Browsing by Author "Tapia, Pablo"

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    A cosmogenic nuclide-derived chronology of pre-Last Glacial Cycleglaciations during MIS 8 and MIS 6 in northern Patagonia
    (2023) Leger, Tancrede P. M.; Hein, Andrew S.; Rodes, Angel; Bingham, Robert G.; Schimmelpfennig, Irene; Fabel, Derek; Tapia, Pablo
    The precise environmental mechanisms control-ling Quaternary glacial cycles remain ambiguous. To address this problem, it is critical to better comprehend the drivers of spatio-temporal variability in ice-sheet evolution by establishing reliable chronologies of former outlet-glacier advances. When spanning multiple glacial cycles, such chronologies have the capacity to contribute to knowledge on the topic of interhemispheric phasing of glaciations and climate events. In southern Argentina, reconstructions of this kind are achievable, as Quaternary expansions of the Patagonian Ice Sheet have emplaced a well-preserved geomorphological record covering several glacial cycles. More-over, robust ice-sheet reconstructions from Patagonia are powerful barometers of former climate change, as Patagonian glaciers are influenced by the Southern Westerly Winds and the Antarctic Circumpolar Current coupled to them. It is essential to better constrain former shifts in these circulation mechanisms as they may have played a critical role in pacing regional and possibly global Quaternary climate change. Here, we present a new set of cosmogenic 10Be and 26Al exposure ages from pre-Last Glacial Cycle moraine boulder, glaciofluvial outwash cobble, and bedrock samples. This dataset constitutes the first direct chronology dating pre-Last Glacial Maximum (LGM) glacier advances in northern Patagonia and completes our effort to date the entire pre-served moraine record of the Rio Corcovado valley system (43 degrees S, 71 degrees W). We find that the outermost margins of the study site depict at least three distinct pre-Last Glacial Cycle stadials occurring around 290-270, 270-245, and 130- 150 ka. Combined with the local LGM chronology, we dis-cover that a minimum of four distinct Pleistocene stadials occurred during Marine Isotope Stages 8, 6, and 2 in northern Patagonia. Evidence for Marine Isotope Stage 4 and 3 deposits were not found at the study site. This may illustrate former longitudinal and latitudinal asynchronies in the Patagonian Ice Sheet mass balance during these Marine Isotope Stages. We find that the most extensive middle-to-late Pleistocene expansions of the Patagonian Ice Sheet appear to be out of phase with local summer insolation intensity but synchronous with orbitally controlled periods of longer and colder winters. Our findings thus enable the exploration of the potential roles of seasonality and seasonal duration in driving the southern mid-latitude ice-sheet mass balance, and they facilitate novel glacio-geomorphological interpretations for the study region. They also provide empirical constraints on former ice-sheet extent and dynamics that are essential for calibrating numerical ice-sheet and glacial isostatic adjustment models.
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    AGPAT2 deficiency impairs adipogenic differentiation in primary cultured preadipocytes in a non-autophagy or apoptosis dependent mechanism
    (2015) Fernandez Galilea, Marta; Tapia, Pablo; Cautivo Reyes, Kelly Margarita; Morselli, Eugenia; Cortés Mora, Víctor Antonio
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    Circulating Endothelial Cells From Septic Shock Patients Convert to Fibroblasts Are Associated With the Resuscitation Fluid Dose and Are Biomarkers for Survival Prediction.
    (2019) Tapia, Pablo; Gatica, Sebastian; Cortés-Rivera, Cristian; Otero, Carolina; Becerra, Álvaro; Riedel, Claudia A.; Cabello-Verrugio, Claudio; Kalergis, Alexis M.; Simon, Felipe
    OBJECTIVES:To determine whether circulating endothelial cells from septic shock patients and from nonseptic shock patients are transformed in activated fibroblast by changing the expression level of endothelial and fibrotic proteins, whether the level of the protein expression change is associated with the amount of administered resuscitation fluid, and whether this circulating endothelial cell protein expression change is a biomarker to predict sepsis survival. DESIGN:Prospective study. SETTING:Medical-surgical ICUs in a tertiary care hospital. PATIENTS:Forty-three patients admitted in ICU and 22 healthy volunteers. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Circulating mature endothelial cells and circulating endothelial progenitor cells from septic shock and nonseptic shock patients showed evidence of endothelial fibrosis by changing the endothelial protein expression pattern. The endothelial proteins were downregulated, whereas fibroblast-specific markers were increased. The magnitude of the expression change in endothelial and fibrotic proteins was higher in the septic shock nonsurvivors patients but not in nonseptic shock. Interestingly, the decrease in the endothelial protein expression was correlated with the administered resuscitation fluid better than the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores in the septic shock nonsurvivors patients but not in nonseptic shock. Notably, the significant difference between endothelial and fibrotic protein expression indicated a nonsurvival outcome in septic shock but not in nonseptic shock patients. Remarkably, area under the receiver operating characteristic curve analysis showed that endothelial protein expression levels predicted the survival outcome better than the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores in septic shock but not in nonseptic shock patients. CONCLUSIONS:Circulating endothelial cells from septic shock patients are acutely converted into fibroblasts. Endothelial and fibrotic protein expression level are associated with resuscitation fluid administration magnitude and can be used as biomarkers for an early survival diagnosis of sepsis.
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    Dexmedetomidine ameliorates gut lactate production and impairment of exogenous lactate clearance in an endotoxic sheep model
    (2015) Hernández P., Glenn; Tapia, Pablo; Bruhn, Alejandro; Soto, Dagoberto; Alegría, Leyla; Jarufe Cassis, Nicolás; Menchaca, Rodrigo; Meissner, Arturo; Vives, María Ignacia; Ospina Tascón, Gustavo A.; Luengo, Cecilia; Bakker, Jan
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    Early and severe impairment of lactate clearance in endotoxic shock is not related to liver hypoperfusion: preliminary report
    (2014) Tapia, Pablo; Soto, Dagoberto; Bruhn, Alejandro; Regueira Heskia, Tomás; Jarufe Cassis, Nicolás; Alegría, Leyla; Bachler, J. P.; Leon, F.; Vicuña, C.; Hernández P., Glenn
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    Effect of a lung rest strategy during ECMO in a porcine acute lung injury model
    (2015) Araos, J.; Tapia, Pablo; Alegría, Leyla; García Cañete, Patricia; Rodríguez, F.; Amthauer, M.; Castro, G.; Soto, Dagoberto; Damiani Rebolledo, L. Felipe; Bugedo Tarraza, Guillermo; Bruhn, Alejandro; Cruces, Pablo; Salomon, Tatiana; Erranz, B.; Carreño, P.; Medina, T.
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    Effects of dexmedetomidine and esmolol on systemic hemodynamics and exogenous lactate clearance in early experimental septic shock
    (2016) Hernández P., Glenn; Tapia, Pablo; Alegría, Leyla; Soto, Dagoberto; Jarufe Cassis, Nicolás; Achurra Tirado, Pablo; Rebolledo, Rolando; Bruhn, Alejandro; Castro, Ricardo; Kattan Tala, Eduardo José; Bakker, Jan; Luengo, Cecilia; Gomez, Jussara; Ospina Tascón, Gustavo
    Abstract Background Persistent hyperlactatemia during septic shock is multifactorial. Hypoperfusion-related anaerobic production and adrenergic-driven aerobic generation together with impaired lactate clearance have been implicated. An excessive adrenergic response could contribute to persistent hyperlactatemia and adrenergic modulation might be beneficial. We assessed the effects of dexmedetomidine and esmolol on hemodynamics, lactate generation, and exogenous lactate clearance during endotoxin-induced septic shock. Methods Eighteen anesthetized and mechanically ventilated sheep were subjected to a multimodal hemodynamic/perfusion assessment including hepatic and portal vein catheterizations, total hepatic blood flow, and muscle microdialysis. After monitoring, all received a bolus and continuous infusion of endotoxin. After 1 h they were volume resuscitated, and then randomized to endotoxin-control, endotoxin-dexmedetomidine (sequential doses of 0.5 and 1.0 μg/k/h) or endotoxin-esmolol (titrated to decrease basal heart rate by 20 %) groups. Samples were taken at four time points, and exogenous lactate clearance using an intravenous administration of sodium L-lactate (1 mmol/kg) was performed at the end of the experiments. Results Dexmedetomidine and esmolol were hemodynamically well tolerated. The dexmedetomidine group exhibited lower epinephrine levels, but no difference in muscle lactate. Despite progressive hypotension in all groups, both dexmedetomidine and esmolol were associated with lower arterial and portal vein lactate levels. Exogenous lactate clearance was significantly higher in the dexmedetomidine and esmolol groups. Conclusions Dexmedetomidine and esmolol were associated with lower arterial and portal lactate levels, and less impairment of exogenous lactate clearance in a model of septic shock. The use of dexmedetomidine and esmolol appears to be associated with beneficial effects on gut lactate generation and lactate clearance and exhibits no negative impact on systemic hemodynamics.Abstract Background Persistent hyperlactatemia during septic shock is multifactorial. Hypoperfusion-related anaerobic production and adrenergic-driven aerobic generation together with impaired lactate clearance have been implicated. An excessive adrenergic response could contribute to persistent hyperlactatemia and adrenergic modulation might be beneficial. We assessed the effects of dexmedetomidine and esmolol on hemodynamics, lactate generation, and exogenous lactate clearance during endotoxin-induced septic shock. Methods Eighteen anesthetized and mechanically ventilated sheep were subjected to a multimodal hemodynamic/perfusion assessment including hepatic and portal vein catheterizations, total hepatic blood flow, and muscle microdialysis. After monitoring, all received a bolus and continuous infusion of endotoxin. After 1 h they were volume resuscitated, and then randomized to endotoxin-control, endotoxin-dexmedetomidine (sequential doses of 0.5 and 1.0 μg/k/h) or endotoxin-esmolol (titrated to decrease basal heart rate by 20 %) groups. Samples were taken at four time points, and exogenous lactate clearance using an intravenous administration of sodium L-lactate (1 mmol/kg) was performed at the end of the experiments. Results Dexmedetomidine and esmolol were hemodynamically well tolerated. The dexmedetomidine group exhibited lower epinephrine levels, but no difference in muscle lactate. Despite progressive hypotension in all groups, both dexmedetomidine and esmolol were associated with lower arterial and portal vein lactate levels. Exogenous lactate clearance was significantly higher in the dexmedetomidine and esmolol groups. Conclusions Dexmedetomidine and esmolol were associated with lower arterial and portal lactate levels, and less impairment of exogenous lactate clearance in a model of septic shock. The use of dexmedetomidine and esmolol appears to be associated with beneficial effects on gut lactate generation and lactate clearance and exhibits no negative impact on systemic hemodynamics.
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    Endotoxin-Induced Endothelial Fibrosis Is Dependent on Expression of Transforming Growth Factors beta 1 and beta 2
    (2014) Echeverría, César; Montorfano, Ignacio; Tapia, Pablo; Riedel, Claudia; Cabello Verrugio, Claudio Alejandro; Simon, Felipe
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    Endotoxin-induced vascular endothelial cell migration is dependent on TLR4/NF-¿B pathway, NAD(P)H oxidase activation, and transient receptor potential melastatin 7 calcium channel activity
    (2014) Sarmiento, D.; Montorfano, I.; Cáceres, M.; Echeverría, C.; Fernández, R.; Cabello Verrugio, Claudio Alejandro; Cerda, O.; Tapia, Pablo; Simón, F.
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    Extended extracorporeal lung support in a porcine acute lung injury model. Feasibility and preliminary data
    (2014) Bruhn, Alejandro; Cruces, P.; Tapia, Pablo; García Cañete, Patricia; Alegría, Leyla; Araos, J.; Soto, Dagoberto; Rodríguez, F.; Amthauer, M.; Rodríguez, D.
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    Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel
    (2015) Sarmiento, Daniela; Montorfano, Ignacio; Cerda, Oscar; Caceres, Monica; Becerra, Alvaro; Cabello-Verrugio, Claudio; Elorza, Alvaro A.; Riedel, Claudia; Tapia, Pablo; Velasquez, Luis A.; Varela, Diego; Simon, Felipe
    A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer. Oxidative stress mediates several pathological functions, including an exacerbated EC migration. Because cell migration critically depends on calcium channel-mediated Ca2+ influx, the molecular identification of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense investigation.
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    Liquid extracorporeal carbon dioxide removal: use of THAM (tris-hydroxymethyl aminomethane) coupled to hemofiltration to control hypercapnic acidosis in a porcine model of protective mechanical ventilation
    (2016) Tapia, Pablo; Lillo, Felipe; Soto, Dagoberto; Escobar, Leslie; Simon, Felipe; Hernandez, Karina; Alegria, Leyla; Bruhn, Alejandro
    A promising approach to facilitate protective mechanical ventilation is the use of extracorporeal CO2 removal techniques. Several strategies based on membrane gas exchangers have been developed. However, these techniques are still poorly available. The goal of this study was to assess the efficacy and safety of THAM infusion coupled to hemofiltration for the management of hypercapnic acidosis. A severe respiratory acidosis was induced in seven anesthetized pigs. Five of them were treated with THAM 8-mmol . kg(-1) . h(-1) coupled to hemofiltration (THAM+HF group) at 100 mL . kg(-1) . h(-1). After 18-hours of treatment the THAM infusion was stopped but hemofiltration was kept on until 24-hours. The 2 other animals were treated with THAM but without hemofiltration. After 1-hour of treatment in THAM+HF, PaCO2 rapidly decreased from a median of 89.0 (IQR) (80.0, 98.0) to 71.3 (65.8, 82.0) mmHg (P<0.05), while pH increased from 7.12 (7.01, 7.15) to 7.29 (7.27, 7.30) (P<0.05). Thereafter PaCO2 remained stable between 60-70 mmHg, while pH increased above 7.4. After stopping THAM at 18 hours of treatment a profound rebound effect was observed with severe hypercapnic acidosis. The most important side effect we observed was hyperosmolality, which reached a maximum of 330 (328, 332) mOsm . kg H2O-1 at T18. The animals treated only with THAM developed severe hypercapnia, despite the fact that pH returned to normal values, and died after 12 hours. Control-group had an uneven evolution until the end of the experiment. A combined treatment with THAM coupled to hemofiltration may be an effective treatment to control severe hypercapnic acidosis.
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    Procoagulant phenotype induced by oxidized high-density lipoprotein associates with acute kidney injury and death
    (2023) Prado, Yolanda; Perez, Lorena; Eltit, Felipe; Echeverria, Cesar; Llancalahuen, Felipe M.; Tapia, Pablo; Gonzalez, Pablo A.; Kalergis, Alexis M.; Cabello-Verrugio, Claudio; Simon, Felipe
    Background: Oxidative stress derived from severe systemic inflammation promotes conversion from high-density lipoprotein HDL to oxidized HDL (oxHDL), which interacts with vascular endothelial cells (ECs). OxHDL acquires procoagulant features playing a role in modulating coagulation, which has been linked with organ failure in ICU patients. However, whether oxHDL elicits a ECs-mediated procoagulant phenotype generating organ failure and death, and the underlying molecular mechanism is not known. Therefore, we studied whether oxHDL-treated rats and high-oxHDL ICU patients exhibit a procoagulant phenotype and its association with kidney injury and mortality and the endothelial underlying molecular mechanism. Methods: Human ECs, oxHDL-treated rats and ICU patients were subjected to several cellular and molecular studies, coagulation analyses, kidney injury assessment and mortality determination. Results: OxHDL-treated ECs showed a procoagulant protein expression reprograming characterized by increased E-/P-selectin and vWF mRNA expression through specific signaling pathways. OxHDL-treated rats exhibited a procoagulant phenotype and modified E-/P-selectin, vWF, TF and t-PA mRNA expression correlating with plasma TF, t-PA and D-dimer. Also, showed increased death events and the relative risk of death, and increased creat-inine, urea, BUN/creatinine ratio, KIM-1, NGAL, beta 2M, and decreased eGFR, all concordant with kidney injury, correlated with plasma TF, t-PA and D-dimer. ICU patients showed correlation between plasma oxHDL and increased creatinine, cystatin, BUN, BUN/creatinine ratio, KIM-1, NGAL, beta 2M, and decreased GFR. Notably, ICU high-oxHDL patients showed decreased survival. Interestingly, altered coagulation factors TF, t-PA and D-dimer correlated with both increased oxHDL levels and kidney injury markers, indicating a connection between these factors. Conclusion: Increased circulating oxHDL generates an endothelial-dependent procoagulant phenotype that as-sociates with acute kidney injury and increased risk of death.
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    Social support, self-rated health, treatment adherence and effectiveness in patients with type II diabetes and hypertension
    (2018) Poblete A., Fernando; Barticevic Lantadilla, Nicolás A.; Sapag Muñoz de la Peña, Jaime; Tapia, Pablo; Bastías, Gabriel; Quevedo, Diego; Valdés Martinic, Camila Fernanda; Bustamante Troncoso, Claudia Raquel; Alcayaga Rojas, Claudia Andrea; Pérez, Gabriel
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    Spheroids derived from the stromal vascular fraction of adipose tissue self-organize in complex adipose organoids and secrete leptin
    (2023) Robledo Plaza, Fermín Alberto; González Hódar, Lila Alejandra; Tapia, Pablo; Figueroa Toledo, Ana Maria; Ezquer, Fernando; Cortes Mora, Victor Antonio
    Abstract Background Adipose tissue-derived stromal vascular fraction (SVF) harbors multipotent cells with potential therapeutic relevance. We developed a method to form adipose spheroids (AS) from the SVF with complex organoid structure and enhanced leptin secretion upon insulin stimulation. Methods SVF was generated from the interscapular brown adipose tissue of newborn mice. Immunophenotype and stemness of cultured SVF were determined by flow cytometry and in vitro differentiation, respectively. Spheroids were generated in hanging drops and non-adherent plates and compared by morphometric methods. The adipogenic potential was compared between preadipocyte monolayers and spheroids. Extracellular leptin was quantified by immunoassay. Lipolysis was stimulated with isoprenaline and quantified by colorimetric methods. AS viability and ultrastructure were determined by confocal and transmission electron microscopy analyses. Results Cultured SVF contained Sca1 + CD29 + CD44 + CD11b- CD45- CD90- cells with adipogenic and chondrogenic but no osteogenic potential. Culture on non-adherent plates yielded the highest quantity and biggest size of spheroids. Differentiation of AS for 15 days in a culture medium supplemented with insulin and rosiglitazone resulted in greater Pparg, Plin1, and Lep expression compared to differentiated adipocytes monolayers. AS were viable and maintained leptin secretion even in the absence of adipogenic stimulation. Glycerol release after isoprenaline stimulation was higher in AS compared to adipocytes in monolayers. AS were composed of outer layers of unilocular mature adipocytes and an inner structure composed of preadipocytes, immature adipocytes and an abundant loose extracellular matrix. Conclusion Newborn mice adipose SVF can be efficiently differentiated into leptin-secreting AS. Prolonged stimulation with insulin and rosiglitazone allows the formation of structurally complex adipose organoids able to respond to adrenergic lipolytic stimulation.