Browsing by Author "Aguilar, G."

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    Chronology of Glacial Advances and Deglaciation in the Encierro River Valley (29° Lat. S), Southern Atacama Desert, Based on Geomorphological Mapping and Cosmogenic 10Be Exposure Ages
    (2022) Aguilar, G.; Riquelme, R.; Lohse, P.; Cabre, A.; Garcia, J. -L.
    The high mountain segments of the valleys of the southernmost Atacama Desert of Chile present Late Quaternary glacial landforms that developed in already incised valleys. Glacier advances and deglaciation have left a geomorphic imprint in the southernmost Atacama Desert. In this work, the glacial landforms of the Encierro River Valley (29.1 degrees S-69.9 degrees W) have been revisited and new detailed geomorphological mapping is provided. This work also includes new Be-10 exposure ages from moraine boulders and one age from an ice-molded bedrock surface. The former glacier of the El Encierro valley extended 16 km down the valley during the last local glacial maximum recorded by a terminal moraine (ENC 1a) with an exposure age of similar to 40 ka. Four inboard moraine arcs were deposited upstream in telescopic patterns (ENC 1b-d), whose exposure ages range between similar to 25 and similar to 33 ka (ENC 1d). Exposure ages between similar to 17-24 ka on lateral moraines (ENC 1L) developed during the later ice recession of the ENC 1 drift. Thus, the ice mostly disappeared in the main valley before similar to 18 ka, as is also supported by the exposure age obtained from an ice-molded bedrock surface. Seven kilometers up the valley from the ENC 1, the ENC 2a-d moraine arcs correspond to a small ice advance by similar to 17-20 ka. The last glacial advance (ENC 2), which occurred after deglaciation of the last local glacial maximum (ENC 1), coincides with the start of the Heinrich Stadial Event 1 (HS1; 18-14.5 ka), which is thought to play a direct role in the last glacial termination in the Andes.
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    S-Nitrosylation in endothelial cells contributes to tumor cell adhesion and extravasation during breast cancer metastasis
    (2023) Koning, T.; Cordova, F.; Aguilar, G.; Sarmiento, J.; Mardones, G. A.; Boric P., Mauricio; Varas-Godoy, M.; Lladser, A.; Duran, W. N.; Ehrenfeld, P.; Sanchez, F. A.
    Background Nitric oxide is produced by different nitric oxide synthases isoforms. NO activates two signaling pathways, one dependent on soluble guanylate cyclase and protein kinase G, and other where NO post-translationally modifies proteins through S-nitrosylation, which is the modification induced by NO in free-thiol cysteines in proteins to form S-nitrosothiols. High levels of NO have been detected in blood of breast cancer patients and increased NOS activity has been detected in invasive breast tumors compared to benign or normal breast tissue, suggesting a positive correlation between NO biosynthesis, degree of malignancy and metastasis. During metastasis, the endothelium plays a key role allowing the adhesion of tumor cells, which is the first step in the extravasation process leading to metastasis. This step shares similarities with leukocyte adhesion to the endothelium, and it is plausible that it may also share some regulatory elements. The vascular cell adhesion molecule-1 (VCAM-1) expressed on the endothelial cell surface promotes interactions between the endothelium and tumor cells, as well as leukocytes. Data show that breast tumor cells adhere to areas in the vasculature where NO production is increased, however, the mechanisms involved are unknown. Results We report that the stimulation of endothelial cells with interleukin-8, and conditioned medium from breast tumor cells activates the S-nitrosylation pathway in the endothelium to induce leukocyte adhesion and tumor cell extravasation by a mechanism that involves an increased VCAM-1 cell surface expression in endothelial cells. We identified VCAM-1 as an S-nitrosylation target during this process. The inhibition of NO signaling and S-nitrosylation blocked the transmigration of tumor cells through endothelial monolayers. Using an in vivo model, the number of lung metastases was inhibited in the presence of the S-nitrosylation inhibitor N-acetylcysteine (NAC), which was correlated with lower levels of S-nitrosylated VCAM-1 in the metastases. Conclusions S-Nitrosylation in the endothelium activates pathways that enhance VCAM-1 surface localization to promote binding of leukocytes and extravasation of tumor cells leading to metastasis. NAC is positioned as an important tool that might be tested as a co-therapy against breast cancer metastasis.
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    The identification of two subgroups of obese women with differing endometrial proliferation levels: potential consequences in the development of endometrial cancer
    (2012) Villavicencio, A.; Aguilar, G.; Acuna, J.; Gabler, F.; Soto, E.; Gaete, F.; Penaloza, P.; Celis, M.; Owen, G. I.
    Enhanced endometrial proliferation correlates obesity to type-I (estrogen-dependent) endometrial cancer (EC). Our aim was to distinguish obese women (without EC) with differing endometrial proliferation. Endometrial and blood samples were obtained from normal-weight and obese women without EC. Type-I EC samples were obtained from obese patients. On measuring endometrial proliferation (Ki67 and phosphorylated histone H3 (p-H3)), two groups of obese women without EC were identified: obese(High Proliferating) (O-HP) and obese(Low Proliferating) (O-LP). Increased Ki67 (88.5%, P<0.001), p-H3 (62.6%, P<0.01), 17 beta-estradiol/progesterone ratio (46.3%, P<0.01) and endometrial estrogen receptor alpha (ER alpha) (82.2%, P<0.001) were observed in O-HP compared with O-LP patients. ECs possessed similar ER alpha and enhanced proliferation as O-HP, suggesting that O-HP women are at higher risk of type-I EC. O-LP women were indistinguishable from normal-weight women regarding these determinants of endometrial proliferation, ER alpha and 17 beta-estradiol/progesterone ratio. Our data may further define the obesity phenotype in regards to type-I EC risk and may help identify obese women more susceptible to develop type-I EC, allowing early intervention and a potential reduction in mortality.
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    Towards the personalization of septic shock resuscitation: The fundamentals of ANDROMEDA-SHOCK-2 trial
    (2024) Ramasco, F.; Aguilar, G.; Aldecoa, C.; Bakker, J.; Carmona, P.; Dominguez, D.; Galiana, M.; Hernandez, G.; Kattan, E.; Olea, C.; Ospina-Tascon, G.; Perez, A.; Ramos, K.; Ramos, S.; Tamayo, G.; Tuero, G.
    Septic shock is a highly lethal and prevalent disease. Progressive circulatory dysfunction leads to tissue hypoperfusion and hypoxia, eventually evolving to multiorgan dysfunction and death. Prompt resuscitation may revert these pathogenic mechanisms, restoring oxygen delivery and organ function. High heterogeneity exists among the determinants of circulatory dysfunction in septic shock, and current algorithms provide a stepwise and standardized approach to conduct resuscitation. This review provides the pathophysiological and clinical rationale behind ANDROMEDA-SHOCK2, an ongoing multicenter randomized controlled trial that aims to compare a personalized resuscitation strategy based on clinical phenotyping and peripheral perfusion assessment, versus standard of care, in early septic shock resuscitation. (c) 2023 Published by Elsevier Espana, S.L.U. on behalf of Sociedad Espanola de Anestesiologia, Reanimacion y Terapeutica del Dolor.