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result sql = Essential role of nitric oxide in sepsis-induced impairment of endothelium-derived hyperpolarizing factor-mediated relaxation in rat pulmonary artery.
Essential role of nitric oxide in sepsis-induced impairment of endothelium-derived hyperpolarizing factor-mediated relaxation in rat pulmonary artery.
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char = e;code = 101
char = s;code = 115
char = p;code = 112
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = e;code = 101
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = e;code = 101
char = N;code = 78
char = O;code = 79
char = S;code = 83
char = );code = 41
char = ;code = 32
char = m;code = 109
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = -;code = 45
char = e;code = 101
char = N;code = 78
char = O;code = 79
char = S;code = 83
char = ;code = 32
char = (;code = 40
char = p;code = 112
char = -;code = 45
char = e;code = 101
char = N;code = 78
char = O;code = 79
char = S;code = 83
char = );code = 41
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 = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = p;code = 112
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = x;code = 120
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = y;code = 121
char = l;code = 108
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = A;code = 65
char = C;code = 67
char = h;code = 104
char = );code = 41
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = N;code = 78
char = O;code = 79
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = y;code = 121
char = l;code = 108
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = -;code = 45
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = N;code = 78
char = O;code = 79
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = u;code = 117
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = G;code = 71
char = M;code = 77
char = P;code = 80
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = e;code = 101
char = p;code = 112
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = s;code = 115
char = h;code = 104
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = N;code = 78
char = (;code = 40
char = G;code = 71
char = );code = 41
char = -;code = 45
char = N;code = 78
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = -;code = 45
char = l;code = 108
char = -;code = 45
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = (;code = 40
char = L;code = 76
char = -;code = 45
char = N;code = 78
char = A;code = 65
char = M;code = 77
char = E;code = 69
char = );code = 41
char = /;code = 47
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = x;code = 120
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = E;code = 69
char = D;code = 68
char = H;code = 72
char = F;code = 70
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = e;code = 101
char = );code = 41
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = y;code = 121
char = l;code = 108
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = 1;code = 49
char = 4;code = 52
char = 0;code = 48
char = 0;code = 48
char = W;code = 87
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = l;code = 108
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 = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = N;code = 78
char = O;code = 79
char = S;code = 83
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = E;code = 69
char = D;code = 68
char = H;code = 72
char = F;code = 70
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = t;code = 116
char = y;code = 121
char = l;code = 108
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = -;code = 45
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = x;code = 120
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = N;code = 78
char = O;code = 79
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = f;code = 102
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 = a;code = 97
char = l;code = 108
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = N;code = 78
char = O;code = 79
char = S;code = 83
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = N;code = 78
char = O;code = 79
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = i;code = 105
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = E;code = 69
char = D;code = 68
char = H;code = 72
char = F;code = 70
char = -;code = 45
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = x;code = 120
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
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 = d;code = 100
char = ;code = 32
char = b;code = 98
char = a;code = 97
char = s;code = 115
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = N;code = 78
char = O;code = 79
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = N;code = 78
char = O;code = 79
char = S;code = 83
char = ;code = 32
char = m;code = 109
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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 = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = u;code = 117
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = E;code = 69
char = D;code = 68
char = H;code = 72
char = F;code = 70
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
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result sql = Both endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) are important vasodilators in pulmonary circulation. Sepsis is known to impair endothelium-dependent dilation in the pulmonary vasculature, but the mechanisms are incompletely understood. We have examined the relative contribution of EDHF/NO to the attenuated endothelium-dependent relaxation of pulmonary artery in sepsis, and the role of inducible nitric oxide synthase (iNOS)-derived NO in this mechanism. Sepsis was induced in male adult Wistar rats by caecal ligation and puncture. At 18h after surgery, left and right branches of pulmonary arteries were isolated for tension recording, NO/cyclic guanosine monophosphate (cGMP) measurements, mRNA and protein expressions. Despite a marked decrease in the arterial endothelial nitric oxide synthase (eNOS) mRNA and phosphorylated-eNOS (p-eNOS) protein expressions in sepsis, endothelium-dependent relaxation to acetylcholine (ACh) mediated by NO, acetylcholine-stimulated NO release and tissue cGMP levels were moderately inhibited. Sepsis however abolished the N(G)-Nitro-l-arginine methyl ester (L-NAME)/indomethacin-resistant arterial relaxation (EDHF response) to acetylcholine in this vessel. In vitro treatment of the arterial rings from septic rats with 1400W, a selective inhibitor of iNOS restored the EDHF response, but had no effect on the acetylcholine-induced relaxation mediated by endothelial NO. The functional role of iNOS-derived NO in impairing EDHF-mediated relaxation was coincident with an increased basal NO production, iNOS mRNA and protein expressions in the rat pulmonary artery. In conclusion, the loss of the EDHF response may be primarily responsible for the endothelial dysfunction in sepsis, and its restoration by a selective iNOS inhibitor may improve pulmonary vasodilation.

Publication: Eur. J. Pharmacol. 2010 Mar 25 ;630(1-3)::84-91. :doi: 10.1016/j.ejphar.2009.12.026.
Publication Date: 2010 Mar 25
Study Author(s): Subramani, Jaganathan;Leo, Marie Dennis Marcus;Kathirvel, Kandaswamy;Arunadevi, Rathinam;Singh, Thakur Uttam;Prakash, Vellanki Ravi;Mishra, Santosh Kumar;
Institution: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar-243 122 (U.P), India.
Shortcut link to this study:
Both endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) are important vasodilators in pulmonary circulation. Sepsis is known to impair endothelium-dependent dilation in the pulmonary vasculature, but the mechanisms are incompletely understood. We have examined the relative contribution of EDHF/NO to the attenuated endothelium-dependent relaxation of pulmonary artery in sepsis, and the role of inducible nitric oxide synthase (iNOS)-derived NO in this mechanism. Sepsis was induced in male adult Wistar rats by caecal ligation and puncture. At 18h after surgery, left and right branches of pulmonary arteries were isolated for tension recording, NO/cyclic guanosine monophosphate (cGMP) measurements, mRNA and protein expressions. Despite a marked decrease in the arterial endothelial nitric oxide synthase (eNOS) mRNA and phosphorylated-eNOS (p-eNOS) protein expressions in sepsis, endothelium-dependent relaxation to acetylcholine (ACh) mediated by NO, acetylcholine-stimulated NO release and tissue cGMP levels were moderately inhibited. Sepsis however abolished the N(G)-Nitro-l-arginine methyl ester (L-NAME)/indomethacin-resistant arterial relaxation (EDHF response) to acetylcholine in this vessel. In vitro treatment of the arterial rings from septic rats with 1400W, a selective inhibitor of iNOS restored the EDHF response, but had no effect on the acetylcholine-induced relaxation mediated by endothelial NO. The functional role of iNOS-derived NO in impairing EDHF-mediated relaxation was coincident with an increased basal NO production, iNOS mRNA and protein expressions in the rat pulmonary artery. In conclusion, the loss of the EDHF response may be primarily responsible for the endothelial dysfunction in sepsis, and its restoration by a selective iNOS inhibitor may improve pulmonary vasodilation.
PMID: 20035746

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