2,709 research outputs found

    Dimethylarginine Dimethylaminohydrolase Promotes Endothelial Repair After Vascular Injury

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    ObjectivesWe sought to determine if a reduction in asymmetric dimethylarginine (ADMA) enhances endothelial regeneration.BackgroundAsymmetric dimethylarginine is an endogenous inhibitor of nitric oxide synthase (NOS). Increased plasma levels of ADMA are associated with endothelial vasodilator dysfunction in patients with vascular disease or risk factors. Asymmetric dimethylarginine is eliminated largely by the action of dimethylarginine dimethylaminohydrolase (DDAH), which exists in 2 isoforms. Dimethylarginine dimethylaminohydrolase-1 transgenic (TG) mice manifest increased DDAH activity, reduced plasma and tissue ADMA levels, increased nitric oxide synthesis, and reduced systemic vascular resistance.MethodsThe left femoral arteries of DDAH1 TG mice and wild-type (WT) mice were injured by a straight spring wire, and regeneration of the endothelial cell (EC) monolayer was assessed. Endothelial sprouting was assayed with growth factor-reduced Matrigel.ResultsRegeneration of the EC monolayer was more complete 1 week after injury in TG mice (WT vs. TG: 40.0 ± 6.5% vs. 61.2 ± 6.4%, p < 0.05). The number of CD45 positive cells at the injured sites was reduced by 62% in DDAH TG mice (p < 0.05). Four weeks after injury, the neointima area and intima/media ratio were attenuated in DDAH TG mice (WT vs. TG: 0.049 ± 0.050 mm2vs. 0.031 ± 0.060 mm2, 3.1 ± 0.5 vs. 1.7 ± 0.2, respectively, p < 0.05). Endothelial cell sprouting from vascular segments increased in TG mice (WT vs. TG: 24.3 ± 3.9 vs. 39.0 ± 2.2, p < 0.05).ConclusionsWe find for the first time an important role for DDAH in EC regeneration and in neointima formation. Strategies to enhance DDAH expression or activity might be useful in restoring the endothelial monolayer and in treating vascular disease

    Long-term microparticle flux variability indicated by comparison of Interplanetary Dust Experiment (IDE) timed impacts for LDEF's first year in orbit with impact data for the entire 5.77-year orbital lifetime

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    The electronic sensors of the Interplanetary Dust Experiment (IDE) recorded precise impact times and approximate directions for submicron to approximately 100 micron size particles on all six primary sides of the spacecraft for the first 346 days of the LDEF orbital mission. Previously-reported analyses of the timed impact data have established their spatio-temporal features, including the demonstration that a preponderance of the particles in this regime are orbital debris and that a large fraction of the debris particles are encountered in megameter-size clouds. Short-term fluxes within such clouds can rise several orders of magnitude above the long-term average. These unexpectedly large short-term variations in debris flux raise the question of how representative an indication of the multi-year average flux is given by the nearly one year of timed data. One of the goals of the IDE was to conduct an optical survey of impact sites on detectors that remained active during the entire LDEF mission, to obtain full-mission fluxes. We present here the comparisons and contrasts among the new IDE optical survey impact data, the IDE first-year timed impact data, and impact data from other LDEF micrometeoroid and debris experiments. The following observations are reported: (1) the 5.77 year long-term integrated microparticle impact fluxes recorded by IDE detectors matched the integrated impact fluxes measured by other LDEF investigators for the same period; (2) IDE integrated microparticle impact fluxes varied by factors from 0.5 to 8.3 for LDEF days 1-346, 347-2106 and 1-2106 (5.77 years) on rows 3 (trailing edge, or West), 6 (South side), 12 (North side), and the Earth and Space ends; and (3) IDE integrated microparticle impact fluxes varied less than 3 percent for LDEF days 1-346, 347-2106 and 1-2106 (5.77 years) on row 9 (leading edge, or East). These results give further evidence of the accuracy and internal consistency of the recorded IDE impact data. This leads to the further conclusion that the utility of long-term ratios for impacts on various sides of a stabilized satellite in low Earth orbit (LEO) is extremely limited. These observations and their consequences highlight the need for continuous, real time monitoring of the dynamic microparticle environment in LEO

    The orbital characteristics of debris particle rings as derived from IDE observations of multiple orbit intersections with LDEF

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    During the first 346 days of the LDEF's almost 6 year stay in space, the metal oxide silicon detectors of the Interplanetary Dust Experiment (IDE) recorded over 15,000 impacts, most of which were separated in time by integer multiples of the LDEF orbital period (called multiple orbit event sequences, or MOES). Simple celestial mechanics provides ample reason to expect that a good deal of information about the orbits of the impacting debris particles can be extracted from these MOES, and so a procedure, based on the work of Greenberg, has been developed and applied to one of these events, the so-called 'May swarm'. This technique, the 'Method of Differential Precession,' allows for the determination of the geometrical elements of a particle orbit from the change in the position of the impact point with time. The application of this approach to the May swarm gave the following orbital elements for the orbit of the particles striking LDEF during this MOES: a = 6746.5 km; 0.0165 less than e less than 0.025; i = 66.55 deg; Omega(sub 0) = 179.0 deg plus or minus 0.2 deg; omega = 178.1 deg plus or minus 0.2 deg

    A new HPLC-ELSD method to quantify indican in Polygonum tinctorium L. and to evaluate beta-glucosidase hydrolysis of indican for indigo production.

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    A method to quantify the indigo precursor indican (indoxyl-beta-D-glucoside) in Polygonum tinctorium L. has been developed. Plant material was extracted in deionized water, and indican was identified and quantified using high performance liquid chromatography (HPLC) coupled to an evaporative light scattering detector (ELSD). Results confirmed that with this method it is possible to measure indican content in a short time, obtaining reliable and reproducible data. Using this method, leaf indican content was quantified every 15 days during the growing season (from May to October) in P. tinctorium crops grown in a field experiment in Central Italy. Results showed that indican increased along the growing season until flowering and was positively affected by photosynthetic active radiation (PAR). Indican is naturally hydrolyzed by native beta-glucosidase to indoxyl and glucose, the indoxyl yielding indigo. The activity of two enzymes, sweet almond beta-glucosidase and Novarom G preparation, were compared with P. tinctorium native beta-glucosidase to evaluate indigo production. Results showed that the ability to promote indigo formation increased as follows: almond beta-glucosidase <or= Novarom G

    Murine Model of Hindlimb Ischemia

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    In the United States, peripheral arterial disease (PAD) affects about 10 million individuals, and is also prevalent worldwide. Medical therapies for symptomatic relief are limited. Surgical or endovascular interventions are useful for some individuals, but long-term results are often disappointing. As a result, there is a need for developing new therapies to treat PAD. The murine hindlimb ischemia preparation is a model of PAD, and is useful for testing new therapies. When compared to other models of tissue ischemia such as coronary or cerebral artery ligation, femoral artery ligation provides for a simpler model of ischemic tissue. Other advantages of this model are the ease of access to the femoral artery and low mortality rate
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