|
|
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 = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = i;code = 105
char = v;code = 118
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char = t;code = 116
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char = f;code = 102
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char = c;code = 99
char = o;code = 111
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char = a;code = 97
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char = l;code = 108
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char = b;code = 98
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = .;code = 46
result sql = In vitro and in vivo study of octacosanol metabolism.
In vitro and in vivo study of octacosanol metabolism.char = <;code = 60
char = b;code = 98
char = >;code = 62
char = B;code = 66
char = A;code = 65
char = C;code = 67
char = K;code = 75
char = G;code = 71
char = R;code = 82
char = O;code = 79
char = U;code = 85
char = N;code = 78
char = D;code = 68
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = P;code = 80
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = x;code = 120
char = t;code = 116
char = u;code = 117
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char = e;code = 101
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char = o;code = 111
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char = ;code = 32
char = v;code = 118
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char = r;code = 114
char = y;code = 121
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char = l;code = 108
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char = g;code = 103
char = -;code = 45
char = c;code = 99
char = h;code = 104
char = a;code = 97
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char = n;code = 110
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char = a;code = 97
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char = i;code = 105
char = p;code = 112
char = h;code = 104
char = a;code = 97
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char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = l;code = 108
char = c;code = 99
char = o;code = 111
char = h;code = 104
char = o;code = 111
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char = ;code = 32
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char = i;code = 105
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char = r;code = 114
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char = c;code = 99
char = a;code = 97
char = n;code = 110
char = e;code = 101
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char = w;code = 119
char = a;code = 97
char = x;code = 120
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = c;code = 99
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char = o;code = 111
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char = s;code = 115
char = t;code = 116
char = e;code = 101
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char = o;code = 111
char = l;code = 108
char = -;code = 45
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
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 = s;code = 115
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
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char = o;code = 111
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char = a;code = 97
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char = o;code = 111
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char = a;code = 97
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char = .;code = 46
char = ;code = 32
char = S;code = 83
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = c;code = 99
char = e;code = 101
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char = d;code = 100
char = a;code = 97
char = t;code = 116
char = a;code = 97
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char = a;code = 97
char = b;code = 98
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
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char = o;code = 111
char = l;code = 108
char = i;code = 105
char = s;code = 115
char = m;code = 109
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = o;code = 111
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char = a;code = 97
char = c;code = 99
char = o;code = 111
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = o;code = 111
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char = t;code = 116
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char = c;code = 99
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char = a;code = 97
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char = l;code = 108
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = e;code = 101
char = n;code = 110
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char = p;code = 112
char = u;code = 117
char = b;code = 98
char = l;code = 108
char = i;code = 105
char = s;code = 115
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char = e;code = 101
char = d;code = 100
char = .;code = 46
char = <;code = 60
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char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = M;code = 77
char = E;code = 69
char = T;code = 84
char = H;code = 72
char = O;code = 79
char = D;code = 68
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = H;code = 72
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = b;code = 98
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char = b;code = 98
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char = s;code = 115
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char = e;code = 101
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char = ;code = 32
char = (;code = 40
char = 3;code = 51
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char = H;code = 72
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char = g;code = 103
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char = 0;code = 48
char = .;code = 46
char = 5;code = 53
char = ,;code = 44
char = ;code = 32
char = 2;code = 50
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = 4;code = 52
char = ;code = 32
char = h;code = 104
char = .;code = 46
char = ;code = 32
char = L;code = 76
char = i;code = 105
char = p;code = 112
char = i;code = 105
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 = s;code = 115
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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 = l;code = 108
char = y;code = 121
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = t;code = 116
char = h;code = 104
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char = n;code = 110
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char = a;code = 97
char = y;code = 121
char = e;code = 101
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char = ;code = 32
char = c;code = 99
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char = r;code = 114
char = a;code = 97
char = t;code = 116
char = s;code = 115
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char = a;code = 97
char = n;code = 110
char = d;code = 100
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char = M;code = 77
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char = a;code = 97
char = c;code = 99
char = a;code = 97
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char = a;code = 97
char = r;code = 114
char = c;code = 99
char = t;code = 116
char = o;code = 111
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char = d;code = 100
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = k;code = 107
char = e;code = 101
char = y;code = 121
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = R;code = 82
char = a;code = 97
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = o;code = 111
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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char = a;code = 97
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char = m;code = 109
char = i;code = 105
char = n;code = 110
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char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = l;code = 108
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char = 6;code = 54
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char = m;code = 109
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char = g;code = 103
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char = d;code = 100
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = e;code = 101
char = e;code = 101
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char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
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char = o;code = 111
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char = a;code = 97
char = n;code = 110
char = d;code = 100
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char = o;code = 111
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char = t;code = 116
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
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char = c;code = 99
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char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = G;code = 71
char = C;code = 67
char = -;code = 45
char = M;code = 77
char = S;code = 83
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = M;code = 77
char = o;code = 111
char = n;code = 110
char = k;code = 107
char = e;code = 101
char = y;code = 121
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 = o;code = 111
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
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char = e;code = 101
char = n;code = 110
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = l;code = 108
char = y;code = 121
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char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = e;code = 101
char = e;code = 101
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char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
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char = o;code = 111
char = s;code = 115
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char = l;code = 108
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char = c;code = 99
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char = a;code = 97
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char = o;code = 111
char = s;code = 115
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char = n;code = 110
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char = i;code = 105
char = c;code = 99
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char = ;code = 32
char = s;code = 115
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char = m;code = 109
char = e;code = 101
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char = c;code = 99
char = h;code = 104
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = d;code = 100
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char = F;code = 70
char = A;code = 65
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = v;code = 118
char = e;code = 101
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char = t;code = 116
char = i;code = 105
char = g;code = 103
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
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char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = W;code = 87
char = h;code = 104
char = e;code = 101
char = n;code = 110
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char = f;code = 102
char = i;code = 105
char = b;code = 98
char = r;code = 114
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char = b;code = 98
char = l;code = 108
char = a;code = 97
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char = t;code = 116
char = s;code = 115
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char = w;code = 119
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char = r;code = 114
char = e;code = 101
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char = t;code = 116
char = u;code = 117
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char = d;code = 100
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char = p;code = 112
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char = e;code = 101
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char = f;code = 102
char = ;code = 32
char = (;code = 40
char = 3;code = 51
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char = H;code = 72
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char = o;code = 111
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char = t;code = 116
char = a;code = 97
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char = a;code = 97
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = e;code = 101
char = e;code = 101
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char = s;code = 115
char = p;code = 112
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char = t;code = 116
char = s;code = 115
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char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = f;code = 102
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = :;code = 58
char = ;code = 32
char = a;code = 97
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char = f;code = 102
char = i;code = 105
char = r;code = 114
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = o;code = 111
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char = e;code = 101
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char = c;code = 99
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char = r;code = 114
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char = s;code = 115
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char = n;code = 110
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char = e;code = 101
char = d;code = 100
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char = o;code = 111
char = c;code = 99
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char = s;code = 115
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char = d;code = 100
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char = ;code = 32
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char = s;code = 115
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char = c;code = 99
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char = t;code = 116
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char = o;code = 111
char = c;code = 99
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char = a;code = 97
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char = s;code = 115
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char = l;code = 108
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char = a;code = 97
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char = t;code = 116
char = h;code = 104
char = i;code = 105
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char = e;code = 101
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char = r;code = 114
char = e;code = 101
char = m;code = 109
char = a;code = 97
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char = d;code = 100
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char = u;code = 117
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char = d;code = 100
char = e;code = 101
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char = i;code = 105
char = f;code = 102
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = r;code = 114
char = a;code = 97
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char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = h;code = 104
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char = s;code = 115
char = p;code = 112
char = o;code = 111
char = t;code = 116
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char = f;code = 102
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char = o;code = 111
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char = a;code = 97
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char = g;code = 103
char = h;code = 104
char = t;code = 116
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char = a;code = 97
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char = a;code = 97
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char = s;code = 115
char = p;code = 112
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char = .;code = 46
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char = O;code = 79
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char = a;code = 97
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char = p;code = 112
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char = a;code = 97
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char = m;code = 109
char = a;code = 97
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char = k;code = 107
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char = y;code = 121
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char = a;code = 97
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char = l;code = 108
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char = t;code = 116
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char = a;code = 97
char = n;code = 110
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char = l;code = 108
char = .;code = 46
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char = I;code = 73
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char = a;code = 97
char = d;code = 100
char = d;code = 100
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char = t;code = 116
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char = a;code = 97
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char = m;code = 109
char = a;code = 97
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char = a;code = 97
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char = p;code = 112
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char = e;code = 101
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char = s;code = 115
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char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
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char = f;code = 102
char = r;code = 114
char = e;code = 101
char = e;code = 101
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char = a;code = 97
char = t;code = 116
char = u;code = 117
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = m;code = 109
char = i;code = 105
char = t;code = 116
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char = c;code = 99
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result sql = BACKGROUND : Policosanol is a mixture of very-long-chain aliphatic alcohols purified from sugar cane wax with cholesterol-lowering effects, whose main component is octacosanol. Scarce data about the metabolism of octacosanol and the other fatty alcohols composing policosanol have been published.
METHODS : Human fibroblasts were cultured in presence of (3)H-octacosanol during 0.5, 2 and 4 h. Lipid extracts were analyzed by thin layer chromatography, and the spots corresponding to octacosanol and octacosanoic acid were identified comparing with authentic standards. Spots were scraped, transferred to vials and radioactivity was measured. For corroborating the presence of octacosanol and octacosanoic acid, samples were analyzed by gas chromatography-mass spectrometry (GC-MS). The in vivo study of octacosanol metabolism was conducted in rats and Macaca arctoides monkeys. Rats were orally administered with policosanol (60 mg/kg) and free octacosanol and octacosanoic acid were identified in liver and plasma by GC-MS at various time intervals. Monkeys were orally and endovenously treated with policosanol (10 mg/kg) and the presence of free octacosanol, octacosanoic acid and some chain-shortened FA was investigated.
RESULTS : When fibroblasts were cultured in presence of (3)H-octacosanol, three spots were found: a first one corresponded to octacosanoic acid, a second to octacosanol and a third one remained unidentified. The radioactivity on the spot of octacosanoic acid slightly decreased throughout the incubation but increased in the third spot. Octacosanol and free octacosanoic acids were also identified in plasma of monkeys orally administered with policosanol. In addition, plasma samples showed free saturated acids, palmitic acid being the most abundant, followed by oleic and mystiric acids. Unsaturated acids (oleic and palmitoleic) were also observed.
CONCLUSIONS : The present study demonstrates that octacosanoic acid is formed after incubation of fibroblast cultures with (3)H-octacosanol and after oral dosing with policosanol to rats. In addition, we demonstrated that shortened saturated (myristic, palmitic and stearic) and unsaturated (oleic, palmitoleic) FA are also formed after oral dosing with policosanol to monkeys. The present results are consistent with the fact that octacosanol metabolism is linked to FA metabolism via beta-oxidation, but further studies need to explore the occurrence of more metabolites proving such hypothesis.
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result sql = In vitro and in vivo study of octacosanol metabolism.
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char = ;code = 32
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = l;code = 108
char = c;code = 99
char = o;code = 111
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = e;code = 101
char = d;code = 100
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 = u;code = 117
char = g;code = 103
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = e;code = 101
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char = w;code = 119
char = a;code = 97
char = x;code = 120
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = -;code = 45
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
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 = s;code = 115
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = c;code = 99
char = e;code = 101
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char = d;code = 100
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = m;code = 109
char = e;code = 101
char = t;code = 116
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 = m;code = 109
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = y;code = 121
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char = a;code = 97
char = l;code = 108
char = c;code = 99
char = o;code = 111
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = u;code = 117
char = b;code = 98
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 = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = M;code = 77
char = E;code = 69
char = T;code = 84
char = H;code = 72
char = O;code = 79
char = D;code = 68
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = H;code = 72
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
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 = c;code = 99
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = (;code = 40
char = 3;code = 51
char = );code = 41
char = H;code = 72
char = -;code = 45
char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
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char = o;code = 111
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 5;code = 53
char = ,;code = 44
char = ;code = 32
char = 2;code = 50
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 4;code = 52
char = ;code = 32
char = h;code = 104
char = .;code = 46
char = ;code = 32
char = L;code = 76
char = i;code = 105
char = p;code = 112
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
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 = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = z;code = 122
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = n;code = 110
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char = l;code = 108
char = a;code = 97
char = y;code = 121
char = e;code = 101
char = r;code = 114
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char = c;code = 99
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = h;code = 104
char = y;code = 121
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = s;code = 115
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = s;code = 115
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char = c;code = 99
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char = r;code = 114
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char = s;code = 115
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char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = c;code = 99
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char = s;code = 115
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char = o;code = 111
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char = a;code = 97
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char = d;code = 100
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char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
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char = o;code = 111
char = s;code = 115
char = a;code = 97
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char = i;code = 105
char = c;code = 99
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char = a;code = 97
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char = i;code = 105
char = d;code = 100
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char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = i;code = 105
char = d;code = 100
char = e;code = 101
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char = t;code = 116
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
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char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
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 = u;code = 117
char = t;code = 116
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char = e;code = 101
char = n;code = 110
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char = i;code = 105
char = c;code = 99
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char = s;code = 115
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char = a;code = 97
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char = d;code = 100
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = s;code = 115
char = c;code = 99
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = e;code = 101
char = d;code = 100
char = ,;code = 44
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char = r;code = 114
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char = f;code = 102
char = e;code = 101
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = d;code = 100
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char = t;code = 116
char = o;code = 111
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = s;code = 115
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char = a;code = 97
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char = d;code = 100
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char = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = o;code = 111
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char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = o;code = 111
char = c;code = 99
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char = a;code = 97
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char = s;code = 115
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char = o;code = 111
char = l;code = 108
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char = s;code = 115
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char = d;code = 100
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char = r;code = 114
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char = a;code = 97
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char = s;code = 115
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char = s;code = 115
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char = m;code = 109
char = e;code = 101
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char = y;code = 121
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char = (;code = 40
char = G;code = 71
char = C;code = 67
char = -;code = 45
char = M;code = 77
char = S;code = 83
char = );code = 41
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = i;code = 105
char = n;code = 110
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char = v;code = 118
char = i;code = 105
char = v;code = 118
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char = s;code = 115
char = t;code = 116
char = u;code = 117
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char = o;code = 111
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char = a;code = 97
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char = t;code = 116
char = a;code = 97
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char = i;code = 105
char = s;code = 115
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char = w;code = 119
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char = a;code = 97
char = t;code = 116
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char = a;code = 97
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char = M;code = 77
char = a;code = 97
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char = a;code = 97
char = c;code = 99
char = a;code = 97
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char = a;code = 97
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char = d;code = 100
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char = o;code = 111
char = n;code = 110
char = k;code = 107
char = e;code = 101
char = y;code = 121
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char = .;code = 46
char = ;code = 32
char = R;code = 82
char = a;code = 97
char = t;code = 116
char = s;code = 115
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char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
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char = o;code = 111
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char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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char = a;code = 97
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char = m;code = 109
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char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = p;code = 112
char = o;code = 111
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char = i;code = 105
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
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char = l;code = 108
char = ;code = 32
char = (;code = 40
char = 6;code = 54
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char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = );code = 41
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = e;code = 101
char = e;code = 101
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char = o;code = 111
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char = s;code = 115
char = a;code = 97
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char = o;code = 111
char = l;code = 108
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = G;code = 71
char = C;code = 67
char = -;code = 45
char = M;code = 77
char = S;code = 83
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = M;code = 77
char = o;code = 111
char = n;code = 110
char = k;code = 107
char = e;code = 101
char = y;code = 121
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 = o;code = 111
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = k;code = 107
char = g;code = 103
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = F;code = 70
char = A;code = 65
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = W;code = 87
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
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 = c;code = 99
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = (;code = 40
char = 3;code = 51
char = );code = 41
char = H;code = 72
char = -;code = 45
char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = t;code = 116
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 = f;code = 102
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = :;code = 58
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = r;code = 114
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = r;code = 114
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 = d;code = 100
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = r;code = 114
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
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 = s;code = 115
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = l;code = 108
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
char = l;code = 108
char = y;code = 121
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 = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = u;code = 117
char = b;code = 98
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
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 = 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 = t;code = 116
char = h;code = 104
char = i;code = 105
char = r;code = 114
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = .;code = 46
char = ;code = 32
char = O;code = 79
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
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 = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = m;code = 109
char = a;code = 97
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = k;code = 107
char = e;code = 101
char = y;code = 121
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = a;code = 97
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = l;code = 108
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
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char = b;code = 98
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = U;code = 85
char = n;code = 110
char = s;code = 115
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = l;code = 108
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = i;code = 105
char = c;code = 99
char = );code = 41
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = l;code = 108
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char = ;code = 32
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char = o;code = 111
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = m;code = 109
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char = ;code = 32
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char = ;code = 32
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char = e;code = 101
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char = e;code = 101
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char = u;code = 117
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char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = r;code = 114
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char = s;code = 115
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char = s;code = 115
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char = n;code = 110
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char = ;code = 32
char = s;code = 115
char = u;code = 117
char = c;code = 99
char = h;code = 104
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char = h;code = 104
char = y;code = 121
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char = o;code = 111
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result sql = BACKGROUND : Policosanol is a mixture of very-long-chain aliphatic alcohols purified from sugar cane wax with cholesterol-lowering effects, whose main component is octacosanol. Scarce data about the metabolism of octacosanol and the other fatty alcohols composing policosanol have been published.
METHODS : Human fibroblasts were cultured in presence of (3)H-octacosanol during 0.5, 2 and 4 h. Lipid extracts were analyzed by thin layer chromatography, and the spots corresponding to octacosanol and octacosanoic acid were identified comparing with authentic standards. Spots were scraped, transferred to vials and radioactivity was measured. For corroborating the presence of octacosanol and octacosanoic acid, samples were analyzed by gas chromatography-mass spectrometry (GC-MS). The in vivo study of octacosanol metabolism was conducted in rats and Macaca arctoides monkeys. Rats were orally administered with policosanol (60 mg/kg) and free octacosanol and octacosanoic acid were identified in liver and plasma by GC-MS at various time intervals. Monkeys were orally and endovenously treated with policosanol (10 mg/kg) and the presence of free octacosanol, octacosanoic acid and some chain-shortened FA was investigated.
RESULTS : When fibroblasts were cultured in presence of (3)H-octacosanol, three spots were found: a first one corresponded to octacosanoic acid, a second to octacosanol and a third one remained unidentified. The radioactivity on the spot of octacosanoic acid slightly decreased throughout the incubation but increased in the third spot. Octacosanol and free octacosanoic acids were also identified in plasma of monkeys orally administered with policosanol. In addition, plasma samples showed free saturated acids, palmitic acid being the most abundant, followed by oleic and mystiric acids. Unsaturated acids (oleic and palmitoleic) were also observed.
CONCLUSIONS : The present study demonstrates that octacosanoic acid is formed after incubation of fibroblast cultures with (3)H-octacosanol and after oral dosing with policosanol to rats. In addition, we demonstrated that shortened saturated (myristic, palmitic and stearic) and unsaturated (oleic, palmitoleic) FA are also formed after oral dosing with policosanol to monkeys. The present results are consistent with the fact that octacosanol metabolism is linked to FA metabolism via beta-oxidation, but further studies need to explore the occurrence of more metabolites proving such hypothesis.
Publication: Arch. Med. Res. 2005 Mar-Apr ;36(2)::113-9.
Publication Date: 2005 Mar-Apr
Study Author(s): Menéndez, Roberto;Marrero, David;Más, Rosa;Fernández, Ivon;González, Luis;González, Rosa Maria;
Institution: Center of Natural Products, National Center for Scientific Research, Havana City, Cuba. [email protected]
Shortcut link to this study:
Publication Date: 2005 Mar-Apr
Study Author(s): Menéndez, Roberto;Marrero, David;Más, Rosa;Fernández, Ivon;González, Luis;González, Rosa Maria;
Institution: Center of Natural Products, National Center for Scientific Research, Havana City, Cuba. [email protected]
Shortcut link to this study:
BACKGROUND : Policosanol is a mixture of very-long-chain aliphatic alcohols purified from sugar cane wax with cholesterol-lowering effects, whose main component is octacosanol. Scarce data about the metabolism of octacosanol and the other fatty alcohols composing policosanol have been published.
METHODS : Human fibroblasts were cultured in presence of (3)H-octacosanol during 0.5, 2 and 4 h. Lipid extracts were analyzed by thin layer chromatography, and the spots corresponding to octacosanol and octacosanoic acid were identified comparing with authentic standards. Spots were scraped, transferred to vials and radioactivity was measured. For corroborating the presence of octacosanol and octacosanoic acid, samples were analyzed by gas chromatography-mass spectrometry (GC-MS). The in vivo study of octacosanol metabolism was conducted in rats and Macaca arctoides monkeys. Rats were orally administered with policosanol (60 mg/kg) and free octacosanol and octacosanoic acid were identified in liver and plasma by GC-MS at various time intervals. Monkeys were orally and endovenously treated with policosanol (10 mg/kg) and the presence of free octacosanol, octacosanoic acid and some chain-shortened FA was investigated.
RESULTS : When fibroblasts were cultured in presence of (3)H-octacosanol, three spots were found: a first one corresponded to octacosanoic acid, a second to octacosanol and a third one remained unidentified. The radioactivity on the spot of octacosanoic acid slightly decreased throughout the incubation but increased in the third spot. Octacosanol and free octacosanoic acids were also identified in plasma of monkeys orally administered with policosanol. In addition, plasma samples showed free saturated acids, palmitic acid being the most abundant, followed by oleic and mystiric acids. Unsaturated acids (oleic and palmitoleic) were also observed.
CONCLUSIONS : The present study demonstrates that octacosanoic acid is formed after incubation of fibroblast cultures with (3)H-octacosanol and after oral dosing with policosanol to rats. In addition, we demonstrated that shortened saturated (myristic, palmitic and stearic) and unsaturated (oleic, palmitoleic) FA are also formed after oral dosing with policosanol to monkeys. The present results are consistent with the fact that octacosanol metabolism is linked to FA metabolism via beta-oxidation, but further studies need to explore the occurrence of more metabolites proving such hypothesis.
METHODS : Human fibroblasts were cultured in presence of (3)H-octacosanol during 0.5, 2 and 4 h. Lipid extracts were analyzed by thin layer chromatography, and the spots corresponding to octacosanol and octacosanoic acid were identified comparing with authentic standards. Spots were scraped, transferred to vials and radioactivity was measured. For corroborating the presence of octacosanol and octacosanoic acid, samples were analyzed by gas chromatography-mass spectrometry (GC-MS). The in vivo study of octacosanol metabolism was conducted in rats and Macaca arctoides monkeys. Rats were orally administered with policosanol (60 mg/kg) and free octacosanol and octacosanoic acid were identified in liver and plasma by GC-MS at various time intervals. Monkeys were orally and endovenously treated with policosanol (10 mg/kg) and the presence of free octacosanol, octacosanoic acid and some chain-shortened FA was investigated.
RESULTS : When fibroblasts were cultured in presence of (3)H-octacosanol, three spots were found: a first one corresponded to octacosanoic acid, a second to octacosanol and a third one remained unidentified. The radioactivity on the spot of octacosanoic acid slightly decreased throughout the incubation but increased in the third spot. Octacosanol and free octacosanoic acids were also identified in plasma of monkeys orally administered with policosanol. In addition, plasma samples showed free saturated acids, palmitic acid being the most abundant, followed by oleic and mystiric acids. Unsaturated acids (oleic and palmitoleic) were also observed.
CONCLUSIONS : The present study demonstrates that octacosanoic acid is formed after incubation of fibroblast cultures with (3)H-octacosanol and after oral dosing with policosanol to rats. In addition, we demonstrated that shortened saturated (myristic, palmitic and stearic) and unsaturated (oleic, palmitoleic) FA are also formed after oral dosing with policosanol to monkeys. The present results are consistent with the fact that octacosanol metabolism is linked to FA metabolism via beta-oxidation, but further studies need to explore the occurrence of more metabolites proving such hypothesis.
PMID: 15847942
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