations (sculpture sur citrouilles et maquillage) et d'autres surpises ! Tarifs pour nos membres : Entrée "Zone terrestre": 23 € au lieu de 29 €. Entrée gratuite pour les enfants de moins de 3 ans, avec accès aux attractions limité. Parking gratuit.

  2. NOAA NOS SOS, EXPERIMENTAL - Conductivity

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have conductivity data. *These services are for testing and evaluation use...

  3. NOAA NOS SOS, EXPERIMENTAL - Wind

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have wind data. *These services are for testing and evaluation use only*...

  4. NOAA NOS SOS, EXPERIMENTAL - Salinity

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have salinity data. *These services are for testing and evaluation use...

  5. NOAA NOS SOS, EXPERIMENTAL - Currents

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have currents data. *These services are for testing and evaluation use...

  6. Production of superoxide from photosystem II-light harvesting complex II supercomplex in STN8 kinase knock-out rice mutants under photoinhibitory illumination.

    Science.gov (United States)

    Poudyal, Roshan Sharma; Nath, Krishna; Zulfugarov, Ismayil S; Lee, Choon-Hwan

    2016-09-01

    When phosphorylation of Photosystem (PS) II core proteins is blocked in STN8 knock-out mutants of rice (Oryza sativa) under photoinhibitory illumination, the mobilization of PSII supercomplex is prevented. We have previously proposed that more superoxide (O2(-)) is produced from PSII in the mutant (Nath et al., 2013, Plant J. 76, 675-686). Here, we clarify the type and site for the generation of reactive oxygen species (ROS). Using both histochemical and fluorescence probes, we observed that, compared with wild-type (WT) leaves, levels of ROS, including O2(-) and hydrogen peroxide (H2O2), were increased when leaves from mutant plants were illuminated with excess light. However, singlet oxygen production was not enhanced under such conditions. When superoxide dismutase was inhibited, O2(-) production was increased, indicating that it is the initial event prior to H2O2 production. In thylakoids isolated from WT leaves, kinase was active in the presence of ATP, and spectrophotometric analysis of nitrobluetetrazolium absorbance for O2(-) confirmed that PSII-driven superoxide production was greater in the mutant thylakoids than in the WT. This contrast in levels of PSII-driven superoxide production between the mutants and the WT plants was confirmed by conducting protein oxidation assays of PSII particles from osstn8 leaves under strong illumination. Those assays also demonstrated that PSII-LHCII supercomplex proteins were oxidized more in the mutant, thereby implying that PSII particles incur greater damage even though D1 degradation during PSII-supercomplex mobilization is partially blocked in the mutant. These results suggest that O2(-) is the major form of ROS produced in the mutant, and that the damaged PSII in the supercomplex is the primary source of O2(-).

  7. Association analysis of nitric oxide synthases: NOS1, NOS2A and NOS3 genes, with multiple sclerosis.

    Science.gov (United States)

    AlFadhli, Suad; Mohammed, Eiman M A; Al Shubaili, Asmahan

    2013-07-01

    Multiple sclerosis (MS) is a chronic inflammatory autoimmune disorder of the central nervous system. To explore the genetic basis of three nitric oxide synthase (NOS) genes: NOS1, NOS2A and NOS3, with susceptibility to MS. A total of 122 MS patients and 118 healthy controls screened for NOS1 (rs2682826, rs41279104), NOS2A (CCTTT)n/(TAAA)n and NOS3 (rs1800783, rs1800779, rs2070744, 27bpVNTR) markers, using TaqMan®SNP Genotyping Assays and fragment analysis were enrolled in this study. QRT-PCR and ELISA were used to analyse the expression of NOS3 mRNA and Nitric Oxide (NO) levels. Two NOS3 markers were associated with susceptibility to MS and early disease development. The NOS3 rs1800779 G-allele (p = 0.04) and GG-genotype (p = 0.02) showed association with susceptibility to MS. Short NOS2 (CCTTT)n (p = 0.03) and short/long repeat (p = 0.04) genotypes also showed associations with MS. These associations were intensified by sub-division of patients into Kuwaiti Arabs and Persians (p NOS3-27 bp-VNTR a-allele was associated with early MS disease onset ≤26 years (p = 0.04). The NOS3-27 bp-VNTR a/b-genotype resulted in 23% lower NO production and the NOS3-rs1800779 AA-genotype resulted in lower NOS3 expression. Haplotypes obtained from NOS2A and NOS3 showed increased susceptibility to MS. NOS1 showed no significant association with MS. This study provides evidence for the association between selected NOS2 and NOS3 markers and MS susceptibility.

  8. A Internet que nos protege

    Directory of Open Access Journals (Sweden)

    Luana Negrelly Saraiva

    2001-02-01

    Full Text Available A partir de uma análise das relações interpessoais nos canais de chat, pretende-se mostrar a Internet como um espaço de proteção da mesma sociedade repressora que a criou, abrindo portas para o desenvolvimento e o resgate dos valores humanos.

  9. AFLATOXICOSE EM SUÍNOS

    Directory of Open Access Journals (Sweden)

    Luciana Silveira Flôres Schoenau

    1994-01-01

    Full Text Available RESUMO É descrito um surto de aflatoxicose em suínos Duroc de 2 a 6 meses, que consumiam ração contaminada por 519 ppb de aflatoxinas. A morbidade foi de 97%. A mortalidade foi alta, mas não determinada com exatidão. Os sinais clínicos incluíam recusa do alimento, pouco ganho ou perda de peso, diarreia e icterícia. Lesões subagudas e crônicas foram observadas em 4 porcos necropsiados. Nas lesões subagudas o fígado era escuro, com áreas centrolobulares hemorrágicas deprimidas, havia edema da parede da vesícula biliar e bile viscosa. Nos casos crônicos o fígado apresentava-se firme e amarelo-alaranjado. Havia líquido citrino nas cavidades e edema no cólon espiral. Havia avermelhamento da mucosa gástrica da região fúndica. Alterações subagudas eram necrose e hemorragias centrolobulares, hepatomegalocitose, fibrose e hiperplasia ductal. Nos casos crônicos havia fibrose, hiperplasia ductal, megalocitose e degeneração gordurosa hepatocelular. O diagnóstico de aflatoxicose foi feito baseado nos sinais clínicos, nos achados morfológicos e na presença de níveis significativos de aflatoxina na ração dos porcos (B1 = 484,3ppb, B2 = 110,8ppb, G1 = 343,7ppb e G2 = 99,2ppb. Frangos submetidos à mesma alimentação também desenvolveram lesões da toxicose.

  10. Pontos referenciais nos acessos cranianos

    Directory of Open Access Journals (Sweden)

    Sebastião Gusmão

    2003-06-01

    Full Text Available O conhecimento da topografia cranioencefálica permite delimitar os acessos cranianos. Sistematiza-se os pontos referenciais, definidos em relação aos pontos craniométricos, usados nos diferentes acessos cranianos. Dos 22 pontos referenciais descritos, os doze primeiros estão em relação com a base do crânio e os demais com a convexidade.

  11. A epilepsia nos tumores cerebrais

    Directory of Open Access Journals (Sweden)

    Luís Marques-Assis

    1969-03-01

    Full Text Available De 411 casos de tumores cerebrais foram estudados 86 (19,4% que apresentaram manifestações epilépticas. A epilepsia foi estudada quanto à duração, ao tipo de manifestação e à severidade, em relação à natureza e à localização dos tumores cerebrais. A análise dos resultados permitiu aos autores chegarem às seguintes conclusões: 1 a epilepsia incidiu em 19,4% dos casos; 2 o oligodendroglioma, as metástases carcinomatosas e o glioblastoma multiforme foram, pela ordem, os tumores mais epileptogênicos; 3 as áreas frontal, parietal e temporal foram, nessa ordem, as localizações mais epileptogênicas; 4 os carcinomas metastáticos predominaram nos casos com epilepsia com menos de um ano de evolução, enquanto que os astrocitomas predominaram nos casos com mais de três anos; quanto à topografia, predominou a região frontal no primeiro grupo e a temporal, no segundo; 5 nas formas mais severas de epilepsia predominaram os oligodendrogliomas e os meningeomas, quanto à natureza, e a região frontotemporal e a foice, quanto à localização; 6 os craniofaringeomas e os meduloblastomas foram os tumores que mais freqüentemente determinaram o aparecimento de convulsões puras; nesses casos, a sela túrsica e a fossa posterior foram as sedes mais freqüentes; 7 os carcinomas metastáticos e os meningeomas, quanto à natureza, e as regiões frontoparietal e parietal, quanto à localização, foram os mais freqüentemente encontrados nos casos com crises de tipo bravais-jacksoniano.

  12. 9 CFR 50.8 - Payment of expenses for transporting and disposing of infected, exposed, and suspect animals.

    Science.gov (United States)

    2010-01-01

    ... Veterinarian in Charge with a copy of either a receipt for expenses paid or a bill for services rendered. Any bill for services rendered by the owner must not be greater than the normal fee for similar...

  13. Relative contributions of NOS isoforms during experimental colitis : endothelial-derived NOS maintains mucosal integrity

    NARCIS (Netherlands)

    Vallance, BA; Dijkstra, G; Qiu, BS; van der Waaij, LA; van Goor, H; Jansen, PLM; Mashimo, H; Collins, SM

    2004-01-01

    The role of nitric oxide (NO) in inflammatory bowel diseases has traditionally focused on the inducible form of NO synthase (iNOS). However, the constitutive endothelial (eNOS) and neuronal (nNOS) isoforms may also impact on colitis, either by contributing to the inflammation or by regulating

  14. NOAA NOS SOS, EXPERIMENTAL - Air Temperature

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have air temperature data. *These services are for testing and evaluation...

  15. NOAA NOS SOS, EXPERIMENTAL - Water Temperature

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have water temperature data. *These services are for testing and evaluation...

  16. NOAA NOS SOS, EXPERIMENTAL - Barometric Pressure

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have barometric pressure data. *These services are for testing and...

  17. NOAA NOS SOS, EXPERIMENTAL - Water Level

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA NOS SOS server is part of the IOOS DIF SOS Project. The stations in this dataset have water surface height above a reference datum. *These services are for...

  18. PODE A ARTE NOS SALVAR?

    Directory of Open Access Journals (Sweden)

    Rodrigo Rizério de Almeida e Pessoa

    2014-09-01

    Full Text Available O desenvolvimento do caráter técnico-científico-industrial da civilização moderna trouxe consigo um renovado interesse em se discutir o homem e seu lugar no mundo. Durante o século XX, seja na arte, literatura ou filosofia, não faltaram vozes anunciando para o futuro o fim do homem ou a submissão de seu pensamento a níveis cada vez maiores de alienação. O interesse ou mesmo a necessidade de se questionar um modo de resistência capaz de trazer o homem de volta a si mesmo deu origem a diferentes leituras acerca do lugar do homem no mundo moderno. Entre elas, destacamos a interpretação da essência humana desenvolvida por Martin Heidegger. Segundo o autor alemão, cumpre-nos romper com o tradicional paradigma da subjetividade, que orientou o modo como a modernidade entendeu o ser do homem. Ora, a intenção dessa pesquisa é justamente demarcar as consequências dessa ruptura com a subjetividade para a compreensão do homem e enfim problematizar as suas implicações teóricas ou filosóficas mais gerais. De fato, desde que o homem se arvorou o título de “senhor da terra” parece que ele se encontra em todos oslugares, quando, na verdade, é justamente no domínio da técnica que ele se encontra o mais distante de si mesmo ou de sua essência. Para reencontrar-se consigo mesmo, faz-se necessário a preparação para o advento do novo homem, e está reservada à arte, ao que parece, abrir caminhos na densa floresta que separa o homem de sua autenticidade. Cabe a nós, portanto, questionar se e em que medida a arte pode cumprir essa tarefa, ou se, ao contrário, estamos esperando dela mais do que pode oferecer.

  19. Nitric Oxide Synthase Enzymes in the Airways of Mice Exposed to Ovalbumin: NOS2 Expression Is NOS3 Dependent

    Directory of Open Access Journals (Sweden)

    Jennifer M. Bratt

    2010-01-01

    Full Text Available Objectives and Design. The function of the airway nitric oxide synthase (NOS isoforms and the lung cell types responsible for its production are not fully understood. We hypothesized that NO homeostasis in the airway is important to control inflammation, which requires upregulation, of NOS2 protein expression by an NOS3-dependent mechanism. Materials or Subjects. Mice from a C57BL/6 wild-type, NOS1−/−, NOS2−/−, and NOS3−/− genotypes were used. All mice strains were systemically sensitized and exposed to filtered air or ovalbumin (OVA aerosol for two weeks to create a subchronic model of allergen-induced airway inflammation. Methods. We measured lung function, lung lavage inflammatory and airway epithelial goblet cell count, exhaled NO, nitrate and nitrite concentration, and airway NOS1, NOS2, and NOS3 protein content. Results. Deletion of NOS1 or NOS3 increases NOS2 protein present in the airway epithelium and smooth muscle of air-exposed animals. Exposure to allergen significantly reduced the expression of NOS2 protein in the airway epithelium and smooth muscle of the NOS3−/− strain only. This reduction in NOS2 expression was not due to the replacement of epithelial cells with goblet cells as remaining epithelial cells did not express NOS2. NOS1−/− animals had significantly reduced goblet cell metaplasia compared to C57Bl/6 wt, NOS2−/−, and NOS3−/− allergen-exposed mice. Conclusion. The airway epithelial and smooth muscle cells maintain a stable airway NO concentration under noninflammatory conditions. This “homeostatic” mechanism is unable to distinguish between NOS derived from the different constitutive NOS isoforms. NOS3 is essential for the expression of NOS2 under inflammatory conditions, while NOS1 expression contributes to allergen-induced goblet cell metaplasia.

  20. Nitric oxide synthase enzymes in the airways of mice exposed to ovalbumin: NOS2 expression is NOS3 dependent.

    Science.gov (United States)

    Bratt, Jennifer M; Williams, Keisha; Rabowsky, Michelle F; Last, Michael S; Franzi, Lisa M; Last, Jerold A; Kenyon, Nicholas J

    2010-01-01

    The function of the airway nitric oxide synthase (NOS) isoforms and the lung cell types responsible for its production are not fully understood. We hypothesized that NO homeostasis in the airway is important to control inflammation, which requires upregulation, of NOS2 protein expression by an NOS3-dependent mechanism. Mice from a C57BL/6 wild-type, NOS1(-/-), NOS2(-/-), and NOS3(-/-) genotypes were used. All mice strains were systemically sensitized and exposed to filtered air or ovalbumin (OVA) aerosol for two weeks to create a subchronic model of allergen-induced airway inflammation. We measured lung function, lung lavage inflammatory and airway epithelial goblet cell count, exhaled NO, nitrate and nitrite concentration, and airway NOS1, NOS2, and NOS3 protein content. Deletion of NOS1 or NOS3 increases NOS2 protein present in the airway epithelium and smooth muscle of air-exposed animals. Exposure to allergen significantly reduced the expression of NOS2 protein in the airway epithelium and smooth muscle of the NOS3(-/-) strain only. This reduction in NOS2 expression was not due to the replacement of epithelial cells with goblet cells as remaining epithelial cells did not express NOS2. NOS1(-/-) animals had significantly reduced goblet cell metaplasia compared to C57Bl/6 wt, NOS2(-/-), and NOS3(-/-) allergen-exposed mice. The airway epithelial and smooth muscle cells maintain a stable airway NO concentration under noninflammatory conditions. This "homeostatic" mechanism is unable to distinguish between NOS derived from the different constitutive NOS isoforms. NOS3 is essential for the expression of NOS2 under inflammatory conditions, while NOS1 expression contributes to allergen-induced goblet cell metaplasia.

  1. 5-HT对大鼠丘脑底核神经元自发放电活动的影响%Effect of 5-hydroxytrptamine on Spontaneous Firing Activities of STN Neurons

    Institute of Scientific and Technical Information of China (English)

    冉红梅; 高东明

    2007-01-01

    目的 观察5-羟色胺(5-HT)对丘脑底核(STN)神经元放电的影响,探索中缝背核(DRN)与STN的联系.方法 应用细胞外记录的方法观察微电泳5-HT、赛庚定及氟西汀对STN神经元放电的影响.结果 微电泳5-HT可使60.34%(35/58)STN神经元的放电频率降低(P<0.01);微电泳赛庚定使35.71%(10/28)神经元自发放电频率增加,多数神经元不受影响;但在微电泳5-HT过程中,给予赛庚定可使大多数(58.06%)神经元放电频率增加;氟西汀使56.255(9/16)STN神经元放电频率降低.结论 5-HT对STN神经元主要为抑制作用,赛庚定可拮抗其作用,氟西汀与5-HT作用效果一致.

  2. Synthesis by spark plasma sintering of a novel protonic/electronic conductor composite: BaCe0.2Zr0.7Y0.1O3−δ /Sr0.95Ti0.9Nb0.1O3−δ (BCZY27/STN95)

    DEFF Research Database (Denmark)

    Fish, Jason; Ricote, Sandrine; Lenrick, Filip

    2013-01-01

    A novel two-phase ceramic composite (cercer) material consisting of a solid solution of barium cerate and -zirconate doped with yttrium (BaCe0.2Zr0.7Y0.1O3−δ : BCZY27), together with niobium-doped strontium titanate (Sr0.95Ti0.9Nb0.1O3−δ : STN95), has been synthesized by solid-state reaction...... %) and showed less reaction between phases. A pseudo-optimum SPS profile was developed, accounting for the effects of thermal expansion mismatch between BCZY27 and STN95. X-ray diffraction indicated secondary phases exist, but there was no indication of their presence at grain boundaries based on thorough study...

  3. Multifaceted NOS Instruction: Contextualizing Nature of Science with Documentary Films

    Science.gov (United States)

    Bloom, Mark; Binns, Ian C.; Koehler, Catherine

    2015-01-01

    This research focuses on inservice science teachers' conceptions of nature of science (NOS) before and after a two-week intensive summer professional development (PD). The PD combined traditional explicit NOS instruction, numerous interactive interventions that highlighted NOS aspects, along with documentary films that portrayed NOS in context of…

  4. mNos2 deletion and human NOS2 replacement in Alzheimer disease models.

    Science.gov (United States)

    Colton, Carol A; Wilson, Joan G; Everhart, Angela; Wilcock, Donna M; Puoliväli, Jukka; Heikkinen, Taneli; Oksman, Juho; Jääskeläinen, Olli; Lehtimäki, Kimmo; Laitinen, Teemu; Vartiainen, Nina; Vitek, Michael P

    2014-08-01

    Understanding the pathophysiologic mechanisms underlying Alzheimer disease relies on knowledge of disease onset and the sequence of development of brain pathologies. We present a comprehensive analysis of early and progressive changes in a mouse model that demonstrates a full spectrum of characteristic Alzheimer disease-like pathologies. This model demonstrates an altered immune redox state reminiscent of the human disease and capitalizes on data indicating critical differences between human and mouse immune responses, particularly in nitric oxide levels produced by immune activation of the NOS2 gene. Using the APPSwDI(+)/(+)mNos2(-/-) (CVN-AD) mouse strain, we show a sequence of pathologic events leading to neurodegeneration,which include pathologically hyperphosphorylated tau in the perforant pathway at 6 weeks of age progressing to insoluble tau, early appearance of β-amyloid peptides in perivascular deposits around blood vessels in brain regions known to be vulnerable to Alzheimer disease, and progression to damage and overt loss in select vulnerable neuronal populations in these regions. The role of species differences between hNOS2 and mNos2 was supported by generating mice in which the human NOS2 gene replaced mNos2. When crossed with CVN-AD mice, pathologic characteristics of this new strain (APPSwDI(+)/(-)/HuNOS2(tg+)/(+)/mNos2(-/-)) mimicked the pathologic phenotypes found in the CVN-AD strain.

  5. Cristais de gases raros nos metais

    OpenAIRE

    Cendotec, Cendotec; CENDOTEC - São Paulo

    1989-01-01

    Durante a fissão, o aumento de volume do combustível no caroço dos reatores nucleares deve-se ao acúmulo de bolhas de gases raros encerrados nos produtos de fissão do urânio. Agora, uma equipe de pesquisadores franceses demonstrou que essas bolhas, supostamente gasosas, eram na verdade sólidos cristalinos quando o bombardeio de íons nos materiais se realizava em temperatura ambiente, e que a elevação da temperatura provoca uma transformação sólido/líquido, perfeitamente reversível. Descobrira...

  6. Pharm GKB: Acute necrosis of liver NOS [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available MeSH: Massive Hepatic Necrosis (D047508) SnoMedCT: Acute necrosis of liver NOS (197273006) UMLS: C0001364 (C...000011090) Common Searches Search Medline Plus Search CTD Pharm GKB: Acute necrosis of liver NOS ...

  7. ¿Las emociones nos distraen?

    Directory of Open Access Journals (Sweden)

    Antonia Pilar Pacheco-Unguetti

    2014-06-01

    Full Text Available ¿Leerás este artículo hasta el final sin interrupciones? Puede que, mientras lo intentas, recibas algún mensaje de whatsapp, se abra una ventana emergente en tu ordenador con una oferta de viajes al Caribe o el cartero llame dos veces a tu puerta. También puede ser que simplemente no tengas un buen día y te resulte especialmente difícil concentrarte. Vivimos expuestos a multitud de estímulos distractores externos, algunos tan inesperados o extraños que entorpecen irremediablemente nuestra concentración en una tarea (distracción por novedad. Pero la distracción también puede tener una causa interna y cómo nos sentimos puede influir en cuánto nos distraemos.

  8. Renal nerves and nNOS

    DEFF Research Database (Denmark)

    Kompanowska-Jezierska, Elzbieta; Wolff, Helle; Kuczeriszka, Marta

    2008-01-01

    It was hypothesized that renal sympathetic nerve activity (RSNA) and neuronal nitric oxide synthase (nNOS) are involved in the acute inhibition of renin secretion and the natriuresis following slow NaCl loading (NaLoad) and that RSNA participates in the regulation of arterial blood pressure (MABP......). This was tested by NaLoad after chronic renal denervation with and without inhibition of nNOS by S-methyl-thiocitrulline (SMTC). In addition, the acute effects of renal denervation on MABP and sodium balance were assessed. Rats were investigated in the conscious, catheterized state, in metabolic cages...... of acutely and chronically denervated rats were less than control (15% and 9%, respectively, P renal denervation (14.5 +/- 0.2 vs. 19.3 +/- 1.3 mIU/l, P

  9. ¿Comer carne nos hizo inteligentes?

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Marmelada

    2007-12-01

    Full Text Available La inteligencia abstracta es lo que más nos diferencia de los restantes animales. Su origen continúa siendo un misterio sujeto a debate. Hay quienes afirman que emergió paulatinamente. En este sentido se ha propuesto que incorporar la carne a la dieta de los homínidos pudo haber sido el detonante que la hizo surgir. Pero esta hipótesis tiene sus lagunas.

  10. Correlação do tipo de biópsia e sua validade diagnóstica nos tumores músculo-esqueléticos em distintas topografias Correlation of the type of biopsy and its diagnostic validity in musculoskeletal tumors in different locations

    Directory of Open Access Journals (Sweden)

    Karina Levy Siqueira

    2008-02-01

    Full Text Available OBJETIVO: O propósito deste estudo foi aquilatar a precisão das biópsias por trefina de Jamshidi, realizadas no Serviço de Ortopedia Oncológica da UNIFESP/EPM, em tumores músculo-esqueléticos, em distintas topografias, tendo como objetivo propor uma classificação para categorizar as biópsias conforme a sua efetividade. MÉTODOS: Foram analisados de modo retrospectivo 107 pacientes que haviam sido biopsiados com agulha de Jamshidi e posteriormente submetidos a ressecção do tumor seguida de exame anatomopatológico da peça cirúrgica. A média de idade dos pacientes foi de 23,5 anos (2,7 a 68,7 anos. Quanto ao sexo, 40,2% eram mulheres e 50,8% homens. Desse universo, 86 apresentavam tumor ósseo (80,4% e 21, tumor de partes moles (19,6%. Quanto à localização, os tumores encontravam-se preferencialmente nos membros inferiores (72%, seguidos dos membros superiores (22,4% e pelve (5,6%. Foi proposta conjuntamente uma classificação para categorizar as biópsias conforme o seu resultado em excelente, bom, regular e mau. RESULTADOS: A análise dos dados gerais demonstrou resultados excelentes em 80,4% das biópsias, bons em 8,4%, regulares em 2,8% e ruins em 8,4%. Somando-se os resultados excelentes e bons, encontram-se 88,8% dos casos. Nos casos avaliados, encontraram-se 3,7% de complicações; em nenhum caso a biópsia contra-indicou a cirurgia conservadora com preservação do membro. CONCLUSÃO: As biópsias com agulha de Jamshidi representam método bastante eficiente de diagnóstico das lesões músculo-esqueléticas, com baixo índice de complicações e bons resultados comparáveis aos das biópsias abertas.OBJECTIVE:The purpose of this study is to evaluate trephine biopsies with Jamshidi needle performed at the Oncologic Orthopedics Service at UNIFESP/EPM, in musculoskeletal tumors in different locations, in order to propose an effectiveness classification of biopsy categories. METHODS: A retrospective analysis was made of 107

  11. Mito da guerra nos Estados Unidos

    OpenAIRE

    Spini, Ana Paula; UFU

    2011-01-01

    Este artigo tem como objetivo compreender aspectos do mito da guerra nos Estados Unidos, em uma abordagem que prioriza as dissensões internas acerca da legitimidade de uma guerra e os dispositivos midiáticos de criação do consenso nacional. Procura-se, assim, demonstrar que o mito da guerra é constantemente reformulado à luz da conjuntura internacional, da prática da guerra, da propaganda e da resistência interna às intervenções militares. Palavras-Chave: Guerra; Estados Unidos; Mídia....

  12. O riso nos desenhos do cartunista Lage

    OpenAIRE

    Cabral, Alexandre da Costa

    2015-01-01

    Este trabalho trata as Caricaturas de Hélio Roberto Lage sob análise Semiótica da corrente gremasiana das tiras de humor Ânsia de Amar e suas características gerais; e também nas charges, desvelando o sentido das piadas nas ilustrações. Objetivando a compreensão deste tema foram perscrutadas as categorias que envolveram o objeto de produção do caricaturista estudado. Essas categorias envolvem a história e os conceitos das vertentes da Caricatura, os fatores de motivação para o riso nos desenh...

  13. Lesão muscular nos atletas

    OpenAIRE

    Barroso,Guilherme Campos; Thiele,Edilson Schwansee

    2011-01-01

    Este artigo tem por objetivo demonstrar a fisiologia, o diagnóstico e o tratamento das lesões musculares com foque nos atletas, suas demandas e expectativas. As lesões musculares estão entre as queixas mais comuns no atendimento ortopédico, ocorrendo tanto em atletas como em não atletas. Estas lesões caracterizam um desafio para os especialistas, haja vista a lenta recuperação que afasta o atleta dos treinamentos e competições, as frequentes sequelas e a recorrência das lesões. A maior parte ...

  14. Single nucleotide polymorphisms in the NOS2 and NOS3 genes are associated with exhaled nitric oxide.

    Science.gov (United States)

    Dahgam, Santosh; Nyberg, Fredrik; Modig, Lars; Naluai, Asa Torinsson; Olin, Anna-Carin

    2012-03-01

    Polymorphisms in nitric oxide synthase genes (NOS1, NOS2, and NOS3) have been suggested to have a major impact on fraction of exhaled nitric oxide (FENO), a biomarker of airway inflammation. However, the genetic contribution of NOS polymorphisms to FENO is not fully understood. The aim of this study was to investigate comprehensively the association between single nucleotide polymorphisms (SNPs) in all three NOS genes and FENO in an adult population, and to assess whether such associations are modified by asthma or atopy. In 1737 adults from a Swedish general population sample, FENO was measured and genetic variation in the NOS genes was assessed using 49 SNPs. The genetic effect of NOS polymorphisms on FENO, asthma, and atopy was estimated using multiple regression methods. In a multi-SNP model based on stepwise regression analysis, two SNPs in NOS2 and one in NOS3 showed independent associations with levels of FENO. For NOS2 SNP rs9901734, subjects had 5.3% (95% CI 1.0% to 9.7%) higher levels of FENO per G allele, and for rs3729508, subjects with CC or CT genotypes had 9.4% (95% CI 3.1% to 15.2%) higher levels compared with TT. For NOS3 SNP rs7830, subjects with GT or TT had 5.6% (95% CI 0.4% to 11.1%) higher levels than GG; the genetic effect of this SNP was stronger in asthmatics (21.9%, 95% CI 4.6% to 42.0%). These results suggest that NOS2 is the major NOS gene determining variability in exhaled nitric oxide in the healthy adult population, while NOS3 may play a more important role in asthmatic adults.

  15. Expression of zebrafish nos2b surrounds oral cavity.

    Science.gov (United States)

    Poon, Kar-Lai; Richardson, Michael; Korzh, Vladimir

    2008-06-01

    Inducible nitric oxide synthase (NOS2) catalyzes the production of nitric oxide (NO), and is one of the factors establishing innate immunity. In zebrafish, Nos2 is represented by nos2a and nos2b. Here, we report the cloning and expression pattern of the zebrafish nos2b gene, which does not seem to participate in induced immune response. nos2b was mapped to zebrafish linkage group 15. The spatial and temporal expression pattern of nos2b in embryonic zebrafish was analyzed by whole-mount in situ hybridization. nos2b is expressed constitutively in two primordia located along the ventral midline. The first group of cells contributes to the neurohypophysis. Initially at the level of the ventral hindbrain, the second group of cells migrates closely with the thyroid primordium to its final position at the basihyal by 3 dpf. Thus, the analysis of expression pattern of nos2b reveals complex morphogenetic movements resulting in its expression surrounding the oral cavity.

  16. The Relationship Between Endothelial Nitric Oxide Synthase Gene (NOS3) Polymorphisms, NOS3 Expression, and Varicocele.

    Science.gov (United States)

    Kahraman, Cigdem Yuce; Tasdemir, Sener; Sahin, Ibrahim; Marzioglu Ozdemir, Ebru; Yaralı, Oguzhan; Ziypak, Tevfik; Adanur, Senol; Kahraman, Mustafa; Tatar, Abdulgani

    2016-04-01

    Varicocele is an abnormal enlargement of the pampiniform venous plexus in the scrotum. Varicocele is the most common cause of secondary male infertility. Nitric oxide (NO), which has a role on varicocele pathophysiology, is synthesized by endothelial nitric oxide synthase gene (NOS3). In our study, we aimed to explain the relationship between varicocele, three common NOS3 polymorphisms (T-786C, G894T, 4b/a), and NOS3 mRNA expression levels. We investigated NOS3 T-786C, G894T, and 4b/a polymorphisms in 102 patients with varicocele and 100 healthy controls. Twenty-four patients and 17 controls were chosen for expression studies based on polymorphism subgroupings. Subgroup 1 includes patients who have no minor allele polymorphisms, and subgroups 2, 3, and 4 have T-786C, G894T, and 4b/a polymorphisms, respectively. The 4b/a polymorphism demonstrated significantly elevated levels in both allele and genotype analysis in the control group compared to the patient group. The G894T polymorphism was statistically elevated for genotypic frequencies in the patient group compared to the control group, but this finding did not extend to allelic frequencies. There were no statistically significant differences in either the allelic or genotypic frequencies between patients and control groups for the T-786C polymorphism. When patient and control expression levels were compared without considering the subgroups, the NOS3 expression level was found to be statistically higher in the patient group. There were no statistically significant differences in the patient and control group expression levels when stratified by subgroup, nor was there any effect of the polymorphisms under study on expression levels. The 4b/a polymorphism may have a protective effect for varicocelem and G894T polymorphism may contribute to varicocele occurrence by lowering the level of NO. The higher NOS3 expression levels in the patient group may be a kind of dilator compensatory mechanism to protect vascular

  17. COMPOSTAGEM DE DEJETOS DE SUÍNOS

    Directory of Open Access Journals (Sweden)

    Eduardo Gonçalves Xavier

    2008-06-01

    Full Text Available A compostagem, como forma de tratamento para os dejetos de suínos, pode ser uma alternativa viável para gerenciar osefluentes desta importante atividade agropecuária. Deste modo, foi conduzido um estudo em condições de campo em 16 granjas deprodutores de suínos, no sistema de integração com a Perdigão Agroindustrial S/A Regional RS no Sistema Vertical Terminador(SVT, onde os produtores recebem os animais na saída da creche e realizam as fases de crescimento e terminação. Odelineamento experimental utilizado foi o completamente casualizado, com os seguintes tratamentos: Tratamento 1-substratocomposto por serragem, Tratamento 2-substrato composto por maravalha, Tratamento 3-substrato composto por cama de aviário eTratamento 4-Sistema convencional de tratamento de dejetos. Os tratamentos foram distribuídos às unidades experimentais(granjas de maneira aleatória, onde cada tratamento teve quatro repetições. Foram analisadas as variáveis meteorológicas,temperatura do processo de compostagem, volume de dejetos produzidos e análise físico-química do composto e dos dejetoslíquidos. Os dados coletados foram submetidos à análise com o uso de um programa estatístico, sendo que as médias dostratamentos foram comparadas através do uso de contrastes ortogonais. Houve efeito de tratamento para as variáveis volume ematéria seca dos dejetos. Conclui-se que o sistema muda as características físicas dos dejetos, reduz o volume e concentranutrientes.

  18. iNOS-dependent sweating and eNOS-dependent cutaneous vasodilation are evident in younger adults, but are diminished in older adults exercising in the heat.

    Science.gov (United States)

    Fujii, Naoto; Meade, Robert D; Alexander, Lacy M; Akbari, Pegah; Foudil-Bey, Imane; Louie, Jeffrey C; Boulay, Pierre; Kenny, Glen P

    2016-02-01

    Nitric oxide synthase (NOS) contributes to sweating and cutaneous vasodilation during exercise in younger adults. We hypothesized that endothelial NOS (eNOS) and neuronal NOS (nNOS) mediate NOS-dependent sweating, whereas eNOS induces NOS-dependent cutaneous vasodilation in younger adults exercising in the heat. Further, aging may upregulate inducible NOS (iNOS), which may attenuate sweating and cutaneous vasodilator responses. We hypothesized that iNOS inhibition would augment sweating and cutaneous vasodilation in exercising older adults. Physically active younger (n = 12, 23 ± 4 yr) and older (n = 12, 60 ± 6 yr) adults performed two 30-min bouts of cycling at a fixed rate of metabolic heat production (400 W) in the heat (35°C). Sweat rate and cutaneous vascular conductance (CVC) were evaluated at four intradermal microdialysis sites with: 1) lactated Ringer (control), 2) nNOS inhibitor (nNOS-I, NPLA), 3) iNOS inhibitor (iNOS-I, 1400W), or 4) eNOS inhibitor (eNOS-I, LNAA). In younger adults during both exercise bouts, all inhibitors decreased sweating relative to control, albeit a lower sweat rate was observed at iNOS-I compared with eNOS-I and nNOS-I sites (all P 0.05). We show that iNOS and eNOS are the main contributors to NOS-dependent sweating and cutaneous vasodilation, respectively, in physically active younger adults exercising in the heat, and that iNOS inhibition does not alter sweating or cutaneous vasodilation in exercising physically active older adults.

  19. Regulation of eNOS-derived superoxide by endogenous methylarginines.

    Science.gov (United States)

    Druhan, Lawrence J; Forbes, Scott P; Pope, Arthur J; Chen, Chun-An; Zweier, Jay L; Cardounel, Arturo J

    2008-07-08

    The endogenous methylarginines, asymmetric dimethylarginine (ADMA) and N (G)-monomethyl- l-arginine (L-NMMA) regulate nitric oxide (NO) production from endothelial NO synthase (eNOS). Under conditions of tetrahydrobiopterin (BH 4) depletion eNOS also generates (*)O 2 (-); however, the effects of methylarginines on eNOS-derived (*)O 2 (-) generation are poorly understood. Therefore, using electron paramagnetic resonance spin trapping techniques we measured the dose-dependent effects of ADMA and L-NMMA on (*)O 2 (-) production from eNOS under conditions of BH 4 depletion. In the absence of BH 4, ADMA dose-dependently increased NOS-derived (*)O 2 (-) generation, with a maximal increase of 151% at 100 microM ADMA. L-NMMA also dose-dependently increased NOS-derived (*)O 2 (-), but to a lesser extent, demonstrating a 102% increase at 100 microM L-NMMA. Moreover, the native substrate l-arginine also increased eNOS-derived (*)O 2 (-), exhibiting a similar degree of enhancement as that observed with ADMA. Measurements of NADPH consumption from eNOS demonstrated that binding of either l-arginine or methylarginines increased the rate of NADPH oxidation. Spectrophotometric studies suggest, just as for l-arginine and L-NMMA, the binding of ADMA shifts the eNOS heme to the high-spin state, indicative of a more positive heme redox potential, enabling enhanced electron transfer from the reductase to the oxygenase site. These results demonstrate that the methylarginines can profoundly shift the balance of NO and (*)O 2 (-) generation from eNOS. These observations have important implications with regard to the therapeutic use of l-arginine and the methylarginine-NOS inhibitors in the treatment of disease.

  20. Pharm GKB: Acute cholecystitis NOS [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Overview Alternate Names: PharmGKB Accession Id: PA165108810 External Vocabularies MeSH: Cholecystitis, Acut...e (D041881) SnoMedCT: Acute cholecystitis NOS (197411000) UMLS: C0149520 (C0149520) MedDRA: Acute... cholecystitis (10000691) NDFRT: Cholecystitis, Acute [Disease/Finding] (N0000010952) Common Searches Search Medline Plus Search CTD Pharm GKB: Acute cholecystitis NOS ...

  1. Pharm GKB: Acute stress reaction NOS [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available MeSH: Stress Disorders, Traumatic, Acute (D040701) SnoMedCT: Acute stress reaction NOS (268657003) UMLS: C02...36816 (C0236816) MedDRA: Acute reaction to stress (10001039) NDFRT: Stress Disorders, Traumatic, Acute [Dise...ase/Finding] (N0000011158) Common Searches Search Medline Plus Search CTD Pharm GKB: Acute stress reaction NOS ...

  2. Face and emotion recognition in MCDD versus PDD-NOS

    NARCIS (Netherlands)

    Herba, Catherine M.; de Bruin, Esther; Althaus, Monika; Verheij, Fop; Ferdinand, Robert F.

    2008-01-01

    Previous studies indicate that Multiple Complex Developmental Disorder (MCDD) children differ from PDD-NOS and autistic children on a symptom level and on psychophysiological functioning. Children with MCDD (n = 21) and PDD-NOS (n = 62) were compared on two facets of social-cognitive functioning: id

  3. Face and Emotion Recognition in MCDD versus PDD-NOS

    Science.gov (United States)

    Herba, Catherine M.; de Bruin, Esther; Althaus, Monika; Verheij, Fop; Ferdinand, Robert F.

    2008-01-01

    Previous studies indicate that Multiple Complex Developmental Disorder (MCDD) children differ from PDD-NOS and autistic children on a symptom level and on psychophysiological functioning. Children with MCDD (n = 21) and PDD-NOS (n = 62) were compared on two facets of social-cognitive functioning: identification of neutral faces and facial…

  4. Stress serration and arch-shaped Lüders stress plateau behaviour of Ti-50.8 at% Ni wire prepared by selective electrical resistance over-aging

    Science.gov (United States)

    Meng, Qinglin; Wu, Zhigang; Bakhtiari, Reza; Zhang, Junsong; Yang, Hong; Liu, Yinong

    2016-11-01

    Joule heating of NiTi shape memory alloy wires is a commonly applied technique for heat treatment and shape setting in many applications. Another innovative use of this method is to produce functionally graded NiTi. In this study, NiTi wires with spatially varied shape memory characteristics along the length were created by electrical resistance over-aging of a Ni-rich superelastic NiTi alloy. The stress-strain behaviour of such wires exhibited some new and unique characteristics during the stress-induced martensitic transformation, including two discrete stress plateaus, stress serration during transition between the two stress plateaus and an arch-shaped stress plateau in the over-aged section. These unique features have direct implications to design using NiTi alloys and the underlying mechanisms are explained in this study.

  5. Subjetividade, alteridade e desamparo nos tempos atuais

    Directory of Open Access Journals (Sweden)

    Tiago Humberto Rodrigues Rocha

    2014-12-01

    Full Text Available Este trabalho vai ao encontro do que foi realizado ao longo da teoria freudiana: contextualizar o homem em sua ordem social circundante e pensar as relações que se estabelecem na configuração do laço social. O objetivo é refletir sobre as possibilidades de outras articulações metapsicológicas, que permitam compreender a relação dos dispositivos contemporâneos criados para lidar com odesamparo, e as implicações de seu uso recorrente na condição desejante.Para tanto, nos deteremos a propósito das tensões entre as três instâncias do aparelho psíquico: id, ego e superego. Analisando as relações que estruturam o laço social, conseguimos repensar proposições psicanalíticas consagradas, tais como alteridade, desejo, pulsão e seus destinos.

  6. O amor nos tempos de Narciso

    Directory of Open Access Journals (Sweden)

    Izabel Cristina Rios

    2008-06-01

    Full Text Available O presente artigo discute a dificuldade do encontro amoroso nos tempos atuais. Parte da leitura psicanalítica sobre as origens dos modos de amar na fase do desenvolvimento psicossexual chamada narcisismo primário, na qual o eu e o outro se constroem dentro de um contexto cultural. Ao longo da vida, a identidade continua sendo modelada pela interação do eu com o mundo em que vive. Do estudo de alguns aspectos do mundo atual, desenvolve a idéia de que a cultura contemporânea apresenta valores e modelos que não sustentam as relações intersubjetivas porque estimulam o modo narcísico de subjetivação. Valores como individualismo, consumismo, culto ao corpo e à imagem, produzem comportamentos que revelam a supremacia do eu. No mundo atual, cada um está voltado para si mesmo, e o outro, como alguém diferente do eu, não é desejável. Essa posição subjetiva impede o autêntico encontro amoroso e sua sobrevivência.

  7. Using a Professional Development Program for Enhancing Chilean Biology Teachers' Understanding of Nature of Science (NOS) and Their Perceptions About Using History of Science to Teach NOS

    Science.gov (United States)

    Pavez, José M.; Vergara, Claudia A.; Santibañez, David; Cofré, Hernán

    2016-05-01

    A number of authors have recognized the importance of understanding the nature of science (NOS) for scientific literacy. Different instructional strategies such as decontextualized, hands-on inquiry, and history of science (HOS) activities have been proposed for teaching NOS. This article seeks to understand the contribution of HOS in enhancing biology teachers' understanding of NOS, and their perceptions about using HOS to teach NOS. These teachers ( N = 8), enrolled in a professional development program in Chile are, according to the national curriculum, expected to teach NOS, but have no specific NOS and HOS training. Teachers' views of NOS were assessed using the VNOS-D+ questionnaire at the beginning and at the end of two modules about science instruction and NOS. Both the pre- and the post-test were accompanied by interviews, and in the second session we collected information about teachers' perceptions of which interventions had been more significant in changing their views on NOS. Finally, the teachers also had to prepare a lesson plan for teaching NOS that included HOS. Some of the most important study results were: significant improvements were observed in teachers' understanding of NOS, although they assigned different levels of importance to HOS in these improvements; and although the teachers improved their understanding of NOS, most had difficulties in planning lessons about NOS and articulating historical episodes that incorporated NOS. The relationship between teachers' improved understanding of NOS and their instructional NOS skills is also discussed.

  8. mRNA expression and localization of bNOS, eNOS and iNOS in human cervix at preterm and term labour

    Directory of Open Access Journals (Sweden)

    Byström Birgitta

    2005-08-01

    Full Text Available Abstract Background Preterm birth is the primary cause of the neonatal mortality and morbidity. There will be no preterm birth without a cervical softening. Nitric oxide (NO is shown to be a mediator of term cervical ripening. The aim of this study was to investigate mRNA expression of the three isomers of NO synthases (NOS and to identify them by immunohistochemistry in the human cervix at preterm birth compared to term. Methods The three isomers of NOS- inducible (iNOS, endothelial (eNOS and neuronal (bNOS – were investigated in the human cervix. The expression of mRNA was determined using Real-Time Multiplex RT-PCR. The localisation of synthases in the cervical tissue was analysed using immunohistochemistry. Cervical biopsies were obtained from 4 groups of women without clinical signs of infection: preterm (PTL, term labour (TL, preterm not in labour (PTnotL and term not in labour (TnotL patients. One-Way ANOVA, Kruskal-Wallis, Student t-test or Mann-Whitney test were applied as appropriate to determine statistically significant differences among the groups. Results Patients in preterm labour had significantly (p Conclusion The mRNA levels were higher in the preterm labour group compared to the women at term labour. The significant increase of the eNOS mRNA expression, from the unripe to the favourable cervical state during labour, may indicate a role of eNOS and supports the role of NO in the cervical ripening process. All the three synthases were identified by immunohistochemistry in all the groups of study.

  9. Inflexões subalternas nos cosmopolitismos vernaculares

    Directory of Open Access Journals (Sweden)

    Sneja Gunew

    2009-01-01

    Full Text Available O conceito sobre o termo relativamentre novo, “cosmopolitismos vernaculares”, identifica as responsabilidades e os contextos globais ao mesmo tempo que reconhece que eles estão sempre enraizados e enredados em interesses locais, os quais incluem os grupos minoritários que competem dentro da nação. Este artigo examina o termo “europeu” com o objetivo de desnudar os debates revisionistas sobre o cosmopolitismo, especialmente em relação aos “cosmopolitismos vernaculares” que funcionam como uma maneira de incluir os “cosmopolitismos subalternos” por meio da desagregação do cosmopolitismo, num movimento análogo à noção de “processo democrático agnóstico” de Stuart Hall. O paradoxo da frase acima reflete o movimento duplo desses debates: no termo cunhado por Homi Bhabha o “doméstico” ou “nativo” vernacular está sempre em uma relação dialógica com a “ação a distância” do cosmopolitismo global. Exploro essa dinâmica ao focalizar os significados discrepantes de “europeu” e dos termos a ele associados. Neste artigo, meu argumento central é: os termos “oeste” e “europeu” devem ser desconstruídos para que não possam mais ser invocados, nos debates pós-coloniais, como incontestáveis categorias heurísticas como, por exemplo, o “oeste e o resto.” Os novos debates sobre cosmopolitismo abrem caminho para se reconhecer, como estados-nação e como parte da União Europeia, a heterogeneidade cultural de tais entidades geopolíticas. Reconhecer o cosmopolitismo dos grupos subalternos facilita esse empreendimento e ajuda a restabelecer uma perspectiva “planetária.”

  10. Synthesis of 21-Thioureido or 21-Ureidocorticosteroids as NOS Inhibitors

    Institute of Scientific and Technical Information of China (English)

    PENG Jiu-He; HAN Chong; LI Bing-Jie; CHENG Jin-Pei

    2003-01-01

    @@ Aryl or alkyl thioureas are known as NOS inhibitors, [1~ 4] in this paper we reported the synthesis of 21-thioureido or 21-ureidocorticosteroids as potential NOS inhibitors. The title compounds were prepared from primary 21aminocorticosteroids and in vivo generated aryl isothiocynates. For comparison, 21-ureidocorticoids were synthesized in a similar way. Scheme 1 shows the preparation of 21-thioureido and 21-ureidoprednisolone. Other corticosteroids' 2 1-thioureido or ureido derivatives, such as hydrocortisone' s, methylprednisolne' s, dexamethasone' s, betamethasone' s, RS' s, cortisone' s and prednisone' s, were also prepared. Preliminary pharmacology evaluation showed that they possessed NOS inhibiting activities.

  11. Regulation of eNOS enzyme activity by posttranslational modification.

    Science.gov (United States)

    Heiss, Elke H; Dirsch, Verena M

    2014-01-01

    The regulation of endothelial NO synthase (eNOS) employs multiple different cellular control mechanisms impinging on level and activity of the enzyme. This review aims at summarizing the current knowledge on the posttranslational modifications of eNOS, including acylation, nitrosylation, phosphorylation, acetylation, glycosylation and glutathionylation. Sites, mediators and impact on enzyme localization and activity of the single modifications will be discussed. Moreover, interdependence, cooperativity and competition between the different posttranslational modifications will be elaborated with special emphasis on the susceptibility of eNOS to metabolic cues.

  12. A teoria fundamentada nos dados como abordagem da pesquisa interpretativa

    OpenAIRE

    Cassiani, Silvia Helena De Bortoli; Caliri,Maria Helena Larcher; Pelá,Nilza Teresa Rotter

    1996-01-01

    Pesquisa interpretativa envolve os estudos da linha qualitativa e a pesquisa indutiva. Na classificação apresentada por LOWENBERG (1994) a teoria fundamentada nos dados é um tipo de pesquisa interpretativa situada como uma variante dentro do interacionismo simbólico. Face à pouca utilização desta metodologia nos estudos nacionais, este estudo teve por objetivo tratar da teoria fundamentada nos dados, enquanto referencial metodológico, apresentando e indicando seu método. As seguintes etapas f...

  13. Association of common eNOS/NOS3 polymorphisms with preeclampsia in Tunisian Arabs.

    Science.gov (United States)

    Ben Ali Gannoun, Marwa; Zitouni, Hedia; Raguema, Nozha; Maleh, Wided; Gris, Jean-Christophe; Almawi, Wassim; Mahjoub, Touhami

    2015-09-15

    We investigated the association of endothelial nitric oxide synthase (NOS3) polymorphisms -786T>C, 27-bp repeat 4b/4a, and Glu298Asp with preeclampsia (PE). This was a case-control study involving 345 unrelated Tunisian women with PE and 289 unrelated age- and ethnically matched control women. The -786C allele was significantly increased in PA patients when compared to healthy controls (P=0.015). In contrast, MAF of Glu298Asp (P=0.103) and 4b/4a (P=0.168) were not significantly different between the study groups. Higher frequencies of heterozygous Glu298/298Asp and homozygous -786T/-786T genotypes were seen in PE cases compared to healthy subjects. The combination of genotypes 221 (-786T>C, Glu298Asp, 4a/4a) was more in PE cases compared with control women (17.68% vs. 8.36%; P=0.029). Multivariate regression analysis confirmed this association. Genetic variation at the NOS3 locus represents a genetic risk factor for increased susceptibility to PE. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Intracerebrally localized sarcoma NOS - an interdisciplinary challenge; Intrazerebral lokalisiertes Sarkom NOS - eine interdisziplinaere Herausforderung

    Energy Technology Data Exchange (ETDEWEB)

    Holzmeister, R.; Spiegl, K.; Hammer, J. [Krankenhaus Barmherzige Schwestern, Linz (Austria). Abt. Radioonkologie; Schindler, C. [Landes-Nervenklinik Wagner-Jauregg, Linz (Austria). Inst. fuer Pathologie; Aichholzer, M. [Landes-Nervenklinik Wagner-Jauregg, Linz (Austria). Abt. fuer Neurochirurgie; Pichler, J. [Landes-Nervenklinik Wagner-Jauregg, Linz (Austria). Interne Ambulanz; Trenkler, J. [Landes-Nervenklinik Wagner-Jauregg, Linz (Austria). Inst. fuer Radiologie

    2007-06-15

    Background: In the literature, surveys of malignant intracerebral nerve sheath tumors are very rare. Therapeutic guidelines do not exist. Case Report: A 28-year-old female patient presented with a tumor in the postcentral region of the left parietal lobe. The specimen could not be categorized into a common tumor entity and was classified as sarcoma NOS. Shortly after surgery, a recurrence occurred followed by a further excision. Due to the rapid tumor growth irradiation with CT-aided treatment planning has been started immediately afterwards. A dose of 5,400 cGy in 22 fractions was administered. Result: 2 weeks after treatment, the patient presented with a noticeable tumor regression (magnetic resonance imaging). She developed pulmonary metastases. A partial remission could be achieved by systemic chemotherapy. Unfortunately, the patient died because of an exacerbation of a hepatic encephalopathy. Conclusion: In cases of intracerebrally localized sarcomas NOS, the earliest possible start of radiotherapy after surgery seems useful because of the noticed radiosensitivity of these tumors. In regard of the local control, this tumor entity shows a documented excellent response to radiotherapy. Expectedly, distant metastases cannot be influenced. Interdisciplinary cooperation is mandatory to enhance the diagnostic process, the treatment decisions, and the results. (orig.)

  15. Effect of Cerous Nitrate on NOS Activity and iNOS mRNA Level in Rat Liver

    Institute of Scientific and Technical Information of China (English)

    杨维东; 刘洁生; 王艇; 雷衡毅; 龚孟濂; 杨燕生

    2001-01-01

    The effect of cerous nitrate on activity of NOS and expression of iNOS in rat hepatocyte was studied by means of reverse transcription-polymerase chain reaction (RT-PCR). The result shows that neither high (50 mg·kg-1) nor low(1 mg·kg-1) dose of cerous nitrate can induce the increase of expression of iNOS mRNA, but an increase of activity was observed after administration of cerous nitrate. Possible mechanism for these phenomena was discussed.

  16. NOAA/NOS and USCGS Seabed Descriptions from Hydrographic Surveys

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA/NOS and USCGS Seabed Descriptions from Hydrographic Surveys database is a compilation of surficial sediment composition from multiple sources for over...

  17. NOS CO-OPS Meteorological Data, Visibility, 6-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has Visibility data from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS). WARNING: These preliminary data have not been...

  18. NOS CO-OPS Meteorological Data, Air Temperature, 6-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has Air Temperature data from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS). WARNING: These preliminary data have not...

  19. NOS CO-OPS Water Level Data, Verified, 6-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has verified (quality-controlled), 6-minute, water level (tide) data from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS)....

  20. NOS CO-OPS Meteorological Data, Water Temperature, 6-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has Water Temperature data from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS). WARNING: These preliminary data have not...

  1. NOS CO-OPS Meteorological Data, Relative Humidity, 6-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has Relative Humidity data from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS). WARNING: These preliminary data have not...

  2. NOS CO-OPS Water Level Data, Verified, High Low

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has verified (quality-controlled), daily, high low water level (tide) data from NOAA NOS Center for Operational Oceanographic Products and Services...

  3. NOS CO-OPS Meteorological Data, Conductivity, 6-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has Conductivity data from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS). WARNING: These preliminary data have not been...

  4. NOS CO-OPS Meteorological Data, Rain Fall, 6-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has Rain Fall data from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS). WARNING: These preliminary data have not been...

  5. NOS CO-OPS Meteorological Data, Wind, 6-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has Wind data from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS). WARNING: These preliminary data have not been subjected...

  6. NOS CO-OPS Meteorological Data, Barometric Pressure, 6-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has Barometric Pressure data from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS). WARNING: These preliminary data have not...

  7. 78 FR 50395 - Endangered Species; File Nos. 17557 and 17273

    Science.gov (United States)

    2013-08-19

    ... NOS Lab and used to support law enforcement actions, research studies (primarily genetics), and... parts and samples would be used to support law enforcement actions, research studies (primarily genetics...

  8. NOS CO-OPS Water Level Data, Verified, Hourly

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has verified (quality-controlled), hourly, water level (tide) data from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS)....

  9. NOS CO-OPS Active Currents Data, 6-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has surface Active Currents data from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS). WARNING: These raw data have not...

  10. NOS CO-OPS Water Level Data, Preliminary, 1-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has recent, preliminary (not quality-controlled), 1-minute, water level (tide) data from NOAA NOS Center for Operational Oceanographic Products and...

  11. METAFICÇÃO NOS ROMANCES DE MACHADO DE ASSIS

    Directory of Open Access Journals (Sweden)

    Janine Resende Rocha

    2010-05-01

    Full Text Available Nos romances de Machado de Assis, a metaficção é caracterizada de maneira permanente. Este ensaio pretende observar o efeito provocado nessas narrativas pela reflexão do ficcional produzida por elas.

  12. NOS CO-OPS Water Level Data, Preliminary, 6-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has recent, preliminary (not quality-controlled), 6-minute, water level (tide) data from NOAA NOS Center for Operational Oceanographic Products and...

  13. A ciência nos jornais

    Directory of Open Access Journals (Sweden)

    Isaltina Maria de Azevedo Mello Gomes

    2008-11-01

    Full Text Available O objetivo central deste artigo é apontar os fenômenos lingüí­sticos envolvidos na transposição de entrevistas realizadas com cientistas em textos jornalí­sticos publicados na imprensa diária. Tomamos como objeto de análise conjuntos de textos (entrevistas e matérias jornalí­sticas publicados no Jornal do Commercio, que nos permitiram identificar as principais operações lingüí­sticas e as repercussões dessa transformação no conteíºdo proposicional. Nossa análise mostra modificações substanciais entre a entrevista e o texto jornalí­stico, mas normalmente a idéia básica do texto original é preservada. Asimprecisões atribuí­das pelos cientistas aos textos jornalí­sticos de divulgação cientí­fica são muito mais uma questão de mudança da perspectiva de interesse do que propriamente distorção de informações. Mesmo se tratando de um estudo de caso, acreditamos que nossas conclusões indicam o que geralmente ocorre na retextualização de entrevistas em textos de divulgação cientí­fica para a imprensa diária.Abstract: The main purpose of this article is to point out linguistic phenomena involved in the transformation of interviews with scientists into news texts published by the daily press. For the analysis, we used sets of texts (interview-journalistic text published by the Jornal do Commercio, that permited us to identify the main linguistic operations and the effects of this kind of transformation on the propositional content. Our analysis showed substantial changes between interview and journalistic text, but, in general, the main idea from the original text is preserved. The inexactness attributed by scientists to scientific news texts are much more a question of a change in the point of interest than a question of informational distortion. Although a case study, we believe that our conclusions indicate what frequently happens in the transformation of interviews into texts of scientific

  14. eNOS-uncoupling in age-related erectile dysfunction

    Science.gov (United States)

    Johnson, JM; Bivalacqua, TJ; Lagoda, GA; Burnett, AL; Musicki, B

    2011-01-01

    Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH4) on erectile function in the aged rats. Male Fischer 344 ‘young’ (4-month-old) and ‘aged’ (19-month-old) rats were treated with a BH4 precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS production, but did not affect eNOS uncoupling in the penis of aged rats. These findings suggest that aging induces eNOS uncoupling in the penis, resulting in increased oxidative stress and ED. PMID:21289638

  15. 76 FR 61391 - Biweekly Notice Applications and Amendments to Facility Operating Licenses Involving No...

    Science.gov (United States)

    2011-10-04

    ... and image files of the NRC's public documents. If you do not have access to ADAMS or if there are... Company, et al., Docket Nos. STN 50-528, STN 50- 529, and STN 50-530, Palo Verde Nuclear Generating... Avenue, New Orleans, Louisiana 70113. NRC Branch Chief: Michael T. Markley. Exelon Generation...

  16. Endothelial (NOS3 E298D) and inducible (NOS2 exon 22) nitric oxide synthase polymorphisms, as well as plasma NOx, influence sepsis development.

    Science.gov (United States)

    Martin, Guadalupe; Asensi, Víctor; Montes, A Hugo; Collazos, Julio; Alvarez, Victoria; Pérez-Is, Laura; Carton, José A; Taboada, Francisco; Valle-Garay, Eulalia

    2014-11-15

    Nitric oxide (NO) influences susceptibility to infection and hemodynamic failure (HF) in sepsis. NOS3 and NOS2 SNPs might modify plasma nitrite/nitrate (NOx) levels, sepsis development, hemodynamics and survival. 90 severely septic and 91 non-infected ICU patients were prospectively studied. NOS3 (E298D), NOS3 (-786 T/C), NOS3 (27 bp-VNTR), and NOS2A (exon 22) SNPs and plasma NOx levels were assessed. 21 patients (11.6%) died, 7 with sepsis. TT homozygotes and T allele carriers of NOS3 (E298D) and AG carriers of the NOS2A (exon 22) SNPs were more frequent among septic compared to non-infected ICU patients (p NOS3 (E298D) SNP (p = 0.006). Sepsis independently associated with HF, increased NOx, peripheral neutrophils, and fibrinogen levels, decreased prothrombin and the presence of the NOS3 (E298D) and NOS2A (exon 22) SNPs. A low APACHE II score was the only variable associated with sepsis survival. NOx was independently associated with sepsis, HF, decreased neutrophils and higher APACHE. NOS3 (E298D) and NOS2A (exon 22) SNPs, individually and in combination, and plasma NOx, associated with sepsis development. NOx associated with HF and fatal outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Pedagogical Reflections by Secondary Science Teachers at Different NOS Implementation Levels

    Science.gov (United States)

    Herman, Benjamin C.; Clough, Michael P.; Olson, Joanne K.

    2017-02-01

    This study investigated what 13 secondary science teachers at various nature of science (NOS) instruction implementation levels talked about when they reflected on their teaching. We then determined if differences exist in the quality of those reflections between high, medium, and low NOS implementers. This study sought to answer the following questions: (1) What do teachers talk about when asked general questions about their pedagogy and NOS pedagogy and (2) what qualitative differences, if any, exist within variables across teachers of varying NOS implementation levels? Evidence derived from these teachers' reflections indicated that self-efficacy and perceptions of general importance for NOS instruction were poor indicators of NOS implementation. However, several factors were associated with the extent that these teachers implemented NOS instruction, including the utility value they hold for NOS teaching, considerations of how people learn, understanding of NOS pedagogy, and their ability to accurately and deeply self-reflect about teaching. Notably, those teachers who effectively implemented the NOS at higher levels value NOS instruction for reasons that transcend immediate instructional objectives. That is, they value teaching NOS for achieving compelling ends realized long after formal schooling (e.g., lifelong socioscientific decision-making for civic reasons), and they deeply reflect about how to teach NOS by drawing from research about how people learn. Low NOS implementers' simplistic notions and reflections about teaching and learning appeared to be impeding factors to accurate and consistent NOS implementation. This study has implications for science teacher education efforts that promote NOS instruction.

  18. Expression analysis of NOS family and HSP genes during thermal stress in goat ( Capra hircus)

    Science.gov (United States)

    Yadav, Vijay Pratap; Dangi, Satyaveer Singh; Chouhan, Vikrant Singh; Gupta, Mahesh; Dangi, Saroj K.; Singh, Gyanendra; Maurya, Vijay Prakash; Kumar, Puneet; Sarkar, Mihir

    2016-03-01

    Approximately 50 genes other than heat shock protein (HSP) expression changes during thermal stress. These genes like nitric oxide synthase (NOS) need proper attention and investigation to find out their possible role in the adaptation to thermal stress in animals. So, the present study was undertaken to demonstrate the expressions of inducible form type II NOS (iNOS), endothelial type III NOS (eNOS), constitutively expressed enzyme NOS (cNOS), HSP70, and HSP90 in peripheral blood mononuclear cells (PBMCs) during different seasons in Barbari goats. Real-time polymerase chain reaction, western blot, and immunocytochemistry were applied to investigate messenger RNA (mRNA) expression, protein expression, and immunolocalization of examined factors. The mRNA and protein expressions of iNOS, eNOS, cNOS, HSP70, and HSP90 were significantly higher ( P < 0.05) during peak summer, and iNOS and eNOS expressions were also observed to be significantly higher ( P < 0.05) during peak winter season as compared with moderate season. The iNOS, eNOS, cNOS, HSP70, and HSP90 were mainly localized in plasma membrane and cytoplasm of PBMCs. To conclude, data generated in the present study indicate the possible involvement of the NOS family genes in amelioration of thermal stress so as to maintain cellular integrity and homeostasis in goats.

  19. Aqueous Humor Outflow Physiology in NOS3 Knockout Mice.

    Science.gov (United States)

    Lei, Yuan; Zhang, Xuejin; Song, Maomao; Wu, Jihong; Sun, Xinghuai

    2015-07-01

    To investigate the role of endothelial nitric oxide synthase (eNOS) on conventional outflow function using NOS3 knockout (KO) mice. Intraocular pressure was measured in both NOS3 KO and wild type (WT) by rebound tonometry. Outflow facility was measured by perfusing enucleated mouse eyes at multiple pressure steps. A subset of eyes was sectioned and stained for histology. Mock aqueous humor ± the nitric oxide (NO) donors nitroprusside dihydrate (SNP) or S-Nitroso-N-Acetyl-D,L-Penicillamine (SNAP) was perfused into enucleated eyes. SNP and SNAP was administered topically at 0, 1, 2, and 3 hours while the contralateral eyes served as vehicle controls. Intraocular pressure was measured in both eyes before and after the last drug treatment. Intraocular pressure was higher in KO mice (18.2 ± 0.7 mm Hg vs. 13.9 ± 0.5 mm Hg, mean ± SEM, n = 30, P NOS3 KO mice have elevated IOP, which is likely the result of reduced pressure-dependent drainage. These findings are consistent with human data showing polymorphisms in the NOS3 gene associate with ocular hypertension and the development of glaucoma.

  20. NOS3 Protects Against Systemic Inflammation and Myocardial Dysfunction in Murine Polymicrobial Sepsis

    OpenAIRE

    Bougaki, Masahiko; Searles, Robert J.; Kida, Kotaro; Yu, JiaDe; Buys, Emmanuel; Ichinose, Fumito

    2010-01-01

    NO has been implicated in the pathogenesis of septic shock. However, the role of NO synthase 3 (NOS3) during sepsis remains incompletely understood. Here, we examined the impact of NOS3 deficiency on systemic inflammation and myocardial dysfunction during peritonitis-induced polymicrobial sepsis. Severe polymicrobial sepsis was induced by colon ascendens stent peritonitis (CASP) in wild-type (WT) and NOS3-deficient (NOS3KO) mice. NOS3KO mice exhibited shorter survival time than did WT mice af...

  1. Exploring Elementary Science Methods Course Contexts to Improve Preservice Teachers' NOS of Science Conceptions and Understandings of NOS Teaching Strategies

    Science.gov (United States)

    Akerson, Valarie L.; Weiland, Ingrid; Rogers, Meredith Park; Pongsanon, Khemmawaddee; Bilican, Kader

    2014-01-01

    We explored adaptations to an elementary science methods course to determine how varied contexts could improve elementary preservice teachers' conceptions of NOS as well as their ideas for teaching NOS to elementary students. The contexts were (a) NOS Theme in which the course focused on the teaching of science through the consistent teaching…

  2. Lo que los automóviles nos dicen.

    OpenAIRE

    Rogelio, Rodríguez Pellicer

    2012-01-01

    En el presente artículo reflexionamos sobre la presencia en nuestro día a día de los significados sociales, aquellos significados que otorgamos a lo que nos rodea por influencia de la cultura recibida. Para ello, partimos del significado denotativo que los automóviles estacionados en las vías públicas nos proporcionan, tanto a través de signos lingüísticos como de los no lingüísticos, y observamos que un artilugio tan habitual como un coche conlleva una gran variedad de significados connotati...

  3. The Characteristics and Regulatory Mechanisms of Superoxide Generation from eNOS Reductase Domain.

    Directory of Open Access Journals (Sweden)

    Hu Peng

    Full Text Available In addition to superoxide (O2.- generation from nitric oxide synthase (NOS oxygenase domain, a new O2.- generation site has been identified in the reductase domain of inducible NOS (iNOS and neuronal NOS (nNOS. Cysteine S-glutathionylation in eNOS reductase domain also induces O2.- generation from eNOS reductase domain. However, the characteristics and regulatory mechanism of the O2.- generation from NOS reductase domain remain unclear. We cloned and purified the wild type bovine eNOS (WT eNOS, a mutant of Serine 1179 replaced with aspartic acid eNOS (S1179D eNOS, which mimics the negative charge caused by phosphorylationand truncated eNOS reductase domain (eNOS RD. Both WT eNOS and S1179D eNOS generated significant amount of O2.- in the absence of BH4 and L-arginine. The capacity of O2.- generation from S1179D eNOS was significantly higher than that of WT eNOS (1.74:1. O2.- generation from both WT eNOS and S1179D eNOS were not completely inhibited by 100nM tetrahydrobiopterin(BH4. This BH4 un-inhibited O2.- generation from eNOS was blocked by 10mM flavoprotein inhibitor, diphenyleneiodonium (DPI. Purified eNOS reductase domain protein confirmed that this BH4 un-inhibited O2.- generation originates at the FMN or FAD/NADPH binding site of eNOS reductase domain. DEPMPO-OOH adduct EPR signals and NADPH consumptions analyses showed that O2.- generation from eNOS reductase domain was regulated by Serine 1179 phosphorylation and DPI, but not by L-arginine, BH4 or calmodulin (CaM. In addition to the heme center of eNOS oxygenase domain, we confirmed another O2.- generation site in the eNOS reductase domain and characterized its regulatory properties.

  4. Differential cardiovascular responses to blockade of nNOS or iNOS in rostral ventrolateral medulla of the rat

    Science.gov (United States)

    Chan, Samuel H H; Wang, Ling-Lin; Wang, Shu-Huei; Chan, Julie Y H

    2001-01-01

    We investigated the contribution of neuronal or inducible nitric oxide synthase (nNOS or iNOS) at the rostral ventrolateral medulla (RVLM) to central cardiovascular regulation by endogenous nitric oxide (NO), using Sprague-Dawley rats anaesthetized and maintained with propofol.Microinjection bilaterally into the RVLM of a NO trapping agent, carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-l-oxy-l-3-oxide (10, 50 or 100 nmoles) resulted in significant hypotension and bradycardia.Similar application of a selective antagonist of nNOS, 7-nitroindazole (1, 2.5 or 5 pmoles), or selective antagonists of iNOS, aminoguanidine (125, 250 or 500 pmoles), N6-(l-iminoethyl)-L-lysine (250 pmoles) or S-methylisothiourea (250 pmoles), induced respectively a reduction or an enhancement in systemic arterial pressure, heart rate and power density of the vasomotor components in the spectrum of arterial blood pressure signals, the experimental index for sympathetic neurogenic vasomotor tone.Both hypotension and bradycardia induced by the NO precursor, L-arginine (100 nmoles), were significantly blunted when aminoguanidine (250 pmoles) was co-microinjected bilaterally into the RVLM. On the other hand, co-administered 7-nitroindazole (2.5 pmoles) was ineffective.Whereas low doses of S-nitro-N-acetylpenicillamine (0.25 or 0.5 nmoles) elicited hypertension and tachycardia, high doses of this non-nitrate NO donor (5 nmoles) induced hypotension and bradycardia.Reverse transcription – polymerase chain reaction analysis revealed that both iNOS and nNOS mRNA were expressed in the ventrolateral medulla.We conclude that the prevalence of nNOS over iNOS activity at the RVLM and the associated dominance of sympathoexcitation over sympathoinhibition may underlie the maintenance of sympathetic vasomotor outflow and stable systemic arterial pressure by the endogenous NO. PMID:11399678

  5. Los medios de comunicación ¿nos igualan o nos diferencian?

    Directory of Open Access Journals (Sweden)

    Javier BALLESTA PAGÁN

    2009-05-01

    Full Text Available RESUMEN: En este artículo presentamos los resultados obtenidos en una investigación llevada a cabo en los centros educativos de Educación Secundaria Obligatoria de la Región de Murcia donde se ha pretendido valorar el equipamiento, el acceso a la información y el consumo de medios de comunicación en el hogar, por parte del alumnado inmigrante en comparación con el autóctono. Los datos aportados de dicho estudio nos confirman que la mayoría de los recursos más utilizados en el hogar es menor en los hogares del alumnado inmigrante de Educación Secundaria Obligatoria (ESO respecto al resto de la muestra en general de los alumnos. Por otra parte, el acceso a los medios, para estos alumnos inmigrantes, corrobora que son considerados recursos de gran importancia como vehículos en su acercamiento al aprendizaje y al entretenimiento. En cuanto al uso personal de dichos medios de comunicación observamos que mientras el ordenador, el móvil y el DVD son muy utilizados, comprobamos cómo desciende su uso e interés cuando abordamos otros medios de papel impreso, entre los que destacamos el libro y el periódico. Sin embargo, el uso de la televisión es bastante similar en ambos colectivos. Con relación al acceso a Internet, los resultados analizados parecen confirmar que el hogar se convierte en el lugar adecuado para su uso en ambas muestras, por encima de otros espacios públicos o privados. Sin embargo, si comprobamos la disponibilidad de acceso al mismo en el hogar por parte del alumnado inmigrante, destacamos que es menor de la que disponen los hogares autóctonos. En relación con la lectura, el nivel lector de estos jóvenes inmigrantes es también menor, aunque no existe una gran diferencia, respecto de la muestra de alumnos autóctonos. Al valorar el uso que hacen de la biblioteca comprobamos que más de la mitad de los alumnos afirman ir a ella, pero preferentemente a la pública más que la biblioteca del centro o a la de otras

  6. Las Rocas Nos Cuentan (Rocks Tell Their Stories)

    Science.gov (United States)

    Llerandi-Roman, Pablo A.

    2012-01-01

    Many Earth science lessons today still focus on memorizing the names of rocks and minerals. This led the author to develop a lesson that reveals the fascinating stories told by rocks through the study of their physical properties. He first designed the lesson for Puerto Rican teachers, hence its Spanish title: "Las Rocas Nos Cuentan Su Historia."…

  7. Las Rocas Nos Cuentan (Rocks Tell Their Stories)

    Science.gov (United States)

    Llerandi-Roman, Pablo A.

    2012-01-01

    Many Earth science lessons today still focus on memorizing the names of rocks and minerals. This led the author to develop a lesson that reveals the fascinating stories told by rocks through the study of their physical properties. He first designed the lesson for Puerto Rican teachers, hence its Spanish title: "Las Rocas Nos Cuentan Su Historia."…

  8. 78 FR 21112 - Marine Mammals; File Nos. 16992 and 14535

    Science.gov (United States)

    2013-04-09

    ..., Ph.D., Hawaii Institute of Marine Biology, University of Hawaii, P.O. Box 1106, Kailua, HI 96734, has... of Marine Biology in Kaneohe, HI. Researchers would conduct hearing measurements using suction cup... National Oceanic and Atmospheric Administration RIN 0648-XB161 Marine Mammals; File Nos. 16992 and...

  9. First light of the NIRISS Optical Simulator (NOS)

    Science.gov (United States)

    St-Antoine, Jonathan; Albert, Loïc.; Doyon, René; Vallée, Philippe; Artigau, Étienne; Hernandez, Olivier; Thibault, Simon; Brousseau, Denis

    2016-07-01

    The Near Infrared Imager and Slitless Spectrograph (NIRISS) Optical Simulator (NOS) is a laboratory simulation of the single-object slitless spectroscopy and aperture masking interferometry modes of the NIRISS instrument onboard the James Webb Space Telescope (JWST). A transiting exoplanet can be simulated by periodically eclipsing a small portion (1% - 10ppm) of a super continuum laser source (0.4 μm - 2.4 μm) with a dichloromethane filled cell. Dichloromethane exhibits multiple absorption features in the near infrared domain hence the net effect is analogous to the atmospheric absorption features of an exoplanet transiting in front of its host star. The NOS uses an HAWAII-2RG and an ASIC controller cooled to cryogenic temperatures. A separate photometric beacon provides a flux reference to monitor laser variations. The telescope jitter can be simulated using a high-resolution motorized pinhole placed along the optical path. Laboratory transiting spectroscopy data produced by the NOS will be used to refine analysis methods, characterize the noise due to the jitter, characterize the noise floor and to develop better observation strategies. We report in this paper the first exoplanet transit event simulated by the NOS. The performance is currently limited by relatively high thermal background in the system and high frequency temporal variations of the continuum source.

  10. Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS

    Directory of Open Access Journals (Sweden)

    Mohamed A. Morsy

    2014-01-01

    Full Text Available Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p. for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS expression, while expression of endothelial nitric oxide synthase (eNOS was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production.

  11. Contribution of the nos-pdt operon to virulence phenotypes in methicillin-sensitive Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    April M Sapp

    Full Text Available Nitric oxide (NO is emerging as an important regulator of bacterial stress resistance, biofilm development, and virulence. One potential source of endogenous NO production in the pathogen Staphylococcus aureus is its NO-synthase (saNOS enzyme, encoded by the nos gene. Although a role for saNOS in oxidative stress resistance, antibiotic resistance, and virulence has been recently-described, insights into the regulation of nos expression and saNOS enzyme activity remain elusive. To this end, transcriptional analysis of the nos gene in S. aureus strain UAMS-1 was performed, which revealed that nos expression increases during low-oxygen growth and is growth-phase dependent. Furthermore, nos is co-transcribed with a downstream gene, designated pdt, which encodes a prephenate dehydratase (PDT enzyme involved in phenylalanine biosynthesis. Deletion of pdt significantly impaired the ability of UAMS-1 to grow in chemically-defined media lacking phenylalanine, confirming the function of this enzyme. Bioinformatics analysis revealed that the operon organization of nos-pdt appears to be unique to the staphylococci. As described for other S. aureus nos mutants, inactivation of nos in UAMS-1 conferred sensitivity to oxidative stress, while deletion of pdt did not affect this phenotype. The nos mutant also displayed reduced virulence in a murine sepsis infection model, and increased carotenoid pigmentation when cultured on agar plates, both previously-undescribed nos mutant phenotypes. Utilizing the fluorescent stain 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM diacetate, decreased levels of intracellular NO/reactive nitrogen species (RNS were detected in the nos mutant on agar plates. These results reinforce the important role of saNOS in S. aureus physiology and virulence, and have identified an in vitro growth condition under which saNOS activity appears to be upregulated. However, the significance of the operon organization of nos-pdt and

  12. Endothelin-1 Overexpression Improves Renal Function in eNOS Knockout Mice

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    Oleg Tsuprykov

    2015-10-01

    Full Text Available Background/Aims: To investigate the renal phenotype under conditions of an activated renal ET-1 system in the status of nitric oxide deficiency, we compared kidney function and morphology in wild-type, ET-1 transgenic (ET+/+, endothelial nitric oxide synthase knockout (eNOS-/- and ET+/+eNOS-/- mice. Methods: We assessed blood pressure, parameters of renal morphology, plasma cystatin C, urinary protein excretion, expression of genes associated with glomerular filtration barrier and tissue remodeling, and plasma metabolites using metabolomics. Results: eNOS-/- and ET+/+eNOS-/- mice developed hypertension. Osteopontin, albumin and protein excretion were increased in eNOS-/- and restored in ET+/+eNOS-/- animals. All genetically modified mice developed renal interstitial fibrosis and glomerulosclerosis. Genes involved in tissue remodeling (serpine1, TIMP1, Col1a1, CCL2 were up-regulated in eNOS-/-, but not in ET+/+eNOS-/- mice. Plasma levels of free carnitine and acylcarnitines, amino acids, diacyl phosphatidylcholines, lysophosphatidylcholines and hexoses were descreased in eNOS-/- and were in the normal range in ET+/+eNOS-/- mice. Conclusion: eNOS-/- mice developed renal dysfunction, which was partially rescued by ET-1 overexpression in eNOS-/- mice. The metabolomics results suggest that ET-1 overexpression on top of eNOS knockout is associated with a functional recovery of mitochondria (rescue effect in β-oxidation of fatty acids and an increase in antioxidative properties (normalization of monounsaturated fatty acids levels.

  13. Endothelial nitric oxide synthase: From biochemistry and gene structure to clinical implications of NOS3 polymorphisms.

    Science.gov (United States)

    Oliveira-Paula, Gustavo H; Lacchini, Riccardo; Tanus-Santos, Jose E

    2016-01-10

    Nitric oxide (NO) is an important vasodilator with a well-established role in cardiovascular homeostasis. While mediator is synthesized from L-arginine by neuronal, endothelial, and inducible nitric oxide synthases (NOS1,NOS3 and NOS2 respectively), NOS3 is the most important isoform for NO formation in the cardiovascular system. NOS3 is a dimeric enzyme whose expression and activity are regulated at transcriptional, posttranscriptional,and posttranslational levels. The NOS3 gene, which encodes NOS3, exhibits a number of polymorphic sites including single nucleotide polymorphisms (SNPs), variable number of tandem repeats (VNTRs), microsatellites, and insertions/deletions. Some NOS3 polymorphisms show functional effects on NOS3 expression or activity, thereby affecting NO formation. Interestingly, many studies have evaluated the effects of functional NOS3 polymorphisms on disease susceptibility and drug responses. Moreover, some studies have investigated how NOS3 haplotypes may impact endogenous NO formation and disease susceptibility. In this article,we carried out a comprehensive review to provide a basic understanding of biochemical mechanisms involved in NOS3 regulation and how genetic variations in NOS3 may translate into relevant clinical and pharmacogenetic implications.

  14. Association of NOS2 and NOS3 gene polymorphisms with susceptibility to type 2 diabetes mellitus and diabetic nephropathy in the Chinese Han population.

    Science.gov (United States)

    Chen, Feng; Li, Yu-Mei; Yang, Lin-Qing; Zhong, Cai-Gao; Zhuang, Zhi-Xiong

    2016-07-01

    Inducible nitric oxide synthase (NOS2) and endothelial nitric oxide synthase (NOS3) gene play important roles in the susceptibility to type 2 diabetes mellitus (T2DM). The present study aims to detect the potential association of NOS2 and NOS3 gene polymorphisms with the susceptibility toT2DM and diabetic nephropathy (DN) in the Chinese Han population. Four hundred and ninety T2DM patients and 485 healthy controls were enrolled in this case-control study. The genotypes of NOS2 and NOS3 gene polymorphisms were analyzed by the polymerase chain reaction (PCR)-ligase detection reaction (LDR) method. Our data demonstrated that the NOS2 rs2779248 and NOS2 rs1137933 genetic polymorphisms were significantly associated with the increased susceptibility to T2DM in the heterozygote comparison, dominant model, and allele contrast; and NOS3 rs3918188 genetic polymorphism was significantly associated with the increased susceptibility to T2DM in the homozygote comparison and recessive model. The allele-C and genotype-TC of NOS2 rs2779248, allele-A and genotype-GA of NOS2 rs1137933 and genotype-AA of NOS3 rs3918188 genetic polymorphisms might be the risk factors for increasing the susceptibility to T2DM. And a significant haplotype effect of NOS2 rs10459953/C- rs1137933/G- rs2779248/T was found between T2DM cases and controls. Moreover, NOS3 rs1800783 polymorphism was significantly associated with the increased susceptibility to DN in the heterozygote comparison, recessive model and allele contrast. At last, a positive correlation of family history of diabetes with NOS3 rs11771443 polymorphism was found in DN. These preliminary findings indicate that the NOS2 rs2779248, NOS2 rs1137933, and NOS3 rs3918188 genetic polymorphisms are potentially related to the susceptibility to T2DM, and the rs1800783 polymorphism might be considered as genetic risk factors for diabetic nephropathy, and family history of diabetes was closely associated with rs11771443 polymorphism in DN, and the

  15. EFICIÊNCIA NOS MERCADOS FUTUROS AGROPECUÁRIOS BRASILEIROS

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    MARCOS AURELIO RODRIGUES

    2015-06-01

    Full Text Available ResumoObjetivou-se testar a hipótese de passeio aleatório a contratos futuros agropecuários negociados na BM&FBOVESPA. Refutá-la, significa possível previsibilidade e, por conseguinte, osmercados não seriamfracamente eficientes. Correlações seriais e testes de razão de variância foram utilizados para verificá-las. Os resultados deram suporte à hipótese de passeio aleatório nos mercados futuros de café e da soja, eficientes na forma fraca, e evidências contrárias foram encontradas nos mercados do boi gordo, milho e etanol.

  16. ANGIOTENSIN II DECREASES NOS3 EXPRESSION VIA NITRIC OXIDE AND SUPEROXIDE IN THE THICK ASCENDING LIMB

    OpenAIRE

    Ramseyer, Vanesa D.; Garvin, Jeffrey L.

    2008-01-01

    Nitric oxide (NO) produced by NO synthase type 3 (NOS3) in medullary thick ascending limbs (mTHALs) inhibits Cl− reabsorption. Acutely, angiotensin II stimulates THAL NO production. In endothelial cells NO inhibits NOS3 expression. Therefore, we hypothesized that angiotensin II decreases NOS3 expression via NO in mTHALs. After 24 hrs, 10 and 100 nmol/L angiotensin II decreased NOS3 expression by 23 ± 9% (n=6, p

  17. Participação nos Lucros ou Resultados

    Directory of Open Access Journals (Sweden)

    Luiz Felipe Ferreira

    2007-03-01

    Full Text Available A participação nos lucros ou resultados é uma forma de remuneração variável, pela qual não há incidência de encargos sociais, além de incentivar o aumento da produtividade, podendo assim ser utilizada pelas empresas como estratégia, para enfrentarem os desafios dinâmicos e competitivos em que atuam. Esta pesquisa caracteriza-se como sendo exploratória, com abordagem qualitativa e tem como objetivo conceituar e explanar as formas pela quais são praticadas a participação nos lucros ou resultados em empresas do setor alimentício em Santa Catarina, que foram escolhidas por meio do critério de acessibilidade e disponibilidade. Dos dados coletados, pode-se verificar que as empresas: COC Alimentos, Moinho Catarinense e Pepsico do Brasil utilizam a participação nos resultados e a Perdigão utiliza a participação mista. A Moinho Catarinense distribui para todos os empregados um salário nominal, como a CDC Alimentos, exceto para os gerentes. A Perdigão beneficia todos os empregados, sendo que 60% da distribuição é pelo lucro líquido e 40% por indicadores de desempenho. A Pepsico do Brasil distribui aos empregados operacionais 50% de um salário nominal e para os empregados da administração central um salário nominal, atrelado ao cumprimento de metas, especificadas no programa de participação nos lucros ou resultados.

  18. Ecocrítica e erotismo nos poemas de Magma

    OpenAIRE

    Santana, Patricia Maria dos Santos; UFRJ

    2013-01-01

    Olga Savary nos mostra, através da poesia registrada no livro Magma, que a força erótica e a interdependência do homem com a Natureza são fatores que regem seu trabalho criativo no que tange a valorização da mulher como um ser que tem domínio de seu próprio corpo e que sabe muito bem o que realmente quer. 

  19. [Malignant fibrous histiocytoma: pleomorphic sarcoma NOS or pleomorphic fibrosarcoma].

    Science.gov (United States)

    Meister, P

    2005-03-01

    The entity and nosology of pleomorphic malignant fibrous histiocytoma (MFH) is still ambiguous. The actual WHO-Classification uses pleomorphic malignant fibrous histiocytoma (MFH) and pleomorphic sarcoma NOS (not otherwise specified) synonymously. On the other hand text and illustrations convey the impression, that these tumors also could be pleomorphic lipo-, leio- or rhabdomyosarcomas etc. It would have been more informative to emphasize, that with the above mentioned specific sarcoma types MFH-like appearance may occur. Furthermore it would have been more up to date to consider pleomorphic sarcomas NOS as pleomorphic fibrosarcomas and include them in the chapter of fibroblastic and myofibroblastic tumors. This concept already has been carried out for the former myxoid variant of MFH, nowadays preferentially called myxofibrosarcoma. There is controversial discussion about the clinical significance of exact typing of pleomorphic sarcomas. Problems may also occur due to the lack of standards, which degree of desmin expression signifies leiomyosarcoma or just indicates myofibroblasts in MFH. The requirement of exclusion of other tumor-types before diagnosing pleomorphic fibrosarcoma still remains obligatory. After verification of the diagnosis pleomorphic sarcoma NOS or pleomorphic fibrosarcoma, grading e.g. according to criteria of the FFCCS can be carried out. Most cases of pleomorphic fibrosarcoma will qualify as high grade malignant.

  20. Pragmatismo e os pragmáticos nos estudos organizacionais

    Directory of Open Access Journals (Sweden)

    Francis Kanashiro Meneghetti

    Full Text Available O objetivo central deste ensaio teórico é avaliar as contribuições do pragmatismo nos Estudos Organizacionais e, os específicos, avaliar se as contribuições teóricas de Charles Peirce e John Dewey possibilitam afirmar o pragmatismo como senso comum, ciência ou teoria do conhecimento; analisar as contribuições - possibilidadese limites - do pragmatismo como conhecimento científico; compreender os percursos do pragmatismo nos Estudos Organizacionais. Chaga-se a conclusão de que ser pragmático é diferente de conceber estudos articulados no campo epistemológico do pragmatismo. O sujeito pragmático vê na sua utilidade e na necessidade deação, o ponto de tensão que coloca em dúvida a veracidade dos pressupostos do pragmatismo como ciência. O que ocorre nos Estudos Organizacionais éa conversão do pragmatismo como conhecimento científico emsubordinação irracional à utilidade e à ação prática, sobretudo, no campo da economia, da política, da ciência, da cultura, da educação, e assim por diante.

  1. Neoplasmas em suínos: 37 casos

    Directory of Open Access Journals (Sweden)

    Juliana S. Brum

    2015-06-01

    Full Text Available Resumo: Neoplasmas em suínos são raros. Esse trabalho descreve os neoplasmas encontrados em suínos na rotina diagnóstica de um laboratório de patologia veterinária localizado na Região Central do Rio Grande do Sul. Durante um período de 49 anos, 2.266 casos de várias afecções em suínos foram encontrados, dos quais 37 (1,6% eram neoplasmas. Em ordem decrescente de frequência, os seguintes neoplasmas foram encontrados: Linfoma (11/37, nefroblastoma (11/37, melanoma (8/37 e papiloma (2/37. Adicionalmente, um caso de cada um dos seguintes tumores foi observado: Adenoma hepatocelular, carcinoma hepatocelular, colangiocarcinoma, histiocitoma fibroso maligno e sarcoma granulocítico. O aspecto macroscópico e histológico desses tumores é descrito e a sua epidemiologia é comparada com os dados disponíveis na literatura para neoplasia suína.

  2. Exercise does not activate the β3 adrenergic receptor-eNOS pathway, but reduces inducible NOS expression to protect the heart of obese diabetic mice.

    Science.gov (United States)

    Kleindienst, Adrien; Battault, Sylvain; Belaidi, Elise; Tanguy, Stephane; Rosselin, Marie; Boulghobra, Doria; Meyer, Gregory; Gayrard, Sandrine; Walther, Guillaume; Geny, Bernard; Durand, Gregory; Cazorla, Olivier; Reboul, Cyril

    2016-07-01

    Obesity and diabetes are associated with higher cardiac vulnerability to ischemia-reperfusion (IR). The cardioprotective effect of regular exercise has been attributed to β3-adrenergic receptor (β3AR) stimulation and increased endothelial nitric oxide synthase (eNOS) activation. Here, we evaluated the role of the β3AR-eNOS pathway and NOS isoforms in exercise-induced cardioprotection of C57Bl6 mice fed with high fat and sucrose diet (HFS) for 12 weeks and subjected or not to exercise training during the last 4 weeks (HFS-Ex). HFS animals were more sensitive to in vivo and ex vivo IR injuries than control (normal diet) and HFS-Ex mice. Cardioprotection in HFS-Ex mice was not associated with increased myocardial eNOS activation and NO metabolites storage, possibly due to the β3AR-eNOS pathway functional loss in their heart. Indeed, a selective β3AR agonist (BRL37344) increased eNOS activation and had a protective effect against IR in control, but not in HFS hearts. Moreover, iNOS expression, nitro-oxidative stress (protein s-nitrosylation and nitrotyrosination) and ROS production during early reperfusion were increased in HFS, but not in control mice. Exercise normalized iNOS level and reduced protein s-nitrosylation, nitrotyrosination and ROS production in HFS-Ex hearts during early reperfusion. The iNOS inhibitor 1400 W reduced in vivo infarct size in HFS mice to control levels, supporting the potential role of iNOS normalization in the cardioprotective effects of exercise training in HFS-Ex mice. Although the β3AR-eNOS pathway is defective in the heart of HFS mice, regular exercise can protect their heart against IR by reducing iNOS expression and nitro-oxidative stress.

  3. Comparison of iNOS inhibition by antisense and pharmacological inhibitors after spinal cord injury.

    Science.gov (United States)

    Pearse, D D; Chatzipanteli, K; Marcillo, A E; Bunge, M B; Dietrich, W D

    2003-11-01

    Inducible nitric oxide synthase (iNOS) is a key mediator of inflammation during pathological conditions. We examined, through the use of selective iNOS inhibitors, the role of iNOS in specific pathophysiological processes after spinal cord injury (SCI), including astrogliosis, blood-spinal cord barrier (BSCB) permeability, polymorphonuclear leukocyte infiltration, and neuronal cell death. Administration of iNOS antisense oligonucleotides (ASOs) (intraspinally at 3 h) or the pharmacological inhibitors, N-[3(Aminomethyl) benzyl] acetamidine (1400 W) (i.v./i.p. 3 and 9 h) or aminoguanidine (i.p. at 3 and 9 h) after moderate contusive injury decreased the number of iNOS immunoreactive cells at the injury site by 65.6% (iNOS ASOs), 62.1% (1400 W), or 59% (aminoguanidine) 24 h postinjury. iNOS activity was reduced 81.8% (iNOS ASOs), 56.7% (1400 W), or 67.9% (aminoguanidine) at this time. All iNOS inhibitors reduced the degree of BSCB disruption (plasma leakage of rat immunoglobulins), with iNOS ASO inhibition being more effective (reduced by 58%). Neutrophil accumulation within the injury site was significantly reduced by iNOS ASOs and 1400 W by 78.8% and 20.9%, respectively. Increased astrogliosis was diminished with iNOS ASOs but enhanced following aminoguanidine. Detection of necrotic and apoptotic neuronal cell death by propidium iodide and an FITC-conjugated Annexin V antibody showed that iNOS inhibition could significantly retard neuronal cell death rostral and caudal to the injury site. These novel findings indicate that acute inhibition of iNOS is beneficial in reducing several pathophysiological processes after SCI. Furthermore, we demonstrate that the antisense inhibition of iNOS is more efficacious than currently available pharmacological agents.

  4. Fluorinated indazoles as novel selective inhibitors of nitric oxide synthase (NOS): synthesis and biological evaluation.

    Science.gov (United States)

    Claramunt, Rosa M; López, Concepción; Pérez-Medina, Carlos; Pérez-Torralba, Marta; Elguero, José; Escames, Germaine; Acuña-Castroviejo, Darío

    2009-09-01

    In order to find new compounds with neuroprotective activity and NOS-I/NOS-II selectivity, we have designed, synthesized, and characterized 14 new NOS inhibitors with an indazole structure. The first group corresponds to 4,5,6,7-tetrahydroindazoles (4-8), the second to the N-methyl derivatives (9-12) of 7-nitro-1H-indazole (1) and 3-bromo-7-nitro-1H-indazole (2), and the latter to 4,5,6,7-tetrafluoroindazoles (13-17). Compound 13 (4,5,6,7-tetrafluoro-3-methyl-1H-indazole) inhibited NOS-I by 63% and NOS-II by 83%. Interestingly, compound 16 (4,5,6,7-tetrafluoro-3-perfluorophenyl-1H-indazole) inhibited NOS-II activity by 80%, but it did not affect to NOS-I activity. Structural comparison between these new indazoles further supports the importance of the aromatic indazole skeleton for NOS inhibition and indicate that bulky groups or N-methylation of 1 and 2 diminish their effect on NOS activity. The fluorination of the aromatic ring increased the inhibitory potency and NOS-II selectivity, suggesting that this is a promising strategy for NOS selective inhibitors.

  5. Suppression of eNOS-derived superoxide by caveolin-1: a biopterin-dependent mechanism.

    Science.gov (United States)

    Karuppiah, Kanchana; Druhan, Lawrence J; Chen, Chun-an; Smith, Travis; Zweier, Jay L; Sessa, William C; Cardounel, Arturo J

    2011-09-01

    In the vasculature, nitric oxide (NO) is generated by endothelial NO synthase (eNOS) in a calcium/calmodulin-dependent reaction. In the absence of the requisite eNOS cofactor tetrahydrobiopterin (BH(4)), NADPH oxidation is uncoupled from NO generation, leading to the production of superoxide. Although this phenomenon is apparent with purified enzyme, cellular studies suggest that formation of the BH(4) oxidation product, dihydrobiopterin, is the molecular trigger for eNOS uncoupling rather than BH(4) depletion alone. In the current study, we investigated the effects of both BH(4) depletion and oxidation on eNOS-derived superoxide production in endothelial cells in an attempt to elucidate the molecular mechanisms regulating eNOS oxidase activity. Results demonstrated that pharmacological depletion of endothelial BH(4) does not result in eNOS oxidase activity, whereas BH(4) oxidation gave rise to significant eNOS-oxidase activity. These findings suggest that the endothelium possesses regulatory mechanisms, which prevent eNOS oxidase activity from pterin-free eNOS. Using a combination of gene silencing and pharmacological approaches, we demonstrate that eNOS-caveolin-1 association is increased under conditions of reduced pterin bioavailability and that this sequestration serves to suppress eNOS uncoupling. Using small interfering RNA approaches, we demonstrate that caveolin-1 gene silencing increases eNOS oxidase activity to 85% of that observed under conditions of BH(4) oxidation. Moreover, when caveolin-1 silencing was combined with a pharmacological inhibitor of AKT, BH(4) depletion increased eNOS-derived superoxide to 165% of that observed with BH(4) oxidation. This study identifies a critical role of caveolin-1 in the regulation of eNOS uncoupling and provides new insight into the mechanisms through which disease-associated changes in caveolin-1 expression may contribute to endothelial dysfunction.

  6. Using a Professional Development Program for Enhancing Chilean Biology Teachers' Understanding of Nature of Science (NOS) and Their Perceptions about Using History of Science to Teach NOS

    Science.gov (United States)

    Pavez, José M.; Vergara, Claudia A.; Santibañez, David; Cofré, Hernán

    2016-01-01

    A number of authors have recognized the importance of understanding the nature of science (NOS) for scientific literacy. Different instructional strategies such as decontextualized, hands-on inquiry, and history of science (HOS) activities have been proposed for teaching NOS. This article seeks to understand the contribution of HOS in enhancing…

  7. Influence of intravascular low level He-Ne laser irradiation on iNOS, total-NOS, and ET-1 in acute spinal cord-injured rabbits

    Science.gov (United States)

    Yin, Zhenchun; Dong, Yinghai; Zhu, Jing

    2005-07-01

    Objective To research the influence of intravascular low level Laser irradiation (ILLLI) on total NOS, iNOS, and ET-1 in spinal cord following acute spinal cord injury (ASCI), and discuss the protective effects of ILLLI on neurons .Methods 72 rabbits were randomly divided into 3 groups: treatment group, injury group and control group. In treatment group and injury group, after laminectomy at the level of T-13, ASCI was performed by using Allen"s method with slight modification (6g×10cm) on rabbits. After injury, rabbits were treated immediately with He-Ne laser (power 5 mW, 1 hour per day for 10 days). At the day of 10th after treatment, total-NOS, iNOS, and ET-1 in spinal cord tissues were measured. Results The expression level of total-NOS, iNOS, and ET-1 in spinal cord in injury group were significantly higher than those in control group (Pspinal cord. It indicates that ILLLI can relieve the overexpression of total-NOS, iNOS, and ET-1 ,and thus can perform protective effects on neurons in the course of secondary spinal cord injury (SSCI) following ASCI

  8. Using a Professional Development Program for Enhancing Chilean Biology Teachers' Understanding of Nature of Science (NOS) and Their Perceptions about Using History of Science to Teach NOS

    Science.gov (United States)

    Pavez, José M.; Vergara, Claudia A.; Santibañez, David; Cofré, Hernán

    2016-01-01

    A number of authors have recognized the importance of understanding the nature of science (NOS) for scientific literacy. Different instructional strategies such as decontextualized, hands-on inquiry, and history of science (HOS) activities have been proposed for teaching NOS. This article seeks to understand the contribution of HOS in enhancing…

  9. Arquitectura nos videojogos: espaço, narrativa e gameplay.

    OpenAIRE

    Piteira, José Pedro Subtil Lopes

    2015-01-01

    Mestrado Integrado em Arquitetura Os videojogos tem-se revelado uma área em exponencial evolução nos últimos anos. Uma área que tem criado, também, uma estreita relação com a arquitetura quer sob o ponto de vista do seu processo de conceção quer sob o ponto de vista da necessidade de criar espaços habitáveis. Principalmente desde que a experiência dos lugares passou a afetar e a integrar, organicamente tanto a narrativa como o universo criado para cada videojogo, tornando-se as...

  10. Pronounced hypothermic synergy between systemic baclofen and NOS inhibitor.

    Science.gov (United States)

    Rawls, Scott M; Baron, David A; Gomez, Teresa; Jacobs, Kyle; Tallarida, Ronald J

    2004-10-19

    Baclofen was administered to rats systemically (intraperitoneal, i.p.) by itself or with L-NAME. Baclofen (1-7.5 mg/kg, i.p.) evoked dose-dependent hypothermia. L-NAME (50 mg/kg, i.p.) was ineffective. For combined administration, L-NAME increased the relative potency of baclofen (F=10.77, p<0.05), indicating multiplicative interaction and synergism. The present data reveal a surprising and significant interaction between nitric oxide synthase (NOS) and baclofen-induced hypothermia.

  11. Medo de que? : uma historia do horror nos filmes brasileiros

    OpenAIRE

    Laura Loguercio Canepa

    2008-01-01

    Resumo: Neste trabalho, examinam-se as manifestações do gênero horror nos longas-metragens sonoros brasileiros realizados entre 1937 e 2007, elaborando-se um panorama histórico desses filmes, desde os primeiros registros cinematográficos deste gênero de ficção no cinema nacional até os mais recentes, e propondo-se um modelo descritivo para as configurações do horror ficcional no cinema brasileiro. Para isso, partiu-se dos estudos de gêneros cinematográficos, de história do cinema mundial e de...

  12. Colonialismo e nacionalismo nos escritos de Marx sobre a Irlanda

    OpenAIRE

    Rafael Afonso da Silva

    2013-01-01

    Esta pesquisa tem como objeto a reflexão de Marx sobre o tema do colonialismo conduzido por países capitalistas ou, mais concretamente, pelo país capitalista que dominava o maior império colonial à época, a Inglaterra. De modo ainda mais específico, a pesquisa concentra-se nos escritos de Marx sobre a Irlanda. Esses escritos são examinados contra o pano de fundo de um conjunto mais amplo de escritos de Marx em torno do impacto do colonialismo britânico, expondo as contínuas reavaliações e rev...

  13. Nitrotyrosinylation, remodeling and endothelial-myocyte uncoupling in iNOS, cystathionine beta synthase (CBS) knockouts and iNOS/CBS double knockout mice.

    Science.gov (United States)

    Kundu, Soumi; Kumar, Munish; Sen, Utpal; Mishra, Paras K; Tyagi, Neetu; Metreveli, Naira; Lominadze, David; Rodriguez, Walter; Tyagi, Suresh C

    2009-01-01

    Increased levels of homocysteine (Hcy), recognized as hyperhomocysteinemia (HHcy), were associated with cardiovascular diseases. There was controversy regarding the detrimental versus cardio protective role of inducible nitric oxide synthase (iNOS) in ischemic heart disease. The aim of this study was to test the hypothesis that the Hcy generated nitrotyrosine by inducing the endothelial nitric oxide synthase, causing endothelial-myocyte (E-M) coupling. To differentiate the role of iNOS versus constitutive nitric oxide synthase (eNOS and nNOS) in Hcy-mediated nitrotyrosine generation and matrix remodeling in cardiac dysfunction, left ventricular (LV) tissue was analyzed from cystathionine beta synthase (CBS) heterozygote knockout, iNOS homozygote knockout, CBS-/+/iNOS-/- double knockout, and wild-type (WT) mice. The levels of nitrotyrosine, MMP-2 and -9 (zymographic analysis), and fibrosis (by trichrome stain) were measured. The endothelial-myocyte function was determined in cardiac rings. In CBS-/+ mice, homocysteine was elevated and in iNOS-/- mice, nitric oxide was significantly reduced. The nitrotyrosine and matrix metalloproteinase-9 (MMP-9) levels were elevated in double knockout and CBS-/+ as compared to WT mice. Although MMP-2 levels were similar in CBS-/+, iNOS-/-, and CBS-/+/iNOS-/-, the levels were three- to fourfold higher than WT. The levels of collagen were similar in CBS-/+ and iNOS-/-, but they were threefold higher than WT. Interesting, the levels of collagen increased sixfold in double knockouts, compared to WT, suggesting synergism between high Hcy and lack of iNOS. Left ventricular hypertrophy was exaggerated in the iNOS-/- and double knockout, and mildly increased in the CBS-/+, compared to WT mice. The endothelial-dependent relaxation was attenuated to the same extent in the CBS-/+ and iNOS-/-, compared to WT, but it was robustly blunted in double knockouts. The results concluded that homocysteine generated nitrotyrosine in the vicinity of

  14. Adaptive Runge-Kutta integration for stiff systems: Comparing Nosé and Nosé-Hoover dynamics for the harmonic oscillator

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    Graham Hoover, William; Clinton Sprott, Julien; Griswold Hoover, Carol

    2016-10-01

    We describe the application of adaptive (variable time step) integrators to stiff differential equations encountered in many applications. Linear harmonic oscillators subject to nonlinear thermal constraints can exhibit either stiff or smooth dynamics. Two closely related examples, Nosé's dynamics and Nosé-Hoover dynamics, are both based on Hamiltonian mechanics and generate microstates consistent with Gibbs' canonical ensemble. Nosé's dynamics is stiff and can present severe numerical difficulties. Nosé-Hoover dynamics, although it follows exactly the same trajectory, is smooth and relatively trouble-free. We emphasize the power of adaptive integrators to resolve stiff problems such as the Nosé dynamics for the harmonic oscillator. The solutions also illustrate the power of computer graphics to enrich numerical solutions.

  15. Zinc regulates iNOS-derived nitric oxide formation in endothelial cells

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    Miriam M. Cortese-Krott

    2014-01-01

    Full Text Available Aberrant production of nitric oxide (NO by inducible NO synthase (iNOS has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation.

  16. Zinc regulates iNOS-derived nitric oxide formation in endothelial cells.

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    Cortese-Krott, Miriam M; Kulakov, Larissa; Opländer, Christian; Kolb-Bachofen, Victoria; Kröncke, Klaus-D; Suschek, Christoph V

    2014-01-01

    Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein) and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation.

  17. A sociologia funcionalista nos estudos organizacionais: foco em Durkheim

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    Augusto Cabral

    Full Text Available O tema que estrutura este ensaio é o da sociologia funcionalista, particularmente em termos de sua influência nos estudos organizacionais. O seu foco de análise é duplo. Em um primeiro momento, as obras de Durkheim. Em um segundo momento, o impacto e a supremacia dos enfoques funcionalistas nos estudos organizacionais. Embora seus segmentos estejam inter-relacionados, ele é composto de quatro partes. Na primeira, é feita uma análise histórica da emergência e sistematização das ciências sociais, de modo a traçar sua evolução até o surgimento dos trabalhos de Durkheim. Na segunda, tomando como referencial a obra de Burrell e Morgan (1979, é estudado o paradigma funcionalista em termos de sua origem e expoentes, com destaque para Comte e Spencer, visando chegar a uma compreensão inicial do pensamento de Durkheim e de sua sociologia. Na terceira, a vida e as principais obras de Durkheim são sumariadas e discutidas. Por fim, o status atual dos estudos organizacionais -vistos como um conjunto impreciso, elástico e eclético de teorias e pesquisas sociais voltados para os problemas das organizações -é analisado em termos de seus pressupostos epistemológicos e ontológicos subjacentes, como meio de explicitar a supremacia dos enfoques positivistas-funcionalistas.

  18. Paraphilia NOS, nonconsent: not ready for the courtroom.

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    Frances, Allen; First, Michael B

    2011-01-01

    Sexually violent predators (SVP) constitute a serious potential risk to public safety, especially when they are released after too short a prison sentence. Twenty states and the federal government have developed a seemingly convenient way to reduce this risk. They have passed statutes that allow for the involuntary (often lifetime) psychiatric commitment of mentally disordered sexual offenders after prison time is up. In three separate cases, the Supreme Court has accepted the constitutionality of this procedure, but only if the offender's dangerousness is caused by a mental disorder and is not a manifestation of simple criminality. The idea that paraphilic rape should be an official category in the psychiatric diagnostic manual has been explicitly rejected by Diagnostic and Statistical Manual of Mental Disorders (DSM)-III, DSM-III-R, DSM-IV, and, recently, DSM-5. Despite this, paraphilia NOS, nonconsent, is still frequently used by mental health evaluators in SVP cases to provide a mental disorder diagnosis that legitimizes psychiatric commitment and makes it appear constitutional. This commentary will show how the diagnosis paraphilia NOS, nonconsent, is based on a fundamental misreading of the original intent of the DSM-IV Paraphilia Workgroup and represents a misuse of psychiatry, all in the admittedly good cause of protecting public safety.

  19. Fantasia e metaficcionalidade nos romances de Zamonien de Walter Moers

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    Laura Alves do Prado

    2014-06-01

    Full Text Available Walter Moers é um dos grandes autores da vertente fantástica dentro da literatura alemã atual. Desde a publicação de seu primeiro romance, em 1999, o escritor consagrou-se como autor de best-sellers. Nos seis romances publicados até a presente data tem-se um elemento comum, que serve de fio condutor às obras: o continente fictício de "Zamonien", um mundo maravilhoso criado por Moers. Esse mundo inventado é palco para inúmeras aventuras, lutas, jornadas, conquistas, mistérios, disputas, perigos, criaturas inusitadas e cenários desconhecidos. Se, por um lado, as obras fantásticas de Moers estão de acordo com as convenções do gênero da Fantasy; por outro, elas trazem consigo uma proposta literária inovadora, que rompe com algumas convenções desse gênero. É o caso da metaficcionalidade, presente de forma marcante em seus romances. Pretende-se nesse trabalho apresentar brevemente um romance de Walter Moers, Die Stadt der träumenden Bücher (2004, discorrer sobre os elementos constitutivos que inserem a obra no gênero da Fantasy e, por fim, aprofundar-se nos aspectos da metaficcionalidade encontrados na obra em questão.

  20. Exercise-induced cardioprotection: a role for eNOS uncoupling and NO metabolites.

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    Farah, C; Kleindienst, A; Bolea, G; Meyer, G; Gayrard, S; Geny, B; Obert, P; Cazorla, O; Tanguy, S; Reboul, Cyril

    2013-11-01

    Exercise is an efficient strategy for myocardial protection against ischemia-reperfusion (IR) injury. Although endothelial nitric oxide synthase (eNOS) is phosphorylated and activated during exercise, its role in exercise-induced cardioprotection remains unknown. This study investigated whether modulation of eNOS activation during IR could participate in the exercise-induced cardioprotection against IR injury. Hearts isolated from sedentary or exercised rats (5 weeks training) were perfused with a Langendorff apparatus and IR performed in the presence or absence of NOS inhibitors [N-nitro-L-arginine methyl ester, L-NAME or N5-(1-iminoethyl)-L-ornithine, L-NIO] or tetrahydrobiopterin (BH₄). Exercise training protected hearts against IR injury and this effect was abolished by L-NAME or by L-NIO treatment, indicating that exercise-induced cardioprotection is eNOS dependent. However, a strong reduction of eNOS phosphorylation at Ser1177 (eNOS-PSer1177) and of eNOS coupling during early reperfusion was observed in hearts from exercised rats (which showed higher eNOS-PSer1177 and eNOS dimerization at baseline) in comparison to sedentary rats. Despite eNOS uncoupling, exercised hearts had more S-nitrosylated proteins after early reperfusion and also less nitro-oxidative stress, indexed by lower malondialdehyde content and protein nitrotyrosination compared to sedentary hearts. Moreover, in exercised hearts, stabilization of eNOS dimers by BH4 treatment increased nitro-oxidative stress and then abolished the exercise-induced cardioprotection, indicating that eNOS uncoupling during IR is required for exercise-induced myocardial cardioprotection. Based on these results, we hypothesize that in the hearts of exercised animals, eNOS uncoupling associated with the improved myocardial antioxidant capacity prevents excessive NO synthesis and limits the reaction between NO and O₂·- to form peroxynitrite (ONOO⁻), which is cytotoxic.

  1. Expression of inducible nitric oxide synthase (iNOS) in microglia of the developing quail retina.

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    Sierra, Ana; Navascués, Julio; Cuadros, Miguel A; Calvente, Ruth; Martín-Oliva, David; Ferrer-Martín, Rosa M; Martín-Estebané, María; Carrasco, María-Carmen; Marín-Teva, José L

    2014-01-01

    Inducible nitric oxide synthase (iNOS), which produce large amounts of nitric oxide (NO), is induced in macrophages and microglia in response to inflammatory mediators such as LPS and cytokines. Although iNOS is mainly expressed by microglia that become activated in different pathological and experimental situations, it was recently reported that undifferentiated amoeboid microglia can also express iNOS during normal development. The aim of this study was to investigate the pattern of iNOS expression in microglial cells during normal development and after their activation with LPS by using the quail retina as model. iNOS expression was analyzed by iNOS immunolabeling, western-blot, and RT-PCR. NO production was determined by using DAR-4M AM, a reliable fluorescent indicator of subcellular NO production by iNOS. Embryonic, postnatal, and adult in situ quail retinas were used to analyze the pattern of iNOS expression in microglial cells during normal development. iNOS expression and NO production in LPS-treated microglial cells were investigated by an in vitro approach based on organotypic cultures of E8 retinas, in which microglial cell behavior is similar to that of the in situ retina, as previously demonstrated in our laboratory. We show here that amoeboid microglia in the quail retina express iNOS during normal development. This expression is stronger in microglial cells migrating tangentially in the vitreal part of the retina and is downregulated, albeit maintained, when microglia differentiate and become ramified. LPS treatment of retina explants also induces changes in the morphology of amoeboid microglia compatible with their activation, increasing their lysosomal compartment and upregulating iNOS expression with a concomitant production of NO. Taken together, our findings demonstrate that immature microglial cells express iNOS during normal development, suggesting a certain degree of activation. Furthermore, LPS treatment induces overactivation of amoeboid

  2. Compensatory lung growth in NOS3 knockout mice suggests synthase isoform redundancy.

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    Pokall, Stefan; Maldonado, Arturo R; Klanke, Charles A; Katayama, Shuichi; Morris, Lee M; Vuletin, Jose F; Lim, Foong-Yen; Crombleholme, Timothy M

    2012-04-01

    Nitric oxide synthase 3 (NOS3) produces nitric oxide (NO) in endothelial cells, which stimulates cyclic guanosine monophosphate (cGMP) production and thereby mediates pulmonary vasodilation. Inhibition of cGMP enzymatic cleavage by sildenafil might be involved in lung growth stimulating processes in pulmonary hypoplasia. The aim of this study was to discover insights into the transcriptional regulation of NOS3 in a mouse model of compensatory lung growth (CLG). CLG was studied in wild type animals (WT) and NOS3 knockout mice (NOS3-/-) by dry weight, DNA, and protein quantification as well as relative quantification of NOS mRNA. All assessments were done on adult female mice, 10 days after left pneumonectomy (PNX) or sham thoracotomy. Weight ratios of right NOS3-/- lungs were no different than controls. There was a compensatory increase in DNA and a noncompensating increase in protein ratios in NOS3-/- mice compared with controls. Pharmacological knockdown with the pan-NOS inhibitor l-NAME (nitro-arginine methyl ester) reduced CLG by only 8% compared with the d-NAME treated control mice. Relative quantification of lung mRNA revealed no up-regulation of NOS3 expression in WT lungs after PNX, but NOS3-/- lungs showed a 2.6-fold higher inducible NOS2 expression compared with shams. These data suggest that NOS3 loss of function alone does not impair CLG in mice, possibly because of redundancy mechanisms involving NOS2. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. Coupled Nosé-Hoover lattice: A set of the Nosé-Hoover equations with different temperatures

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    Fukuda, Ikuo

    2016-07-01

    A simple scheme was presented to couple any number of the Nosé-Hoover equations with different heat-bath temperatures. In general, several practical procedures can be considered to realize such a coupling, where the system is under nonequilibrium. However, the current scheme provides an equilibrium distribution, namely, a smooth invariant measure for the present system. This is attained by a very simple idea, that is, a force scaling. The current scheme realizes coupled differential equations, analogous to coupled maps. Its theoretical possibilities, mathematical framework, and practical utilities are discussed. Numerical validations applying the method to a simple two-oscillator system are provided.

  4. Methylene Blue Attenuates iNOS Induction Through Suppression of Transcriptional Factor Binding Amid iNOS mRNA Transcription.

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    Huang, Chao; Tong, Lijuan; Lu, Xu; Wang, Jia; Yao, Wenjuan; Jiang, Bo; Zhang, Wei

    2015-08-01

    Inducible nitric oxide synthase (iNOS) critically contributes to the development of endotoxin-mediated inflammation. It can be induced by cytokines or endotoxins via distinct signaling pathways. Lipopolysaccharide (LPS) triggers iNOS expression through activation of the inhibitor of κB-α (IκB-α)-nuclear factor κB (NF-κB) cascade, whereas interferon-γ (IFN-γ) acts primarily through Janus kinase (JAK)-signal transducer and activator of transcription 1 (STAT1). Methylene blue (MB), an agent used clinically to treat numerous ailments, has been shown to reduce NO accumulation through suppression of iNOS activity. But it remains unclear whether MB affects iNOS induction. This knowledge gap is addressed in the present study using cultured cells and endotoxemic mice. With mouse macrophages, MB treatment prevented the LPS- and/or IFN-γ-stimulated iNOS protein expression. Real-time PCR experiments showed that iNOS mRNA transcription was robustly blocked by MB treatment. The inhibitory effect of MB on iNOS expression was confirmed in vivo in endotoxemic mice. Further analysis showed that MB had no significant effect on IκB-α degradation and NF-κB or STAT1 phosphorylation in LPS/IFN-γ-stimulated cells. The nuclear transport of active NF-κB or STAT1 was also not affected by MB treatment. But MB treatment markedly reduced the binding of NF-κB and STAT1 to their DNA elements. Chromatin immunoprecipitation assays confirmed that MB reduced NF-κB and STAT1 bindings to iNOS promoter inside the cell. These studies show that MB attenuates transcriptional factor binding amid iNOS mRNA transcription, providing further insight into the molecular mechanism of MB in disease therapy.

  5. Timed and targeted differential regulation of nitric oxide synthase (NOS) and anti-NOS genes by reward conditioning leading to long-term memory formation.

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    Korneev, Sergei A; Straub, Volko; Kemenes, Ildikó; Korneeva, Elena I; Ott, Swidbert R; Benjamin, Paul R; O'Shea, Michael

    2005-02-02

    In a number of neuronal models of learning, signaling by the neurotransmitter nitric oxide (NO), synthesized by the enzyme neuronal NO synthase (nNOS), is essential for the formation of long-term memory (LTM). Using the molluscan model system Lymnaea, we investigate here whether LTM formation is associated with specific changes in the activity of members of the NOS gene family: Lym-nNOS1, Lym-nNOS2, and the antisense RNA-producing pseudogene (anti-NOS). We show that expression of the Lym-nNOS1 gene is transiently upregulated in cerebral ganglia after conditioning. The activation of the gene is precisely timed and occurs at the end of a critical period during which NO is required for memory consolidation. Moreover, we demonstrate that this induction of the Lym-nNOS1 gene is targeted to an identified modulatory neuron called the cerebral giant cell (CGC). This neuron gates the conditioned feeding response and is an essential part of the neural network involved in LTM formation. We also show that the expression of the anti-NOS gene, which functions as a negative regulator of nNOS expression, is downregulated in the CGC by training at 4 h after conditioning, during the critical period of NO requirement. This appears to be the first report of the timed and targeted differential regulation of the activity of a group of related genes involved in the production of a neurotransmitter that is necessary for learning, measured in an identified neuron of known function. We also provide the first example of the behavioral regulation of a pseudogene.

  6. Haplotypes of NOS3 Gene Polymorphisms in Dilated Cardiomyopathy

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    Matsa, Lova Satyanarayana; Rangaraju, Advithi; Vengaldas, Viswamitra; Latifi, Mona; Jahromi, Hossein Mehraban; Ananthapur, Venkateshwari; Nallari, Pratibha

    2013-01-01

    Dilated Cardiomyopathy (DCM) is characterized by systolic dysfunction, followed by heart failure necessitating cardiac transplantation. The genetic basis is well established by the identification of mutations in sarcomere and cytoskeleton gene/s. Modifier genes and environmental factors are also considered to play a significant role in the variable expression of the disease, hence various mechanisms are implicated and one such mechanism is oxidative stress. Nitric Oxide (NO), a primary physiological transmitter derived from endothelium seems to play a composite role with diverse anti-atherogenic effects as vasodilator. Three functional polymorphisms of endothelial nitric oxide synthase (NOS3) gene viz., T-786C of the 5′ flanking region, 27bp VNTR in intron4 and G894T of exon 7 were genotyped to identify their role in DCM. A total of 115 DCM samples and 454 controls were included. Genotyping was carried out by PCR -RFLP method. Allelic and genotypic frequencies were computed in both control & patient groups and appropriate statistical tests were employed. A significant association of TC genotype (T-786C) with an odds ratio of 1.74, (95% CI 1.14 - 2.67, p = 0.01) was observed in DCM. Likewise the GT genotypic frequency of G894T polymorphism was found to be statistically significant (OR 2.10, 95% CI 1.34–3.27, p = 0.0011), with the recessive allele T being significantly associated with DCM (OR 1.64, 95% CI 1.18 - 2.30, p = 0.003). The haplotype carrying the recessive alleles of G894T and T-786C, C4bT was found to exhibit 7 folds increased risk for DCM compared to the controls. Hence C4bT haplotype could be the risk haplotype for DCM. Our findings suggest the possible implication of NOS3 gene in the disease phenotype, wherein NOS3 may be synergistically functioning in DCM associated heart failure via the excessive production of NO in cardiomyocytes resulting in decreased myocardial contractility and systolic dysfunction, a common feature of DCM

  7. Haplotypes of NOS3 gene polymorphisms in dilated cardiomyopathy.

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    Lova Satyanarayana Matsa

    Full Text Available Dilated Cardiomyopathy (DCM is characterized by systolic dysfunction, followed by heart failure necessitating cardiac transplantation. The genetic basis is well established by the identification of mutations in sarcomere and cytoskeleton gene/s. Modifier genes and environmental factors are also considered to play a significant role in the variable expression of the disease, hence various mechanisms are implicated and one such mechanism is oxidative stress. Nitric Oxide (NO, a primary physiological transmitter derived from endothelium seems to play a composite role with diverse anti-atherogenic effects as vasodilator. Three functional polymorphisms of endothelial nitric oxide synthase (NOS3 gene viz., T-786C of the 5' flanking region, 27bp VNTR in intron4 and G894T of exon 7 were genotyped to identify their role in DCM. A total of 115 DCM samples and 454 controls were included. Genotyping was carried out by PCR -RFLP method. Allelic and genotypic frequencies were computed in both control & patient groups and appropriate statistical tests were employed. A significant association of TC genotype (T-786C with an odds ratio of 1.74, (95% CI 1.14 - 2.67, p = 0.01 was observed in DCM. Likewise the GT genotypic frequency of G894T polymorphism was found to be statistically significant (OR 2.10, 95% CI 1.34-3.27, p = 0.0011, with the recessive allele T being significantly associated with DCM (OR 1.64, 95% CI 1.18 - 2.30, p = 0.003. The haplotype carrying the recessive alleles of G894T and T-786C, C4bT was found to exhibit 7 folds increased risk for DCM compared to the controls. Hence C4bT haplotype could be the risk haplotype for DCM. Our findings suggest the possible implication of NOS3 gene in the disease phenotype, wherein NOS3 may be synergistically functioning in DCM associated heart failure via the excessive production of NO in cardiomyocytes resulting in decreased myocardial contractility and systolic dysfunction, a common feature of DCM

  8. Dual role of nNOS in ischemic injury and preconditioning

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    Barua Anupama

    2010-08-01

    Full Text Available Abstract Background Nitric oxide (NO is cardioprotective and a mediator of ischemic preconditioning (IP. Endothelial nitric oxide synthase (eNOS is protective against myocardial ischemic injury and a component of IP but the role and location of neuronal nitric oxide synthase (nNOS remains unclear. Therefore, the aims of these studies were to: (i investigate the role of nNOS in ischemia/reoxygenation-induced injury and IP, (ii determine whether its effect is species-dependent, and (iii elucidate the relationship of nNOS with mitoKATP channels and p38MAPK, two key components of IP transduction pathway. Results Ventricular myocardial slices from rats and wild and nNOS knockout mice, and right atrial myocardial slices from human were subjected to 90 min ischemia and 120 min reoxygenation (37°C. Specimens were randomized to receive various treatments (n = 6/group. Both the provision of exogenous NO and the inhibition of endogenous NO production significantly reduced tissue injury (creatine kinase release, cell necrosis and apoptosis, an effect that was species-independent. The cardioprotection seen with nNOS inhibition was as potent as that of IP, however, in nNOS knockout mice the cardioprotective effect of non-selective NOS (L-NAME and selective nNOS inhibition and also that of IP was blocked while the benefit of exogenous NO remained intact. Additional studies revealed that the cardioprotection afforded by exogenous NO and by inhibition of nNOS were unaffected by the mitoKATP channel blocker 5-HD, although it was abrogated by p38MAPK blocker SB203580. Conclusions nNOS plays a dual role in ischemia/reoxygenation in that its presence is necessary to afford cardioprotection by IP and its inhibition reduces myocardial ischemic injury. The role of nNOS is species-independent and exerted downstream of the mitoKATP channels and upstream of p38MAPK.

  9. Arginase-1 deficiency regulates arginine concentrations and NOS2-mediated NO production during endotoxemia.

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    Karolina A P Wijnands

    Full Text Available RATIONALE AND OBJECTIVE: Arginase-1 is an important component of the intricate mechanism regulating arginine availability during immune responses and nitric oxide synthase (NOS activity. In this study Arg1(fl/fl/Tie2-Cre(tg/- mice were developed to investigate the effect of arginase-1 related arginine depletion on NOS2- and NOS3-dependent NO production and jejunal microcirculation under resting and endotoxemic conditions, in mice lacking arginase-1 in endothelial and hematopoietic cells. METHODS AND RESULTS: Arginase-1-deficient mice as compared with control mice exhibited higher plasma arginine concentration concomitant with enhanced NO production in endothelial cells and jejunal tissue during endotoxemia. In parallel, impaired jejunal microcirculation was observed in endotoxemic conditions. Cultured bone-marrow-derived macrophages of arginase-1 deficient animals also presented a higher inflammatory response to endotoxin than control littermates. Since NOS2 competes with arginase for their common substrate arginine during endotoxemia, Nos2 deficient mice were also studied under endotoxemic conditions. As Nos2(-/- macrophages showed an impaired inflammatory response to endotoxin compared to wild-type macrophages, NOS2 is potentially involved. A strongly reduced NO production in Arg1(fl/fl/Tie2-Cre(tg/- mice following infusion of the NOS2 inhibitor 1400W further implicated NOS2 in the enhanced capacity to produce NO production Arg1(fl/fl/Tie2-Cre(tg/- mice. CONCLUSIONS: Reduced arginase-1 activity in Arg1(fl/fl/Tie2-Cre(tg/- mice resulted in increased inflammatory response and NO production by NOS2, accompanied by a depressed microcirculatory flow during endotoxemia. Thus, arginase-1 deficiency facilitates a NOS2-mediated pro-inflammatory activity at the expense of NOS3-mediated endothelial relaxation.

  10. Genetic deletion of NOS3 increases lethal cardiac dysfunction following mouse cardiac arrest.

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    Beiser, David G; Orbelyan, Gerasim A; Inouye, Brendan T; Costakis, James G; Hamann, Kimm J; McNally, Elizabeth M; Vanden Hoek, Terry L

    2011-01-01

    Cardiac arrest mortality is significantly affected by failure to obtain return of spontaneous circulation (ROSC) despite cardiopulmonary resuscitation (CPR). Severe myocardial dysfunction and cardiovascular collapse further affects mortality within hours of initial ROSC. Recent work suggests that enhancement of nitric oxide (NO) signaling within minutes of CPR can improve myocardial function and survival. We studied the role of NO signaling on cardiovascular outcomes following cardiac arrest and resuscitation using endothelial NO synthase knockout (NOS3(-/-)) mice. Adult female wild-type (WT) and NOS3(-/-) mice were anesthetized, intubated, and instrumented with left-ventricular pressure-volume catheters. Cardiac arrest was induced with intravenous potassium chloride. CPR was performed after 8min of untreated arrest. ROSC rate, cardiac function, whole-blood nitrosylhemoglobin (HbNO) concentrations, heart NOS3 content and phosphorylation (p-NOS3), cyclic guanosine monophosphate (cGMP), and phospho-troponin I (p-TnI) were measured. Despite equal quality CPR, NOS3(-/-) mice displayed lower rates of ROSC compared to WT (47.6% [10/21] vs. 82.4% [14/17], pNOS3(-/-) vs. WT mice exhibited increased left-ventricular dysfunction and 120min mortality. Prior to ROSC, myocardial effectors of NO signaling including cGMP and p-TnI were decreased in NOS3(-/-) vs. WT mice (pNOS3-dependent increases in circulating HbNO were seen by 120min. Significant increases in cardiac p-NOS3 occurred between end-arrest and 15min post-ROSC, while total NOS3 content was increased by 120min post-ROSC (pNOS3 decreases ROSC rate and worsens post-ROSC left-ventricular function. Poor cardiovascular outcomes are associated with differences in NOS3-dependent myocardial cGMP signaling and circulating NO metabolites. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Nos3 protects against systemic inflammation and myocardial dysfunction in murine polymicrobial sepsis.

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    Bougaki, Masahiko; Searles, Robert J; Kida, Kotaro; Yu, JiaDe; Buys, Emmanuel S; Ichinose, Fumito

    2010-09-01

    NO has been implicated in the pathogenesis of septic shock. However, the role of NO synthase 3 (NOS3) during sepsis remains incompletely understood. Here, we examined the impact of NOS3 deficiency on systemic inflammation and myocardial dysfunction during peritonitis-induced polymicrobial sepsis. Severe polymicrobial sepsis was induced by colon ascendens stent peritonitis (CASP) in wild-type (WT) and NOS3-deficient (NOS3KO) mice. NOS3KO mice exhibited shorter survival time than did WT mice after CASP. NOS3 deficiency worsened systemic inflammation assessed by the expression of inflammatory cytokines in the lung, liver, and heart. Colon ascendens stent peritonitis markedly increased the number of leukocyte infiltrating the liver and heart in NOS3KO but not in WT mice. The exaggerated systemic inflammation in septic NOS3KO mice was associated with more marked myocardial dysfunction than in WT mice 22 h after CASP. The detrimental effects of NOS3 deficiency on myocardial function after CASP seem to be caused by impaired Ca handling of cardiomyocytes. The impaired Ca handling of cardiomyocytes isolated from NOS3KO mice subjected to CASP was associated with depressed mitochondrial ATP production, a determinant of the Ca cycling capacity of sarcoplasmic reticulum Ca-ATPase. The NOS3 deficiency-induced impairment of the ability of mitochondria to produce ATP after CASP was at least in part attributable to reduction in mitochondrial respiratory chain complex I activity. These observations suggest that NOS3 protects against systemic inflammation and myocardial dysfunction after peritonitis-induced polymicrobial sepsis in mice.

  12. Inhibition of Rho protein stimulates iNOS expression in rat vascular smooth muscle cells.

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    Muniyappa, R; Xu, R; Ram, J L; Sowers, J R

    2000-06-01

    Inducible nitric oxide synthase (iNOS) in vascular smooth muscle cells (VSMCs) is upregulated in arterial injury and plays a role in regulating VSMC proliferation and restenosis. Inflammatory cytokines [e.g., interleukin-1beta (IL-1beta)] released during vascular injury induce iNOS. Small GTP-binding proteins of the Ras superfamily play a major role in IL-1beta-dependent signaling pathways. In this study, we examined the role of Rho GTPases in regulating iNOS expression in VSMCs. Treatment of VSMCs with mevastatin, which inhibits isoprenylation of Rho and other small GTP-binding proteins, produced significantly higher amounts of IL-1beta-evoked NO and iNOS protein compared with control. Similarly, bacterial toxins [Toxin B from Clostridium difficile and C3 ADP-ribosyl transferase (C3) toxin from Clostridium botulinium] that specifically inactivate Rho proteins increased NOS products (NO and citrulline) and iNOS expression. Toxin B increased the activity of iNOS promoter-reporter construct in VSMCs. Both toxins enhanced IL-1beta-stimulated iNOS expression and NO production. These data demonstrate for the first time that inhibition of Rho induces iNOS and suggest a role for Rho protein in IL-1beta-stimulated NO production in VSMCs.

  13. EL NOS-OTROS-ORIGINARIO: Sobre la posibilidad de respetar los derechos de el-otro

    OpenAIRE

    Fager Sáenz, Nayid Abú

    2016-01-01

    Este texto plantea la posibilidad de recuperar el nos-otros-originario como clave para la superación del «sufrimiento inútil» del sujeto; de este modo, muestra al nos-otros-originario como una zona de protección de los derechos de el-otro, hace una crítica en contra del nos-otros-caído como vulnerador de derechos fundamentales, y aborda la posibilidad de recuperar el nos-otros-originario a través de una consumación definitiva de la "justicia". This article shows the possibility of recoveri...

  14. [Genetics of the neuronal NO synthase (NOS1) in the etiology of bronchial asthma].

    Science.gov (United States)

    Grasemann, H

    2001-08-01

    The free radical nitric oxide (NO) is endogenously produced by enzymes known as NO synthases. NO in the airways is involved in a number of pathophysiological processes, such as airway inflammation, allergic reactions, and asthma. Asthma is a multifactorial disease that is caused by environmental and genetic factors. Genome wide screening approaches in families revealed evidence for linkage between chromosomal region 12q and allergic diseases, increased serum IgE levels as well as the development of asthma. The gene encoding for neuronal NOS (NOS1) is an attractive candidate gene for asthma, not only because it is localized in chromosomal region 12q24. Experimental studies in animals and humans suggest that NOS1 plays an important role in asthma. For instance, in a murine model of allergic asthma, NOS1 has been shown to be important for the development of bronchial hyperresponsiveness, since mice deficient for the nos1 gene were less responsive to airway challenge than both wild-type mice and mice deficient for the nos2 gene. Case-control studies in humans revealed allelic associations between polymorphic markers in the NOS1 gene and the diagnosis of asthma. Furthermore, increased concentrations of NO in the airways of asthmatics are closely related to the size of an intronic (AAT)(n)-repeat polymorphism in the NOS1 gene. The purpose of this review is to summarize studies that provide evidence for an involvement of NOS1 in the genetics of asthma.

  15. Crime e castigo nos Estados Unidos: de Nixon a Clinton

    Directory of Open Access Journals (Sweden)

    Loïc Wacquant

    1999-11-01

    Full Text Available Este artigo analisa o crescimento exponencial do número de detentos ocorrido nos Estados Unidos a partir de meados dos anos 70. Procura mostrar que esse crescimento não corresponde a um aumento da criminalidade, mas à conjugação de três séries causais, quais sejam: o declínio do "ideal de reabilitação" dos prisioneiros, a instrumentalização do medo da violência pelos políticos e pela mídia e a função de mecanismo de controle racial assumido pelo sistema penal americano. Em suma, a hiperflação carcerária revela a contraface do enfraquecimento do Estado de Bem-Estar Social e a sua substituição por um Estado penal.

  16. Lévi-Strauss nos 90 voltas ao passado

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    Lévi-Strauss Claude

    1998-01-01

    Full Text Available Este artigo responde às críticas formuladas por Christian Delacampagne e Bernard Traimond em "A Polêmica Sartre/Lévi-Strauss Revisitada. Nas Raízes das Ciências Sociais de Hoje", publicado em Les Temps Modernes 596 (novembro-dezembro de 1997. Para fazê-lo, recorda inicialmente o caráter relativo da oposição entre "sociedades frias" e "sociedades quentes". Em seguida, refuta a tese de que Maurice Merleau-Ponty, sob a capa de um elogio, teria dirigido críticas veladas ao autor. Finalmente, reconhecendo o afastamento da antropologia de hoje em face das posições do autor, admite, sem se pronunciar sobre o valor desse movimento, que temas de ar sartriano ressurgem nos antropólogos contemporâneos.

  17. Tecnologia dos sonhos em Artemidoro, Freud, Jung e nos Warlpiri

    Directory of Open Access Journals (Sweden)

    Abrahão de Oliveira Santos

    2014-08-01

    Full Text Available Apresentaremos distintas tecnologias dos sonhos: em Artemidoro, Freud, Jung e nos Warlpiri. Artemidoro revela a mensagem onírica imprescindível à condução do cidadão, com os elementos das instituições, da cidade, do cosmo. Com Freud, no moderno mundo europeu, o sonho recebe o sentido da interioridade. Outra leitura é de Carl Jung. O uso dos sonhos tem seu sentido histórico, se relacionando com as práticas de governo, os modos de condução da vida e da cidade. Para além das tradições eurodescendentes e mentalistas vigentes, apresentaremos a tecnologia coletiva dos sonhos dos Warlpiri e uma nova possibilidade de lidarmos com a experiência onírica.

  18. "Meninas": vidas em devir nos circuitos de vulnerabilidade social

    Directory of Open Access Journals (Sweden)

    Denise Cordeiro

    2008-06-01

    Full Text Available Neste artigo pretendemos discutir, a partir do filme Meninas, de Sandra Werneck, as trajetórias de vida e de trabalho de jovens pobres no Rio de Janeiro, nos circuitos de vulnerabilidade social. As aproximações do olhar cinematográfico vão expressar um "tempo comum", presente no referido documentário, que se materializa em nossas pesquisas: gravidez precoce, violência, desemprego, baixa escolaridade, pouca qualificação e inserção no tráfico de drogas, por exemplo. Nesses circuitos de vulnerabilidade, perguntamos como é possível ampliar a potência de vida dos jovens, que não perdem a possibilidade de escrever sua própria história. É nessa direção que caminha o presente estudo.

  19. O FANTÁSTICO NOS ROMANCES DE JOSÉ SARAMAGO

    Directory of Open Access Journals (Sweden)

    Pál Ferenc

    2012-01-01

    Full Text Available Nos romances de José Saramago abundam os elementos fantásticos desde o olhar mágico de Blimunda que vê o interior das pessoas até a morte suspendida temporalmente num país. O presente estudo analisa os assomos do fantástico nestes romances, aproveitando a teoria de Tzvetan Todorov e as afirmações de vários estudiosos brasileiros e portugueses,chegando a conclusão que com exepção do último romance, Intermitências da Morte, as obras do romancista português são alegorias onde os motivos ou momentos aparentemente fantásticos são na realidade maravilhosos ou estranhos e têm uma função de por em movimento da acção do romance.

  20. Identification of chicken eNOS gene and differential expression in highland versus lowland chicken breeds.

    Science.gov (United States)

    Peng, J F; Ling, Y; Gou, W Y; Zhang, H; Wu, C X

    2012-09-01

    Nitric oxide (NO), an endothelium-derived relaxing factor, is synthesized from l-arginine by endothelial nitric oxide synthase (eNOS) in the endothelium. The objective of the present study was to preliminarily illuminate the expression of the eNOS gene in hypoxic adaptation of chicken embryonic development. The eNOS expression profiles between the Tibet and Shouguang chickens incubated under both normoxic and hypoxic conditions were detected by TaqMan real-time PCR. In this study, the chicken eNOS gene was found by both in silico cloning and RACE approaches. From the eNOS gene, we obtained a 3,310-bp mRNA sequence and a 10,666-bp DNA sequence and discovered that it was located on chicken chromosome 2 and had 7 unique transcripts. eNOS mRNA was detected in abundant amounts in some chick embryo organs (i.e., heart, liver, chorio-allantoic membrane, and lung), and expressed stably with the lowest levels in the brain. We observed that when exposed to hypoxia (13% O(2)) different embryo organ tissues had various sensitivities to hypoxia as determined by their eNOS expression profiles. Compared with the Shouguang chicken, the eNOS expression in the Tibet chicken was higher in the lung and liver, lower in the heart, and similar in the brain. In chorio-allantoic membranes, eNOS expression was higher in the Shouguang chicken than the Tibet chicken under hypoxic conditions, but not markedly different under normoxic conditions. The differences of eNOS expression between the 2 breeds may be relative to the hypoxic adaptation ability in Tibet chickens during embryonic development. This work will provide reference for future studies on the role of eNOS in hypoxic adaptation and response.

  1. Role of SIRT1 and FOXO factors in eNOS transcriptional activation by resveratrol.

    Science.gov (United States)

    Xia, Ning; Strand, Susanne; Schlufter, Frank; Siuda, Daniel; Reifenberg, Gisela; Kleinert, Hartmut; Förstermann, Ulrich; Li, Huige

    2013-08-01

    Many of the cardiovascular protective effects of resveratrol are attributable to an enhanced production of nitric oxide (NO) by the endothelial NO synthase (eNOS). Resveratrol has been shown to enhance eNOS gene expression as well as eNOS enzymatic activity. The aim of the present study was to analyze the molecular mechanisms of eNOS transcriptional activation by resveratrol. Treatment of human EA.hy 926 endothelial cells with resveratrol led to a concentration-dependent upregulation of eNOS expression. In luciferase reporter gene assay, resveratrol enhanced the activity of human eNOS promoter fragments (3500, 1600, 633 and 263bp in length, respectively), indicating that the proximal promoter region is required for resveratrol-induced eNOS transcriptional activation. Knockdown of the NAD(+)-dependent protein deacetylase sirtuin 1 (SIRT1) by siRNA prevented the upregulation of eNOS mRNA and protein by resveratrol. Forkhead box O (FOXO) transcription factors are established downstream targets of SIRT1. siRNA-mediated knockdown of FOXO1 and FOXO3a abolished the effect of resveratrol on eNOS expression, indicating the involvement of these factors. Resveratrol treatment enhanced the expression of FOXO1 and FOXO3a in EA.hy 926 cells. Reporter gene assay using promoter containing forkhead response elements showed increased FOXO factor activity by resveratrol. In electrophoretic mobility shift assay, the enhanced binding of nuclear proteins to the eNOS promoter regions by resveratrol could be blocked by antibodies against FOXO1 and FOXO3a. In conclusion, resveratrol enhances the expression and activity of FOXO transcription factors. The SIRT1/FOXO factor axis is involved in resveratrol-induced eNOS transcriptional activation.

  2. Depletion of arginine by recombinant arginine deiminase induces nNOS-activated neurotoxicity in neuroblastoma cells.

    Science.gov (United States)

    Lin, Shan-Erh; Wu, Fe-Lin Lin; Wei, Ming-Feng; Shen, Li-Jiuan

    2014-01-01

    The abnormal regulation of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) is associated with neurodegenerative disorders. Recombinant arginine deiminase (rADI) is a selective NO modulator of iNOS and eNOS in endothelial cells, and it also exhibits neuroprotective activity in an iNOS-induced neuron-microglia coculture system. However, the effect of rADI on nNOS remains unknown. Addressing this issue is important for evaluating the potential application of rADI in neurodegenerative diseases. SH-SY5Y cells were treated with N-methyl-D-aspartic acid (NMDA) to activate nNOS. NMDA increased NO production by 39.7 ± 3.9% via nNOS under arginine-containing conditions, but there was no significant increase in both arginine-free and rADI pretreated arginine-containing (citrulline) buffer. Subsequently, neither NMDA nor rADI alone caused cytotoxicity, whereas cotreatment with NMDA and rADI resulted in dissipation of the cell mitochondrial membrane potential and decreased cell viability. The mechanism of rADI cytotoxicity in the presence of NMDA is caused by the inhibition of NO production via nNOS mediated by the NMDA receptor, which was abolished when extracellular arginine was absent, even in the presence of citrulline. rADI not only reduced NO production but also caused cellular toxicity in nNOS-activated SH-SY5Y cells, suggesting a dual role for rADI in NOS-mediated neurotoxicity.

  3. Depletion of Arginine by Recombinant Arginine Deiminase Induces nNOS-Activated Neurotoxicity in Neuroblastoma Cells

    Directory of Open Access Journals (Sweden)

    Shan-Erh Lin

    2014-01-01

    Full Text Available The abnormal regulation of inducible nitric oxide synthase (iNOS and neuronal nitric oxide synthase (nNOS is associated with neurodegenerative disorders. Recombinant arginine deiminase (rADI is a selective NO modulator of iNOS and eNOS in endothelial cells, and it also exhibits neuroprotective activity in an iNOS-induced neuron-microglia coculture system. However, the effect of rADI on nNOS remains unknown. Addressing this issue is important for evaluating the potential application of rADI in neurodegenerative diseases. SH-SY5Y cells were treated with N-methyl-D-aspartic acid (NMDA to activate nNOS. NMDA increased NO production by 39.7 ± 3.9% via nNOS under arginine-containing conditions, but there was no significant increase in both arginine-free and rADI pretreated arginine-containing (citrulline buffer. Subsequently, neither NMDA nor rADI alone caused cytotoxicity, whereas cotreatment with NMDA and rADI resulted in dissipation of the cell mitochondrial membrane potential and decreased cell viability. The mechanism of rADI cytotoxicity in the presence of NMDA is caused by the inhibition of NO production via nNOS mediated by the NMDA receptor, which was abolished when extracellular arginine was absent, even in the presence of citrulline. rADI not only reduced NO production but also caused cellular toxicity in nNOS-activated SH-SY5Y cells, suggesting a dual role for rADI in NOS-mediated neurotoxicity.

  4. Expression of beta-catenin, COX-2 and iNOS in colorectal cancer: relevance of COX-2 adn iNOS inhibitors for treatment in Malaysia.

    Science.gov (United States)

    Hong, Seok Kwan; Gul, Yunus A; Ithnin, Hairuszah; Talib, Arni; Seow, Heng Fong

    2004-01-01

    Promising new pharmacological agents and gene therapy targeting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) could modulate treatment of colorectal cancer in the future. The aim of this study was to elucidate the expression fo beta-catenin and teh presence of COX-2 and iNOS in colorectal cancer specimens in Malaysia. This is a useful prelude to future studies investigating interventions directed towards COX-2 adn iNOS. A cross-section study using retrospective data over a 2-year period (1999-2000) involved 101 archival, formalin-fixed, paraffin-embedded tissue samples of colorectal cancers that were surgically resected in a tertiary referral. COX-2 production was detected in adjacent normal tissue in 34 sample (33.7%) and in tumour tissue in 60 samples (59.4%). More tumours expressed iNOS (82/101, 81.2%) than COX-2. No iNOS expression was detected in adjacent normal tissue. Intense beta-catenin immunoreactivity at the cell-to-cell border. Poorly differentiated tumours had significantly lower total beta-catenin (p = 0.009) and COX-2 scores (p = 0.031). No significant relationships were established between pathological stage and beta-catenin, COX-2 and iNOS scores. the accumulation of beta-catenin does not seem to be sufficient to activate pathways that lead to increased COX-2 and iNOS expression. A high proportion of colorectal cancers were found to express COX-2 and a significant number produced iNOS, suggesting that their inhibitors may be potentially useful as chemotherapeutic agents in the management of colorectal cancer.

  5. Tetrahydrobiopterin (BH4), a cofactor for nNOS, restores gastric emptying and nNOS expression in female diabetic rats

    OpenAIRE

    2010-01-01

    Gastroparesis is a debilitating disease predominantly affecting young women. Recently, dysregulation of neuronal nitric oxide synthase (nNOS) in myenteric plexus neurons has been implicated for delayed solid gastric emptying/gastroparesis in diabetic patients. In this study, we have explored the role of tetrahydrobiopterin (BH4), a major cofactor for nNOS activity and NO synthesis in diabetic gastroparesis. Diabetes was induced with single injection of streptozotocin (55 mg/kg body wt, ip) in...

  6. Asiatic Acid Alleviates Hemodynamic and Metabolic Alterations via Restoring eNOS/iNOS Expression, Oxidative Stress, and Inflammation in Diet-Induced Metabolic Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Poungrat Pakdeechote

    2014-01-01

    Full Text Available Asiatic acid is a triterpenoid isolated from Centella asiatica. The present study aimed to investigate whether asiatic acid could lessen the metabolic, cardiovascular complications in rats with metabolic syndrome (MS induced by a high-carbohydrate, high-fat (HCHF diet. Male Sprague-Dawley rats were fed with HCHF diet with 15% fructose in drinking water for 12 weeks to induce MS. MS rats were treated with asiatic acid (10 or 20 mg/kg/day or vehicle for a further three weeks. MS rats had an impairment of oral glucose tolerance, increases in fasting blood glucose, serum insulin, total cholesterol, triglycerides, mean arterial blood pressure, heart rate, and hindlimb vascular resistance; these were related to the augmentation of vascular superoxide anion production, plasma malondialdehyde and tumor necrosis factor-alpha (TNF-α levels (p < 0.05. Plasma nitrate and nitrite (NOx were markedly high with upregulation of inducible nitric oxide synthase (iNOS expression, but dowregulation of endothelial nitric oxide synthase (eNOS expression (p < 0.05. Asiatic acid significantly improved insulin sensitivity, lipid profiles, hemodynamic parameters, oxidative stress markers, plasma TNF-α, NOx, and recovered abnormality of eNOS/iNOS expressions in MS rats (p < 0.05. In conclusion, asiatic acid improved metabolic, hemodynamic abnormalities in MS rats that could be associated with its antioxidant, anti-inflammatory effects and recovering regulation of eNOS/iNOS expression.

  7. Diesel Particulate Exposed Macrophages Alter Endothelial Cell Expression of eNOS, iNOS, MCP1, and Glutathione Synthesis Genes

    Science.gov (United States)

    Weldy, Chad S.; Wilkerson, Hui-Wen; Larson, Timothy V.; Stewart, James A.; Kavanagh, Terrance J.

    2011-01-01

    There is considerable debate regarding inhaled diesel exhaust particulate (DEP) causing impairments in vascular reactivity. Although there is evidence that inhaled particles can translocate from the lung into the systemic circulation, it has been suggested that inflammatory factors produced in the lung following macrophage particle engulfment also pass into the circulation. To investigate these differing hypotheses, we used in vitro systems to model each exposure. By using a direct exposure system and a macrophage-endothelial cell co-culture model, we compared the effects of direct DEP exposure and exposure to inflammatory factors produced by DEP-treated macrophages, on endothelial cell mRNA levels for eNOS, iNOS, endothelin-1, and endothelin-converting-enzyme-1. As markers of oxidative stress, we measured the effects of DEP treatment on glutathione (GSH) synthesis genes and on total GSH. In addition, we analyzed the effect of DEP treatment on monocyte chemo-attractant protein-1. Direct DEP exposure increased endothelial GCLC and GCLM as well as total GSH in addition to increased eNOS, iNOS and Mcp1 mRNA. Alternatively, inflammatory factors released from DEP-exposed macrophages markedly up-regulated endothelial iNOS and Mcp1 while modestly down-regulating eNOS. These data support both direct exposure to DEP and the release of inflammatory cytokines as explanations for DEP-induced impairments in vascular reactivity. PMID:21920430

  8. NOS2 expression is restricted to neurons in the healthy brain but is triggered in microglia upon inflammation.

    Science.gov (United States)

    Béchade, Catherine; Colasse, Sabrina; Diana, Marco A; Rouault, Martin; Bessis, Alain

    2014-06-01

    Nitric oxide (NO) is a diffusible second messenger with a great variety of functions in the brain. NO is produced by three isoforms of NO synthase (NOS), NOS1, NOS2, and NOS3. Although broad agreement exists regarding the expression of NOS1 and NOS3 in neurons and endothelial cells, the pattern of NOS2 expression is still controversial and remains elusive. We have now generated a novel transgenic mouse that expresses the fluorescent reporter tdTomato and the CRE recombinase under the control of the Nos2 gene regulatory regions. Such tool allows the reliable tracking of NOS2 expression in tissue and further unravels episodes of transient NOS2 expression. Using this transgenic mouse, we show that in the healthy brain, NOS2 is only transiently expressed in neurons scattered in the piriform and entorhinal cortex, the amygdaloid nuclei, the medial part of the thalamus, the hypothalamus, the dentate gyrus, and the cerebellum. NOS2 expression was rarely detected in microglia. We further show that inflammation, induced by intracerebral injection of LPS and IFNγ, triggers transient expression of NOS2 in microglia but not in neurons. This novel transgenic tool has thus allowed us to clarify the NOS2 expression pattern and its differential profile in neurons and microglia in healthy and inflammatory conditions. Copyright © 2014 Wiley Periodicals, Inc.

  9. Nitric Oxide and eNOS Gene in Essential Hypertension

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    Kamna Srivastava

    2009-04-01

    Full Text Available Background: Currently hypertension grips around 25% of the entire world population. More than 90% of the hypertensive patients suffer from essential hypertension. In Asian Indians hypertension is the predominant risk factor for Coronary Artery Disease among others. Nitric Oxide (NO is synonymous with endothelial derived relaxation factor. Acting via cGMP (cyclic guanosine monophosphate it causes smooth muscle relaxation, prevents platelet aggregation and acts as an anti-inflammatory agent. iNOS (inducible Nitric oxide synthase, nNOS(neuronal nitric oxide synthase and eNOS (endothelial nitric oxide synthase are the three enzymes producing the gas nitric oxide in the human body. eNOS is the main source of NO under physiological conditions. It is known to have a number of polymorphisms. The most well known ones being the G to T polymorphism in exon 7, the T to C polymorphism in the promoter region and the a/b polymorphism in the intron 4. While the G to T polymorphism has been associated with hypertension in many races including the north Indian population, the association of other polymorphisms has been more of a controversy. Not much study has been done on the Asians especially those in India regarding these polymorphisms. Aims: To elucidate the association between the intron4a/b polymorphism in the eNOS gene and nitric oxide levels and essential hypertension. Objectives: 1. To determine the genotype frequencies of the above mentioned polymorphism in patients and controls2. To study the levels of NO in the plasma of the patients and controls3. To find out correlation if any between this polymorphism and plasma NO levels4. To find a correlation if any between this polymorphism and essential hypertension Materials and Methods: The study design was a case control study. 10 ml of venous blood was taken from 45 patients (selected from the department of Cardiology All India Institute of Medical Sciences, ages between 25 to 55 yrs and not on any

  10. Recensão de "Nos 50 anos de Árvore - Folhas de Poesia"

    OpenAIRE

    2005-01-01

    Recensão - COLÓQUIO "NOS 50 ANOS DE ÁRVORE - FOLHAS DE POESIA", Porto, 2003 - Nos 50 anos de Árvore - folhas de poesia : actas do Colóquio realizado em 16 de Maio de 2003. Porto : Universidade Fernando Pessoa, 2005. 128 p.. ISBN 972-8830-33-5

  11. Suggesting a NOS Map for Nature of Science for Science Education Instruction

    Science.gov (United States)

    Oh, Jun-Young

    2017-01-01

    The aims of this research are 1) to explore the inter-relationships within the individual elements or tenets of Nature of Science (NOS), based on the dimensions of scientific knowledge in science learning, and 2) to consider Kuhn's concept of how scientific revolution takes place. This study suggests that instruction according to our NOS Flowchart…

  12. NOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: The Atherosclerosis Risk in Communities study

    Science.gov (United States)

    Endothelial nitric oxide synthase (NOS3) activity and cigarette smoking significantly influence endothelial function. We sought to determine whether cigarette smoking modified the association between NOS3 polymorphisms and risk of coronary heart disease or stroke. All 1085 incident coronary heart di...

  13. Suggesting a NOS Map for Nature of Science for Science Education Instruction

    Science.gov (United States)

    Oh, Jun-Young

    2017-01-01

    The aims of this research are 1) to explore the inter-relationships within the individual elements or tenets of Nature of Science (NOS), based on the dimensions of scientific knowledge in science learning, and 2) to consider Kuhn's concept of how scientific revolution takes place. This study suggests that instruction according to our NOS Flowchart…

  14. Umbilical Cord Blood NOS1 as a Potential Biomarker of Neonatal Encephalopathy.

    Science.gov (United States)

    Lei, Jun; Paules, Cristina; Nigrini, Elisabeth; Rosenzweig, Jason M; Bahabry, Rudhab; Farzin, Azadeh; Yang, Samuel; Northington, Frances J; Oros, Daniel; McKenney, Stephanie; Johnston, Michael V; Graham, Ernest M; Burd, Irina

    2017-01-01

    There are no definitive markers to aid in diagnosis of neonatal encephalopathy (NE). The purpose of our study was (1) to identify and evaluate the utility of neuronal nitric oxide synthase (NOS1) in umbilical cord blood as a NE biomarker and (2) to identify the source of NOS1 in umbilical cord blood. This was a nested case-control study of neonates >35 weeks of gestation. ELISA for NOS1 in umbilical cord blood was performed. Sources of NOS1 in umbilical cord were investigated by immunohistochemistry, western blot, ELISA, and quantitative PCR. Furthermore, umbilical cords of full-term neonates were subjected to 1% hypoxia ex vivo. NOS1 was present in umbilical cord blood and increased in NE cases compared with controls. NOS1 was expressed in endothelial cells of the umbilical cord vein, but not in artery or blood cells. In ex vivo experiments, hypoxia was associated with increased levels of NOS1 in venous endothelial cells of the umbilical cord as well as in ex vivo culture medium. This is the first study to investigate an early marker of NE. NOS1 is elevated with hypoxia, and further studies are needed to investigate it as a valuable tool for early diagnosis of neonatal brain injury.

  15. Inducible nitric oxide synthase (NOS II) is constitutive in human neutrophils.

    Science.gov (United States)

    Cedergren, Jan; Follin, Per; Forslund, Tony; Lindmark, Maria; Sundqvist, Tommy; Skogh, Thomas

    2003-10-01

    The objective was to study the expression of inducible nitric oxide synthase (NOS II) in and NO production by human blood neutrophils and in in vivo exudated neutrophils. Cellular expression of NOS II was evaluated by flow cytometry in whole blood, in isolated blood neutrophils, and in neutrophils obtained by exudation in vivo into skin chambers. Neutrophil NOS II was also demonstrated by Western blotting. Uptake of 3H-labelled L-arginine was studied in vitro and NOS activity measured in a whole cell assay by the conversion of 3H-arginine to 3H-citrulline. In contrast to unseparated blood cells, NOS II was demonstrable both in isolated blood neutrophils and exudated cells. The failure to detect NOS II by flow cytometry in whole blood cells thus proved to be due to the quenching effect of hemoglobin. Western blotting revealed a 130 kD band corresponding to NOS II in isolated blood neutrophils, but detection was dependent on diisopropylfluorophosphate for proteinase inhibition. L-arginine was taken up by neutrophils, but enzymatic activity could not be demonstrated. We conclude that human neutrophils constitutively express NOS II, but that its demonstration by FITC-labelling is inhibited by hemoglobin-mediated quenching in whole blood samples.

  16. Location and Quantification of iNOS in Testis of Dahl Hypertensive Rats

    Institute of Scientific and Technical Information of China (English)

    Jing LIU; Rui-li LI; Huan-Ying ZHAO; Xiu-Ling YIN

    2004-01-01

    Objective To study the effect of hypertension on inducible isoform of nitrogen oxide syntheses (iNOS) expression and reproductive function in testes of Dahl hypertensive rats Method The iNOS expression in Dahl rat testes was localized and assayed semi-quan titatively by immunohistochemistry.Results iNOS was expressed and localized predominantly in the cytoplasm of Sertoli and Leydig cells in both normal and hypertensive rats. However, in the early stage of hypertension, the expression of iNOS was stronger in testes than that of the normal rats (P<0. 05). With the development, the staining intensity of iNOS decreased gradually in the late stage. Moreover, the level of testosterone decreased with the increase of blood pressure. But in vitro, there was no difference in the expression of iNOS between cultured Sertoli cells from normal rats and hypertensive rats.Conclusion High-salt food induced hypertension in Dahl rats, which was characterized by the high expression of iNOS in rat Sertoli and Leydig cells; excessive NO produced by iNOS reduced the level of testosterone in testicle artery, and may thus affect the reproductive function of rats testis.

  17. Animal and human Ehrlichiosis/ Erliquiose nos animais e no homem

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    Odilon Vidotto

    2001-05-01

    Full Text Available Ehrlichiosis is a disease caused by gram negative obligate intracellular bacterial organisms belonging to the Rickettsiales Order, Anaplasmataceae Family, Genus Ehrlichia and Anaplasma. These organisms may parasite leukocytes, erythrocytes or platelets, leading to abnormalities in many organs. Clinical signs are variable depending on the severity of the infection, host immune response, affected organs, the specific Ehrlichia species involved, and the presence of coinfection with other Ehrlichiae or tickborne disease. The incidence of ehrlichiosis has increased over the last years in both animals and men. The etiological diagnosis is important for adequate epidemiological monitoring. Most tests currently being used have limitations. The recent use of molecular biology diagnostic techniques allow the characterization of the specie or species that are infecting a given patient.A erliquiose é uma doença causada por bactérias gram negativas estritamente intracelulares, pertencentes a Ordem Rickettsiales, Família Anaplasmataceae, Gêneros Ehrlichia e Anaplasma. As diferentes erlíquias podem parasitar leucócitos, eritrócitos e plaquetas levando a alterações em vários órgãos. Os sinais clínicos variam com a severidade da infecção, a resposta imunológica do hospedeiro, os órgãos atingidos, a espécie de erlíquia envolvida e a presenca de co-infecção com outras erlíquias ou outros microrganismos transmitidos pelo mesmo vetor. A incidência de erliquiose vem aumentando nos últimos anos tanto nos animais como no homem. O diagnóstico etiológico é importante para o monitoramento epidemiológico, porém a maioria dos testes usados rotineiramente apresenta limitações. A recente introdução de técnicas diagnósticas que empregam biologia molecular permitem caracterizar quais espécies de erlíquia estão infectando o paciente.

  18. Pitiose em ovinos nos estados de Pernambuco e Bahia

    Directory of Open Access Journals (Sweden)

    Manuel V. Carrera

    2013-04-01

    Full Text Available A pitiose é uma doença infecciosa causada pelo oomiceto aquático P. insidiosum que acomete animais e o homem, especialmente habitantes de áreas úmidas. A enfermidade apresenta como característica principal a formação de lesões com aspecto granulomatoso nos hospedeiros. Neste trabalho, relatou-se a ocorrência da pitiose em ovinos nos estados de Pernambuco (PE e Bahia (BA, Nordeste do Brasil, bem como foi avaliada a eficácia de um imunoterápico frente a esta enfermidade. Amostras de sangue de 53 ovinos foram coletadas, sendo 49 animais oriundos de propriedades localizadas em PE e quatro animais provenientes da BA. Sete ovinos demonstraram sinais clínicos de pitiose ovina. Um dos animais foi submetido à eutanásia e sua cabeça e linfonodo submandibular foram coletados e enviados para análises laboratoriais. Seis ovinos foram submetidos à imunoterapia, sendo mantidos nas instalações do setor de ovinocultura da Univasf/Petrolina-PE durante o tratamento. As técnicas de ELISA, cultura fúngica e reação em cadeia da polimerase (PCR foram utilizadas como métodos diagnósticos da pitiose ovina, sendo eficientes para confirmação dos casos clínicos no rebanho. Ao exame microscópico do material coletado da cavidade nasal de um animal eutanasiado, observou-se uma área focalmente extensa de necrose com presença de infiltrado difuso de neutrófilos íntegros e degenerados margeando a cartilagem. Somente um animal apresentou cura clínica, indicando uma eficiência no tratamento da pitiose de 16,7% (1/6. O aumento de casos de pitiose tem sido denotado em diversos municípios de PE e da BA. Neste contexto, o emprego do imunoterápico pode ser uma alternativa a ser pesquisada. Portanto, estudos futuros devem ser realizados para investigar o efeito da imunoterapia aplicada à pitiose em ovinos.

  19. Possible relation between the NOS3 gene GLU298ASP polymorphism and bladder cancer in Turkey.

    Science.gov (United States)

    Verim, Levent; Toptas, Bahar; Ozkan, Nazli Ezgi; Cacina, Canan; Turan, Saime; Korkmaz, Gurbet; Yaylim, Ilhan

    2013-01-01

    Endothelial nitric oxide synthase (eNOS), encoded by the NOS3 gene, has been suggested to play an important role in uncontrolled cell growth in several cancer types. The objective of this study was to evaluate the role of the NOS3 Glu298Asp polymorphism in bladder cancer susceptibility in a Turkish population. We determined the genotypes of 66 bladder cancer cases and 88 healthy controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. A significant association for NOS3 Glu298Asp heterozygotes genotypes and T allely were found between healthy controls and bladder cancer, respectively (pNOS3 GT genotype in bladder cancer susceptibility in our Turkish population.

  20. [Research Progress of NOS3 Participation in Regulatory Mechanisms of Cardiovascular Diseases].

    Science.gov (United States)

    Sun, Ting; Chi, Qingjia; Wang, Guixue

    2016-02-01

    Cardiovascular disease has been a major threat to human's health and lives for many years. It is of great importance to explore the mechanisms and develop strategies to prevent the pathogenesis. Generally, cardiovascular disease is associated with endothelial dysfunction, which is closely related to the nitric oxide (NO)-mediated vasodilatation. The release of NO is regulated by NOS3 gene in mammals' vascular system. A great deal of evidences have shown that the polymorphism and epigenetic of NOS3 gene play vital roles in the pathological process of cardiovascular disease. To gain insights into the role of NOS3 in the cardiovascular diseases, we reviewed the molecular mechanisms underlying the development of cardiovascular diseases in this paper, including the uncoupling of NOS3 protein, epigenetic and polymorphism of NOS3 gene. The review can also offer possible strategies to prevent and treat cardiovascular diseases.

  1. Obesity, inflammation, and exercise training: relative contribution of iNOS and eNOS in the modulation of vascular function in the mouse aorta

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    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. ChAT and NOS in human myenteric neurons: co-existence and co-absence.

    Science.gov (United States)

    Beck, Martin; Schlabrakowski, Anne; Schrödl, Falk; Neuhuber, Winfried; Brehmer, Axel

    2009-10-01

    Most myenteric neurons contain one of the two generating enzymes for major excitatory and inhibitory neurotransmitters: choline acetyltransferase (ChAT) or neuronal nitric oxide synthase (NOS). Two minor groups of myenteric neurons contain either both enzymes or neither. Our study had two aims: (1) to compare the proportions of neurons stained for ChAT and/or NOS in human small and large intestinal whole-mounts by co-staining with an antibody against the human neuronal protein Hu C/D (HU); (2) to characterize these neurons morphologically by co-staining with a neurofilament (NF) antibody. In small intestinal whole-mounts co-stained with HU, we counted more ChAT-positive (ChAT+) than NOS+ neurons (52% vs. 38%), whereas the large intestine exhibited fewer ChAT+ than NOS+ neurons (38% vs. 50%). Neurons co-reactive for both ChAT and NOS accounted for about 3% in both regions, whereas neurons negative for both enzymes accounted for 7% in the small intestine and 8% in the large intestine. Co-staining with NF revealed that, in both small and large intestine, ChAT+/NOS+ neurons were either spiny (type I) neurons or displayed smaller perikarya that were weakly or not NF-stained. Of all spiny neurons, almost one third was co-reactive for ChAT and NOS, whereas nearly two thirds were positive only for NOS. Neurons negative for both ChAT and NOS were heterogeneous in size and NF reactivity. Thus, neither the co-existence nor the co-absence of ChAT and NOS in human myenteric neurons is indicative for particular neuron types, with several qualitative and quantitative parameters showing a wide range of interindividual variability.

  3. A SOCIEDADE CARIOCA NOS CONTOS DE NELSON RODRIGUES

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    Valdemar Valente Junior (UniverCidade

    2013-10-01

    Full Text Available A coletânea de contos intitulada A vida como ela é..., de Nelson Rodrigues, como um retrato da classe média suburbana do Rio de Janeiro nos anos cinquenta. As situações que envolvem sexo e violência no contexto de transformações econômicas e sociais da sociedade brasileira. A decadência da moral burguesa embutida nessas narrativas como uma continuidade dos temas explorados em suas peças.PALAVRAS-CHAVE: Narrativa. Sociedade. Violência. Casamento. Adultério. Abstract The collection of short-stories named A vida como ela é…, by Nelson Rodrigues, as a picture of the suburban middle class of Rio de Janeiro in the fifties. The situations that involve sex and violence in the context of economic and social transformations of the brazilian society. The decadence of the bourgeois moral inserted in that narratives like a continuity of the themes explored in his plays.KEYWORDS: Narrative. Society. Violence. Wedding. Adultery

  4. Heterose em suínos na fase de aleitamento

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    José Bento Sterman Ferraz

    1991-12-01

    Full Text Available Visando avaliar o ganho de produtividade, advindo da heterose, no peso de suínos em fase de aleitamento, analisaram-se os pesos ao nascimento(PO, 21 dias de idade (P21 e desmama (PD de 746leitões, sendo 201 da raça Landrace, 136 Wessex-Saddleback e 409 mestiços, pelo método dos quadrados mínimos, considerando-se, ainda, os efeitos fixos de época e ano de nascimento, ordem do parto, sexo do leitão e tamanho da leitegada, além de raças paterna e materna e suas interações. Os efeitos não genéticos tiveram influência significativa em quase todas as características. Os mestiços mostraram, em geral, pesos superiores aos puros, com estimativas de heterose de 2,6% para PO, 9,7% para P21 e 13,9% para PD, indicando a importância da herança não aditiva à medida que os leitões ficam menos dependentes de suas mães. Os efeitos de interação entre as raças paterna e materna foram cada vez maiores com o avançar da idade. Os resultados indicam haver ganho de produtividade coma utilização deste tipo de cruzamento.

  5. A simbologia presente nos estilos de Karate-Dō

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    Brandel José Pacheco LOPES FILHO

    2015-09-01

    Full Text Available ResumoO objetivo deste estudo é interpretar os diferentes significados existentes nos emblemas/símbolos de estilos e escolas de Karate-Dō, analisando seus elementos internos e sua importância dentro dessa prática. Para sua realização, foram realizadas três etapas distintas: 1 catalogação e investigação dos estilos e escolas de Karate-Dō com maior representatividade histórica, cultural e política; 2 identificação dos símbolos utilizados por cada um desses estilos e escolas; e 3 análise de cada um desses símbolos. Essa análise torna-se importante para uma compreensão mais profunda dos diferentes significados envolvidos na prática do Karate-Dō, pois, apesar de seguirem um conjunto de valores comum a todos os Budō, as escolas possuem sua própria visão de mundo, utilizando seus símbolos para reforçar ou externar tais conceitos. A maior parte dos símbolos analisados demonstra um aprofundamento cultural em seus grafismos, sendo reconhecidos alguns elementos até de aspecto espiritual ou religioso. Esse simbolismo, em si, mostra um aspecto relevante para a compreensão do próprio fenômeno multicultural nomeado Karate-Dō.

  6. Assédio moral nos ambientes corporativos

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    Yumara Lúcia Vasconcelos

    Full Text Available Resumo:Esse artigo teve como objetivo caracterizar o assédio moral nos ambientes corporativos à luz do paradigma conceitual do que se concebe como "dignidade humana" e violação do princípio jurídico da boa-fé. Especificamente, visou identificar padrões na argumentação jurídica e no enquadramento de práticas nocivas à saúde mental do trabalhador. O estudo, de natureza qualitativa, tomou por base o estudo de situações jurídicas, orientando-se pela demanda por definição e caracterização da prática assediadora no âmbito organizacional e dos limites do conceito da dignidade humana. Como principal resultado, o estudo colocou em contraste a necessidade de contextualização do fato propulsor da denúncia e caracterização do assédio, sem olvidar a relevância do significado ou sentido atribuído pelo indivíduo ao fenômeno analisado.

  7. NASA Operational Simulator for Small Satellites (NOS3)

    Science.gov (United States)

    Zemerick, Scott

    2015-01-01

    The Simulation-to-Flight 1 (STF-1) CubeSat mission aims to demonstrate how legacy simulation technologies may be adapted for flexible and effective use on missions using the CubeSat platform. These technologies, named NASA Operational Simulator (NOS), have demonstrated significant value on several missions such as James Webb Space Telescope, Global Precipitation Measurement, Juno, and Deep Space Climate Observatory in the areas of software development, mission operationstraining, verification and validation (VV), test procedure development and software systems check-out. STF-1 will demonstrate a highly portable simulation and test platform that allows seamless transition of mission development artifacts to flight products. This environment will decrease development time of future CubeSat missions by lessening the dependency on hardware resources. In addition, through a partnership between NASA GSFC, the West Virginia Space Grant Consortium and West Virginia University, the STF-1 CubeSat will hosts payloads for three secondary objectives that aim to advance engineering and physical-science research in the areas of navigation systems of small satellites, provide useful data for understanding magnetosphere-ionosphere coupling and space weather, and verify the performance and durability of III-V Nitride-based materials.

  8. Institucionalizacao da saude publica paulista nos anos 1930-1940

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    Andre Mota

    2013-10-01

    Full Text Available O objetivo do estudo foi interpretar e compreender a institucionalização da saúde pública paulista nos anos 1930-1940, com base na história das especialidades médicas. Foram analisadas novas fontes documentais em diálogo com a literatura existente, levando à identificação de novos indícios relativamente à questão eugênica e à presença de crenças religiosas de médicos como um movimento social. Os médicos, à medida que se especializavam como sanitaristas, propunham um projeto para elevar a raça brasileira, mesclando discursos higienistas com ações sanitárias. São Paulo buscou a primazia nesse projeto, por se acreditar um Estado detentor de uma raça já constituída de “homens historicamente saudáveis”. Crenças religiosas influenciaram o debate e as decisões de época para a ordem sanitária. Historicamente, o discurso sanitário compõe questões técnico-científicas com as político-ideológicas e as culturais, produzindo uma mescla dos diferentes interesses e perspectivas de ordem corporativa da profissão.

  9. Identification of hamster inducible nitric oxide synthase (iNOS) promoter sequences that influence basal and inducible iNOS expression.

    Science.gov (United States)

    Saldarriaga, Omar A; Travi, Bruno L; Choudhury, Goutam Ghosh; Melby, Peter C

    2012-07-01

    IFN-γ/LPS-activated hamster (Mesocricetus auratus) macrophages express significantly less iNOS (NOS2) than activated mouse macrophages, which contributes to the hamster's susceptibility to intracellular pathogens. We determined a mechanism responsible for differences in iNOS promoter activity in hamsters and mice. The HtPP (1.2 kb) showed low basal and inducible promoter activity when compared with the mouse, and sequences within a 100-bp region (-233 to -133) of the mouse and hamster promoters influenced this activity. Moreover, within this 100 bp, we identified a smaller region (44 bp) in the mouse promoter, which recovered basal promoter activity when swapped into the hamster promoter. The mouse homolog (100-bp region) contained a cis-element for NF-IL-6 (-153/-142), which was absent in the hamster counterpart. EMSA and supershift assays revealed that the hamster sequence did not support the binding of NF-IL-6. Introduction of a functional NF-IL-6 binding sequence into the hamster promoter or its alteration in the mouse promoter revealed the critical importance of this transcription factor for full iNOS promoter activity. Furthermore, the binding of NF-IL-6 to the iNOS promoter (-153/-142) in vivo was increased in mouse cells but was reduced in hamster cells after IFN-γ/LPS stimulation. Differences in the activity of the iNOS promoters were evident in mouse and hamster cells, so they were not merely a result of species-specific differences in transcription factors. Thus, we have identified unique DNA sequences and a critical transcription factor, NF-IL-6, which contribute to the overall basal and inducible expression of hamster iNOS.

  10. eNOS protects from atherosclerosis despite relevant superoxide production by the enzyme in apoE mice.

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    Padmapriya Ponnuswamy

    Full Text Available BACKGROUND: All three nitric oxide synthase (NOS isoforms are expressed in atherosclerotic plaques. NOS enzymes in general catalyse NO production. However, under conditions of substrate and cofactor deficiency, the enzyme directly catalyse superoxide formation. Considering this alternative chemistry, the effects of NOS on key events in spontaneous hyperlipidemia driven atherosclerosis have not been investigated yet. Here, we evaluate how endothelial nitric oxide synthase (eNOS modulates leukocyte/endothelial- (L/E and platelet/endothelial- (P/E interactions in atherosclerosis and the production of nitric oxide (NO and superoxide by the enzyme. PRINCIPAL FINDINGS: Intravital microscopy (IVM of carotid arteries revealed significantly increased L/E-interactions in apolipoproteinE/eNOS double knockout mice (apoE(-/-/eNOS(-/-, while P/E-interactions did not differ, compared to apoE(-/-. eNOS deficiency increased macrophage infiltration in carotid arteries and vascular cell adhesion molecule-1 (VCAM-1 expression, both in endothelial and smooth muscle cells. Despite the expression of other NOS isoforms (inducible NOS, iNOS and neuronal NOS, nNOS in plaques, Electron Spin Resonance (ESR measurements of NO showed significant contribution of eNOS to total circulating and vascular wall NO production. Pharmacological inhibition and genetic deletion of eNOS reduced vascular superoxide production, indicating uncoupling of the enzyme in apoE(-/- vessels. CONCLUSION: Overt plaque formation, increased vascular inflammation and L/E- interactions are associated with significant reduction of superoxide production in apoE(-/-/eNOS(-/- vessels. Therefore, lack of eNOS does not cause an automatic increase in oxidative stress. Uncoupling of eNOS occurs in apoE(-/- atherosclerosis but does not negate the enzyme's strong protective effects.

  11. TUMOR NECROSIS FACTOR ALPHA DECREASES NOS3 EXPRESSION PRIMARILY VIA RHO/RHO KINASE IN THE THICK ASCENDING LIMB

    Science.gov (United States)

    Ramseyer, Vanesa; Hong, Nancy; Garvin, Jeffrey L.

    2013-01-01

    Inappropriate Na+ reabsorption by thick ascending limbs (THALs) induces hypertension. Nitric oxide (NO) produced by NO synthase type 3 (NOS3 or eNOS) inhibits NaCl reabsorption by THALs. Tumor necrosis factor alpha (TNF-α) decreases NOS3 expression in endothelial cells and contributes to increases in blood pressure. However, the effects of TNF-α on THAL NOS3 and the signaling cascade are unknown. TNF-α activates several signaling pathways including Rho/Rho kinase (ROCK) which is known to reduce NOS3 expression in endothelial cells. Therefore, we hypothesized that TNF-α decreases NOS3 expression via Rho/ROCK in rat THAL primary cultures. THAL cells were incubated with either vehicle or 1 nmol/L TNF-α for 24 hrs and NOS3 expression was measured by Western blot. TNF-α decreased NOS3 expression by 51±6% (pNOS3 expression by 30±8% (pNOS3 expression by 66±15 % (pNOS3 expression. We conclude that TNF-α decreases NOS3 expression primarily via Rho/ROCK in rat THALs. These data suggest that some of the beneficial effects of ROCK inhibitors in hypertension could be due to the mitigation of TNF-α-induced reduction in NOS3 expression. PMID:22566503

  12. 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

  13. O LÚDICO NOS ADULTOS: UM ESTUDO EXPLORATÓRIO NOS FREQÜENTADORES DO CEPE - NATAL/RN

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    Andréa Francos Ferreira

    2007-12-01

    Full Text Available O presente artigo tem como objetivo analisar a manifestação do fenômeno lúdico nos adultos, que freqüentam o Clube dos Empregados da Petrobrás em Natal/RN. Tal estudo está pautado sob a concepção e perspectiva do lúdico, enquanto fenômeno social. Para se atingir o objetivo utilizou-se uma metodologia caracterizada como qualitativa, sendo, também, do tipo exploratória. Os dados foram coletados, através de diversas visitas ao local, durante o mês de maio de 2003, dentre as quais foram utilizados questionários de entrevistas com o dirigente da Instituição e os com usuários do Clube, além de observação não-participante a qual utilizou-se de métodos descritivos visando colher detalhadamente as características do objeto em estudo. Os resultados obtidos vieram evidenciar e dar veracidade às afirmações feitas pelos estudiosos do lazer, de que o ser humano, à medida que vai se tornando adulto deixa para trás o significado do lúdico, devido ao uso da racionalidade exacerbada e, também, por causa das convenções impostas pela sociedade. Palavras-chave: CEPE/RN, Lúdico e Adulto.

  14. Baclofen and NOS inhibitors interact to evoke synergistic hypothermia in rats.

    Science.gov (United States)

    Rawls, Scott M; Jacobs, Kyle; Tallarida, Ronald J

    2006-01-11

    Our laboratory recently demonstrated that a drug combination of baclofen and L-NAME, a nonspecific nitric oxide synthase (NOS) inhibitor, evokes synergistic hypothermia in rats. These data are the first demonstration of synergy between a GABA agonist and NOS inhibitor. While the hypothermic synergy suggests a role for NOS in baclofen pharmacology, it is unclear whether the super-additive hypothermia is specific for baclofen and L-NAME or extends to drug combinations of baclofen and other NOS inhibitors. The site of action (central or peripheral) and isoforms of NOS that mediate the synergy are also unknown. Here, we confirm the hypothermic synergy with additional data and discuss potential mechanisms of the drug interaction. Baclofen (2.5, 3.5, 5 and 7.5 mg/kg, i.p.) was administered to rats by itself or with 7-nitroindazole (7-NI), a neuronal NOS inhibitor. 7-NI (10 mg/kg, i.p.) did not affect body temperature. For combined administration, 7-NI (10 mg/kg, i.p.) increased the relative potency of baclofen (F=18.9, P<0.05). The present data validate the hypothermic synergy caused by the drug combination of baclofen and L-NAME and implicate nNOS in the synergy. In a context broader than thermoregulation, NO production and transmission may play an important role in baclofen pharmacology.

  15. Electroacupuncture Delays Hypertension Development through Enhancing NO/NOS Activity in Spontaneously Hypertensive Rats

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    Hye Suk Hwang

    2011-01-01

    Full Text Available Using spontaneously hypertensive rats (SHR, this study investigated whether electroacupuncture (EA could reduce early stage hypertension by examining nitric oxide (NO levels in plasma and nitric oxide synthase (NOS levels in the mesenteric resistance artery. EA was applied to the acupuncture point Governor Vessel 20 (GV20 or to a non-acupuncture point in the tail twice weekly for 3 weeks under anesthesia. In conscious SHR and normotensive Wistar Kyoto (WKY rats, blood pressure was determined the day after EA treatment by the tail-cuff method. We measured plasma NO concentration, and evaluated endothelial NO syntheses (eNOS and neuronal NOS (nNOS protein expression in the mesenteric artery. Systolic blood pressure (SBP and diastolic blood pressure (DBP were lower after 3 weeks of GV20 treatment than EA at non-acupuncture point and no treatment control in SHR. nNOS expression by EA was significantly different between both WKY and no treatment SHR control, and EA at GV20 in SHR. eNOS expression was significantly high in EA at GV 20 compared with no treatment control. In conclusion, EA could attenuate the blood pressure elevation of SHR, along with enhancing NO/NOS activity in the mesenteric artery in SHR.

  16. PGE1 analog alprostadil induces VEGF and eNOS expression in endothelial cells.

    Science.gov (United States)

    Haider, Dominik G; Bucek, Robert A; Giurgea, Aura G; Maurer, Gerald; Glogar, Helmut; Minar, Erich; Wolzt, Michael; Mehrabi, Mohammad R; Baghestanian, Mehrdad

    2005-11-01

    Endothelial nitric oxide synthase (eNOS), VEGF, and hypoxia-inducible factor 1-alpha (HIF-1alpha) are important regulators of endothelial function, which plays a role in the pathophysiology of heart failure (HF). PGE1 analog treatment in patients with HF elicits beneficial hemodynamic effects, but the precise mechanisms have not been investigated. We have investigated the effects of the PGE1 analog alprostadil on eNOS, VEGF, and HIF-1alpha expression in human umbilical vein endothelial cells (HUVEC) using RT-PCR and immunoblotting under normoxic and hypoxic conditions. In addition, we studied protein expression by immunohistochemical staining in explanted hearts from patients with end-stage HF, treated or untreated with systemic alprostadil. Alprostadil causes an upregulation of eNOS and VEGF protein and mRNA expression in HUVEC and decreases HIF-1alpha. Hypoxia potently increased eNOS, VEGF, and HIF-1alpha synthesis. The alprostadil-induced upregulation of eNOS and VEGF was prevented by inhibition of MAPKs with PD-98056 or U-0126. Consistently, the expression of eNOS and VEGF was increased, and HIF-1alpha was reduced in failing hearts treated with alprostadil. The potent effects of alprostadil on endothelial VEGF and eNOS synthesis may be useful for patients with HF where endothelial dysfunction is involved in the disease process.

  17. Identification and molecular characterization of nitric oxide synthase (NOS) gene in the intertidal copepod Tigriopus japonicus.

    Science.gov (United States)

    Jeong, Chang-Bum; Kang, Hye-Min; Seo, Jung Soo; Park, Heum Gi; Rhee, Jae-Sung; Lee, Jae-Seong

    2016-02-10

    In copepods, no information has been reported on the structure or molecular characterization of the nitric oxide synthase (NOS) gene. In the intertidal copepod Tigriopus japonicus, we identified a NOS gene that is involved in immune responses of vertebrates and invertebrates. In silico analyses revealed that nitric oxide (NO) synthase domains, such as the oxygenase and reductase domains, are highly conserved in the T. japonicus NOS gene. The T. japonicus NOS gene was highly transcribed in the nauplii stages, implying that it plays a role in protecting the host during the early developmental stages. To examine the involvement of the T. japonicus NOS gene in the innate immune response, the copepods were exposed to lipopolysaccharide (LPS) and two Vibrio sp. After exposure to different concentrations of LPS and Vibrio sp., T. japonicus NOS transcription was significantly increased over time in a dose-dependent manner, and the NO/nitrite concentration increased as well. Taken together, our findings suggest that T. japonicus NOS transcription is induced in response to an immune challenge as part of the conserved innate immunity.

  18. Inducible nitric oxide synthase, Nos2, does not mediate optic neuropathy and retinopathy in the DBA/2J glaucoma model

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    Savinova Olga V

    2007-12-01

    Full Text Available Abstract Background Nitric oxide synthase 2 (NOS2 contributes to neural death in some settings, but its role in glaucoma remains controversial. NOS2 is implicated in retinal ganglion cell degeneration in a rat glaucoma model in which intraocular pressure (IOP is experimentally elevated by blood vessel cauterization, but not in a rat glaucoma model where IOP was elevated by injection of hypertonic saline. To test the importance of NOS2 for an inherited glaucoma, in this study we both genetically and pharmacologically decreased NOS2 activity in the DBA/2J mouse glaucoma model. Methods The expression of Nos2 in the optic nerve head was analyzed at both the RNA and protein levels at different stages of disease pathogenesis. To test the involvement of Nos2 in glaucomatous neurodegeneration, a null allele of Nos2 was backcrossed into DBA/2J mice and the incidence and severity of glaucoma was assessed in mice of each Nos2 genotype. Additionally, DBA/2J mice were treated with the NOS2 inhibitor aminoguanidine and the disease compared to untreated mice. Results Optic nerve head Nos2 RNA levels varied and increased during moderate but decreased at early and severe stages of disease. Despite the presence of a few NOS2 positive cells in the optic nerve head, NOS2 protein was not substantially increased during the glaucoma. Genetic deficiency of Nos2 or aminoguanidine treatment did not alter the IOP profile of DBA/2J mice. Additionally, neither Nos2 deficiency nor aminoguanidine had any detectable affect on the glaucomatous optic nerve damage. Conclusion Glaucomatous neurodegeneration in DBA/2J mice does not require NOS2 activity. Further experiments involving various models are needed to assess the general importance of Nos2 in glaucoma.

  19. Tratamento adjuvante nos GISTs Adjuvant treatment in GISTs

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    Laercio Gomes Lourenço

    2011-09-01

    Full Text Available INTRODUÇÃO: O tumor estromal gastrointestinal (GIST é o sarcoma mais comum do aparelho digestivo. Essa neoplasia ocorre devido à mutação do gene KIT com consequente ativação constitutiva da proteína KIT. O tratamento primário é cirúrgico e consiste na sua ressecção completa. Entretanto, alguns grupos de pacientes apresentam risco elevado de recorrência mesmo após operação com ressecção completa (R0, indicando diferenças no comportamento biológico. Estudos clínicos comprovaram a atividade clínica do mesilato de imatinibe, fazendo dele a primeira linha de tratamento padrão nos GISTs metastáticos ou irressecáveis, mudando muito o desfecho clínico dessa doença em relação aos benefícios anteriormente obtidos com a quimioterapia antineoplásica. MÉTODO: Foi realizada revisão da literatura com consulta nos periódicos das bases Medline/Pubmed, Scielo e Lilacs cruzando os descritores: tumor estromal gastrointestinal, Gist, tratamento, adjuvância. Além desta revisão foi adicionada a experiência pessoal dos autores. CONCLUSÃO: Melhor refinamento dos critérios de prognóstico tem permitido selecionar de forma mais adequada pacientes para o tratamento adjuvante com imatinibe. Os resultados de maior evidência até o momento respaldam o tratamento adjuvante por um ano, o que produz benefício significativo na sobrevida livre de recidiva, mas não na sobrevida global desses pacientes.INTRODUCTION: Gastrointestinal stromal tumor (GIST is the most common sarcoma of the digestive tract. This cancer occurs due to mutation of the KIT gene resulting in constitutive activation of KIT protein. The primary treatment is surgical and consists of complete resection. However, some groups of patients at high risk of recurrence even after surgery with complete resection (R0, indicate differences in biological behavior. Clinical studies have demonstrated the clinical activity of imatinib mesylate, making it the standard first

  20. (INTERSUBJETIVIDADE NOS ESTUDOS DE REDES SOCIAIS: DISSOLVENDO FRONTEIRAS

    Directory of Open Access Journals (Sweden)

    Sayonara Costa

    2014-11-01

    Full Text Available As redes sociais da internet (RSI se multiplicam e todas elas, embora tenham esquemas enunciativos distintos, ampliam as possibilidades de por em cena (intersubjetividades. Muitos papeis sociais são desempenhados nesses ambientes digitais que dão guarida às múltiplas faces de um sujeito que se (desconstrói em meio a um processo heterogêneo. Diante disso, a pergunta que norteia esse ensaio é: Como estudar esse processo de (desconstrução da subjetividade em redes sociais? A proposição que defendemos neste trabalho é a de que o sujeito adepto das redes sociais da internet encontra-se em um tempo-espaço propício a excitações que vão muito além das percepções idiossincráticas de cada indivíduo. Em função disso, propomos que estudar as (intersubjetividades nas RSI pode ser produtivo se relacionarmos as noções de caosmose (Guattari, self (Goffman e enunciação linguística (Benveniste. A conclusão a que chegamos é a de que o viés da enunciação linguística pode ser uma alternativa metodológica que auxilie na conexão entre uma concepção mais transversalista da subjetividade e a tese de que a interação social assemelha-se a uma encenação teatral e, por isso, pode tomar rumos diversos, de acordo com roteiros pré-estabelecidos e socialmente partilhados nos cenários digitais das RSI.

  1. (INTERSUBJETIVIDADE NOS ESTUDOS DE REDES SOCIAIS: DISSOLVENDO FRONTEIRAS

    Directory of Open Access Journals (Sweden)

    Sayonara Costa

    2014-07-01

    Full Text Available As redes sociais da internet (RSI se multiplicam e todas elas, embora tenham esquemas enunciativos distintos, ampliam as possibilidades de por em cena (intersubjetividades. Muitos papeis sociais são desempenhados nesses ambientes digitais que dão guarida às múltiplas faces de um sujeito que se (desconstrói em meio a um processo heterogêneo. Diante disso, a pergunta que norteia esse ensaio é: Como estudar esse processo de (desconstrução da subjetividade em redes sociais? A proposição que defendemos neste trabalho é a de que o sujeito adepto das redes sociais da internet encontra-se em um tempo-espaço propício a excitações que vão muito além das percepções idiossincráticas de cada indivíduo. Em função disso, propomos que estudar as (intersubjetividades nas RSI pode ser produtivo se relacionarmos as noções de caosmose (Guattari, self (Goffman e enunciação linguística (Benveniste. A conclusão a que chegamos é a de que o viés da enunciação linguística pode ser uma alternativa metodológica que auxilie na conexão entre uma concepção mais transversalista da subjetividade e a tese de que a interação social assemelha-se a uma encenação teatral e, por isso, pode tomar rumos diversos, de acordo com roteiros pré-estabelecidos e socialmente partilhados nos cenários digitais das RSI.

  2. Association of the NOS3 intron-4 VNTR polymorphism with aneurysmal subarachnoid hemorrhage

    DEFF Research Database (Denmark)

    Staalsø, Jonatan Myrup; Edsen, Troels; Kotinis, Alexandros;

    2014-01-01

    OBJECT: The nitric oxide system has been linked to the pathogenesis of aneurysmal subarachnoid hemorrhage (SAH). The authors performed a case-control study to investigate the association between SAH and common genetic variants within the endothelial nitric oxide synthase gene (NOS3). METHODS: Three......-VNTR. Haplotype analysis revealed that no single haplotype containing the b-allele was responsible for the observed genotype effect. CONCLUSIONS: The authors' results suggest that the NOS3 27-bp-VNTR b/b genotype independent of other risk factors act in concert with male sex to substantially increase risk of SAH....... This effect is not mediated by any single NOS3 haplotype....

  3. Effect on eNOS/NO Pathway in MIRI rats with preconditioning of GFPC from Dang Gui Si Ni decoction

    Directory of Open Access Journals (Sweden)

    Guo-qiang Qian

    2014-01-01

    Full Text Available Objective: In order to discover whether the eNOS/NO (endothelial nitric oxide synthase/nitric oxide pathway is involved in the protective mechanisms of ischemic myocardium of DGSND (Dang Gui Si Ni Decoction in MIRI (myocardial ischemia-reperfusion injury SD rats. Materials and Methods: We made I/R (ischemia-reperfusion model by ligating the left anterior-descending branch of the coronary artery (LAD for 30 min and releasing the ligature for 120 min. eNOS (nitric oxide synthase mRNA (message ribonucleic acid and iNOS (inducible nitric oxide synthase mRNA were measured by the methods of real-time RT-PCR (Real time Polychainase Chain Reaction, peNOS (phosphorylated eNOS and iNOS protein were measured by the means of western blot. Results: In PPC group, real-time RT-PCR and western-blot analysis showed that eNOS mRNA and peNOS protein increased markedly (P < 0.05; iNOS mRNA and protein decreased significantly (P < 0.05. Conclusion: These results indicate that ischemic preconditioning (IPC of GFPC from DGSND plays a protective role in I/R heart through regulating the eNOS/NO signal pathway, which could increase the eNOS gene expression and decrease the expression of iNOS mRNA.

  4. 精神分裂症与NOS1多态性的关联研究%Association study of NOS1 gene polymorphisms and schizophrenia

    Institute of Scientific and Technical Information of China (English)

    王佳; 李涛; 马小红; 向波; 吴俊瑶; 王英成; 邓伟; 李名立; 王强; 何宗岭

    2012-01-01

    Objective To assess the association between nitric oxide synthase 1 (NOS1)gene polymorphisms and schizophrenia.Methods Twenty eight tag single nucleotide polymorphisms (SNPs) of NOS1 in 382 schizophrenic patients and 448 healthy individuals sampled from Chinese Han population were analyzed by a Illumina GoldenGate Genotyping Assay.Results One SNP (rs1520811) was found to be associated with schizophrenia,which however becomes negative after Bonferroni correction (P> 0.05).Further analysis has failed to identify any association between particular haplotypes and the disease.Conclusion Our results did not support a significant association between NOS1 gene polymorphisms and schizophrenia.%目的 探讨一氧化氮合酶1(nitric oxide synthase 1,NOS1)基因多态性与精神分裂症易感性的相关性.方法 选取NOS1区域的28个标签单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点,应用Illumina GoldenGate定制芯片对382例汉族精神分裂症患者和448名正常人的DNA进行分型,并分析其与精神分裂症的相关性.结果 单位点分析提示SNP位点rs1520811与精神分裂症存在关联,但是经过Bonferroni多重校正后差异无统计学意义(P>0.05).单体型分析未发现单体型与精神分裂症的相关性.结论 未证实NOS1为精神分裂症的易感基因.

  5. Differential engagements of glutamate and GABA receptors in cardiovascular actions of endogenous nNOS or iNOS at rostral ventrolateral medulla of rats

    Science.gov (United States)

    Chan, Samuel H H; Wang, Ling-Lin; Chan, Julie Y H

    2003-01-01

    We evaluated in Sprague–Dawley rats anaesthetized with propofol the engagement of soluble guanylyl cyclase (sGC)/cGMP cascade, glutamatergic and GABAergic neurotransmission in the cardiovascular actions of endogenous nitric oxide (NO) at the rostral ventrolateral medulla (RVLM). Microinjection bilaterally into the RVLM of a selective iNOS inhibitor, S-methylisothiourea (SMT, 250 pmoles), or a selective nNOS inhibitor, 7-nitroindazole (7-NI, 5 pmoles), induced respectively an enhancement or a reduction in systemic arterial pressure, heart rate and power density of the vasomotor components in the spectrum of arterial blood pressure signals, our experimental index for sympathetic neurogenic vasomotor tone. The cardiovascular actions of SMT or 7-NI in the RVLM were significantly antagonized by co-administration into the RVLM of the sGC inhibitor, 1H-[1,2,4]Oxadiazole[4,3-α]quinoxalin-1-one (ODQ, 250 or 500 pmoles). The cardiovascular excitatory effects after blockade of endogenous iNOS activity were significantly attenuated when N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (20 or 50 pmoles), or non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (250 or 500 pmoles), was co-microinjected bilaterally into the RVLM. On the other hand, the cardiovascular depressive responses to blockade of endogenous nNOS activity were significantly antagonized on co-administration of GABAA receptor antagonist, bicuculline methiodine (5 or 10 pmoles), but not GABAB receptor antagonist, 2-hydroxy saclofen (50 or 100 pmoles). We conclude that the cardiovascular actions of endogenous NO in the RVLM engage the sGC/cGMP pathway. In addition, whereas NO derived from nNOS induced sympathoexcitation via both NMDA and non-NMDA receptors in the RVLM, NO generated by iNOS elicited sympathoinhibition via GABAA receptors. PMID:12598412

  6. CENTRALIDADE DA CRÍTICA AO TRABALHO: APONTAMENTOS SOBRE A CATEGORIA TRABALHO NOS MANUSCRITOS DE 1844 E NOS GRUNDRISSE DE MARX

    OpenAIRE

    Xavier, Vinicius dos Santos

    2016-01-01

    *Mestre em Filosofia pela Universidade Federal de São Carlos (UFSCar). Professor Efetivo de Filosofia do Ensino Médio da Rede Estadual de Educação Básica do Estado de São Paulo.Centralidade da crítica ao trabalho: apontamentos sobre a categoria trabalho nos Manuscritos de 1844 e nos Grundrisse de MarxResumo: O objetivo do artigo é refletir criticamente acerca da categoria trabalho em dois momentos da teoria marxiana: os Manuscritos Econômico-Filosóficos, texto de juventude de Marx, e os Grund...

  7. CENTRALIDADE DA CRÍTICA AO TRABALHO: APONTAMENTOS SOBRE A CATEGORIA TRABALHO NOS MANUSCRITOS DE 1844 E NOS GRUNDRISSE DE MARX

    OpenAIRE

    Xavier, Vinicius dos Santos

    2016-01-01

    * Mestre em Filosofia pela Universidade Federal de São Carlos (UFSCar). Professor Efetivo de Filosofia do Ensino Médio da Rede Estadual de Educação Básica do Estado de São Paulo.Apoio: CNPq Centralidade da crítica ao trabalho: apontamentos sobre a categoria trabalho nos manuscritos de 1844 e nos Grundrisse de MarxResumo: O objetivo do artigo é refletir criticamente acerca da categoria trabalho em dois momentos da teoria marxiana: os Manuscritos Econômico-Filosóficos, texto de juventude de Mar...

  8. Nox2-dependent glutathionylation of endothelial NOS leads to uncoupled superoxide production and endothelial barrier dysfunction in acute lung injury.

    Science.gov (United States)

    Wu, Feng; Szczepaniak, William S; Shiva, Sruti; Liu, Huanbo; Wang, Yinna; Wang, Ling; Wang, Ying; Kelley, Eric E; Chen, Alex F; Gladwin, Mark T; McVerry, Bryan J

    2014-12-15

    Microvascular barrier integrity is dependent on bioavailable nitric oxide (NO) produced locally by endothelial NO synthase (eNOS). Under conditions of limited substrate or cofactor availability or by enzymatic modification, eNOS may become uncoupled, producing superoxide in lieu of NO. This study was designed to investigate how eNOS-dependent superoxide production contributes to endothelial barrier dysfunction in inflammatory lung injury and its regulation. C57BL/6J mice were challenged with intratracheal LPS. Bronchoalveolar lavage fluid was analyzed for protein accumulation, and lung tissue homogenate was assayed for endothelial NOS content and function. Human lung microvascular endothelial cell (HLMVEC) monolayers were exposed to LPS in vitro, and barrier integrity and superoxide production were measured. Biopterin species were quantified, and coimmunoprecipitation (Co-IP) assays were performed to identify protein interactions with eNOS that putatively drive uncoupling. Mice exposed to LPS demonstrated eNOS-dependent increased alveolar permeability without evidence for altered canonical NO signaling. LPS-induced superoxide production and permeability in HLMVEC were inhibited by the NOS inhibitor nitro-l-arginine methyl ester, eNOS-targeted siRNA, the eNOS cofactor tetrahydrobiopterin, and superoxide dismutase. Co-IP indicated that LPS stimulated the association of eNOS with NADPH oxidase 2 (Nox2), which correlated with augmented eNOS S-glutathionylation both in vitro and in vivo. In vitro, Nox2-specific inhibition prevented LPS-induced eNOS modification and increases in both superoxide production and permeability. These data indicate that eNOS uncoupling contributes to superoxide production and barrier dysfunction in the lung microvasculature after exposure to LPS. Furthermore, the results implicate Nox2-mediated eNOS-S-glutathionylation as a mechanism underlying LPS-induced eNOS uncoupling in the lung microvasculature.

  9. NODC Standard Format NOS Coastal Wave Program (F182) Data (1979-1983) (NODC Accession 0014203)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data type was designed for analyzed wave data originating from the National Ocean Service (NOS) Coastal Wave Program. The data are organized into 3 record...

  10. NOS CO-OPS Water Level Data, Tide Prediction, 6-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has High Low Tide Predictions from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS). The official Tide and Tidal Current...

  11. NOS CO-OPS Water Level Data, High Low Tide Prediction

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has High Low Tide Predictions from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS). The official Tide and Tidal Current...

  12. NOS CO-OPS Water Level Data, Tide Prediction, 60-Minute

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has High Low Tide Predictions from NOAA NOS Center for Operational Oceanographic Products and Services (CO-OPS). The official Tide and Tidal Current...

  13. TNF-α expression, not iNOS expression, is correlated with NF-κB ...

    African Journals Online (AJOL)

    Jane

    2011-07-11

    Jul 11, 2011 ... (iNOS) following chronic constriction nerve injury (CCI) in rats. CCI induced a ... transection or spinal cord compression triggers NF-kB activation (Sakaue et al., ... attenuate bilateral mechanical allodynia (Milligan et al.,. 2003).

  14. Genese, desenvolvimento, crise e reformas nos servigos publicos de extensao rural durante a decada de 1990

    National Research Council Canada - National Science Library

    Augusto Da Ros, Cesar

    2012-01-01

    Este artigo traga um painel historico sobre a genese, desenvolvimento, crise e reformas realizadas nos servigos publicos de extensao rural ao longo da decada de 1990, oferecendo uma visao geral sobre...

  15. Evidence of Aortopathy in Mice with Haploinsufficiency of Notch1 in Nos3-Null Background.

    Science.gov (United States)

    Koenig, Sara N; Bosse, Kevin M; Nadorlik, Holly A; Lilly, Brenda; Garg, Vidu

    Thoracic aortic aneurysms (TAA) are a significant cause of morbidity and mortality in humans. While the exact etiology is unknown, genetic factors play an important role. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV) and aortopathy in humans. The aim of this study was to determine if haploinsufficiency of Notch1 contributes to aortopathy using Notch1(+/-); Nos3(-/-) mice. Echocardiographic analysis of Notch1(+/-); Nos3(-/-) mice reveals effacement of the sinotubular junction and a trend toward dilation of the aortic sinus. Furthermore, examination of the proximal aorta of Notch1(+/-); Nos3(-/-) mice reveals elastic fiber degradation, a trend toward increased matrix metalloproteinase 2 expression, and increased smooth muscle cell apoptosis, features characteristic of aneurysmal disease. Although at a lower penetrance, we also found features consistent with aortopathic changes in Notch1 heterozygote mice and in Nos3-null mice. Our findings implicate a novel role for Notch1 in aortopathy of the proximal aorta.

  16. Selective potentiation of NMDA-induced neuronal injury following induction of astrocytic iNOS.

    Science.gov (United States)

    Hewett, S J; Csernansky, C A; Choi, D W

    1994-08-01

    Nitric oxide (NO) produced by the constitutive NO synthase (cNOS) in neurons has been implicated in mediating excitotoxic neuronal death. In our murine cortical cell culture system, NMDA neurotoxicity was not blocked by addition of the NOS inhibitors, NG-nitro-L-arginine or aminoguanidine. However, following activation of inducible NOS in astrocytes by interleukin-1 beta plus interferon-gamma, NMDA but not kainate neurotoxicity was markedly potentiated. This selective potentiation of NMDA neurotoxicity was blocked by NOS inhibition or antioxidants (superoxide dismutase/catalase or Tempol) and could be mimicked by NO generators (SIN-1 or SNAP) or the oxygen radical generator, pyragallol. These results raise the possibility that NO production by astrocytes may contribute to NMDA receptor-mediated neuronal death, perhaps through interaction with oxygen radicals.

  17. Development of nNOS-positive neurons in the rat sensory and sympathetic ganglia.

    Science.gov (United States)

    Masliukov, P M; Emanuilov, A I; Madalieva, L V; Moiseev, K Y; Bulibin, A V; Korzina, M B; Porseva, V V; Korobkin, A A; Smirnova, V P

    2014-01-03

    Neurochemical features in sympathetic and afferent neurons are subject to change during development. Nitric oxide (NO) plays a developmental role in the nervous system. To better understand the neuroplasticity of sympathetic and afferent neurons during postnatal ontogenesis, the distribution of neuronal NO synthase (nNOS) immunoreactivity was studied in the sympathetic para- and prevertebral, nodose ganglion (NG) and Th2 and L4 dorsal root ganglia (DRG) from female Wistar rats of different ages (newborn, 10-day-old, 20-day-old, 30-day-old, 2-month-old, 6-month-old, 1-year-old, and 3-year-old). nNOS-positive neurons were revealed in all sensory ganglia but not in sympathetic ones from birth onward. The percentage of nNOS-immunoreactive (IR) neurons increased during first 10 days of life from 41.3 to 57.6 in Th2 DRG, from 40.9 to 59.1 in L4 DRG and from 31.6 to 38.5 in NG. The percentage of nNOS-IR neurons did not change in the NG later during development and senescence. However, in Th2 and L4 DRG the proportion of nNOS-IR neurons was high in animals between 10 and 30days of life and decreased up to the second month of life. In 2-month-old rats, the percentage of nNOS-IR neurons was 52.9 in Th2 DRG and 51.3 in L4 DRG. We did not find statistically significant differences in the percentage of nNOS-IR neurons between Th2 and L4 DRG and between young and aged rats. In NG and DRG of 10-day-old and older rats, a high proportion of nNOS-IR neurons binds isolectin B4. In newborn animals, only 41.3%, 45.3% and 28.4% of nNOS neuron profiles bind to IB4 in Th2, L4 DRG and NG, respectively. In 10-day-old and older rats, the number of sensory nNOS-IR neurons binding IB4 reached more than 90% in DRG and more than 80% in NG. Only a small number of nNOS-positive cells showed immunoreactivity to calcitonin gene-related peptide, neurofilament 200, calretinin. The information provided here will also serve as a basis for future studies investigating mechanisms of the development of

  18. Combined effects of antioxidant vitamin and NOS3 genetic polymorphisms on breast cancer risk in women.

    Science.gov (United States)

    Lee, Sang-Ah; Lee, Kyoung-Mu; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Kang, Daehee

    2012-02-01

    It is becoming increasingly clear that there is wide heterogeneity in genetic predisposition to breast cancer and that breast cancer risk is determined by interactive effect between genetic and environmental factors. We investigated the combined effects of antioxidant vitamin intake and NOS3 genetic polymorphisms on breast cancer risk in a Korean population (Seoul Breast Cancer Study). Histologically confirmed breast cancer cases (n = 512) and age, menopause status-matched controls (n = 512) with no present or previous history of cancer were recruited from several teaching hospitals in Seoul during 2001-2003. Two genetic polymorphisms of NOS3 (298G > T and -786 T > C) were assessed by single base extension assays. No overall association between the individual NOS3 genotypes or diplotypes and breast cancer risk was found, although the difference between cases and controls in the frequency of the NOS3 894 G > T polymorphism showed borderline significance (OR = 0.74, 95% CI = 0.52-1.06). There was no significant difference in energy intake or the intake of antioxidant vitamins between cases and controls, with the exception of vitamin E (OR = 0.49 lowest vs. highest quartile, P(trend) NOS3 -786 T > C or 894 G > T genetic polymorphisms on breast cancer risk. Although a multiplicative interaction was not observed, the protective effect of β-carotene intake on breast cancer risk was observed predominantly in individuals with the TG:TG diplotype of NOS3 (OR = 0.68) but not observed with others diplotype. An inverse association between vitamin E intake and breast cancer risk was observed for individuals with the NOS3 786 TC + TT genotype and the NOS3 894 GG genotype. In addition, folic acid had a protective effect in the NOS3 786 TT and NOS3 894 GT + TT genotype. Our results suggest that intake of antioxidant vitamins might modify the association between genetic polymorphisms of NOS3 and breast cancer risk. Copyright © 2011 Elsevier Ltd and

  19. RBC-NOS-dependent S-nitrosylation of cytoskeletal proteins improves RBC deformability.

    Directory of Open Access Journals (Sweden)

    Marijke Grau

    Full Text Available BACKGROUND: Red blood cells (RBC possess a nitric oxide synthase (RBC-NOS whose activation depends on the PI3-kinase/Akt kinase pathway. RBC-NOS-produced NO exhibits important biological functions like maintaining RBC deformability. Until now, the cellular target structure for NO, to exert its influence on RBC deformability, remains unknown. In the present study we analyzed the modification of RBC-NOS activity by pharmacological treatments, the resulting influence on RBC deformability and provide first evidence for possible target proteins of RBC-NOS-produced NO in the RBC cytoskeletal scaffold. METHODS/FINDINGS: Blood from fifteen male subjects was incubated with the NOS substrate L-arginine to directly stimulate enzyme activity. Direct inhibition of enzyme activity was induced by L-N5-(1-Iminoethyl-ornithin (L-NIO. Indirect stimulation and inhibition of RBC-NOS were achieved by applying insulin and wortmannin, respectively, substances known to affect PI3-kinase/Akt kinase pathway. The NO donor sodium nitroprusside (SNP and the NO scavenger 2-(4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO were additionally applied as NO positive and negative controls, respectively. Immunohistochemical staining was used to determine phosphorylation and thus activation of RBC-NOS. As a marker for NO synthesis nitrite was measured in plasma and RBCs using chemiluminescence detection. S-nitrosylation of erythrocyte proteins was determined by biotin switch assay and modified proteins were identified using LC-MS. RBC deformability was determined by ektacytometry. The data reveal that activated RBC-NOS leads to increased NO production, S-nitrosylation of RBC proteins and RBC deformability, whereas RBC-NOS inhibition resulted in contrary effects. CONCLUSION/SIGNIFICANCE: This study first-time provides strong evidence that RBC-NOS-produced NO modifies RBC deformability through direct S-nitrosylation of cytoskeleton proteins, most likely α- and

  20. Functional link between ETB receptors and eNOS maintain tissue oxygenation in the normal liver.

    Science.gov (United States)

    Paxian, Markus; Keller, Steve A; Baveja, Rajiv; Korneszczuk, Katarzyna; Huynh, Toan T; Clemens, Mark G

    2004-01-01

    Endothelins and their receptors play a crucial role in regulating liver microcirculation in pathophysiological conditions. The authors investigated the functional significance of the coupling of ET(B) receptors and eNOS in maintaining regional perfusion and tissue oxygenation in the normal liver. The effect of endothelin-1 or the ET(B) agonist IRL1620 on oxygen consumption was determined in isolated perfused liver and isolated hepatocytes. Oxygen delivery to the liver tissue was determined in vivo. Following eNOS or iNOS blockade, either ET-1 or IRL1620 was infused via the portal vein. Hepatic tissue oxygenation, redox state, and microcirculation were investigated by intravital microscopy. Injury was estimated by serum LDH. Although IRL1620 and endothelin-1 increased oxygen consumption in isolated hepatocytes, in intact liver, endothelin decreased oxygen consumption while IRL1620 produced no change. In vivo, ET(B) stimulation modestly altered hepatic tissue P(O(2)), redox potential, and microcirculation. eNOS inhibition and ET(B) activation dramatically reduced microcirculatory blood flow, oxygen supply, and increased LDH release. Inhibition of iNOS resulted in small but not significant changes in these parameters. Concomitant ET(A)/ET(B) receptor activation increased microcirculatory failure and decreased tissue oxygen even without NOS inhibition. In contrast, hepatocellular injury was significantly increased following eNOS inhibition. Coupling between ET(B) receptor stimulation and eNOS activation decreases sinusoidal constriction and plays a functionally important role in maintaining microcirculation and tissue oxygenation in the normal liver.

  1. Development of nNOS-positive neurons in the rat sensory ganglia after capsaicin treatment.

    Science.gov (United States)

    Masliukov, Petr M; Moiseev, Konstantin Y; Korzina, Marina B; Porseva, Valentina V

    2015-08-27

    To gain a better understanding of the neuroplasticity of afferent neurons during postnatal ontogenesis, the distribution of neuronal nitric oxide synthase (nNOS) immunoreactivity was studied in the nodose ganglion (NG) and Th2 and L4 dorsal root ganglia (DRG) from vehicle-treated and capsaicin-treated female Wistar rats at different ages (10-day-old, 20-day-old, 30-day-old, and two-month-old). The percentage of nNOS-immunoreactive (IR) neurons decreased after capsaicin treatment in all studied ganglia in first 20 days of life, from 55.4% to 36.9% in the Th2 DRG, from 54.6% to 26.1% in the L4 DRG and from 37.1% to 15.0% in the NG. However, in the NG, the proportion of nNOS-IR neurons increased after day 20, from 11.8% to 23.9%. In the sensory ganglia of all studied rats, a high proportion of nNOS-IR neurons bound isolectin B4. Approximately 90% of the sensory nNOS-IR neurons bound to IB4 in the DRG and approximately 80% in the NG in capsaicin-treated and vehicle-treated rats. In 10-day-old rats, a large number of nNOS-IR neurons also expressed TrkA, and the proportion of nNOS(+)/TrkA(+) neurons was larger in the capsaicin-treated rats compared with the vehicle-treated animals. During development, the percentage of nNOS(+)/TrkA(+) cells decreased in the first month of life in both groups. The information provided here will also serve as a basis for future studies investigating mechanisms of sensory neuron development.

  2. Angiotensin II blockade causes acute renal failure in eNOS-deficient mice

    Directory of Open Access Journals (Sweden)

    Jürgen Schnermann

    2001-03-01

    Full Text Available Compared with wild-type mice, adult endothelial nitric oxide synthase (eNOS knockout mice (eight months of age have increased blood pressure (BP (126±9 mmHg vs. 100±4 mmHg, and an increased renal vascular resistance (155±16 vs. 65±4 mmHg.min/ml. Renal vascular resistance responses to i.v. administration of noradrenaline were markedly enhanced in eNOS knockout mice. Glomerular filtration rate (GFR of anaesthetised eNOS -/- mice was 324±57 µl/min gKW, significantly lower than the GFR of 761±126 µl/min.gKW in wild-type mice. AT1-receptor blockade with i.v. candesartan (1—1.5 mg/kg reduced arterial blood pressure and renal vascular resistance, and increased renal blood flow (RBF to about the same extent in wild-type and eNOS -/- mice. Candesartan did not alter GFR in wild-type mice (761±126 vs. 720±95 µl/min.gKW, but caused a marked decrease in GFR in eNOS -/- mice (324.5±75.2 vs. 77±18 µl/min.gKW. A similar reduction in GFR of eNOS deficient mice was also caused by angiotensin-converting enzyme (ACE inhibition. Afferent arteriolar granularity, a measure of renal renin expression, was found to be reduced in eNOS -/- compared with wild-type mice. In chronically eNOS-deficient mice, angiotensin II (Ang II is critical for maintaining glomerular filtration pressure and GFR, presumably through its effect on efferent arteriolar tone.

  3. Endogenous angiotensin II modulates nNOS expression in renovascular hypertension

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    T.M.C. Pereira

    2009-07-01

    Full Text Available Nitric oxide (NO influences renal blood flow mainly as a result of neuronal nitric oxide synthase (nNOS. Nevertheless, it is unclear how nNOS expression is modulated by endogenous angiotensin II, an inhibitor of NO function. We tested the hypothesis that the angiotensin II AT1 receptor and oxidative stress mediated by NADPH oxidase contribute to the modulation of renal nNOS expression in two-kidney, one-clip (2K1C hypertensive rats. Experiments were performed on male Wistar rats (150 to 170 g body weight divided into 2K1C (N = 19 and sham-operated (N = 19 groups. nNOS expression in kidneys of 2K1C hypertensive rats (N = 9 was compared by Western blotting to that of 2K1C rats treated with low doses of the AT1 antagonist losartan (10 mg·kg-1·day-1; N = 5 or the superoxide scavenger tempol (0.2 mmol·kg-1·day-1; N = 5, which still remain hypertensive. After 28 days, nNOS expression was significantly increased by 1.7-fold in the clipped kidneys of 2K1C rats and by 3-fold in the non-clipped kidneys of 2K1C rats compared with sham rats, but was normalized by losartan. With tempol treatment, nNOS expression increased 2-fold in the clipped kidneys and 1.4-fold in the non-clipped kidneys compared with sham rats. The changes in nNOS expression were not followed by changes in the enzyme activity, as measured indirectly by the cGMP method. In conclusion, AT1 receptors and oxidative stress seem to be primary stimuli for increased nNOS expression, but this up-regulation does not result in higher enzyme activity.

  4. (−)-Epicatechin activation of endothelial cell eNOS, NO and related signaling pathways

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    Ramirez-Sanchez, Israel; Maya, Lisandro; Ceballos, Guillermo; Villarreal, Francisco

    2010-01-01

    Recent reports indicate that (−)-epicatechin can exert cardioprotective actions, which may involve eNOS-mediated nitric oxide production in endothelial cells. However, the mechanism by which (−)-epicatechin activates eNOS remains unclear. In this study, we proposed to identify the intracellular pathways involved in (−)-epicatechin-induced effects on eNOS, utilizing human coronary artery endothelial cells in culture. Treatment of cells with (−)-epicatechin leads to time- and dose-dependent effects, which peaked at 10 min at 1 μmol/L. (−)-Epicatechin treatment activates eNOS via serine-633 and serine-1177 phosphorylation and threonine-495 dephosphorylation. Using specific inhibitors, we have established the participation of the PI3K pathway in eNOS activation. (−)-Epicatechin induces eNOS uncoupling from caveolin-1 and its association with calmodulin-1, suggesting the involvement of intracellular calcium. These results allowed us to propose that (−) epicatechin effects may be dependent on actions exerted at the cell membrane level. To test this hypothesis, cells were treated with the phospholipase C inhibitor U73122, which blocked (−)-epicatechin-induced eNOS activation. We also demonstrated inositol phosphate accumulation in (−)-epicatechin-treated cells. The inhibitory effects of the pre-incubation of cells with the CaMKII inhibitor KN-93 indicate that (−)-epicatechin-induced eNOS activation is at least partially mediated via the Ca2+/CaMKII pathway. The (−)-epicatechin stereoisomer catechin was only able to partially stimulate nitric oxide production in cells. Altogether, these results strongly suggest the presence of a cell surface acceptor-effector for the cacao flavanol (−)-epicatechin, which may mediate its cardiovascular effects. PMID:20404222

  5. Circulating NOS3 modulates left ventricular remodeling following reperfused myocardial infarction.

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    Gorressen, Simone; Stern, Manuel; van de Sandt, Annette M; Cortese-Krott, Miriam M; Ohlig, Jan; Rassaf, Tienush; Gödecke, Axel; Fischer, Jens W; Heusch, Gerd; Merx, Marc W; Kelm, Malte

    2015-01-01

    Nitric oxide (NO) is constitutively produced and released from the endothelium and several blood cell types by the isoform 3 of the NO synthase (NOS3). We have shown that NO protects against myocardial ischemia/reperfusion (I/R) injury and that depletion of circulating NOS3 increases within 24 h of ischemia/reperfusion the size of myocardial infarction (MI) in chimeric mice devoid of circulating NOS3. In the current study we hypothesized that circulating NOS3 also affects remodeling of the left ventricle following reperfused MI. To analyze the role of circulating NOS3 we transplanted bone marrow of NOS3-/- and wild type (WT) mice into WT mice, producing chimerae expressing NOS3 only in vascular endothelium (BC-/EC+) or in both, blood cells and vascular endothelium (BC+/EC+). Both groups underwent 60 min of coronary occlusion in a closed-chest model of reperfused MI. During the 3 weeks post MI, structural and functional LV remodeling was serially assessed (24 h, 4 d, 1 w, 2 w and 3 w) by echocardiography. At 72 hours post MI, gene expression of several extracellular matrix (ECM) modifying molecules was determined by quantitative RT-PCR analysis. At 3 weeks post MI, hemodynamics were obtained by pressure catheter, scar size and collagen content were quantified post mortem by Gomori's One-step trichrome staining. Three weeks post MI, LV end-systolic (53.2±5.9 μl; ***p≤0.001; n = 5) and end-diastolic volumes (82.7±5.6 μl; *pNOS3 ameliorates maladaptive left ventricular remodeling following reperfused myocardial infarction.

  6. Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian population.

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    Kallel, Amani; Sbaï, Mohamed Hédi; Sediri, Yousra; Abdessalem, Salem; Mourali, Mohamed Sami; Feki, Moncef; Mechmeche, Rachid; Jemaa, Riadh; Kaabachi, Naziha

    2013-12-01

    Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with myocardial infarction (MI) have been reported. This study investigated the relationship of the -786T>C (rs2070744), 894G>T (rs1799983) and 4a4b polymorphisms of the NOS3 gene with the presence of MI in the Tunisian population. In addition, we also examined the association of NOS3 gene haplotypes with MI in Tunisian subjects. A total of 303 patients with MI and 225 controls were included in the study. The 894G>T and -786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR. There was significant linkage disequilibrium between the three NOS3 polymorphisms (pNOS3 4a4b, but not -786T>C and 894G>T, polymorphism was significantly different between MI patients and controls. The univariate logistic regression analysis showed a significant association of the 4a4b polymorphism and MI according to co-dominant, dominant and recessive models (co-dominant model OR: 4.38, 95%CI: 1.24-15.41; p=0.021, dominant model OR: 1.66, 95%CI: 1.14-2.42); p=0.007, and recessive model OR: 3.85, 95%CI: 1.10-13.47; p=0.035). The multivariate analysis, adjusted for traditional cardiovascular risk factors, revealed that the NOS3 4a4a genotype was an independent predisposing factor to MI, according to the models considered. In addition, a haplotype 7 (C-T-4a), (OR=12.05, p=0.010) was a risk factor of MI after controlling for classical risk factors. These finding suggest that the 4a4b polymorphism of the NOS3 gene was associated with MI in Tunisian patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Disrupted NOS signaling in lymphatic endothelial cells exposed to chronically increased pulmonary lymph flow.

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    Datar, Sanjeev A; Gong, Wenhui; He, Youping; Johengen, Michael; Kameny, Rebecca J; Raff, Gary W; Maltepe, Emin; Oishi, Peter E; Fineman, Jeffrey R

    2016-07-01

    Associated abnormalities of the lymphatic circulation are well described in congenital heart disease. However, their mechanisms remain poorly elucidated. Using a clinically relevant ovine model of a congenital cardiac defect with chronically increased pulmonary blood flow (shunt), we previously demonstrated that exposure to chronically elevated pulmonary lymph flow is associated with: 1) decreased bioavailable nitric oxide (NO) in pulmonary lymph; and 2) attenuated endothelium-dependent relaxation of thoracic duct rings, suggesting disrupted lymphatic endothelial NO signaling in shunt lambs. To further elucidate the mechanisms responsible for this altered NO signaling, primary lymphatic endothelial cells (LECs) were isolated from the efferent lymphatic of the caudal mediastinal node in 4-wk-old control and shunt lambs. We found that shunt LECs (n = 3) had decreased bioavailable NO and decreased endothelial nitric oxide synthase (eNOS) mRNA and protein expression compared with control LECs (n = 3). eNOS activity was also low in shunt LECs, but, interestingly, inducible nitric oxide synthase (iNOS) expression and activity were increased in shunt LECs, as were total cellular nitration, including eNOS-specific nitration, and accumulation of reactive oxygen species (ROS). Pharmacological inhibition of iNOS reduced ROS in shunt LECs to levels measured in control LECs. These data support the conclusion that NOS signaling is disrupted in the lymphatic endothelium of lambs exposed to chronically increased pulmonary blood and lymph flow and may contribute to decreased pulmonary lymphatic bioavailable NO.

  8. Role of glypican-1 in endothelial NOS activation under various steady shear stress magnitudes.

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    Zeng, Ye; Liu, Jingxia

    2016-11-01

    Blood flow patterns in proatherogenic and antiatherogenic regions are rather different. We hypothesize that the laminar flow with steady shear stress increased nitric oxide (NO) bioavailability while disturbed flow with low shear stress reduced it, which is mediating by glypican-1. Thus, we detected the expression of glypican-1 under different shear stress magnitudes, and tested whether the magnitude of shear stress determines the level of endothelial NO synthase (eNOS) via glypican-1 by using phosphatidylinositol phospholipase C (PI-PLC). Results revealed that the expression of glypican-1 depends on the magnitude and duration of shear stress loading. Activation of eNOS in HUVECs is downregulated by 4dyn/cm(2) of shear stress, but is upregulated by 15dyn/cm(2). Removal of glypican-1 significantly suppressed the 15dyn/cm(2) shear stress-induced eNOS activity, and further reduced the 4dyn/cm(2)-inhibited eNOS activity. Therefore, eNOS activation depends on shear stress magnitudes and is mediated by glypican-1. The role of glypican-1 in mediating the eNOS activation under shear stress might involve in protecting the endothelial function against disturbed flow and enhancing the sensitive of the endothelial cell to laminar flow, supporting a potential role of glypican-1 against atherosclerosis.

  9. Activation of Endothelial Nitric Oxide (eNOS Occurs through Different Membrane Domains in Endothelial Cells.

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    Jason Tran

    Full Text Available Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC with cholesterol and the oxysterol 7-ketocholesterol (7KC. Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1 colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells.

  10. The role of eNOS phosphorylation in causing drug-induced vascular injury.

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    Tobin, Grainne A McMahon; Zhang, Jun; Goodwin, David; Stewart, Sharron; Xu, Lin; Knapton, Alan; González, Carlos; Bancos, Simona; Zhang, Leshuai; Lawton, Michael P; Enerson, Bradley E; Weaver, James L

    2014-06-01

    Previously we found that regulation of eNOS is an important part of the pathogenic process of Drug-induced vascular injury (DIVI) for PDE4i. The aims of the current study were to examine the phosphorylation of eNOS in mesentery versus aorta at known regulatory sites across DIVI-inducing drug classes and to compare changes across species. We found that phosphorylation at S615 in rats was elevated 35-fold 2 hr after the last dose of CI-1044 in mesentery versus 3-fold in aorta. Immunoprecipitation studies revealed that many of the upstream regulators of eNOS activation were associated with eNOS in 1 or more signalosome complexes. Next rats were treated with drugs from 4 other classes known to cause DIVI. Each drug was given alone and in combination with SIN-1 (NO donor) or L-NAME (eNOS inhibitor), and the level of eNOS phosphorylation in mesentery and aorta tissue was correlated with the extent of vascular injury and measured serum nitrite. Drugs or combinations produced altered serum nitrite levels as well as vascular injury score in the mesentery. The results suggested that phosphorylation of S615 may be associated with DIVI activity. Studies with the species-specific A2A adenosine agonist CI-947 in rats versus primates showed a similar pattern.

  11. Depletion of circulating blood NOS3 increases severity of myocardial infarction and left ventricular dysfunction.

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    Merx, Marc W; Gorressen, Simone; van de Sandt, Annette M; Cortese-Krott, Miriam M; Ohlig, Jan; Stern, Manuel; Rassaf, Tienush; Gödecke, Axel; Gladwin, Mark T; Kelm, Malte

    2014-01-01

    Nitric oxide (NO) derived from endothelial NO synthase (NOS3) plays a central role in myocardial ischemia/reperfusion (I/R)-injury. Subsets of circulating blood cells, including red blood cells (RBCs), carry a NOS3 and contribute to blood pressure regulation and RBC nitrite/nitrate formation. We hypothesized that the circulating blood born NOS3 also modulates the severity of myocardial infarction in disease models. We cross-transplanted bone marrow in wild-type and NOS3(-/-) mice with wild-type mice, producing chimeras expressing NOS3 only in vascular endothelium (BC-/EC+) or in both blood cells and vascular endothelium (BC+/EC+). After 60-min closed-chest coronary occlusion followed by 24 h reperfusion, cardiac function, infarct size (IS), NOx levels, RBCs NO formation, RBC deformability, and vascular reactivity were assessed. At baseline, BC-/EC+ chimera had lower nitrite levels in blood plasma (BC-/EC+: 2.13 ± 0.27 μM vs. BC+/EC+ 3.17 ± 0.29 μM; *p NOS3 in an acute model of myocardial I/R in chimeric mice.

  12. Association study of NOS3 gene polymorphisms and hypertension in the Han Chinese population.

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    Wang, Linhong; Shen, Chong; Yang, Song; Chen, Yanchun; Guo, Daoxia; Jin, Yuelong; He, Lianping; Chen, Jinfeng; Zhao, Xianghai; Zhao, Hailong; Yao, Yingshui

    2015-12-01

    Recent studies have reported that NOS3 plays an important role in cardiovascular pathology, whereas the association of NOS3 and hypertension (HT) has been controversial between African Americans and European whites. Here, we aimed to further investigate the genetic effect of unexplored loci at NOS3 on the susceptibility of HT in the Han Chinese population. The association of three polymorphisms; rs4496877, rs1808593 and rs3918186 to HT was tested in a case control study that included 2012 HT cases and 2210 controls. Association analysis showed that there was no significant association between rs4496877, rs1808593 and rs3918186 of NOS3 and HT in the whole study population. Stratification analysis indicated that rs3918186 was significantly associated with HT in the ≥55-year-old population (OR = 1.245, 95% CI = 1.010-1.534, P = 0.04). The rs4496877 and rs1808593 were significantly associated with HT in the male population (P = 0.015) and NOS3 contribute to the genetic susceptibility of HT and that rs3918186 was associated with SBP in the Chinese population. Age and gender might modify the genetic effect of NOS3 on HT, and drinking significantly interacts with rs3918186. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Adenovirus-mediated eNOS expression augments liver injury after ischemia/reperfusion in mice.

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    Arun P Palanisamy

    Full Text Available Hepatic ischemia/reperfusion (l/R injury continues to be a critical problem. The role of nitric oxide in liver I/R injury is still controversial. This study examines the effect of endothelial nitric oxide synthase (eNOS over-expression on hepatic function following I/R. Adenovirus expressing human eNOS (Ad-eNOS was administered by tail vein injection into C57BL/6 mice. Control mice received either adenovirus expressing LacZ or vehicle only. Sixty minutes of total hepatic ischemia was performed 3 days after adenovirus treatment, and mice were sacrificed after 6 or 24 hrs of reperfusion to assess hepatic injury. eNOS over expression caused increased liver injury as evidenced by elevated AST and ALT levels and decreased hepatic ATP content. While necrosis was not pervasive in any group, TUNEL demonstrated significantly increased apoptosis in Ad-eNOS infected livers. Western blotting demonstrated increased levels of protein nitration and upregulation of the pro-apoptotic proteins bax and p53. Our data suggest that over-expression of eNOS is detrimental in the setting of hepatic I/R.

  14. Mutation screening of NOS1AP gene in a large sample of psychiatric patients and controls

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    Nygren Gudrun

    2010-07-01

    Full Text Available Abstract Background The gene encoding carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (NOS1AP is located on chromosome 1q23.3, a candidate region for schizophrenia, autism spectrum disorders (ASD and obsessive-compulsive disorder (OCD. Previous genetic and functional studies explored the role of NOS1AP in these psychiatric conditions, but only a limited number explored the sequence variability of NOS1AP. Methods We analyzed the coding sequence of NOS1AP in a large population (n = 280, including patients with schizophrenia (n = 72, ASD (n = 81 or OCD (n = 34, and in healthy volunteers controlled for the absence of personal or familial history of psychiatric disorders (n = 93. Results Two non-synonymous variations, V37I and D423N were identified in two families, one with two siblings with OCD and the other with two brothers with ASD. These rare variations apparently segregate with the presence of psychiatric conditions. Conclusions Coding variations of NOS1AP are relatively rare in patients and controls. Nevertheless, we report the first non-synonymous variations within the human NOS1AP gene that warrant further genetic and functional investigations to ascertain their roles in the susceptibility to psychiatric disorders.

  15. Epigenetic regulation of nitric oxide synthase 2, inducible (Nos2) by NLRC4 inflammasomes involves PARP1 cleavage

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    Buzzo, Carina de Lima; Medina, Tiago; Branco, Laura M.; Lage, Silvia L.; Ferreira, Luís Carlos de Souza; Amarante-Mendes, Gustavo P.; Hottiger, Michael O.; De Carvalho, Daniel D.; Bortoluci, Karina R.

    2017-01-01

    Nitric oxide synthase 2, inducible (Nos2) expression is necessary for the microbicidal activity of macrophages. However, NOS2 over-activation causes multiple inflammatory disorders, suggesting a tight gene regulation is necessary. Using cytosolic flagellin as a model for inflammasome-dependent NOS2 activation, we discovered a surprising new role for NLRC4/caspase-1 axis in regulating chromatin accessibility of the Nos2 promoter. We found that activation of two independent mechanisms is necessary for NOS2 expression by cytosolic flagellin: caspase-1 and NF-κB activation. NF-κB activation was necessary, but not sufficient, for NOS2 expression. Conversely, caspase-1 was necessary for NOS2 expression, but dispensable for NF-κB activation, indicating that this protease acts downstream NF-κB activation. We demonstrated that epigenetic regulation of Nos2 by caspase-1 involves cleavage of the chromatin regulator PARP1 (also known as ARTD1) and chromatin accessibility of the NF-κB binding sites located at the Nos2 promoter. Remarkably, caspase-1-mediated Nos2 transcription and NO production contribute to the resistance of macrophages to Salmonella typhimurium infection. Our results uncover the molecular mechanism behind the constricted regulation of Nos2 expression and open new therapeutic opportunities based on epigenetic activities of caspase-1 against infectious and inflammatory diseases. PMID:28150715

  16. Nitrotyrosinylation, Remodeling and Endothelial-Myocyte Uncoupling in iNOS, Cystathionine Beta Synthase (CBS) Knockouts and iNOS/CBS Double Knockout Mice

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    Kundu, Soumi; Kumar, Munish; Sen, Utpal; Mishra, Paras K.; Tyagi, Neetu; Metreveli, Naira; Lominadze, David; Rodriguez, Walter; Tyagi, Suresh C.

    2009-01-01

    Increased levels of homocysteine (Hcy), recognized as hyperhomocysteinemia (HHcy), were associated with cardiovascular diseases. There was controversy regarding the detrimental versus cardio protective role of inducible nitric oxide synthase (iNOS) in ischemic heart disease. The aim of this study was to test the hypothesis that the Hcy generated nitrotyrosine by inducing the endothelial nitric oxide synthase, causing endothelial-myocyte (E–M) coupling. To differentiate the role of iNOS versus constitutive nitric oxide synthase (eNOS and nNOS) in Hcy-mediated nitrotyrosine generation and matrix remodeling in cardiac dysfunction, left ventricular (LV) tissue was analyzed from cystathionine beta synthase (CBS) heterozygote knockout, iNOS homozygote knockout, CBS−/+/iNOS−/− double knockout, and wild-type (WT) mice. The levels of nitrotyrosine, MMP-2 and -9 (zymographic analysis), and fibrosis (by trichrome stain) were measured. The endothelial-myocyte function was determined in cardiac rings. In CBS−/+ mice, homocysteine was elevated and in iNOS−/− mice, nitric oxide was significantly reduced. The nitrotyrosine and matrix metalloproteinase-9 (MMP-9) levels were elevated in double knockout and CBS−/+ as compared to WT mice. Although MMP-2 levels were similar in CBS−/+, iNOS−/−, and CBS−/+/iNOS−/−, the levels were three- to fourfold higher than WT. The levels of collagen were similar in CBS−/+ and iNOS−/−, but they were threefold higher than WT. Interesting, the levels of collagen increased sixfold in double knockouts, compared to WT, suggesting synergism between high Hcy and lack of iNOS. Left ventricular hypertrophy was exaggerated in the iNOS−/− and double knockout, and mildly increased in the CBS−/+, compared to WT mice. The endothelial-dependent relaxation was attenuated to the same extent in the CBS−/+ and iNOS−/−, compared to WT, but it was robustly blunted in double knockouts. The results concluded that homocysteine

  17. Liposomal tetrahydrobiopterin preserves eNOS coupling in the post-ischemic heart conferring in vivo cardioprotection.

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    Xie, Lin; Talukder, M A Hassan; Sun, Jian; Varadharaj, Saradhadevi; Zweier, Jay L

    2015-09-01

    Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS), and reduced BH4 availability leads to endothelial NOS (eNOS) uncoupling and increased reactive oxygen species (ROS) generation. Questions remain regarding the functional state of eNOS and role of BH4 availability in the process of in vivo myocardial ischemia-reperfusion (I/R) injury. Rats were subjected to 60min of in vivo left coronary artery occlusion and varying periods of reperfusion with or without pre-ischemic liposomal BH4 supplementation (1mg/kg, iv). Myocardial infarction was correlated with cardiac BH4 content, eNOS protein level, NOS enzyme activity, and ROS generation. In the vehicle group, 60-min ischemia drastically reduced myocardial BH4 content in the area at risk (AAR) compared to non-ischemic (NI) area and the level remained lower during early reperfusion followed by recovery after 24-h reperfusion. Total eNOS, activated eNOS protein level (eNOS Ser1177 phosphorylation) and NOS activity were also significantly reduced during ischemia and/or early reperfusion, but recovered after 24-h reperfusion. With liposomal BH4 treatment, BH4 levels were identical in the AAR and NI area during ischemia and/or early reperfusion, and were significantly higher than with vehicle. BH4 pre-treatment preserved eNOS Ser1177 phosphorylation and NOS activity in the AAR, and significantly reduced myocardial ROS generation and infarction compared to vehicle. These findings provide direct evidence that in vivo I/R induces eNOS dysfunction secondary to BH4 depletion, and that pre-ischemic liposomal BH4 administration preserves eNOS function conferring cardioprotection with reduced oxidative stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Correlated NOS-Imu and myf5 expression by satellite cells in mdx mouse muscle regeneration during NOS manipulation and deflazacort treatment.

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    Anderson, Judy E; Vargas, Cinthya

    2003-06-01

    Satellite cells, muscle precursor cells in skeletal muscle, are normally quiescent and become activated by disease or injury. A lack of dystrophin and changes in the expression or activity of neuronal nitric oxide synthase (NOS-I) affect the timing of activation in vivo. Nitric oxide synthase inhibition delays muscle repair in normal mice, and worsens muscular dystrophy in the mdx mouse, a genetic homologue of Duchenne muscular dystrophy. However, the potential role of activation and repair events mediated by nitric oxide in determining the outcome of steroid or other treatments for muscular dystrophy is not clear. We tested the hypothesis that the extent of repair in dystrophic muscles of mdx mice is partly dependent on NOS-Imu expression and activity. Myotube formation in regenerating muscle was promoted by deflazacort treatment of mdx dystrophic mice (PImu mRNA expression and activity were present in satellite cells and very new myotubes of regenerating and dystrophic muscle. Deflazacort treatment resulted in increased NOS-Imu expression in regenerating muscles in a strong and specific correlation with myf5 expression (r=0.95, PImu and myf5 expression in the diaphragm without affecting the diameter of non-regenerating fibres. These in vivo studies suggest that gains in NOS-Imu expression and nitric oxide synthase activity in satellite cells can increase the extent and speed of repair, even in the absence of dystrophin in muscle fibres. NOS-Imu may be a useful therapeutic target to augment the effects of steroidal or other treatments of muscular dystrophy.

  19. Striatal NOS1 has dimorphic expression and activity under stress and nicotine sensitization.

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    Díaz, David; Murias, Azucena Rodrigo; Ávila-Zarza, Carmelo Antonio; Muñoz-Castañeda, Rodrigo; Aijón, José; Alonso, José Ramón; Weruaga, Eduardo

    2015-10-01

    Nicotine exerts its addictive influence through the meso-cortico-limbic reward system, where the striatum is essential. Nicotine addiction involves different neurotransmitters, nitric oxide (NO) being especially important, since it triggers the release of the others by positive feedback. In the nervous system, NO is mainly produced by nitric oxide synthase 1 (NOS1). However, other subtypes of synthases can also synthesize NO, and little is known about the specific role of each isoform in the process of addiction. In parallel, NOS activity and nicotine addiction are also affected by stress and sexual dimorphism. To determine the specific role of this enzyme, we analyzed both NOS expression and NO synthesis in the striatum of wild-type and NOS1-knocked out (KO) mice of both sexes in situations of nicotine sensitization and stress. Our results demonstrated differences between the caudate-putamen (CP) and nucleus accumbens (NA). With respect to NOS1 expression, the CP is a dimorphic region (27.5% lower cell density in males), but with a stable production of NO, exclusively due to this isoform. Thus, the nitrergic system of CP may not be involved in stress or nicotine addiction. Conversely, the NA is much more variable and strongly involved in both situations: its NO synthesis displays dimorphic variations at both basal (68.5% reduction in females) and stress levels (65.9% reduction in males), which disappear when nicotine is infused. Thus, the KO animals showed an increase in NO production (21.7%) in the NA, probably by NOS3, in an attempt to compensate the lack of NOS1.

  20. Phosphomimetic modulation of eNOS improves myocardial reperfusion and mimics cardiac postconditioning in mice.

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    Terrence Pong

    Full Text Available OBJECTIVE: Myocardial infarction resulting from ischemia-reperfusion injury can be reduced by cardiac postconditioning, in which blood flow is restored intermittently prior to full reperfusion. Although key molecular mechanisms and prosurvival pathways involved in postconditioning have been identified, a direct role for eNOS-derived NO in improving regional myocardial perfusion has not been shown. The objective of this study is to measure, with high temporal and spatial resolution, regional myocardial perfusion during ischemia-reperfusion and postconditioning, in order to determine the contribution of regional blood flow effects of NO to infarct size and protection. METHODS AND RESULTS: We used myocardial contrast echocardiography to measure regional myocardial blood flow in mice over time. Reperfusion after myocardial ischemia-reperfusion injury is improved by postconditioning, as well as by phosphomimetic eNOS modulation. Knock-in mice expressing a phosphomimetic S1176D form of eNOS showed improved myocardial reperfusion and significantly reduced infarct size. eNOS knock-out mice failed to show cardioprotection from postconditioning. The size of the no-reflow zone following ischemia-reperfusion is substantially reduced by postconditioning and by the phosphomimetic eNOS mutation. CONCLUSIONS AND SIGNIFICANCE: Using myocardial contrast echocardiography, we show that temporal dynamics of regional myocardial perfusion restoration contribute to reduced infarct size after postconditioning. eNOS has direct effects on myocardial blood flow following ischemia-reperfusion, with reduction in the size of the no-reflow zone. These results have important implications for ongoing clinical trials on cardioprotection, because the degree of protective benefit may be significantly influenced by the regional hemodynamic effects of eNOS-derived NO.

  1. Sleep disturbances in pediatric bipolar disorder: A comparison between Bipolar I and Bipolar NOS

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    Argelinda eBaroni

    2012-03-01

    Full Text Available Introduction: The diagnosis of Bipolar Disorder (BD in youths has been controversial, especially for the subtype BD Not Otherwise Specified (BD-NOS. In spite of growing evidence that sleep is a core feature of BD, few studies characterize and compare sleep disturbances in youth with BD type I (BD-I and BD-NOS. Sleep disturbances are frequently reported in clinical descriptions of children and adolescents with BD, however the reporting of the frequency and characteristics of sleep symptoms in youth with BD NOS and BD I during episodes remain poor. This study compares symptom of sleep disturbance as occurring in manic and depressive episodes in BD I and BD NOS youth using KSADS-PL interview data. The study also addresses whether symptoms of sleep disturbance vary in different age groups. Material and Methods: The sample consisted of 70 children and adolescent outpatients at an urban specialty clinic (42M/28F, 10.8±3.6 years old including 24 BP-I and 46 BP-NOS assessed using K-SADS-PL-parent interview. Results: Sleep disturbances including insomnia and decreased need for sleep were reported by 84.3% of the sample. Enuresis was diagnosed in 27% of sample. There were no significant differences in frequency of sleep symptoms between BD-I and BD-NOS. Regardless of BD subtype, current functioning was negatively correlated with decreased need for sleep but not insomnia, and regardless of BD subtype. Conclusion: The majority of youth with BD presents with sleep symptoms during mood episodes. BD NOS presents with the same proportion of sleep symptoms as BD I in our sample.

  2. Genetic Deletion of the NOS3 Gene in CAV1-/- Mice Restores Aqueous Humor Outflow Function.

    Science.gov (United States)

    Song, Maomao; Wu, Jihong; Lei, Yuan; Sun, Xinghuai

    2017-10-01

    The purpose of this study was to investigate the impact of genetic deletion of NOS3 in CAV1-/- mice on aqueous humor outflow function using a mouse genetic double knockout model (DKO, NOS3-/- CAV1-/-). IOP was measured in DKO, NOS3 KO, CAV1 KO, and wild-type (WT) mice by rebound tonometry. Outflow facility was measured by perfusing enucleated mouse eyes at multiple pressure steps. Sodium nitroprusside (SNP) and L-NG-nitroarginine methyl ester (L-NAME) was administered topically, whereas the contralateral eyes served as vehicle controls. IOP was measured in both eyes before drug treatment and 1 hour after the last drug treatment. Mock aqueous humor ± the nitric oxide (NO) donor SNP or NOS inhibitor L-NAME was perfused into enucleated eyes. IOP was 11 ± 0.23 mm Hg in DKO mice, which was similar to WT mice and significantly lower than CAV1 KO mice (n = 18, P > 0.05). NOS3 deletion in CAV1-/- mice resulted in a 1.9-fold increase in conventional outflow facility (Ccon) compared with CAV1 KO mice (n = 7, P 0.05) or Ccon in DKO mice (SNP, n = 20; vehicle, n = 11, P > 0.05). Topical application of L-NAME significantly increased IOP in WT, DKO, and CAV1 mice by reducing Ccon. Nitrotyrosine and PKG levels of DKO mice were similar to, whereas sGC was lower than, WT mice (P NOS3 in CAV1-deficient mice restored IOP and conventional aqueous humor drainage to WT level. NOS3 and CAV1 interaction is important to IOP regulation.

  3. Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway

    Energy Technology Data Exchange (ETDEWEB)

    Nagane, Masaki; Yasui, Hironobu; Sakai, Yuri; Yamamori, Tohru [Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818 (Japan); Niwa, Koichi [Laboratory of Biochemistry, Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493 (Japan); Hattori, Yuichi [Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194 (Japan); Kondo, Takashi [Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194 (Japan); Inanami, Osamu, E-mail: inanami@vetmed.hokudai.ac.jp [Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818 (Japan)

    2015-01-02

    Highlights: • eNOS activity is increased in BAECs exposed to X-rays. • ATM is involved in this increased eNOS activity. • HSP90 modulates the radiation-induced activation of ATM and eNOS. - Abstract: In this study, the involvement of ataxia telangiectasia mutated (ATM) kinase and heat shock protein 90 (HSP90) in endothelial nitric oxide synthase (eNOS) activation was investigated in X-irradiated bovine aortic endothelial cells. The activity of nitric oxide synthase (NOS) and the phosphorylation of serine 1179 of eNOS (eNOS-Ser1179) were significantly increased in irradiated cells. The radiation-induced increases in NOS activity and eNOS-Ser1179 phosphorylation levels were significantly reduced by treatment with either an ATM inhibitor (Ku-60019) or an HSP90 inhibitor (geldanamycin). Geldanamycin was furthermore found to suppress the radiation-induced phosphorylation of ATM-Ser1181. Our results indicate that the radiation-induced eNOS activation in bovine aortic endothelial cells is regulated by ATM and HSP90.

  4. Prolonged Action Potential and After depolarizations Are Not due to Changes in Potassium Currents in NOS3 Knockout Ventricular Myocytes.

    Science.gov (United States)

    Wang, Honglan; Bonilla, Ingrid M; Huang, Xin; He, Quanhua; Kohr, Mark J; Carnes, Cynthia A; Ziolo, Mark T

    2012-01-01

    Ventricular myocytes deficient in endothelial nitric oxide synthase (NOS3(-/-)) exhibit prolonged action potential (AP) duration and enhanced spontaneous activity (early and delayed afterdepolarizations) during β-adrenergic (β-AR) stimulation. Studies have shown that nitric oxide is able to regulate various K(+) channels. Our objective was to examine if NOS3(-/-) myocytes had altered K(+) currents. APs, transient outward (I(to)), sustained (I(Ksus)), and inward rectifier (I(K1)) K(+) currents were measured in NOS3(-/-) and wild-type (WT) myocytes. During β-AR stimulation, AP duration (measured as 90% repolarization-APD(90)) was prolonged in NOS3(-/-) compared to WT myocytes. Nevertheless, we did not observe differences in I(to), I(Ksus), or I(K1) between WT and NOS3(-/-) myocytes. Our previous work showed that NOS3(-/-) myocytes had a greater Ca(2+) influx via L-type Ca(2+) channels with β-AR stimulation. Thus, we measured β-AR-stimulated SR Ca(2+) load and found a greater increase in NOS3(-/-) versus WT myocytes. Hence, our data suggest that the prolonged AP in NOS3(-/-) myocytes is not due to changes in I(to), I(Ksus), or I(K1). Furthermore, the increase in spontaneous activity in NOS3(-/-) myocytes may be due to a greater increase in SR Ca(2+) load. This may have important implications for heart failure patients, where arrhythmias are increased and NOS3 expression is decreased.

  5. Involvement of NOS3 in RA-Induced neural differentiation of human NT2/D1 cells.

    Science.gov (United States)

    Jezierski, Anna; Deb-Rinker, Paromita; Sodja, Caroline; Walker, P Roy; Ly, Dao; Haukenfrers, Julie; Sandhu, Jagdeep K; Bani-Yaghoub, Mahmud; Sikorska, Marianna

    2012-12-01

    Nitric oxide (NO) plays a key role in neurogenesis as a regulator of cell proliferation and differentiation. NO is synthesized from the amino acid L-arginine by nitric oxide synthases (NOS1, NOS2, and NOS3), which are encoded by separate genes and display different tissue distributions. We used an in vitro model of RA-induced neural differentiation of NT2 cells to examine which of the three NO-synthesizing enzymes is involved in this process. The results revealed a transient induction of NOS3 (known as the constitutively expressed endothelial nitric oxide synthase; eNOS) during the time course of the RA treatment. The peak of gene expression and the nuclear presence of NOS3 protein coincided with cell cycle exit of NT2-derived neuronal precursors. The subsequent analysis of cytosine methylation and histone H3 acetylation of the human NOS3 5' regulatory sequences indicated that epigenetic modifications, especially upstream of the proximal promoter (-734 to -989, relative to exon 2 TSS at +1), were also taking place. NOS1 was expressed only in the differentiated neurons (NT2-N), whereas NOS2 was not expressed at all in this cellular model. Thus, a burst of NO production, possibly required to inhibit neural cell proliferation, was generated by the transient expression of NOS3. This pattern of gene expression, in turn, required epigenetic remodeling of its regulatory region. Copyright © 2012 Wiley Periodicals, Inc.

  6. Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes.

    Science.gov (United States)

    Ryk, Charlotta; Koskela, Lotta Renström; Thiel, Tomas; Wiklund, N Peter; Steineck, Gunnar; Schumacher, Martin C; de Verdier, Petra J

    2015-12-01

    Bacillus Calmette-Guérin (BCG)-treatment is an established treatment for bladder cancer, but its mechanisms of action are not fully understood. High-risk non-muscle invasive bladder-cancer (NMIBC)-patients failing to respond to BCG-treatment have worse prognosis than those undergoing immediate radical cystectomy and identification of patients at risk for BCG-failure is of high priority. Several studies indicate a role for nitric oxide (NO) in the cytotoxic effect that BCG exerts on bladder cancer cells. In this study we investigated whether NO-synthase (NOS)-gene polymorphisms, NOS2-promoter microsatellite (CCTTT)n, and the NOS3-polymorphisms-786T>C (rs2070744) and Glu298Asp (rs1799983), can serve as possible molecular markers for outcome after BCG-treatment for NMIBC. All NMIBC-patients from a well-characterized population based cohort were analyzed (n=88). Polymorphism data were combined with information from 15-years of clinical follow-up. The effect of BCG-treatment on cancer-specific death (CSD), recurrence and progression in patients with varying NOS-genotypes were studied using Cox proportional hazard-models and log rank tests. BCG-treatment resulted in significantly better survival in patients without (Log rank: p=0.006; HR: 0.12, p=0.048), but not in patients with a long version ((CCTTT)n ≧13 repeats) of the NOS2-promoter microsatellite. The NOS3-rs2070744(TT) and rs1799983(GG)-genotypes showed decreased risk for CSD (Log rank(TT): p=0.001; Log rank(GG): p=0.010, HR(GG): 0.16, p=0.030) and progression (Log rank(TT): p<0.001, HR(TT): 0.05, p=0.005; Log rank(GG): p<0.001, HR(GG): 0.10, p=0.003) after BCG-therapy compared to the other genotypes. There was also a reduction in recurrence in BCG-treated patients that was mostly genotype independent. Analysis of combined genotypes identified a subgroup of 30% of the BCG-treated patients that did not benefit from BCG-treatment. Our results suggest that the investigated polymorphisms influence patient response

  7. iNOS-dependent increase in colonic mucus thickness in DSS-colitic rats.

    Directory of Open Access Journals (Sweden)

    Olof Schreiber

    Full Text Available AIM: To investigate colonic mucus thickness in vivo in health and during experimental inflammatory bowel disease. METHODS: Colitis was induced with 5% DSS in drinking water for 8 days prior to experiment, when the descending colonic mucosa of anesthetized rats was studied using intravital microscopy. Mucus thickness was measured with micropipettes attached to a micromanipulator. To assess the contributions of NOS and prostaglandins in the regulation of colonic mucus thickness, the non-selective NOS-inhibitor L-NNA (10 mg/kg bolus followed by 3 mg/kg/h, the selective iNOS-inhibitor L-NIL (10 mg/kg bolus followed by 3 mg/kg/h and the non-selective COX-inhibitor diclofenac (5 mg/kg were administered intravenously prior to experiment. To further investigate the role of iNOS in the regulation of colonic mucus thickness, iNOS -/- mice were used. RESULTS: Colitic rats had a thicker firmly adherent mucus layer following 8 days of DSS treatment than untreated rats (88±2 µm vs 76±1 µm. During induction of colitis, the thickness of the colonic mucus layer initially decreased but was from day 3 significantly thicker than in untreated rats. Diclofenac reduced the mucus thickness similarly in colitic and untreated rats (-16±5 µm vs -14±2 µm. While L-NNA had no effect on colonic mucus thickness in DSS or untreated controls (+3±2 µm vs +3±1 µm, L-NIL reduced the mucus thickness significantly more in colitic rats than in controls (-33±4 µm vs -10±3 µm. The importance of iNOS in regulating the colonic mucus thickness was confirmed in iNOS-/- mice, which had thinner colonic mucus than wild-type mice (35±3 µm vs 50±2 µm, respectively. Furthermore, immunohistochemistry revealed increased levels of iNOS in the colonic surface epithelium following DSS treatment. CONCLUSION: Both prostaglandins and nitric oxide regulate basal colonic mucus thickness. During onset of colitis, the thickness of the mucus layer is initially reduced followed by an iNOS

  8. Specific PKC isoforms regulate LPS-stimulated iNOS induction in murine microglial cells

    Directory of Open Access Journals (Sweden)

    Zhang Yumin

    2011-04-01

    Full Text Available Abstract Background Excessive production of nitric oxide (NO by inducible nitric oxide synthase (iNOS in reactive microglia is a major contributor to initiation/exacerbation of inflammatory and degenerative neurological diseases. Previous studies have indicated that activation of protein kinase C (PKC can lead to iNOS induction. Because of the existence of various PKC isoforms and the ambiguous specificity of PKC inhibitors, it is unclear whether all PKC isoforms or a specific subset are involved in the expression of iNOS by reactive microglia. In this study, we employed molecular approaches to characterize the role of each specific PKC isoform in the regulation of iNOS expression in murine microglia. Methods Induction of iNOS in response to bacterial endotoxin lipopolysaccharide (LPS was measured in BV-2 murine microglia treated with class-specific PKC inhibitors, or transfected with siRNA to silence specific PKC isoforms. iNOS expression and MAPK phosphorylation were evaluated by western blot. The role of NF-κB in activated microglia was examined by determining NF-κB transcriptional response element- (TRE- driven, promoter-mediated luciferase activity. Results Murine microglia expressed high levels of nPKCs, and expressed relatively low levels of cPKCs and aPKCs. All PKC inhibitors attenuated induction of iNOS in LPS-activated microglia. Knockdown of PKC δ and PKC β attenuated ERK1/2 and p38 phosphorylation, respectively, and blocked NF-κB activation that leads to the expression of iNOS in reactive microglia. Conclusions Our results identify PKC δ and β as the major PKC isoforms regulating iNOS expression in reactive microglia. The signaling pathways mediated by PKC involve phosphorylation of distinct MAPKs and activation of NF-κB. These results may help in the design of novel and selective PKC inhibitors for the treatment of many inflammatory and neurological diseases in which production of NO plays a pathogenic role.

  9. NCAM1, TACR1 and NOS genes and temperament: a study on suicide attempters and controls.

    Science.gov (United States)

    Giegling, Ina; Calati, Raffaella; Porcelli, Stefano; Hartmann, Annette M; Möller, Hans-Jürgen; De Ronchi, Diana; Rujescu, Dan; Serretti, Alessandro

    2011-01-01

    Suicide, one of the leading causes of death among young adults, seems to be plausibly modulated by both genetic and personality factors. The aim of this study was to dissect the potential association between genetics and temperament in a sample of 111 suicide attempters and 289 healthy controls. We focused on 4 genes previously investigated in association with suicide on the same sample: the nitric oxide synthase 1 and 3 (NOS1 and NOS3), the neuronal cell adhesion molecule 1 (NCAM1), and the tachykinin receptor 1 (TACR1) genes. In particular, we investigated whether a set of genetic variants in these genes (NOS1: rs2682826, rs1353939, rs693534; NOS3: rs2070744, rs1799983, rs891512; NCAM1: rs2301228, rs1884, rs1245113, rs1369816, rs2196456, rs584427; TACR1: rs3771810, rs3771825, rs726506, rs1477157) were associated with temperamental traits at the Temperament and Character Inventory (TCI). No strong evidence was found for the association between TCI personality traits and the polymorphisms considered in the 4 genes, with the exception of an association between reward dependence trait and the rs2682826 SNP in NOS1 in the healthy sample. However, this result could be plausibly interpreted as a false-positive finding. In conclusion, our study did not support the thesis of a direct modulation of these genes on temperament; however, further studies on larger samples are clearly required in order to confirm our preliminary findings and to exclude any possible minor influence.

  10. Effects of Dietary Decosahexaenoic Acid (Dha) on eNOS in Human Coronary Artery Endothelial Cells

    Science.gov (United States)

    Stebbins, Charles L.; Stice, James P.; Hart, C. Michael; Mbai, Fiona N.; Knowlton, Anne A.

    2015-01-01

    Endothelial dysfunction occurs in heart disease, and may reduce functional capacity via attenuations in peripheral blood flow. Dietary DHA may improve this dysfunction, but the mechanism is unknown. We determined if DHA enhances expression and activity of eNOS in cultured human coronary artery endothelial cells (HCAEC). HCAEC from 4 donors were treated with 5 nM, 50 nM, or 1 μM DHA for 7 days to model chronic DHA exposure. A trend for increased expression of eNOS and phospho-eNOS was observed with 5 and 50 nM DHA. DHA also enhanced expression of two proteins instrumental in activation of eNOS; phospho-Akt (5 and 50 nM) and HSP90 (50 nM and 1 μM). VEGF-induced activation of Akt increased NOx in treated (50 nM DHA) vs. untreated HCAEC (9.2±1.0 vs. 3.3±1.1 μmols/μg protein/μl). Findings suggest that DHA enhances eNOS and Akt activity, augments HSP90 expression, and increases NO bioavailability in response to Akt kinase activation PMID:18682551

  11. Inorganic polyphosphate suppresses lipopolysaccharide-induced inducible nitric oxide synthase (iNOS expression in macrophages.

    Directory of Open Access Journals (Sweden)

    Kana Harada

    Full Text Available In response to infection, macrophages produce a series of inflammatory mediators, including nitric oxide (NO, to eliminate pathogens. The production of these molecules is tightly regulated via various mechanisms, as excessive responses are often detrimental to host tissues. Here, we report that inorganic polyphosphate [poly(P], a linear polymer of orthophosphate ubiquitously found in mammalian cells, suppresses inducible nitric oxide synthase (iNOS expression induced by lipopolysaccharide (LPS, a cell wall component of Gram-negative bacteria, in mouse peritoneal macrophages. Poly(P with longer chains is more potent than those with shorter chains in suppressing LPS-induced iNOS expression. In addition, poly(P decreased LPS-induced NO release. Moreover, poly(P suppressed iNOS mRNA expression induced by LPS stimulation, thereby indicating that poly(P reduces LPS-induced iNOS expression by down-regulation at the mRNA level. In contrast, poly(P did not affect the LPS-induced release of TNF, another inflammatory mediator. Poly(P may serve as a regulatory factor of innate immunity by modulating iNOS expression in macrophages.

  12. TERMOS AMBIENTAIS E SOCIAIS NOS RELATÓRIOS DA ADMINISTRAÇÃO

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    Ilse Maria Beuren

    2012-07-01

    Full Text Available O estudo objetiva verificar a tendência dos termos ambientais e sociais evidenciados nos relatórios da administração de 1997 a 2006 de empresas familiares brasileiras. Realizou-se pesquisa exploratória, com abordagem qualitativa, por meio de pesquisa documental e da técnica de análise de conteúdo nos RA de 1997 a 2006. No universo das 500 maiores empresas listadas na Revista Exame, edição 2006, identificaram-se 21 empresas familiares de capital aberto e de controle acionário brasileiro, mas dessas somente 16 publicaram seu RA nos dez anos considerados. Os resultados mostram que a oscilação na quantidade de páginas dos RA ao longo dos anos apresenta relação com algum evento ocorrido nas empresas. A evidenciação dos termos ambientais está mais relacionada às medidas tomadas para cuidar e preservar o meio ambiente do que aos passivos ambientais. A evidenciação dos termos sociais foi direcionada de maneira equilibrada ao público interno e externo. Conclui-se que há uma tendência nos termos ambientais e sociais evidenciados nos RA de 1997 a 2006 das empresas pesquisadas, ainda que tenham sido incorporados vários termos novos ao longo do período.

  13. Impact of historical science short stories on students' attitudes and NOS understanding

    Science.gov (United States)

    Hall, Garrett

    This study examines the impact of historical short stories on upper and lower level high school chemistry students in the second semester of a two-semester course at a large Midwestern suburban school. Research focused on improved understanding of six fundamental nature of science (NOS) concepts made explicit in the stories, recollection of historical examples from the stories that supported student NOS thinking; student attitudes toward historical stories in comparison to traditional textbook readings as well as student attitudes regarding scientists and the development of science ideas. Data collection included surveys over six NOS concepts, attitudes towards science and reading, and semi-structured interviews. Analysis of the data collected in this study indicated significant increases in understanding for three of the six NOS concepts within the upper-level students and one of the six concepts for lower level students. Students were able to draw upon examples from the stories to defend their NOS views but did so more frequently when responding verbally in comparison to written responses on the surveys. The analysis also showed that students in both levels would rather utilize historical short stories over a traditional textbook and found value in learning about scientists and how scientific ideas are developed.

  14. Interaction of nNOS with PSD-95 negatively controls regenerative repair after stroke.

    Science.gov (United States)

    Luo, Chun-Xia; Lin, Yu-Hui; Qian, Xiao-Dan; Tang, Ying; Zhou, Hai-Hui; Jin, Xing; Ni, Huan-Yu; Zhang, Feng-Yun; Qin, Cheng; Li, Fei; Zhang, Yu; Wu, Hai-Yin; Chang, Lei; Zhu, Dong-Ya

    2014-10-01

    Stroke is a major public health concern. The lack of effective therapies heightens the need for new therapeutic targets. Mammalian brain has the ability to rewire itself to restore lost functionalities. Promoting regenerative repair, including neurogenesis and dendritic remodeling, may offer a new therapeutic strategy for the treatment of stroke. Here, we report that interaction of neuronal nitric oxide synthase (nNOS) with the protein postsynaptic density-95 (PSD-95) negatively controls regenerative repair after stroke in rats. Dissociating nNOS-PSD-95 coupling in neurons promotes neuronal differentiation of neural stem cells (NSCs), facilitates the migration of newborn cells into the injured area, and enhances neurite growth of newborn neurons and dendritic spine formation of mature neurons in the ischemic brain of rats. More importantly, blocking nNOS-PSD-95 binding during the recovery stage improves stroke outcome via the promotion of regenerative repair in rats. Histone deacetylase 2 in NSCs may mediate the role of nNOS-PSD-95 association. Thus, nNOS-PSD-95 can serve as a target for regenerative repair after stroke. Copyright © 2014 the authors 0270-6474/14/3413535-14$15.00/0.

  15. Sociodemographic, neuropsychiatric and cognitive characteristics of pathological gambling and impulse control disorders NOS in Parkinson's disease.

    Science.gov (United States)

    Pontieri, Francesco E; Assogna, Francesca; Pellicano, Clelia; Cacciari, Claudia; Pannunzi, Sara; Morrone, Annalucia; Danese, Emanuela; Caltagirone, Carlo; Spalletta, Gianfranco

    2015-01-01

    Despite of previous evidence supporting the association between impulse control disorder (ICD) and several demographic, clinical and therapeutic features in Parkinson's disease (PD), the relationships between pathological gambling (PG) or other variants of ICD (ICD-NOS) and specific neuropsychiatric or cognitive domains are not entirely defined. In this study, 155 PD patients without dementia or cognitive impairment underwent: i. the ICD diagnoses, using the Questionnaire for Impulsive-Compulsive Disorders, ii. the mood and anxiety disorders diagnoses, according to the DSM-IV-TR criteria, and iii. a comprehensive battery for measuring severity of psychopathology and neuropsychology domains. Patients were divided in those with pathological gambling (PG), ICDs not otherwise specified (ICD-NOS), or the lack of ICD (No-ICD). There was a progression in age and age at onset from the younger PG subjects throughout ICD-NOS to No-ICD. PG and ICD-NOS subjects had longer disease duration and were taking significantly higher dosages of antiparkinsonian drugs than No-ICD ones. PG subjects had significantly higher severity of depressive and anxious symptoms with respect to the other 2 groups. Both PG and ICD-NOS subjects suffer from increased severity of psychotic symptoms than No-ICD ones. The 3 groups did not differ in any cognitive measure. Our results support the concept that the different sociodemographic and neuropsychiatric profiles of PD patients are associated with different ICDs. Moreover, we clearly demonstrate the lack of relationship between ICD and cognitive performances in undemented PD patients.

  16. NOS3 Variants, Physical Activity, and Blood Pressure in the European Youth Heart Study

    DEFF Research Database (Denmark)

    Grøntved, Anders; Andersen, Lars Bo; Franks, Paul W

    2011-01-01

    BackgroundIn this study, we examined the influence of genetic variation in NOS3 on resting blood pressure (BP) in children and adolescents from the European Youth Heart Study (EYHS). Because the NOS3 gene expression is altered by physical activity (PA), we also tested for interaction between...... habitual PA and NOS3 variants on BP.MethodsA cross-sectional, random sample of 8-10-year old children (n = 1,214) and 14-16-year old adolescents (n = 1,141) from Denmark and Estonia were genotyped for four NOS3 tagging polymorphisms (rs1800783, rs1799983 (Glu298Asp), rs3918227, rs743507). PA was measured...... in inactive individuals. However, none of the interactions persisted after correcting for multiple testing.ConclusionsThe NOS3 Glu298Asp variant may associate with resting BP in adolescence but not in childhood, an effect that could be modified by PA.American Journal of Hypertension (2011). doi:10.1038/ajh...

  17. Association between Alzheimer's disease and the NOS3 gene Glu298Asp polymorphism.

    Science.gov (United States)

    Hua, Ye; Zhao, Hui; Kong, Yuenan; Lu, Xiaojie

    2014-04-01

    The Glu298Asp gene polymorphism in NOS3 gene has been extensively investigated for association to Alzheimer's disease (AD), however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of NOS3 Glu298Asp polymorphism and AD risk by using meta-analysis. All eligible case-control studies were searched in PubMed and Embase. Odds ratios (OR) with the 95% confidence intervals (CI) were used to assess the association. A total of 5522 cases and 4877 controls in 20 case-control studies were included. Obvious heterogeneity among studies was detected, and no significant association was observed between the NOS3 Glu298Asp polymorphism and AD risk. After exclusion of three studies, the heterogeneity disappeared and still no association was observed. In the subgroup analysis by ethnicity, we did not find any significant association between this polymorphism and AD risk in both Asians and Caucasians. This meta-analysis suggested that the NOS3 Glu298Asp gene polymorphism is not a strong risk factor for AD. To further evaluate gene-to-gene and gene-to-environmental interactions between polymorphisms of NOS3 gene and AD risk, more studies with large groups of patients are required.

  18. Nitric oxide synthase 2 (NOS2) expression in histologically normal margins of oral squamous cell carcinoma.

    Science.gov (United States)

    Morelatto, Rosana; Itoiz, María-Elina; Guiñazú, Natalia; Piccini, Daniel; Gea, Susana; López-de Blanc, Silvia

    2014-05-01

    The activity of Nitric Oxide Synthase 2 (NOS2) was found in oral squamous cell carcinomas (OSCC) but not in normal mucosa. Molecular changes associated to early carcinogenesis have been found in mucosa near carcinomas, which is considered a model to study field cancerization. The aim of the present study is to analyze NOS2 expression at the histologically normal margins of OSCC. Eleven biopsy specimens of OSCC containing histologically normal margins (HNM) were analyzed. Ten biopsies of normal oral mucosa were used as controls. The activity of NOS2 was determined by immunohistochemistry. Salivary nitrate and nitrite as well as tobacco and alcohol consumption were also analyzed. The Chi-squared test was applied. Six out of the eleven HNM from carcinoma samples showed positive NOS2 activity whereas all the control group samples yielded negative (p=0.005). No statistically significant association between enzyme expression and tobacco and/or alcohol consumption and salivary nitrate and nitrite was found. NOS2 expression would be an additional evidence of alterations that may occur in a state of field cancerization before the appearance of potentially malignant morphological changes.

  19. Comparação entre indivíduos hemiparéticos com e sem histórico de quedas com base nos componentes da Classificação Internacional de Funcionalidade, Incapacidade e Saúde Comparison between post-stroke hemiparetic subjects with and without history of falls on the basis of the International Classification of Functioning, Disability and Health

    Directory of Open Access Journals (Sweden)

    Christina Danielli Coelho de Morais Faria

    2010-09-01

    Full Text Available O objetivo deste estudo foi comparar hemiparéticos com e sem histórico de quedas nos últimos seis meses (caidores e não-caidores segundo os componentes da Classificação Internacional de Funcionalidade, Incapacidade e Saúde. Dezesseis hemiparéticos não-caidores (62,3±16,6 anos, com tempo de acidente vascular encefálico (AVE de 38,0±48,3 meses, e 16 caidores (61,0±17,0 anos, tempo de AVE de 48,0±50,7 meses, de ambos os sexos, comunitários e deambuladores, foram avaliados quanto a funções e estruturas do corpo (torque do músculo quadríceps do lado parético e escala de depressão geriátrica, atividade - velocidade de marcha (VM natural e máxima, teste de levantar e caminhar cronometrado (timed up & go e escala de equilíbrio de Berg - e participação (pelo perfil de saúde de Nottingham e escala de qualidade de vida específica para AVE. Os dados foram tratados estatisticamente, com nível de significância αThe aim of this study was to compare post-stroke hemiparetic subjects with and without history of falls over the last six months by using the International Classification of Functioning, Disability and Health (ICF components. Sixteen community-dwelling hemiparetic subjects without history of falls (62.3±16.6 years, time since stroke 38±48.3 months, and 16 with history of fall(s (60.9±17 years, time since stroke 47.9±50.8 months of both sexes and able to walk, with or without assistive devices, were assessed as to ICF components body functions and structures (torque of the paretic limb quadriceps muscle and depression, by the geriatric depression scale, activities (natural and maximal gait speed, timed up-and-go test and Berg balance scale, and participation (by the Nottingham health profile and the stroke-specific quality of life scale. Groups were statistically compared at significance level α<0.05. No statistically significant differences were found between the groups as to age, gender or time since stroke (0.56

  20. Nitric oxide synthase (NOS) in the trigeminal vascular system and other brain structures related to pain in rats

    DEFF Research Database (Denmark)

    Ramachandran, Roshni; Ploug, Kenneth Beri; Hay-Schmidt, Anders;

    2010-01-01

    Nitric oxide (NO) is considered to be a key mediator in the pathophysiology of migraine but the localisation of NO synthesizing enzymes (NOS) throughout the pain pathways involved in migraine has not yet been fully investigated. We have used quantitative real-time PCR and Western blotting...... to measure the respective levels of mRNA and protein for nNOS and eNOS in peripheral and central tissues involved in migraine pain: dura mater, pial arteries, trigeminal ganglion (TG) trigeminal nucleus caudalis (TNC), periaqueductal grey (PAG), thalamus, hypothalamus, cortex, pituitary gland, hippocampus...... concentration in cortex. The same pattern of expression was also observed with the eNOS protein. In conclusion, we found both nNOS and eNOS located to areas relevant to migraine supporting the involvement of NO in migraine mechanisms....

  1. Experiência e imagens da infância nos contos de Miguel Sanches Neto

    OpenAIRE

    Alzira Fabiana de Christo

    2013-01-01

    O tema desta tese é compreender a representação da infância nos contos de Miguel Sanches Neto a partir da fundamentação teórica que entende a experiência da infância como possibilidade para a mudança da sociedade e os rumos da própria História. Diante da vasta produção de pesquisa sobre a infância – quase sempre ligada a aspectos cronológicos e históricos – e sua relação com a arte e a literatura, nos pareceu importante investigar um campo que ainda vem ganhando espaço nos estudos literários:...

  2. Comparison of AFITPAC versus NOS and a packet radio network design

    Science.gov (United States)

    Iannelli, Thomas A.

    1991-12-01

    This thesis encompasses two themes: (1) A comparison of the Network Operating System (NOS) software package, developed by Phil Karn and others, and AFITPAC, written by Marsh and Geier at the Air Force Institute of Technology. The comparison is based on the Air Force Logistics Command's requirements for the development of a Packet Radio Network program. The results of the comparison are a recommendation that use of the NOS package be pursued because it can meet all twelve of the requirements and compiles with five of the Military Standard Protocols. (2) The design of a personal computer Packet Radio Network Simulator used to analyze the network performance of AFITPAC and NOS is proposed. The proposal concludes with a discussion of problems in development of the simulation which used MODSIM IITM, C++, and a 80386/25Mhz personal computer. Recommendations are made for pursuing the simulation effort on other hardware platforms and for improvements to the design.

  3. Reflexões sobre o pesquisador nas trilhas da Teoria Fundamentada nos Dados

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    Joséte Luzia Leite

    2012-06-01

    Full Text Available Estudo de natureza descritivo-reflexiva, objetivando apresentar as características do pesquisador que utiliza o método Teoria Fundamentada nos Dados e delinear reflexões sobre o desenvolvimento das aptidões do pesquisador para tornar-se um Teórico Fundamentado. A discussão teórica foi embasada nos referenciais dessa metodologia e apoiada na literatura. O artigo apresenta as principais demandas de estudos qualitativos com a Grounded Theory e importantes comportamentos, atitudes e características desenvolvidas pelos pesquisadores. Constata-se que a aprendizagem acerca da Teoria Fundamentada nos Dados vai além da habilidade para operacionalizar um conjunto de procedimentos e técnicas. Implica, também, em desafios de transformação na postura como pesquisador e em novas formas de pensar e pesquisar, reunindo conhecimentos a partir dos dados para formar uma teoria.

  4. AFLATOXINAS - ASPECTOS CLÍNICOS E TOXICOLÓGICOS EM SUÍNOS

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    Carlos Augusto Mallmann

    1994-12-01

    Full Text Available Aflatoxinas são metabólitos fúngicos produzidos por linhagens de Aspergillus flavus var. parasiticus encontrados ubiquitariamente nos substratos alimentares que compõe a dieta dos suínos. A aflatoxicose dos suínos é uma doença dependente da dose ingerida e do tempo de exposição, caracterizando-se principalmente pela atividade hepatotóxica desta micotoxina. Na suinocultura os maiores problemas são provocados por doses subclínicas onde esta intoxicação se manifesta na forma de prejuízos sobre o desempenho traduzidos principalmente por uma baixa conversão alimentar e por imunodepressão.

  5. Mild mitochondrial uncoupling and calorie restriction increase fasting eNOS, akt and mitochondrial biogenesis.

    Directory of Open Access Journals (Sweden)

    Fernanda M Cerqueira

    Full Text Available Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR. Since treatment of mice with dinitrophenol (DNP promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis.

  6. Characterization of iNOS+ Neutrophil-like ring cell in tumor-bearing mice

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    Virtuoso Lauren P

    2012-07-01

    Full Text Available Abstract Background Myeloid-derived Suppressor Cells (MDSC have been identified as tumor-induced immature myeloid cells (IMC with potent immune suppressive activity in cancer. Whereas strict phenotypic classification of MDSC has been challenging due to the highly heterogeneous nature of cell surface marker expression, use of functional markers such as Arginase and inducible nitric oxide synthase (iNOS may represent a better categorization strategy. In this study we investigated whether iNOS could be utilized as a specific marker for the identification of a more informative homogenous MDSC subset. Methods Single-cell suspensions from tumors and other organs were prepared essentially by enzymatic digestion. Flow cytometric analysis was performed on a four-color flow cytometer. Morphology, intracellular structure and localization of iNOS+ ring cells in the tumor were determined by cytospin analysis, immunofluorescence microscopy and immunohistochemistry, respectively. For functional analysis, iNOS+ ring subset were sorted and tested in vitro cell culture experiments. Pharmacologic inhibition of iNOS was performed both in vivo and in vitro. Results The results showed that intracellular iNOS staining distinguished a granular iNOS+ SSChi CD11b+ Gr-1dim F4/80+ subset with ring-shaped nuclei (ring cells among the CD11b+ Gr-1+ cell populations found in tumors. The intensity of the ring cell infiltrate correlated with tumor size and these cells constituted the second major tumor-infiltrating leukocyte subset found in established tumors. Although phenotypic analysis demonstrated that ring cells shared characteristics with tumor-associated macrophages (TAM, morphological analysis revealed a neutrophil-like appearance as detected by cytospin and immunofluorescence microscopy analysis. The presence of distinct iNOS filled granule-like structures located next to the cell membrane suggested that iNOS was stored in pre-formed vesicles and available for rapid

  7. Role of Endothelial Nitric Oxide Synthase in Diabetic Nephropathy: Lessons from Diabetic eNOS Knockout Mice

    OpenAIRE

    Takamune Takahashi; Harris, Raymond C.

    2014-01-01

    Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in many countries. The animal models that recapitulate human DN undoubtedly facilitate our understanding of this disease and promote the development of new diagnostic markers and therapeutic interventions. Based on the clinical evidence showing the association of eNOS dysfunction with advanced DN, we and others have created diabetic mice that lack eNOS expression and shown that eNOS-deficient diabetic mice exhibit advan...

  8. Religião e patriotismo: o anticomunismo católico nos Estados Unidos e no Brasil nos anos da Guerra Fria

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    Carla Simone Rodeghero

    2002-01-01

    Full Text Available O artigo analisa e compara o anticomunismo católico no Brasil e nos Estados Unidos no período da Guerra Fria. Depois de situar o campo de estudos constituído no Brasil sobre o tema, discute as relações entre americanismo e anticomunismo, procurando situar o catolicismo norte-americano neste meio. Utiliza-se de uma produção recente sobre cultura da Guerra Fria nos Estados Unidos. Levanta, finalmente, uma série de elementos de comparação sobre a forma que o anticomunismo católico assumiu nos dois países.This article analyses and compares the Catholic anticommunism in the Brazil and in United States during the Cold War years. After showing the recent studies produced in Brazil about the fight against communism, it discusses the relationship between Americanism, anticommunism and Catholicism. This step is based on recent historical research about the Cold War culture in the United States. Finally, it makes comparisons between the forms that anticommunism assumed in each country.

  9. Effects of Paracetamol on NOS, COX, and CYP Activity and on Oxidative Stress in Healthy Male Subjects, Rat Hepatocytes, and Recombinant NOS

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    Arne Trettin

    2014-01-01

    Full Text Available Paracetamol (acetaminophen is a widely used analgesic drug. It interacts with various enzyme families including cytochrome P450 (CYP, cyclooxygenase (COX, and nitric oxide synthase (NOS, and this interplay may produce reactive oxygen species (ROS. We investigated the effects of paracetamol on prostacyclin, thromboxane, nitric oxide (NO, and oxidative stress in four male subjects who received a single 3 g oral dose of paracetamol. Thromboxane and prostacyclin synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1α, respectively. Endothelial NO synthesis was assessed by measuring nitrite in plasma. Urinary 15(S-8-iso-prostaglanding F2α was measured to assess oxidative stress. Plasma oleic acid oxide (cis-EpOA was measured as a marker of cytochrome P450 activity. Upon paracetamol administration, prostacyclin synthesis was strongly inhibited, while NO synthesis increased and thromboxane synthesis remained almost unchanged. Paracetamol may shift the COX-dependent vasodilatation/vasoconstriction balance at the cost of vasodilatation. This effect may be antagonized by increasing endothelial NO synthesis. High-dosed paracetamol did not increase oxidative stress. At pharmacologically relevant concentrations, paracetamol did not affect NO synthesis/bioavailability by recombinant human endothelial NOS or inducible NOS in rat hepatocytes. We conclude that paracetamol does not increase oxidative stress in humans.

  10. Neuronal nitric oxide synthase (nNOS, NOS1) rs693534 and rs7977109 variants and risk for restless legs syndrome.

    Science.gov (United States)

    Jiménez-Jiménez, Félix Javier; Alonso-Navarro, Hortensia; Martínez, Carmen; Zurdo, Martín; Turpín-Fenoll, Laura; Millán-Pascual, Jorge; Adeva-Bartolomé, Teresa; Cubo, Esther; Navacerrada, Francisco; Rojo-Sebastián, Ana; Rubio, Lluisa; Calleja, Marisol; Plaza-Nieto, José Francisco; Pilo-de-la-Fuente, Belén; Arroyo-Solera, Margarita; García-Albea, Esteban; García-Martín, Elena; Agúndez, José A G

    2015-06-01

    Several biochemical, neuropathological, and experimental data suggest a possible role of nitric oxide (NO) in the pathophysiology of restless legs syndrome (RLS). Two single nucleotide polymorphisms (SNPs) neuronal nitric oxide synthase (nNOS or NOS1) gene (rs7977109 and rs693534) have been found to be associated with the risk for RLS in Germans, although only one of them (rs7977109) remained as significant after multiple comparison tests. The aim of our study was to replicate the possible association between these SNPs and risk for RLS in the Spanish population. We studied the allelic and genotype frequencies of the SNPs rs7977109 and rs693534 in 205 patients with RLS and 328 healthy controls using TaqMan genotyping. The rs7977109 and rs693534 genotypes and allelic frequencies did not significantly differ between patients with RLS and controls and were unrelated with the age at onset of RLS, gender, ferritin levels, and response to dopaminergic or gabaergic agents. The rs7999109GA genotype was overrepresented in RLS patients with positive family history of RLS, and in patients with symptomatic response to clonazepam. The results of our study suggest that these two NOS1 SNPs are not related to the overall risk for RLS in the Spanish population.

  11. Key role of endothelium in the eNOS-dependent cardioprotection with exercise training.

    Science.gov (United States)

    Farah, C; Nascimento, A; Bolea, G; Meyer, G; Gayrard, S; Lacampagne, A; Cazorla, O; Reboul, C

    2017-01-01

    Modulation of endothelial nitric oxide synthase (eNOS) activation is recognized as a main trigger of the cardioprotective effects of exercise training on heart vulnerability to ischemia-reperfusion (IR). However, this enzyme is expressed both in coronary endothelial cells and cardiomyocytes and the contribution of each one to such cardioprotection has never been challenged. The aim of this study was to investigate the role of eNOS from the cardiomyocytes vs. the endothelium in the exercise cardioprotection. Male Wistar rats were assigned to a chronic aerobic training (Ex) (vs. sedentary group; Sed) and we investigated the role of eNOS in the effects of exercise on sensitivity to IR or anoxia-reoxygenation (A/R) at whole heart, isolated cardiomyocytes and left coronary artery (LCA) levels. We observed that exercise increased eNOS activation (Ser1177 phosphorylation) and protein S-nitrosylation in whole heart but not at cardiomyocyte level, suggesting the specific target of endothelial cells by exercise. Consistently, in isolated cardiomyocytes submitted to the A/R procedure, exercise reduced cell death and improved cells contractility, but independently of the eNOS pathway. Next, to evaluate the contribution of endothelial cells in exercise cardioprotection, LCA were isolated before and after an IR procedure performed on Langendorff hearts. Exercise improved basal relaxation sensitivity to acetylcholine and markedly reduced the alteration of endothelium-dependent coronary relaxation induced by IR. Furthermore, inactivation of coronary endothelial cells activity just before IR, obtained with a bolus of Triton X-100, totally suppressed cardioprotective effects of exercise on both left ventricular functional recovery after IR and infarct size, whereas no effect of Triton X-100 was observed in Sed group. In conclusion, these results show that coronary endothelial cells rather than cardiomyocytes play a key role in the eNOS-dependent cardioprotection of exercise.

  12. ROS mediated cytotoxicity of porcine adrenocortical cells induced by QdNOs derivatives in vitro.

    Science.gov (United States)

    Huang, Xian-Ju; Zhang, Hua-Hai; Wang, Xu; Huang, Ling-Li; Zhang, Ling-Yan; Yan, Cai-Xia; Liu, Yu; Yuan, Zong-Hui

    2010-05-14

    Quinoxaline 1,4-dioxides (QdNOs) derivatives, the potent synthetic antibacterial group used in food-producing animals, are assumed to have pro-oxidant properties. However, how oxidative stress mediated their adrenal toxicity is far from clear. The aim of this study was to assess the ability of three QdNOs, i.e. olaquindox (OLA), mequindox (MEQ), and cyadox (CYA), to produce reactive oxygen species (ROS) and oxidative cell damage in porcine adrenocortical cells. Multiple approaches such as cell activity assay, biochemical detectation, flow cytometry and fluorescent were used to study the integrated role of ROS homeostasis, mitochondrial redox metabolism and cell apoptosis as well as chemical stability of these drugs. The results showed that OLA and MEQ treatment evoked a significant dose and time-dependent cell damage in adrenocortical cells, well CYA displayed much less toxicity. As for the intracellular ROS production, OLA irritated a persistent and utmost release of ROS while MEQ made a similar but weaker reaction. CYA, however, had a short and unstable release of intracellular ROS. On the other hand, quinoxalinine-2-carboxylie acid (QCA), one of the metabolites of OLA and MEQ, did not cause any significant production of ROS and showed relatively lower toxicity than its parents. Moreover, an imbalance in the redox metabolism and mitochondrial membrane damage has been implicated in adrenal toxicity of QdNOs. ROS scavengers partially reversed QdNOs-induced mitochondrial damage, indicating that mitochondria may be a major target and critical for ROS-mediated cell death. In a word, these results suggested that ROS is a key mediator of QdNOs-induced cell death via mitochondria-dependent pathway in adrenocortical cells. The results provide a mechanism approach in understanding the characterize of adrenal damage caused by QdNOs in vitro, which would in turn, help in designing the appropriate therapeutic strategies of these kind of feed additives.

  13. Intoxicação experimental de suínos por fumonisinas

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    Dilkin Paulo

    2004-01-01

    Full Text Available Os efeitos da exposição oral prolongada (28 dias à fumonisina foram estudados em suínos jovens. Os animais foram divididos em três grupos experimentais e alimentados com ração ad libitum contendo: A 0mg de FB1.kg-1 (controle; B 10mg de FB1.kg-1; C 30mg de FB1.kg-1. Os suínos foram observados duas vezes por dia; seus pesos e consumo alimentar foram registrados semanalmente. Entre o 20º e 24º dia de intoxicação, os suínos do tratamentos C apresentaram diminuição do consumo de ração e ganho de peso, sinais característicos de edema pulmonar, razão pela qual um animal foi levado a óbito aos 23 dias de intoxicação. Após 28 dias, os animais foram necropsiados e os órgãos submetidos a análises macroscópica, histopatológica e ao estudo da morfologia e histologia intestinal. Nos suínos que apresentaram sinais clínicos de intoxicação, observaram-se lesões pulmonares, hepáticas e diminuição de altura das vilosidades e profundidade das criptas e hiperplasia glandular em segmentos intestinais. Conclui-se, portanto, que substanciais perdas de produtividade podem ser induzidas em suínos alimentados com ração contaminada com baixos níveis de fumonisinas.

  14. Association between NOS3 genetic variants and coronary artery disease in the Han population.

    Science.gov (United States)

    Zhao, G L; Li, Q J; Lu, H Y

    2016-06-03

    The enzyme endothelial nitric oxide synthase (NOS3) is an important mediator of atherosclerotic disease and is associated with coronary artery disease (CAD). There is growing evidence that polymorphisms in NOS3 influence the progression of CAD; however, there is also a controversy regarding the association of polymorphisms in the gene encoding NOS3 and CAD. To determine if the NOS3 genetic variants are associated with CAD in the Han Chinese, we examined the potential association between CAD and eight single nucleotide polymorphisms (rs1799983, rs2070744, rs11771443, rs3918188, rs2853796, rs7830, rs1541861, and rs2853792) of the NOS3 using the MassARRAY system. The allelic and genotypic frequencies of the rs1799983 (promoter regions) and rs2070744 (intron 1) polymorphisms in patients with CAD were significantly different from those in healthy controls. These patients had significantly higher frequencies of the rs1799983 T allele (χ2 = 7.717, P = 0.007, OR = 1.649, 95%CI = 1.41-2.382) and the rs2070744 G allele (χ2 = 4.548, P = 0.033, OR = 1.490, 95%CI = 1.031-2.153). Strong linkage disequilibrium was observed in three blocks (D' > 0.9). In block 1, significantly more T-T-C haplotypes (χ2 = 5.537, P = 0.019, OR = 0.632, 95%CI = 0.430-0.927) were found in controls. These findings point to a role for NOS3 polymorphisms in CAD in the Chinese Han population, and may be useful for future investigations on the pathogenesis of CAD.

  15. Localization of NOS-like protein in guard cells of Vicia faba L. And its possible function

    Institute of Scientific and Technical Information of China (English)

    LIU Xin; WANG YouQun; JIA WenSuo; LOU ChengHou; ZHANG ShuQiu

    2007-01-01

    Using the immuno-fluorescence and immuno-gold electron microscope technology, localization of nitric oxide synthase (NOS)-like proteins was determined in guard cells of Vicia faba L. NOS is mainly localized in nucleus, cytoplasm, chloroplast, mitochondria and the cell wall of guard cells. Scorch and exogenous JA can enhance the level of nitric oxide (NO) and increase NOS activity in both leaf and epidermis, and the changing pattern of NOS activity was consistent with the change of NO. NOS inhibitor, L-NAME, inhibited JA-induced NO generation. From the results, we presumed that NO generation from NOS pathway is the main pathway in the stress and JA responses. The pharmacological experiment showed that increasing the Ca2+ at a suitable concentration promoted leaf NOS activity and the NO level, indicating that NOS activity together with the distribution of NO is Ca2+-dependent. NOS and NO are possibly involved in the regulation of stomatal movement thus playing an important role in plant stress responses.

  16. Acute Myeloid Leukemia NOS | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available abel Study of Sargramostim Among Patients Receiving Myelosuppressive Induction Chemotherapy for Acute Myelog...g Myelosuppressive Induction Chemotherapy for Acute Myelogenous Leukemia A.4.1Sponsor's protocol code number...r disease under investigation E.1.1Medical condition(s) being investigated Acute ...Myeloid Leukemia NOS E.1.1.1Medical condition in easily understood language Acute Myeloid Leukemia NOS E.1.1...r investigation E.1.2Version 18.0 E.1.2Level PT E.1.2Classification code 10000880 E.1.2Term Acute

  17. Brucelose em suínos : estudo caso no distrito de Castelo Branco

    OpenAIRE

    Martins, Manuel Vicente de Freitas

    1993-01-01

    Foi realizado um estudo sobre a brucelose em suínos no distrito de Castelo Branco. De 1920 sangues colhidos no matadouro, 4,3 % dos soros foram positivos no teste do Rosa Bengala, enquanto apenas 0,68 % apresentaram títulos positivos (1+ ou mais na diluição 1:8) ao teste da Fixação do Complemento. Nenhum soro foi classificado como positivo no teste de Aglutinação Lenta em Tubo. Foram colhidos amostras de orgãos em 202 animais, 122 reprodutores e 80 suínos de engorda, não tendo sido isolada...

  18. A vast amount of various invariant tori in the Nosé-Hoover oscillator

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lei [School of Mathematics and Statistics, Huazhong University of Science and Technology, Wuhan 430074 (China); Department of Mathematics and Physics, Hefei University, Hefei 230601 (China); Yang, Xiao-Song, E-mail: yangxs@hust.edu.cn [School of Mathematics and Statistics, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2015-12-15

    This letter restudies the Nosé-Hoover oscillator. Some new averagely conservative regions are found, each of which is filled with different sequences of nested tori with various knot types. Especially, the dynamical behaviors near the border of “chaotic region” and conservative regions are studied showing that there exist more complicated and thinner invariant tori around the boundaries of conservative regions bounded by tori. Our results suggest an infinite number of island chains in a “chaotic sea” for the Nosé-Hoover oscillator.

  19. O papel de imunoglobulinas na nefropatia da leptospirose em suínos

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    Larissa M.F. Gonçalves

    2014-06-01

    Full Text Available A leptospirose é uma antropozoonose endêmica em todo o mundo, que afeta o homem e várias espécies de animais domésticos e silvestres. No início da infecção há produção de IgM para o controle da infecção e após alguns dias, IgG são produzidas e provocam lise das leptospiras circulantes. Objetivou-se neste estudo identificar depósitos de antígeno de leptospiras e imunoglobulinas no tecido renal, para avaliar o papel de imunoglobulinas na patogênese da nefropatia da leptospirose em suínos. Foram colhidas 139 amostras de sangue e rim de suínos das cidades de Teresina/PI e Timon/MA, que foram avaliadas pela SAM, imunoistoquímica e PCR. Nefrite intersticial, fibrose, vasculite, tumefação do tufo glomerular e hipercelularidade difusa foram as principais alterações histopatológicas encontradas. A imunoistoquímica detectou antígeno de leptospira em 60 suínos. Depósitos de IgG, IgM e IgA foram observados no endotélio de capilares glomerulares, dos capilares intertubulares e na cápsula de Bowman, com marcação focal, difusa, global e segmentar. A deposição de IgM e IgA foi significantemente maior nos suínos infectados. Estranhamente depósitos de IgG foi significantemente maior nos suínos não infectados, onde não havia presença de antígeno de leptospiras e nem lesão túbulo-intersticial. Concluímos que antígeno de leptospiras no rim de suínos está relacionado a depósitos de IgM e IgA mas não a depósitos de IgG.

  20. Circulating NOS3 modulates left ventricular remodeling following reperfused myocardial infarction.

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    Simone Gorressen

    Full Text Available Nitric oxide (NO is constitutively produced and released from the endothelium and several blood cell types by the isoform 3 of the NO synthase (NOS3. We have shown that NO protects against myocardial ischemia/reperfusion (I/R injury and that depletion of circulating NOS3 increases within 24 h of ischemia/reperfusion the size of myocardial infarction (MI in chimeric mice devoid of circulating NOS3. In the current study we hypothesized that circulating NOS3 also affects remodeling of the left ventricle following reperfused MI.To analyze the role of circulating NOS3 we transplanted bone marrow of NOS3-/- and wild type (WT mice into WT mice, producing chimerae expressing NOS3 only in vascular endothelium (BC-/EC+ or in both, blood cells and vascular endothelium (BC+/EC+. Both groups underwent 60 min of coronary occlusion in a closed-chest model of reperfused MI. During the 3 weeks post MI, structural and functional LV remodeling was serially assessed (24 h, 4 d, 1 w, 2 w and 3 w by echocardiography. At 72 hours post MI, gene expression of several extracellular matrix (ECM modifying molecules was determined by quantitative RT-PCR analysis. At 3 weeks post MI, hemodynamics were obtained by pressure catheter, scar size and collagen content were quantified post mortem by Gomori's One-step trichrome staining.Three weeks post MI, LV end-systolic (53.2±5.9 μl; ***p≤0.001; n = 5 and end-diastolic volumes (82.7±5.6 μl; *p<0.05; n = 5 were significantly increased in BC-/EC+, along with decreased LV developed pressure (67.5±1.8 mm Hg; n = 18; ***p≤0.001 and increased scar size/left ventricle (19.5±1.5%; n = 13; **p≤0.01 compared to BC+/EC+ (ESV: 35.6±2.2 μl; EDV: 69.1±2.6 μl n = 8; LVDP: 83.2±3.2 mm Hg; n = 24; scar size/LV13.8±0.7%; n = 16. Myocardial scar of BC-/EC+ was characterized by increased total collagen content (20.2±0.8%; n = 13; ***p≤0.001 compared to BC+/EC+ (15.9±0.5; n = 16, and increased collagen type I and III subtypes

  1. Tetrahydrobiopterin (BH4), a cofactor for nNOS, restores gastric emptying and nNOS expression in female diabetic rats.

    Science.gov (United States)

    Gangula, Pandu R R; Mukhopadhyay, Sutapa; Ravella, Kalpana; Cai, Shijie; Channon, Keith M; Garfield, Robert E; Pasricha, Pankaj J

    2010-05-01

    Gastroparesis is a debilitating disease predominantly affecting young women. Recently, dysregulation of neuronal nitric oxide synthase (nNOS) in myenteric plexus neurons has been implicated for delayed solid gastric emptying/gastroparesis in diabetic patients. In this study, we have explored the role of tetrahydrobiopterin (BH4), a major cofactor for nNOS activity and NO synthesis in diabetic gastroparesis. Diabetes was induced with single injection of streptozotocin (55 mg/kg body wt, ip) in female rats, with experiments performed on week 3 or 9 following induction, with or without 3-wk BH4 supplementation. Gastric pyloric BH4 levels were significantly decreased in diabetic female rats compared with control (18.6 +/- 1.45 vs. 31.0 +/- 2.31 pmol/mg protein). In vitro studies showed that 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of BH4 synthesis, significantly decreased gastric NO release and nitrergic relaxation. Three-week dietary supplementation of BH4 either from day 1 or week 6 significantly attenuated diabetes-induced delayed gastric emptying for solids (3 wk: BH4, 67 +/- 6.7 vs. diabetic, 36.05 +/- 7.09; 9 wk: BH4, 57 +/- 8.45 vs. diabetic, 33 +/- 9.91) and diabetes-induced reduction in pyloric nNOS-alpha protein expression in female rats. Supplementation of BH4 significantly restored gastric nNOS-alpha dimerization in 9-wk-old diabetic female rats. In addition, BH4 treatment reversed (17.23 +/- 5.81 vs. 42.0 +/- 2.70 mmHg x s) the diabetes-induced changes in intragastric pressures (IGP) and gastric pyloric nitrergic relaxation (-0.62 +/- 0.01 vs. -0.22 +/- 0.07). BH4 deficiency plays a critical role in diabetes-induced alterations including delayed solid gastric emptying, increased IGP, reduced pyloric nitrergic relaxation, and nNOS-alpha expression in female rats. Supplementation of BH4 accelerates gastric emptying by restoring nitrergic system in diabetic female rats. Therefore, BH4 supplementation is a potential therapeutic option for female

  2. Carbon monoxide increases inducible NOS expression that mediates CO-induced myocardial damage during ischemia-reperfusion.

    Science.gov (United States)

    Meyer, Grégory; André, Lucas; Kleindienst, Adrien; Singh, François; Tanguy, Stéphane; Richard, Sylvain; Obert, Philippe; Boucher, François; Jover, Bernard; Cazorla, Olivier; Reboul, Cyril

    2015-04-01

    We investigated the role of inducible nitric oxide (NO) synthase (iNOS) on ischemic myocardial damage in rats exposed to daily low nontoxic levels of carbon monoxide (CO). CO is a ubiquitous environmental pollutant that impacts on mortality and morbidity from cardiovascular diseases. We have previously shown that CO exposure aggravates myocardial ischemia-reperfusion (I/R) injury partly because of increased oxidative stress. Nevertheless, cellular mechanisms underlying cardiac CO toxicity remain hypothetical. Wistar rats were exposed to simulated urban CO pollution for 4 wk. First, the effects of CO exposure on NO production and NO synthase (NOS) expression were evaluated. Myocardial I/R was performed on isolated perfused hearts in the presence or absence of S-methyl-isothiourea (1 μM), a NOS inhibitor highly specific for iNOS. Finally, Ca(2+) handling was evaluated in isolated myocytes before and after an anoxia-reoxygenation performed with or without S-methyl-isothiourea or N-acetylcystein (20 μM), a nonspecific antioxidant. Our main results revealed that 1) CO exposure altered the pattern of NOS expression, which is characterized by increased neuronal NOS and iNOS expression; 2) cardiac NO production increased in CO rats because of its overexpression of iNOS; and 3) the use of a specific inhibitor of iNOS reduced myocardial hypersensitivity to I/R (infarct size, 29 vs. 51% of risk zone) in CO rat hearts. These last results are explained by the deleterious effects of NO and reactive oxygen species overproduction by iNOS on diastolic Ca(2+) overload and myofilaments Ca(2+) sensitivity. In conclusion, this study highlights the involvement of iNOS overexpression in the pathogenesis of simulated urban CO air pollution exposure.

  3. The -786T>C promoter polymorphism of the NOS3 gene is associated with prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Goulart Luiz R

    2008-09-01

    Full Text Available Abstract Background There is no biological or epidemiological data on the association between NOS3 promoter polymorphisms and prostate cancer. The polymorphisms in the promoter region of NOS3 gene may be responsible for variations in the plasma NO, which may promote cancer progression by providing a selective growth advantage to tumor cells by angiogenic stimulus and by direct DNA damage. Methods This study aimed evaluating the NOS3 promoter polymorphisms by PCR-SSCP and sequencing, associating genotypes and haplotypes with NOS3 expression levels through semi-quantitative RT-PCR, and with PCA3 mRNA detection, a specific tumor biomarker, in the peripheral blood of pre-surgical samples from 177 patients; 83 PCa and 94 BPH. Results Three novel SNPs were identified -764A>G, -714G>T and -649G>A in the NOS3 gene promoter region, which together with the -786T>C generated four haplotypes (N, T, C, A. NOS3 gene expression levels were affected by the -786T>C polymorphism, and there was a 2-fold increase in NOS3 levels favored by the incorporation of each C allele. NOS3 levels higher than 80% of the constitutive gene expression level (B2M presented a 4-fold increase in PCa occurrence. Conclusion The -786T>C polymorphism was the most important promoter alteration of the NOS3 gene that may affect the PCa progression, but not its occurrence, and the incorporation of the C allele is associated with increased levels of NOS3 transcripts. The NOS3 transcript levels presented a bimodal behavior in tumor development and may be used as a biomarker together with the PCA3 marker for molecular staging of the prostate cancer.

  4. The -786T>C promoter polymorphism of the NOS3 gene is associated with prostate cancer progression.

    Science.gov (United States)

    Marangoni, Karina; Araújo, Thaíse G; Neves, Adriana F; Goulart, Luiz R

    2008-09-29

    There is no biological or epidemiological data on the association between NOS3 promoter polymorphisms and prostate cancer. The polymorphisms in the promoter region of NOS3 gene may be responsible for variations in the plasma NO, which may promote cancer progression by providing a selective growth advantage to tumor cells by angiogenic stimulus and by direct DNA damage. This study aimed evaluating the NOS3 promoter polymorphisms by PCR-SSCP and sequencing, associating genotypes and haplotypes with NOS3 expression levels through semi-quantitative RT-PCR, and with PCA3 mRNA detection, a specific tumor biomarker, in the peripheral blood of pre-surgical samples from 177 patients; 83 PCa and 94 BPH. Three novel SNPs were identified -764A>G, -714G>T and -649G>A in the NOS3 gene promoter region, which together with the -786T>C generated four haplotypes (N, T, C, A). NOS3 gene expression levels were affected by the -786T>C polymorphism, and there was a 2-fold increase in NOS3 levels favored by the incorporation of each C allele. NOS3 levels higher than 80% of the constitutive gene expression level (B2M) presented a 4-fold increase in PCa occurrence. The -786T>C polymorphism was the most important promoter alteration of the NOS3 gene that may affect the PCa progression, but not its occurrence, and the incorporation of the C allele is associated with increased levels of NOS3 transcripts. The NOS3 transcript levels presented a bimodal behavior in tumor development and may be used as a biomarker together with the PCA3 marker for molecular staging of the prostate cancer.

  5. Human umbilical cord expresses several vasoactive peptides involved in the local regulation of vascular tone: protein and gene expression of Orphanin, Oxytocin, ANP, eNOS and iNOS

    Directory of Open Access Journals (Sweden)

    Aldo Gerbino

    2011-07-01

    Full Text Available Full-term human umbilical cord contains three blood vessels: two arteries coiled around a vein and surrounded by Wharton’s jelly, a mucous tissue with few mesenchymal stromal cells and abundant extracellular matrix. Umbilical vessels lack innervations, thus endothelial cells must play a role in the control of blood flow. The aim of this study was to investigate in human umbilical cord the expression of five peptides that could be involved in the regulation of vascular tone: Orphanin FQ, Oxytocin, Atrial Natriuretic Peptide (ANP, endothelial Nitric Oxide Synthase (eNOS and inducible Nitric Oxide Synthase (iNOS. The expression of these molecules in full-term human umbilical cord was investigated through immunohistochemistry and RT-PCR. Immunoreactivity for Orphanin FQ was detected in Wharton’s jelly, vessel musculature and endothelium; Oxytocin, ANP and eNOS were expressed by the umbilical epithelium, Wharton’s jelly and endothelium, whereas iNOS only by endothelial cells. RT-PCR analysis showed transcriptional expression of Oxytocin, ANP and eNOS mRNAs. The presence of Orphanin, Oxytocin, ANP, eNOS and iNOS proteins was identified in the human umbilical cord. mRNA expression for Oxytocin, ANP and eNOS suggest that these molecules are synthesized by umbilical cord cells themselves. The expression of these vasoactive molecules could be part of a general mechanism locally regulating vascular tone. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 211–218

  6. Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin

    Directory of Open Access Journals (Sweden)

    Carla I. Nieto

    2015-08-01

    Full Text Available A series of new (E-3(5-[β-(aryl-ethenyl]-5(3-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding β-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (1H, 13C, 19F and 15N spectroscopy in solution and in solid state. Three structures have been solved by X-ray diffraction analysis, confirming the tautomeric forms detected by solid state NMR. The in vitro study of their inhibitory potency and selectivity on the activity of nNOS and eNOS (calcium-calmodulin dependent as well as iNOS (calcium-calmodulin independent isoenzymes is presented. A qualitative structure–activity analysis allowed the establishment of a correlation between the presence/ absence of different substituents with the inhibition data proving that fluorine groups enhance the biological activity. (E-3(5-[β-(3-Fluoro-4-hydroxyphenyl-ethenyl]-5(3-phenyl-1H-pyrazole (13, is the best inhibitor of iNOS, being also more selective towards the other two isoforms.

  7. Muscle fatigue, nNOS and muscle fiber atrophy in limb girdle muscular dystrophy.

    Science.gov (United States)

    Angelini, Corrado; Tasca, Elisabetta; Nascimbeni, Anna Chiara; Fanin, Marina

    2014-12-01

    Muscle fatigability and atrophy are frequent clinical signs in limb girdle muscular dystrophy (LGMD), but their pathogenetic mechanisms are still poorly understood. We review a series of different factors that may be connected in causing fatigue and atrophy, particularly considering the role of neuronal nitric oxide synthase (nNOS) and additional factors such as gender in different forms of LGMD (both recessive and dominant) underlying different pathogenetic mechanisms. In sarcoglycanopathies, the sarcolemmal nNOS reactivity varied from absent to reduced, depending on the residual level of sarcoglycan complex: in cases with complete sarcoglycan complex deficiency (mostly in beta-sarcoglycanopathy), the sarcolemmal nNOS reaction was absent and it was always associated with early severe clinical phenotype and cardiomyopathy. Calpainopathy, dysferlinopathy, and caveolinopathy present gradual onset of fatigability and had normal sarcolemmal nNOS reactivity. Notably, as compared with caveolinopathy and sarcoglycanopathies, calpainopathy and dysferlinopathy showed a higher degree of muscle fiber atrophy. Males with calpainopathy and dysferlinopathy showed significantly higher fiber atrophy than control males, whereas female patients have similar values than female controls, suggesting a gender difference in muscle fiber atrophy with a relative protection in females. In female patients, the smaller initial muscle fiber size associated to endocrine factors and less physical effort might attenuate gender-specific muscle loss and atrophy.

  8. The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI): I. Construct validity.

    Science.gov (United States)

    Wilde, Elisabeth A; McCauley, Stephen R; Kelly, Tara M; Weyand, Annie M; Pedroza, Claudia; Levin, Harvey S; Clifton, Guy L; Schnelle, Kathleen P; Shah, Monika V; Moretti, Paolo

    2010-06-01

    The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) is a measure adapted from the National Institutes of Health Stroke Scale (NIHSS), and is intended to capture essential neurological deficits impacting individuals with traumatic brain injury (TBI) (see Wilde et al., 2010 ). In the present study we evaluate the measure's construct validity via comparison with a quantified neurological examination performed by a neurologist. Spearman rank-order correlation between the NOS-TBI and the neurological examination was rho = 0.76, p TBI compared favorably to the neurological examination items, with correlations ranging from 0.60 to 0.99 (all p TBI, and on the NOS-TBI neurological impairment was evident in all but one participant. This study documents the presence of measurable neurological sequelae in a sample of patients with TBI in a post-acute rehabilitation setting, underscoring the need for formal measurement of the frequency and severity of neurological deficits in this population. The results suggest that the NOS-TBI is a valid measure of neurological functioning in patients with TBI.

  9. Effects of NOS inhibitor on dentate gyrus neurogenesis after diffuse brain injury in the adult rats

    Institute of Scientific and Technical Information of China (English)

    SunLi-Sha; XuJiang-ping

    2004-01-01

    Objective To investigate the effects of selective nitric oxide synthase (NOS) inhibitors on dentate gyrus neurogenesis after diffuse brain injury (DBI) in the adult rat brain. Methods Adult male SD rats were subjected to diffuse brain injury (DBI) model. By using systemic bromodeoxyuridine (BrdU) to label dividing cells, we compared the proliferation rate of

  10. From Orthodoxy to Plurality in the Nature of Science (NOS) and Science Education: A Metacommentary

    Science.gov (United States)

    Bazzul, Jesse

    2017-01-01

    This article provides a metacommentary on the special issue on nature of science (NOS). The issue is composed of senior scholars discussing Hodson and Wong's (2017, this issue) critique of the consensus view of nature of science, which on a basic level states that there are agreed-upon aspects of science that can be taught in K-12 schools. Each…

  11. Using Video Modeling to Teach Children with PDD-NOS to Respond to Facial Expressions

    Science.gov (United States)

    Axe, Judah B.; Evans, Christine J.

    2012-01-01

    Children with autism spectrum disorders often exhibit delays in responding to facial expressions, and few studies have examined teaching responding to subtle facial expressions to this population. We used video modeling to train 3 participants with PDD-NOS (age 5) to respond to eight facial expressions: approval, bored, calming, disapproval,…

  12. 75 FR 39206 - Marine Mammals; File Nos. 87-1851 and 555-1870

    Science.gov (United States)

    2010-07-08

    ... biology and ecology of harbor seals (Phoca vitulina) in California, Oregon, Washington, and Alaska... National Oceanic and Atmospheric Administration RIN 0648-XS41 Marine Mammals; File Nos. 87-1851 and 555-1870 AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric...

  13. The Langevin Limit of the Nosé-Hoover-Langevin Thermostat

    NARCIS (Netherlands)

    Frank, J.E.; Gottwald, G.A.

    2011-01-01

    In this note we study the asymptotic limit of large variance in a stochastically perturbed thermostat model, the Nos\\'{e}-Hoover-Langevin device. We show that in this limit, the model reduces to a Langevin equation with one-dimensional Wiener process, and that the perturbation is in the direction of

  14. The Langevin limit of the Nosé-Hoover-Langevin thermostat

    NARCIS (Netherlands)

    Frank, J.; Gottwald, G.A.

    2011-01-01

    In this note we study the asymptotic limit of large variance in a stochastically perturbed thermostat model, the Nosé-Hoover-Langevin device. We show that in this limit, the model reduces to a Langevin equation with one-dimensional Wiener process, and that the perturbation is in the direction of the

  15. Disrupting nNOS-PSD-95 coupling in the hippocampal dentate gyrus promotes extinction memory retrieval.

    Science.gov (United States)

    Li, Jun; Han, Zhou; Cao, Bo; Cai, Cheng-Yun; Lin, Yu-Hui; Li, Fei; Wu, Hai-Ying; Chang, Lei; Luo, Chun-Xia; Zhu, Dong-Ya

    2017-09-06

    Granule cells in the dentate gyrus regenerate constantly in adult hippocampus and then integrate into neural circuits in the hippocampus thereby providing the neural basis for learning and memory. Promoting the neurogenesis in the hippocampus facilitates learning and memory such as spatial learning, object identification, and extinction learning. The interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein-95 (PSD-95) is reported to negatively regulate neurogenesis in brain, so we hypothesized that disrupting this interaction might facilitate the neurogenesis in the dentate gyrus (DG) and thus enhance the extinction memory retrieval of fear learning. We found that uncoupling the nNOS-PSD-95 complex in remote contextual fear condition promoted both neuronal proliferation and survival in the DG, contributing to an enhanced retrieval of the extinction memory. Moreover, the nNOS-PSD-95 uncoupling-induced neurogenesis may be mediated by the extracellular signal-regulated kinase (ERK) as the phosphorylation level of ERK1/2 was increased after uncoupling. These findings suggest that the nNOS-PSD-95 complex may serve as a novel target for the treatment of post-traumatic stress disorder (PTSD). Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Identifying Demographic Variables Influencing the Nature of Science (NOS) Conceptions of Teachers

    Science.gov (United States)

    Karaman, Ayhan

    2017-01-01

    In this survey research study, the views of practicing teachers in select aspects of NOS were investigated in connection with the effects of several variables (teaching discipline, gender, education level, teaching experience and regional work location). The instrument used to collect data was an adapted version of "Scientific Epistemological…

  17. Recapitulating the History of Sickle-Cell Anemia Research: Improving Students' NOS Views Explicitly and Reflectively

    Science.gov (United States)

    Howe, Eric Michael; Rudge, David Wyss

    2005-01-01

    This paper provides an argument in favor of a specific pedagogical method of using the history of science to help students develop more informed views about nature of science (NOS) issues. The paper describes a series of lesson plans devoted to encouraging students to engage, "unbeknownst to them", in similar reasoning that led…

  18. Evidence of Aortopathy in Mice with Haploinsufficiency of Notch1 in Nos3-Null Background

    Directory of Open Access Journals (Sweden)

    Sara N. Koenig

    2015-03-01

    Full Text Available Thoracic aortic aneurysms (TAA are a significant cause of morbidity and mortality in humans. While the exact etiology is unknown, genetic factors play an important role. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV and aortopathy in humans. The aim of this study was to determine if haploinsufficiency of Notch1 contributes to aortopathy using Notch1+/−; Nos3−/− mice. Echocardiographic analysis of Notch1+/−; Nos3−/− mice reveals effacement of the sinotubular junction and a trend toward dilation of the aortic sinus. Furthermore, examination of the proximal aorta of Notch1+/−; Nos3−/− mice reveals elastic fiber degradation, a trend toward increased matrix metalloproteinase 2 expression, and increased smooth muscle cell apoptosis, features characteristic of aneurysmal disease. Although at a lower penetrance, we also found features consistent with aortopathic changes in Notch1 heterozygote mice and in Nos3-null mice. Our findings implicate a novel role for Notch1 in aortopathy of the proximal aorta.

  19. NOS3 gene variants and male infertility: Association of 4a/4b with oligoasthenozoospermia.

    Science.gov (United States)

    Vučić, N L J; Nikolić, Z Z; Vukotić, V D; Tomović, S M; Vuković, I I; Kanazir, S D; Savić-Pavićević, D L J; Brajušković, G N

    2017-05-03

    Results of recent studies confirmed that oxidative stress negatively affects sperm motility and causes sperm DNA damage. Produced by nitric oxide synthase 3 (NOS3), nitric oxide is considered to be one of the important mediators of oxidative stress in testis tissue. The aim of this study was to assess the possible association of three genetic variants (rs2070744, rs1799983 and intron variant 4a/4b) in NOS3 gene and infertility occurrence in two groups of infertile men (idiopathic azoospermia and oligoasthenozoospermia) and fertile controls. Genotypes for the single-nucleotide genetic variants rs1799983 and rs2070744 were determined by PCR-RFLP, while genotyping of intron 4 variant 4a/4b was performed by gel electrophoresis of PCR products. Statistical analysis was performed by SNPStats software. No significant association between the three genetic variants of the NOS3 gene and infertility risk was determined comparing allele and genotype frequencies among group of patients diagnosed with azoospermia and the control group. Nevertheless, there was a significant positive association between 4a/4b and infertility in the group of males diagnosed with oligoasthenozoospermia, under overdominant genetic model. Our findings suggest that tandem repeat variant within intron 4 of the NOS3 gene is associated with an increased risk of infertility in men diagnosed with idiopathic oligoasthenozoospermia. © 2017 Blackwell Verlag GmbH.

  20. The -786T > C polymorphism in the NOS3 gene is associated with increased cancer risk.

    Science.gov (United States)

    Zhang, Yonggang; Jia, Qingyi; Xue, Pei; Liu, Yuqi; Xiong, Tianyuan; Yang, Jiqiao; Song, Chenxi; He, Qing; Du, Liang

    2014-04-01

    The -786T > C polymorphism in NOS3 gene may affect the DNA repair pathways and be associated with risk of cancer. However, the results of previous studies are inconsistent. The objective of this study is to investigate the association between the -786T > C polymorphism in NOS3 and risk of cancer by meta-analysis. We searched PubMed, Embase, CNKI, and Wanfang databases and the last search was updated on Sept. 20, 2013. Statistical analysis was performed using Revman4.2 and Stata10.0 software. A total of 9 case-control studies concerning 4,089 cases and 3,847 controls were included. The results suggested a significant association between the -786T > C polymorphism in NOS3 and cancer risk (CC vs. TT + CT; OR = 1.30, 95% CI = 1.07-1.57, P = 0.007) in total analysis. In the subgroup analysis by ethnicity and cancer types, significant associations were found in the breast cancer subgroup (OR 1.51, 95% CI 1.07-2.12; P = 0.02) and European subgroup (OR 1.26, 95% CI 1.01-1.58; P = 0.04). The current meta-analysis suggested that the -786T > C polymorphisms in NOS3 may be a risk factor for cancer. In the future, more case-control studies are needed to validate our results.

  1. Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis.

    Science.gov (United States)

    Campbell, Katherine A; Li, Xing; Biendarra, Sherri M; Terzic, Andre; Nelson, Timothy J

    2015-10-01

    Through genome-wide transcriptional comparisons, this study interrogates the capacity of in vitro differentiation of induced pluripotent stem cells (iPSCs) to accurately model pathogenic signatures of developmental cardiac defects. Herein, we studied the molecular etiology of cardiac defects in Nos3(-/-) mice via transcriptional analysis of stage-matched embryonic tissues and iPSC-derived cells. In vitro comparisons of differentiated cells were calibrated to in utero benchmarks of health and disease. Integrated systems biology analysis of WT and Nos3(-/-) transcriptional profiles revealed 50% concordant expression patterns between in utero embryonic tissues and ex vivo iPSC-derived cells. In particular, up-regulation of glucose metabolism (p-value=3.95×10(-12)) and down-regulation of fatty acid metabolism (p-value=6.71×10(-12)) highlight a bioenergetic signature of early Nos3 deficiency during cardiogenesis that can be recapitulated in iPSC-derived differentiated cells. The in vitro concordance of early Nos3(-/-) disease signatures supports the utility of iPSCs as a cellular model of developmental heart defects. Moreover, this study supports the use of iPSCs as a platform to pinpoint initial stages of congenital cardiac pathogenesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Genetic Association Analysis of NOS3 and Methamphetamine-Induced Psychosis Among Japanese.

    Science.gov (United States)

    Okochi, T; Kishi, T; Ikeda, M; Kitajima, T; Kinoshita, Y; Kawashima, K; Okumura, T; Tsunoka, T; Fukuo, Y; Inada, T; Yamada, M; Uchimura, N; Iyo, M; Sora, I; Ozaki, N; Ujike, H; Iwata, N

    2011-03-01

    Endothelial nitric oxide synthase (NOS3) is one of the enzymes influencing nitric oxide (NO) function in the human brain. NO is a gaseous neurotransmitter that is involved in a variety of mechanisms in the central nervous system, such as N-methyl-D-aspartate receptor activation and oxidative stress. The evidence from animal pharmacological studies and postmortem studies supports an association between NO and psychotic disorders. Methamphetamine (METH) use disorder is a known psychotic disorder, and we therefore conducted a gene-based case-control study between tagging single nucleotide polymorphisms (SNPs) (rs2070744, rs1799983) in NOS3 and METH-induced psychosis in Japanese subjects (183 with METH-induced psychosis and 267 controls). Written informed consent was obtained from each subject. No significant association was found between any tagging SNP in NOS3 and METH-induced psychosis in the allele/genotype-wise or haplotype-wise analyses. In conclusion, we suggest that NOS3 might not contribute to the risk of METH-induced psychosis in the Japanese population.

  3. Animal Certifié Conforme: Déchiffrer nos Relations avec le Vivant

    Directory of Open Access Journals (Sweden)

    Daniel W. Gade

    2014-01-01

    Full Text Available Review of Animal Certifié Conforme: Déchiffrer nos Relations avec le Vivant. Bernadette Lizet and Jacqueline Milliet, eds. 2012. Dunod/Muséum National d’Histoire Naturelle, Paris. Pp 256. €22 (paperback. ISBN 9782100582853.

  4. Fluctuation theorem applied to the Nosé-Hoover thermostated Lorentz gas

    Science.gov (United States)

    Gilbert, Thomas

    2006-03-01

    We present numerical evidence supporting the validity of the Gallavotti-Cohen fluctuation theorem applied to the driven Lorentz gas with Nosé-Hoover thermostating. It is moreover argued that the asymptotic form of the fluctuation formula is independent of the amplitude of the driving force in the limit where it is small.

  5. Association of SP-D, MBL and I-NOS genetic variants with pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Vaid Mudit

    2006-01-01

    Full Text Available Background : Pulmonary tuberculosis is caused by Mycobacterium tuberculosis . It is a multifactorial disease with both host as well as pathogen factors contributing to susceptibility and protection from the disease. Various reports have highlighted important roles of lung surfactant protein D (SP-D, mannan-binding lectin (MBL and I-NOS in innate immune defense against M. tuberculosis Aims : The present study investigated the role of polymorphisms in three candidate genes encoding Lung surfactant protein D, Mannan binding lectin and Inducible Nitric oxide synthase, in susceptibility and protection to pulmonary tuberculosis. Settings and Design : A case-control association study of SNP′s in lung surfactant protein D (SP-D, mannan-binding lectin (MBL and I-NOS with pulmonary tuberculosis in Indian population was carried out. This involved sequencing of all the coding exons of lung surfactant protein D (SP-D , while, exon 1 (collagen region and exon 4 (carbohydrate recognition domain of mannan-binding lectin (MBL and exons 2, 8 and 16 of I-NOS and their flanking intronic regions for single nucleotide polymorphisms in DNA samples isolated from 30 pulmonary tuberculosis patients and 30 controls of Indian population. Statistical analysis: Various allele frequencies were calculated using online two by two table (home.clara.net/sisa/. Odds ratio and P values were calculated at 95% confidence interval (CI. Results : A total of fourteen single nucleotide polymorphisms (5 in SP-D , 5 in MBL and 4 in I-NOS were observed of which four (G459A SP-D , G274T I-NOS , G1011A and T357G MBL have not been reported earlier. Four single nucleotide polymorphisms viz. G459A of exon 7 of SP-D ( P =0.00, odds ratio (OR = 4.96, 2.18 P = 0.00 or= 3.85 1.66 P =0.00 or=4.04, 2.20< OR< 7.42 and G274T of intron 16 of I-NOS ( P =0.00 or=4.46, 2.40 Conclusion: The present study has led to identification of 4 SNP′s in SP-D , MBL and I-NOS associated with pulmonary tuberculosis

  6. Phenotypic characterization by high-resolution three-dimensional magnetic resonance imaging evidences differential effects of embryo genotype on intrauterine growth retardation in NOS3-deficient mice.

    Science.gov (United States)

    Pallares, Pilar; Perez-Solana, Maria L; Torres-Rovira, Laura; Gonzalez-Bulnes, Antonio

    2011-05-01

    The Nos3-knockout mouse, deficient for endothelial constitutive nitric oxide synthase (NOS3), is affected by a reduction in the number and weight of the embryos and constitutes a good model for some features of preeclampsia and intrauterine growth retardation (IUGR). Deficiencies in conceptus growth and survival may result from factors inherent in the embryo itself or from deficiencies in uterine function. In the current study, we aimed to determine the effects of embryonic genotype independently of maternal genotype, which can affect uterine environment. Therefore, by using magnetic resonance imaging (MRI), we characterized the phenotypes of NOS3-defective (Nos3(-/-); n = 6), normal wild-type (Nos3(+/+); n = 5), and heterozygous (Nos3(+/-); n = 16) mouse fetuses. All of them were littermates obtained by breeding heterozygous mice (Nos3(+/-)); therefore, the maternal genotype was the same for all the fetuses. At Day 13.5 (i.e., Theiler stage TS 21-22), females were anesthetized and scanned with three-dimensional MRI. Analysis of the different measurements of the embryos and the gestational annexes showed no significant differences between Nos3(+/+) and Nos3(+/-); however, there was a trend toward larger sizes in Nos3(+/+), and values in Nos3(-/-) were significantly smaller than in Nos3(+/+) and Nos3(+/-). The reduction in the crown-rump length of Nos3(-/-) reached 12% when compared to Nos3(+/+) (P Nos3(-/-) to wild-type Nos3(+/+). Finally, Nos3(-/-) showed a reduction of 29% in the maximum thickness of the placenta, which may be related to the appearance of IUGR due to compromised nutritional delivery to the fetus.

  7. Common Variation in the NOS1AP Gene Is Associated With Drug-Induced QT Prolongation and Ventricular Arrhythmia

    NARCIS (Netherlands)

    Jamshidi, Yalda; Nolte, Ilja M.; Dalageorgou, Chrysoula; Zheng, Dongling; Johnson, Toby; Bastiaenen, Rachel; Ruddy, Suzanne; Talbott, Daniel; Norris, Kris J.; Snieder, Harold; George, Alfred L.; Marshall, Vanessa; Shakir, Saad; Kannankeril, Prince J.; Munroe, Patricia B.; Camm, A. John; Jeffery, Steve; Roden, Dan M.; Behr, Elijah R.

    2012-01-01

    Objectives This study sought to determine whether variations in NOS1AP affect drug-induced long QT syndrome (LQTS). Background Use of antiarrhythmic drugs is limited by the high incidence of serious adverse events including QT prolongation and torsades de pointes. NOS1AP gene variants play a role in

  8. Exercise training restores coronary arteriolar dilation to NOS activation distal to coronary artery occlusion - Role of hydrogen peroxide

    NARCIS (Netherlands)

    Thengchaisri, Naris; Shipley, Robert; Ren, Yi; Parker, Janet; Kuo, Lih

    2007-01-01

    Objective - Exercise training has been shown to restore vasodilation to nitric oxide synthase (NOS) activation in arterioles distal to coronary artery occlusion. Because reactive oxygen species are generated during NOS uncoupling and the production of vasodilator H2O2 is increased during exercise in

  9. 78 FR 49305 - Luminant Generation Company LLC, Comanche Peak Nuclear Power Plant, Unit Nos. 1 and 2...

    Science.gov (United States)

    2013-08-13

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Luminant Generation Company LLC, Comanche Peak Nuclear Power Plant, Unit Nos. 1 and 2; Application... Nuclear Power Plant, Unit Nos. 1 and 2, respectively, located in Somervell County, Texas. The...

  10. 75 FR 66802 - Calvert Cliffs Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2...

    Science.gov (United States)

    2010-10-29

    ... COMMISSION Calvert Cliffs Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2... Regulatory Commission (the Commission) has granted the request of Calvert Cliffs Nuclear Power Plant, LLC... Operating License Nos. DPR-53 and DPR-69 for the Calvert Cliffs Nuclear Power Plant, Unit......

  11. 76 FR 4391 - Calvert Cliffs Nuclear Power Plant, LLC, Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2...

    Science.gov (United States)

    2011-01-25

    ... COMMISSION Calvert Cliffs Nuclear Power Plant, LLC, Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2; Exemption 1.0 Background Calvert Cliffs Nuclear Power Plant, LLC, the licensee, is the holder of Facility Operating License Nos. DPR-53 and DPR-69 which authorizes operation of the Calvert Cliffs Nuclear...

  12. 76 FR 39908 - Calvert Cliffs Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2...

    Science.gov (United States)

    2011-07-07

    ... COMMISSION Calvert Cliffs Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2.... DPR-53 and DPR-69, for the Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2 (CCNPP), respectively... (ISFSI), currently held by Calvert Cliffs Nuclear Power Plant, LLC as owner and licensed......

  13. eNOS uncoupling in the cerebellum after BBB disruption by exposure to Phoneutria nigriventer spider venom.

    Science.gov (United States)

    Soares, Edilene Siqueira; Mendonça, Monique Culturato Padilha; da Cruz-Höfling, Maria Alice

    2015-09-15

    Numerous studies have shown that the venom of Phoneutria nigriventer (PNV) armed-spider causes excitotoxic signals and blood-brain barrier breakdown (BBBb) in rats. Nitric oxide (NO) is a signaling molecule which has a role in endothelium homeostasis and vascular health. The present study investigated the relevance of endothelial NO synthase (eNOS) uncoupling to clinical neurotoxic evolution induced by PNV. eNOS immunoblotting of cerebellum lysates processed through low-temperature SDS-PAGE revealed significant increased monomerization of the enzyme at critical periods of severe envenoming (1-2 h), whereas eNOS dimerization reversal paralleled to amelioration of animals condition (5-72 h). Moreover, eNOS uncoupling was accompanied by increased expression in calcium-sensing calmodulin protein and calcium-binding calbindin-D28 protein in cerebellar neurons. It is known that greater eNOS monomers than dimers implies the inability of eNOS to produce NO leading to superoxide production and endothelial/vascular barrier dysfunction. We suggest that transient eNOS deactivation and disturbances in calcium handling reduce NO production and enhance production of free radicals thus contributing to endothelial dysfunction in the cerebellum of envenomed rats. In addition, eNOS uncoupling compromises the enzyme capacity to respond to shear stress contributing to perivascular edema and it is one of the mechanisms involved in the BBBb promoted by PNV.

  14. CD151 gene delivery increases eNOS activity and induces ECV304 migration, proliferation and tube formation

    Institute of Scientific and Technical Information of China (English)

    Zhen-zhong ZHENO; Zheng-xiang LIU

    2007-01-01

    Aim: To investigate the effects of CD151 on the activity of endothelial NO syn-thase (eNOS), and ECV304 migration, proliferation and tube formation. Methods:pAAV-CD151 and pAAV-anti-CD151 were constructed and used to transiently transfect ECV304 mediated with Lipofectamine 2000. After transfection, the ex-pression of CD151 was measured by Western blotting. Cell migration assay was performed using Boyden transwell; proliferation assay was evaluated using the 3-[4,5-dimethylthiazol-2-yl]-2,5, diphenyltetrazolium bromide (MTT) method, and tube formation test was examined on matrigel, eNOS activity was assayed by L-[3H]citrulline production from L-[3H]arginine. The involvement of eNOS was ex-plored using an eNOS inhibitor (L-NAME) and the effects in the process were observed. Results: CD151 promotes cell migration, proliferation and tube formation.In addition, CD151 increases eNOS activity. Moreover, cell migration, prolifera-tion and tube formation induced by CD151 are inhibited when L-NAME is used,which indicates that there is an involvement of eNOS in CD151-induced cell migration, cell proliferation and tube formation. Conclusion: CD151 promotes ECV304 migration, proliferation and tube formation. The mechanism is that CD151 increases eNOS activity. This result also suggests that eNOS is involved in the angiogenic effects of CD151.

  15. ONE PROBABLE MECHANISM OF THE LEARNING-MEMORY DAMAGE BY LEAD: THE CHANGES OF NOS IN HIPPOCAMPUS

    Institute of Scientific and Technical Information of China (English)

    王静; 赵义; 杨章民; 张进; 李积胜; 司履生; 王一理

    2003-01-01

    Objective To study the effects of lead on the activity and expression of nitric oxide synthase (NOS) and relationship between the effects of lead on learning-memory and changes of NOS in subfields of hippocampus. Methods Y-maze test was used to study the effects of lead on ability of learning-memory; NADPH-d histochemistry and immunohistochemistry methods were used to investigate the changes of NOS in subfields of hippocampus. Results Compared with the control group, the ability of learning- memory in lead-exposed rats was significantly decreased (P<0.05); the number of NOS positive neurons in CA1 region and dentate gyrus of lead-exposed rats was significantly decreased(P<0.05), but no marked changes in CA3 region; the number of nNOS positive neurons in CA1 of lead-exposed rats was also significantly decreased(P<0.05), but no obvious changes in CA3. Conclusion Lead could damage the ability of learning-memory in rats. Lead could decrease the activity and expression of NOS in hippocampus and had different effects on NOS in different subfields of hippocampus. The changes of NOS in hippocampus induced by lead may be the mechanism of the learning-memory damage by lead.

  16. Et si nos déchets devenaient la source de nouveaux produits. Notion d'économie circulaire

    OpenAIRE

    2015-01-01

    Notre objectif et nos recherches se concentrent sur l'utilisation des déchets agricoles et forestiers, les déchets végétaux et industriels et nos déchets ménagers pour produire une gamme de nouveaux produits, biocarburants ou molécules chimiques.

  17. 75 FR 14634 - Dominion Nuclear Connecticut, Inc.; Millstone Power Station, Unit Nos. 1, 2, and 3; Environmental...

    Science.gov (United States)

    2010-03-26

    ... part 73, for certain uninterruptible power supply requirements. The proposed action, an extension of... COMMISSION Dominion Nuclear Connecticut, Inc.; Millstone Power Station, Unit Nos. 1, 2, and 3; Environmental... Power Station, Unit Nos. 1, 2, and 3 (MPS1, MPS2, and MPS3, respectively), located in New London...

  18. Effect of NOS3 gene polymorphism on response to Tricyclic antidepressants in migraine attacks.

    Science.gov (United States)

    Molana, Aliasghar; Mehrpour, Masoud; Vousooghi, Nasim; Hajighasem, Mahmoud Reza; Joghataei, Mohammad Taghi

    2014-07-04

    Migraine is a chronic neurological disorder, characterized by recurrent moderate to severe headaches. Worldwide migraine affects nearly 15%. Studies suggest that genes involved in the production of nitric oxide (NO) may act as genetic factors for migraine. NO synthase 3 (NOS3) by expressing enzyme NOS regulates endothelial derived NO. One class of medications used as first-line treatment in migraine prophylaxis is tricyclic antidepressants (TCAs). The aim of this study was to determine effects of NOS3 gene Glu298Asp polymorphism in the production of NO and response of patients to TCAs in migraine attacks. A total of 80 migraine patients were invited to participate in the study. Patients recorded the characteristics of their migraine attacks such as frequency of attacks and intensity of headaches for the 1(st) month of the study. Then peripheral blood samples were taken from all subjects in order to determine patients' genotype distribution, mRNA expression level of NOS3 and NO content of plasma. Patients were then instructed to use 25 mg nortriptyline at night before bed for 3 months. At the end of 3(rd) month of the treatment patients again recorded the migraine characteristics for 1 month and blood sampling was performed in order to determine the level of plasma NO. The patients' genotype distribution for TT, GT, and GG was 9, 24, and 47 subjects, respectively. Mean NO level in patients with TT genotype was less in comparison to GT and GG genotypes before and after use of TCAs (P NOS3 Glu298Asp polymorphism particularly in TT genotype (P < 0.05). Presence of T allele of the Glu298Asp polymorphism may be a factor for TT genotype patients to produce less NO and is a favorable factor for better response to TCAs in reducing migraine attacks in comparison to GT and GG genotypes.

  19. NOS3 variants, physical activity, and blood pressure in the European Youth Heart Study.

    Science.gov (United States)

    Grøntved, Anders; Andersen, Lars B; Franks, Paul W; Verhage, Bas; Wareham, Nicholas J; Ekelund, Ulf; Loos, Ruth J F; Brage, Søren

    2011-04-01

    In this study, we examined the influence of genetic variation in NOS3 on resting blood pressure (BP) in children and adolescents from the European Youth Heart Study (EYHS). Because the NOS3 gene expression is altered by physical activity (PA), we also tested for interaction between habitual PA and NOS3 variants on BP. A cross-sectional, random sample of 8-10-year old children (n = 1,214) and 14-16-year old adolescents (n = 1,141) from Denmark and Estonia were genotyped for four NOS3 tagging polymorphisms (rs1800783, rs1799983 (Glu298Asp), rs3918227, rs743507). PA was measured objectively using a hip-mounted accelerometer and through self-reported bicycling and TV-viewing. Permutation testing was used to correct for multiple testing, yielding an α level of 0.006. Glu298Asp showed age-group-dependent associations with BP. In adolescents, Asp298 allele homozygotes had 0.19 s.d. (95% confidence interval (CI): 0.06; 0.13, P = 0.004) higher diastolic BP (DBP) and 0.25 s.d. (95% CI: 0.05; 0.46, P = 0.015) higher systolic BP (SBP), compared to Glu298 allele carriers. None of the three other single-nucleotide polymorphisms (SNPs) were associated with BP in adolescents. In children, none of the SNPs were associated with BP. No evidence of interaction between Glu298Asp and objectively measured PA was observed. Both self-reported bicycling and TV-viewing nominally modified the association between Glu298Asp and BP in adolescents (P NOS3 Glu298Asp variant may associate with resting BP in adolescence but not in childhood, an effect that could be modified by PA.

  20. The effect of embryo and maternal genotypes on prolificacy, intrauterine growth retardation and postnatal development of Nos3-knockout mice.

    Science.gov (United States)

    Pallares, Pilar; Gonzalez-Bulnes, Antonio

    2010-11-01

    Mice deficient for endothelial nitric oxide synthase (NOS3(-/-)) may represent a good model for studying embryo loss and intrauterine growth retardation caused by vascular deficiencies. We determined the effects of embryo genotype (homozygous vs. heterozygous descendants with paternal or maternal source of the non-functional NOS3 allele) and maternal environment (NOS3(-/-) vs. wild-type NOS3(+/+) females) on the appearance of estrus, fertility and prolificacy rates and live weight in the first week of life as well as phenotypic characteristics of offspring during the postnatal period. The results indicated that pregnancy outcomes and postnatal development of NOS3(-/-) mice seem to be related to deficiencies in fetal programming mainly determined by maternal genotype.

  1. Depressed nNOS expression during spine transition in the developing hippocampus of FMR1 KO mice

    Directory of Open Access Journals (Sweden)

    Qin Xu

    2012-12-01

    Full Text Available Nitric oxide (NO, synthesized as needed by NO synthase (NOS, is involved in spinogenesis and synaptogenesis. Immature spine morphology is characteristic of fragile X syndrome (FXS. The objective of this research was to investigate and compare changes of postnatal neuronal NOS (nNOS expression in the hippocampus of male fragile X mental retardation 1 gene knockout mice (FMR1 KO mice, the animal model of FXS and male wild-type mice (WT at postnatal day 7 (P7, P14, P21, and P28. nNOS mRNA levels were analyzed by real-time quantitative PCR (N = 4-7 and nNOS protein was estimated by Western blot (N = 3 and immunohistochemistry (N = 1. In the PCR assessment, primers 5’-GTGGCCATCGTGTCCTACCATAC-3’ and 5’-GTTTCGAGGCAGGTGGAAGCTA-3’ were used for the detection of nNOS and primers 5’-CCGTTTCTCCTGGCTCAGTTTA-3’ and 5’-CCCCAATACCACATCATCCAT-3’ were used for the detection of β-actin. Compared to the WT group, nNOS mRNA expression was significantly decreased in FMR1 KO mice at P21 (KO: 0.2857 ± 0.0150, WT: 0.5646 ± 0.0657; P < 0.05. Consistently, nNOS immunoreactivity also revealed reduced staining intensity at P21 in the FMR1 KO group. Western blot analysis validated the immunostaining results by demonstrating a significant reduction in nNOS protein levels in the FMR1 KO group compared to the WT group at P21 (KO: 0.3015 ± 0.0897, WT: 1.7542 ± 0.5455; P < 0.05. These results suggest that nNOS was involved in the postnatal development of the hippocampus in FXS and impaired NO production may retard spine maturation in FXS.

  2. Depressed nNOS expression during spine transition in the developing hippocampus of FMR1 KO mice

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Qin; Zhu, Zhiwei; Xu, Jialu [Department of Children' s Health Care, Children' s Hospital, Zhejiang University, Hangzhou Zhejiang (China); Gu, Weizhong [Department of Pathology, Children' s Hospital, Zhejiang University, Hangzhou Zhejiang (China); Zhao, Zhengyan [Department of Children' s Health Care, Children' s Hospital, Zhejiang University, Hangzhou Zhejiang (China)

    2012-10-05

    Nitric oxide (NO), synthesized as needed by NO synthase (NOS), is involved in spinogenesis and synaptogenesis. Immature spine morphology is characteristic of fragile X syndrome (FXS). The objective of this research was to investigate and compare changes of postnatal neuronal NOS (nNOS) expression in the hippocampus of male fragile X mental retardation 1 gene knockout mice (FMR1 KO mice, the animal model of FXS) and male wild-type mice (WT) at postnatal day 7 (P7), P14, P21, and P28. nNOS mRNA levels were analyzed by real-time quantitative PCR (N = 4-7) and nNOS protein was estimated by Western blot (N = 3) and immunohistochemistry (N = 1). In the PCR assessment, primers 5′-GTGGCCATCGTGTCCTACCATAC-3′ and 5′-GTTTCGAGGCAGGTGGAAGCTA-3′ were used for the detection of nNOS and primers 5′-CCGTTTCTCCTGGCTCAGTTTA-3′ and 5′-CCCCAATACCACATCATCCAT-3′ were used for the detection of β-actin. Compared to the WT group, nNOS mRNA expression was significantly decreased in FMR1 KO mice at P21 (KO: 0.2857 ± 0.0150, WT: 0.5646 ± 0.0657; P < 0.05). Consistently, nNOS immunoreactivity also revealed reduced staining intensity at P21 in the FMR1 KO group. Western blot analysis validated the immunostaining results by demonstrating a significant reduction in nNOS protein levels in the FMR1 KO group compared to the WT group at P21 (KO: 0.3015 ± 0.0897, WT: 1.7542 ± 0.5455; P < 0.05). These results suggest that nNOS was involved in the postnatal development of the hippocampus in FXS and impaired NO production may retard spine maturation in FXS.

  3. Prolonged Action Potential and After depolarizations Are Not due to Changes in Potassium Currents in NOS3 Knockout Ventricular Myocytes

    Directory of Open Access Journals (Sweden)

    Honglan Wang

    2012-01-01

    Full Text Available Ventricular myocytes deficient in endothelial nitric oxide synthase (NOS3−/− exhibit prolonged action potential (AP duration and enhanced spontaneous activity (early and delayed afterdepolarizations during β-adrenergic (β-AR stimulation. Studies have shown that nitric oxide is able to regulate various K+ channels. Our objective was to examine if NOS3-/- myocytes had altered K+ currents. APs, transient outward (to, sustained (Ksus, and inward rectifier (K1 K+ currents were measured in NOS3-/- and wild-type (WT myocytes. During β-AR stimulation, AP duration (measured as 90% repolarization-APD90 was prolonged in NOS3−/− compared to WT myocytes. Nevertheless, we did not observe differences in to, Ksus, or K1 between WT and NOS3−/− myocytes. Our previous work showed that NOS3−/− myocytes had a greater Ca2+ influx via L-type Ca2+ channels with β-AR stimulation. Thus, we measured β-AR-stimulated SR Ca2+ load and found a greater increase in NOS3−/− versus WT myocytes. Hence, our data suggest that the prolonged AP in NOS3−/− myocytes is not due to changes in to, Ksus, or K1. Furthermore, the increase in spontaneous activity in NOS3−/− myocytes may be due to a greater increase in SR Ca2+ load. This may have important implications for heart failure patients, where arrhythmias are increased and NOS3 expression is decreased.

  4. Biochemical consequences of the NOS3 Glu298Asp variation in human endothelium: altered caveolar localization and impaired response to shear.

    Science.gov (United States)

    Joshi, Mandar S; Mineo, Chieko; Shaul, Philip W; Bauer, John Anthony

    2007-09-01

    Human endothelial nitric oxide synthase (NOS3) gene polymorphism at Exon 7 (Glu298Asp) has been linked to vascular endothelial dysfunction, but the mechanisms are not defined. Shear is a key modulator of NOS3 function in vivo and association with caveolae is important for the control of NOS3 protein activity. Here we tested the hypothesis that altered enrichment of NOS3 in the caveolar membrane defines Glu298Asp genotype-specific responses and NOS3 activity. Basal caveolar membrane enrichment was carried out to quantitate the NOS3 enrichment in caveolae. Cells were subjected to shear and NOS3 protein levels, phosphorylation, enzyme function were investigated. Variant genotypes had lower NOx production pre- and post-shear, but no genotype-dependent alterations in pNOS3 were observed. Asp variants had significantly lower NOS3 enrichment in the caveolar membrane fraction. Further, immunoprecipitation studies demonstrated that Asp variants had substantially less NOS3/Cav-1 association (approximately 40%) during static conditions. Furthermore, acute shear causes impaired NOS3/Cav-1 dissociation in Asp variants. The results from immunoprecipitation studies were in complete agreement with caveolar membrane preparation findings. Collectively, these data demonstrate functional consequences of the Glu298Asp NOS3 variation and further define disruption of NOS3 caveolar localization and shear-induced mobilization as the primary mechanism responsible for these differences.

  5. A Teoria Fundamentada nos Dados nos estudos de Pós-Graduação Stricto Sensu da Enfermagem brasileira

    Directory of Open Access Journals (Sweden)

    Marcelle Miranda da Silva

    2011-12-01

    Full Text Available Estudo documental e quantitativo, que objetivou identificar as teses e dissertações defendidas nos Programas de Pós- Graduação em Enfermagem do Brasil que utilizaram o referencial metodológico da Teoria Fundamentada nos Dados (TFD e analisar os aspectos epistemológicos destacados. Os dados foram coletados no Banco de Teses da CAPES, no recorte temporal entre 1996 a 2010. Foram levantados 99 resumos. Realizou-se a leitura analítica dos mesmos para constituição do tema ou problema da pesquisa e do enquadramento teórico. O maior número de produção foi em 2005, na soma dos dois níveis acadêmicos, e 54% das defesas foram sediadas na USP. As áreas temáticas mais expressivas foram: Saúde da Criança/Adolescente; Gestão em Saúde/Enfermagem; Saúde Coletiva e Saúde da Mulher. O principal referencial teórico utilizado foi o Interacionismo Simbólico. A TFD compreende uma metodologia que pode ser empregada na enfermagem, capaz de contribuir no desenvolvimento de novas investigações para o seu aprimoramento contínuo.

  6. Gallic Acid Enriched Fraction of Phyllanthus emblica Potentiates Indomethacin-Induced Gastric Ulcer Healing via e-NOS-Dependent Pathway

    Directory of Open Access Journals (Sweden)

    Ananya Chatterjee

    2012-01-01

    Full Text Available The healing activity of gallic acid enriched ethanolic extract (GAE of Phyllanthus emblica fruits (amla against the indomethacin-induced gastric ulceration in mice was investigated. The activity was correlated with the ability of GAE to alter the cyclooxygenase- (COX- dependent healing pathways. Histology of the stomach tissues revealed maximum ulceration on the 3rd day after indomethacin (18 mg/kg, single dose administration that was associated with significant increase in inflammatory factors, namely, mucosal myeloperoxidase (MPO activity and inducible nitric oxide synthase (i-NOS expression. Proangiogenic parameters such as the levels of prostaglandin (PG E2, vascular endothelial growth factor (VEGF, hepatocyte growth factor (HGF, von Willebrand Factor VIII, and endothelial NOS (e-NOS were downregulated by indomethacin. Treatment with GAE (5 mg/kg/day and omeprazole (3 mg/kg/day for 3 days led to effective healing of the acute ulceration, while GAE could reverse the indomethacin-induced proinflammatory changes of the designated biochemical parameters. The ulcer healing activity of GAE was, however, compromised by coadministration of the nonspecific NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME, but not the i-NOS-specific inhibitor, L-N6-(1-iminoethyl lysine hydrochloride (L-NIL. Taken together, these results suggested that the GAE treatment accelerates ulcer healing by inducing PGE2 synthesis and augmenting e-NOS/i-NOS ratio.

  7. Gallic Acid Enriched Fraction of Phyllanthus emblica Potentiates Indomethacin-Induced Gastric Ulcer Healing via e-NOS-Dependent Pathway.

    Science.gov (United States)

    Chatterjee, Ananya; Chatterjee, Sirshendu; Biswas, Angshuman; Bhattacharya, Sayanti; Chattopadhyay, Subrata; Bandyopadhyay, Sandip K

    2012-01-01

    The healing activity of gallic acid enriched ethanolic extract (GAE) of Phyllanthus emblica fruits (amla) against the indomethacin-induced gastric ulceration in mice was investigated. The activity was correlated with the ability of GAE to alter the cyclooxygenase- (COX-) dependent healing pathways. Histology of the stomach tissues revealed maximum ulceration on the 3rd day after indomethacin (18 mg/kg, single dose) administration that was associated with significant increase in inflammatory factors, namely, mucosal myeloperoxidase (MPO) activity and inducible nitric oxide synthase (i-NOS) expression. Proangiogenic parameters such as the levels of prostaglandin (PG) E(2), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), von Willebrand Factor VIII, and endothelial NOS (e-NOS) were downregulated by indomethacin. Treatment with GAE (5 mg/kg/day) and omeprazole (3 mg/kg/day) for 3 days led to effective healing of the acute ulceration, while GAE could reverse the indomethacin-induced proinflammatory changes of the designated biochemical parameters. The ulcer healing activity of GAE was, however, compromised by coadministration of the nonspecific NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME), but not the i-NOS-specific inhibitor, L-N6-(1-iminoethyl) lysine hydrochloride (L-NIL). Taken together, these results suggested that the GAE treatment accelerates ulcer healing by inducing PGE(2) synthesis and augmenting e-NOS/i-NOS ratio.

  8. Diethyldithiocarbamate inhibits iNOS expression in human lens epithelial cells stimulated by IFN-gamma and LPS

    Institute of Scientific and Technical Information of China (English)

    De-xin LI; Si-ling WANG; Yoshimasa ITO; Jing-hai ZHANG; Chun-fu WU

    2005-01-01

    Aim: To investigate the biological activity of human lens epithelial cells (HLEC) in producing inducible nitric oxide synthase (iNOS) and nitric oxide (NO), and to assesse the effect of diethyldithiocarbamate (DDC) on iNOS mRNA levels and expression of NOS. Methods: The human lens epithelial cell line SRA 01/04 was used in this experiment. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to detect, respectively, iNOS mRNA expression and protein production. Results: A costimulation by interferon gamma (IFN-γ) and lipopolysaccharide (LPS) was necessary for iNOS expression in HLEC. The expression of iNOS was significantly reduced in a dosedependent manner by adding DDC from 10 μmol/L to 1 mmol/L. Conclusion:The expression of iNOS in HLEC needs co-stimulation with IFN-γ and LPS and it is inhibited by DDC.

  9. VEGF and eNOS Expression in Umbilical Cord from Pregnancy Complicated by Hypertensive Disorder with Different Severity

    Directory of Open Access Journals (Sweden)

    K. Bhavina

    2014-01-01

    Full Text Available Background. Reduced blood flow in hypertensive pregnancy may influence the production vasoconstrictors; subsequently the vessel remains in highly contracted state. NO is a vasodilator; VEGF influences its synthesis by regulating eNOS production. Aim of our study was to evaluate the expression of VEGF and eNOS in different severity of hypertensive pregnancy. Methods. Study was conducted in 4 groups with 40 members: group 1—control, group 2—gestational hypertension, group 3—mild preeclampsia, and group 4—severe preeclampsia. Fetal end of umbilical cord was taken and follows IHC staining protocol for VEGF and eNOS antibody. Staining intensity were measured by semiquantitative scoring method. Mann Whitney U test was used to compare each group. Results. Decreased expression of both VEGF and eNOS was found in hypertensive condition than in normal condition. Among hypertensive group, severe preeclamptic group showed more intensity in staining than gestational hypertension and mild preeclampsia. Conclusion. Reduction of VEGF and eNOS in gestational hypertension may lead to hypoperfusion and subsequent hypoxia of fetus in hypertensive pregnancy. The developed hypoxic state may upregulate the synthesis of VEGF and thereby eNOS. Increased expression of VEGF and eNOS in severe group may be a compensatory mechanism to dilate the blood vessels and to improve blood flow of fetus.

  10. The effects of NOS3 Glu298Asp variant on colorectal cancer risk and progression in Turkish population.

    Science.gov (United States)

    Arıkan, Soykan; Cacina, Canan; Guler, Erkan; Çulcu, Serdar; Tuna, Gulay; Yaylım-Eraltan, Ilhan

    2012-03-01

    Endothelial nitric oxide synthase (eNOS), coded by the gene NOS3, may play an important role in uncontrollable cellular growth in several cancer types. Our study was performed to test the association between Glu298Asp polymorphisms in the NOS3 gene and colorectal cancer risk and progression. In this study, NOS3 Glu298Asp polymorphism was genotyped in 84 patients with colorectal cancer and 99 healthy subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. There were significant differences in the distribution of NOS3 genotypes and frequencies of the alleles between colorectal cancer patients and controls (P = 0.016, P = 0.006, respectively). The increased frequency of NOS3 Glu298Asp homozygotes genotypes in patients who had advanced tumour stage was statistically significant (P = 0.042). Our findings have suggested that NOS3 Glu298Asp polymorphism might be associated with the risk and progression of colorectal cancer in Turkish population.

  11. Plgf-/-eNos-/- mice show defective angiogenesis associated with increased oxidative stress in response to tissue ischemia.

    Science.gov (United States)

    Gigante, Bruna; Morlino, Giulia; Gentile, Maria Teresa; Persico, Maria Graziella; De Falco, Sandro

    2006-05-01

    Neo-angiogenesis is a complex phenomenon modulated by the concerted action of several molecular factors. We have generated a congenic line of knockout mice carrying null mutations of both placental growth factor (PlGF) and endothelial nitric oxide synthase (eNOS), two genes that play a pivotal role in the regulation of pathological angiogenesis. In the present study, we describe the phenotype of this new experimental animal model after surgically induced hind-limb ischemia. Plgf-/-, eNos-/-, Plgf-/- eNos-/-, and wild-type C57BL/6J mice were studied. Plgf-/- eNos-/- mice showed the most severe phenotype: self-amputation, and death occurred in up to 47% of the animals studied; in ischemic legs, capillary density was severely reduced; macrophage infiltration and oxidative stress increased as compared to the other groups of animals. These changes were associated with an up-regulation of both inducible NOS (iNOS) expression and vascular endothelial growth factor (VEGF) protein levels in ischemic limbs, and to an increased extent of protein nitration. Our results demonstrate that the deletion of these two genes, Plgf, which acts in synergism with VEGF, and eNos, a downstream mediator of VEGF, determines a significant change in the vascular response to an ischemic stimulus and that oxidative stress within the ischemic tissue represents a crucial factor to maintain tissue homeostasis.

  12. Eficiência Adaptativa nos Mercados Futuros Agropecuários Brasileiros

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    Marcos Aurelio Rodrigues

    2016-06-01

    Full Text Available Objetivou-se neste estudo analisar a eficiência dos mercados futuros agropecuários brasileiros, sob a hipótese adaptativa de mercado. Utilizando propostas recentes à não linearidade e razão de variância, encontrou-se que as elevadas rejeições à hipótese de diferença martingal se encontram nos mercados em que as intervenções governamentais se fazem presentes: milho e etanol. Nos mercados de café, boi gordo e soja ocorreram menores rejeições à hipótese martingal e, portanto, houve maior eficiência informacional. Essas evidências - consistentes com a hipótese adaptativa dos mercados -justificam operações de hedge dinâmicas, bem como a gerência de carteiras de investimentos de forma ativa.

  13. Lack of association between endothelial nitric oxide synthase (NOS3 gene polymorphisms and suicide attempts

    Directory of Open Access Journals (Sweden)

    Bousoño Manuel

    2007-07-01

    Full Text Available Abstract Objective The aim of this study is to investigate the association between two polymorphisms of endothelial nitric oxide synthase (NOS3 and suicide attempts. Methods We genotyped 186 suicide attempters and 420 unrelated healthy controls. The following polymorphisms were analysed: T-786C and 27-bp repeat in intron 4. Results No significant differences were found in genotype or in allelic distribution of the aforesaid polymorphisms. There were also no differences in the genotype distribution or allelic frequencies when separately assessing males and females or impulsive and non-impulsive attempters and normal controls. Estimated haplotype frequencies were similar in both groups. Conclusion Our data do not support the hypothesis that genetically determined changes in the NOS3 gene confer increased susceptibility for suicidal behavior.

  14. Montagem por interferência de rodas dentadas nos veios de redutores industriais

    OpenAIRE

    Barros, Pedro Lacerda Correia de

    2011-01-01

    Dissertação para obtenção do Grau de Mestre em Engenharia Mecânica Existem diversos tipos de fixação entre veios e rodas dentadas. Pode-se classificar esses tipos de fixação em dois grandes grupos: fixação por forma e por atrito. Nos tipos de fixação por forma incluem-se a fixação por intermédio de chavetas, de cavaletes, veios estriados e fixações poligonais. Nos de fixação por atrito, ou seja, os que utilizam o atrito entre os componentes como meio de fixação (e não o obstáculo com...

  15. Contrato preliminar: eficácia nos negócios jurídicos complexos

    OpenAIRE

    Alem, Fabio Pedro

    2010-01-01

    A proposta desta dissertação é analisar criticamente o contrato preliminar nos negócios jurídicos complexos, com destaque para os graus de obrigatoriedade ou os níveis de predeterminação do conteúdo do contrato definitivo (fraco, médio e forte) e as consequências práticas do contrato preliminar nos negócios complexos. O ponto de partida do trabalho é a análise histórica e evolutiva da aplicação do contrato preliminar, seguida por uma apresentação de suas características f...

  16. Topografia do Brasil profundo: votos, cargos e alinhamentos nos municípios brasileiros

    Directory of Open Access Journals (Sweden)

    André Marenco dos Santos

    2013-06-01

    Full Text Available O propósito deste artigo é identificar os padrões preponderantes da competição política realizada nos municípios brasileiros. Pretende-se analisar dois problemas: em primeiro lugar, considerando-se a estrutura federativa do Estado brasileiro e a presença de governo dividido, busca-se identificar as forças que presidem as relações intergovernamentais entre governo federal, estadual e municipal. Em segundo lugar, procura-se analisar em que medida o incremento na competição eleitoral ao nível nacional tem contribuído para incentivar disputas locais e minar as bases tradicionais de poder nos mais de 5,5 mil municípios brasileiros.

  17. Science learning based on local potential: Overview of the nature of science (NoS) achieved

    Science.gov (United States)

    Wilujeng, Insih; Zuhdan Kun, P.; Suryadarma, IGP.

    2017-08-01

    The research concerned here examined the effectiveness of science learning conducted with local potential as basis from the point of a review of the NoS (nature of science) achieved. It used the non equivalent control group design and took place in the regions of Magelang and Pati, Province of Central Java, and the regions of Bantul and Sleman, Province of the Special Region of Yogyakarta. The research population consisted of students of the first and second grades at each junior high school chosen with research subjects sampled by means of cluster sampling. The instruments used included: a) an observation sheet, b) a written test, and c) a questionnaire. The learning and research instruments had been declared valid and reliable according to previous developmental research. In conclusion, the science learning based on local potential was effective in terms of all the NoS aspects.

  18. Resveratrol Prevented Lipopolysaccharide-Induced Endothelial Dysfunction in Rat Thoracic Aorta Through Increased eNOS Expression

    Science.gov (United States)

    Uğurel, Seda Sultan; Kuşçu, Nilay; Özenci, Çiler Çelik; Dalaklıoğlu, Selvinaz; Taşatargil, Arda

    2016-01-01

    Background: The cardiovascular benefits of Resveratrol (RVT) have been well established by previous experimental and clinical studies. Aims: The goal of this study was to test the effectiveness of RVT administration on the impaired endothelial function induced by lipopolysaccharide (LPS), and to elucidate the role of endothelial nitric oxide synthase (eNOS)/Sirtuin 1 (SIRT1) pathway. Study Design: Animal experiment. Methods: Endotoxemia was induced by intraperitoneal injection of 10 mg/kg LPS, and the thoracic aorta was isolated six hours later. RVT was injected intraperitoneally 15 minutes before LPS administration. Six hours after LPS injection, potassium chloride (KCl), phenylephrine (Phe), acetylcholine (ACh), and sodium nitroprusside (SNP) were used to examine to vascular reactivity and endothelial function. eNOS, phospho-eNOS (p-eNOS) (Ser 1177), and SIRT1 expressions in thoracic aorta were evaluated by Western blot. Results: LPS administration significantly inhibited the relaxation response induced by ACh, while the relaxation to SNP was not significantly altered. Phe- and KCl-induced contractile responses in the thoracic aorta significantly decreased in LPS-injected group. eNOS and p-eNOS expression decreased significantly in arteries obtained from LPS group rats. The impaired vasoreactivity as well as decreased expressions of eNOS, p-eNOS, and SIRT1 in vessels from LPS-injected rats were improved by RVT treatment. Conclusion: The endothelium-dependent vasodilatation of the thoracic aorta was significantly inhibited by LPS administration, and RVT treatment may improve vascular endothelial function. The protective effect of RVT might be associated with increased eNOS expression and activity. PMID:27403381

  19. Syringin may exert sleep-potentiating effects through the NOS/NO pathway.

    Science.gov (United States)

    Cui, Yue; Zhang, Ying; Liu, Gang

    2015-04-01

    Sleep is essential for basic survival as well as for optimal physical and cognitive performance in both human beings and animals. To investigate the effect of syringin on sleep of anesthetized mice and the potential mechanisms, 35 male Kunming mice were randomly divided into six experimental groups (n = 5) and one control group (n = 5). Sleep latency and sleep duration, as well as nitric oxide (NO) content and nitric oxide synthase (NOS) activity, were determined after syringin administration. The NO precursor l-Arginine (l-Arg) or NOS inhibitor NG-Nitro-l-arginine methyl ester (l-NAME) was administered alone or in combination with syringin, and time for sleep latency and duration was recorded. After intragastric administration of syringin, sleep latency decreased in a dose- and time-dependent manner, concomitant with increased sleep duration. The optimal sleep performance was obtained when syringin was given at a dose of 80 mg/kg for eight consecutive days. Syringin significantly reduced NO concentration and NOS activity. Administration of l-Arg prolonged sleep latency and shortened sleep duration, and the effects were fully reversed by syringin coadministration. Administration of L-NAME induced a significant reduction in sleep latency and a corresponding increase in sleep duration, and coadministration of syringin further enhanced the effects. The finding of our study demonstrated that syringin could exert sleep-potentiating effects on anesthetized mice in a time- and dose-dependent manner, and these effects may be intimately correlated with the NO/NOS pathway. © 2014 Société Française de Pharmacologie et de Thérapeutique.

  20. Association of polymorphisms in NOS3 with the ankle-brachial index in hypertensive adults.

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    Kullo, Iftikhar J; Greene, M Todd; Boerwinkle, Eric; Chu, Jian; Turner, Stephen T; Kardia, Sharon L R

    2008-02-01

    We investigated the association of 14 polymorphisms in the endothelial nitric oxide synthase gene (NOS3) with ankle brachial index (ABI) in non-Hispanic white hypertensives belonging to hypertensive sibships. Subjects (n=659, mean age 61+/-9 years, 54% women) underwent measurement of ABI using a standard protocol, and the lowest of 4 ABI values was used in the analyses. Non-synonymous SNPs with a minor allele frequency >0.02 and tag SNPs selected based on a measure of linkage disequilibrium (r(2)) were genotyped. We reduced the chance of false positives by testing for replication, randomly selecting 1 hypertensive sib from each sibship to create Subset 1 (n=330) and Subset 2 (n=329). Multivariable linear regression models were used to assess the associations of single NOS3 polymorphisms and haplotypes with ABI after adjustment for covariates (age, sex, body mass index, smoking, total cholesterol, HDL cholesterol, and diabetes). Two specific SNPs in significant LD with each other (rs891512 and rs1808593) were significantly associated with ABI in both subsets. Based on a sliding window approach with a window size of 2, estimated haplotypes from 2 SNP pairs (rs2070744-rs3918226 and rs1808593-rs7830) were also significantly associated with ABI in both subsets. In conclusion, specific NOS3 SNPs and haplotypes were associated with inter-individual variation in ABI, a non-invasive marker of peripheral arterial disease, in replicate subsets of hypertensive subjects. These findings motivate further investigation of the role of NOS3 variants in determining susceptibility to peripheral arterial disease.

  1. ASK1 Inhibitor Halts Progression of Diabetic Nephropathy in Nos3-Deficient Mice.

    Science.gov (United States)

    Tesch, Greg H; Ma, Frank Y; Han, Yingjie; Liles, John T; Breckenridge, David G; Nikolic-Paterson, David J

    2015-11-01

    p38 mitogen-activated protein kinase (MAPK) signaling promotes diabetic kidney injury. Apoptosis signal-regulating kinase (ASK)1 is one of the upstream kinases in the p38 MAPK-signaling pathway, which is activated by inflammation and oxidative stress, suggesting a possible role for ASK1 in diabetic nephropathy. In this study, we examined whether a selective ASK1 inhibitor can prevent the induction and progression of diabetic nephropathy in mice. Diabetes was induced in hypertensive endothelial nitric oxide synthase (Nos3)-deficient mice by five low-dose streptozotocin (STZ) injections. Groups of diabetic Nos3(-/-) mice received ASK1 inhibitor (GS-444217 delivered in chow) as an early intervention (2-8 weeks after STZ) or late intervention (weeks 8-15 after STZ). Control diabetic and nondiabetic Nos3(-/-) mice received normal chow. Treatment with GS-444217 abrogated p38 MAPK activation in diabetic kidneys but had no effect upon hypertension in Nos3(-/-) mice. Early intervention with GS-444217 significantly inhibited diabetic glomerulosclerosis and reduced renal dysfunction but had no effect on the development of albuminuria. Late intervention with GS-444217 improved renal function and halted the progression of glomerulosclerosis, renal inflammation, and tubular injury despite having no effect on established albuminuria. In conclusion, this study identifies ASK1 as a new therapeutic target in diabetic nephropathy to reduce renal inflammation and fibrosis independent of blood pressure control. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  2. Association between -T786C NOS3 polymorphism and resistant hypertension: a prospective cohort study

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    Martín-Luengo Cándido

    2009-08-01

    Full Text Available Abstract Background It is estimated that 5% of the hypertensive patients are resistant to conventional antihypertensive therapy. Polymorphisms in the endothelial nitric oxide synthase (NOS3 gene have been associated with high blood pressure levels, but not with resistant hypertension. The aim of the present study was to investigate if the -786T>C and G894T (Glu298Asp polymorphisms of the NOS3 gene were associated with resistant hypertension. Methods A prospective case-control observational study was performed. From a series of 950 consecutive patients followed up during 42 months, 48 patients with resistant hypertension were detected. 232 patients with controlled high blood pressure were also included. Results No differences were observed in the distribution of G894T (Glu298Asp NOS3 genotypes between the resistant hypertension group and the controlled hypertension patients. However, genotype -786CC was more frequent in the group of patients with resistant hypertension (33.3% than in the group of patients with controlled high blood pressure (17.7% (p 0.03. Furthermore carriers of allele T (-786TC and -786TT were more frequent in patients with controlled hypertension (82.3% than those with resistant hypertension (66.7% (Multivariate analysis; RR 2.09; 95% CI 1.03–4.24; p 0.004. Conclusion Our results indicate that genotype -786CC of the NOS3 gene increase the susceptibility to suffer resistant hypertension, which suggest that resistance to conventional therapy could be determined at the endothelial level.

  3. COX2 and NOS3 gene polymorphisms in women with gestational diabetes.

    Science.gov (United States)

    Tarnowski, Maciej; Tkacz, Marta; Dziedziejko, Violetta; Safranow, Krzysztof; Pawlik, Andrzej

    2017-08-01

    Gestational diabetes (GDM) is carbohydrate intolerance occurring in pregnancy. Low-grade inflammation plays an important role in the pathogenesis of this disorder. The present study aimed to examine the association between COX2 (rs6681231) and NOS3 (rs1799983 and rs2070744) gene polymorphisms and GDM. The study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75-g oral glucose tolerance test at 24-28 weeks of gestation. We observed an increased frequency of COX2 rs6681231 CC and GC genotype carriers among women with GDM (CC + GC versus GG, odds ratio = 1.55, 95% confidence interval = 1.01-2.36, p = 0.043; C versus G, odds ratio = 1.59, 95% confidence interval = 1.10-2.30, p = 0.013). There were no statistically significant differences in the distribution of NOS3 rs1799983 and rs2070744 between GDM and healthy women. Moreover, among women treated with insulin, we observed an increased frequency of COX2 rs6681231 CC and NOS3 rs1799983 TT genotype carriers. The results of the present study suggest that the CC genotype of the COX2 rs6681231 polymorphism is associated with an increased risk of GDM and the need for insulin therapy, whereas the TT genotype of the NOS3 rs1799983 polymorphism may be associated with the need for insulin therapy in women with GDM. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Fluctuation formula in the Nosé-Hoover thermostated Lorentz gas

    Science.gov (United States)

    Dolowschiák, M.; Kovács, Z.

    2005-02-01

    In this paper we examine numerically the Gallavotti-Cohen fluctuation formula for phase-space contraction rate and entropy production rate fluctuations in the Nosé-Hoover thermostated periodic Lorentz gas. Our results indicate that while the phase-space contraction rate fluctuations violate the fluctuation formula near equilibrium states, the entropy production rate fluctuations obey this formula near and far from equilibrium states as well.

  5. Simultaneous abrogation of NOS-2 and COX-2 activities is lethal in partially hepatectomised mice.

    Science.gov (United States)

    Zeini, Miriam; Hortelano, Sonsoles; Través, Paqui G; Martín-Sanz, Paloma; Boscá, Lisardo

    2004-06-01

    We have investigated the role of the nitric oxide (NO) and prostaglandins (PGs), respectively, synthesized by nitric oxide synthase 2 (NOS-2) and cyclooxygenase-2 (COX-2), in the outcome of liver regeneration after partial hepatectomy (PH). Liver mass recovery and molecular parameters related to cell proliferation and apoptotic death have been determined. NOS-2 and COX-2 are normally both expressed in the remnant liver after PH, and inhibition of either one delays regeneration. We found, however, that simultaneous suppression of the activities of NOS-2 (by gene knockout) and COX-2 (by pharmacological inhibition) resulted in animal death between 24 and 72 h after PH. Analysis of liver mass recovery and molecular parameters related to cell proliferation and apoptotic death revealed increased liver-cell apoptosis and an insufficient proliferative response. Broad-specificity caspase inhibitors, such as z-Val-Ala-Asp.fmk (z-VAD), or administration of NO-donors, rescued animals from death, revealing a critical apoptotic bias at this stage of proliferation. These findings demonstrate that simultaneous signaling by NO and prostaglandins plays an important role in the mechanism of liver regeneration after PH by protecting the remnant tissue from apoptotic death.

  6. The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI): II. Reliability and convergent validity.

    Science.gov (United States)

    McCauley, Stephen R; Wilde, Elisabeth A; Kelly, Tara M; Weyand, Annie M; Yallampalli, Ragini; Waldron, Eric J; Pedroza, Claudia; Schnelle, Kathleen P; Boake, Corwin; Levin, Harvey S; Moretti, Paolo

    2010-06-01

    A standardized measure of neurological dysfunction specifically designed for TBI currently does not exist and the lack of assessment of this domain represents a substantial gap. To address this, the Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) was developed for TBI outcomes research through the addition to and modification of items specifically relevant to patients with TBI, based on the National Institutes of Health Stroke Scale. In a sample of 50 participants (mean age = 33.3 years, SD = 12.9) TBI, internal consistency of the NOS-TBI was high (Cronbach's alpha = 0.942). Test-retest reliability also was high (rho = 0.97, p TBI total score was excellent (W = 0.995). Convergent validity was demonstrated through significant Spearman rank-order correlations between the NOS-TBI and the concurrently administered Disability Rating Scale (rho = 0.75, p TBI is a reliable and valid measure of neurological functioning in patients with moderate to severe TBI.

  7. Diagnosticos de enfermagem em pacientes classificados nos niveis I e II de prioridade do Protocolo Manchester

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    Cristiane Chaves de Souza

    2013-12-01

    Full Text Available O estudo objetivou identificar possíveis diagnósticos de enfermagem em pacientes classificados nos níveis I e II de prioridade do protocolo Manchester. Trata-se de estudo descritivo retrospectivo, cuja amostra foi de 40 prontuários de pacientes classificados nos níveis I e II de prioridade. Para identificação dos diagnósticos de enfermagem dois especialistas analisaram sinais e sintomas registrados nos prontuários dos pacientes no momento da classificação de risco. No nível I de prioridade, os diagnósticos de enfermagem mais frequentes foram: dor aguda (65,0%, padrão respiratório ineficaz (45,0% e troca de gases prejudicada (40,0%. No nível II de prioridade foram: dor aguda (80,0%, náusea (10,0% e risco de desequilíbrio eletrolítico (10,0%. Percebeu-se que a utilização do protocolo de Manchester favorece a identificação de características definidoras e fatores relacionados/fatores de risco que subsidiam a elaboração de diagnósticos de enfermagem na classificação de risco.

  8. Anemia nos pacientes com insuficiência cardíaca avançada

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    Juliano Cardoso

    2010-10-01

    Full Text Available FUNDAMENTO: Anemia está associada à pior evolução nos pacientes com insuficiência cardíaca (IC. Entretanto, há poucos estudos sobre a anemia nos pacientes com IC avançada. OBJETIVO: Avaliar as características da anemia na IC em fase avançada. MÉTODOS: Foram incluídos 99 pacientes hospitalizados para compensação de IC (CF IV/NYHA, com idade > 18 anos e FEVE 12 g/dl. A anemia foi marcador independente de mau prognóstico na análise multivariada (mortalidade 47% vs 24,6%, p = 0,016, risco relativo 2,54. CONCLUSÃO: Anemia acomete, aproximadamente, 1/3 dos pacientes com IC avançada, e a deficiência de ferro é uma importante etiologia. Pacientes anêmicos são mais idosos e apresentaram função renal mais deteriorada. A melhora da congestão não foi suficiente para melhorar a anemia na maioria dos casos. Nos pacientes com IC avançada, a anemia é marcador independente de mau prognóstico.

  9. O ENSINO DE TEATRO NOS CURSOS TÉCNICOS INTEGRADOS DO IFRN

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    Marinalva Nicácio de Moura

    2011-12-01

    Full Text Available Nesse trabalho, apresentamos uma reflexão sobre a sensibilidade estética expressa no corpo e nos gestos da narração de história em sala de aula, com intuito de ensinar teatro. O desenvolvimento dessa reflexão se dá a partir da atitude fenomenológica inspirada no filósofo francês Maurice Merleau-Ponty, na qual o corpo deixa de ser só um instrumento para significar no acontecimento teatral, realizando uma comunicação sensível na reflexibilidade corpórea. Os gestos do narrador nos dão a ver e a pensar sobre a linguagem e a comunicação do corpo, oferecendo-nos processos sensíveis e modos criativos de aprendizagem. Nessa perspectiva, a reflexão sobre o fenômeno do acontecimento teatral realizado em sala de aula, apresenta a narrativa de história como processo educativo do corpo, configurando-se como uma aprendizagem do fazer teatral. Um conhecimento sensível que pode contribuir com as reflexões sobre teatro e educação.

  10. PRIMITIVISMO E IMAGINÁRIO ETNOGRÁFICO NOS PRIMEIROS ESCRITOS DE MICHEL LEIRIS

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    Osvaldo Fontes Filho

    Full Text Available Resumo Nos anos 20 e 30, pari passu com a formação da etnologia como disciplina academicamente postada, o primitivo surge como trunfo retórico das invectivas mais críticas contra os marasmos da civilização branca. Michel Leiris (1901-1990, nos primeiros tempos de sua formação de etnólogo, desperta para as possibilidades de desvio expressivo que ofereciam as artes ditas primitivas. Engajado em uma autorretratística literária afeita à deambulação imaginária pelos lugares da Cultura, da Mitologia e da História, o autor de L'Afrique fantôme (1934 sedimenta seus recursos estilísticos em artigos sulfurosos para a revista de vanguarda Documents (1929-1931, nos quais é possível observar a formação inicial de seu imaginário etnográfico e do que se convenciona chamar, a seu respeito, uma "etnografia de si". Este texto revisita alguns momentos da escrita leirisiana que ajudaram a impregnar de jogos de linguagem e de ficção uma nascente consciência antropológica e etnográfica, pouco propensa à objetividade imparcial e à neutra documentação científica do Outro.

  11. Bilirubin exerts pro-angiogenic property through Akt-eNOS-dependent pathway.

    Science.gov (United States)

    Ikeda, Yasumasa; Hamano, Hirofumi; Satoh, Akiho; Horinouchi, Yuya; Izawa-Ishizawa, Yuki; Kihira, Yoshitaka; Ishizawa, Keisuke; Aihara, Ken-Ichi; Tsuchiya, Koichiro; Tamaki, Toshiaki

    2015-11-01

    Low serum bilirubin levels are associated with the risk of cardiovascular diseases including peripheral artery disease. Bilirubin is known to exert its property such as antioxidant effect or the enhancement of flow-mediated vasodilation, however, bilirubin action on angiogenesis remains unclear. To investigate the molecular mechanism of bilirubin on angiogenic effect, we first employed C57BL/6J mice with unilateral hindlimb ischemia surgery and divided the mice into two groups (vehicle-treated group and bilirubin-treated group). The analysis of laser speckle blood flow demonstrated the enhancement of blood flow recovery in response to ischemia of mice with bilirubin treatment. The density of capillaries was significantly higher in ischemic-adductor muscles of bilirubin-treated mice. The phosphorylated levels of endothelial nitric oxide synthase (eNOS) and Akt were increased in ischemic skeletal muscles of mice with bilirubin treatment compared with vehicle treatment. In in vitro experiments by using human aortic endothelial cells, bilirubin augmented eNOS and Akt phosphorylation, cell proliferation, cell migration and tube formation. These bilirubin actions on endothelial cell activation were inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. In conclusion, bilirubin promotes angiogenesis through endothelial cells activation via Akt-eNOS-dependent manner.

  12. A Socioscientific Curriculum Facilitating the Development of Distal and Proximal NOS Conceptualizations

    Science.gov (United States)

    Schalk, Kelly A.

    2012-01-01

    This study reports the effects of an innovative introductory microbiology course for undergraduates that used a socioscientific issues (SSI)-based curriculum. The study illustrates how an SSI-based intervention provides learners with pragmatic opportunities for cultivating their scientific literacy subsuming the nature of science (NOS). Empirical data measured 26 undergraduates' distal and proximal knowledge of the NOS with respect to their ability to reason. The instruments used in this case study yielded qualitative data, which were coded using NVivo7 and inductively analyzed. All data analyses were subject to instrumental triangulation, inter-rater reliability, and member-checking. These analyses determined that undergraduates' formal epistemological knowledge of professional science matured. These changes accompanied improved reasoning skills and matured beliefs about the NOS. In particular, students' reasoning changed as they realized that scientific knowledge is never absolute or certain but tentative and subject to change. In general, the findings suggest that this SSI-based curriculum enhanced collegiate students' understanding of social issues that affect their lives. Implications of this research are discussed.

  13. Effect of magnesium supplementation on blood rheology in NOS inhibition-induced hypertension model.

    Science.gov (United States)

    Cengiz, Melike; Ülker, Pinar; Üyüklü, Mehmet; Yaraş, Nazmi; Özen, Nur; Aslan, Mutay; Özyurt, Dilek; Basralı, Filiz

    2016-01-27

    This study investigated the effects of magnesium on blood rheological properties and blood pressure in nitric oxide synthase (NOS) inhibition-induced hypertension model. Hypertension was induced by oral administration of the nonselective NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg/day) for 6 weeks and systolic blood pressure was measured by the tail-cuff method. The groups receiving magnesium supplementation were fed with rat chow containing 0.8% magnesium oxide during the experiment. At the end of experiment, blood samples were obtained from abdominal aorta, using ether anesthesia. Plasma and erythrocyte magnesium levels were determined by the atomic absorption spectrometer. RBC deformability and aggregation were determined by rotational ektacytometry. Plasma fibrinogen concentration was evaluated by ELISA. Whole blood and plasma viscosities were determined by viscometer and intracellular free Ca++ level was measured by using spectroflurometric method. Blood pressure was elevated in hypertensive groups and suppressed by magnesium therapy. Plasma viscosity and RBC aggregation were found to be higher in hypertensive rats than control animals and these parameters significantly decreased in magnesium supplemented hypertensive animals. Other measurements were not different between experimental groups. These results confirm that blood pressure, plasma viscosity and RBC aggregation increased in NOS inhibition-induced hypertension model and oral magnesium supplementation improved these parameters.

  14. Association of NOS3 tag polymorphisms with hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Kuzmanić Samija, Radenka; Primorac, Dragan; Resić, Biserka; Lozić, Bernarda; Krzelj, Vjekoslav; Tomasović, Maja; Stoini, Eugenio; Samanović, Ljubo; Benzon, Benjamin; Pehlić, Marina; Boraska, Vesna; Zemunik, Tatijana

    2011-06-01

    To test the association of NOS3 gene with hypoxic-ischemic encephalopathy (HIE). The study included 110 unrelated term or preterm born children (69 boys and 41 girls) with HIE and 128 term and preterm born children (60 boys and 68 girls) without any neurological problems after the second year of life. Children with perinatal HIE fulfilled the diagnostic criteria for perinatal asphyxia. All children were admitted to the Clinical Hospital Split between 1992 and 2008. We analyzed 6 tagging single nucleotide polymorphisms (SNP) within NOS3 gene (rs3918186, rs3918188, rs1800783, rs1808593, rs3918227, rs1799983), in addition to previously confirmed NOS3-associated SNP rs1800779. Genotyping was conducted using real-time polymerase chain reaction (PCR). Association analyses were performed according to allelic and genotypic distribution. Allelic test did not show any SNP association with HIE. SNP rs1808593 showed genotype association (P=0.008) and rs1800783-rs1800779 TG haplotype showed an association with HIE (PNOS3 polymorphisms with HIE.

  15. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

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    Kuzmanić Šamija, R. [Department of Pediatrics, University Hospital Split, Split (Croatia); Primorac, D. [School of Medicine Split, University of Split, Split (Croatia); Department of Pediatrics, School of Medicine, University of Osijek, Osijek (Croatia); Eberly College of Science, Penn State University, University Park, PA (United States); St. Catherine Speciality Hospital, Zabok (Croatia); Rešić, B. [School of Medicine Split, University of Split, Split (Croatia); Pavlov, V. [Department of Neonatology, University Hospital Split, Split (Croatia); Čapkun, V. [Department of Nuclear Medicine, University Hospital Split, Split (Croatia); Punda, H. [School of Medicine Split, University of Split, Split (Croatia); Lozić, B. [Department of Pediatrics, University Hospital Split, Split (Croatia); Zemunik, T. [Department of Medical Biology, School of Medicine Split, University of Split, Split (Croatia)

    2014-08-15

    The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

  16. Correlation of interactions between NOS3 polymorphisms and oxygen therapy with retinopathy of prematurity susceptibility.

    Science.gov (United States)

    Yu, Chunhong; Yi, Jinglin; Yin, Xiaolong; Deng, Yan; Liao, Yujun; Li, Xiaobing

    2015-01-01

    This study was aimed to detect the correlation of nitric oxide synthase 3 (NOS3) gene polymorphisms (T-786C and G894T) and retinopathy of prematurity (ROP) susceptibility. Interaction between NOS3 gene polymorphisms and the duration of oxygen therapy was also explored in ROP babies. Genotypes of NOS3 gene polymorphisms were genotyped by MassArray method. Hardy-Weinberg equilibrium (HWE) was used to calculate the representativeness of the cases and controls. Crossover analysis was utilized to explore the gene environment interactions. Relative risk of ROP was presented by odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs). Among the subject features, oxygen therapy had obvious difference between case and control groups (PNOS3 gene polymorphisms and oxygen therapy duration. When the duration of oxygen therapy was less than 17 days, both -786CC genotype and 894GT genotype were correlated with ROP susceptibility (P=0.020, OR=0.115, 95% CI=0.014-0.960; P=0.011, OR=0.294, 95% CI=0.100-0.784). -786C allele might have a protective effect for ROP. Interactions of -786CC and 894GT genotype with oxygen therapy duration (less than 17 days) were both protection factors of ROP.

  17. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Kuzmanić Šamija, R; Primorac, D; Rešić, B; Pavlov, V; Čapkun, V; Punda, H; Lozić, B; Zemunik, T

    2014-10-01

    The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

  18. Plasma gelsolin improves lung host defense against pneumonia by enhancing macrophage NOS3 function.

    Science.gov (United States)

    Yang, Zhiping; Chiou, Terry Ting-Yu; Stossel, Thomas P; Kobzik, Lester

    2015-07-01

    Plasma gelsolin (pGSN) functions as part of the "extracellular actin-scavenging system," but its potential to improve host defense against infection has not been studied. In a mouse model of primary pneumococcal pneumonia, recombinant human pGSN (rhu-pGSN) caused enhanced bacterial clearance, reduced acute inflammation, and improved survival. In vitro, rhu-pGSN rapidly improved lung macrophage uptake and killing of bacteria (Streptococcus pneumoniae, Escherichia coli, and Francisella tularensis). pGSN triggers activating phosphorylation (Ser(1177)) of macrophage nitric oxide synthase type III (NOS3), an enzyme with important bactericidal functions in lung macrophages. rhu-pGSN failed to enhance bacterial killing by NOS3(-/-) macrophages in vitro or bacterial clearance in NOS3(-/-) mice in vivo. Prophylaxis with immunomodulators may be especially relevant for patients at risk for secondary bacterial pneumonia, e.g., after influenza. Treatment of mice with pGSN challenged with pneumococci on postinfluenza day 7 (the peak of enhanced susceptibility to secondary infection) caused a ∼15-fold improvement in bacterial clearance, reduced acute neutrophilic inflammation, and markedly improved survival, even without antibiotic therapy. pGSN is a potential immunomodulator for improving lung host defense against primary and secondary bacterial pneumonia. Copyright © 2015 the American Physiological Society.

  19. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

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    R. Kuzmani? ?amija

    2014-10-01

    Full Text Available The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

  20. História Brasileira nos Estados Unidos: perspectivas teóricas e historiográficas

    OpenAIRE

    Blake, Stanley E.

    2010-01-01

    Desde o início nos anos 1990, os historiadores que trabalham com o Brasil nos Estados Unidos começaram a produzir estudos sob a influência da Nova História Cultural. Esses historiadores, influenciados pelas tendências da história, dos estudos literários e das ciências sociais nos Estados Unidos, na Europa e na América Latina, adotaram o estudo da cultura e passaram a questionar as tradicionais abordagens teóricas, metodológicas e  epistemológicas da história. Neste sentido, iremos discutir no...

  1. KONSUMSI MIKRONUTRIEN DAN EKSPRESI GEN eNOS3 ALEL INTRO 4a4b PADA PENDERITA HIPERTENSI ETNIK MINANGKABAU

    Directory of Open Access Journals (Sweden)

    Delmi Sulastri

    2011-05-01

    Full Text Available AbstrakGen eNOS3 varian intron 4a4b merupakan salah satu gen yang berhubungan dengan kejadian hipertensi esensial. Kemampuan Gen eNOS3 varian ini untuk mensintesis enzim nitric oxide synthase (NOS berkurang sehingga sintesis Nitric oxide (NO menurun. Senyawa NO adalah suatu senyawa vasoaktif yang menyebabkan vasodilatasi pembuluh darah.Penelitian pada subjek hipertensi dan normotensi berusia 30-65 tahun bertujuan untuk melihat pengaruh mikronutrien terhadap ekspresi gen eNOS3 alel intron 4a4b. 130 subjek, diwawancara pola makannya lalu dilakukan analisis asupan mikronutrien, gen eNOS3, serta kadar NO plasma. Data yang diperoleh dianalisis menggunakan uji T dan chi-square.Kadar NO plasma penderita hipertensi adalah 26.91 + 15.40 μM/L dan normotensi 25.79 + 15.04 μM/L. 55.5% subjek hipertensi memiliki gen eNOS3 varian intron 4b dan 69% subjek normotensi mempunyai varian intron 4a4b. Kadar NO plasma rendah, (66.7% ditemukan pada subjek hipertensi dengan varian intron 4b. Tidak terdapat hubungan bermakna asupan mikronutrien dengan kadar NO plasma pada subjek hipertensi.Hasil ini tidak mendukung pengaruh konsumsi mikronutrien terhadap kadar NO plasma pada penderita hipertensi dengan gen eNOS3 varian intron 4a4b.Kata Kunci : hipertensi esensial, gen eNOS3, kadar NO plasmaAbstracteNOS 3 gene intron 4a4b allel is one of the important genes which is related to hypertesion essensial. This gene expresses the nitric oxide synthase (NOS enzyme which regulates the synthesis of Nitric oxide (NO in human body. NO causes vasodilatation, which decreases peripheral resistant and blood pressure.A research has been done based on cross sectional study on hypertension patients and those with normal blood pressure in the range of 30-65 years old. The main of this research is to evaluate the influence of micronutrient consumption on eNOS3 gene intron 4a4b allel expression in hypertension subjects in Minangkabau ethnicity. 130 subjects interviewed about micronutrient

  2. Effect of NOS3 gene polymorphism on response to Tricyclic antidepressants in migraine attacks.

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    Aliasghar Molana

    2014-09-01

    Full Text Available Migraine is a chronic neurological disorder, characterized by recurrent moderate to severe headaches. Worldwide migraine affects nearly 15%. Studies suggest that genes involved in the production of nitric oxide (NO may act as genetic factors for migraine. NO synthase 3 (NOS3 by expressing enzyme NOS regulates endothelial derived NO. One class of medications used as first-line treatment in migraine prophylaxis is tricyclic antidepressants (TCAs. The aim of this study was to determine effects of NOS3 gene Glu298Asp polymorphism in the production of NO and response of patients to TCAs in migraine attacks.A total of 80 migraine patients were invited to participate in the study. Patients recorded the characteristics of their migraine attacks such as frequency of attacks and intensity of headaches for the 1(st month of the study. Then peripheral blood samples were taken from all subjects in order to determine patients' genotype distribution, mRNA expression level of NOS3 and NO content of plasma. Patients were then instructed to use 25 mg nortriptyline at night before bed for 3 months. At the end of 3(rd month of the treatment patients again recorded the migraine characteristics for 1 month and blood sampling was performed in order to determine the level of plasma NO.The patients' genotype distribution for TT, GT, and GG was 9, 24, and 47 subjects, respectively. Mean NO level in patients with TT genotype was less in comparison to GT and GG genotypes before and after use of TCAs (P < 0.05. Mean intensity of headaches in patients with TT genotype was lower in comparison to GT and GG genotypes before and after use of TCAs (based on verbal numerical rating scale. Mean frequency of migraine attacks after use of TCAs was significantly decreased in all genotypes of NOS3 Glu298Asp polymorphism particularly in TT genotype (P < 0.05.Presence of T allele of the Glu298Asp polymorphism may be a factor for TT genotype patients to produce less NO and is a favorable

  3. Polymorphisms of the NOS3 gene in Tunisian patients with Behçet's disease.

    Science.gov (United States)

    Kallel, A; Sbaï, M H; Houman, M H; Sediri, Y; Ouertani, D; Smiti Khanfir, M; Ben Ghorbel, I; Jemaa, R; Kaabachi, N

    2015-04-01

    Behçet's disease (BD) is a multisystem inflammatory disease characterized by recurrent orogenital ulceration, ocular inflammation and skin lesions. Reduced plasma nitric oxide (NO) levels in patients with BD have been implicated in the development of the endothelial abnormalities and thrombotic complications occurring in these patients. Polymorphisms in the endothelial nitric oxide synthase gene (NOS3) have been inconsistently associated with BD. This inconsistency may derive from population stratification secondary to ethnic diversity, and consideration limited to only one rather than combinations of polymorphisms. We studied three genetic variations in the NOS3 gene: a single nucleotide polymorphism in the promoter region -786T>C, in exon 7 (Glu298Asp), and a variable number of tandem repeats in intron 4 (4a4b) of the NOS3 gene in 100 unrelated Tunisian patients with BD and 148 healthy controls. In addition, we also examined the association of NOS3 gene haplotypes with BD. Analyses of the Glu298Asp, -786T>C and 4a4b polymorphisms were made by the polymerase chain reaction (PCR) restriction fragment length polymorphism technique and PCR genotyping, respectively. The distribution of the Glu298Asp genotype differed significantly between patients with BD and controls (P = 0.01). Allele Asp298 was significantly more frequent in patients with BD than in controls (P = 0.005, OR = 1.70, 95% CI 1.14-2.54). In contrast, distribution of alleles and genotypes of -786T>C and 4a4b polymorphisms was not different between the control and BD group. However, the frequency of Asp-T-4b haplotype was significantly higher in patients with BD than in healthy controls. By gender, the signification remained only for heterozygous men (P = 0.03) and homozygous women (P = 0.02). These results suggest that Glu298Asp polymorphism of the NOS3 gene is associated with BD susceptibility in Tunisian patients. © 2015 John Wiley & Sons Ltd.

  4. Modificações do processo avaliativo da aprendizagem nos anos iniciais do ensino fundamental

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    Mônica de Almeida Mendes

    2011-07-01

    Full Text Available A presente pesquisa aborda a temática: Modificações do processo avaliativo da aprendizagem nos anos iniciais do Ensino Fundamental. Apresentamos os aspectos que envolvem a avaliação no método tradicional de ensino, bem como, a metodologia utilizada na Escola Organizada por Ciclos de Formação Humana, que traz uma nova metodologia de ensino e uma nova forma de avaliar, chamada de avaliação formativa, que tem por objetivo buscar a interação professor/aluno, respeitando as capacidades, oportunizando-os momentos de expressar suas idéias. Embasamo-nos em autores como Jussara Hoffmann e Jefferson Mainardes, que colaboram para o entendimento de questões como: O que é avaliar e Qual a importância da avaliação na Educação tradicional e nos Ciclos. Utilizamos a Lei de Diretrizes e Bases, para nos informar quanto à forma de organização curricular, como a avaliação deve ocorrer de modo que promova o desenvolvimento do aluno. Para contemplar as questões que nortearam a investigação, utilizamos o método de pesquisa qualitativo, por meio de questionários, bem como realização de entrevista com uma profissional do Centro de Formação e Atualização dos Profissionais da Educação Básica de Sinop – MT, que nos apresentou a visão atual dos problemas e evoluções deste modelo de avaliação. Por fim, consideramos a avaliação no dia a dia da educação, apresentando a necessidade de todos os tipos de avaliação de maneira que são apresentadas as situações em que cada uma é utilizada, e quais seus objetivos ao serem aplicadas.Palavras-chave: educação; avaliação; instrumento de aprendizagem; avaliação formativa; avaliação somativa.

  5. Engenho e temperamentos nos catálogos e no pensamento da Companhia de Jesus nos séculos XVII e XVIII

    OpenAIRE

    2008-01-01

    O artigo visa entender as relações entre a potência psíquica do "engenho", algumas qualidades temperamentais específicas e as funções a serem exercidas pelo indivíduo possuidor destas características delineadas nos Catálogos da Companhia de Jesus ao longo dos séculos XVII e XVIII. Evidencia a presença destas associações como lugar-comum na literatura jesuítica da época, a importância do engenho como qualidade exigida para exercer ministérios relevantes na Ordem, e necessidade do indivíduo pos...

  6. Engenho e temperamentos nos catálogos e no pensamento da Companhia de Jesus nos séculos XVII e XVIII

    Directory of Open Access Journals (Sweden)

    Marina Massimi

    2008-12-01

    Full Text Available O artigo visa entender as relações entre a potência psíquica do "engenho", algumas qualidades temperamentais específicas e as funções a serem exercidas pelo indivíduo possuidor destas características delineadas nos Catálogos da Companhia de Jesus ao longo dos séculos XVII e XVIII. Evidencia a presença destas associações como lugar-comum na literatura jesuítica da época, a importância do engenho como qualidade exigida para exercer ministérios relevantes na Ordem, e necessidade do indivíduo possuir uma complexão física adequada a estas exigências.

  7. Archive of information about geosamples curated by NMNH collected during NOAA/NOS and USCGS hydrographic surveys

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Prior to August 2001, physical sediment samples collected by U.S. Coast and Geodetic Survey (USCGS) and NOAA National Ocean Service (NOS) personnel during...

  8. Transient Acidosis during Early Reperfusion Attenuates Myocardium Ischemia Reperfusion Injury via PI3k-Akt-eNOS Signaling Pathway

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    Xin Qiao

    2013-01-01

    Full Text Available In this paper, we concluded that transient acidosis reperfusion conferred cardioprotection against myocardial ischemia reperfusion injury in isolated rat hearts through activating PI3K-Akt-eNOS pathway.

  9. Study on the NO Concentration and NOS Activity in the Serum and Tissues of Ducklings with Selenium Poisoning

    Institute of Scientific and Technical Information of China (English)

    WU Rui; KANG Shi-liang; XU Shi-wen; WANG Wei; LIN Hong-jin

    2003-01-01

    One-day-old healthy ducklings (n=100) were divided into control group and experimental group randomly, and selenium poisoning of ducklings was artificially caused by feeding ration containing 8 lng kg-1 Se every day. The dynamic changes of No content and NOS activity in the serum and tissues were determined by means of the method of nitric acid reductase. Results showed that the NO content and NOS activity in serum and tissues in experimental group increased significantly (P<0.05) and they were time-dependent.It was suggested that the high level of selenium in bodies could increase the NOS activity and NO content as it destroyed the metabolism of material and energy as well as structure and function of tissues and cells. These changes of NO content and NOS activity might be involved in the metabolism of selenium poisoning.

  10. National Ocean Service (NOS) Cartographic Codes for Bottom Character in the Gulf of Maine region (NOSGOM shapefile)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data were collected by the National Ocean Service (NOS, formerly the U.S. Coast and Geodetic Survey) for the purpose of charting the coastal waters and...

  11. Effects of polymorphisms of NOS3 and GNB3 genes on skin microvascular reactivity in normal pregnancy.

    Science.gov (United States)

    Radkov, O V; Volf, Ju V

    2013-05-01

    We studied the relationship between endothelial NO-synthase gene (NOS3) and G protein β3 subunit gene (GNB3) polymorphisms and reactivity of skin microvessels during physiological gestation. T-786C NOS3 polymorphism influenced the maximum blood flow rate in skin microvessels and the severity of postocclusive reactive hyperemia during the third trimester of pregnancy. The relationship between G894T NOS3 polymorphism and the duration of postocclusive reactive hyperemia was revealed. C825T GNB3 polymorphism affects the duration and severity of postocclusive reactive hyperemia during the first and third trimesters of pregnancy. Thus, NOS3 and GNB3 polymorphisms affect blood flow in the skin microvessels during physiological gestation.

  12. Expression dynamics of HSP90 and nitric oxide synthase (NOS) isoforms during heat stress acclimation in Tharparkar cattle

    Science.gov (United States)

    Bharati, Jaya; Dangi, S. S.; Bag, S.; Maurya, V. P.; Singh, G.; Kumar, P.; Sarkar, M.

    2017-08-01

    Six male Tharparkar cattle of 2-3 years old were selected for the study. After 15-day acclimation at thermoneutral zone (TNZ) in psychrometric chamber, animals were exposed at 42 °C for 6 h up to 23 days followed by 12 days of recovery period. Blood samples were collected during control period at TNZ (days 1, 5, and 12), after heat stress exposure (day 1, immediate heat stress acclimation (IHSA); days 2 to 10, short-term heat stress acclimation (STHSA); days 15 to 23, long-term heat stress acclimation (LTHSA); days 7 and 12, recovery period), and peripheral blood mononuclear cells (PBMCs) were isolated for RNA and protein extraction. The messenger RNA (mRNA) and protein expression in PBMCs were determined by qPCR and western blot, respectively. Samples at TNZ were taken as control. The mRNA expression of HSP90, iNOS, and eNOS was significantly upregulated ( P < 0.05) on day 1 (ISHA) as compared to control, remained consistent during STHSA, again increased during LTHSA, and finally reduced to basal level during recovery period. The protein expression of HSP90, iNOS, and eNOS were akin to their transcript pattern. PBMC culture study was conducted to study transcriptional abundance of HSP90, iNOS, and eNOS at different temperature-time combinations. The present findings indicate that HSP90, iNOS, and eNOS could possibly play an important role in mitigating thermal insults and confer thermotolerance during long-term heat stress exposure in Tharparkar cattle.

  13. Endotoxin mediated-iNOS induction causes insulin resistance via ONOO⁻ induced tyrosine nitration of IRS-1 in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Geneviève Pilon

    Full Text Available BACKGROUND: It is believed that the endotoxin lipopolysaccharide (LPS is implicated in the metabolic perturbations associated with both sepsis and obesity (metabolic endotoxemia. Here we examined the role of inducible nitric oxide synthase (iNOS in skeletal muscle insulin resistance using LPS challenge in rats and mice as in vivo models of endotoxemia. METHODOLOGY/PRINCIPAL FINDINGS: Pharmacological (aminoguanidine and genetic strategies (iNOS⁻/⁻ mice were used to counter iNOS induction in vivo. In vitro studies using peroxynitrite (ONOO⁻ or inhibitors of the iNOS pathway, 1400 W and EGCG were conducted in L6 myocytes to determine the mechanism by which iNOS mediates LPS-dependent insulin resistance. In vivo, both pharmacological and genetic invalidation of iNOS prevented LPS-induced muscle insulin resistance. Inhibition of iNOS also prevented insulin resistance in myocytes exposed to cytokine/LPS while exposure of myocytes to ONOO⁻ fully reproduced the inhibitory effect of cytokine/LPS on both insulin-stimulated glucose uptake and PI3K activity. Importantly, LPS treatment in vivo and iNOS induction and ONOO⁻ treatment in vitro promoted tyrosine nitration of IRS-1 and reduced insulin-dependent tyrosine phosphorylation. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates that iNOS-mediated tyrosine nitration of IRS-1 is a key mechanism of skeletal muscle insulin resistance in endotoxemia, and presents nitrosative modification of insulin signaling proteins as a novel therapeutic target for combating muscle insulin resistance in inflammatory settings.

  14. Clustering of cardiovascular risk factors mimicking the human metabolic syndrome X in eNOS null mice.

    OpenAIRE

    Cook, S; Hugli, O; Egli, M; Vollenweider, P.; Burcelin, R.; Nicod, P; Thorens, B.; Scherrer, U

    2003-01-01

    AIMS/HYPOTHESIS: The metabolic syndrome comprises a clustering of cardiovascular risk factors but the underlying mechanism is not known. Mice with targeted disruption of endothelial nitric oxide synthase (eNOS) are hypertensive and insulin resistant. We wondered, whether eNOS deficiency in mice is associated with a phenotype mimicking the human metabolic syndrome. METHODS AND RESULTS: In addition to arterial pressure and insulin sensitivity (euglycaemic hyperinsulinaemic clamp), we measured t...

  15. Pharmacogenetic Association of NOS3 Variants with Cardiovascular Disease in Patients with Hypertension: The GenHAT Study

    OpenAIRE

    Xue Zhang; Lynch, Amy I; Davis, Barry R.; Ford, Charles E.; Eric Boerwinkle; Eckfeldt, John H.; Catherine Leiendecker-Foster; Arnett, Donna K.

    2012-01-01

    Nitric oxide synthase 3 (NOS3) catalyzes production of NO in the endothelium and may play a role in cardiovascular disease (CVD). We assessed the pharmacogenetic associations of three NOS3 polymorphisms and three antihypertensive drugs with CVD outcomes. Hypertensive subjects (n = 30,280) from a multi-center, double-blind clinical trial were randomized to chlorthalidone, amlodipine, or lisinopril treatment (mean follow up, 4.9 years). Outcomes included coronary heart disease (CHD: fatal CHD a...

  16. Diminished neurogenic femoral artery vasoconstrictor response in a Zucker obese rat model: differential regulation of NOS and COX derivatives.

    Directory of Open Access Journals (Sweden)

    Ana Cristina Martínez

    Full Text Available OBJECTIVE: Peripheral arterial disease is one of the macrovascular complications of type 2 diabetes mellitus. This study addresses femoral artery regulation in a prediabetic model of obese Zucker rats (OZR by examining cross-talk between endothelial and neural factors. METHODS AND RESULTS: Arterial preparations from lean (LZR and OZR were subjected to electrical field stimulation (EFS on basal tone. Nitric oxide synthase (NOS and cyclooxygenase (COX isoform expression patterns were determined by immunohistochemical labelling and Western blotting. Results indicate significantly reduced noradrenergic contractions in preparations from OZR compared with those of LZR. Functional inhibition of endothelial NOS (eNOS indicated a predominant role of this isoform in LZR and its modified activity in OZR. Neural (nNOS and inducible NOS (iNOS were activated and their expression was higher in femoral arteries from OZR. Neurotransmission modulated by large-conductance Ca2+-activated (BKCa or voltage-dependent (KV K+ channels did not seem compromised in the obese animals. Endothelial COX-1 and COX-2 were expressed in LZR and an additional adventitial location of COX-2 was also observed in OZR, explaining the higher COX-2 protein levels detected in this group. Prostanoids derived from both isoforms helped maintain vasoconstriction in LZR while in OZR only COX-2 was active. Superoxide anion inhibition reduced contractions in endothelium-intact arteries from OZR. CONCLUSIONS: Endothelial dysfunction led to reduced neurogenic vasoconstriction in femoral arteries from OZR. In a setting of obesity, NO-dependent nNOS and iNOS dilation activity could be an alternative mechanism to offset COX-2- and reactive oxygen species-mediated vasoconstriction, along with impaired endothelial NO relaxation.

  17. Human red blood cells at work: identification and visualization of erythrocytic eNOS activity in health and disease.

    Science.gov (United States)

    Cortese-Krott, Miriam M; Rodriguez-Mateos, Ana; Sansone, Roberto; Kuhnle, Gunter G C; Thasian-Sivarajah, Sivatharsini; Krenz, Thomas; Horn, Patrick; Krisp, Christoph; Wolters, Dirk; Heiß, Christian; Kröncke, Klaus-Dietrich; Hogg, Neil; Feelisch, Martin; Kelm, Malte

    2012-11-15

    A nitric oxide synthase (NOS)-like activity has been demonstrated in human red blood cells (RBCs), but doubts about its functional significance, isoform identity and disease relevance remain. Using flow cytometry in combination with the nitric oxide (NO)-imaging probe DAF-FM we find that all blood cells form NO intracellularly, with a rank order of monocytes > neutrophils > lymphocytes > RBCs > platelets. The observation of a NO-related fluorescence within RBCs was unexpected given the abundance of the NO-scavenger oxyhemoglobin. Constitutive normoxic NO formation was abolished by NOS inhibition and intracellular NO scavenging, confirmed by laser-scanning microscopy and unequivocally validated by detection of the DAF-FM reaction product with NO using HPLC and LC-MS/MS. Using immunoprecipitation, ESI-MS/MS-based peptide sequencing and enzymatic assay we further demonstrate that human RBCs contain an endothelial NOS (eNOS) that converts L-(3)H-arginine to L-(3)H-citrulline in a Ca(2+)/calmodulin-dependent fashion. Moreover, in patients with coronary artery disease, red cell eNOS expression and activity are both lower than in age-matched healthy individuals and correlate with the degree of endothelial dysfunction. Thus, human RBCs constitutively produce NO under normoxic conditions via an active eNOS isoform, the activity of which is compromised in patients with coronary artery disease.

  18. Role of Endothelial Nitric Oxide Synthase in Diabetic Nephropathy: Lessons from Diabetic eNOS Knockout Mice

    Directory of Open Access Journals (Sweden)

    Takamune Takahashi

    2014-01-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease in many countries. The animal models that recapitulate human DN undoubtedly facilitate our understanding of this disease and promote the development of new diagnostic markers and therapeutic interventions. Based on the clinical evidence showing the association of eNOS dysfunction with advanced DN, we and others have created diabetic mice that lack eNOS expression and shown that eNOS-deficient diabetic mice exhibit advanced nephropathic changes with distinct features of progressive DN, including pronounced albuminuria, nodular glomerulosclerosis, mesangiolysis, and arteriolar hyalinosis. These studies clearly defined a critical role of eNOS in DN and developed a robust animal model of this disease, which enables us to study the pathogenic mechanisms of progressive DN. Further, recent studies with this animal model have explored the novel mechanisms by which eNOS deficiency causes advanced DN and provided many new insights into the pathogenesis of DN. Therefore, here we summarize the findings obtained with this animal model and discuss the roles of eNOS in DN, unresolved issues, and future investigations of this animal model study.

  19. Impact of Lifestyle Intervention on HDL-Induced eNOS Activation and Cholesterol Efflux Capacity in Obese Adolescent

    Directory of Open Access Journals (Sweden)

    Jenny Wesnigk

    2016-01-01

    Full Text Available Background. Endothelial dysfunction occurs in obese children and adolescent and is regarded as a key step in the development of atherosclerosis. Important components for the development of endothelial dysfunction are reduced activity of endothelial nitric oxide synthase (eNOS and an increase in cholesterol deposition in the vessel wall, due to reduced reverse cholesterol transport (RCT activity. High density lipoprotein (HDL exhibits antiatherosclerotic properties including modulation of eNOS activity and cholesterol efflux capacity. Lifestyle intervention programs can modify endothelial dysfunction in obese adolescents, but their impact on HDL-mediated eNOS activation and RCT is unknown so far. Methods. Obese adolescents (15±1 years, BMI > 35 kg/m2 where randomized either to an intervention group (IG, n=8; restricted diet and exercise or to a usual care group (UC, n=8. At the beginning and after 10 months of treatment HDL-mediated eNOS phosphorylation and cholesterol efflux capacity were evaluated. Results. Ten months of treatment resulted in a substantial weight loss (−31%, an improvement of endothelial function, and an increase in HDL-mediated eNOS-Ser1177 phosphorylation and RCT. A correlation between change in eNOS-Ser1177 phosphorylation or RCT and change in endothelial function was noted. Conclusion. A structured lifestyle intervention program improves antiatherosclerotic HDL functions, thereby positively influencing endothelial function.

  20. Mesenchymal Stem Cells with eNOS Over-Expression Enhance Cardiac Repair in Rats with Myocardial Infarction.

    Science.gov (United States)

    Chen, Leilei; Zhang, Yuan; Tao, Liangliang; Yang, Zhijian; Wang, Liansheng

    2017-02-01

    Transplantation of mesenchymal stem cells (MSCs) is a promising therapeutic option for patients with acute myocardial infarction. We show here that the ectopic overexpression of endothelial nitric oxide synthases (eNOS), an endothelial form of NOS, could enhance the ability of MSCs in treating ischemic heart damage after the occlusion of the coronary artery. Adenoviral delivery of human eNOS gene into mouse bone marrow-derived MSCs (BM-MSCs) conferred resistance to oxygen glucose deprivation (OGD)-induced cell death in vitro, and elevated the bioavailability of nitric oxide when injected into the myocardium in vivo. In a rat model of acute myocardial infarction, the transplantation of eNOS-overexpressing BM-MSCs significantly reduced myocardial infarct size, corrected hemodynamic parameters and increased capillary density. We also found that the synergistic effects were consistently better than either treatment alone. These findings reveal a positive role of elevated eNOS expression in cardiac repair, and suggest the combination of eNOS and MSC transplant therapy as a potential approach for treating myocardial infarction.

  1. Ivabradine Prevents Low Shear Stress Induced Endothelial Inflammation and Oxidative Stress via mTOR/eNOS Pathway.

    Science.gov (United States)

    Li, Bing; Zhang, Junxia; Wang, Zhimei; Chen, Shaoliang

    2016-01-01

    Ivabradine not only reduces heart rate but has other cardiac and vascular protective effects including anti-inflammation and anti-oxidation. Since endothelial nitric oxide synthase (eNOS) is a crucial enzyme in maintaining endothelial activity, we aimed to investigate the impact of ivabradine in low shear stress (LSS) induced inflammation and endothelial injury and the role of eNOS played in it. Endothelial cells (ECs) were subjected to LSS at 2dyne/cm2, with 1 hour of ivabradine (0.04μM) or LY294002 (10μM) pre-treatment. The mRNA expression of IL-6, VCAM-1 along with eNOS were measured by QPCR. Reactive oxygen species (ROS) was detected by dihydroethidium (DHE) and DCF, and protein phosphorylation was detected by western blot. It demonstrated that ivabradine decreased LSS induced inflammation and oxidative stress in endothelial cells. Western blot showed reduced rictor and Akt-Ser473 as well as increased eNOS-Thr495 phosphorylation. However, mTORC1 pathway was only increased when LSS applied within 30 minutes. These effects were reversed by ivabradine. It would appear that ivabradine diminish ROS generation by provoking mTORC2/Akt phosphorylation and repressing mTORC1 induced eNOS-Thr495 activation. These results together suggest that LSS induced endothelial inflammation and oxidative stress are suppressed by ivabradine via mTORC2/Akt activation and mTORC1/eNOS reduction.

  2. Polymorphisms of the endothelial nitric oxide synthase (NOS3 gene in preeclampsia: a candidate-gene association study

    Directory of Open Access Journals (Sweden)

    Messinis Ioannis E

    2011-11-01

    Full Text Available Abstract Background The endothelial nitric oxide synthase gene (NOS3 has been proposed as a candidate gene for preeclampsia. However, studies so far have produced conflicting results. This study examines the specific role of variants and haplotypes of the NOS3 gene in a population of Caucasian origin. Methods We examined the association of three common variants of the NOS3 gene (4b/a, T-786C and G894T and their haplotypes in a case-control sample of 102 patients with preeclampsia and 176 women with a history of uncomplicated pregnancies. Genotyping for the NOS3 variants was performed and odds ratios and 95% confidence intervals were obtained to evaluate the association between NOS3 polymorphisms and preeclampsia. Results The single locus analysis for the three variants using various genetic models and a model-free approach revealed no significant association in relation to clinical status. The analysis of haplotypes also showed lack of significant association. Conclusions Given the limitations of the candidate-gene approach in investigating complex traits, the evidence of our study does not support the major contributory role of these common NOS3 variants in preeclampsia. Future larger studies may help in elucidating the genetics of preeclampsia further.

  3. Effects of TNFα, NOS3, MDR1 Gene Polymorphisms on Clinical Parameters, Prognosis and Survival of Multiple Myeloma Cases.

    Science.gov (United States)

    Basmaci, C; Pehlivan, M; Tomatir, Ag; Sever, T; Okan, V; Yilmaz, M; Oguzkan-Balci, S; Pehlivan, S

    2016-01-01

    It is not clear how gene polymorphisms affecting drugs can contributes totheir efficacy in multiple myeloma (MM). We here aimed to explore associations among gene polymorphisms of tumor necrosis factor alpha (TNFα), nitric oxide synthesis 3 (NOS3) and multi-drug resistance 1 (MDR1), clinical parameters, prognosis and survival in MM patients treated with VAD (vincristine-adriamycine-dexamethasone), MP (mephalane-prednisolone), autolougus stem cell transplantation (ASCT), BODEC (bortezomib-dexamethasone-cyclophosphamide) and TD (thalidomide-dexamethasone). We analyzed TNFα, NOS 3 and MDR1 in 77 patients with MM and 77 healthy controls. The genotyping was performed with PCR and/or PCR-RFLP. There was no clinically significant difference between MM and control groups when TNF α(-238) and (-857) and MDR1 gene polymorphisms were studied. However, the TNFαgene polymorphism (-308) GG genotype (p=0.012) and NOS3 (+894) TT genotype (p=0.008) were more common in the MM group compared to healthy controls. NOS3 (VNTR) AA (p=0.007) and NOS3 (+894) GG genotypes (p=0.004) were decreased in the MM group in contrast. In conclusion, the NOS3 (+894) TT and TNF α(-308) GG genotypes may have roles in myeloma pathogenesis.

  4. Polymorphisms of the endothelial nitric oxide synthase (NOS3) gene in preeclampsia: a candidate-gene association study.

    Science.gov (United States)

    Zdoukopoulos, Nikos; Doxani, Chrysa; Messinis, Ioannis E; Stefanidis, Ioannis; Zintzaras, Elias

    2011-11-03

    The endothelial nitric oxide synthase gene (NOS3) has been proposed as a candidate gene for preeclampsia. However, studies so far have produced conflicting results. This study examines the specific role of variants and haplotypes of the NOS3 gene in a population of Caucasian origin. We examined the association of three common variants of the NOS3 gene (4b/a, T-786C and G894T) and their haplotypes in a case-control sample of 102 patients with preeclampsia and 176 women with a history of uncomplicated pregnancies. Genotyping for the NOS3 variants was performed and odds ratios and 95% confidence intervals were obtained to evaluate the association between NOS3 polymorphisms and preeclampsia. The single locus analysis for the three variants using various genetic models and a model-free approach revealed no significant association in relation to clinical status. The analysis of haplotypes also showed lack of significant association. Given the limitations of the candidate-gene approach in investigating complex traits, the evidence of our study does not support the major contributory role of these common NOS3 variants in preeclampsia. Future larger studies may help in elucidating the genetics of preeclampsia further.

  5. Association of a NOS3 gene polymorphism with Behçet's disease but not with Vogt-Koyanagi-Harada syndrome in Han Chinese.

    Science.gov (United States)

    Zhou, Yan; Yu, Hongsong; Hou, Shengping; Fang, Jing; Qin, Jieying; Yuan, Gangxiang; Kijlstra, Aize; Yang, Peizeng

    2016-01-01

    Previous studies have identified that nitric oxide synthase (NOS) genes are associated with several immune-mediated diseases. This study aimed to investigate whether NOS2 and NOS3 gene polymorphisms are associated with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Han Chinese population. An association analysis of NOS2/rs4795067, NOS3/rs1799983 and NOS3/rs1800779 was performed in 733 patients with BD, 800 patients with VKH syndrome, and 1,359 controls using PCR restriction fragment length polymorphism (PCR-RFLP) assay. Statistical analysis was performed with the chi-square test followed by the Bonferroni correction. The result showed a decreased frequency of the NOS3/rs1799983 GG genotype and an increased frequency of NOS3/rs1799983 GT genotype in the patients with BD (Bonferroni correction test [Pc]=0.02, odds ratio [OR]=0.74; Pc=2.1×10(-3), OR=1.57, respectively). No significant association was found between rs1799983 and VKH syndrome. NOS2/ rs4795067 and NOS3/rs1800779 were not associated with either BD or VKH syndrome. Our findings suggest that a NOS3/rs1799983polymorphism is associated with susceptibility to BD in Han Chinese.

  6. Association of a NOS3 gene polymorphism with Behçet’s disease but not with Vogt-Koyanagi-Harada syndrome in Han Chinese

    Science.gov (United States)

    Zhou, Yan; Yu, Hongsong; Hou, Shengping; Fang, Jing; Qin, Jieying; Yuan, Gangxiang; Kijlstra, Aize

    2016-01-01

    Purpose Previous studies have identified that nitric oxide synthase (NOS) genes are associated with several immune-mediated diseases. This study aimed to investigate whether NOS2 and NOS3 gene polymorphisms are associated with Behçet’s disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Han Chinese population. Methods An association analysis of NOS2/rs4795067, NOS3/rs1799983 and NOS3/rs1800779 was performed in 733 patients with BD, 800 patients with VKH syndrome, and 1,359 controls using PCR restriction fragment length polymorphism (PCR-RFLP) assay. Statistical analysis was performed with the chi-square test followed by the Bonferroni correction. Results The result showed a decreased frequency of the NOS3/rs1799983 GG genotype and an increased frequency of NOS3/rs1799983 GT genotype in the patients with BD (Bonferroni correction test [Pc]=0.02, odds ratio [OR]=0.74; Pc=2.1×10−3, OR=1.57, respectively). No significant association was found between rs1799983 and VKH syndrome. NOS2/ rs4795067 and NOS3/rs1800779 were not associated with either BD or VKH syndrome. Conclusions Our findings suggest that a NOS3/rs1799983polymorphism is associated with susceptibility to BD in Han Chinese. PMID:27114698

  7. Vasoactive and radioprotective properties of isothiourea derivatives having NOS-inhibitory activity

    Energy Technology Data Exchange (ETDEWEB)

    Filimonova, Marina V.; Shevchenko, Ludmila I.; Ulyanenko, Stepan E.; Makarchuk, Victorya M.; Kuznetsova, Mary N.; Shevchuk, Aza S.; Lushnikova, Galina A.; Chesnakova, Ekaterina A. [Medical Radiological Research Center Health Ministry of Russia, 4, Korolev street, Obninsk, 249036, Kaluga region (Russian Federation)

    2014-07-01

    We studied vasoactive and radioprotective properties of new original N-acyl, S-alkyl isothiourea derivatives which are potent inhibitors of nitric oxide synthases (preferably eNOS and iNOS). These compounds have a moderate toxicity (LD50 - 400-550 mg/kg), and are stable in aqueous solutions. In hemodynamic studies, these compounds exhibited high vasotropic activity. The use of these compounds in doses of 5-15 mg/kg (0,01-0,03 LD{sub 50}) in the experimental animals in a state of the severe hemorrhagic or endo-toxic shock causes a potent vasopressor effect, accompanied by a significant and continuous rise in blood pressure. The increasing of vascular tone developed over 2-5 min after injection and persisted for at least 60-90 minutes, excelling at least 3-5 times the duration of α1-adreno-mimetic vasopressor action. The rapid increase in vascular tone under the influence of these compounds in normo-tonic animals caused protective baroreflex to prevent high blood pressure. At doses of 10-15 mg/kg the reflex reaction was mild, but at higher doses (30-40 mg/kg) the reaction was fierce and prolonged, and was accompanied by severe bradycardia, decreasing of the cardiac output and a significant weakening of the peripheral blood flow. In all cases, the hemodynamic response was reflexive and easily eliminated by atropine. The ability of these compounds to induce circulatory hypoxia was the basis for the study of their radioprotective properties. The study of radioprotective effect on the survival of animals exposed to lethal doses of γ-radiation (10 Gy) and on the survival of hematopoietic clonogenic cells showed that these compounds in doses of 80-150 mg/kg (0,2-0,3 LD50) have considerable radioprotective action, which is comparable with the protective effect of the maximum tolerated dose of cystamine. The factor of change in dose for γ-radiation, estimated by the LD{sub 50}, was 1,42-1,58. We also investigated the ability of the test compounds, due to their hypoxic

  8. A novel multiplex PCR-RFLP method for simultaneous detection of the MTHFR 677 C > T, eNOS +894 G > T and - eNOS -786 T > C variants among Malaysian Malays

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    Loo Keat

    2012-05-01

    Full Text Available Abstract Background Hyperhomocysteinemia as a consequence of the MTHFR 677 C > T variant is associated with cardiovascular disease and stroke. Another factor that can potentially contribute to these disorders is a depleted nitric oxide level, which can be due to the presence of eNOS +894 G > T and eNOS −786 T > C variants that make an individual more susceptible to endothelial dysfunction. A number of genotyping methods have been developed to investigate these variants. However, simultaneous detection methods using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP analysis are still lacking. In this study, a novel multiplex PCR-RFLP method for the simultaneous detection of MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants was developed. A total of 114 healthy Malay subjects were recruited. The MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants were genotyped using the novel multiplex PCR-RFLP and confirmed by DNA sequencing as well as snpBLAST. Allele frequencies of MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C were calculated using the Hardy Weinberg equation. Methods The 114 healthy volunteers were recruited for this study, and their DNA was extracted. Primer pair was designed using Primer 3 Software version 0.4.0 and validated against the BLAST database. The primer specificity, functionality and annealing temperature were tested using uniplex PCR methods that were later combined into a single multiplex PCR. Restriction Fragment Length Polymorphism (RFLP was performed in three separate tubes followed by agarose gel electrophoresis. PCR product residual was purified and sent for DNA sequencing. Results The allele frequencies for MTHFR 677 C > T were 0.89 (C allele and 0.11 (T allele; for eNOS +894 G > T, the allele frequencies were 0.58 (G allele and 0.43 (T allele; and for eNOS −786 T > C, the allele

  9. Lactate dilates cochlear capillaries via type V fibrocyte-vessel coupling signaled by nNOS.

    Science.gov (United States)

    Dai, Min; Yang, Yue; Shi, Xiaorui

    2011-10-01

    Transduction of sound in the inner ear demands tight control over delivery of oxygen and glucose. However, the mechanisms underlying the control of regional blood flow are not yet fully understood. In this study, we report a novel local control mechanism that regulates cochlear blood flow to the stria vascularis, a high energy-consuming region of the inner ear. We found that extracellular lactate had a vasodilatory effect on the capillaries of the spiral ligament under both in vitro and in vivo conditions. The lactate, acting through monocarboxylate transporter 1 (MCT1), initiated neuronal nitric oxide (NO) synthase (nNOS) and catalyzed production of NO for the vasodilation. Blocking MCT1 with the MCT blocker, α-cyano-4-hydroxycinnamate (CHC), or a suppressing NO production with either the nonspecific inhibitor of NO synthase, N(G)-nitro-L-arginine methyl ester (L-NAME), or either of two selective nNOS inhibitors, 3-bromo-7-nitroindazole or (4S)-N-(4-amino-5[aminoethyl]aminopentyl)-N'-nitroguanidine (TFA), totally abolished the lactate-induced vasodilation. Pretreatment with the selective endothelial NO synthase inhibitor, L-N(5)-(1-iminoethyl)ornithine (L-NIO), eliminated the inhibition of lactate-induced vessel dilation. With immunohistochemical labeling, we found the expression of MCT1 and nNOS in capillary-coupled type V fibrocytes. The data suggest that type V fibrocytes are the source of the lactate-induced NO. Cochlear microvessel tone, regulated by lactate, is mediated by an NO-signaled coupling of fibrocytes and capillaries.

  10. Renal medullary ETB receptors produce diuresis and natriuresis via NOS1.

    Science.gov (United States)

    Nakano, Daisuke; Pollock, Jennifer S; Pollock, David M

    2008-05-01

    Endothelin-1 (ET-1) plays an important role in the regulation of salt and water excretion in the kidney. Considerable in vitro evidence suggests that the renal medullary ET(B) receptor mediates ET-1-induced inhibition of electrolyte reabsorption by stimulating nitric oxide (NO) production. The present study was conducted to test the hypothesis that NO synthase 1 (NOS1) and protein kinase G (PKG) mediate the diuretic and natriuretic effects of ET(B) receptor stimulation in vivo. Infusion of the ET(B) receptor agonist sarafotoxin S6c (S6c: 0.45 microg x kg(-1) x h(-1)) in the renal medulla of anesthetized, male Sprague-Dawley rats markedly increased the urine flow (UV) and urinary sodium excretion (UNaV) by 67 and 120%, respectively. This was associated with an increase in medullary cGMP content but did not affect blood pressure. In addition, S6c-induced diuretic and natriuretic responses were absent in ET(B) receptor-deficient rats. Coinfusion of N(G)-propyl-l-arginine (10 microg x kg(-1) x h(-1)), a selective NOS1 inhibitor, suppressed S6c-induced increases in UV, UNaV, and medullary cGMP concentrations. Rp-8-Br-PET-cGMPS (10 microg x kg(-1) x h(-1)) or RQIKIWFQNRRMKWKK-LRK(5)H-amide (18 microg x kg(-1) x h(-1)), a PKG inhibitor, also inhibited S6c-induced increases in UV and UNaV. These results demonstrate that renal medullary ET(B) receptor activation induces diuretic and natriuretic responses through a NOS1, cGMP, and PKG pathway.

  11. Bilirubin inhibits iNOS expression and NO production in response to endotoxin in rats.

    Science.gov (United States)

    Wang, Weizheng W; Smith, Darcey L H; Zucker, Stephen D

    2004-08-01

    The inducible isoform of heme oxygenase (HO), HO-1, has been shown to play an important role in attenuating tissue injury. Because HO-1 catalyzes the rate-limiting step in bilirubin synthesis, we examined the hypothesis that bilirubin is a key mediator of HO-1 cytoprotection, employing a rat model of endotoxemia. Bilirubin treatment resulted in improved survival and attenuated liver injury in response to lipopolysaccharide infusion. Serum levels of NO and tumor necrosis factor alpha, key mediators of endotoxemia, and hepatic inducible nitric oxide synthase (iNOS) expression were significantly lower in bilirubin-treated rodents versus control animals. Both intraperitoneal and local administration of bilirubin also was found to ameliorate hindpaw inflammation induced by the injection of lambda-carrageenan. Consistent with in vivo results, bilirubin significantly inhibited iNOS expression and suppressed NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. In contrast, bilirubin treatment induced a threefold increase in LPS-mediated prostaglandin synthesis in the absence of significant changes in cyclooxygenase expression or activity, suggesting that bilirubin enhances substrate availability for eicosanoid synthesis. Bilirubin had no effect on LPS-mediated activation of nuclear factor kappaB or p38 mitogen-activated protein kinase, consistent with a nuclear factor kappaB-independent mechanism of action. Taken together, these data support a cytoprotective role for bilirubin that is mediated, at least in part, through the inhibition of iNOS expression and, potentially, through stimulation of local prostaglandin E2 production. In conclusion, our findings suggest a role for bilirubin in mollifying tissue injury in response to inflammatory stimuli and support the possibility that the phenomenon of "jaundice of sepsis" represents an adaptive physiological response to endotoxemia. Supplementary material for this article can be found on the

  12. Association of the NOS3 intron-4 VNTR polymorphism with aneurysmal subarachnoid hemorrhage.

    Science.gov (United States)

    Staalsø, Jonatan Myrup; Edsen, Troels; Kotinis, Alexandros; Romner, Bertil; Springborg, Jacob Bertram; Olsen, Niels Vidiendal

    2014-09-01

    The nitric oxide system has been linked to the pathogenesis of aneurysmal subarachnoid hemorrhage (SAH). The authors performed a case-control study to investigate the association between SAH and common genetic variants within the endothelial nitric oxide synthase gene (NOS3). Three hundred thirty-three Caucasian SAH patients and 498 controls were genotyped for the -922A > G (rs 1800779), -786T > C (rs2070744), and 894G > T (rs1799983) single nucleotide polymorphisms and the intron-4 27-bp variable number of tandem repeats polymorphism (27-bp-VNTR). The b/b (5 repeats) genotype of the 27-bp-VNTR was overrepresented in cases (77%) versus controls (69%) (p = 0.02). In male patients the b/b genotype was found in 85% compared with 67% in male controls, whereas in women, the frequencies were 73% and 72%, respectively. This corresponds to an odds ratio of 2.8 (95% CI 1.5-5.6, p = 0.0005) for SAH in men with the b/b genotype versus men with a/b or a/a. In women, no such association was found (OR 1.1, 95% CI 0.7-1.6, p = 0.76). Stepwise logistic regression including arterial hypertension, smoking, sex, and age with interactions yielded similar effect estimates of the 27-bp-VNTR. Haplotype analysis revealed that no single haplotype containing the b-allele was responsible for the observed genotype effect. The authors' results suggest that the NOS3 27-bp-VNTR b/b genotype independent of other risk factors act in concert with male sex to substantially increase risk of SAH. This effect is not mediated by any single NOS3 haplotype.

  13. IL-10 and NOS2 modulate antigen-specific reactivity and nerve infiltration by T cells in experimental leprosy.

    Directory of Open Access Journals (Sweden)

    Deanna A Hagge

    2014-09-01

    Full Text Available Although immunopathology dictates clinical outcome in leprosy, the dynamics of early and chronic infection are poorly defined. In the tuberculoid region of the spectrum, Mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur. The evolution and maintenance of chronic inflammatory processes like those observed in the leprosy granuloma involve an ongoing network of communications via cytokines. IL-10 has immunosuppressive properties and IL-10 genetic variants have been associated with leprosy development and reactions.The role of IL-10 in resistance and inflammation in leprosy was investigated using Mycobacterium leprae infection of mice deficient in IL-10 (IL-10-/-, as well as mice deficient in both inducible nitric oxide synthase (NOS2-/- and IL-10 (10NOS2-/-. Although a lack of IL-10 did not affect M. leprae multiplication in the footpads (FP, inflammation increased from C57Bl/6 (B6NOS2-/-<10NOS2-/-. While IL-10-/- mice exhibited modest FP induration compared to B6, NOS2-/- and 10NOS2-/- mice developed markedly enlarged FP marking distinct phases: early (1 month, peak (3-4 months, and chronic (8 months. IFN-γ-producing CD4+CD44+ cells responding to M. leprae cell wall, membrane, and cytosol antigens and ML2028 (Ag85B were significantly increased in the evolved granuloma in NOS2-/- FP compared to B6 and IL-10-/- during early and peak phases. In 10NOS2-/- FP, CD4+CD44+ and especially CD8+CD44+ responses were augmented even further to these antigens as well as to ML0380 (GroES, ML2038 (bacterioferritin, and ML1877 (EF-Tu. Moreover, fragmented nerves containing CD4+ cells were present in 10NOS2-/- FP.The 10NOS2-/- strain offers insight on the regulation of granuloma formation and maintenance by immune modulators in the resistant forms of leprosy and presents a new model for investigating the pathogenesis of neurological involvement.

  14. IL-10 and NOS2 Modulate Antigen-Specific Reactivity and Nerve Infiltration by T Cells in Experimental Leprosy

    Science.gov (United States)

    Hagge, Deanna A.; Scollard, David M.; Ray, Nashone A.; Marks, Vilma T.; Deming, Angelina T.; Spencer, John S.; Adams, Linda B.

    2014-01-01

    Background Although immunopathology dictates clinical outcome in leprosy, the dynamics of early and chronic infection are poorly defined. In the tuberculoid region of the spectrum, Mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur. The evolution and maintenance of chronic inflammatory processes like those observed in the leprosy granuloma involve an ongoing network of communications via cytokines. IL-10 has immunosuppressive properties and IL-10 genetic variants have been associated with leprosy development and reactions. Methodology/Principal Findings The role of IL-10 in resistance and inflammation in leprosy was investigated using Mycobacterium leprae infection of mice deficient in IL-10 (IL-10−/−), as well as mice deficient in both inducible nitric oxide synthase (NOS2−/−) and IL-10 (10NOS2−/−). Although a lack of IL-10 did not affect M. leprae multiplication in the footpads (FP), inflammation increased from C57Bl/6 (B6)NOS2−/−<10NOS2−/−. While IL-10−/− mice exhibited modest FP induration compared to B6, NOS2−/− and 10NOS2−/− mice developed markedly enlarged FP marking distinct phases: early (1 month), peak (3–4 months), and chronic (8 months). IFN-γ-producing CD4+CD44+ cells responding to M. leprae cell wall, membrane, and cytosol antigens and ML2028 (Ag85B) were significantly increased in the evolved granuloma in NOS2−/− FP compared to B6 and IL-10−/− during early and peak phases. In 10NOS2−/− FP, CD4+CD44+ and especially CD8+CD44+ responses were augmented even further to these antigens as well as to ML0380 (GroES), ML2038 (bacterioferritin), and ML1877 (EF-Tu). Moreover, fragmented nerves containing CD4+ cells were present in 10NOS2−/− FP. Conclusions/Significance The 10NOS2−/− strain offers insight on the regulation of granuloma formation and maintenance by immune modulators in the resistant forms of leprosy and presents a new model for investigating the

  15. Investigar o desenvolvimento musical da criança nos primeiros anos de escolaridade

    OpenAIRE

    Mota, Graça

    1999-01-01

    Este artigo discute, em geral, os problemas que se colocam na investigação em contexto de sala de aula e, em particular, na investigação sobre o desenvolvimento musical. Na primeira parte apresentam-se algumas perspectivas teóricas acerca da avaliação das capacidades mus icais de crianças nos primeiros anos de escolaridade, bem como investigação nesta área do conhecimento. Na segunda parte discutem-se alguns exemplos práticos extraídos de um estudo levado a cabo pela autora, tendo...

  16. POLÍTICAS CURRICULARES NO BRASIL NOS GOVERNOS FHC E LULA: CONTINUIDADE?

    Directory of Open Access Journals (Sweden)

    Mariclei Przylepa

    2015-08-01

    Full Text Available O presente artigo objetiva problematizar as políticas curriculares elaboradas e efetivadas nos governos FHC e Lula, a partir do contexto de reforma de Estado materializada na década de 1990. Nessa direção o estudo inicia abordando a política curricular no contexto da reforma de Estado, evidencia a proposta educacional do governo FHC, discute sua política curricular, via parâmetros curriculares nacionais, e finaliza analisando a política curricular implementada no primeiro ano do governo Lula.

  17. A disrupção pervasiva da tecnologia na privacidade e nos processos de aprendizagem

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    Patricia Zeni Marchiori

    2016-07-01

    Full Text Available A equipe editorial da AtoZ apresenta os artigos desta edição, nos quais os autores avaliam espaços de informação e de aprendizagem em distintas condições de uso intensivo de tecnologias. Os entrevistados ampliam discussões relativas às metodologias e resultados derivados de questionamento quanto à formação de profissionais da informação e os desafios para as instituições envolvidas.

  18. Metáforas sobre el exilio en "Dios nos quiere contentos" de Griselda Gambarro.

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    Ariadna Castellarnau

    2010-01-01

    Full Text Available El presente artículo analiza la novela Dios no nos quiere contentos, de la escritora argentina Griselda Gambaro, desde la perspectiva de la literatura de exilio. Esto significa trazar una lectura de la obra no tanto desde lo vivencial (como trasunto literario de la propia experiencia de la autora como desterrada durante el período de la última dictadura militar argentina como desde lo universal: analizando la experiencia del exilio como un hecho en abstracto, aplicable a cualquier contexto nacional e histórico, a través de las metáforas sobre las que trabaja Gambaro.

  19. Envolvimento nos direitos humanos e sistemas de valores Involvement in human rights and value systems

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    Cícero Pereira

    2004-04-01

    Full Text Available Com base no modelo da análise quantitativa das representações sociais, o estudo (N = 300 tratou do posicionamento de estudantes universitários em relação aos Direitos Humanos (DHs e à ancoragem social desse posicionamento nos sistemas de valores dos estudantes. Os resultados mostram que as representações dos estudantes sobre o envolvimento nos DHs envolvem quatro princípios organizadores: pessoal-abstrato; pessoal-concreto; governamental-abstrato; governamental-concreto. Em relação à ancoragem social dos princípios organizadores do envolvimento nos DHs, observou-se que os valores pós-materialistas se relacionaram positivamente com o envolvimento pessoal-abstrato, enquanto a adesão aos valores religiosos implicou maior envolvimento no princípio pessoal-concreto. Além disso, a adesão aos valores materialistas levou a uma avaliação mais positiva do envolvimento do Governo Brasileiro nos DHs, ao passo que os valores pós-materialistas contribuíram com uma avaliação mais crítica desse governo. As discussões abordam a centralidade dos valores na formação das representações sociais dos DHs.Based on the quantitative analysis model of social representations, a study (N=300 was carried out concerning the opinion of university students on Human Rights (HR, and the social link of this positioning in the students system of values. The results show that the students representations of the involvement in HR comprise four organizing principles: personal-abstract; personal-concrete; governmental-abstract; governmental-concrete. With regard to the social anchorage of the organizing principles of involvement in HR, it has been observed that post-materialist values were positively related to the involvement personal-abstract, whereas adherence to religious values implied a greater involvement in the personal-concrete principle. In addition, adherence to materialist values led to a more positive appraisal of the Brazilian Government

  20. Da caligrafia à escrita: experiências escolanovistas com caligrafia muscular nos anos 30

    OpenAIRE

    Vidal Diana Gonçalves

    1998-01-01

    A partir de uma análise da experiência com a caligrafia muscular, realizada nas Escolas Primária e de professores do Instituto de Educação, nos anos 30, o artigo pretende discutir como, apoiado em discursos escolanovistas, se foi constituindo, no Brasil, uma didática racional da escrita.Starting from the analyses of na experience on th teaching of muscular calligraphy, happened in the Primary School and Teacher Schhol of Instituto de Educação (Rio de Janeiro, 1930’s), this article intends to ...

  1. Humor e irreverência nos impressos estudantis de escolas normais rurais (RS, 1945-1983)

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    Werle,Flávia Obino Corrêa

    2013-01-01

    Este estudo discute um tipo de cultura escolar que contribui para a formação dos estudantes e revela práticas pedagógicas. O foco da discussão são os impressos estudantis, os quais são analisados como espaço educativo, de expressão e organização dos alunos. Aspectos relacionados ao humor e irreverência são analisados nos impressos produzidos por estudantes de duas escolas normais rurais do Rio Grande do Sul, Brasil.

  2. Risco de brucelose zoonótica associado a suínos de abate clandestino

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    José Arimatéa Freitas; Glaucio Antonio Rocha Galindo; Eváldson Joaquim Corrêa dos Santos; Karine de Almeida Sarraf; Jefferson Pinto de Oliveira

    2001-01-01

    Um total de 59 amostras de soros de suínos, procedentes de vários locais de abate clandestino, apresentaram ao "card test" e à soroaglutinação rápida anticorpos anti-Brucella e títulos de anticorpos sugestivos de infecção brucélica. Ações e medidas de vigilância sanitária são recomendadas para prevenir o risco potencial de infecção brucélica zoonótica.

  3. Nietzsche para pensar o mal nos filmes sobre a ditadura militar brasileira

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    Stigger, Helena

    2009-01-01

    Full Text Available Depois de anunciada a morte de Deus, refutamos a verdade absoluta e, em seu lugar, passamos a adotar o perspectivismo. Deste modo, podemos compreender a atenção que a filmografia brasileira, nestes últimos anos, tem reservado à produção de filmes sobre a ditadura militar, pois a tortura e a repressão não são atos aceitos em nossa sociedade. Assim, utilizando- se da teoria nietziana como metodologia no sentido de revelar a moral representada nos filmes sobre a ditadura militar, podemos analisar como o mal está caracterizado nestas obras

  4. O ensino nos anos de alfabetizacão matemática

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    Lopes,Rosemara Perpetua

    2015-01-01

    v. 11, n. 2, 2015. Apresenta-se uma pesquisa que tem como objetivo geral investigar o tratamento conferido à alfabetização matemática nos dois primeiros anos escolares, com vistas à melhoria do ensino dos conteúdos dessa área no Ensino Fundamental I. O estudo adquire relevância em face da dificuldade dos alunos em aprender Matemática, do baixo rendimento que apresentam nesse campo, da escassez e precariedade do tratamento conferido à mesma na Educação Infantil, da falta de familiaridade do...

  5. Imperialismo e internacionalização dos mercados Latino-Americanos nos anos 1950

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    De Campos, Fábio Antonio

    2016-01-01

    Tendo como destaque o debate clássico sobre o imperialismo, o objetivo do artigo é mostrar a particularidade da internacionalização do mercado interno latino-americano após a Segunda Guerra, em especial o caso brasileiro, por meio do investimento direto estrangeiro (IDE). Para tanto, analisaremos a especificidade imperialista das empresas multinacionais nos anos 50 do século XX e os motivos de seu deslocamento para a América Latina. Em seguida, abordaremos as condições concretas de internacio...

  6. Interações imunocerebrais e implicações nos transtornos psiquiátricos

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    Marques, Andrea H; Cizza, Giovanni; Sternberg,Esther

    2007-01-01

    OBJETIVO: Nesta revisão será focado o papel das citocinas no sistema nervoso central e suas implicações para o quadro depressivo. Posteriormente, serão discutidos os principais achados sobre medidas de citocinas em pacientes com depressão maior. MÉTODO: Foi realizada uma pesquisa no Pubmed selecionando estudos entre 1999-2007, utilizando as seguintes palavras-chave: "depression, cytokine"; "depressive disorder, cytokine". Focou-se nos estudos de medidas de citocinas pró-inflamatórias em pacie...

  7. Association of Polymorphisms in NOS3 with the Ankle-Brachial Index in Hypertensive Adults

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    Kullo, Iftikhar J.; Greene, M. Todd; Boerwinkle, Eric; Chu, Jian; Turner, Stephen T; Kardia, Sharon L.R.

    2007-01-01

    We investigated the association of 14 polymorphisms in the endothelial nitric oxide synthase gene (NOS3) with ankle brachial index (ABI) in non-Hispanic white hypertensives belonging to hypertensive sibships. Subjects (n = 659, mean age 61±9 y, 54% women) underwent measurement of ABI using a standard protocol, and the lowest of 4 ABI values was used in the analyses. Non-synonymous SNPs with a minor allele frequency > 0.02 and tag SNPs selected based on a measure of linkage disequilibrium (r2)...

  8. Inserção profissional: os desafios nos primeiros anos de ensino

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    Santos, Arnaldo José Cristóvão dos

    2012-01-01

    A problemática da inserção profissional dos novos professores tem sido largamente estudada sob várias perspetivas das quais destacamos, as dificuldades enfrentadas no início do seu desempenho como docentes (Alen y Sardi, 2009) Krichesky y Merodo (2009), o vinculo entre inserção e identidade profissional (Martineau y Portelance, 2005), o desenvolvimento da competência ética nos novos professores (St. Vincent 2011) e as trajetórias de emprego, entre outras.Os resultados destas pesquisas têm rev...

  9. Topografia do Brasil profundo: votos, cargos e alinhamentos nos municípios brasileiros

    OpenAIRE

    André Marenco dos Santos

    2013-01-01

    O propósito deste artigo é identificar os padrões preponderantes da competição política realizada nos municípios brasileiros. Pretende-se analisar dois problemas: em primeiro lugar, considerando-se a estrutura federativa do Estado brasileiro e a presença de governo dividido, busca-se identificar as forças que presidem as relações intergovernamentais entre governo federal, estadual e municipal. Em segundo lugar, procura-se analisar em que medida o incremento na competição eleitoral ao nível na...

  10. O conceito de trabalho nos manuscritos econômico-filosóficos de Karl Marx

    OpenAIRE

    Farias, Tarcisio Fagner Aleixo

    2010-01-01

    Este estudo tem o objetivo de compreender a teia conceitual que permeia a noção de trabalho apresentada por Marx nos Manuscritos Econômico-filosóficos. Relacionamos a noção de trabalho enquanto atividade produtiva humana a três outros conceitos: essência humana; estranhamento e liberdade. Na relação entre trabalho e essência humana o trabalho deve ser visto de maneira geral, como a atividade de metabolismo entre o homem e a natureza, e nesse sentido ele é a marca peculiar dos homens perante o...

  11. A relevância atual da infografia nos jornais Público e The Times

    OpenAIRE

    Fidalgo, Ana Cristina de Jesus

    2015-01-01

    A infografia é vista constantemente no nosso dia a dia como principal objectivo de nos informar de uma forma gráfica e visual, relativamente a um determinado tema ou momento, trabalhando sempre com informações reais e verdadeiras. O aumento do número e da importância da infografia na comunicação social tem sido exponencial, e notavelmente, a partir das edições online das publicações. Este relatório está dividido em três partes. A primeira tenta enquadrar, muito brevemente, o tema da inf...

  12. A missão nos dois primeiros séculos do cristianismo

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    Corbellini, Vital

    2008-01-01

    Full Text Available Este artigo trata da missão como anúncio de Jesus Cristo aos povos num determinado tempo: os primeiros dois séculos. Esse período é importante, porque se colocaram as bases da missão que provinha do Oriente, mas que se espalhou pouco a pouco na Ásia, Europa e África do Norte. Diversos motivos porporcionaram a conversão à doutrina cristã nos povos, bem como muitas pessoas se empenharam em divulgar a pessoa de Jesus Cristo

  13. Branca de Neve multim?dia: a personagem na literatura, no cinema e nos quadrinhos

    OpenAIRE

    Miranda., Allana Dilene de Ara?jo de

    2011-01-01

    Objetivando estudar a categoria personagem e sua manifesta??o em tr?s diferentes m?dias, este trabalho analisa Branca de Neve e sua constru??o na literatura, no cinema, e nas hist?rias em quadrinhos. O corpus utilizado foi o conto Branca de Neve e os sete an?es, assinado pelos irm?os Wilhelm e Jacob Grimm; a anima??o de 1937, produzida pelos est?dios Disney, hom?nima; e o primeiro volume da miniss?rie As mil e uma noites, derivada da revista mensal F?bulas, de Bill Willingham. Nos tr?s primei...

  14. Resenha crítica - a literatura convencional sobre crises financeiras nos países "emergentes": os modelos desenvolvidos nos anos 90

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    Daniela Magalhães Prates

    2005-06-01

    Full Text Available As sucessivas crises financeiras dos países "emergentes", na segunda metade dos anos 90, despertaram o interesse dos economistas do mainstream, uma vez que os modelos de crises cambiais de primeira geração, desenvolvidos nos anos 80, revelaram-se insuficientes para a compreensão destes eventos. Nesse contexto, foram desenvolvidos novos modelos que incorporaram, como condicionantes destas crises, fatos estilizados, que têm caracterizado o sistema financeiro internacional contemporâneo, dentre os quais os ataques especulativos auto-realizáveis e o comportamento de manada dos investidores estrangeiros. Este artigo pretende apresentar as principais características desses novos modelos. Primeiramente, apresentam-se os modelos desenvolvidos após a crise mexicana, que seguiram a tradição dos modelos de segunda geração desenvolvidos após a crise do Sistema Monetário Europeu. Em seguida, são examinados os modelos que surgem após a crise asiática, denominados "modelos de terceira geração", nos quais a crise cambial está intrinsecamente associada a uma crise bancária. Seguem-se algumas considerações finais.In the 90s, the succession of financial crises in the so called "emergent countries", with characteristics that haven't been considered by the first-generation models of exchange crises developed in the 80s, was followed by the emergency of new models of exchange crisis. The purpose of this article is to present these models, which have introduced in their analytical framework new elements, how the self-fulfilling expectations and the volatility of the capital flows. Firstly, we analyze the models developed after the Mexican crise, which have followed the tradition of the second-generation models that emerged after the European monetary system crise. Secondly, we examine the models developed after the Asian crise, labeled "third generation models", in which the exchange crise is intrinsically linked with a banking crise. We end up

  15. Endothelial function does not improve with high-intensity continuous exercise training in SHR: implications of eNOS uncoupling.

    Science.gov (United States)

    Battault, Sylvain; Singh, François; Gayrard, Sandrine; Zoll, Joffrey; Reboul, Cyril; Meyer, Grégory

    2016-02-01

    Exercise training is a well-recognized way to improve vascular endothelial function by increasing nitric oxide (NO) bioavailability. However, in hypertensive subjects, unlike low- and moderate-intensity exercise training, the beneficial effects of continuous high-intensity exercise on endothelial function are not clear, and the underlying mechanisms remain unknown. The aim of this study was to investigate the impact of high-intensity exercise on vascular function, especially on the NO pathway, in spontaneous hypertensive rats (SHR). These effects were studied on WKY, sedentary SHR and SHR that exercised at moderate (SHR-MOD) and high intensity (SHR-HI) on a treadmill (1 h per day; 5 days per week for 6 weeks at 55% and 80% of their maximal aerobic velocity, respectively). Endothelial function and specific NO contributions to acetylcholine-mediated relaxation were evaluated by measuring the aortic ring isometric forces. Endothelial nitric oxide synthase (eNOS) expression and phosphorylation (ser1177) were evaluated by western blotting. The total aortic and eNOS-dependent reactive oxygen species (ROS) production was assessed using electron paramagnetic resonance in aortic tissue. Although the aortas of SHR-HI had increased eNOS levels without alteration of eNOS phosphorylation, high-intensity exercise had no beneficial effect on endothelium-dependent vasorelaxation, unlike moderate exercise. This result was associated with increased eNOS-dependent ROS production in the aortas of SHR-HI. Notably, the use of the recoupling agent BH4 or a thiol-reducing agent blunted eNOS-dependent ROS production in the aortas of SHR-HI. In conclusion, the lack of a positive effect of high-intensity exercise on endothelial function in SHR was mainly explained by redox-dependent eNOS uncoupling, resulting in a switch from NO to O2(-) generation.

  16. IL-17A synergizes with IFN-γ to upregulate iNOS and NO production and inhibit chlamydial growth.

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    Yongci Zhang

    Full Text Available IFN-γ-mediated inducible nitric oxide synthase (iNOS expression is critical for controlling chlamydial infection through microbicidal nitric oxide (NO production. Interleukin-17A (IL-17A, as a new proinflammatory cytokine, has been shown to play a protective role in host defense against Chlamydia muridarum (Cm infection. To define the related mechanism, we investigated, in the present study, the effect of IL-17A on IFN-γ induced iNOS expression and NO production during Cm infection in vitro and in vivo. Our data showed that IL-17A significantly enhanced IFN-γ-induced iNOS expression and NO production and inhibited Cm growth in Cm-infected murine lung epithelial (TC-1 cells. The synergistic effect of IL-17A and IFN-γ on Chlamydia clearance from TC-1 cells correlated with iNOS induction. Since one of the main antimicrobial mechanisms of activated macrophages is the release of NO, we also examined the inhibitory effect of IL-17A and IFN-γ on Cm growth in peritoneal macrophages. IL-17A (10 ng/ml synergizes with IFN-γ (200 U/ml in macrophages to inhibit Cm growth. This effect was largely reversed by aminoguanidine (AG, an iNOS inhibitor. Finally, neutralization of IL-17A in Cm infected mice resulted in reduced iNOS expression in the lung and higher Cm growth. Taken together, the results indicate that IL-17A and IFN-γ play a synergistic role in inhibiting chlamydial lung infection, at least partially through enhancing iNOS expression and NO production in epithelial cells and macrophages.

  17. Toxicological Effect of Manganese on NF-κB/iNOS-COX-2 Signaling Pathway in Chicken Testes.

    Science.gov (United States)

    Du, Ye; Zhu, Yihao; Teng, Xiaojie; Zhang, Kun; Teng, Xiaohua; Li, Shu

    2015-11-01

    Manganese (Mn) pollution can cause tissue and organ dysfunction and structural damage. The toxicity of Mn in poultry was reported, but inflammatory damage that Mn induced in the testicular tissue has not been reported. The aim of this study was to investigate the effect of Mn poisoning on NF-κB/iNOS-COX-2 signaling pathway in chicken testes. One hundred eighty Hyline male chickens at 7 days of age were fed either commercial diet or MnCl2-added commercial diet containing 600, 900, and 1800 mg/kg Mn for 30, 60, and 90 days, respectively. The messenger RNA (mRNA) expression of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), nitric oxide (NO) content, iNOS activity, and histopathology were examined in chicken testes. The results showed that excess Mn upregulated mRNA expression of NF-κB, COX-2, TNF-α, and iNOS, NO content, and iNOS activity at 60th and 90th day. Mn had a time-dependent effect on NF-κB and TNF-α mRNA expression. Mn had a dose- and time-dependent effect on NO content and iNOS activity. Mn exposure induced chicken testis histological changes in dose- and time-dependent manner. It indicated that Mn exposure resulted in inflammatory injury of chicken testis tissue through NF-κB/iNOS-COX-2 signaling pathway.

  18. Paradoxical regulation of ChAT and nNOS expression in animal models of Crohn's colitis and ulcerative colitis.

    Science.gov (United States)

    Winston, John H; Li, Qingjie; Sarna, Sushil K

    2013-08-15

    Morphological and functional changes in the enteric nervous system (ENS) have been reported in inflammatory bowel disease. We examined the effects of inflammation on the expression of choline acetyltransferase (ChAT) and nNOS in the muscularis externae of two models of colonic inflammation, trinitrobenzene sulfonic acid (TNBS)-induced colitis, which models Crohn's disease-like inflammation, and DSS-induced colitis, which models ulcerative Colitis-like inflammation. In TNBS colitis, we observed significant decline in ChAT, nNOS, and protein gene product (PGP) 9.5 protein and mRNA levels. In DSS colitis, ChAT and PGP9.5 were significantly upregulated while nNOS levels did not change. The nNOS dimer-to-monomer ratio decreased significantly in DSS- but not in TNBS-induced colitis. No differences were observed in the percentage of either ChAT (31 vs. 33%)- or nNOS (37 vs. 41%)-immunopositive neurons per ganglia or the mean number of neurons per ganglia (55 ± 5 vs. 59 ± 5, P > 0.05). Incubation of the distal colon muscularis externae in vitro with different types of inflammatory mediators showed that cytokines decreased ChAT and nNOS expression, whereas H₂O₂, a component of oxidative stress, increased their expression. NF-κB inhibitor MG-132 did not prevent the IL-1β-induced decline in either ChAT or nNOS expression. These findings showed that TNBS- and DSS-induced inflammation differentially regulates the expression of two critical proteins expressed in the colonic myenteric neurons. These differences are likely due to the exposure of the myenteric plexus neurons to different combinations of Th1-type inflammatory mediators and H₂O₂ in each model.

  19. Enhanced astrocytic nitric oxide production and neuronal modifications in the neocortex of a NOS2 mutant mouse.

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    Yossi Buskila

    Full Text Available BACKGROUND: It has been well accepted that glial cells in the central nervous system (CNS produce nitric oxide (NO through the induction of a nitric oxide synthase isoform (NOS2 only in response to various insults. Recently we described rapid astroglial, NOS2-dependent, NO production in the neocortex of healthy mice on a time scale relevant to neuronal activity. To explore a possible role for astroglial NOS2 in normal brain function we investigated a NOS2 knockout mouse (B6;129P2-Nos2(tm1Lau/J, Jackson Laboratory. Previous studies of this mouse strain revealed mainly altered immune responses, but no compensatory pathways and no CNS abnormalities have been reported. METHODOLOGY/PRINCIPAL FINDINGS: To our surprise, using NO imaging in brain slices in combination with biochemical methods we uncovered robust NO production by neocortical astrocytes of the NOS2 mutant. These findings indicate the existence of an alternative pathway that increases basal NOS activity. In addition, the astroglial mutation instigated modifications of neuronal attributes, shown by changes in the membrane properties of pyramidal neurons, and revealed in distinct behavioral abnormalities characterized by an increase in stress-related parameters. CONCLUSIONS/SIGNIFICANCE: The results strongly indicate the involvement of astrocytic-derived NO in modifying the activity of neuronal networks. In addition, the findings corroborate data linking NO signaling with stress-related behavior, and highlight the potential use of this genetic model for studies of stress-susceptibility. Lastly, our results beg re-examination of previous studies that used this mouse strain to examine the pathophysiology of brain insults, assuming lack of astrocytic nitrosative reaction.

  20. Relationships between polymorphisms in NOS3 and MPO genes, cigarette smoking and risk of post-menopausal breast cancer.

    Science.gov (United States)

    Yang, Jun; Ambrosone, Christine B; Hong, Chi-Chen; Ahn, Jiyoung; Rodriguez, Carmen; Thun, Michael J; Calle, Eugenia E

    2007-06-01

    NOS3 and MPO genes encode endothelial nitric oxide synthase and myeloperoxidase (MPO), respectively, which generate nitric oxide and reactive oxygen species. Because cigarette smoking generates reactive species, we hypothesized that NOS3 and MPO polymorphisms could influence susceptibility to breast cancer, particularly among smokers. We examined the associations between NOS3 Glu298Asp and MPO G-463A polymorphisms and breast cancer risk by cigarette smoking among post-menopausal women in the American Cancer Society's Cancer Prevention Study II Nutrition Cohort. Included in this analysis were 502 women who provided blood samples and were diagnosed with breast cancer between 1992 and 2001 and 505 cancer-free controls who were matched to the cases by age, race/ethnicity and date of blood donation. Genotyping for NOS3 and MPO was performed using TaqMan, and unconditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). No statistically significant relationships were found between NOS3 and MPO genotypes and breast cancer risk. When considering smoking, variant NOS3 genotypes (GT and TT) were significantly associated with reduced breast cancer risk among never smokers (OR = 0.67, 95% CI = 0.45-0.99), but were associated with higher risk among ever smokers (OR = 1.59, 95% CI = 1.05-2.41) and 2-fold increase in risk for those who smoked >10 cigarettes per day (OR = 2.19, 95% CI = 1.21-3.97). NOS3 genotypes appeared to be associated with risk of post-menopausal breast cancer among smokers, supporting the hypothesis that subgroups of women based upon genetic profiles may be at higher risk of breast cancer when exposed to tobacco smoke.

  1. Ilusão das imagens: olhar psicossocial sobre fumar nos filmes brasileiros

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    Rosa Vargas

    2014-01-01

    Full Text Available Este estudo amplia o olhar psicossocial sobre o tabagismo. Descreve um quadro de ocorrências de imagens de produtos de tabaco e de seu consumo em uma amostragem de vinte filmes de longa-metragem brasileiros para exibição comercial. Nos resultados foram observadas imagens com esse conteúdo em metade dos filmes da amostra, e, em 70% daqueles em que ocorreram essas cenas, havia também a exibição relevante de embalagens de produtos ou marcas comerciais. Como conclusão, a utilização da mídia de entretenimento aparece entre os dados pesquisados como importante conteúdo a ser avaliado nos filmes. A presença nas telas, não apenas de imagens de consumo de cigarros e embalagens de produtos, mas também de marcas comerciais, pode contribuir para influenciar crianças e jovens a experimentar cigarros e reforçar o ato de fumar como comportamento normativo ou padrão entre as pessoas.

  2. Abordagem da amamentação nos primeiros anos do ensino fundamental

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    Dulce Maria Pereira Garcia Galvão

    2013-04-01

    Full Text Available Para analisar os currículos e os livros escolares adotados nos primeiros cinco anos do Ensino Fundamental na disciplina de Ciências quanto à presença ou não de termos relacionados à prática da amamentação, realizamos um estudo descritivo analisando o currículo e 16 manuais de 25 escolas públicas de três municípios do interior paulista, de setembro/2010 a fevereiro/2011. Definimos previamente alguns conceitos considerados imprescindíveis para ensinar e explicar à criança noções de amamentação. Verificamos que nenhum bloco temático do currículo aborda explicitamente a temática amamentação. Nove dos 16 conteúdos definidos estavam presentes em oito dos 16 livros. Da análise emergiu a categoria apoio e ajuda da família. Três obras utilizavam ilustrações associadas à alimentação artificial. No programa e nos manuais escolares existem diversas oportunidades de incluir este tema. Aconselha-se a integração dos conteúdos em todos os manuais de Ciências dos primeiros anos do ensino fundamental.

  3. Pobreza multidimensional nos municípios da Região Nordeste

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    Janaina Ottonelli

    2014-10-01

    Full Text Available Na abordagem das capacitações de Sen (1981, 1985, 2000, 2001, a pobreza significa privação em diferentes aspectos da vida. O objetivo deste estudo é mensurar a pobreza multidimensional nos municípios da Região Nordeste por meio da teoria dos conjuntos fuzzy e dados do Censo Demográfico (IBGE, 2010. São utilizados 19 indicadores (funcionamentos distribuídos em quatro dimensões: educação, saúde, condições habitacionais e renda. Os resultados indicam pobreza, com destaque nas dimensões da renda e da educação, principalmente nos estados de Maranhão, Alagoas, Piauí e Paraíba. Políticas de redução da pobreza precisam considerar quais são as privações sofridas pelas pessoas e as particularidades do local onde vivem.

  4. O Rio de Janeiro nos livros didáticos franceses: imagens degradadas, lugares à margem

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    Leonardo Moreira Ulhôa

    2015-07-01

    Full Text Available Este artigo é um desdobramento da tese de doutorado em que analisamos as imagens do Brasil nos livros didáticos franceses, considerando a produção da iconografia e o ativo papel que desempenham no ensino de Geografia. Na ocasião, constatamos que algumas cidades brasileiras nunca conseguiram desvencilhar de sua imagem o reflexo da balbúrdia urbana, uma vez que, arraigadas no predominante modelo da desordem e do caos, projetavam oblíquos olhares sobre as mazelas de nosso país. Nesse contexto, também se inserem as narrativas e as apocalípticas imagens do espaço urbano do Rio de Janeiro em tais obras, sendo frequentemente associadas à violência desenfreada, aos cenários de mendicância, ao descontrole populacional e às desigualdades socioeconômicas. A uniformidade desses discursos, geralmente em tons pejorativos, contribui para solidificar uma ideia bastante unilateral e particularizada sobre essa cidade. Diante disso, propusemo-nos a refletir sobre os sentidos implícitos que se encontram na construção iconográfica dos manuais escolares franceses, numa tentativa de abrir caminhos para decodificar alguns significados consagrados em relação ao Rio de Janeiro ao longo de décadas.

  5. Participação efetiva do enfermeiro no planejamento: foco nos custos

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    Thais Cristina Albano

    2013-06-01

    Full Text Available Trata-se de uma pesquisa que buscou verificar se os enfermeiros de uma instituição hospitalar privada da cidade de São Paulo-SP possuem visão de gerenciamento de custos e observar como ocorre a participação destes profissionais nos níveis de planejamento, com ênfase nos custos. Foram entrevistados 40 enfermeiros, durante seu turno de trabalho, através da aplicação de um questionário a respeito de gerenciamento de custos assistenciais e dos níveis de planejamento organizacional. Observou-se que 85% dos entrevistados afirmaram não participar do gerenciamento de custos assistenciais, sendo que 45% dos participantes não soube explicar a importância desse conhecimento. A maioria dos entrevistados (62,5% afirmou não participar do planejamento estratégico institucional e dentre os que participaram a maior parte não soube explicar sua participação.

  6. SERT and nNOS expression in the choroid plexus of buffalo brain

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    G. Scala

    2010-02-01

    Full Text Available Serotonin (5-HT is a well recognized neurotransmitter in the mammalian central nervous system (CNS. It regulates a variety of physiological functions such as sleep, pain, thermoregulation, feeding, sexual behaviour, and mood. An important component of the 5-HT system is the serotonin transporter SERT which regulates 5-HT homeostasis. Nitric oxide (NO acts as an intercellular messenger in the CNS, and exerts profound effects on the neuroendocrine functions and behaviour. Within neurons, NO is produced by the activity of one of the isoform of NO synthases present in the organism, namely neuronal NO synthase (nNOS. Although a different anatomical distribution of the central neurons synthetizing 5-HT and NO-producing neurons, functional interactions have been demonstrated between the central 5-HT- and NO-generating systems. Recent data indicate that NO may regulate both the intracellular amount of the amine and its intracellular availability by controlling the release and uptake of 5-HT. In this study, we demonstrated the expression of both SERT and nNOS in the choroid plexuses of buffalo brain by scanning electron microscopy (SEM and biochemical analyses. Our findings may provide some insights into the mechanism by which the choroid plexus specific barrier acts for the regulation of the most basic neural functions.

  7. Religando as arenas institucionais: uma proposta de abordagens multidimensionais nos estudos legislativos

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    Paulo Peres

    2012-10-01

    Full Text Available A área de estudos legislativos foi uma das linhas de pesquisa que mais se desenvolveram no Brasil nos últimos anos. Ela formou-se em torno da oposição entre as explicações "distributivistas" e as explicações "partidárias" do processo legislativo. Seus achados empíricos e seu debate teórico certamente trouxeram grandes contribuições à Ciência Política do país e, até mesmo, ao debate de política comparada. Não obstante, essa linha de investigação incorreu no problema de adotar abordagens monodimensionais do fenômeno. A explicação partidária promoveu certo "insulamento" do poder Legislativo em relação às outras arenas institucionais, analisando-o em função de sua autodeterminação. A abordagem distributivista investiu quase exclusivamente no sistema eleitoral como variável explicativa, deixando em segundo plano outras arenas institucionais. Diante disso, nossa proposta é analisar os limites dessas abordagens presentes nos estudos legislativos, de forma a destacar algumas lacunas explicativas que poderiam ser preenchidas por meio de uma agenda de pesquisas multidimensionais, que considerem, por exemplo, as organizações partidárias e o poder Judiciário.

  8. O uso da música nos cuidados paliativos: humanizando o cuidado e facilitando o adeus

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    Natalie Hidemi Seki

    2010-06-01

    Full Text Available O convívio com uma doença ameaçadora da vida pode afetar o sujeito e a família em diversas dimensões - física, emocional, espiritual, social e econômica - e demandar cuidados sensíveis e atentos de uma equipe multidisciplinar ao enfrentar tal situação única e delicada. O artigo tem como objetivo refletir sobre as contribuições do uso da música nos cuidados paliativos e na humanização do cuidado da pessoa fora de possibilidades terapêuticas de cura. Com esse propósito, foi realizada pesquisa bibliográfica, mediante busca eletrônica de artigos indexados em bases de dados e por varredura manual dos periódicos não indexados considerados relevantes. A pesquisa mostra que o uso da música nos processos saúde-doença-cuidado pode promover conforto e qualidade de vida para a pessoa adoecida e ser um recurso de ajuda na relação da família com a despedida de seu ente querido. Pode também auxiliar na manutenção de uma equipe de saúde saudável e integrada.

  9. Coupled Nosé-Hoover equations of motions without time scaling

    Science.gov (United States)

    Fukuda, Ikuo; Moritsugu, Kei

    2017-01-01

    The Nosé-Hoover (NH) equation of motion is widely used in molecular dynamics simulations. It enables us to set a constant temperature and produce the canonical distribution for a target physical system. For the purpose of investigating the physical system under fluctuating temperature, we have introduced a coupled Nosé-Hoover equation in our previous work (Fukuda and Moritsugu 2015 J. Phys. A: Math. Theor. 48 455001). The coupled NH equation implements a fluctuating heat-bath temperature in the NH equation of the physical system, and also keeps a statistically complete description via an invariant measure of the total system composed of the physical system and a ‘temperature system’. However, a difficulty lies in that the time development of the physical system may not correspond to the realistic physical process, because of the need of a scaled time average to compute thermodynamical quantities. The current work gives a solution by presenting a new scheme, which is free from the scaled time but retains the statistical description. By use of simple model systems, we validate the current scheme and compare with the original scheme. The sampling property of the current scheme is also clarified to investigate the effect of function setting used for the distribution of the total system.

  10. An NOS3 Haplotype Is Protective against Hypertension in a Caucasian Population

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    Georgios D. Kitsios

    2010-01-01

    Full Text Available The endothelial nitric oxide synthase gene (NOS3 has been implicated in the development of hypertension, although the specific role of variants and haplotypes has not been clarified. In this study, the association of three polymorphisms (promoter T786C, intronic 4a/b, and nonsynonymous G894T was tested in a case-control sample of 230 patients with essential hypertension and 306 healthy controls. Haplotype analysis was also performed. The mutant allele a∗ of the 4a/b polymorphism showed a protective effect against hypertension under a dominant model (odds ratio=0.64, 95% confidence interval (0.44–0.93, although this effect was not significant after the adjustment for covariates (=0.06. The estimated frequency of the haplotype composed of the T786∗, 4a∗, and G894∗ alleles was significantly higher in controls (5.5% compared to cases (2%. These results indicate that although individual NOS3 polymorphisms are not associated with hypertension, a rare haplotype of the gene might be protective against the development of hypertension.

  11. The Glu298Asp polymorphism in the NOS3 gene and the risk of prostate cancer.

    Science.gov (United States)

    Zhang, Yonggang; Jia, Qingyi; He, Qing; Shen, Jiani; Yang, Jiqiao; Xue, Pei; Ma, Mengmeng; Xu, Rui; Du, Liang

    2014-05-01

    The Glu298Asp polymorphism in the NOS3 gene has been implicated as a risk factor for prostate cancer. To date, several studies have evaluated the associations between the Glu298Asp polymorphism and prostate cancer risk; however, the results were inconclusive. The aim of the current study was to perform a meta-analysis to investigate the association between the polymorphism and the risk of prostate cancer. A total of 3,206 cases and 3,880 controls from eight case-control studies were included for data synthesis. The overall results suggested no significant association between the polymorphism and the risk of prostate cancer (OR=1.01, 95% CI=0.92-1.11, p = 0.83 for Asp/Asp+Glu/Asp vs. Glu/Glu). In the stratified analysis according to ethnicity, no significant associations were observed in Asians and Europeans. The current meta-analysis suggested that the Glu298Asp polymorphism of the NOS3 gene might not contribute to the risk of prostate cancer.

  12. Association between polymorphisms in NOS3 and KCNH2 and social memory

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    Susanne eHenningsson

    2015-10-01

    Full Text Available Social memory, including the ability to recognize faces and voices, is essential for social relationships. It has a large heritable component, but the knowledge about the contributing genes is sparse. The genetic variation underlying inter-individual differences in social memory was investigated in an exploratory sample (n=55, genotyped with a chip comprising approximately 200.000 single nucleotide polymorphisms (SNPs, and in a validation sample (n=582, where 30 SNPs were targeted. In the exploratory study face identity recognition was measured. The validation study also measured vocal sound recognition, as well as recognition of faces and vocal sounds combined (multimodal condition. In the exploratory study, the 30 SNPs that were associated with face recognition at puncorrected<0.001 and located in genes, were chosen for further study. In the validation study two of the SNPs showed significant associations with recognition of faces, vocal sounds, and multimodal stimuli: rs1800779 in the gene encoding nitric oxide synthase 3 (NOS3 and rs3807370 in the gene encoding the voltage-gated channel, subfamily H, member 2 (KCNH2, in strong linkage disequilibrium with each other. The uncommon alleles were associated with superior performance, and the effects were present for men only (p<0.0002. The exploratory study also showed a weaker but significant association with (non-emotional word recognition, an effect that was independent of the effect on face recognition. This study demonstrates evidence for an association between NOS3 and KCNH2 SNPs and social memory.

  13. Association between polymorphisms in NOS3 and KCNH2 and social memory.

    Science.gov (United States)

    Henningsson, Susanne; Zettergren, Anna; Hovey, Daniel; Jonsson, Lina; Svärd, Joakim; Cortes, Diana S; Melke, Jonas; Ebner, Natalie C; Laukka, Petri; Fischer, Håkan; Westberg, Lars

    2015-01-01

    Social memory, including the ability to recognize faces and voices, is essential for social relationships. It has a large heritable component, but the knowledge about the contributing genes is sparse. The genetic variation underlying inter-individual differences in social memory was investigated in an exploratory sample (n = 55), genotyped with a chip comprising approximately 200,000 single nucleotide polymorphisms (SNPs), and in a validation sample (n = 582), where 30 SNPs were targeted. In the exploratory study face identity recognition was measured. The validation study also measured vocal sound recognition, as well as recognition of faces and vocal sounds combined (multimodal condition). In the exploratory study, the 30 SNPs that were associated with face recognition at p uncorrected NOS3) and rs3807370 in the gene encoding the voltage-gated channel, subfamily H, member 2 (KCNH2), in strong linkage disequilibrium with each other. The uncommon alleles were associated with superior performance, and the effects were present for men only (p NOS3 and KCNH2 SNPs and social memory.

  14. Examen quinquennal 2010 : confirmation de la dérive de nos salaires

    CERN Multimedia

    STAFF ASSOCIATION

    2010-01-01

    Examen quinquennal 2010 : confirmation de la dérive de nos salaires Un examen général de nos conditions financières et sociales a lieu tous les cinq ans : « l’examen quinquennal », dont l’annexe A1 des Statut et Règlement du personnel décrit les principes et la procédure. L’objet de l’examen quinquennal est d’assurer que les conditions financières et sociales offertes par l’Organisation permettent à celle-ci d’engager, dans tous ses Etats membres, et de retenir en son sein les titulaires de la plus haute compétence et de la plus grande intégrité nécessaires à l’exécution de sa mission. L’examen quinquennal inclut, à titre obligatoire, les traitements de base (les salaires de base des titulaires, les mens...

  15. O paradoxo dos documentos de identidade: relato de uma experiência nos Estados Unidos

    Directory of Open Access Journals (Sweden)

    Mariza Peirano

    2009-12-01

    Full Text Available No mundo moderno, documentos são objetos indispensáveis, sem os quais não conseguimos demonstrar que somos quem dizemos que somos. Precisamos de provas materiais que atestem a veracidade da nossa autoidentificação. Este artigo relata a experiência de pesquisa sobre documentos de identidade nos Estados Unidos, por meio de dois eventos em que Eliot Spitzer, governador do estado de Nova Iorque de janeiro de 2007 a março de 2008, foi figura central, e nos quais os documentos foram um subtexto importante. Uma comparação com o caso brasileiro está presente ao longo do artigo, que termina examinando o fenômeno conhecido como ID theft.In the modern world, IDs are indispensable objects, without which we cannot prove that we are who we say we are. We need material substantiation that attests to the authenticity of our self-identification. This paper is an account of an ethnographic experience about IDs and identification processes in the US, based on the examination of two events in which Eliot Spitzer, the New York State governor from January 2007 to March 2008, was a central figure. A comparison with the Brazilian scenario is present throughout the paper, and it ends by focusing on the ID theft phenomenon.

  16. Um mundo metafísico nos trópicos

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    Else Ribeiro Pires Vieira

    2008-04-01

    Full Text Available A fonte torna-se a estrela inatingível e pura que, sem se deixar contaminar, contamina, brilha para os artistas dos países da América Latina... ilumina os movimentos das mãos, mas ao mesmo tempo torna os artistas súditos do seu magnetismo superior.. Silviano Santiago, Uma literatura nos trópicos Afastando-me do discurso crítico em torno das influências e do caráter tributário a ele inerente, sobre o qual nos adverte Santiago já em ensaio de 1971,1 afastando-me, igualmente, de Polarizações hierarquizadas como fonte/alvo, situando-me na fronteira fluida do transformar de escritas/reescritas e nela privilegiando áreas de permeabilidade entre os discursos e o seu jogo relacional, ofereço, neste texto, reflexões em torno da poesia metafísica inglesa traduzida entre 1978 e 1991 na sua interseção com outras produções textuais brasileiras no período de início da abertura política, gestação e nascimento da Nova República2 . Traduzir a Inglaterra, ler o Brasil. O que se traduz? Quem se traduz? Por que se traduz? Como se traduz?

  17. Acarbose Accelerates Wound Healing via Akt/eNOS Signaling in db/db Mice

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    Xue Han

    2017-01-01

    Full Text Available Refractory wound is a dreaded complication of diabetes and is highly correlated with EPC dysfunction caused by hyperglycemia. Acarbose is a widely used oral glucose-lowering drug exclusively for T2DM. Previous studies have suggested the beneficial effect of acarbose on improving endothelial dysfunction in patients with T2DM. However, no data have been reported on the beneficial efficacy of acarbose in wound healing impairment caused by diabetes. We herein investigated whether acarbose could improve wound healing in T2DM db/db mice and the possible mechanisms involved. Acarbose hastened wound healing and enhanced angiogenesis, accompanied by increased circulating EPC number in db/db mice. In vitro, a reversed BM-EPC dysfunction was observed after the administration of acarbose in db/db mice, as reflected by tube formation assay. In addition, a significantly increased NO production was also witnessed in BM-EPCs from acarbose treated db/db mice, with decreased O2 levels. Akt inhibitor could abolish the beneficial effect of acarbose on high glucose induced EPC dysfunction in vitro, accompanied by reduced eNOS activation. Acarbose displayed potential effect in promoting wound healing and improving angiogenesis in T2DM mice, which was possibly related to the Akt/eNOS signaling pathway.

  18. Negligible effect of eNOS palmitoylation on fatty acid regulation of contraction in ventricular myocytes from healthy and hypertensive rats.

    Science.gov (United States)

    Jin, Chun Li; Wu, Yu Na; Jang, Ji Hyun; Zhao, Zai Hao; Oh, Goo Taeg; Kim, Sung Joon; Zhang, Yin Hua

    2017-04-25

    S-palmitoylation is an important post-translational modification that affects the translocation and the activity of target proteins in a variety of cell types including cardiomyocytes. Since endothelial nitric oxide synthase (eNOS) is known to be palmitoylated and the activity of eNOS is essential in fatty acid-dependent β-oxidation in muscle, we aimed to test whether palmitoylation of eNOS is involved in palmitic acid (PA) regulation of left ventricular (LV) myocyte contraction from healthy (sham) and hypertensive (HTN) rats. Our results showed that PA, a predominant metabolic substrate for cardiac β-oxidation, significantly increased contraction and oxygen consumption rate (OCR) in LV myocytes from sham. Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) or eNOS gene deletion prevented PA regulation of the myocyte contraction or OCR, indicating the pivotal role of eNOS in mediating the effects of PA in cardiac myocytes. PA increased the palmitoylation of eNOS in LV myocytes and depalmitoylation with 2-bromopalmitate (2BP; 100 μM) abolished the increment. Furthermore, although PA did not increase eNOS-Ser(1177), 2BP reduced eNOS-Ser(1177) with and without PA. Intriguingly, PA-induced increases in contraction and OCR were unaffected by 2BP treatment. In HTN, PA did not affect eNOS palmitoylation, eNOS-Ser(1177), or myocyte contraction. However, 2BP diminished eNOS palmitoylation and eNOS-Ser(1177) in the presence and absence of PA but did not change myocyte contraction. Collectively, our results confirm eNOS palmitoylation in LV myocytes from sham and HTN rats and its upregulation by PA in sham. However, such post-transcriptional modification plays negligible role in PA regulation of myocyte contraction and mitochondrial activity in sham and HTN.

  19. The Development of In-Service Science Teachers' Understandings of and Orientations to Teaching the Nature of Science within a PCK-Based NOS Course

    Science.gov (United States)

    Faikhamta, Chatree

    2013-04-01

    The nature of science (NOS) has become a central goal of science education in many countries. This study sought an understanding of the extent to which a nature of science course (NOSC), designed according to the conceptualization of pedagogical content knowledge (PCK) for teaching nature of science (NOS), affects in-service science teachers' understanding and learning of NOS, and their orientations towards teaching it. A qualitative research approach was employed as a research methodology, drawing upon pre- and post-instruction NOS questionnaires, field notes, and in-service teachers' weekly journal entries and assignments. Open-ended NOS questionnaires, used to assess participants' understandings of NOS, were analysed and categorized as either informed, partially informed and naive. Other qualitative data were analysed through an inductive process to identify ways in-service teachers engaged and learned in the NOSC. The results indicate that at the beginning of the course, a majority of the in-service science teachers held naive understandings of NOS, particularly with respect to the definition of science, scientific inquiry, and differences between laws and theories. They viewed implicit project-based science and science process skills as goals of NOS instruction. By engaging in the course, the in-service science teachers developed an understanding of NOS and orientations to teaching NOS based on various elements, especially reflective and explicit instruction, role modelling, and content- and non-content embedded instruction. The aim of this study is to help science teacher educators, consider how to support and develop science teachers' understandings of NOS while being mindful of PCK for NOS, and develop methods for teaching NOS frameworks.

  20. Neuronal nitric oxide synthase-rescue of dystrophin/utrophin double knockout mice does not require nNOS localization to the cell membrane.

    Directory of Open Access Journals (Sweden)

    Michelle Wehling-Henricks

    Full Text Available Survival of dystrophin/utrophin double-knockout (dko mice was increased by muscle-specific expression of a neuronal nitric oxide synthase (nNOS transgene. Dko mice expressing the transgene (nNOS TG+/dko experienced delayed onset of mortality and increased life-span. The nNOS TG+/dko mice demonstrated a significant decrease in the concentration of CD163+, M2c macrophages that can express arginase and promote fibrosis. The decrease in M2c macrophages was associated with a significant reduction in fibrosis of heart, diaphragm and hindlimb muscles of nNOS TG+/dko mice. The nNOS transgene had no effect on the concentration of cytolytic, CD68+, M1 macrophages. Accordingly, we did not observe any change in the extent of muscle fiber lysis in the nNOS TG+/dko mice. These findings show that nNOS/NO (nitric oxide-mediated decreases in M2c macrophages lead to a reduction in the muscle fibrosis that is associated with increased mortality in mice lacking dystrophin and utrophin. Interestingly, the dramatic and beneficial effects of the nNOS transgene were not attributable to localization of nNOS protein at the cell membrane. We did not detect any nNOS protein at the sarcolemma in nNOS TG+/dko muscles. This important observation shows that sarcolemmal localization is not necessary for nNOS to have beneficial effects in dystrophic tissue and the presence of nNOS in the cytosol of dystrophic muscle fibers can ameliorate the pathology and most importantly, significantly increase life-span.

  1. Phosphodiesterase 5 restricts NOS3/Soluble guanylate cyclase signaling to L-type Ca2+ current in cardiac myocytes.

    Science.gov (United States)

    Wang, Honglan; Kohr, Mark J; Traynham, Christopher J; Ziolo, Mark T

    2009-08-01

    Endothelial nitric oxide synthase (NOS3) regulates the functional response to beta-adrenergic (beta-AR) stimulation via modulation of the L-type Ca(2+) current (I(Ca)). However, the NOS3 signaling pathway modulating I(Ca) is unknown. This study investigated the contribution of soluble guanylate cyclase (sGC) and phosphodiesterase type 5 (PDE5), a cGMP-specific PDE, in the NOS3-mediated regulation of I(Ca). Myocytes were isolated from NOS3 knockout (NOS3(-/-)) and wildtype (WT) mice. We measured I(Ca) (whole-cell voltage-clamp), and simultaneously measured Ca(2+) transients (Fluo-4 AM) and cell shortening (edge detection). Zaprinast (selective inhibitor of PDE5), decreased beta-AR stimulated (isoproterenol, ISO)-I(Ca), and Ca(2+) transient and cell shortening amplitudes in WT myocytes. However, YC-1 (NO-independent activator of sGC) only reduced ISO-stimulated I(Ca), but not cardiac contraction. We further investigated the NOS3/sGC/PDE5 pathway in NOS3(-/-) myocytes. PDE5 is mislocalized in these myocytes and we observed dissimilar effects of PDE5 inhibition and sGC activation compared to WT. That is, zaprinast had no effect on ISO-stimulated I(Ca), or Ca(2+) transient and cell shortening amplitudes. Conversely, YC-1 significantly decreased both ISO-stimulated I(Ca), and cardiac contraction. Further confirming that PDE5 localizes NOS3/cGMP signaling to I(Ca); YC-1, in the presence of zaprinast, now significantly decreased ISO-stimulated Ca(2+) transient and cell shortening amplitudes in WT myocytes. The effects of YC-1 on I(Ca) and cardiac contraction were blocked by KT5823 (a selective inhibitor of the cGMP-dependent protein kinase, PKG). Our data suggests a novel physiological role for PDE5 in restricting the effects of NOS3/sGC/PKG signaling pathway to modulating beta-AR stimulated I(Ca), while limiting effects on cardiac contraction.

  2. Effects of rat urotensin II on coronary flow and myocardial eNOS protein expression in isolated rat heart

    Institute of Scientific and Technical Information of China (English)

    LingLI; Wen-junYUAN; Ding-fengSU

    2004-01-01

    AIM: To examine the effects of urotensin Ⅱ, a recently discovered endogenous peptide, on coronary flow (CF),cardiac function, and endothelial nitric oxide synthase (eNOS) expression in isolated rat hearts. METHODS: Heart was isolated and perfused retrogradely via the aorta in Langendorff mode. Rat urotensin Ⅱ was administered in the perfusion solution. The eNOS content in myocardium was determined by Western blot. RESULTS: Rat urotensin Ⅱ had no effect on the heart rate, left ventricular systolic pressure, left ventricular end-diastolic pressure, or±dp/dt max. While rat urotensin Ⅱ dose-dependently increased CF. CF was increased by 11.43%, 6.67%, 6.62%,6.56%, 6.36%, and 5.86% respectively in a time-dependent manner at 5, 10, 15, 20, 25, and 30 min after injection of rat urotensin Ⅱ 6.66×10-2μg. The maximal effect on CF was found at 5 min following urotensin Ⅱ administration.NG-nitro-L-arginine methyl ester (L-NAME) did not prevent the increased CF in response to urotensin Ⅱ. Rat urotensin Ⅱ dose-dependently increased the cardiac eNOS protein expression and this effect was not inhibited by L-NAME. CONCLUSION: Rat urotensin Ⅱ did not alter cardiac function but increased CF and the amount of myocardial eNOS protein in the isolated rat heart. The increased CF was independent of the involvement of eNOS.

  3. Substrate-Tuned Catalysis of the Radical S-Adenosyl-L-Methionine Enzyme NosL Involved in Nosiheptide Biosynthesis.

    Science.gov (United States)

    Ji, Xinjian; Li, Yongzhen; Ding, Wei; Zhang, Qi

    2015-07-27

    NosL is a radical S-adenosyl-L-methionine (SAM) enzyme that converts L-Trp to 3-methyl-2-indolic acid, a key intermediate in the biosynthesis of a thiopeptide antibiotic nosiheptide. In this work we investigated NosL catalysis by using a series of Trp analogues as the molecular probes. Using a benzofuran substrate 2-amino-3-(benzofuran-3-yl)propanoic acid (ABPA), we clearly demonstrated that the 5'-deoxyadenosyl (dAdo) radical-mediated hydrogen abstraction in NosL catalysis is not from the indole nitrogen but likely from the amino group of L-Trp. Unexpectedly, the major product of ABPA is a decarboxylated compound, indicating that NosL was transformed to a novel decarboxylase by an unnatural substrate. Furthermore, we showed that, for the first time to our knowledge, the dAdo radical-mediated hydrogen abstraction can occur from an alcohol hydroxy group. Our study demonstrates the intriguing promiscuity of NosL catalysis and highlights the potential of engineering radical SAM enzymes for novel activities.

  4. Identificação de artrite em suínos utilizando imagem termográfica

    Directory of Open Access Journals (Sweden)

    Daniela Espangue Graciano

    2014-01-01

    Full Text Available Nos sistemas intensivos de produção de suíno uma das afecções mais prevalentes são as artrites, que causam dor aos animais podendo afetar seu desempenho e bem-estar. Deste modo, o diagnóstico precoce torna-se importante para que se dispense aos animais tratamento adequado em tempo hábil. Objetivou-se com este estudo de caso, avaliar a eficiência do uso das imagens termográficas para identificação de artrite, ou de lesões em suínos. Foram utilizados cinco animais com suspeita de artrite nos membros posteriores. A temperatura superficial (TS dos membros posteriores foi registrada por meio de imagens termográficas utilizando o termovisor da Testo®. Foram calculadas as médias de 10 pontos da TS de cada membro posterior dos suínos, sendo posteriormente comparadas utilizando o teste t-Student, com confiabilidade de 95%. Os valores médios de TS foram menores (P≤0,05 no membro sadio (33,6°C, do que naquele com artrite (35,6°C evidenciando que, por meio de imagens termográficas, é possível a identificação de processos inflamatórios em suínos.

  5. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease

    Science.gov (United States)

    Besler, Christian; Heinrich, Kathrin; Rohrer, Lucia; Doerries, Carola; Riwanto, Meliana; Shih, Diana M.; Chroni, Angeliki; Yonekawa, Keiko; Stein, Sokrates; Schaefer, Nicola; Mueller, Maja; Akhmedov, Alexander; Daniil, Georgios; Manes, Costantina; Templin, Christian; Wyss, Christophe; Maier, Willibald; Tanner, Felix C.; Matter, Christian M.; Corti, Roberto; Furlong, Clement; Lusis, Aldons J.; von Eckardstein, Arnold; Fogelman, Alan M.; Lüscher, Thomas F.; Landmesser, Ulf

    2011-01-01

    Therapies that raise levels of HDL, which is thought to exert atheroprotective effects via effects on endothelium, are being examined for the treatment or prevention of coronary artery disease (CAD). However, the endothelial effects of HDL are highly heterogeneous, and the impact of HDL of patients with CAD on the activation of endothelial eNOS and eNOS-dependent pathways is unknown. Here we have demonstrated that, in contrast to HDL from healthy subjects, HDL from patients with stable CAD or an acute coronary syndrome (HDLCAD) does not have endothelial antiinflammatory effects and does not stimulate endothelial repair because it fails to induce endothelial NO production. Mechanistically, this was because HDLCAD activated endothelial lectin-like oxidized LDL receptor 1 (LOX-1), triggering endothelial PKCβII activation, which in turn inhibited eNOS-activating pathways and eNOS-dependent NO production. We then identified reduced HDL-associated paraoxonase 1 (PON1) activity as one molecular mechanism leading to the generation of HDL with endothelial PKCβII-activating properties, at least in part due to increased formation of malondialdehyde in HDL. Taken together, our data indicate that in patients with CAD, HDL gains endothelial LOX-1– and thereby PKCβII-activating properties due to reduced HDL-associated PON1 activity, and that this leads to inhibition of eNOS-activation and the subsequent loss of the endothelial antiinflammatory and endothelial repair–stimulating effects of HDL. PMID:21701070

  6. Polymorphisms in NOS3, ACE and PAI-1 genes and risk of spontaneous recurrent miscarriage in the Gaza Strip.

    Science.gov (United States)

    Al Sallout, Rami J; Sharif, Fadel A

    2010-01-01

    This study was conducted to investigate the correlation between spontaneous recurrent miscarriage (RM) and common polymorphisms in angiotensin-converting enzyme (ACE), plasminogen activator inhibitor 1 (PAI-1) and endothelium-derived nitric oxide synthase 3 (NOS3) genes among women experiencing RM in the Gaza Strip. The presence of these genetic profiles was determined for 100 women who had had at least 3 constitutive abortions and 100 controls without any history of abortion using molecular biological techniques. The ACE D/D polymorphism was present in 49% of the study population and in 54% of the controls (p = 0.479). Similarly, there was no significant difference detected in the distribution of polymorphisms for PAI-1, with the 4G/4G genotype present in the study group and in controls (p = 1.00). NOS3 4a/4a was present in 4% of the study group and in none of the 100 controls (p = 0.123). In this study, we also discovered a new variant in the NOS3 gene which was named 4c allele and was encountered in 1 patient and in 1 control subject. There was no significant association between ACE I/D, PAI-1 4G/5G and NOS3 4a/4b and the occurrence of first-trimester RM. In-depth investigation of the association of NOS3 4a/4a with RM is strongly recommended. Copyright 2010 S. Karger AG, Basel.

  7. Right Ventricular Adaptation Is Associated with the Glu298Asp Variant of the NOS3 Gene in Elite Athletes.

    Science.gov (United States)

    Szelid, Zsolt; Lux, Árpád; Kolossváry, Márton; Tóth, Attila; Vágó, Hajnalka; Lendvai, Zsuzsanna; Kiss, Loretta; Maurovich-Horvat, Pál; Bagyura, Zsolt; Merkely, Béla

    2015-01-01

    Nitric oxide (NO), an important endogenous pulmonary vasodilator is synthetized by the endothelial NO synthase (NOS3). Reduced NO bioavailability and thus the Glu298Asp polymorphism of NOS3 may enhance right ventricular (RV) afterload and hypertrophic remodeling and influence athletic performance. To test this hypothesis world class level athletes (water polo players, kayakers, canoeists, rowers, swimmers, n = 126) with a VO2 maximum greater than 50ml/kg/min were compared with non-athletic volunteers (n = 155). Cardiopulmonary exercise tests and cardiac magnetic resonance imaging (cMRI) were performed to determine structural or functional changes. Genotype distribution of the NOS3 Glu298Asp polymorphism was not affected by gender or physical performance. Cardiac MRI showed increased stroke volume with eccentric hypertrophy in all athletes regardless of their genotype. However, the Asp allelic variant carriers had increased RV mass index (32±6g versus 27±6g, pNOS3 Glu298Asp polymorphism and RV structure and dimension in elite athletes emphasizes the importance of NOS3 gene function and NO bioavailability in sport related cardiac adaptation.

  8. Right Ventricular Adaptation Is Associated with the Glu298Asp Variant of the NOS3 Gene in Elite Athletes.

    Directory of Open Access Journals (Sweden)

    Zsolt Szelid

    Full Text Available Nitric oxide (NO, an important endogenous pulmonary vasodilator is synthetized by the endothelial NO synthase (NOS3. Reduced NO bioavailability and thus the Glu298Asp polymorphism of NOS3 may enhance right ventricular (RV afterload and hypertrophic remodeling and influence athletic performance. To test this hypothesis world class level athletes (water polo players, kayakers, canoeists, rowers, swimmers, n = 126 with a VO2 maximum greater than 50ml/kg/min were compared with non-athletic volunteers (n = 155. Cardiopulmonary exercise tests and cardiac magnetic resonance imaging (cMRI were performed to determine structural or functional changes. Genotype distribution of the NOS3 Glu298Asp polymorphism was not affected by gender or physical performance. Cardiac MRI showed increased stroke volume with eccentric hypertrophy in all athletes regardless of their genotype. However, the Asp allelic variant carriers had increased RV mass index (32±6g versus 27±6g, p<0.01 and larger RV stroke volume index (71±10ml versus 64±10ml, p<0.01 than athletes with a Glu/Glu genotype. Genotype was not significantly associated with athletic performance. In the non-athletic group no genotype related differences were detected. The association between the NOS3 Glu298Asp polymorphism and RV structure and dimension in elite athletes emphasizes the importance of NOS3 gene function and NO bioavailability in sport related cardiac adaptation.

  9. The Association between NOS3 Gene Polymorphisms and Hypoxic-Ischemic Encephalopathy Susceptibility and Symptoms in Chinese Han Population

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    Yongqin Wu

    2016-01-01

    Full Text Available Endothelial NOS (NOS3 has a potential role in the prevention of neuronal injury in hypoxic-ischemic encephalopathy (HIE. Thus, we aimed to explore the association between NOS3 gene polymorphisms and HIE susceptibility and symptoms in a Chinese Han population. Three single nucleotide polymorphisms (SNPs in the NOS3 gene, rs1800783, rs1800779, and rs2070744, were detected in 226 children with HIE and 212 healthy children in a Chinese Han population. Apgar scores and magnetic resonance image scans were used to estimate the symptoms and brain damage. The association analyses were conducted by using SNPStats and SPSS 18.0 software. The genotype and allele distributions of rs1800779 and rs1799983 displayed no significant differences between the patients and the controls, while the rs2070744 allele distribution was significantly different (corrected P=0.009. For clinical characteristics, the rs2070744 genotype distribution was significantly different in patients with different Apgar scores (≤5, TT/TC/CC = 6/7/5; 6~7, TT/TC/CC = 17/0/0; 8~9, TT/TC/CC = 6/2/0; 10, TT/TC/CC = 7/1/0; corrected P=0.006 in the 1001 to 1449 g birth weight subgroup. The haplotype test did not show any associations with the risk and clinical characteristics of HIE. The results suggest that NOS3 gene SNP rs2070744 was significantly associated with HIE susceptibility and symptom expression in Chinese Han population.

  10. The Association between NOS3 Gene Polymorphisms and Hypoxic-Ischemic Encephalopathy Susceptibility and Symptoms in Chinese Han Population.

    Science.gov (United States)

    Wu, Yongqin; Zhu, Zhiling; Fang, Xiaoxia; Yin, Ling; Liu, Yuxia; Xu, Shouxia; Li, Aixue

    2016-01-01

    Endothelial NOS (NOS3) has a potential role in the prevention of neuronal injury in hypoxic-ischemic encephalopathy (HIE). Thus, we aimed to explore the association between NOS3 gene polymorphisms and HIE susceptibility and symptoms in a Chinese Han population. Three single nucleotide polymorphisms (SNPs) in the NOS3 gene, rs1800783, rs1800779, and rs2070744, were detected in 226 children with HIE and 212 healthy children in a Chinese Han population. Apgar scores and magnetic resonance image scans were used to estimate the symptoms and brain damage. The association analyses were conducted by using SNPStats and SPSS 18.0 software. The genotype and allele distributions of rs1800779 and rs1799983 displayed no significant differences between the patients and the controls, while the rs2070744 allele distribution was significantly different (corrected P = 0.009). For clinical characteristics, the rs2070744 genotype distribution was significantly different in patients with different Apgar scores (≤5, TT/TC/CC = 6/7/5; 6~7, TT/TC/CC = 17/0/0; 8~9, TT/TC/CC = 6/2/0; 10, TT/TC/CC = 7/1/0; corrected P = 0.006) in the 1001 to 1449 g birth weight subgroup. The haplotype test did not show any associations with the risk and clinical characteristics of HIE. The results suggest that NOS3 gene SNP rs2070744 was significantly associated with HIE susceptibility and symptom expression in Chinese Han population.

  11. The NOS1 variant rs6490121 is associated with variation in prefrontal function and grey matter density in healthy individuals.

    LENUS (Irish Health Repository)

    Rose, Emma J

    2012-03-01

    A common polymorphism within the nitric oxide sythanse-1 (NOS1) gene (rs6490121), initially identified as risk variant for schizophrenia, has been associated with variation in working memory and IQ. Here we investigated how this variation might be mediated at the level of brain structure and function. In healthy individuals (N=157), voxel based morphometry was used to compare grey matter (GM) volume between homozygous and heterozygous carriers of the \\'G\\' allele (i.e. the allele associated with impaired cognition and schizophrenia risk) and homozygous carriers of the non-risk \\'A\\' allele. Functional brain imaging data were also acquired from 48 participants during performance of a spatial working memory (SWM) task, and analysed to determine any effect of NOS1 risk status. An a priori region-of-interest analysis identified a significant reduction in ventromedial prefrontal GM volume in \\'G\\' allele carriers. Risk carriers also exhibited altered patterns of activation in the prefrontal cortex, caudate, and superior parietal lobe, which were characteristic of abnormal increases in activation in frontoparietal working memory networks and a failure to disengage regions of the default mode network. These functional changes suggest a NOS1-mediated processing inefficiency, which may contribute to cognitive dysfunction in schizophrenia. While the mechanisms by which NOS1 may influence brain structure and\\/or function have not yet been well delineated, these data provide further evidence for a role of NOS1 in risk for schizophrenia via an impact upon cognitive function.

  12. Detecção de locos de características quantitativas com efeito da origem parental dos alelos nos cromossomos 1, 2 e 4 de suínos

    OpenAIRE

    Silva Filho,Miguel Inácio da

    2010-01-01

    Com o objetivo de detectar QTL com efeito da origem parental dos alelos, foram utilizados dados de uma população F2 de suínos, composta de 600 animais, obtidos a partir do cruzamento de machos Piau e fêmeas comerciais. Nos animais F2, foram avaliadas características de desempenho, carcaça, órgãos e vísceras, cortes de carcaça e qualidade de carne. Para a genotipagem de todos os animais, foram utilizados 16 locos de microssatélites distribuídos nos cromossomos 1, 2 e 4. Com o resultado da g...

  13. Fisiopatologia das diarréias em suínos Pathophysiology of swine diarrhea

    Directory of Open Access Journals (Sweden)

    Fábio Augusto Vannucci

    2009-10-01

    Full Text Available A diarréia é a principal manifestação clínica das infecções entéricas. O desequilíbrio entre os processos de absorção e secreção intestinal decorrentes de alterações no transporte de água e eletrólitos é determinante na patogênese dos processos diarréicos. Os mecanismos fisiopatológicos estão associados às características particulares de cada patógeno. Dessa forma, a interação específica entre os patógenos entéricos e o epitélio intestinal resulta em diferentes tipos de diarréias. Na produção de suínos, o conhecimento da fisiopatologia das infecções entéricas é fundamental no desenvolvimento de métodos de diagnóstico e, em um futuro próximo, na elaboração de estratégias de prevenção e controle dessas afecções. Com base nos processos fisiológicos característicos do trato gastrointestinal, esta revisão tem como objetivo descrever aspectos relevantes e atuais dos mecanismos fisiopatológicos das diarréias em suínos. Serão enfatizadas as alterações patológicas no transporte intestinal de íons e nutrientes decorrentes da ação de patógenos entéricos importantes na produção suinícola.Diarrhea is the main clinical manifestation of enteric infections. Imbalance between absorption and intestinal secretion process due to changes in the water and electrolytes transport is critical in the diarrheal diseases pathogenesis. The pathophysiological mechanisms are associated to specific characteristics of each pathogen. Therefore, specific interaction between enteric pathogens and intestinal epithelium result in different types of diarrhea. In swine production, the knowledge about the enteric infections pathophysiology is important for the development of diagnostic methods and, in a near future improvement of prevention and control strategies. The aim of this review is to describe different relevant aspects of the swine diarrhea pathophysiology based on the physiological processes typical of

  14. Análise quantitativa de fluoretos nos alginatos para uso odontológico

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    A. C.C. Spadaro

    2009-01-01

    Full Text Available

    Este trabalho teve como proposta analisar quantitativamente o conteúdo de fluoretos nos alginatos para uso odontológico e a liberação de fluoretos de moldes desses alginatos em água milliQ, saliva artificial e ácido clorídrico 0,1 mol/l. Foram investigadas sete marcas de alginatos disponíveis comercialmente no Brasil, sendo analisados dois lotes de cada material. As concentrações de fluoretos nas diferentes amostras foram determinadas por potenciometria direta, utilizando o eletrodo seletivo combinado de fluoreto. Os materiais que apresentaram maiores concentrações médias de fluoreto total foram Hydrogum (7052,87µg/g, Jeltrate Plus (6519,68µg/g e Orthoprint (6218,18µg/g. Apenas os materiais das marcas Hydrogum e Jeltrate apresentaram diferenças nas concentrações de fluoretos entre os lotes um e dois. Os materiais apresentaram diferenças na liberação de fluoretos dos moldes, cujas maiores concentrações médias foram liberadas pelas marcas Hydrogum e Orthoprint. O meio influenciou na liberação de fluoreto, sendo que na saliva foi menor que na água e nesta foi inferior ao ácido. Os moldes dos materiais que mais liberaram fluoretos nos três meios (saliva, água e ácido foram os do Hydrogum e Orthoprint. Considerando que as concentrações de fluoretos encontradas nos alginatos são altas e que existem diferentes fontes de exposição aos fluoretos, há necessidade de constante monitoramento dos alginatos para uso odontológico. Palavras chaves: Fluoretos, alginato, intoxicação, hidrocolóide irreversível, material dentário.

  15. [Protective effects of a new glutamic acid derivative against stress after nNOS blockade].

    Science.gov (United States)

    Tyurenkov, I N; Popova, T A; Perfilova, V N; Prokofiev, I I; Borisov, A V; Kustova, M V; Zaypullaev, G I; Ostrovskij, О V

    2017-01-01

    We studied the effects of a new glutamic acid derivative, glufimet, on oxidative stress, activity of antioxidant enzymes, mitochondrial respiration, endothelial vasodilation and anti-platelet activity in female rats after exposure to 24-hour immobilization pain stress and 7-nitroindazole, a neuronal nitric oxide synthase (nNOS) inhibitor. A single dose administration of glufimet (29 mg/kg intraperitoneally) 10 minutes before stress exposure caused a decrease of NO metabolites in serum (by 27.2%) and heart homogenate (33.5% (p£0.05), respectively, compared with the control group. Administration of 7-nitroindazole with glufimet also decreased the studied parameters by 14.3% in the heart homogenate and by 30,3% in the brain (p£0.05) compared with stress exposed rats receiving only the nNOS inhibitor. Glufimet decreased the levels of primary and secondary products of lipid peroxidation (LPO), conjugated dienes by 20% (p£0.05) and 17.3% (p£0.05), ketodienes by 16% and 13.7%, malondialdehyde by 15% (p£0.05) and 26.6% (p£0.05) in the heart and brain mitochondria of stress exposed rats, respectively, compared with the control group. Glufimet administration also increased SOD activity (by 14.4% and 13.1%, respectively), catalase (by 19% and 26.8%, respectively) and glutathione peroxidase (GPx) activity (by 45.5% (p£0.05) and 7.3%, respectively). The antioxidant effect of glufimet may be also attributed to increased coupling between the processes of mitochondria respiration and oxidative phosphorylation. This was evidenced by an increase in the respiratory control ratio (RCR) (by 46.0% (p£0.05) for malate/glutamate and by 49,7% (p£0.05) for succinate) in the heart mitochondria. A statistically significant increase in RCR (by 37.3% (p£0.05)) was observed in stress exposed female rat brain mitochondria for succinate. RCRs differed significantly for succinate in the heart and brain of rats receiving glufimet after nNOS blockade. RCR increased by 62.3% (p£0.05) in the

  16. Acolhimento ao familiar da pessoa em sofrimento psíquico nos estudos de enfermagem

    Directory of Open Access Journals (Sweden)

    Cristiene Barbosa Lima

    2013-12-01

    Full Text Available Objetivo: Evidenciar o conhecimento publicado no campo da enfermagem sobre acolhimento aos familiares de pessoas em sofrimento psíquico nos serviços de saúde.Métodos: Revisão integrativa, realizada nos meses de junho e julho de 2012, nas bases de dados LILACS, BDENF, IBECS, MEDLINE e SciELO, com os descritores “saúde mental”, “acolhimento” e “família”. Atenderam à inclusão 14 textos, escritos por profissionais e acadêmicos de enfermagem, em idioma português, publicados entre 2007 e 2011. Os dados foram apresentados de forma sintética em quatro tabelas e uma figura, sendo analisados sob o referencial de acolhimento pela Política Nacional de Humanização. Resultados: Não se pode afirmar uma tendência relacionada a estudos sobre acolhimento. A maioria das publicações analisadas adota abordagem qualitativa e análise de conteúdo, sendo de evidência tipo III. Há predominância de pesquisas tendo como sujeitos profissionais de saúde, no entanto, a família e outros atores começam a ser envolvidos. Cuidar de modo análogo da família e da pessoa que sofre é destaque em todos os estudos analisados. Evidenciou-se necessidade de interação entre os serviços de saúde e a rede especializada em saúde mental, e de preparo da equipe para minimizar as dificuldades enfrentadas pela família. Conclusão: O acolhimento à família foi apontado com frequência como dispositivo facilitador da reabilitação. Há muito por fazer rumo ao seu acolhimento nos serviços de saúde, a fim de permitir que a família perceba que sua vida não é necessariamente a continuidade da dificuldade que o outro enfrenta.

  17. Sarna sarcóptica em suínos na região da Benedita

    OpenAIRE

    Baptista, N.R.; Brida, T.; Matos, A.C.; Martins, M.V.

    2009-01-01

    Poster apresentado no VI Congresso da Ordem dos Médicos Veterinários que decorreu em Lisboa de 3 a 5 de Outubro de 2009. A importância dos parasitas externos na produção animal varia de região para região, devido a diferenças no clima e nos sistemas de produção. O controlo de doenças endémicas nos animais de produção tem assumido importância devido aos grandes investimentos, principalmente nos sistemas intensivos. A sarna sarcóptica (Sarcoptes scabiei var. suis) tem sido considera...

  18. Deletion of UCP2 in iNOS deficient mice reduces the severity of the disease during experimental autoimmune encephalomyelitis.

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    Caroline Aheng

    Full Text Available Uncoupling protein 2 is a member of the mitochondrial anion carrier family that is widely expressed in neurons and the immune cells of humans. Deletion of Ucp2 gene in mice pre-activates the immune system leading to higher resistance toward infection and to an increased susceptibility to develop chronic inflammatory diseases as previously exemplified with the Experimental Autoimmune Encephalomyelitis (EAE, a mouse model for multiple sclerosis. Given that oxidative stress is enhanced in Ucp2-/- mice and that nitric oxide (NO also plays a critical function in redox balance and in chronic inflammation, we generated mice deficient for both Ucp2 and iNos genes and submitted them to EAE. Mice lacking iNos gene exhibited the highest clinical score (3.4+/-0.5 p<0.05. Surprisingly, mice deficient for both genes developed milder disease with reduced immune cell infiltration, cytokines and ROS production as compared to iNos-/- mice.

  19. A sociologia da saúde nos Estados Unidos, Grã-Bretanha e França: panorama geral

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    Everardo Duarte Nunes

    2003-01-01

    Full Text Available O trabalho tem como objetivo apresentar um panorama geral da sociologia médica/sociologia da saúde nos Estados Unidos, Grã-Bretanha e França, das suas origens até hoje, situando a produção científica mais expressiva desse campo nesses países. A moderna sociologia médica/saúde emerge em diferentes momentos: nos Estados Unidos logo após a Segunda Guerra; na Grã-Bretanha, nos anos 60; e na França, na década de 1970. O estudo dessas trajetórias nacionais mostra que, na atualidade, constitui um campo estabelecido e em franco desenvolvimento com uma temática bastante diversificada e uma pluralidade de abordagens teóricas.

  20. Suppressed injury-induced rise in spinal prostaglandin E2 production and reduced early thermal hyperalgesia in iNOS-deficient mice.

    Science.gov (United States)

    Gühring, H; Görig, M; Ates, M; Coste, O; Zeilhofer, H U; Pahl, A; Rehse, K; Brune, K

    2000-09-01

    It is widely accepted that peripheral injury increases spinal inducible cyclooxygenase (COX-2) expression and prostaglandin E(2) (PGE(2)) formation as key mediators of nociceptive sensitization. Here, we used inducible nitric oxide synthase (iNOS) gene-deficient (iNOS-/-) mice to determine the contribution of iNOS-derived nitric oxide (NO) to this process. iNOS-/- mice exhibited reduced thermal hyperalgesia after zymosan injection. Spinal NO and PGE(2) formation both remained at baseline levels, in contrast to wild-type (wt) mice. In wt mice reduced hyperalgesia similar to that seen in iNOS-/- mice was induced by local spinal, but not by systemic treatment with the iNOS inhibitor l-NIL, suggesting that the reduced heat sensitization in iNOS-/- mice was attributable to the lack of spinal rather than peripheral iNOS. Two additional observations indicate that the antinociceptive effects of iNOS inhibition are dependent on a loss of stimulation of PG synthesis. First, intrathecal injection of the COX inhibitor indomethacin, which exerted pronounced antinociceptive effects in wt mice, was completely ineffective in iNOS-/- mice. Second, treatment with the NO donor RE-2047 not only completely restored spinal PG production and thermal sensitization in iNOS-/- mice but also its sensitivity to indomethacin. In both types of mice induction of thermal hyperalgesia was accompanied by similar increases in COX-1 and COX-2 mRNA expression. The stimulation of PG production by NO therefore involves an increase in enzymatic activity, rather than an alteration of COX gene expression. These results indicate that NO derived from spinal iNOS acts as a fast inductor of spinal thermal hyperalgesia.