Browsing by Author "Salas, Jose D."

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    Extracellular gentamicin reduces the activity of con nexin hemichannels and interferes with purinergic Ca2+ signaling in HeLa cells
    (2014) Figueroa, Vania A.; Retamal, Mauricio A.; Cea, Luis A.; Salas, Jose D.; Vargas, Anibal A.; Verdugo, Christian A.; Jara, Oscar; Martinez, Agustin D.; Saez, Juan C.
    Gap junction channels (GJCs) and hemichannels (HCs) are composed of protein subunits termed connexins (Cxs) and are permeable to ions and small molecules. In most organs, GJCs communicate the cytoplasm of adjacent cells, while HCs communicate the intra and extracellular compartments. In this way, both channel types coordinate physiological responses of cell communities. Cx mutations explain several genetic diseases, including about 50% of autosomal recessive non-syndromic hearing loss. However, the possible involvement of Cxs in the etiology of acquired hearing loss remains virtually unknown. Factors that induce post-lingual hearing loss are diverse, exposure to gentamicin an aminoglycoside antibiotic, being the most common. Gentamicin has been proposed to block GJCs, but its effect on HCs remains unknown. In this work, the effect of gentamicin on the functional state of HCs was studied and its effect on GJCs was reevaluated in HeLa cells stably transfected with Cxs. We focused on Cx26 because it is the main Cx expressed in the cochlea of mammals where it participates in purinergic signaling pathways. We found that gentamicin applied extracellularly reduces the activity of HCs, while dye transfer across GJCs was not affected. HCs were also blocked by streptomycin, another aminoglycoside antibiotic. Gentamicin also reduced the adenosine triphosphate release and the HC-dependent oscillations of cytosolic free-Ca2+ signal. Moreover, gentamicin drastically reduced the Cx26 HC-mediated membrane currents in Xenopus laevis oocytes. Therefore, the extracellular gentamicin-induced inhibition of Cx HCs may adversely affect autocrine and paracrine signaling, including the purinergic one, which might partially explain its ototoxic effects.
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    RETURN PERIOD AND RISK OF HYDROLOGIC EVENTS. I: MATHEMATICAL FORMULATION
    (1999) Fernandez, Bonifacio; Salas, Jose D.
    The estimation of return periods of hydrological events and the corresponding risks of failure of hydraulic structures that are associated with such events are important aspects in many water resources studies. For simple hydrologic events such as those related to independent annual floods, both the return period and the risk of failure can be readily calculated. However, no general applicable methods are available for the estimation of return periods, risk of failure, and reliability of service in cases of more complex hydrological events such as those related to dependent annual flows and droughts. In this paper, the definitions commonly employed for return period and risk of failure are reexamined and a general procedure for their estimation are presented, which may be applicable to a wide range of hydrological events related to floods, droughts, minimum flows, aquifer levels, and reservoir levels and outflows. Part II of this paper includes numerical examples and applications.
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    RETURN PERIOD AND RISK OF HYDROLOGIC EVENTS. II: APPLICATIONS
    (ASCE-AMER SOC CIVIL ENGINEERS, 1999) Fernandez, Bonifacio; Salas, Jose D.
    A mathematical formulation to estimate return periods and risks of failure of complex hydrologic events such as those arising from dependent floods and droughts have been examined in the first part of this paper. Specifically, some relationships and algorithms for computing return periods and associated risks for runs arising from independent and dependent events assuming that dependence is represented by a two-state Markov chain have been proposed. The applicability of these procedures is illustrated herein, considering several types of hydrological events with emphasis on those where dependence is important. First, meteorological droughts based on annual precipitation are considered as examples of events consisting of runs in independent trials. Then, minimum streamflows and maximum annual lake outflows are included as examples of dependent events, assuming that dependence is represented by a simple Markov chain. Also, hydrological droughts based on annual streamflow series are considered. In addition, the estimation of return period and risk are illustrated by data generation.