Browsing by Author "Olmos Coelho, Pablo Roberto"

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    Acute lung injury by gastric fluid instillation: activation of myofibroblast apoptosis during injury resolution
    (2018) Ayala, Pedro; Torres, Jorge; Vivar, Raúl; Meneses, Manuel; Olmos Coelho, Pablo Roberto; San Martín, Tamara; Borzone, Gisella
    Abstract Background Gastric contents aspiration in humans has variable consequences depending on the volume of aspirate, ranging from subclinical pneumonitis to respiratory failure with up to 70% mortality. Several experimental approaches have been used to study this condition. In a model of single orotracheal instillation of gastric fluid we have shown that severe acute lung injury evolves from a pattern of diffuse alveolar damage to one of organizing pneumonia (OP), that later resolves leaving normal lung architecture. Little is known about mechanisms of injury resolution after a single aspiration that could be dysregulated with repetitive aspirations. We hypothesized that, in a similar way to cutaneous wound healing, apoptosis may participate in lung injury resolution by reducing the number of myofibroblasts and by affecting the balance between proteases and antiproteases. Our aim was to study activation of apoptosis as well as MMP-2/TIMP-2 balance in the sub-acute phase (4–14 days) of gastric fluid-induced lung injury. Methods Anesthesized Sprague-Dawley rats received a single orotracheal instillation of gastric fluid and were euthanized 4, 7 and 14 days later (n = 6/group). In lung tissue we studied caspase-3 activation and its location by double immunofluorescence for cleaved caspase-3 or TUNEL and alpha-SMA. MMP-2/TIMP-2 balance was studied by zymography and Western blot. BALF levels of TGF-β1 were measured by ELISA. Results An OP pattern with Masson bodies and granulomas was seen at days 4 and 7 that was no longer present at day 14. Cleaved caspase-3 increased at day 7 and was detected by immunofluorescence in Masson body-alpha-SMA-positive and –negative cells. TUNEL-positive cells at days 4 and 7 were located mainly in Masson bodies. Distribution of cleaved caspase-3 and TUNEL-positive cells at day 14 was similar to that in controls. At the peak of apoptosis (day 7), an imbalance between MMP-2 activity and TIMP-2 expression was produced by reduction in TIMP-2 expression. Conclusions Apoptosis is activated in Masson body-alpha-SMA–positive and –negative cells during the sub-acute phase of gastric fluid-induced lung injury. This mechanism likely contributes to OP resolution, by reducing myofibroblast number and new collagen production. In addition, pre-formed collagen degradation is favored by an associated MMP-2/TIMP-2 imbalance.
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    Acute lung injury induced by whole gastric fluid: hepatic acute phase response contributes to increase lung antiprotease protection
    (2016) Ayala, Pedro; Meneses, Manuel; Olmos Coelho, Pablo Roberto; Montalva, Rebeca; Droguett Quezada, Karla Denise.; Rios Raggio, Mariana; Borzone, Gisella
    Abstract Background Gastric contents aspiration in humans is a risk factor for severe respiratory failure with elevated mortality. Although aspiration-induced local lung inflammation has been studied in animal models, little is known about extrapulmonary effects of aspiration. We investigated whether a single orotracheal instillation of whole gastric fluid elicits a liver acute phase response and if this response contributes to enrich the alveolar spaces with proteins having antiprotease activity. Methods In anesthetized Sprague-Dawley rats receiving whole gastric fluid, we studied at different times after instillation (4 h −7 days): changes in blood cytokines and acute phase proteins (fibrinogen and the antiproteases alpha1-antitrypsin and alpha2-macroglobulin) as well as liver mRNA expression of the two antiproteases. The impact of the systemic changes on lung antiprotease defense was evaluated by measuring levels and bioactivity of antiproteases in broncho-alveolar lavage fluid (BALF). Markers of alveolar-capillary barrier derangement were also studied. Non-parametric ANOVA (Kruskall-Wallis) and linear regression analysis were used. Results Severe peribronchiolar injury involving edema, intra-alveolar proteinaceous debris, hemorrhage and PMNn cell infiltration was seen in the first 24 h and later resolved. Despite a large increase in several lung cytokines, only IL-6 was found elevated in blood, preceding increased liver expression and blood concentration of both antiproteases. These changes, with an acute phase response profile, were significantly larger for alpha2-macroglobulin (40-fold increment in expression with 12-fold elevation in blood protein concentration) than for alpha1-antitrypsin (2–3 fold increment in expression with 0.5-fold elevation in blood protein concentration). Both the increment in capillary-alveolar antiprotease concentration gradient due to increased antiprotease liver synthesis and a timely-associated derangement of the alveolar-capillary barrier induced by aspiration, contributed a 58-fold and a 190-fold increase in BALF alpha1-antitrypsin and alpha2-macroglobulin levels respectively (p < 0.001). Conclusions Gastric contents-induced acute lung injury elicits a liver acute phase response characterized by increased mRNA expression of antiproteases and elevation of blood antiprotease concentrations. Hepatic changes act in concert with derangement of the alveolar capillary barrier to enrich alveolar spaces with antiproteases. These findings may have significant implications decreasing protease burden, limiting injury in this and other models of acute lung injury and likely, in recurrent aspiration.
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    Assessment of the Role of Metabolic Determinants on the Relationship between Insulin Sensitivity and Secretion
    (2016) Galgani Fuentes, José; Gómez, Carmen; Mizgier Rojas, María Luisa; Gutiérrez, Juan; Santos Martín, José Luis; Olmos Coelho, Pablo Roberto; Mari, Andrea
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    Cetoacidosis diabética : Casuística 2008-2012, epidemiología y fisiopatología
    (2014) Olmos Coelho, Pablo Roberto; Donoso Henríquez, Aníbal Tomás; Arab Verdugo, Juan Pablo; Niklitschek, I.; Mertens, N.; Arce, E.; Lemus, R.; Serrano Larrea, Valentina; Grassi Corrales, Bruno; Strodthoff Simunovic, Kristel; Abbott Cáceres, Eduardo Francisco; Aizman, Andrés; González, M.
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    Changes in the pattern of fibrosis in the rat lung with repetitive orotracheal instillations of gastric contents: evidence of persistent collagen accumulation
    (2018) Ayala, Pedro; Torres, Jorge; Vivar, Raul; Olmos Coelho, Pablo Roberto; Meneses, Manuel; Borzone, Gisella
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    Cost-effectiveness of a diabetes detection program in childbearing women to prevent malformations
    (2020) Olmos Coelho, Pablo Roberto; Borzone Tassara, Gisella Rosa; Poblete L., José A.; Oyarzún Ebensperger, Enrique
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    Development and assessment of the disposition index based on the oral glucose tolerance test in subjects with different glycaemic status
    (2016) Santos Martín, José Luis; Yévenes, I.; Cataldo Bascuñan, Luis Rodrigo; Morales, M.; Galgani Fuentes, José; Arancibia, C.; Vega, J.; Olmos Coelho, Pablo Roberto; Flores, M.; Valderas Igor, Juan Patricio; Pollak, F.
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    Direct Relationship Between Metabolic Flexibility Measured During Glucose Clamp and Prolonged Fast in Men
    (2020) Fernández Verdejo, Rodrigo; Castro Sepúlveda, Mauricio; Gutierrez-Pino, J.; Malo-Vintimilla, L.; López Fuenzalida, Antonio Eduardo; Olmos Coelho, Pablo Roberto; Santos Martín, José Luis; Galgani Fuentes, José
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    Effectiveness on maternal and offspring metabolic control of a home-based dietary counseling intervention and DHA supplementation in obese/overweight pregnant women (MIGHT study) : a randomized controlled trial-Study protocol
    (2018) Garmendia, María Luisa; Corvalán, Camila; Casanello Toledo, Paola Cecilia; Araya, Marcela; Flores, Marcela; Bravo, Alfredo; Kusanovic, Juan Pedro; Olmos Coelho, Pablo Roberto; Uauy, Ricardo
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    Elastin degradation products in acute lung injury induced by gastric contents aspiration
    (2018) Ayala, Pedro; Vivar, Raúl; Montalva, Rebeca; Olmos Coelho, Pablo Roberto; Borzone, Gisella; Meneses, Manuel
    Abstract Background Gastric contents aspiration is a high-risk condition for acute lung injury (ALI). Consequences range from subclinical pneumonitis to respiratory failure, depending on the volume of aspirate. A large increment in inflammatory cells, an important source of elastase, potentially capable of damaging lung tissue, has been described in experimental models of aspiration. We hypothesized that in early stages of aspiration-induced ALI, there is proteolytic degradation of elastin, preceding collagen deposition. Our aim was to evaluate whether after a single orotracheal instillation of gastric fluid, there is evidence of elastin degradation. Methods Anesthesized Sprague-Dawley rats received a single orotracheal instillation of gastric fluid and were euthanized 4, 12 and 24 h and at day 4 after instillation (n = 6/group). We used immunodetection of soluble elastin in lung tissue and BALF and correlated BALF levels of elastin degradation products with markers of ALI. We investigated possible factors involved in elastin degradation and evaluated whether a similar pattern of elastin degradation can be found in BALF samples of patients with interstitial lung diseases known to have aspirated. Non-parametric ANOVA (Kruskall-Wallis) and linear regression analysis were used. Results We found evidence of early proteolytic degradation of lung elastin. Elastin degradation products are detected both in lung tissue and BALF in the first 24 h and are significantly reduced at day 4. They correlate significantly with ALI markers, particularly PMN cell count, are independent of acidity and have a similar molecular weight as those obtained using pancreatic elastase. Evaluation of BALF from patients revealed the presence of elastin degradation products not present in controls that are similar to those found in BALF of rats treated with gastric fluid. Conclusions A single instillation of gastric fluid into the lungs induces early proteolytic degradation of elastin, in relation to the magnitude of alveolar-capillary barrier derangement. PMN-derived proteases released during ALI are mostly responsible for this damage. BALF from patients showed elastin degradation products similar to those found in rats treated with gastric fluid. Long-lasting effects on lung elastic properties could be expected under conditions of repeated instillations of gastric fluid in experimental animals or repeated aspiration events in humans.
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    Fisiopatología de la retinopatía y nefropatía diabéticas
    (2009) Olmos Coelho, Pablo Roberto; Araya del Pino, Andrea Paz; González Carvallo, Cristian; Laso Ulloa, Pablo; Irribarra Pastenes, Verónica; Rubio Quiroz, Lorena Alejandra
    Despite the availability of multiple therapeutic approaches, diabetes mellitus with chronic hyperglycemia remains as the main cause of new cases of blindness and chronic renal failure in the western hemisphere. We herein review the molecular mechanisms by which chronic hyperglycemia causes retinopathy and nephropathy in type I and type 2 diabetic patients. Diabetic retinopathy develops silently along years or decades, producing symptoms only in its very late stages. Its slow development starts with the activation of aldose reductase, shortly followed by the destruction of the retinal pericyte cells, and ends in sudden blindness when vitreous hemorrhage ensues. Nephropathy, on the other hand, centers its pathophysiology in the mesangial cell, that starts as a modified smooth-muscle cell, and turns itself into a myo-fibroblast, produces such amounts of cytoplasm and extracellular protein that strangulates the glomerular capillaries and causes renal failure. After a detailed review of the molecular mechanisms of the aforementioned complications, we conclude that, apart from directing our attention to the emerging medications that are being developed to block these molecular pathways, we should never abandon the struggle for improving the glycemic control of our diabetic patients
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    Fluoxetine Impairs Insulin Secretion without Modifying Extracellular Serotonin Levels in MIN6 β-cells
    (2015) Cataldo Bascuñan, Luis Rodrigo; Cortés Mora, Víctor Antonio; Mizgier Rojas, María Luisa; Aranda, E.; Mezzano, Diego; Olmos Coelho, Pablo Roberto; Galgani Fuentes, José; Suazo, J.; Santos Martín, José Luis
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    Gestational Diabetes : Glycemic Control in the Last Two Weeks Before Delivery Contributes to Newborn Insulinemia
    (2018) Olmos Coelho, Pablo Roberto; Borzone, Gisella; Poblete L., José A.
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    Gestational diabetes and pre-pregnancy overweight: Possible factors involved in newborn macrosomia
    (2012) Olmos Coelho, Pablo Roberto; Borzone, Gisella; Olmos Borzone, Roberto Ignacio; Valencia, Claudio Nicolás; Bravo, Felipe Andrés; Hodgson Bunster, María Isabel; Belmar Jones, Cristián Gastón; Poblete Lizana, José Andrés; Escalona, Manuel Orlando; Gómez, Bernardita
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    Heteroplasmia de la mutación del ADN mitocondrial m.3243A>G en la diabetes y sordera de herencia materna
    (2013) Cataldo Bascuñan, Luis Rodrigo; Olmos Coelho, Pablo Roberto; Smalley Meylan, Susan Valerie; Díez, Alberto; Parada Daza, Alejandra; Gejman Enríquez, Roger; Fadic Ruiz, Ricardo Julio Nicolás; Santos Martín, José Luis
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    La hipótesis de Pedersen no es suficiente : otros nutrientes además de la glucosa explicarían la macrosomía fetal en pacientes diabéticas gestacionales con sobrepeso y buen control glicémico
    (2013) Olmos Coelho, Pablo Roberto; Martelo, G.; Reimer, V.; Rigotti Rivera, Attilio; Busso, Dolores; Belmar Jones, Cristián Gastón; González Pérez, Rogelio Iván; Goldenberg, D.; Samith Catalán, Bárbara Patricia; Santos Martín, José Luis; Escalona, M.; Quezada, T.; Faundez, J.; Nicklitschek, I.
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    In silico evaluation of a control system and algorithm for automated insulin infusion in the ICU setting
    (2010) Ortiz, José L.; Guarini Hermann, Marcelo Walter; Borzone, Gisella; Olmos Coelho, Pablo Roberto
    Abstract Background It is known that tight control of glucose in the Intensive Care Unit reduces morbidity and mortality not only in diabetic patients but also in those non-diabetics who become transiently hyperglycemic. Taking advantage of a recently marketed subcutaneous glucose sensor we designed an Automatic Insulin Infusion System (AIIS) for inpatient treatment, and tested its stability under simulated clinical conditions. Methods The system included: reference glucose, glucose sensor, insulin and glucose infusion controllers and emergency infusion logic. We carried out computer simulations using Matlab/Simulink®, in both common and worst-case conditions. Results The system was capable of controlling glucose levels without entering in a phase of catastrophic instability, even under severe simulated challenges. Care was taken to include in all simulations the 5-10 minute delay of the subcutaneous glucose signal when compared to the real-time serum glucose signal, a well-known characteristic of all subcutaneous glucose sensors. Conclusions When tested in-Silico, a commercially available subcutaneous glucose sensor allowed the stable functioning of a proportional-derivative Automatic Insulin Infusion System, which was able to maintain glucose within acceptable limits when using a well-established glucose response model simulating a patient. Testing of the system in vivo using animal models is now warranted.Abstract Background It is known that tight control of glucose in the Intensive Care Unit reduces morbidity and mortality not only in diabetic patients but also in those non-diabetics who become transiently hyperglycemic. Taking advantage of a recently marketed subcutaneous glucose sensor we designed an Automatic Insulin Infusion System (AIIS) for inpatient treatment, and tested its stability under simulated clinical conditions. Methods The system included: reference glucose, glucose sensor, insulin and glucose infusion controllers and emergency infusion logic. We carried out computer simulations using Matlab/Simulink®, in both common and worst-case conditions. Results The system was capable of controlling glucose levels without entering in a phase of catastrophic instability, even under severe simulated challenges. Care was taken to include in all simulations the 5-10 minute delay of the subcutaneous glucose signal when compared to the real-time serum glucose signal, a well-known characteristic of all subcutaneous glucose sensors. Conclusions When tested in-Silico, a commercially available subcutaneous glucose sensor allowed the stable functioning of a proportional-derivative Automatic Insulin Infusion System, which was able to maintain glucose within acceptable limits when using a well-established glucose response model simulating a patient. Testing of the system in vivo using animal models is now warranted.Abstract Background It is known that tight control of glucose in the Intensive Care Unit reduces morbidity and mortality not only in diabetic patients but also in those non-diabetics who become transiently hyperglycemic. Taking advantage of a recently marketed subcutaneous glucose sensor we designed an Automatic Insulin Infusion System (AIIS) for inpatient treatment, and tested its stability under simulated clinical conditions. Methods The system included: reference glucose, glucose sensor, insulin and glucose infusion controllers and emergency infusion logic. We carried out computer simulations using Matlab/Simulink®, in both common and worst-case conditions. Results The system was capable of controlling glucose levels without entering in a phase of catastrophic instability, even under severe simulated challenges. Care was taken to include in all simulations the 5-10 minute delay of the subcutaneous glucose signal when compared to the real-time serum glucose signal, a well-known characteristic of all subcutaneous glucose sensors. Conclusions When tested in-Silico, a commercially available subcutaneous glucose sensor allowed the stable functioning of a proportional-derivative Automatic Insulin Infusion System, which was able to maintain glucose within acceptable limits when using a well-established glucose response model simulating a patient. Testing of the system in vivo using animal models is now warranted.Abstract Background It is known that tight control of glucose in the Intensive Care Unit reduces morbidity and mortality not only in diabetic patients but also in those non-diabetics who become transiently hyperglycemic. Taking advantage of a recently marketed subcutaneous glucose sensor we designed an Automatic Insulin Infusion System (AIIS) for inpatient treatment, and tested its stability under simulated clinical conditions. Methods The system included: reference glucose, glucose sensor, insulin and glucose infusion controllers and emergency infusion logic. We carried out computer simulations using Matlab/Simulink®, in both common and worst-case conditions. Results The system was capable of controlling glucose levels without entering in a phase of catastrophic instability, even under severe simulated challenges. Care was taken to include in all simulations the 5-10 minute delay of the subcutaneous glucose signal when compared to the real-time serum glucose signal, a well-known characteristic of all subcutaneous glucose sensors. Conclusions When tested in-Silico, a commercially available subcutaneous glucose sensor allowed the stable functioning of a proportional-derivative Automatic Insulin Infusion System, which was able to maintain glucose within acceptable limits when using a well-established glucose response model simulating a patient. Testing of the system in vivo using animal models is now warranted.
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    Maternal Hypertriglyceridemia : A Link Between Maternal Overweight-Obesity and Macrosomia in Gestational Diabetes
    (2014) Olmos Coelho, Pablo Roberto; Rigotti Rivera, Attilio; Busso, Dolores; Berkowitz Fiebich, Loni; Santos Martín, José Luis; Borzone, Gisella; Poblete L., José A.; Vera Pérez-Gacitúa, Claudio Mauricio; Belmar Jones, Cristián Gastón; Samith Catalán, Bárbara Patricia; Goldenberg, Denisse; Acosta, Ana M.; Escalona, Manuel; Niklitschek, Ian; Mandiola, Jorge R.; Mertens, Nicolás