Fernandez-Nistal, A. (Alonso)

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    Characterization of the rat Na+/nucleoside cotransporter 2 and transport of nucleoside-derived drugs using electrophysiological methods.
    (American Physiological Society, 2006) Larrayoz, I.M. (Ignacio M.); Lostao, M.P. (María Pilar); Gallego-Herrera, F. (Fernando); Fernandez-Nistal, A. (Alonso); Gorraiz, E. (Edurne)
    The Na(+)-dependent nucleoside transporter 2 (CNT2) mediates active transport of purine nucleosides and uridine as well as therapeutic nucleoside analogs. We used the two-electrode voltage-clamp technique to investigate rat CNT2 (rCNT2) transport mechanism and study the interaction of nucleoside-derived drugs with the transporter expressed in Xenopus laevis oocytes. The kinetic parameters for sodium, natural nucleosides, and nucleoside derivatives were obtained as a function of membrane potential. For natural substrates, apparent affinity (K(0.5)) was in the low micromolar range (12-34) and was voltage independent for hyperpolarizing membrane potentials, whereas maximal current (I(max)) was voltage dependent. Uridine and 2'-deoxyuridine analogs modified at the 5-position were substrates of rCNT2. Lack of the 2'-hydroxyl group decreased affinity but increased I(max). Increase in the size and decrease in the electronegativity of the residue at the 5-position affected the interaction with the transporter by decreasing both affinity and I(max). Fludarabine and formycin B were also transported with higher I(max) than uridine and moderate affinity (102 +/- 10 and 66 +/- 6 microM, respectively). Analysis of the pre-steady-state currents revealed a half-maximal activation voltage of about -39 mV and a valence of about -0.8. K(0.5) for Na(+) was 2.3 mM at -50 mV and decreased at hyperpolarizing membrane potentials. The Hill coefficient was 1 at all voltages. Direct measurements of radiolabeled nucleoside fluxes with the charge associated showed a ratio of two positive inward charges per nucleoside, suggesting a stoichiometry of two Na(+) per nucleoside. This discrepancy in the number of Na(+) molecules that bind rCNT2 may indicate a low degree of cooperativity between the Na(+) binding sites.
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    Influence of stress and depression on the immune system in patients evaluated in an anti-aging unit
    (Frontiers, 2020) Martínez-Fernández, V. (Vicente); Cañas-González, B. (Beatriz); Fernandez-Nistal, A. (Alonso); Ramírez, J.M. (Juan M.)
    Background: There is compelling evidence pointing out that stress and depression produce a dramatic impact on human well-being mainly through impairing the regular function of the immune system and producing a low-chronic inflammation status that favors the occurrence of infections, metabolic diseases, and even cancer. The present work aims to evaluate the stress/depression levels of some patients treated in an antiaging unit and detect any potential relationship with their immune system status prior of the implementation of a physical/psychological program designed to prevent health deterioration. Methods: We evaluated 48 patients (16 men and 32 women with a mean age of 55.11 ± 10.71 years) from middle-upper class from psychological and immunological points of view. In particular, we analyzed neutrophil chemotaxis and phagocytosis; lymphocyte chemotaxis and proliferation, and natural killer (NK) cell activity. Results: Women showed more depressive symptoms than men. Chemotaxis levels of lymphocytes and neutrophils in women showed a significant reduction compared with those in men. We also found a strong negative correlation between depression and NK cell function. This correlation was also significant independently of gender. Conclusion: We conclude that NK activity is affected at least by depression state, and we propose that a combined treatment consisting of cognitive behavioral therapy and physical activity programs might improve patient health deterioration.