1030-13 Alterations in Endothelial Cell Adenosine Receptors Mediate Endothelium-Dependent Vasoconstriction in Experimental Vein Grafts

Adenosine is a potent endogenous vasodilator which mediates its action through A1 and A2 receptor subtypes located on both vascular endothelial and vascular smooth muscle cells (SMC). Adenosine-mediated relaxation in vein grafts has not been examined. This study assesses the in vitro isometric tension responses to specific adenosine receptor agonists (A1: R-phenyl-isopropyl-adenosine and A2: CSG-21680; 10–9 to 10–4 M) of common carotid external jugular vein bypass grafts (VG) in New Zealand White rabbits. These responses were compared to those obtained in the extemal jugular vein (JV) and in the common carotid artery (CA). All vessels were precontracted with prostaglandin F2a (10–5 M). Endothelialized and de-endothelialized vessels were examined. The A1 mediated relaxation in JV was endothelium-independent, whereas A2 mediated relaxation was endothelium-dependent. In CA, A1 mediated relaxation was partially endothelium-dependent, while A2 mediated relaxation was endotheliumindependent. In VG, Al activation induced endothelium-dependent vasoconstriction. Endothelial denudation restored Al mediated relaxation, but reduced compared to that of JV (max. 19±9%). A2 relaxation in VG was endothelium-independent (max. 39±4%). Primary cultures of arterial and vein graft SMC expressed both A1 and A2 receptors on northern blot analysis. There was, however, a marked reduction in the A1 affinity of the SMC from the VG compared to the arterial SMC (40.9±1.3% arterial binding). This study, therefore, demonstrates that there is a substantial change in the adenosine mediated vasoreactivity in VG compared to JV, due to a change in endothelial A1 receptor mediated response from relaxation to constriction, coupled with a decreased affinity of the A1 receptors on the VG SMC. The adenosine responses of the VG are also different from CA. Therefore, the endothelial celis of VG appear to be unique, in that functionally they neither maintain a venous phenotype nor acquire an arterial phenotype in response to adenosine

Alterations in wall tension and shear stress modulate tyrosine kinase signaling and wall remodeling in experimental vein grafts

AbstractPurpose: Hemodynamic alterations have been implicated as major stimuli for the development of intimal hyperplasia in vein grafts that are implanted in the arterial circulation. Tyrosine kinase is known to mediate cell signaling. However, its role with in vivo mechanotransduction is not yet well defined. We used a novel bioprosthetic collagen tube to provide an external support to vein grafts and examined the subsequent changes in hemodynamics, tyrosine kinase signaling, wall remodeling, and vasomotor function. Methods: Carotid interposition bypass grafting was performed with the reversed jugular vein in New Zealand white rabbits. In the experimental group (n = 15), after the completion of the proximal anastomosis, the vein was passed through a 4-mm collagen tube and the distal anastomosis was performed. The tube support was fashioned to completely cover the vein grafts. The control animals (n = 14) had no tube support. After surgery, the blood pressure and flow rate were measured and the wall tension and shear stress were calculated in the vein grafts on day 3 or day 28 (n = 5 per group). Tyrosine phosphorylation was assessed with the Western blot test in vein grafts at day 3 (n = 4 per group). The intimal and medial dimensions of the vein grafts were assessed with videomorphometry on day 28 (n = 5 per group). The cumulative dose response curves of the vein grafts to contractile and relaxant agonists were determined in isometric tension studies on day 28 (n = 5 per group). Results: The use of tube support reduced wall tension 1.7-fold (P < .01) and increased shear stress 4.8-fold (P < .001) without altering the flow rate or blood pressure. The tyrosine kinase activity was reduced 15-fold (P < .001) in the tube-supported vein grafts. The intimal thickness was reduced by 45% in the tube-supported vein grafts as compared with the control grafts (46 ± 2 mm vs 84 ± 5 mm, respectively; P < .0001), and the media thickness was reduced by 20% (63 ± 8 mm vs 79 ± 4 mm, respectively; P < .05). Isometric tension studies showed preservation of contractile function and modulation of endothelial-dependent dysfunctional relaxation in tube-supported vein grafts. Conclusion: These results show that reduced wall tension and increased shear stress with an external tube support can effectively modulate the signaling, functional, and hyperplastic responses in vein grafts. We conclude that this simple strategy deserves further study and clinical consideration. (J Vasc Surg 1999;29:334-44.

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

MOM-C undersøkelse fra lokalitet Eldviktaren i Jøssundfjorden, Flatanger kommune, september 2013

Denne rapporten omhandler en undersøkelse av miljøforholdene i sjøen ved oppdrettslokaliteten Eldviktaren i Flatanger kommune. Formålet med undersøkelsen var å beskrive miljøtilstanden i området basert på sediment-, kjemi- og bunndyrsundersøkelser utført 12. september 2013. Det ble samlet prøver fra tre stasjoner, to utenfor terskelen som anlegget ligger over og en innenfor terskelen lengre inn i fjorden

MOM-C undersøkelse fra lokalitet Gjerdinga i Nærøysundet nord, Nærøy kommune, august 2013

Denne rapporten omhandler en undersøkelse av de marine miljøforholdene ved oppdrettslokaliteten Gjerdinga i Nærøy kommune. Formålet med undersøkelsen var å beskrive miljøtilstanden i området basert på vann-, sediment-, kjemi- og bunndyrsundersøkelser utført 8. august 2013. Det ble samlet bunnprøver ved tre stasjoner, én ved anlegget, én i overgangssonen og én lengre ut i fjernsonen til fjorden, hvor det ved sistnevnte også ble utført en hydrografisk måling.Sinkaberg-Hansen A

MOM-C undersøkelse fra lokalitet Eldviktaren i Jøssundfjorden, Flatanger kommune, september 2013

Denne rapporten omhandler en undersøkelse av miljøforholdene i sjøen ved oppdrettslokaliteten Eldviktaren i Flatanger kommune. Formålet med undersøkelsen var å beskrive miljøtilstanden i området basert på sediment-, kjemi- og bunndyrsundersøkelser utført 12. september 2013. Det ble samlet prøver fra tre stasjoner, to utenfor terskelen som anlegget ligger over og en innenfor terskelen lengre inn i fjorden.Bjørøya Fiskeopdrett A

MOM-C undersøkelse fra lokalitet Heggvika i Kjellafjorden, Bindal kommune, mars 2014

Denne rapporten omhandler en undersøkelse av de marine miljøforholdene ved oppdrettslokaliteten Heggvika i Bindal kommune. Formålet med undersøkelsen var å beskrive miljøtilstanden i området basert på vann-, sediment-, kjemi- og bunndyrsundersøkelser utført 19. mars 2014. Det ble samlet bunnprøver ved tre stasjoner, én ved anlegget, én i overgangssonen og én i fjernsonen lengre ut fjorden. Ved sistnevnte ble det også utført en hydrografisk måling. Den hydrografiske undersøkelsen viste en avtagende temperatur og en økende saltholdighet fra sjøoverflaten og nedover mot havbunn i fjernsonestasjonen. Oksygenmålingen viste høye verdier i hele vannsøyla. Verdiene sank noe ned mot bunnen, men oksygenkonsentrasjonen havnet fortsatt inn under tilstandsklasse I (Svært god) etter Miljødirektoratets klassifisering. Det er dermed ikke noe som tyder på stagnerende bunnvann og dårlige oksygenforhold i dette fjordområdet.SinkabergHansen A