char = P;code = 80
char = o;code = 111
char = l;code = 108
char = y;code = 121
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char = m;code = 109
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = t;code = 116
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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 = t;code = 116
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = t;code = 116
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
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char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
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char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = P;code = 80
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = c;code = 99
char = y;code = 121
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char = t;code = 116
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = a;code = 97
char = .;code = 46
result sql = Polyamine transport as a target for treatment of Pneumocystis pneumonia.

Polyamine transport as a target for treatment of Pneumocystis pneumonia.

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char = l;code = 108
char = y;code = 121
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = e;code = 101
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 = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = l;code = 108
char = y;code = 121
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 = a;code = 97
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = c;code = 99
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = A;code = 65
char = M;code = 77
char = s;code = 115
char = );code = 41
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 = P;code = 80
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = c;code = 99
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char = s;code = 115
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = (;code = 40
char = P;code = 80
char = C;code = 67
char = P;code = 80
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = a;code = 97
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
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
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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 = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = H;code = 72
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = O;code = 79
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = A;code = 65
char = M;code = 77
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = g;code = 103
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
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char = o;code = 111
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char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = O;code = 79
char = n;code = 110
char = e;code = 101
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 = m;code = 109
char = e;code = 101
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = h;code = 104
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char = e;code = 101
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char = e;code = 101
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char = ;code = 32
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char = e;code = 101
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char = ;code = 32
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char = s;code = 115
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char = o;code = 111
char = l;code = 108
char = y;code = 121
char = a;code = 97
char = m;code = 109
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char = n;code = 110
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
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char = h;code = 104
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char = s;code = 115
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char = y;code = 121
char = ,;code = 44
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char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = t;code = 116
char = i;code = 105
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char = g;code = 103
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
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char = a;code = 97
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char = i;code = 105
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char = e;code = 101
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char = t;code = 116
char = a;code = 97
char = k;code = 107
char = e;code = 101
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char = a;code = 97
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char = ;code = 32
char = a;code = 97
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char = t;code = 116
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char = a;code = 97
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char = e;code = 101
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char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = P;code = 80
char = C;code = 67
char = P;code = 80
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = e;code = 101
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char = a;code = 97
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char = i;code = 105
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char = d;code = 100
char = .;code = 46
char = ;code = 32
char = F;code = 70
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char = r;code = 114
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char = a;code = 97
char = n;code = 110
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = e;code = 101
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char = e;code = 101
char = -;code = 45
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char = d;code = 100
char = ;code = 32
char = o;code = 111
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char = ';code = 39
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char = [;code = 91
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char = t;code = 116
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char = u;code = 117
char = t;code = 116
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char = 4;code = 52
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char = 4;code = 52
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char = e;code = 101
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char = s;code = 115
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char = p;code = 112
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char = 4;code = 52
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char = 4;code = 52
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char = e;code = 101
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char = n;code = 110
char = d;code = 100
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char = t;code = 116
char = o;code = 111
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char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
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char = a;code = 97
char = ;code = 32
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char = e;code = 101
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char = y;code = 121
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char = l;code = 108
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char = w;code = 119
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char = t;code = 116
char = o;code = 111
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char = c;code = 99
char = i;code = 105
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char = t;code = 116
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char = ;code = 32
char = A;code = 65
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char = s;code = 115
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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 = t;code = 116
char = r;code = 114
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char = a;code = 97
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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 = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = i;code = 105
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char = t;code = 116
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char = e;code = 101
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char = a;code = 97
char = p;code = 112
char = e;code = 101
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char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
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char = ;code = 32
char = P;code = 80
char = C;code = 67
char = P;code = 80
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char = i;code = 105
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char = v;code = 118
char = i;code = 105
char = v;code = 118
char = o;code = 111
char = .;code = 46
char = ;code = 32
char = S;code = 83
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char = r;code = 114
char = a;code = 97
char = g;code = 103
char = u;code = 117
char = e;code = 101
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char = D;code = 68
char = a;code = 97
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char = l;code = 108
char = e;code = 101
char = y;code = 121
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char = r;code = 114
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char = t;code = 116
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char = i;code = 105
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char = a;code = 97
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char = ;code = 32
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char = 1;code = 49
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char = m;code = 109
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char = s;code = 115
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char = 4;code = 52
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char = 4;code = 52
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char = 4;code = 52
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char = l;code = 108
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char = o;code = 111
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char = i;code = 105
char = s;code = 115
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char = f;code = 102
char = ;code = 32
char = A;code = 65
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char = .;code = 46
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char = B;code = 66
char = o;code = 111
char = t;code = 116
char = h;code = 104
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char = 4;code = 52
char = 4;code = 52
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char = l;code = 108
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char = 4;code = 52
char = 4;code = 52
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char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = t;code = 116
char = a;code = 97
char = k;code = 107
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
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 = P;code = 80
char = C;code = 67
char = P;code = 80
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
result sql = Polyamine levels are greatly increased in alveolar macrophages (AMs) during Pneumocystis pneumonia (PCP), leading to increased production of H(2)O(2), which causes AMs to undergo apoptosis. One of the mechanisms by which polyamine levels in AMs are elevated is enhanced uptake of exogenous polyamines. In this study, the possibility of targeting polyamine uptake as a treatment for PCP was examined. Four anthracene- and one benzene-polyamine conjugates that are potential polyamine transport inhibitors, including N1-anthracen-9-ylmethyl-butane-1,4-diamine; N-(4-aminobutyl)-N-anthracen-9-ylmethylbutane-1,4-diamine; N-[4-(4-aminobutylamino)butyl]-N-anthracen-9-ylmethylbutane-1,4-diamine; N-(4-amino-butyl)-N'-(10-[[4-(4-amino-butylamino)butylamino]-methyl]anthracen-9-ylmethyl)butane-1,4-diamine (44-Ant-44); and benzene-polyamine conjugate N-(4-amino-butyl)-N'-(4-[[4-(4-amino-butylamino)butylamino]-methyl]benzyl)butane-1,4-diamine (44-Bn-44), were tested. Compounds 44-Ant-44 and 44-Bn-44 were found to have a very low toxicity to AMs in vitro and were evaluated for their therapeutic effect on PCP in vivo. Sprague-Dawley rats infected with P. carinii for 28 days were intranasally instilled with 50 microl of a 1 mM solution of 44-Bn-44 or 44-Ant-44 every 2 days. Twenty-one days after initiation of the treatment, three to five rats from each group were sacrificed and examined for lung pathology, organism burden, and apoptosis of AMs. Both 44-Bn-44 and 44-Ant-44 reduced organism burdens; however, only 44-Ant-44 decreased the severity of the infection with reduced lung inflammation, increased clearance of exudates, increased air space, and decreased apoptosis of AMs. 44-Ant-44 also significantly prolonged the survival of treated animals. These results suggest that polyamine uptake is a potential target for treatment of PCP.

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