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result sql = Role of endothelial nitric oxide synthase-derived nitric oxide in activation and dysfunction of cerebrovascular endothelial cells during early onsets of sepsis.
Role of endothelial nitric oxide synthase-derived nitric oxide in activation and dysfunction of cerebrovascular endothelial cells during early onsets of sepsis.
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char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
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char = r;code = 114
char = a;code = 97
char = c;code = 99
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char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
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char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = o;code = 111
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char = i;code = 105
char = d;code = 100
char = a;code = 97
char = n;code = 110
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char = s;code = 115
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char = n;code = 110
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = o;code = 111
char = r;code = 114
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = r;code = 114
char = o;code = 111
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char = d;code = 100
char = i;code = 105
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char = d;code = 100
char = r;code = 114
char = o;code = 111
char = r;code = 114
char = h;code = 104
char = o;code = 111
char = d;code = 100
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
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char = 1;code = 49
char = 2;code = 50
char = 3;code = 51
char = ;code = 32
char = (;code = 40
char = D;code = 68
char = H;code = 72
char = R;code = 82
char = ;code = 32
char = 1;code = 49
char = 2;code = 50
char = 3;code = 51
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char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = n;code = 110
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char = t;code = 116
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = N;code = 78
char = O;code = 79
char = -;code = 45
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
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char = p;code = 112
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = e;code = 101
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char = ;code = 32
char = D;code = 68
char = A;code = 65
char = F;code = 70
char = -;code = 45
char = F;code = 70
char = M;code = 77
char = ,;code = 44
char = ;code = 32
char = r;code = 114
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char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = e;code = 101
char = r;code = 114
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char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
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char = r;code = 114
char = e;code = 101
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char = a;code = 97
char = c;code = 99
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
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char = j;code = 106
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = M;code = 77
char = C;code = 67
char = V;code = 86
char = E;code = 69
char = C;code = 67
char = ;code = 32
char = c;code = 99
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char = t;code = 116
char = o;code = 111
char = s;code = 115
char = k;code = 107
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = a;code = 97
char = m;code = 109
char = e;code = 101
char = w;code = 119
char = o;code = 111
char = r;code = 114
char = k;code = 107
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
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char = t;code = 116
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char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = F;code = 70
char = I;code = 73
char = T;code = 84
char = C;code = 67
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char = d;code = 100
char = e;code = 101
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char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = (;code = 40
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char = k;code = 107
char = D;code = 68
char = a;code = 97
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char = m;code = 109
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = s;code = 115
char = s;code = 115
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char = ;code = 32
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = x;code = 120
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = M;code = 77
char = C;code = 67
char = V;code = 86
char = E;code = 69
char = C;code = 67
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = o;code = 111
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = p;code = 112
char = e;code = 101
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char = m;code = 109
char = e;code = 101
char = a;code = 97
char = b;code = 98
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char = e;code = 101
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char = c;code = 99
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char = l;code = 108
char = l;code = 108
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char = c;code = 99
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char = l;code = 108
char = t;code = 116
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char = r;code = 114
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char = s;code = 115
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = o;code = 111
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char = s;code = 115
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char = ;code = 32
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char = h;code = 104
char = e;code = 101
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char = a;code = 97
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char = E;code = 69
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char = s;code = 115
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char = b;code = 98
char = l;code = 108
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char = e;code = 101
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char = B;code = 66
char = S;code = 83
char = A;code = 65
char = ;code = 32
char = (;code = 40
char = 6;code = 54
char = 5;code = 53
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char = a;code = 97
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char = m;code = 109
char = o;code = 111
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char = m;code = 109
char = a;code = 97
char = s;code = 115
char = s;code = 115
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char = ;code = 32
char = o;code = 111
char = r;code = 114
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char = F;code = 70
char = I;code = 73
char = T;code = 84
char = C;code = 67
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = x;code = 120
char = t;code = 116
char = r;code = 114
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char = 1;code = 49
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char = D;code = 68
char = a;code = 97
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char = a;code = 97
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char = s;code = 115
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char = ;code = 32
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = x;code = 120
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char = r;code = 114
char = e;code = 101
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char = a;code = 97
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char = f;code = 102
char = e;code = 101
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char = F;code = 70
char = I;code = 73
char = P;code = 80
char = ;code = 32
char = p;code = 112
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char = a;code = 97
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char = s;code = 115
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char = c;code = 99
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char = a;code = 97
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = M;code = 77
char = C;code = 67
char = V;code = 86
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char = C;code = 67
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char = p;code = 112
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char = a;code = 97
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char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = r;code = 114
char = e;code = 101
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
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char = C;code = 67
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char = N;code = 78
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char = N;code = 78
char = A;code = 65
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char = a;code = 97
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char = O;code = 79
char = S;code = 83
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char = (;code = 40
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char = C;code = 67
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char = E;code = 69
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char = w;code = 119
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char = h;code = 104
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char = P;code = 80
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char = T;code = 84
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char = f;code = 102
char = a;code = 97
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char = f;code = 102
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char = e;code = 101
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = N;code = 78
char = O;code = 79
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char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
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char = g;code = 103
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char = h;code = 104
char = a;code = 97
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char = ;code = 32
char = s;code = 115
char = e;code = 101
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result sql = Sepsis-associated encephalopathy is an early manifestation of sepsis, resulting in a diffuse dysfunction of the brain. Recently, nitric oxide (NO) has been proposed to be one of the key molecules involved in the modulation of inflammatory responses in the brain. The aim of this study was to assess the role of NO in cerebrovascular endothelial cell activation/dysfunction during the early onsets of sepsis. To this end, we employed an in vitro model of sepsis in which cultured mouse cerebrovascular endothelial cells (MCVEC) were challenged with blood plasma (20% vol/vol) obtained from sham or septic (feces-induced peritonitis, FIP; 6 h) mice. Exposing MCVEC to FIP plasma for 1 h resulted in increased production of reactive oxygen species and NO as assessed by intracellular oxidation of oxidant-sensitive fluorochrome, dihydrorhodamine 123 (DHR 123), and nitrosation of NO-specific probe, DAF-FM, respectively. The latter events were accompanied by dissociation of tight junction protein, occludin, from MCVEC cytoskeletal framework and a subsequent increase in FITC-dextran (3-kDa mol mass) flux across MCVEC grown on the permeable cell culture supports, whereas Evans blue-BSA (65-kDa mol mass) or FITC-dextran (10-kDa mol mass) flux were not affected. FIP plasma-induced oxidant stress, occludin rearrangement, and MCVEC permeability were effectively attenuated by antioxidant, 1-pyrrolidinecarbodithioic acid (PDTC; 0.5 mM), or interfering with nitric oxide synthase (NOS) activity [0.1 mM nitro-L-arginine methyl ester (L-NAME) or endothelial NOS (eNOS)-deficient MCVEC]. However, treatment of MCVEC with PDTC failed to interfere with NO production, suggesting that septic plasma-induced oxidant stress in MCVEC is primarily a NO-dependent event. Taken together, these data indicate that during early sepsis, eNOS-derived NO exhibits proinflammatory characteristics and contributes to the activation and dysfunction of cerebrovascular endothelial cells.

Publication: Am. J. Physiol. Heart Circ. Physiol. 2008 Oct ;295(4)::H1712-9. :doi: 10.1152/ajpheart.00476.2008.
Publication Date: 2008 Oct
Study Author(s): Handa, Osamu;Stephen, Jancy;Cepinskas, Gediminas;
Institution: Centre for Critical Illness Research, Lawson Health Research Institute, London, Ontario, Canada.
Shortcut link to this study:
Sepsis-associated encephalopathy is an early manifestation of sepsis, resulting in a diffuse dysfunction of the brain. Recently, nitric oxide (NO) has been proposed to be one of the key molecules involved in the modulation of inflammatory responses in the brain. The aim of this study was to assess the role of NO in cerebrovascular endothelial cell activation/dysfunction during the early onsets of sepsis. To this end, we employed an in vitro model of sepsis in which cultured mouse cerebrovascular endothelial cells (MCVEC) were challenged with blood plasma (20% vol/vol) obtained from sham or septic (feces-induced peritonitis, FIP; 6 h) mice. Exposing MCVEC to FIP plasma for 1 h resulted in increased production of reactive oxygen species and NO as assessed by intracellular oxidation of oxidant-sensitive fluorochrome, dihydrorhodamine 123 (DHR 123), and nitrosation of NO-specific probe, DAF-FM, respectively. The latter events were accompanied by dissociation of tight junction protein, occludin, from MCVEC cytoskeletal framework and a subsequent increase in FITC-dextran (3-kDa mol mass) flux across MCVEC grown on the permeable cell culture supports, whereas Evans blue-BSA (65-kDa mol mass) or FITC-dextran (10-kDa mol mass) flux were not affected. FIP plasma-induced oxidant stress, occludin rearrangement, and MCVEC permeability were effectively attenuated by antioxidant, 1-pyrrolidinecarbodithioic acid (PDTC; 0.5 mM), or interfering with nitric oxide synthase (NOS) activity [0.1 mM nitro-L-arginine methyl ester (L-NAME) or endothelial NOS (eNOS)-deficient MCVEC]. However, treatment of MCVEC with PDTC failed to interfere with NO production, suggesting that septic plasma-induced oxidant stress in MCVEC is primarily a NO-dependent event. Taken together, these data indicate that during early sepsis, eNOS-derived NO exhibits proinflammatory characteristics and contributes to the activation and dysfunction of cerebrovascular endothelial cells.
PMID: 18723768

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