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Title: | Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lypodystrophy syndrome. |
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Author: | Domingo, Pere (Domingo Pedrol); Torres Torronteras, Javier; Pomar Solchaga, Virginia; Giralt i Oms, Marta; Domingo i Pedrol, Joan Carles; Gutiérrez, Maria del Mar; Gallego Escuredo, José Miguel; Mateo, Maria Gracia; Cano Soldado, Pedro Javier; Fernández, Irene; Pastor Anglada, Marçal; Vidal, Francesc; Villarroya i Gombau, Francesc; Andreu, Antoni; Martí, Ramon |
Other authors: | Universitat de Barcelona |
Abstract: | Background Uridine has been advocated for the treatment of HIV-1/HAART-associated lipodystrophy (HALS), although its metabolism in HIV-1-infected patients is poorly understood. Methods Plasma uridine concentrations were measured in 35 controls and 221 HIV-1-infected patients and fat uridine in 15 controls and 19 patients. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Uridine was measured by a binary gradient-elution HPLC method. Analysis of genes encoding uridine metabolizing enzymes in fat was performed with TaqMan RT-PCR. Results Median plasma uridine concentrations for HIV-1-infected patients were 3.80 µmol/l (interquartile range: 1.60), and for controls 4.60 µmol/l (IQR: 1.8) (P = 0.0009). In fat, they were of 6.0 (3.67), and 2.8 (4.65) nmol/mg of protein, respectively (P = 0.0118). Patients with a mixed HALS form had a median plasma uridine level of 4.0 (IC95%: 3.40-4.80) whereas in those with isolated lipoatrophy it was 3.25 (2.55-4.15) µmol/l/l (P = 0.0066). The expression of uridine cytidine kinase and uridine phosphorylase genes was significantly decreased in all groups of patients with respect to controls. A higher expression of the mRNAs for concentrative nucleoside transporters was found in HIV-1-infected patients with respect to healthy controls. Conclusions HIV-1 infection is associated with a decrease in plasma uridine and a shift of uridine to the adipose tissue compartment. Antiretroviral therapy was not associated with plasma uridine concentrations, but pure lipoatrophic HALS was associated with significantly lower plasma uridine concentrations. |
Subject(s): | -VIH (Virus) -Antiretrovirals -Síndrome de lipodistròfia associada a VIH -Metabolisme -HIV (Viruses) -Antiretroviral agents -HIV-associated lipodystrophy syndrome -Metabolism |
Rights: | cc-by (c) Domingo, P. et al., 2010
http://creativecommons.org/licenses/by/3.0/es |
Document type: | Article Article - Published version |
Published by: | Public Library of Science (PLoS) |
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