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Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lypodystrophy syndrome.
Domingo, Pere (Domingo Pedrol); Torres Torronteras, J.; 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; Fernández, Irene; Pastor Anglada, Marçal; Vidal, Francesc; Villarroya i Gombau, Francesc; Andreu, Antoni; Martí, Ramon
Universitat de Barcelona
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.
VIH (Virus)
Antiretrovirals
Síndrome de lipodistròfia associada a VIH
Metabolisme
HIV (Viruses)
Antiretroviral agents
HIV-associated lipodystrophy syndrome
Metabolism
cc-by (c) Domingo, P. et al., 2010
http://creativecommons.org/licenses/by/3.0/es
Article
info:eu-repo/semantics/publishedVersion
Public Library of Science (PLoS)
         

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