char = H;code = 72
char = I;code = 73
char = V;code = 86
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = ;code = 32
char = G;code = 71
char = L;code = 76
char = U;code = 85
char = T;code = 84
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char = r;code = 114
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = p;code = 112
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = u;code = 117
char = t;code = 116
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char = ;code = 32
char = d;code = 100
char = e;code = 101
char = c;code = 99
char = o;code = 111
char = m;code = 109
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char = e;code = 101
char = n;code = 110
char = s;code = 115
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char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
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char = ;code = 32
char = f;code = 102
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = u;code = 117
char = r;code = 114
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = o;code = 111
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char = s;code = 115
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char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = m;code = 109
char = y;code = 121
char = o;code = 111
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = .;code = 46
result sql = HIV protease inhibitors that block GLUT4 precipitate acute, decompensated heart failure in a mouse model of dilated cardiomyopathy.
HIV protease inhibitors that block GLUT4 precipitate acute, decompensated heart failure in a mouse model of dilated cardiomyopathy.
char = T;code = 84
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char = a;code = 97
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char = I;code = 73
char = V;code = 86
char = ;code = 32
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char = r;code = 114
char = o;code = 111
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char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = i;code = 105
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char = h;code = 104
char = i;code = 105
char = b;code = 98
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char = i;code = 105
char = s;code = 115
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char = s;code = 115
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char = a;code = 97
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char = m;code = 109
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char = a;code = 97
char = b;code = 98
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char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
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char = t;code = 116
char = h;code = 104
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char = t;code = 116
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char = i;code = 105
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char = e;code = 101
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char = l;code = 108
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char = m;code = 109
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char = c;code = 99
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char = d;code = 100
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char = o;code = 111
char = v;code = 118
char = a;code = 97
char = s;code = 115
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = k;code = 107
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = e;code = 101
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = f;code = 102
char = a;code = 97
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char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
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char = a;code = 97
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char = ;code = 32
char = h;code = 104
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char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = u;code = 117
char = c;code = 99
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char = s;code = 115
char = e;code = 101
char = ,;code = 44
char = ;code = 32
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char = e;code = 101
char = ;code = 32
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char = f;code = 102
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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 = d;code = 100
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char = g;code = 103
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char = x;code = 120
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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 = ;code = 32
char = c;code = 99
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char = d;code = 100
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char = f;code = 102
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char = ;code = 32
char = s;code = 115
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char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = t;code = 116
char = e;code = 101
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char = m;code = 109
char = i;code = 105
char = n;code = 110
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 = 84
char = G;code = 71
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char = m;code = 109
char = i;code = 105
char = c;code = 99
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char = ,;code = 44
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char = i;code = 105
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char = ;code = 32
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char = h;code = 104
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char = C;code = 67
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result sql = The clinical use of HIV protease inhibitors is associated with insulin resistance and other metabolic changes that increase long-term cardiovascular risk. Since the failing heart has increased reliance on glucose, the influence of drug exposure on glucose homeostasis, myocardial glucose uptake, cardiac function, and survival was determined in TG9 mice, an established transgenic model of dilated cardiomyopathy generated by cardiac-specific overexpression of Cre-recombinase, as these animals progressed to overt heart failure. Beginning on day of life 75, TG9 mice and nontransgenic littermate controls were given a daily 10 mg/kg intraperitoneal injection of HIV protease inhibitors (ritonavir, lopinavir/ritonavir 4:1, atazanavir, atazanavir/ritonavir 4:1) or vehicle. Glucose tolerance testing, measurement of in vivo myocardial 2-deoxyglucose uptake, and echocardiography were performed before and 30 min following drug administration. The progression of dilated cardiomyopathy in TG9 animals was accompanied by impaired glucose tolerance, which was acutely exacerbated by exposure to ritonavir. Ritonavir and lopinavir precipitated acute, decompensated heart failure and death from pulmonary edema in TG9 mice. However, atazanavir, which does not inhibit glucose transport, had no effect. These studies demonstrate that, in the presence of dilated cardiomyopathy, HIV protease inhibitors that impair glucose transport induce acute, decompensated heart failure. The potential for HIV protease inhibitors to contribute to or exacerbate cardiomyopathy in human patients warrants further investigation.

Publication: FASEB J. 2008 Jul ;22(7)::2161-7. :doi: 10.1096/fj.07-102269.
Publication Date: 2008 Jul
Study Author(s): Hruz, Paul W;Yan, Qingyun;Struthers, Heidi;Jay, Patrick Y;
Institution: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA. hruz_p@kids.wustl.edu
Shortcut link to this study:
The clinical use of HIV protease inhibitors is associated with insulin resistance and other metabolic changes that increase long-term cardiovascular risk. Since the failing heart has increased reliance on glucose, the influence of drug exposure on glucose homeostasis, myocardial glucose uptake, cardiac function, and survival was determined in TG9 mice, an established transgenic model of dilated cardiomyopathy generated by cardiac-specific overexpression of Cre-recombinase, as these animals progressed to overt heart failure. Beginning on day of life 75, TG9 mice and nontransgenic littermate controls were given a daily 10 mg/kg intraperitoneal injection of HIV protease inhibitors (ritonavir, lopinavir/ritonavir 4:1, atazanavir, atazanavir/ritonavir 4:1) or vehicle. Glucose tolerance testing, measurement of in vivo myocardial 2-deoxyglucose uptake, and echocardiography were performed before and 30 min following drug administration. The progression of dilated cardiomyopathy in TG9 animals was accompanied by impaired glucose tolerance, which was acutely exacerbated by exposure to ritonavir. Ritonavir and lopinavir precipitated acute, decompensated heart failure and death from pulmonary edema in TG9 mice. However, atazanavir, which does not inhibit glucose transport, had no effect. These studies demonstrate that, in the presence of dilated cardiomyopathy, HIV protease inhibitors that impair glucose transport induce acute, decompensated heart failure. The potential for HIV protease inhibitors to contribute to or exacerbate cardiomyopathy in human patients warrants further investigation.
PMID: 18256305

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