81 results on '"Rene Baudrand"'
Search Results
52. The Low-Renin Hypertension Phenotype: Genetics and the Role of the Mineralocorticoid Receptor
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Anand Vaidya and Rene Baudrand
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hypertension ,Somatic cell ,030209 endocrinology & metabolism ,Review ,030204 cardiovascular system & hematology ,Essential hypertension ,Catalysis ,lcsh:Chemistry ,Inorganic Chemistry ,Pathogenesis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Mineralocorticoid receptor ,Renin–angiotensin system ,Animals ,Humans ,Medicine ,genetics ,Physical and Theoretical Chemistry ,Glucocorticoids ,lcsh:QH301-705.5 ,Molecular Biology ,Spectroscopy ,mineralocorticoid receptor ,Genetics ,aldosterone ,Aldosterone ,low-renin ,business.industry ,Mechanism (biology) ,Organic Chemistry ,General Medicine ,medicine.disease ,Phenotype ,3. Good health ,Computer Science Applications ,Receptors, Mineralocorticoid ,renin ,lcsh:Biology (General) ,lcsh:QD1-999 ,chemistry ,business - Abstract
A substantial proportion of patients with hypertension have a low or suppressed renin. This phenotype of low-renin hypertension (LRH) may be the manifestation of inherited genetic syndromes, acquired somatic mutations, or environmental exposures. Activation of the mineralocorticoid receptor is a common final mechanism for the development of LRH. Classically, the individual causes of LRH have been considered to be rare diseases; however, recent advances suggest that there are milder and "non-classical" variants of many LRH-inducing conditions. In this regard, our understanding of the underlying genetics and mechanisms accounting for LRH, and therefore, potentially the pathogenesis of a large subset of essential hypertension, is evolving. This review will discuss the potential causes of LRH, with a focus on implicated genetic mechanisms, the expanding recognition of non-classical variants of conditions that induce LRH, and the role of the mineralocorticoid receptor in determining this phenotype.
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- 2018
53. 11β-hydroxysteroid dehydrogenase type-2 and type-1 (11β-HSD2 and 11β-HSD1) and 5β-reductase activities in the pathogenia of essential hypertension
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Javiera Cornejo, Lorena Mosso, Carlos E. Fardella, Giovanni Faccini, Alexis M. Kalergis, Oliviero Olivieri, Rene Baudrand, Oslando Padilla, Carmen Campino, Javiera Sateler, F Pasini, Betty San Martín, Cristian A. Carvajal, Gareth I. Owen, and Gian Cesare Guidi
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Adult ,Male ,medicine.medical_specialty ,Hydrocortisone ,Endocrinology, Diabetes and Metabolism ,Urinary system ,5β reductase ,11β hsd2 ,Essential hypertension ,Endocrinology ,Tandem Mass Spectrometry ,11-beta-Hydroxysteroid Dehydrogenase Type 2 ,Internal medicine ,Diabetes mellitus ,hypertension ,11beta-hydroxysteroid ,5beta-reductase ,11-beta-Hydroxysteroid Dehydrogenase Type 1 ,medicine ,Humans ,Chile ,Tetrahydrocortisol ,Chromatography, High Pressure Liquid ,17-Hydroxycorticosteroids ,chemistry.chemical_classification ,biology ,Chemistry ,Mineralocorticoid Excess Syndrome, Apparent ,Middle Aged ,3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) ,medicine.disease ,Enzyme assay ,Cortisone ,Enzyme ,Tetrahydrocortisone ,Hypertension ,biology.protein ,Female ,Oxidoreductases ,Algorithms ,medicine.drug - Abstract
Cortisol availability is modulated by several enzymes: 11β-HSD2, which transforms cortisol (F) to cortisone (E) and 11β-HSD1 which predominantly converts inactive E to active F. Additionally, the A-ring reductases (5α- and 5β-reductase) inactivate cortisol (together with 3α-HSD) to tetrahydrometabolites: 5αTHF, 5βTHF, and THE. The aim was to assess 11β-HSD2, 11β-HSD1, and 5β-reductase activity in hypertensive patients. Free urinary F, E, THF, and THE were measured by HPLC-MS/MS in 102 essential hypertensive patients and 18 normotensive controls. 11β-HSD2 enzyme activity was estimated by the F/E ratio, the activity of 11β-HSD1 in compare to 11β-HSD2 was inferred by the (5αTHF + 5βTHF)/THE ratio and 5β-reductase activity assessed using the E/THE ratio. Activity was considered altered when respective ratios exceeded the maximum value observed in the normotensive controls. A 15.7% of patients presented high F/E ratio suggesting a deficit of 11β-HSD2 activity. Of the remaining 86 hypertensive patients, two possessed high (5αTHF + 5βTHF)/THE ratios and 12.8% had high E/THE ratios. We observed a high percentage of alterations in cortisol metabolism at pre-receptor level in hypertensive patients, previously misclassified as essential. 11β-HSD2 and 5β-reductase decreased activity and imbalance of 11β-HSDs should be considered in the future management of hypertensive patients.
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- 2009
54. Non-alcoholic fatty liver disease and its association with obesity, insulin resistance and increased serum levels of C-reactive protein in Hispanics
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Flavio Nervi, Attilio Rigotti, Rosa María Pérez-Ayuso, Manuel Alvarez, Juan Francisco Miquel, Arnoldo Riquelme, Francisco Otarola, Verónica Hernández, María José García-Zattera, Guillermo Marshall, Marco Arrese, Arturo Morales, Robinson G. Gonzalez, Alejandro Soza, Rene Baudrand, and Brenda Medina
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medicine.medical_specialty ,Cirrhosis ,Population ,Liver disease ,Blood serum ,Insulin resistance ,Internal medicine ,Ethnicity ,Prevalence ,medicine ,Humans ,Body Weights and Measures ,Obesity ,Chile ,education ,Ultrasonography ,education.field_of_study ,Hepatology ,business.industry ,Fatty liver ,Odds ratio ,medicine.disease ,Fatty Liver ,C-Reactive Protein ,Logistic Models ,Endocrinology ,Insulin Resistance ,Steatohepatitis ,business - Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder of the liver, which may progress to fibrosis or cirrhosis. Recent studies have shown a significant impact of ethnicity on susceptibility to steatosis-related liver disease. Aims: To estimate the prevalence of NAFLD among Chilean Hispanics as well as the clinical and biochemical variables associated with the disease. Methods: Population-based study among Chilean Hispanics. The diagnosis of NAFLD was made on the basis of ultrasound evidence of fatty liver and absence of significant alcohol consumption and hepatitis C virus infection. Results: A total of 832 Hispanic subjects were included. Ultrasound findings revealed diffuse fatty liver in 23% of the subjects. Variables associated with fatty liver in multivariate analysis were body mass index >26.9 [odds ratio (OR) 6.2; 95% confidence interval (CI) 3.3–11.5], abnormal aspartate aminotransferase levels (OR 14; 95% CI 8.2–23.7), presence of insulin resistance as measured by homoeostasis model assessment-insulin resistance (OR 3; 95% CI 1.8–4.8) and serum levels of high-sensitivity C-reactive protein (hs-CRP) greater than 0.86 mg/L (OR 2.9; 95% CI 1.6–5.2). Among subjects with NAFLD, levels of hs-CRP were similar regardless of the alanine aminotransferase (ALT) level. Conclusions: Chilean Hispanics exhibit a high prevalence of NAFLD. Obesity, insulin resistance, abnormal aminotransferase levels and elevated hs-CRP were independently associated with the presence of NAFLD. ALT elevation underestimates the presence of ultrasonographical fatty liver, whereas hs-CRP is a sensitive independent marker of NAFLD, which may be useful for detecting fatty liver in the general population.
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- 2009
55. Abstract MP11: Striatin Heterozygous Knockout Mice Have Increased Aldosterone Sensitivity
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Amanda E Garza, Luminita Pojoga, Rene Baudrand, Burhanuddin Moize, Tham Yao, Gail K Adler, and Gordon H Williams
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endocrine system ,Internal Medicine - Abstract
Background: We recently demonstrated that mice lacking one copy of the striatin gene (Strn+/-) have salt sensitivity of blood pressure (BP) as compared with WT mice. To determine whether Strn+/- mice have increased sensitivity to aldosterone (ALDO), we assessed the effect on blood pressure of an ALDO infusion in WT and Strn+/- mice fed a liberal sodium diet. Methods: In this study we used 12 week old WT and Strn+/- littermate male mice. For each genotype, mice were placed on HS diet and randomized to either: 1) placebo 2) ALDO (200 μg/Kg/day) or 3) ALDO plus 100 mg/kg/day eplerenone. BP was measured by tail cuff plethysmography at baseline and after treatment. After 21 days of treatment, animals were placed in metabolic cages for 24 hours. Finally, animals were sacrificed and organs excised. Primary endpoints were BP, renal immunohistochemistry, protein analysis by western blot and mRNA expression by RT-PCR. Results: BP increased significantly in Strn+/- mice treated with ALDO (ΔBP: 12 ± 4 mmHg, p=0.03) but not placebo (ΔBP 6± 6 mmHg); the BP effect of ALDO was blunted by eplerenone (Δ 6 ± 3 mmHg). In contrast, none of the treatments had a significant effect on BP in WT mice. Kidney weight was significantly increased after 3 weeks of ALDO treatment in both WT and Strn+/- mice and this increase in kidney weight was prevented by treatment with eplerenone, with no difference between genotypes. WT mice had an increase in glomerular volume (GV) in HS/ALDO treated that was blunted by eplerenone. Interestingly, Strn+/- mice had increased GV across all 3 treatment groups compared with WT mice. pAkt/Akt ratios were reduced in Strn+/- mice versus WT mice across all treatments. Classic genomic MR targets (ENaC and SGK1) and non-genomic targets (pAkt/Akt) were significantly modulated in kidney tissue of Strn+/- mice compared to WT mice with chronic ALDO. Conclusion: Strn+/- mice have an increased sensitivity to infused ALDO (increased BP response and increased rise in renal ENaC and SGK1 protein) as compared to WT mice. Since loss of striatin directly reduces nongenomic not genomic action of ALDO, this study demonstrates for the first time that modifying the nongenomic pathway may under chronic, in vivo conditions led to increased sensitivity to the genomic actions of ALDO.
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- 2015
56. Cortisol dysregulation in obesity-related metabolic disorders
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Rene Baudrand and Anand Vaidya
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medicine.medical_specialty ,Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism ,Tissue level ,Biology ,medicine.disease ,Obesity ,Increased cortisol production ,Article ,Increased adipose tissue ,Endocrinology ,Mineralocorticoid receptor ,Metabolic Diseases ,Cardiovascular Diseases ,Internal medicine ,Internal Medicine ,medicine ,Adrenal function ,Humans ,hormones, hormone substitutes, and hormone antagonists - Abstract
The present review highlights recent investigations in the prior 18 months focusing on the role of dysregulated cortisol physiology in obesity as a potential modifiable mechanism in the pathogenesis of obesity-related cardiometabolic disorders.Given the clinical resemblance of obesity-related metabolic disorders with the Cushing's syndrome, new studies have investigated the intracellular regulation and metabolism of cortisol, new measurements of cortisol in scalp hair as a tool for long-term exposure to cortisol, and the cortisol-mineralocorticoid receptor pathway. Thus, current and future pharmacological interventions in obesity may include specific inhibition of steroidogenic and regulatory enzymes as well as antagonists of the mineralocorticoid and glucocorticoid receptors.The understanding of how adrenal function is challenged by the interplay of our genetic and environmental milieu has highlighted the importance of inappropriate cortisol regulation in cardiometabolic disorders. Increased adipose tissue in obesity is associated with hypothalamic-pituitary-adrenal axis overactivation, increased cortisol production at the local tissue level, and probably higher mineralocorticoid receptor activation in certain tissues.
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- 2015
57. Statin Use And Adrenal Aldosterone Production In Hypertensive And Diabetic Subjects
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Anand Vaidya, Jonathan S. Williams, Paul A. Vöhringer, Gordon H. Williams, Paul N. Hopkins, Luminita H. Pojoga, Xavier Jeunemaitre, Amanda E Garza, Tham M. Yao, Gail K. Adler, and Rene Baudrand
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Adult ,Male ,medicine.medical_specialty ,Statin ,medicine.drug_class ,Stimulation ,Pharmacology ,chemistry.chemical_compound ,Corticosterone ,Physiology (medical) ,Internal medicine ,Diabetes mellitus ,Adrenal Glands ,Diabetes Mellitus ,medicine ,Animals ,Humans ,cardiovascular diseases ,Rats, Wistar ,Aldosterone ,business.industry ,nutritional and metabolic diseases ,Diet, Sodium-Restricted ,Middle Aged ,medicine.disease ,Rats ,Endocrinology ,chemistry ,Hypertension ,Female ,lipids (amino acids, peptides, and proteins) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business ,Ex vivo ,Hormone ,Low sodium - Abstract
Background— Statins substantially reduce cardiovascular mortality and appear to have beneficial effects independent of their lipid-lowering properties. We evaluated the hypothesis that statin use may modulate the secretion of aldosterone, a well-known contributor to cardiovascular disease. Methods and Results— We measured adrenal hormones in 2 intervention studies. In study 1 in hypertensive subjects, aldosterone was analyzed at baseline and after angiotensin II stimulation on both high- and low-sodium diets (1122 observations, 15% on statins for >3 months). Statin users had 33% lower aldosterone levels in adjusted models ( P P P =0.006), particularly those using lipophilic statins. Ex vivo studies in rat adrenal glomerulosa cells confirmed that lipophilic statins acutely inhibited aldosterone, but not corticosterone, in response to different secretagogues. Conclusions— Statin use among hypertensive and diabetic subjects was associated with lower aldosterone secretion in response to angiotensin II and a low-sodium diet in 2 human intervention studies. This effect appeared to be most pronounced with lipophilic statins and higher doses. Future studies to evaluate whether aldosterone inhibition may partially explain the robust cardioprotective effects of statins are warranted.
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- 2015
58. The Expression of RAC1 and Mineralocorticoid Pathway-Dependent Genes are Associated With Different Responses to Salt Intake
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Hernán García, Rodrigo Bancalari, Carolina Valdivia, Alexis M. Kalergis, Marlene Aglony, Carlos E. Fardella, Caroline Hill, Rene Baudrand, Cristian A. Carvajal, Alejandra Tapia-Castillo, Andrea Vecchiola, Claudia A. Riedel, Alejandro Martinez-Aguayo, Carlos F. Lagos, Fidel Allende, Carmen A. Carrasco, Luis Michea, and Carmen Campino
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Adult ,Male ,rac1 GTP-Binding Protein ,medicine.medical_specialty ,medicine.drug_class ,Blood Pressure ,Lipocalin ,Essential hypertension ,chemistry.chemical_compound ,Mineralocorticoid receptor ,Lipocalin-2 ,Internal medicine ,Proto-Oncogene Proteins ,Gene expression ,Internal Medicine ,Medicine ,Humans ,Genetic Predisposition to Disease ,Salt intake ,Sodium Chloride, Dietary ,Hydrocortisone ,Aldosterone ,business.industry ,NF-kappa B ,Middle Aged ,medicine.disease ,Lipocalins ,Oxidative Stress ,Endocrinology ,Cross-Sectional Studies ,Receptors, Mineralocorticoid ,chemistry ,Mineralocorticoid ,Hypertension ,Female ,business ,medicine.drug ,Acute-Phase Proteins ,Signal Transduction - Abstract
background Rac1 upregulation has been implicated in salt-sensitive hypertension as a modulator of mineralocorticoid receptor (MR) activity. Rac1 could affect the expression of oxidative stress markers, such as hemoxigenase-1 (HO1) or nuclear factor-B (NF-κB), and the expression of neutrophil gelatinaseassociated lipocalin (NGAL), a cytokine upregulated upon MR activation. aim We evaluated RAC1 expression in relation of high salt intake and association with MR, NGAL, HO-1, and NF-κB expression, mineralo- and glucocorticoids levels, and inflammatory parameters. subjects and methods We studied 147 adult subjects. A food survey identified the dietary sodium (Na) intake. RAC1 expression was considered high or low according to the value found in normotensive subjects with low salt intake. We determined the gene expression of RAC1, MR, NGAL, HO-1, NF-κB, and 18S, isolated from peripheral leukocytes. We measured aldosterone, cortisol, sodium, potassium excretion, metalloproteinase (MMP9 y MMP2), and C-reactive protein. results We identified 126 subjects with high Na-intake, 18 subjects had high, and 108 low-RAC1 expression. The subjects with high-RAC1 expression showed a significant increase in MR (P = 0.0002), NGAL (P < 0.0001) HO-1 (P = 0.0004), and NF-κB (P < 0.0001) gene expression. We demonstrated an association between RAC1 expression and MR (Rsp 0.64; P
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- 2014
59. Polymorphisms in the rac1 gene are associated with hypertension risk factors in a chilean pediatric population
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Rene Baudrand, Lorena García, Hernán García, Carlos E. Fardella, Andrea Vecchiola, Alejandra Tapia-Castillo, Carlos F. Lagos, Carmen Campino, Alejandro Martinez-Aguayo, Marlene Aglony, Cristian A. Carvajal, Fidel Allende, Cristobal A. Fuentes, Carolina Valdivia, Sandra Solari, and Sergio Lavanderos
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Oncology ,Male ,rac1 GTP-Binding Protein ,medicine.medical_specialty ,Pathology ,Adolescent ,Blood Pressure ,Polymorphism, Single Nucleotide ,Risk Assessment ,chemistry.chemical_compound ,Gene Frequency ,Polymorphism (computer science) ,Risk Factors ,Internal medicine ,Genotype ,Internal Medicine ,Odds Ratio ,Medicine ,Humans ,Genetic Predisposition to Disease ,Chile ,Interleukin 6 ,Child ,Gene ,Chi-Square Distribution ,biology ,business.industry ,C-reactive protein ,Introns ,Pedigree ,Blood pressure ,Cross-Sectional Studies ,Phenotype ,chemistry ,Plasminogen activator inhibitor-1 ,Child, Preschool ,Cohort ,Hypertension ,biology.protein ,Disease Progression ,Female ,Inflammation Mediators ,business ,Biomarkers - Abstract
The GTPase Rac1 has been implicated in hypertension as a modulator of mineralocorticoid receptor activity. Our aim is to investigate the frequency of polymorphisms rs10951982 (intron 1, GA) and rs836478 (intron 3, TC) in the RAC1 gene and perform association studies with clinical and biochemical parameters in a Chilean pediatric cohort.Two hundred two normotensive (NT) subjects (aged 4-16 years) were divided into 2 groups: NT subjects with hypertensive parents (NH; n = 103) and NT subjects with NT parents (NN; n = 99). We measured markers of inflammation (high-sensitivity C-reactive protein, interleukin 6 (IL-6), interleukin 8, and tumor necrosis factor α), endothelial damage (Plasminogen activator inhibitor-1 metalloproteinase-9, and metalloproteinase-2), and oxidative stress (malondialdehyde). Data were expressed as median and interquartile range (IQR).We found differences in polymorphism rs836478 (intron 3, CT) in both genotypic (χ(2) = 15.2, 2 df; P = 0.0005) and allelic (X(2)=5.5, 1 df; P = 0.01) frequencies in NH vs. NN subjects. NH subjects with a TT genotype showed increase MMP9 expression (median = 2.3, IQR - 1.6-3.2; vs. median = 1.6, IQR = 1.6-2.3 AU; P = 0.01) and lower IL-6 expression (median = 8.8, IQR = 7.0-11.8; vs. median = 12.1, IQR = 8.2-14.7 pg/ml; P = 0.02) compared with subjects with TC/CC genotype. No difference in the allelic frequency distribution was seen in the polymorphism rs10951982 (NH vs. NN: χ(2)=0.2, 1 df; P = 0.6). For this SNP, NN subjects with GA/AA genotype showed decreased diastolic BP indexes compared with subjects with native GG genotype (median = 1.08, IQR = 1.0-1.2; vs. median = 0.99, IQR = 0.94-1.1; P = 0.02).We report the frequency of polymorphisms rs836478 and rs10951982 of the RAC1 gene in a Spanish-Amerindian cohort. The polymorphism rs836478 was associated with an increased expression in markers of inflammation and endothelial damage (MMP9 and IL-6) in pediatric subjects with a hypertensive genetic background.
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- 2014
60. Mineralocorticoid receptor throughout the vessel: a key to vascular dysfunction in obesity
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Rene Baudrand, Luminita H. Pojoga, and Gail K. Adler
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Male ,medicine.medical_specialty ,Mineralocorticoid receptor ,Adipose tissue ,Spironolactone ,Diet, High-Fat ,Proinflammatory cytokine ,Endothelial ,chemistry.chemical_compound ,Basic Science ,Internal medicine ,Medicine ,Animals ,Obesity ,Endothelial dysfunction ,Aldosterone ,Mineralocorticoid Receptor Antagonists ,business.industry ,medicine.disease ,Hyperaldosteronism ,Eplerenone ,Endocrinology ,Receptors, Mineralocorticoid ,chemistry ,Endothelium, Vascular ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
This editorial refers to ‘Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity’[†][1], by N. Schafer et al. , on page 3515 Obesity is a highly prevalent chronic condition and a major risk factor for several metabolic and cardiovascular (CV) diseases. Numerous human studies have demonstrated that obesity is associated with hypertension and vascular dysfunction secondary to arterial stiffness, reduced endothelium-dependent relaxation, and atherosclerosis.1 The exact mechanisms implicated in obesity-related vascular dysfunction have not been fully elucidated, but are likely to involve a complex interplay between multiple endocrine and paracrine factors, inflammation, oxidative stress, and structural modifications of the vessel. In recent years there has been a growing interest in the simultaneous worldwide increase in the prevalence of obesity, hypertension, and hyperaldosteronism, and a possible inter-relationship between these conditions. The relevance of aldosterone to human health is supported by prospective studies demonstrating a positive correlation between plasma levels of aldosterone and CV mortality.2 Further, pivotal clinical trials have shown that mineralocorticoid receptor (MR) antagonists, such as spironolactone or eplerenone, markedly improve morbidity and mortality in heart failure.3 We and others have shown that obesity is associated with increased aldosterone production in humans and increased aldosterone and MR levels in obese diabetic mice.4,5 MR blockade improved the proinflammatory cytokine profiles of adipose tissue in the obese mice. These findings led to the hypothesis that elevated aldosterone levels contribute to CV injury, progression of atherosclerosis, and metabolic disorders in obesity ( Figure 1 ). The specific mechanisms for CV injury may be related to aldosterone's renal effects to promote sodium retention and volume expansion as well as to MR activation in multiple extrarenal tissues, including the heart, vasculature, monocytes/macrophages, and adipose tissue. Specifically in vessels, aldosterone and/or MR activation increases vascular macrophage infiltration, enhances the proinflammatory cytokine profile, … [1]: #fn-2
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- 2013
61. Identification of novel 11β-HSD1 inhibitors by combined ligand- and structure-based virtual screening
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Carolina Valdivia, Sandra Solari, Andrea Vecchiola, Rene Baudrand, Gareth I. Owen, Cristian A. Carvajal, Alejandra Tapia-Castillo, Fidel Allende, Pia Villarroel, Carmen Campino, Cristobal A. Fuentes, Mariana Cifuentes, Carlos F. Lagos, Juan E. Tichauer, and Carlos E. Fardella
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Gene isoform ,Hydrocortisone ,In silico ,Gene Expression ,Ligands ,Biochemistry ,Structure-Activity Relationship ,User-Computer Interface ,Endocrinology ,11β-hydroxysteroid dehydrogenase type 1 ,11-beta-Hydroxysteroid Dehydrogenase Type 2 ,Cell Line, Tumor ,11-beta-Hydroxysteroid Dehydrogenase Type 1 ,Drug Discovery ,medicine ,Adipocytes ,Humans ,Enzyme Inhibitors ,Cytotoxicity ,Molecular Biology ,Virtual screening ,biology ,Cell Differentiation ,Ligand (biochemistry) ,Molecular Docking Simulation ,Kinetics ,biology.protein ,Cortisone ,hormones, hormone substitutes, and hormone antagonists ,Intracellular ,medicine.drug - Abstract
11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to cortisol in a NADPH dependent manner. Overexpression of 11β-HSD1 in key metabolic tissues is related to the development of type 2 diabetes, obesity, hypertension and metabolic syndrome. Using crystal structures of human 11β-HSD1 in complex with inhibitors as source of structural information, a combined ligand and structure-based virtual screening approach was implemented to identify novel 11β-HSD1 inhibitors. A selected group of compounds was identified in silico and further evaluated in cell-based assays for cytotoxicity and 11β-HSD1 mediated cortisol production inhibitory capacity. The expression of 11β-HSD1 and 11β-HSD2 in human LS14 adipocytes was assessed during differentiation. Biological evaluation of 39 compounds in adipocytes and steroids quantification by HPLC-MS/MS identify 4 compounds that exhibit 11β-HSD1 mediated cortisol production inhibitory activity with potencies in the micromolar range. Two compounds showed to be selective for the 11β-HSD1 reductase activity and over 11β-HSD2 isoform, and thus represent novel leads for the development of more active derivatives with higher efficacies targeting intracellular cortisol levels in type 2 diabetes and metabolic syndrome.
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- 2013
62. Long-term dietary sodium restriction increases adiponectin expression and ameliorates the proinflammatory adipokine profile in obesity
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Gail K. Adler, J. Li, V. Ricchiuti, Christine G. Lian, Bill Q. Lian, Tham M. Yao, Rene Baudrand, and Gordon H. Williams
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Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Medicine (miscellaneous) ,Adipokine ,Adipose tissue ,Mice, Obese ,Article ,Proinflammatory cytokine ,Interferon-gamma ,Mice ,Insulin resistance ,Adipokines ,Internal medicine ,Diabetes mellitus ,Diabetes Mellitus ,Medicine ,Animals ,Insulin ,Obesity ,Chemokine CCL2 ,Triglycerides ,Nutrition and Dietetics ,Adiponectin ,business.industry ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Body Weight ,Heart ,Sodium, Dietary ,Diet, Sodium-Restricted ,medicine.disease ,Diet ,Endocrinology ,Adipose Tissue ,Insulin Resistance ,Cardiology and Cardiovascular Medicine ,business ,Low sodium - Abstract
Obesity is associated with changes in adiponectin and pro-inflammatory adipokines. Sodium intake can affect adipokine secretion suggesting a role in cardiovascular dysfunction. We tested if long-term dietary sodium restriction modifies the expression of adiponectin and ameliorates the pro-inflammatory profile of obese, diabetic mice.Db/db mice were randomized to high sodium (HS 1.6% Na+, n = 6) or low sodium (LS 0.03% Na+, n = 8) diet for 16 weeks and compared with lean, db/+ mice on HS diet (n = 8). Insulin levels were 50% lower in the db/db mice on LS diet when compared with HS db/db (p0.05). LS diet increased cardiac adiponectin mRNA levels in db/db mice by 5-fold when compared with db/db mice on HS diet and by 2-fold when compared with HS lean mice (both p0.01). LS diet increased adiponectin in adipose tissue compared with db/db mice on HS diet, achieving levels similar to those of lean mice. MCP-1, IL-6 and TNF-α expression were reduced more than 50% in adipose tissue of db/db mice on LS diet when compared with HS db/db mice (all p0.05), to levels observed in the HS lean mice. Further, LS db/db mice had significantly reduced circulating MCP-1 and IL-6 levels when compared with HS db/db mice (both p0.01).In obese-diabetic mice, long-term LS diet increases adiponectin in heart and adipose tissue and reduces pro-inflammatory factors in adipose tissue and plasma. These additive mechanisms may contribute to the potential cardioprotective benefits of LS diet in obesity-related metabolic disorders.
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- 2013
63. Age-related changes in 11 beta-hydroxysteroid dehydrogenase type 2 activity in normotensive subjects
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Oslando Padilla, Alejandro Martinez-Aguayo, Carlos E. Fardella, Hernán García, Alexis M. Kalergis, Carmen Campino, Marlene Aglony, Rene Baudrand, and Cristian A. Carvajal
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Adult ,Male ,medicine.medical_specialty ,Aging ,Adolescent ,Hydrocortisone ,Blood Pressure ,Plasma renin activity ,chemistry.chemical_compound ,Mineralocorticoid receptor ,Interquartile range ,Internal medicine ,11-beta-Hydroxysteroid Dehydrogenase Type 2 ,Renin ,Internal Medicine ,medicine ,Humans ,Child ,Aldosterone ,business.industry ,Middle Aged ,Cortisone ,Endocrinology ,Blood pressure ,Cross-Sectional Studies ,chemistry ,Hypertension ,Female ,business ,Serum cortisol ,medicine.drug - Abstract
Background Impairment in 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity results in inefficient inactivation of cortisol to cortisone, and it can trigger hypertension through activation of the mineralocorticoid receptor. Information about age-related changes in 11β-HSD2 activity and its physiological consequences is scarce. Our aim was to investigate whether 11β-HSD2 activity is age dependent in normotensive subjects. Methods We recruited 196 healthy, normotensive subjects. Of these, 93 were children (Group 1: aged 5–15 years), and 103 were adults who were divided according to their ages: Group 2: aged 30–41 years (n = 10); Group 3: aged 42–53 years (n = 72); and Group 4: aged 54–65 years (n = 21). Fasting serum cortisol, cortisone, aldosterone, and plasma renin activity (PRA) were measured. The 11β-HSD2 activity was estimated by the cortisol/cortisone ratio. The results were expressed as median (interquartile range (IQR)) values and compared using Kruskal–Wallis and Dunn’s multiple-comparison tests. r esults As subject age increased, cortisol concentrations increased (Group 1 median = 8.6, IQR = 6.3–10.8 µg/dl; Group 4 median = 12.4, IQR = 10.7– 14.7 µg/dl; P < 0.001), and cortisone concentrations showed a gradual decrease (Group 2 median = 4.0, IQR = 3.3–4.2 µg/dl; Group 4 median =2.8, IQR = 2.6–3.3 µg/dl; P
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- 2013
64. High sodium intake is associated with increased glucocorticoid production, insulin resistance and metabolic syndrome
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Pa Vöhringer, Gareth I. Owen, Oliviero Olivieri, Giovanni Faccini, Ca Carvajal, Carmen Campino, Jaime Cerda, Gian Cesare Guidi, Ce Fardella, Rene Baudrand, and Am Kalergis
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Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Adolescent ,Hydrocortisone ,Endocrinology, Diabetes and Metabolism ,Urinary system ,metabolic syndrome ,Body Mass Index ,Cohort Studies ,chemistry.chemical_compound ,Young Adult ,Endocrinology ,Insulin resistance ,Internal medicine ,medicine ,Odds Ratio ,Humans ,Obesity ,Aldosterone ,Glucocorticoids ,sodium ,Aged ,Aged, 80 and over ,Adiponectin ,medicine.diagnostic_test ,business.industry ,Sodium, Dietary ,Middle Aged ,medicine.disease ,chemistry ,Hypertension ,Female ,glucocorticoid ,Metabolic syndrome ,Insulin Resistance ,business ,Lipid profile ,Body mass index ,Glucocorticoid ,medicine.drug - Abstract
Objective High sodium (HS) diet is associated with hypertension (HT) and insulin resistance (IR). We evaluated whether HS diet was associated with a dysregulation of cortisol production and metabolic syndrome (MetS). Patients and measurements We recruited 370 adults (18–85 years, BMI 29·3 ± 4·4 kg/m2, 70% women, 72% HT, 61% MetS). HS diet (urinary sodium >150 mEq/day) was observed in 70% of subjects. We measured plasma hormones, lipid profile, urinary free cortisol (UFC) and cortisol tetrahydrometabolites (THM). Results Urinary sodium was correlated with UFC (r = +0·45, P
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- 2013
65. PS 10-19 SERUM CORTISONE AND CORTISOL/CORTISONE RATIO AS TOOL TO IDENTIFY SUBJECTS WITH SEVERE AND PARTIAL 11BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 2 DEFICIENCIES
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Virginia Iturrieta, Carolina Valdivia, Sandra Solari, Rene Baudrand, Constanza Pinochet, Alejandro Martinez-Aguayo, Jaime Lizama, Alejandra Tapia-Castillo, Carmen Campino, Fidel Allende, Cristian A. Carvajal, and Carlos E. Fardella
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medicine.medical_specialty ,Endocrinology ,Physiology ,Cortisol/Cortisone ,business.industry ,Internal medicine ,Internal Medicine ,medicine ,Cortisone ,11beta-Hydroxysteroid Dehydrogenase Type 2 ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Published
- 2016
66. 11 beta-hydroxysteroid dehydrogenase type 2 polymorphisms and activity in a chilean essential hypertensive and normotensive cohort
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Carolina Valdivia, Carlos F. Lagos, Gian Cesare Guidi, Carlos E. Fardella, Mauricio Morales, Juan Thichauer, Cristian A. Carvajal, Carmen Campino, Giovanni Faccini, Alexis M. Kalergis, Oslando Padilla, Hector Quinteros, Oliviero Olivieri, F Pasini, Rene Baudrand, and Gareth I. Owen
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Male ,medicine.medical_specialty ,11-HSD type ,gene polymorphism ,hypertension ,Genotype ,Hydrocortisone ,Population ,Plasma renin activity ,Cohort Studies ,chemistry.chemical_compound ,Polymorphism (computer science) ,11-beta-Hydroxysteroid Dehydrogenase Type 2 ,Internal medicine ,Renin ,Prevalence ,Internal Medicine ,medicine ,Humans ,Tetrahydrocortisone ,Chile ,education ,Aldosterone ,education.field_of_study ,Polymorphism, Genetic ,business.industry ,Tetrahydrocortisol ,Middle Aged ,Cortisone ,Endocrinology ,chemistry ,Case-Control Studies ,Cohort ,Female ,Gene polymorphism ,business ,medicine.drug - Abstract
BACKGROUND 11β-hydroxysteroid dehydrogenase type 2 enzyme (11β-HSD2) inactivates cortisol (F) to cortisone (E); its impairment is associated with hypertension. We reported that 15.7% of the Chilean essential hypertensives possessed a high F/E ratio suggesting a partial deficit in 11β-HSD2 activity. It has been reported that the G534A(Glu178/Glu) polymorphism in the HSD11B2 gene is associated with hypertension. Investigate the frequency of the G534A polymorphism and its correlation with the glucocorticoid profile in Chilean essential hypertensive and normotensive subjects. METHODS Essential hypertensive outpatients (n = 232) and normotensive subjects (n = 74) were recruited. A change in the AluI restriction enzyme digest pattern, caused by the presence of the G534A polymorphism, was utilized to screen DNA isolated from leukocytes within the cohort before confirmation by sequencing. Plasma renin activity (PRA), serum aldosterone, F, and E were measured by radioimmunoassay. Urinary tetrahydrocortisol (THF), 5α-tetrahydrocortisol (5α-THF), and tetrahydrocortisone (THE) were measured by gas chromatography-mass spectrometry. RESULTS G534A polymorphism frequency was similar between hypertensive patients (19 of 232; 8.2%) and normotensive subjects (7 of 74; 9.5%). When categorized by presence or absence of the G534A polymorphism, no significant differences in the serum F/E ratio or other measured biochemical variables were detected. Despite a previous report that the G534A polymorphism is associated with a neighboring C468A (Thr156/Thr) polymorphism, analysis within our cohort showed that only one patient in each group presented with this double polymorphism. CONCLUSIONS We report the frequency of the G534A polymorphism in the Spanish-Amerindian population. No correlation was detected between this polymorphism and the presence of hypertension and biochemical parameters in this Chilean cohort.
- Published
- 2012
67. A new presentation of the chimeric CYP11B1/CYP11B2 gene with low prevalence of primary aldosteronism and atypical gene segregation pattern
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Pamela Trejo, Cristian A. Carvajal, Hernan Garcia, Carlos E. Fardella, Rene Baudrand, Carolina Valdivia, Rodrigo Bancalari, Carmen Campino, Carlos F. Lagos, Cecilia Mellado, Alejandro Martinez-Aguayo, Marlene Aglony, and Juan E. Tichauer
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Aldosterone synthase ,Adult ,Male ,Familial hyperaldosteronism ,medicine.medical_specialty ,Adolescent ,Mutant Chimeric Proteins ,Plasma renin activity ,chemistry.chemical_compound ,Chromosome Breakpoints ,Primary aldosteronism ,Internal medicine ,Chromosome Segregation ,Renin–angiotensin system ,Hyperaldosteronism ,Internal Medicine ,medicine ,Prevalence ,Cytochrome P-450 CYP11B2 ,Humans ,Chile ,Aldosterone ,Family Health ,biology ,medicine.disease ,Penetrance ,Glucocorticoid remediable aldosteronism ,Pedigree ,Endocrinology ,chemistry ,biology.protein ,Steroid 11-beta-Hydroxylase ,Female - Abstract
Familial hyperaldosteronism type I is caused by an unequal crossover of 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes, giving rise to a chimeric CYP11B1/CYP11B2 gene (CG). We describe a family carrying a CG with high levels of free 18-hydroxycortisol but low prevalence of primary aldosteronism (PA) and an atypical CG inheritance pattern in a family of 4 generations with 16 adults and 13 children, we measured the arterial blood pressure, serum aldosterone, and plasma renin activity and then calculated the serum aldosterone:plasma renin activity ratio and urinary free 18-hydroxycortisol. We identified the CG by long-extension PCR and predicted its inheritance pattern. The CG was found in 24 of 29 subjects (10 children and 14 adults). In CG+ patients, hypertension and high 18-hydroxycortisol were prevalent (83% and 100%, respectively). High serum aldosterone:plasma renin activity ratio was more frequent in pediatric than adult patients (80% versus 36%; P r =−0.48; P =0.018). Sequence analysis identified the CYP11B1/CYP11B2 crossover in a 50-bp region spanning intron 3 of CYP11B1 and exon 4 of CYP11B2. The CG segregation differs from an autosomal disease, showing 100% of CG penetrance in generations II and III. Statistical analysis suggests that inheritance pattern was not attributed to random segregation ( P
- Published
- 2011
68. Overexpression of 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue and portal hypercortisolism in non-alcoholic fatty liver disease
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Cristian A. Carvajal, Marco Arrese, Nancy Solís, Gonzalo Carrasco, Carlos E. Fardella, Oslando Padilla, Roberto Candia, Alex Escalona, Rene Baudrand, Arnoldo Riquelme, Mauricio Morales, Gustavo Pérez, Margarita Pizarro, Jaime Cerda, and Camilo Boza
- Subjects
medicine.medical_specialty ,medicine.drug_class ,Adipose tissue ,Mice, Obese ,Enzyme-Linked Immunosorbent Assay ,Intra-Abdominal Fat ,Pathogenesis ,chemistry.chemical_compound ,Mice ,Corticosterone ,11β-hydroxysteroid dehydrogenase type 1 ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,11-beta-Hydroxysteroid Dehydrogenase Type 1 ,medicine ,Odds Ratio ,Animals ,Humans ,Cushing Syndrome ,Triglycerides ,DNA Primers ,Hepatology ,biology ,Gene Expression Profiling ,Fatty liver ,nutritional and metabolic diseases ,Alanine Transaminase ,medicine.disease ,Obesity ,Obesity, Morbid ,Gene expression profiling ,Fatty Liver ,Mice, Inbred C57BL ,Endocrinology ,Cholesterol ,chemistry ,Liver ,ROC Curve ,biology.protein ,Corticosteroid ,hormones, hormone substitutes, and hormone antagonists - Abstract
Background The enzyme 11β-hydroxysteroid-dehydrogenase type 1 (11β-HSD1) catalyses the reactivation of intracellular cortisol. We explored the potential role of 11β-HSD1 overexpression in visceral adipose tissue (VAT) in non-alcoholic fatty liver disease (NAFLD) assessing sequential changes of enzyme expression, in hepatic and adipose tissue, and the occurrence of portal hypercortisolism in obese mice. 11β-HSD1 expression was also assessed in tissues from obese patients undergoing bariatric surgery. Methods Peripheral and portal corticosterone levels and liver histology were assessed in ob/ob mice at two time points (8–12 weeks of age). 11β-HSD1 tissue expression was assessed in by RT-pcr in ob/ob mice and in 49 morbidly obese patients. Results Portal corticosterone serum levels were higher in obese mice with a 26% decrease between 8 and 12 weeks of age (controls: 78.3 ± 19.7 ng/ml, 8-week-old ob/ob: 167.5 ± 14.5 ng/ml and 12-week-old ob/ob: 124.3 ± 28 ng/ml, P
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- 2011
69. Age-Related Changes in the Renin-Aldosterone System in Healthy Subjects
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Rene Baudrand, Carmen Campino, Marlene Aglony, Alejandro Martinez-Aguayo, Cristian A Carvajal, Hernan Garcia, Rodrigo Bancalari, Oslando Padilla, Gareth Owen, Alexis M Kalergis, and Carlos E Fardella
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- 2011
70. A New Presentation of Chimeric CYP11B1/CYP11B2 Gene with Low Prevalence of Primary Aldosteronism and Atypical Gene Segregation Pattern
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Cristian A Carvajal, Carmen M Campino, Juan E Tichauer, Carolina P Valdivia, Rodrigo Bancalari, Marlene Aglony, Alejandro Martinez, Hernan Garcia, Vinka Giadrosich, Patricio A Salman, Pamela L Trejo, Rene Baudrand, and Carlos E Fardella
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- 2011
71. Increased urinary glucocorticoid metabolites are associated with metabolic syndrome, hypoadiponectinemia, insulin resistance and beta-cell dysfunction
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Rene Baudrand, Javiera Cornejo, Carlos E. Fardella, Lorena Mosso, Gareth I. Owen, José Carlos de Miguel Domínguez, Giovanni Faccini, Oliviero Olivieri, Cristian A. Carvajal, Alexis M. Kalergis, Gian Cesare Guidi, Jaime Cerda, Javiera Sateler, Betty San Martín, and Carmen Campino
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Clinical Biochemistry ,Adipokine ,Adipose tissue ,Biochemistry ,metabolic syndrome ,Endocrinology ,Insulin resistance ,Internal medicine ,Insulin-Secreting Cells ,medicine ,Humans ,Obesity ,Molecular Biology ,Pharmacology ,Adiponectin ,glucocorticoids ,hormones ,Chemistry ,Insulin ,Leptin ,Organic Chemistry ,Middle Aged ,medicine.disease ,Lipid Metabolism ,Female ,Metabolic syndrome ,Insulin Resistance ,hormones, hormone substitutes, and hormone antagonists ,Glucocorticoid ,medicine.drug - Abstract
Metabolic syndrome (MetS) may have increased cortisol (F) production caused by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in liver and adipose tissue and/or by HPA axis dysregulation. F is then mainly metabolized by liver reductases into inactive tetrahydrometabolites (THMs). We measured THM levels in patients with or without MetS and evaluate the correlation between THMs and anthropometric and biochemical parameters. We recruited 221 subjects, of whom 130 had MetS by ATP III. We evaluated F, cortisone (E), adipokines, glucose, insulin and lipid profiles as well as urinary (24h) F, E and THM levels. β Cell function was estimated by the HOMA Calculator. We observed that patients with MetS showed higher levels of THMs, HOMA-IR and leptin and lower levels of adiponectin and HOMA-β but no differences in F and E in plasma or urine. THM was associated with weight (r = +0.44, p0.001), waist circumference (r = +0.38, p0.01), glycemia (r = +0.37, p0.01), and triglycerides (r = +0.18, p=0.06) and negatively correlated with adiponectin (r = -0.36, p0.001), HOMA-β (r = -0.21, p0.001) and HDL (r = -0.29, p0.01). In a logistic regression model, THM levels were associated with hypertension, hyperglycemia and dyslipidemia. We conclude that MetS is associated with increased urinary THMs but not with F and E levels in plasma or urine. Increased levels of THM, reflecting the daily cortisol production subsequently metabolized, are correlated with hypoadiponectinemia, hypertension, dyslipidemia, insulin resistance and β cell dysfunction. A subtle increased in glucocorticoid production may further account for the phenotypic and biochemical similarities observed in central obesity and Cushing's syndrome.
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- 2011
72. An ultrasound model to discriminate the risk of thyroid carcinoma
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Eugenio Arteaga, Francisco Cruz, Antonieta Solar, José Carlos de Miguel Domínguez, Rene Baudrand, Carlos E. Fardella, Jaime Cerda, Tatiana Arias, Claudia Campusano, and Lorena Mosso
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Thyroid nodules ,Male ,medicine.medical_specialty ,Biopsy, Fine-Needle ,Sensitivity and Specificity ,Thyroid carcinoma ,Diagnosis, Differential ,Biopsy ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Thyroid Neoplasms ,Thyroid Nodule ,Thyroid cancer ,Ultrasonography ,Likelihood Functions ,medicine.diagnostic_test ,business.industry ,Calcinosis ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Pre- and post-test probability ,Fine-needle aspiration ,Female ,Radiology ,business - Abstract
Rationale and Objectives Thyroid nodules are common on ultrasonographic examination and are mostly benign. Ultrasound characteristics may help discriminate thyroid carcinoma (TC) from benign nodules. The aims of this study were to identify ultrasonographic characteristics associated with TC and to validate a previously proposed model based on the presence of three ultrasonographic characteristics. Materials and Methods From a protocolized prospective registry of 1108 fine needle aspiration biopsies performed during a 16-month period at an ambulatory center, the ultrasonographic characteristics of TC and non-TC biopsies were compared. Adjusted odds ratios (ORs) and likelihood ratios for TC were estimated for eight combinations of three previously identified characteristics (microcalcifications, hypoechogenicity, and irregular borders). Results Microcalcifications (OR, 6.6; 95% confidence interval [CI], 4.4–9.9), hypoechogenicity (OR, 4.7; 95% CI, 2.8–8.0), and irregular borders (OR, 4.3; 95% CI, 2.8–6.5) were independently associated with TC. When added to a logistic regression model, the three ultrasonographic characteristics remained statistically significant. In the absence of these three features, the likelihood ratio for TC was 0.1 (95% CI, 0.0–0.2), while in their simultaneous presence, the likelihood ratio was 11 (95% CI, 6.6–19.0). Conclusions The absence or simultaneous presence of three simple ultrasonographic characteristics generates a large change of pretest probability of TC and could avoid unnecessary fine needle aspiration biopsy.
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- 2010
73. Overexpression of 11 beta-hydroxysteroid dehydrogenase type 1 in hepatic and visceral adipose tissue is associated with metabolic disorders in morbidly obese patients
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Rene Baudrand, Carlos E. Fardella, Camilo Boza, Cristian A. Carvajal, Alex Escalona, Marco Arrese, Nancy Solís, Gustavo Pérez, Angélica Domínguez, Margarita Pizarro, Arnoldo Riquelme, and Mauricio Morales
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Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Subcutaneous Fat ,Adipose tissue ,Comorbidity ,Body Mass Index ,Metabolic Diseases ,11β-hydroxysteroid dehydrogenase type 1 ,Internal medicine ,11-beta-Hydroxysteroid Dehydrogenase Type 1 ,medicine ,Humans ,RNA, Messenger ,Abdominal obesity ,chemistry.chemical_classification ,Nutrition and Dietetics ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Middle Aged ,medicine.disease ,Obesity ,Obesity, Morbid ,Enzyme ,Endocrinology ,Adipose Tissue ,Liver ,chemistry ,biology.protein ,Female ,Surgery ,Cortisone ,medicine.symptom ,business ,Body mass index ,hormones, hormone substitutes, and hormone antagonists ,Glucocorticoid ,medicine.drug - Abstract
The enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes intracellular glucocorticoid reactivation by conversion of cortisone to cortisol in different tissues and have been implicated in several metabolic disorders associated with obesity. The aim of this study was to evaluate the 11beta-HSD1 expression in liver, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) in morbidly obese patients undergoing bariatric surgery and its correlations with clinical, anthropometric, and biochemical variables.A prospective study was conducted over a 27-month period. Hepatic, VAT, and SAT samples were obtained at the time of surgery. 11beta-HSD1 and 18S gene expression was measured using real-time quantitative reverse transcriptase-polymerase chain reaction.Forty nine patients met the inclusion criteria [mean age: 42.2 +/- 10 years, body mass index (BMI): 42 +/- 6 kg/m(2), 71% women and 63% with metabolic syndrome (MS)]. 11beta-HSD1 mRNA levels were higher in liver than fat tissue (p0.001), being higher in SAT than in VAT (p0.001) without gender-specific differences. Hepatic expression of 11beta-HSD1 correlated positively with SAT and VAT, alanine aminotransferase (ALT), and serum glucose and was inversely associated with BMI. 11beta-HSD1 mRNA in VAT correlated positively with insulinemia, ALT, and LDL cholesterol. There were no associations between 11beta-HSD1 mRNA in SAT and the variables analyzed.11beta-HSD1 expression is higher in liver in comparison to adipose tissue in obese patients. The observed correlations between hepatic and VAT 11beta-HSD1 expression with dyslipidemia and insulin resistance suggest that this enzyme might have a pathogenic role in obesity and related metabolic disorders.
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- 2010
74. Diseño de una escala ecográfica predictora de malignidad en nódulos tiroideos: Comunicación preliminar
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José Miguel Domínguez, Claudia Campusano, Gilberto González, Antonieta Solar, Carlos E. Fardella, Eugenio Arteaga, Marcelo Gómez, Gabriel Cavada, Rene Baudrand, Lorena Mosso, Francisco Cruz, Alejandra Pizarro, Javiera Torres, and Tatiana Arias
- Subjects
Univariate analysis ,medicine.medical_specialty ,Multivariate analysis ,medicine.diagnostic_test ,endocrine system diseases ,business.industry ,Biopsy ,fine-needle ,Carcinoma ,Thyroid neoplasms ,General Medicine ,Odds ratio ,medicine.disease ,Gastroenterology ,Confidence interval ,medicine.anatomical_structure ,papillary ,Internal medicine ,medicine ,business ,Lymph node - Abstract
Background: Thyroid nodules are common and associated to a low risk of malignancy. Their clinical assessment usually includes a fine neddle aspiration biopsy (FNAB). Aim To identify ultrasonographic characteristics associated to papillary thyroid carcinoma (PTC) and generate a score that predicts the risk of PTC. Material and methods: Retrospective review of all fine needle aspiration biopsies of the thyroid performed in a lapse of two years. Biopsies that were conclusive for PTC were selected and compared with an equal amount of randomly selected biopsies that disclosed a benign diagnosis. Results: One hundred twenty two biopsies of a total of 1,498 were conclusive for PTC. Univariate analysis showed associations with PTC for the presence of micro-calcifications (Odds ratio (OR) 49.2: 95% confidence intervals (CI) 18.7-140.9), solid predominance (OR 25.1; 95% CI 6-220), hypoechogenicity (OR 23.5, 95% CI 6.5-122.6), irregular borders (OR 17, 95% CI 7.2-42.9), lymph node involvement (OR 12.3, 95% CI2.7-112), central vascularization (OR 12.2, 95% CI 4.8-33.3), local invasion and hyperechogenicity (OR 0.2; CI95% CI 0.03-0.6). Multivariate analysis disclosed microcalcifications (OR 28.1; CI 95% 8.9-89), hypoechogenicity (OR 9.4; 95% CI 1.5-59.5) and irregular borders (OR 4.7; CI 95% 1.5-15) as the variables independently associated with the presence of PTC. The prevalence of PTC in the presence of the three variables was 97.6% (Likelihood ratio (LR) 45) and 5.4% in their absence (LR 0.06). Conclusions: This scale predicts the presence or absence of PTC using simple ultrasound characteristics.
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- 2009
75. Hypoadiponectinemia and its association with liver fibrosis in morbidly obese patients
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Rene Baudrand, Arturo Morales, Catalina Saint-Jean, Gonzalo Carrasco, Leyla Nazal, Nancy Solís, Marco Arrese, Diego Awruch, Oslando Padilla, Juan Francisco Miquel, Flavio Nervi, Manuel Espinoza, Arnoldo Riquelme, María Angélica Domínguez, Stefano Giovanni, María José Concha, Mauricio Burotto, Juan Ignacio Méndez, Margarita Pizarro, and Alex Escalona
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Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Adipokine ,Comorbidity ,Young Adult ,Insulin resistance ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,medicine ,Humans ,Aged ,Univariate analysis ,Nutrition and Dietetics ,Adiponectin ,medicine.diagnostic_test ,business.industry ,Leptin ,Fatty liver ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,Obesity, Morbid ,Fatty Liver ,Endocrinology ,Liver ,ROC Curve ,Liver biopsy ,Case-Control Studies ,Surgery ,Female ,Steatohepatitis ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Reduced serum levels of adiponectin have been associated with insulin resistance and non-alcoholic fatty liver disease (NAFLD). However, the relationship between serum adiponectin levels and hepatic histology in NAFLD is controversial. The aim of this study was to explore associations between plasma adiponectin concentrations and liver histology in morbidly obese patients. We conducted a case–control study including obese patients undergoing bariatric surgery and normal controls. Anthropometric, standard biochemical variables as well as plasma adiponectin and leptin levels were determined. Liver biopsy was performed in all patients at the time of surgery. Seventy morbidly obese patients (mean BMI, 40.6 ± 5.6 kg/m2) met the inclusion criteria and were compared with 69 controls (mean BMI, 22.8 ± 1.6 kg/m2, p = 0.0001). Thirty patients (43%) had NAFLD and 20 (28%) of them fulfilled the histological criteria for steatohepatitis. Obesity was associated with increased leptin and decreased adiponectin levels. NAFLD patients exhibited decreased levels of serum adiponectin compared with matched controls [median (Q1–Q3), 3.9 (3.2–4.3) vs. 8.6 (6.5–9.2) μg/mL, p
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- 2009
76. Actinomycosis: a great pretender. Case reports of unusual presentations and a review of the literature
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Luz M. Letelier, Rene Baudrand, Francisco Acevedo, and Pablo Gaete
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Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,Clinical presentation ,Review ,Gallbladder Diseases ,Actinomycosis ,Pericardial Effusion ,Cardiac tamponade ,Epidemiology ,medicine ,Pericardium ,Humans ,Vein ,Pelvis ,Pericardial actinomycosis ,Genitourinary system ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Dermatology ,Surgery ,medicine.anatomical_structure ,Infectious Diseases ,Gallbladder actinomycosis ,Female ,Presentation (obstetrics) ,business ,Infection - Abstract
SummaryActinomycosis is a rare, chronic disease caused by a group of anaerobic Gram-positive bacteria that normally colonize the mouth, colon, and urogenital tract. Infection involving the cervicofacial area is the most common clinical presentation, followed by pelvic region and thoracic involvement. Due to its propensity to mimic many other diseases and its wide variety of symptoms, clinicians should be aware of its multiple presentations and its ability to be a ‘great pretender’. We describe herein three cases of unusual presentation: an inferior caval vein syndrome, an acute cholecystitis, and an acute cardiac tamponade. We review the literature on its epidemiology, clinical presentation, diagnosis, treatment, and prognosis.
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- 2007
77. Statins and Musculoskeletal Adverse Events
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Rene Baudrand and Gordon H. Williams
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medicine.medical_specialty ,business.industry ,Internal Medicine ,MEDLINE ,Medicine ,Adverse effect ,business ,Intensive care medicine - Published
- 2014
78. Potential Role of Overexpression of 11β-Hydroxysteroid Dehydrogenase Type 1 in Visceral Adipose Tissue and Portal Hypercortisolism in the Pathogenesis of Non-Alcoholic Fatty Liver Disease
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Roberto Candia, Jaime Cerda, Cristian A. Carvajal, Rene Baudrand, Margarita Pizarro, Marco Arrese, Carlos E. Fardella, Camilo Boza, Arnoldo Riquelme, Mauricio Morales, Alex Escalona, Nancy Solís, Gustavo Pérez, and Oslando Padilla
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medicine.medical_specialty ,Hepatology ,biology ,business.industry ,Fatty liver ,Gastroenterology ,Adipose tissue ,Non alcoholic ,Disease ,White adipose tissue ,medicine.disease ,Pathogenesis ,Endocrinology ,11β-hydroxysteroid dehydrogenase type 1 ,Internal medicine ,biology.protein ,Medicine ,business - Published
- 2011
79. 11β-hydroxysteroid dehydrogenase type-2 and type-1 (11β-HSD2 and 11β-HSD1) and 5β-reductase activities in the pathogenia of essential hypertension.
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Carmen Campino, Cristian Carvajal, Javiera Cornejo, Betty Martín, Oliviero Olivieri, Giancesare Guidi, Giovanni Faccini, Francesco Pasini, Javiera Sateler, Rene Baudrand, Lorena Mosso, Gareth Owen, Alexis Kalergis, Oslando Padilla, and Carlos Fardella
- Abstract
Abstract Cortisol availability is modulated by several enzymes: 11β-HSD2, which transforms cortisol (F) to cortisone (E) and 11β-HSD1 which predominantly converts inactive E to active F. Additionally, the A-ring reductases (5α- and 5β-reductase) inactivate cortisol (together with 3α-HSD) to tetrahydrometabolites: 5αTHF, 5βTHF, and THE. The aim was to assess 11β-HSD2, 11β-HSD1, and 5β-reductase activity in hypertensive patients. Free urinary F, E, THF, and THE were measured by HPLC–MS/MS in 102 essential hypertensive patients and 18 normotensive controls. 11β-HSD2 enzyme activity was estimated by the F/E ratio, the activity of 11β-HSD1 in compare to 11β-HSD2 was inferred by the (5αTHF + 5βTHF)/THE ratio and 5β-reductase activity assessed using the E/THE ratio. Activity was considered altered when respective ratios exceeded the maximum value observed in the normotensive controls. A 15.7% of patients presented high F/E ratio suggesting a deficit of 11β-HSD2 activity. Of the remaining 86 hypertensive patients, two possessed high (5αTHF + 5βTHF)/THE ratios and 12.8% had high E/THE ratios. We observed a high percentage of alterations in cortisol metabolism at pre-receptor level in hypertensive patients, previously misclassified as essential. 11β-HSD2 and 5β-reductase decreased activity and imbalance of 11β-HSDs should be considered in the future management of hypertensive patients. [ABSTRACT FROM AUTHOR]
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- 2010
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80. Computed Tomography and Adrenal Venous Sampling in the Diagnosis of Unilateral Primary Aldosteronism
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Stella Bernardi, Andrzej Januszewicz, Fumitoshi Satoh, Tracy Ann Williams, Rene Baudrand, Michael Stowasser, Daniel A. Heinrich, Martin Reincke, Jacopo Burrello, Stella Douma, Gilberta Giacchetti, Marcus Quinkler, Cristiana Catena, Pieter M. Jansen, Christian Adolf, Tomaz Kocjan, Hironobu Umakoshi, Gaelle Saint-Hilary, Paolo Mulatero, Jiří Widimský, Stefanie Hahner, Carlos E. Fardella, Leonardo A. Sechi, Tetsuo Nishikawa, Francesco Fallo, Michalis Doumas, Joanna Matrozova, Felix Beuschlein, Williams, Tracy A, Burrello, Jacopo, Sechi, Leonardo A, Fardella, Carlos E, Matrozova, Joanna, Adolf, Christian, Baudrand, René, Bernardi, Stella, Beuschlein, Felix, Catena, Cristiana, Doumas, Michali, Fallo, Francesco, Giacchetti, Gilberta, Heinrich, Daniel A, Saint-Hilary, Gaëlle, Jansen, Pieter M, Januszewicz, Andrzej, Kocjan, Tomaz, Nishikawa, Tetsuo, Quinkler, Marcu, Satoh, Fumitoshi, Umakoshi, Hironobu, Widimský, Jiří, Hahner, Stefanie, Douma, Stella, Stowasser, Michael, Mulatero, Paolo, and Reincke, Martin
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,prevalence ,adrenalectomy ,aldosterone ,hyperaldosteronism ,quality of life ,renin ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Adrenalectomy ,Aldosterone ,Hyperaldosteronism ,Prevalence ,Quality of life ,Renin ,Adrenal Glands ,Biomarkers ,Blood Specimen Collection ,Female ,Humans ,Middle Aged ,Outcome Assessment (Health Care) ,Retrospective Studies ,Tomography, X-Ray Computed ,Veins ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Primary aldosteronism ,Outcome Assessment, Health Care ,Internal Medicine ,medicine ,Tomography ,business.industry ,Retrospective cohort study ,Odds ratio ,medicine.disease ,Adrenal venous sampling ,X-Ray Computed ,3. Good health ,chemistry ,Radiology ,business - Abstract
Unilateral primary aldosteronism is the most common surgically correctable form of endocrine hypertension and is usually differentiated from bilateral forms by adrenal venous sampling (AVS) or computed tomography (CT). Our objective was to compare clinical and biochemical postsurgical outcomes of patients with unilateral primary aldosteronism diagnosed by CT or AVS and identify predictors of surgical outcomes. Patient data were obtained from 18 internationally distributed centers and retrospectively analyzed for clinical and biochemical outcomes of adrenalectomy of patients with surgical management based on CT (n=235 patients, diagnosed from 1994–2016) or AVS (526 patients, diagnosed from 1994–2015) using the standardized PASO (Primary Aldosteronism Surgical Outcome) criteria. Biochemical outcomes were highly different according to surgical management approach with a smaller proportion in the CT group achieving complete biochemical success (188 of 235 [80%] patients versus 491 of 526 [93%], P P P P =0.013) in the CT but not in the AVS group. In conclusion, patients diagnosed by CT have a decreased likelihood of achieving complete biochemical success compared with a diagnosis by AVS.
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81. LC–MS/MS Method for the Simultaneous Determination of Free Urinary Steroids
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Carmen Campino, Rene Baudrand, Carlos F. Lagos, Andrea Vecchiola, Gareth I. Owen, Fidel Allende, Carolina Valdivia, Sandra Solari, Carlos E. Fardella, and Cristian A. Carvajal
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Analyte ,endocrine system ,Short Communication ,Coefficient of variation ,Clinical Biochemistry ,Urine ,Essential hypertension ,Biochemistry ,Cortisol ,Analytical Chemistry ,chemistry.chemical_compound ,medicine ,Tetrahydrocortisone ,Chromatography ,Mass spectrometry ,Organic Chemistry ,Tetrahydrocortisol ,11β-Hydroxysteroid dehydrogenase ,medicine.disease ,Metabolic syndrome ,chemistry ,Hypertension ,Column liquid chromatography ,Cortisone ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Cortisol homeostasis is implicated in hypertension and metabolic syndrome. Two enzymes modulate cortisol availability; 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) preferentially converts inactive cortisone to cortisol, whereas 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) converts cortisol to cortisone. In contrast, 5α and 5β reductases inactivate cortisol by conversion to its tetrahydrometabolites: tetrahydrocortisol, allo-tetrahydrocortisol and tetrahydrocortisone. A subtle local increase in cortisol can be detected by measuring 24-h urine metabolites, LC–MS/MS being the reference method. The 11β-HSD2 activity is assessed based on the cortisol/cortisone ratio, and the 11β-HSD1 activity on the (tetrahydrocortisol + allo-tetrahydrocortisol)/tetrahydrocortisone ratio. To better understand hypertension and/or metabolic syndrome pathogenesis a method for simultaneous determination of cortisol, cortisone, tetrahydrocortisol, allo-tetrahydrocortisol and tetrahydrocortisone was developed and validated in an LC coupled with the new detector AB Sciex QTrap® 4500 tandem mass spectrometer. The steroids were extracted from 1 mL urine, using cortisol-D4 as internal standard. The quantification range was 0.1–120 ng/mL for cortisol and cortisone, and 1–120 ng/mL for tetrahydrometabolites, with >89 % recovery for all analytes. The coefficient of variation and accuracy was
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