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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.
Author: 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
Keywords: VIH (Virus)
Síndrome de lipodistròfia associada a VIH
HIV (Viruses)
Antiretroviral agents
HIV-associated lipodystrophy syndrome
Issue Date: 2010
Publisher: Public Library of Science (PLoS)
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.
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It is part of: PLoS One, 2010, vol. 5, num. 11, p. e13896
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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