Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lipodystrophy syndrome.
<h4>Background</h4>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.<h4>Methods</h4>Plasma uridine concentrations were measured in 35 controls and 221 HIV-1-inf...
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oai:doaj.org-article:22a61b1f92254da39add10ac81c125f92021-11-18T07:36:52ZUridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lipodystrophy syndrome.1932-620310.1371/journal.pone.0013896https://doaj.org/article/22a61b1f92254da39add10ac81c125f92010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21085568/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.Pere DomingoJavier Torres-TorronterasVirginia PomarMarta GiraltJoan Carles DomingoMaria Del Mar GutierrezJosé M Gallego-EscuredoMaria Gracia MateoPedro Cano-SoldadoIrene FernandezMarçal Pastor-AngladaFrancesc VidalFrancesc VillarroyaAntoni AndreuRamon MartiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 11, p e13896 (2010) |
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Medicine R Science Q Pere Domingo Javier Torres-Torronteras Virginia Pomar Marta Giralt Joan Carles Domingo Maria Del Mar Gutierrez José M Gallego-Escuredo Maria Gracia Mateo Pedro Cano-Soldado Irene Fernandez Marçal Pastor-Anglada Francesc Vidal Francesc Villarroya Antoni Andreu Ramon Marti Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lipodystrophy syndrome. |
| description |
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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. |
| format |
article |
| author |
Pere Domingo Javier Torres-Torronteras Virginia Pomar Marta Giralt Joan Carles Domingo Maria Del Mar Gutierrez José M Gallego-Escuredo Maria Gracia Mateo Pedro Cano-Soldado Irene Fernandez Marçal Pastor-Anglada Francesc Vidal Francesc Villarroya Antoni Andreu Ramon Marti |
| author_facet |
Pere Domingo Javier Torres-Torronteras Virginia Pomar Marta Giralt Joan Carles Domingo Maria Del Mar Gutierrez José M Gallego-Escuredo Maria Gracia Mateo Pedro Cano-Soldado Irene Fernandez Marçal Pastor-Anglada Francesc Vidal Francesc Villarroya Antoni Andreu Ramon Marti |
| author_sort |
Pere Domingo |
| title |
Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lipodystrophy syndrome. |
| title_short |
Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lipodystrophy syndrome. |
| title_full |
Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lipodystrophy syndrome. |
| title_fullStr |
Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lipodystrophy syndrome. |
| title_full_unstemmed |
Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lipodystrophy syndrome. |
| title_sort |
uridine metabolism in hiv-1-infected patients: effect of infection, of antiretroviral therapy and of hiv-1/art-associated lipodystrophy syndrome. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/22a61b1f92254da39add10ac81c125f9 |
| work_keys_str_mv |
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