Gallbladder cholesterolosis is a nosological clinical entity where the central element is the dep... more Gallbladder cholesterolosis is a nosological clinical entity where the central element is the deposit of lipids in immune cells that reside under the gallbladder epithelium. The mechanisms involved in its development are not entirely clear, but they seem to have some resemblances that are observed in the wall of the arteries with atherosclerosis. The lipid-laden cells observed in the gallbladder wall appear to share many of the characteristics of atherosclerosis foam cells, which by means of scavenger receptors have endocited oxidized low-density lipoproteins and accumulate them in their cytoplasm. Foam cells, in themselves, are not dangerous, but in atherosclerosis at least they can become a problem when they are located in vessels and specific anatomic sites. The role they may have in the gallbladder is not known to date. We will review some considerations that seem relevant to us to elucidate if these entities share the same protagonist: macrophages transformed by modified lipids.
Obesity is a worldwide problem that also involves our country. It reduces life expectancy and rep... more Obesity is a worldwide problem that also involves our country. It reduces life expectancy and represents a high economic burden for individual and the society. A large amount of economic and human resources has been allocated for obesity control and prevention. Obesity is associated with the main non-transmissible diseases on this time: cardiovascular diseases, type 2 diabetes mellitus, arterial hypertension, osteoarticular disease and some types of cancer. The development of obesity include genetic, environmental and lifestyle factors. While lipid accumulates into the adipocyte, it becomes in a tissue with hypertrophy and hyperplasia and inflammatory cells infiltrate it. Although it is not known the primary stimulus that triggers this inflammatory phenomenon, it is known this has deleterious consequences in the local and systemic metabolism and give the obese phenotype with insulin resistance, atherogenesis and inflammation. Glucocorticoids are steroidal hormones with multiple acti...
LPS regulates the expression of GRα and GRβ isoforms in a epithelial cell line. HeLa cells were c... more LPS regulates the expression of GRα and GRβ isoforms in a epithelial cell line. HeLa cells were cultured with LPS for 24 h. The expression of GRα and GRβ was determined by Western blot. The median values of three different experiments, plotted as values relative to control are shown. * p
Mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii are associated wi... more Mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii are associated with the failure of sulfa prophylaxis. They can develop by selection in patients receiving sulfa drugs or be acquired via person-to-person transmission. DHPS mutations raise concern about the decreasing efficacy of sulfa drugs, the main available therapeutic tool for Pneumocystis pneumonia (PCP). The prevalence of Pneumocystis DHPS mutations was examined in Pneumocystis isolates from 56 sulfa-prophylaxis-naive adults with a first episode of PCP from 2002 to 2010 in Santiago, Chile. Their clinical history was reviewed to analyze the effect of these mutations on response to trimethoprim-sulfamethoxazole (TMP-SMX) therapy and outcome. Mutant genotypes occurred in 22 (48%) of 46 HIV-infected patients and in 5 (50%) of 10 HIV-uninfected patients. Compared to patients with a wild-type genotype, those with mutant genotypes were more likely to experience sulfa treatment-limiting adverse reactions ...
T U E S D A Y 920 Upregulation Of Glucocorticoids Beta Receptors In Severe Rsv Bronchiolitis In I... more T U E S D A Y 920 Upregulation Of Glucocorticoids Beta Receptors In Severe Rsv Bronchiolitis In Infants P. V. Diaz, R. Mammani, R. A. Pinto, A. A. Gaggero, M. R. Bono, J. Guerrero, A. Goecke; Faculty of Medicine, University of Chile, Santiago, CHILE, Faculty of Science, University of Chile, Santiago, CHILE. RATIONALE: The majority of studies on glucocorticoids treatment in RSV bronchiolitis conclude there are no beneficial effects. We hypothesized that RSV infected patients may have an up-regulation of the GCR-b expression, the isoform that is unable to bind cortisol and exert an antiinflammatory action. METHODS:We studied by RT-PCR the expression of a and bGCR in the peripheral blood mononuclear cells (PBMC) obtained from 50 RSV infected infants (less than 1 year of age) of diverse clinical severity, evaluated by a modified Tal’s clinical score (15mild to 85severe). In plasma we analyzed the level of cortisol by RIA and inflammatory cytokines: IL-6, IL-8,TNF-a, IL-1b, IL-12 and IL-10 by cytometric beads assay. Statistical analysis was performed by ANOVA. RESULTS: There has found a significant up-regulation of b GCR in patients with severe illness compared to those with mild disease (p<0.001) and also to a group of healthy control (p<0.01). The a/b GCR ratio was significantly decreased in infants with severe disease (p<0.05) compared to those with mild illness and with normal controls (p<0.01). The expression of b GCR has been positively correlated with the clinical score of severity (r50.51; p<0.0006). IL-6, IL-8 and cortisol in plasma were significantly increased in severe infected infants compared with mild infected (p<0.05) and healthy controls (p<0.01). CONCLUSIONS: The decrease of the a/bGCR ratio by an up-regulation of b receptors may partly explain the insensitivity to corticoids treatments in RSV infected infants.
... Caroll Beltrán M.(1), Julia Guerrero P.(2), Pedro Castro N.(1), Alexis Peralta B.(1), Carolin... more ... Caroll Beltrán M.(1), Julia Guerrero P.(2), Pedro Castro N.(1), Alexis Peralta B.(1), Carolina Figueroa C.(3), Rodrigo Quera P.(4,5 ... Las CDs intestinales jue-gan un papel crucial en el establecimiento de un balance entre la tolerancia y la inmunidad frente a antígenos ingeridos ...
Cardiovascular disease (CVD) is the most frequent cause of premature death according to data from... more Cardiovascular disease (CVD) is the most frequent cause of premature death according to data from the American Heart Association and World Health Organization. Incidence and prevalence are on the rise. Rheumatoid Arthritis (RA) is the most common autoimmune disease. It is a chronic and systemic disease characterized by articular involvement with deformity ranging from persistent pain to premature disability. CVD is the most frequent cause of death in RA patients, even more than in diabetes mellitus 2 or chronic kidney disease. Multiple CVD risk scales have been tested in order to obtain a more accurate prediction of premature death by stroke or myocardial infarction in RA patients. Most of the scales, even those adjusted including RA features like inflammation and antibodies titles, have failed to properly predict the real CVD risk. Individually, RA specific autoantibodies have been related with increased CVD risk and multiple mechanistic explanations have arisen, generating even a ...
Measurement of exhaled nitric oxide fraction in lung diseases Exhaled Nitric Oxide fraction measu... more Measurement of exhaled nitric oxide fraction in lung diseases Exhaled Nitric Oxide fraction measurement is a new method for the evaluation of respiratory diseases. It has good correlation with airway inflammation and decreases with the administration of corticosteroids. It is useful as a complement for the diagnosis of asthma, Chronic Obstructive Pulmonary Disease, Cystic Fibrosis and Primary Ciliary Dyskinesia among other respiratory diseases that generate inflammation in the airway. Its assessment is easy, non-invasive, and safe, and the result is obtained immediately. It can be used routinely to evaluate the response and adherence to treatments. This article reviews the biology of Nitric Oxide, and the measurement, interpretation, and main clinical uses of Exhaled Nitric Oxide Fraction.
Stress hyperglycemia is frequently diagnosed in septic patients in critical care units (ICU) and ... more Stress hyperglycemia is frequently diagnosed in septic patients in critical care units (ICU) and it is associated with greater illness severity and higher morbimortality rates. In response to an acute injury, high levels of counterregulatory hormones such as glucocorticoids and catecholamines are released causing increased hepatic gluconeogenesis and insulin resistance. Furthermore, during sepsis, proinflammatory cytokines also participate in the pathogenesis of this phenomenon. Septic patients represent a subtype of the critical ill patients in the ICU: this metabolic disarrangement management strategies and insulin therapy recommendations had been inconsistent. In this article, we describe the pathophysiological mechanisms of stress hyperglycemia in critical patients including the action of hormones, inflammatory cytokines and tissue resistance to insulin. In addition, we analyzed the main published studies for the treatment of acute hyperglycemia in critical patients.
Understanding cortisol action in acute inflammation. A view from the adrenal gland to the target ... more Understanding cortisol action in acute inflammation. A view from the adrenal gland to the target cell Glucocorticoids (cortisol in humans) are essential for numerous biological functions. Among critically ill patients, therapy with cortisol has gained strength in recent years, but clinical results have been mixed. A series of events, that may explain the diversity of clinical responses, occur from the synthesis of cortisol in the adrenal gland to the activation of the cortisol receptor by the hormone when it enters the nucleus of the target cell. Some of these events are revised; a proposition for identifying critically ill patients who may benefit with this therapy is suggested.
A young male presented with panhypopituitarism (including diabetes insipidus) and temporal lobe e... more A young male presented with panhypopituitarism (including diabetes insipidus) and temporal lobe epilepsy. A histology specimen of cutaneous papules was diagnostic of non-Langerhans histiocytosis. The diagnosis of xanthoma granulomata was considered based on the clinical and brain MRI findings. Brain lesions significantly worsened over time despite radiotherapy until anakinra induced a complete clinical and radiological remission of all active lesions. Although a single case, the outcome of this patient with xanthoma disseminatum treated with an interleukin-1 receptor antagonist opens and strengthens new and recent physiopathogenic and treatment perspectives for the otherwise difficult-to-treat non-Langerhans cell histiocytosis. Similar results with anakinra have been observed in patients with Erdheim-Chester disease and in multicentric reticulohistiocytosis.
... Zoltán Berger F, Rodrigo Quera P, Jaime Poniachik T, Danny Oksenberg R, Julia Guerrero P. ...... more ... Zoltán Berger F, Rodrigo Quera P, Jaime Poniachik T, Danny Oksenberg R, Julia Guerrero P. ... intrapancreáticas, con particular énfasis en la estimación cuantitativa de la necrosis pancreática, y además las colecciones peripancreáticas, calculando un puntaje de gravedad ...
Intrathoracic blood volume versus pulmonary artery occlusion pressure as estimators of cardiac pr... more Intrathoracic blood volume versus pulmonary artery occlusion pressure as estimators of cardiac preload in critically ill patients Background: Monitoring of cardiac preload by determination of pulmonary artery occlusion pressure (PAOP) has been traditionally used to guide fluid therapy to optimize cardiac output (CO). Since factors such as intrathoracic pressure and ventricular compliance may modify PAOP, volumetric estimators of preload have been developed. The PiCCO system is able to measure CO and intrathoracic blood volume (ITBV) by transpulmonary thermodilution. Aim: To compare a volumetric (ITBV) versus a pressure (PAOP) determination to accurately estimate cardiac preload in severely ill patients. Patients and Methods: From June 2001 to October 2003, 22 mechanically ventilated patients with hemodynamic instability underwent hemodynamic monitoring with pulmonary artery catheter (PAC) and PiCCO system. ITBV index (ITBVI), PAOP and CI were measured simultaneously by both methods. One hundred thirty eight deltas (∆) were obtained from the difference of ITBVI, PAOP, CI-PAC and CI-PiCCO between 6-12 am and 6-12 pm. Linear regression analysis of ∆ ITBVI versus ∆ CI-PiCCO and ∆ PAOP versus ∆ CI-PAC were made. Results: Mean age of patients was 60.8 ± 19.4 years. APACHE II was 23.9 ± 7. Fifteen patients met criteria for acute respiratory distress syndrome (ARDS). Delta ITBVI significantly correlated with ∆ CI-PiCCO (r=0.54; 95% confidence interval = 0.41-0.65; p <0.01). There was no correlation between ∆ PAOP and ∆ CI-PAC. Conclusion: ITBVI correlated better with CI than PAOP, and therefore it seems to be a more accurate estimator of preload in unstable, mechanically ventilated patients (
Gallbladder cholesterolosis is a nosological clinical entity where the central element is the dep... more Gallbladder cholesterolosis is a nosological clinical entity where the central element is the deposit of lipids in immune cells that reside under the gallbladder epithelium. The mechanisms involved in its development are not entirely clear, but they seem to have some resemblances that are observed in the wall of the arteries with atherosclerosis. The lipid-laden cells observed in the gallbladder wall appear to share many of the characteristics of atherosclerosis foam cells, which by means of scavenger receptors have endocited oxidized low-density lipoproteins and accumulate them in their cytoplasm. Foam cells, in themselves, are not dangerous, but in atherosclerosis at least they can become a problem when they are located in vessels and specific anatomic sites. The role they may have in the gallbladder is not known to date. We will review some considerations that seem relevant to us to elucidate if these entities share the same protagonist: macrophages transformed by modified lipids.
Obesity is a worldwide problem that also involves our country. It reduces life expectancy and rep... more Obesity is a worldwide problem that also involves our country. It reduces life expectancy and represents a high economic burden for individual and the society. A large amount of economic and human resources has been allocated for obesity control and prevention. Obesity is associated with the main non-transmissible diseases on this time: cardiovascular diseases, type 2 diabetes mellitus, arterial hypertension, osteoarticular disease and some types of cancer. The development of obesity include genetic, environmental and lifestyle factors. While lipid accumulates into the adipocyte, it becomes in a tissue with hypertrophy and hyperplasia and inflammatory cells infiltrate it. Although it is not known the primary stimulus that triggers this inflammatory phenomenon, it is known this has deleterious consequences in the local and systemic metabolism and give the obese phenotype with insulin resistance, atherogenesis and inflammation. Glucocorticoids are steroidal hormones with multiple acti...
LPS regulates the expression of GRα and GRβ isoforms in a epithelial cell line. HeLa cells were c... more LPS regulates the expression of GRα and GRβ isoforms in a epithelial cell line. HeLa cells were cultured with LPS for 24 h. The expression of GRα and GRβ was determined by Western blot. The median values of three different experiments, plotted as values relative to control are shown. * p
Mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii are associated wi... more Mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii are associated with the failure of sulfa prophylaxis. They can develop by selection in patients receiving sulfa drugs or be acquired via person-to-person transmission. DHPS mutations raise concern about the decreasing efficacy of sulfa drugs, the main available therapeutic tool for Pneumocystis pneumonia (PCP). The prevalence of Pneumocystis DHPS mutations was examined in Pneumocystis isolates from 56 sulfa-prophylaxis-naive adults with a first episode of PCP from 2002 to 2010 in Santiago, Chile. Their clinical history was reviewed to analyze the effect of these mutations on response to trimethoprim-sulfamethoxazole (TMP-SMX) therapy and outcome. Mutant genotypes occurred in 22 (48%) of 46 HIV-infected patients and in 5 (50%) of 10 HIV-uninfected patients. Compared to patients with a wild-type genotype, those with mutant genotypes were more likely to experience sulfa treatment-limiting adverse reactions ...
T U E S D A Y 920 Upregulation Of Glucocorticoids Beta Receptors In Severe Rsv Bronchiolitis In I... more T U E S D A Y 920 Upregulation Of Glucocorticoids Beta Receptors In Severe Rsv Bronchiolitis In Infants P. V. Diaz, R. Mammani, R. A. Pinto, A. A. Gaggero, M. R. Bono, J. Guerrero, A. Goecke; Faculty of Medicine, University of Chile, Santiago, CHILE, Faculty of Science, University of Chile, Santiago, CHILE. RATIONALE: The majority of studies on glucocorticoids treatment in RSV bronchiolitis conclude there are no beneficial effects. We hypothesized that RSV infected patients may have an up-regulation of the GCR-b expression, the isoform that is unable to bind cortisol and exert an antiinflammatory action. METHODS:We studied by RT-PCR the expression of a and bGCR in the peripheral blood mononuclear cells (PBMC) obtained from 50 RSV infected infants (less than 1 year of age) of diverse clinical severity, evaluated by a modified Tal’s clinical score (15mild to 85severe). In plasma we analyzed the level of cortisol by RIA and inflammatory cytokines: IL-6, IL-8,TNF-a, IL-1b, IL-12 and IL-10 by cytometric beads assay. Statistical analysis was performed by ANOVA. RESULTS: There has found a significant up-regulation of b GCR in patients with severe illness compared to those with mild disease (p<0.001) and also to a group of healthy control (p<0.01). The a/b GCR ratio was significantly decreased in infants with severe disease (p<0.05) compared to those with mild illness and with normal controls (p<0.01). The expression of b GCR has been positively correlated with the clinical score of severity (r50.51; p<0.0006). IL-6, IL-8 and cortisol in plasma were significantly increased in severe infected infants compared with mild infected (p<0.05) and healthy controls (p<0.01). CONCLUSIONS: The decrease of the a/bGCR ratio by an up-regulation of b receptors may partly explain the insensitivity to corticoids treatments in RSV infected infants.
... Caroll Beltrán M.(1), Julia Guerrero P.(2), Pedro Castro N.(1), Alexis Peralta B.(1), Carolin... more ... Caroll Beltrán M.(1), Julia Guerrero P.(2), Pedro Castro N.(1), Alexis Peralta B.(1), Carolina Figueroa C.(3), Rodrigo Quera P.(4,5 ... Las CDs intestinales jue-gan un papel crucial en el establecimiento de un balance entre la tolerancia y la inmunidad frente a antígenos ingeridos ...
Cardiovascular disease (CVD) is the most frequent cause of premature death according to data from... more Cardiovascular disease (CVD) is the most frequent cause of premature death according to data from the American Heart Association and World Health Organization. Incidence and prevalence are on the rise. Rheumatoid Arthritis (RA) is the most common autoimmune disease. It is a chronic and systemic disease characterized by articular involvement with deformity ranging from persistent pain to premature disability. CVD is the most frequent cause of death in RA patients, even more than in diabetes mellitus 2 or chronic kidney disease. Multiple CVD risk scales have been tested in order to obtain a more accurate prediction of premature death by stroke or myocardial infarction in RA patients. Most of the scales, even those adjusted including RA features like inflammation and antibodies titles, have failed to properly predict the real CVD risk. Individually, RA specific autoantibodies have been related with increased CVD risk and multiple mechanistic explanations have arisen, generating even a ...
Measurement of exhaled nitric oxide fraction in lung diseases Exhaled Nitric Oxide fraction measu... more Measurement of exhaled nitric oxide fraction in lung diseases Exhaled Nitric Oxide fraction measurement is a new method for the evaluation of respiratory diseases. It has good correlation with airway inflammation and decreases with the administration of corticosteroids. It is useful as a complement for the diagnosis of asthma, Chronic Obstructive Pulmonary Disease, Cystic Fibrosis and Primary Ciliary Dyskinesia among other respiratory diseases that generate inflammation in the airway. Its assessment is easy, non-invasive, and safe, and the result is obtained immediately. It can be used routinely to evaluate the response and adherence to treatments. This article reviews the biology of Nitric Oxide, and the measurement, interpretation, and main clinical uses of Exhaled Nitric Oxide Fraction.
Stress hyperglycemia is frequently diagnosed in septic patients in critical care units (ICU) and ... more Stress hyperglycemia is frequently diagnosed in septic patients in critical care units (ICU) and it is associated with greater illness severity and higher morbimortality rates. In response to an acute injury, high levels of counterregulatory hormones such as glucocorticoids and catecholamines are released causing increased hepatic gluconeogenesis and insulin resistance. Furthermore, during sepsis, proinflammatory cytokines also participate in the pathogenesis of this phenomenon. Septic patients represent a subtype of the critical ill patients in the ICU: this metabolic disarrangement management strategies and insulin therapy recommendations had been inconsistent. In this article, we describe the pathophysiological mechanisms of stress hyperglycemia in critical patients including the action of hormones, inflammatory cytokines and tissue resistance to insulin. In addition, we analyzed the main published studies for the treatment of acute hyperglycemia in critical patients.
Understanding cortisol action in acute inflammation. A view from the adrenal gland to the target ... more Understanding cortisol action in acute inflammation. A view from the adrenal gland to the target cell Glucocorticoids (cortisol in humans) are essential for numerous biological functions. Among critically ill patients, therapy with cortisol has gained strength in recent years, but clinical results have been mixed. A series of events, that may explain the diversity of clinical responses, occur from the synthesis of cortisol in the adrenal gland to the activation of the cortisol receptor by the hormone when it enters the nucleus of the target cell. Some of these events are revised; a proposition for identifying critically ill patients who may benefit with this therapy is suggested.
A young male presented with panhypopituitarism (including diabetes insipidus) and temporal lobe e... more A young male presented with panhypopituitarism (including diabetes insipidus) and temporal lobe epilepsy. A histology specimen of cutaneous papules was diagnostic of non-Langerhans histiocytosis. The diagnosis of xanthoma granulomata was considered based on the clinical and brain MRI findings. Brain lesions significantly worsened over time despite radiotherapy until anakinra induced a complete clinical and radiological remission of all active lesions. Although a single case, the outcome of this patient with xanthoma disseminatum treated with an interleukin-1 receptor antagonist opens and strengthens new and recent physiopathogenic and treatment perspectives for the otherwise difficult-to-treat non-Langerhans cell histiocytosis. Similar results with anakinra have been observed in patients with Erdheim-Chester disease and in multicentric reticulohistiocytosis.
... Zoltán Berger F, Rodrigo Quera P, Jaime Poniachik T, Danny Oksenberg R, Julia Guerrero P. ...... more ... Zoltán Berger F, Rodrigo Quera P, Jaime Poniachik T, Danny Oksenberg R, Julia Guerrero P. ... intrapancreáticas, con particular énfasis en la estimación cuantitativa de la necrosis pancreática, y además las colecciones peripancreáticas, calculando un puntaje de gravedad ...
Intrathoracic blood volume versus pulmonary artery occlusion pressure as estimators of cardiac pr... more Intrathoracic blood volume versus pulmonary artery occlusion pressure as estimators of cardiac preload in critically ill patients Background: Monitoring of cardiac preload by determination of pulmonary artery occlusion pressure (PAOP) has been traditionally used to guide fluid therapy to optimize cardiac output (CO). Since factors such as intrathoracic pressure and ventricular compliance may modify PAOP, volumetric estimators of preload have been developed. The PiCCO system is able to measure CO and intrathoracic blood volume (ITBV) by transpulmonary thermodilution. Aim: To compare a volumetric (ITBV) versus a pressure (PAOP) determination to accurately estimate cardiac preload in severely ill patients. Patients and Methods: From June 2001 to October 2003, 22 mechanically ventilated patients with hemodynamic instability underwent hemodynamic monitoring with pulmonary artery catheter (PAC) and PiCCO system. ITBV index (ITBVI), PAOP and CI were measured simultaneously by both methods. One hundred thirty eight deltas (∆) were obtained from the difference of ITBVI, PAOP, CI-PAC and CI-PiCCO between 6-12 am and 6-12 pm. Linear regression analysis of ∆ ITBVI versus ∆ CI-PiCCO and ∆ PAOP versus ∆ CI-PAC were made. Results: Mean age of patients was 60.8 ± 19.4 years. APACHE II was 23.9 ± 7. Fifteen patients met criteria for acute respiratory distress syndrome (ARDS). Delta ITBVI significantly correlated with ∆ CI-PiCCO (r=0.54; 95% confidence interval = 0.41-0.65; p <0.01). There was no correlation between ∆ PAOP and ∆ CI-PAC. Conclusion: ITBVI correlated better with CI than PAOP, and therefore it seems to be a more accurate estimator of preload in unstable, mechanically ventilated patients (
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