Browsing by Author "Villalon, Manuel J."

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    Blocking ATP-releasing channels prevents high extracellular ATP levels and airway hyperreactivity in an asthmatic mouse model
    (AMER PHYSIOLOGICAL SOC, 2021) Arzola Martinez, Llilian; Benavente, Rebeca; Vega, Genesis; Rios, Mariana; Fonseca, Wendy; Rasky, Andrew J.; Morris, Susan; Lukacs, Nicholas W.; Villalon, Manuel J.
    Allergic asthma is a chronic airway inflammatory response to different triggers like inhaled allergens. Excessive ATP in fluids from patients with asthma is considered an inflammatory signal and an important autocrine/paracrine modulator of airway physiology. Here, we investigated the deleterious effect of increased extracellular ATP (eATP) concentration on the mucociliary clearance (MCC) effectiveness and determined the role of ATP releasing channels during airway inflammation in an ovalbumin (OVA)-sensitized mouse model. Our allergic mouse model exhibited high levels of eATP measured in the tracheal fluid with a luciferin-luciferase assay and reduced MCC velocity determined by microspheres tracking in the trachea ex vivo. Addition of ATP had a dual effect on MCC, where lower ATP concentration (mu M) increased microspheres velocity, whereas higher concentration (mM) transiently stopped microspheres movement. Also, an augmented ethidium bromide uptake by the allergic tracheal airway epithelium suggests an increase in ATP release channel functionality during inflammatory conditions. The use of carbenoxolone, a nonspecific inhibitor of connexin and pannexini channels reduced the eATP concentration in the allergic mouse tracheal fluid and dye uptake by the airway epithelium, providing evidence that these ATP release channels are facilitating the net flux of ATP to the lumen during airway inflammation. However, only the specific inhibition of pannexinl with (10)Panx peptide significantly reduced eATP in bronchoalveolar lavage and decreased airway hyperresponsiveness in OVA-allergic mouse model. These data provide evidence that blocking eATP may be a pharmacological alternative to be explored in rescue therapy during episodes of airflow restriction in patients with asthma.
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    Effect of oestradiol and progesterone on the instant and directional velocity of microsphere movements in the rat oviduct
    (2007) Rios, Mariana; Hermoso, Marcela; Sanchez, Trinidad M.; Croxatto, Horacio B.; Villalon, Manuel J.
    The oviducal transport of eggs to the uterus normally takes 72 - 96 h in the rat, but this is reduced to less than 20 h after a single injection of oestradiol ( E2). This accelerated transport is associated with an increased frequency of pendular movements in the isthmic segment of the oviduct, with increased levels of the gap junction ( GJ) component Connexin ( Cx) 43, and is antagonised by progesterone ( P). In the present study, we investigated the effect of these hormones on the instant and directional velocity of pendular movements and the role of the GJ and its Cx43 component in the kinetic response of the oviduct to E2 and P. Using microspheres as egg surrogates, microsphere instant velocity ( MIV) was measured following treatment with E2, P or P+ E2, which accelerate or delay egg transport. Microspheres were delivered into the oviduct of rats on Day 1 of pregnancy and their movement within the isthmic segment was recorded. Oestrogen increased MIV with faster movement towards the uterus. After P or P+ E2, MIV was similar to that in the control group. Two GJ uncouplers, namely 18 alpha- and 18 beta- glycyrrhetinic acid, blocked the effect of E2 on MIV. Connexin 43 mRNA levels increased over that seen in control with all treatments. In conclusion, the effects of E2 on MIV resulted in faster movements that produced accelerated egg transport towards the uterus. Gap junctions are probably involved as smooth muscle synchronisers in this kinetic effect of E2, but the opposing effects of E2 and P are not exerted at the level of Cx43 transcription.
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    Enhancement of Visual Perception with Use of Dynamic Cues
    (RADIOLOGICAL SOC NORTH AMERICA, 2009) Andia, Marcelo E.; Plett, Johannes; Tejos, Cristian; Guarini, Marcelo W.; Navarro, Maria E.; Razmilic, Dravna; Meneses, Luis; Villalon, Manuel J.; Irarrazaval, Pablo
    Institutional review board approval and signed informed consent were not needed, as medical images included in public databases were used in this study. The purpose of this study was to improve the detection of microcalcifications on mammograms and lung nodules on chest radiographs by using the dynamic cues algorithm and the motion and flickering sensitivity of the human visual system (HVS). Different sets of mammograms from the Mammographic Image Analysis Society database and chest radiographs from the Japanese Society of Radiological Technology database were presented statically, as is standard, and in a video sequence generated with the dynamic cues algorithm. Nine observers were asked to rate the presence of abnormalities with a five-point scale (1, definitely not present; 5, definitely present). The data were analyzed with receiver operating characteristic (ROC) techniques and the Dorfman-Berbaum-Metz method. The video sequence generated with the dynamic cues algorithm increased the rate of detection of microcalcifications by 10.2% (P = .002) compared with that obtained with the standard static method, as measured by the area under the ROC curve. Similar results were obtained for lung nodules, with an increase of 12.3% (P = .0054). The increase in the rate of correct detection did not come just from the image contrast change produced by the algorithm but also from the fact that image frames generated with the dynamic cues algorithm were put together in a video sequence so that the motion sensitivity of the HVS could be used to facilitate the detection of low-contrast objects. (C) RSNA, 2009