Browsing by Author "Baudrand, Rene"

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    11 beta-hydroxysteroid dehydrogenase type-2 and type-1 (11 beta-HSD2 and 11 beta-HSD1) and 5 beta-reductase activities in the pathogenia of essential hypertension
    (HUMANA PRESS INC, 2010) Campino, Carmen; Carvajal, Cristian A.; Cornejo, Javiera; San Martin, Betty; Olivieri, Oliviero; Guidi, Giancesare; Faccini, Giovanni; Pasini, Francesco; Sateler, Javiera; Baudrand, Rene; Mosso, Lorena; Owen, Gareth I.; Kalergis, Alexis M.; Padilla, Oslando; Fardella, Carlos E.
    Cortisol availability is modulated by several enzymes: 11 beta-HSD2, which transforms cortisol (F) to cortisone (E) and 11 beta-HSD1 which predominantly converts inactive E to active F. Additionally, the A-ring reductases (5 alpha- and 5 beta-reductase) inactivate cortisol (together with 3 alpha-HSD) to tetrahydrometabolites: 5 alpha THF, 5 beta THF, and THE. The aim was to assess 11 beta-HSD2, 11 beta-HSD1, and 5 beta-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. 11 beta-HSD2 enzyme activity was estimated by the F/E ratio, the activity of 11 beta-HSD1 in compare to 11 beta-HSD2 was inferred by the (5 alpha THF + 5 beta THF)/THE ratio and 5 beta-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 11 beta-HSD2 activity. Of the remaining 86 hypertensive patients, two possessed high (5 alpha THF + 5 beta THF)/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. 11 beta-HSD2 and 5 beta-reductase decreased activity and imbalance of 11 beta-HSDs should be considered in the future management of hypertensive patients.
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    11β-hydroxysteroid dehydrogenase type 2 polymorphisms and activity in a Chilean essential hypertensive and normotensive cohort.
    (2012) Campino, Carmen; Quinteros, Hector; Owen, Gareth I.; Carvajal, Cristian A.; Morales, Mauricio; Olivieri, Oliviero; Guidi, Giancesare; Faccini, Giovanni; Pasini, Francesco; Baudrand, Rene; Padilla, Oslando; Valdivia, Carolina; Thichauer, Juan; Lagos, Carlos F.; Kalergis, Alexis M.; Fardella, Carlos E.
    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.
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    3-Epi-25 Serum 25-Hydroxyvitamin D3 Concentrations in Chilean Children Between 5 and 8 Years
    (KARGER, 2018) Arancibia, Monica; Seiltgens, Cristian; Poggi, Helena; Allende, Fidel; Solari, Sandra; Peredo, Soledad; Trincado, Claudia; Garcia, Hernan; Moore, Rosario; Dapremont, Ivonne; Andrade, Daniela; Sifaqui, Sofia; Ossa, Jt; Campino, Carmen; Carvajal, Cristian; Fardella, Carlos; Baudrand, Rene; Sanchez, Ximena; Martinez Aguayo, Alejandro
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    An Ultrasound Model to Discriminate the Risk of Thyroid Carcinoma
    (ELSEVIER SCIENCE INC, 2011) Miguel Dominguez, Jose; Baudrand, Rene; Cerda, Jaime; Campusano, Claudia; Fardella, Carlos; Arteaga, Eugenio; Cruz, Francisco; Solar, Antonieta; Arias, Tatiana; Mosso, Lorena
    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 IC and to validate a previously proposed model based on the presence of three ultrasonographic characteristics.,
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    Citosine-Adenine-Repeat Microsatellite of 11 beta-hydroxysteroid dehydrogenase 2 Gene in Hypertensive Children
    (OXFORD UNIV PRESS, 2016) Valdivia, Carolina; Carvajal, Cristian A.; Campino, Carmen; Allende, Fidel; Martinez Aguayo, Alejandro; Baudrand, Rene; Vecchiola, Andrea; Lagos, Carlos F.; Tapia Castillo, Alejandra; Fuentes, Cristobal A.; Aglony, Marlene; Solari, Sandra; Kalergis, Alexis M.; Garcia, Hernan; Owen, Gareth I.; Fardella, Carlos E.
    BACKGROUND
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    Classic and nonclassic apparent mineralocorticoid excess syndrome
    (Endocrine Society, 2020) Carvajal, Cristián A.; Tapia-Castillo, Alejandra; Vecchiola, Andrea; Baudrand, Rene; Fardella, Carlos
    © 2020 Endocrine Society. All rights reserved.Context: Arterial hypertension (AHT) is one of the most frequent pathologies in the general population. Subtypes of essential hypertension characterized by low renin levels allowed the identification of 2 different clinical entities: aldosterone-mediated mineralocorticoid receptor (MR) activation and cortisol-mediated MR activation. Evidence Acquisition: This review is based upon a search of Pubmed and Google Scholar databases, up to August 2019, for all publications relating to endocrine hypertension, apparent mineralocorticoid excess (AME) and cortisol (F) to cortisone (E) metabolism. Evidence Synthesis: The spectrum of cortisol-mediated MR activation includes the classic AME syndrome to milder (nonclassic) forms of AME, the latter with a much higher prevalence (7.1%) than classic AME but different phenotype and genotype. Nonclassic AME (NC-AME) is mainly related to partial 11βHSD2 deficiency associated with genetic variations and epigenetic modifications (first hit) and potential additive actions of endogenous or exogenous inhibitors (ie, glycyrrhetinic acid-like factors [GALFS]) and other factors (ie, age, high sodium intake) (second hit). Subjects with NC-AME are characterized by a high F/E ratio, low E levels, normal to elevated blood pressure, low plasma renin and increased urinary potassium excretion. NCAME condition should benefit from low-sodium and potassium diet recommendations and monotherapy with MR antagonists. Conclusion: NC-AME has a higher prevalence and a milder phenotypical spectrum than AME. NC-AME etiology is associated to a first hit (gene and epigene level) and an additive second hit. NC-AME subjects are candidates to be treated with MR antagonists aimed to improve blood pressure, end-organ damage, and modulate the renin levels.
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    Clinical Presentation and Perioperative Management of Pheochromocytomas and Paragangliomas: A 4-Decade Experience
    (ENDOCRINE SOC, 2021) Uslar, Thomas; San Francisco, Ignacio F.; Olmos, Roberto; Macchiavelo, Stefano; Zuniga, Alvaro; Rojas, Pablo; Garrido, Marcelo; Huete, Alvaro; Mendez, Gonzalo P.; Cortinez, Ignacio; Zemelman, Jose Tomas; Cifuentes, Joaquin; Castro, Fernando; Olivari, Daniela; Dominguez, Jose Miguel; Arteaga, Eugenio; Fardella, Carlos E.; Valdes, Gloria; Tagle, Rodrigo; Baudrand, Rene
    Purpose: Latin American reports on pheochromocytomas and paragangliomas (PPGLs) are scarce. Recent studies demonstrate changes in clinical presentation and management of these patients. Herein, we assessed the main characteristics of PPGL patients in our academic center over the past 4 decades.
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    Corrigendum: Impact of short and long exposure to cafeteria diet on food intake and white adipose tissue lipolysis mediated by glucagon-like peptide 1 receptor
    (FRONTIERS MEDIA SA, 2023) Mattar, Pamela; Jaque, Cristian; Teske, Jennifer A.; Morselli, Eugenia; Kerr, Bredford; Cortes Mora, Víctor Antonio; Baudrand, Rene; Perez-Leighton, Claudio E. E.
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    High prevalence of autoimmune gastropathy, clinical characteristics and association with hypothyroidism: prospective analisys of 921 patients with gastric biopsies by sydney protocol
    (2018) Vargas Domínguez, José Ignacio; Maquilon, Sara; Torres, Javiera; Revelo, Santiago; Vargas, Camila; Garcia-Huidobro, Antonia; Castro, Josefina; Candia, Roberto; Gonzalez, Robinson G.; Baudrand, Rene; Espino, Alberto
    BACKGROUND: The prevalence of autoimmune gastropathy is increasing, and is considered underdiagnosed. The application of the Sydney protocol for gastric biopsies will probably allow to detect more cases at an early stage. AIM: To determine the prevalence of autoimmune gastropathy in gastric biopsies according to Sydney-OLGA protocol, and define its clinical and laboratory characteristics. Explore the association of autoimmune gastropathy with other autoimmune diseases. METHODS: Single center prospective observational study. Evaluation of gastric biopsies according to Sydney protocol between July 2016 and July 2017 to determine prevalence of autoimmune gastropathy. Autoimmune gastropathy was defined by histologic criteria as gastric corporal exclusive or predominant atrophy. Identification of histologic, clinical and laboratory findings of patients with autoimmune gastropathy. Descriptive statistics and inferential analysis comparing histological findings of autoimmune gastropathy and H. pylori-associated gastropathy. RESULTS: 921 gastric biopsies were evaluated. Mean age was 58 years (range 27-87), 58% female gender. The prevalence of autoimmune gastropathy was 8.8% (81/921). Presence of OLGA stages 3-4 was higher in autoimmune gastropathy than in HP-associated gastropathy (33.3 vs 15.8%, p = 0.004). Age was no different between the two groups (p=0.82). In the characterization of patients with autoimmune gastropathy, the prevalence of gastric polyps in autoimmune gastropathy was 11% (9/81), 4 of then were NETs. In patients with autoimmune gastropathy, only 3.3% had a previous diagnosis of pernicious anemia, and in 11% the reasons for endoscopy was the study of anemia. 18.5% had family history of gastric cancer. The prevalence of hypothyroidism was 30% (24/81). Other autoimmune disease was less frequent (13.5%). CONCLUSION: Our study shows a high prevalence of autoimmune gastropathy detected by gastric biopsies with Sydney protocol. In most cases, clinical characteristics of pernicious anemia was absent and the suspicion for this disease prior to endoscopy was low. Presence of advanced stages of gastric atrophy were frequent. The prevalence of thyrogastric syndrome, autoimmune gastropathy associated to hypothyroidism, was also frequent. The use of Sydney protocol for gastric biopsies allows to detect a higher proportion of patients with autoimmune gastropathy at early stages of the disease.
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    Higher Dehydroepiandrosterone Levels in Prepubertal Children Born Very Preterm
    (KARGER, 2018) Mericq, Veronica; Martinez Aguayo, Alejandro; Iniguez, German; Poggi, Helena; D'Apremont, Ivonne; Moore, Rosario; Arancibia, Monica; Garcia, Hernan; Peredo, Soledad; Trincado, Claudia; Sifaqui, Sofia; Tomas Ossa, Jose; Fardella, Carlos; Carvajal, Cristian; Campino, Carmen; Baudrand, Rene; Solari, Sandra; Allende, Fidel
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    Increased urinary glucocorticoid metabolites are associated with metabolic syndrome, hypoadiponectinemia, insulin resistance and beta cell dysfunction
    (ELSEVIER SCIENCE INC, 2011) Baudrand, Rene; Campino, Carmen; Carvajal, Cristian A.; Olivieri, Oliviero; Guidi, Giancesare; Faccini, Giovanni; Sateler, Javiera; Cornejo, Javiera; San Martin, Betty; Dominguez, Jose M.; Cerda, Jaime; Mosso, Lorena M.; Owen, Gareth I.; Kalergis, Alexis M.; Fardella, Carlos E.
    Metabolic syndrome (MetS) may have increased cortisol (F) production caused by 11 beta-hydroxysteroid dehydrogenase 1 (11 beta-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 (24 h) F. E and THM levels. beta 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-beta but no differences in F and E in plasma or urine. THM was associated with weight (r = +0.44, p < 0,001), waist circumference (r = +0.38, p < 0.01). glycemia (r = +0.37, p < 0.01), and triglycerides (r = +0.18, p = 0.06) and negatively correlated with adiponectin (r = -0.36, p < 0.001), HOMA-beta (r = -0.21, p < 0.001) and HDL (r = -0.29, p < 0.01). 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 beta 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. (C) 2011 Elsevier Inc. All rights reserved.
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    Insulin Resistance Parameters in Children Who Were Born Very Preterm and Adequate for Gestational Age
    (KARGER, 2018) Garcia, Hernan; Poggi, Helena; Arancibia, Monica; Peredo, Soledad; Trincado, Claudia; Moore, Rosario; D'Apremont, Ivonne; Andrade, Daniela; Sifaqui, Sofia; Ossa, J. T.; Campino, Carmen; Carvajal, Cristian; Fardella, Carlos; Baudrand, Rene; Solari, Sandra; Allende, Fidel; Martinez Aguayo, Alejandro
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    Mineralocorticoid receptor modulation by dietary sodium influences NAFLD development in mice
    (ELSEVIER ESPANA, 2021) Cabrera, Daniel; Rao, Isabel; Raasch, Fabiola; Solis, Nancy; Pizarro, Margarita; Freire, Mariela; De Urturi, Diego Saenz; Ramirez, Carolina A.; Triantafilo, Nicolas; Leon, Jonathan; Riquelme, Arnoldo; Barrera, Francisco; Baudrand, Rene; Aspichueta, Patricia; Arrese, Marco; Arab, Juan P.
    Introduction and Objectives: Nonalcoholic-fatty-liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome (MetS). Mineralocorticoid receptor (MR) activation is associated with increased risk of MetS but few studies have assessed the role of liver MR on NAFLD. We aimed to evaluate the effect of MR modulation by sodium intake in liver injury in experimental models of NAFLD.
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    Overexpression of 11 beta-Hydroxysteroid Dehydrogenase Type 1 in Hepatic and Visceral Adipose Tissue is Associated with Metabolic Disorders in Morbidly Obese Patients
    (SPRINGER, 2010) Baudrand, Rene; Carvajal, Cristian A.; Riquelme, Arnoldo; Morales, Mauricio; Solis, Nancy; Pizarro, Margarita; Escalona, Alex; Boza, Camilo; Perez, Gustavo; Dominguez, Angelica; Arrese, Marco; Fardella, Carlos E.
    The enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11 beta-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 11 beta-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.
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    Overexpression of 11 beta-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue and portal hypercortisolism in non-alcoholic fatty liver disease
    (WILEY, 2012) Candia, Roberto; Riquelme, Arnoldo; Baudrand, Rene; Carvajal, Cristian A.; Morales, Mauricio; Solis, Nancy; Pizarro, Margarita; Escalona, Alex; Carrasco, Gonzalo; Boza, Camilo; Perez, Gustavo; Padilla, Oslando; Cerda, Jaime; Fardella, Carlos E.; Arrese, Marco
    Background: The enzyme 11 beta-hydroxysteroid-dehydrogenase type 1 (11 beta HSD1) catalyses the reactivation of intracellular cortisol. We explored the potential role of 11 beta-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. 11 beta-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). 11 beta-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 < 0.05). No significant differences were found in peripheral corticosterone serum levels. Expression of 11b-HSD1 was lower in the liver [-45% at 8 weeks and -35% at 12-weeks (P = 0.0001)] and highly overexpressed in VAT in obese mice, compared to controls (128-fold higher in 8-week-old ob/ob and 41-fold higher in 12-week-old ob/ob, P < 0.01). No significant differences were seen in the expression of 11 beta-HSD1 in subcutaneous adipose tissue. In multivariate analysis, human 11 beta-HSD1 expression in VAT (OR: 1.385 +/- 1.010-1.910) was associated with NAFLD. Conclusion: Murine NAFLD is associated with portal hypercortisolism and 11 beta-HSD1 overexpression in VAT. In humans, 11 beta-HSD1 VAT expression was associated with the presence of NAFLD. Thus, local corticosteroid production in VAT may contribute to NAFLD pathogenesis.
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    Polymorphisms in the RAC1 Gene Are Associated With Hypertension Risk Factors in a Chilean Pediatric Population
    (OXFORD UNIV PRESS, 2014) Tapia Castillo, Alejandra; Carvajal, Cristian A.; Campino, Carmen; Vecchiola, Andrea; Allende, Fidel; Solari, Sandra; Garcia, Lorena; Lavanderos, Sergio; Valdivia, Carolina; Fuentes, Cristobal; Lagos, Carlos F.; Martinez Aguayo, Alejandro; Baudrand, Rene; Aglony, Marlene; Garcia, Hernan; Fardella, Carlos E.
    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, G > A) and rs836478 (intron 3, T > C) in the RAC1 gene and perform association studies with clinical and biochemical parameters in a Chilean pediatric cohort.