Browsing by Author "Campino, Carmen"
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- Item11 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.
- Item11β-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.
- Item3-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
- ItemAldosterone, Plasma Renin Activity, and Aldosterone/Renin Ratio in a Normotensive Healthy Pediatric Population(LIPPINCOTT WILLIAMS & WILKINS, 2010) Martinez Aguayo, Alejandro; Aglony, Marlene; Campino, Carmen; Garcia, Hernan; Bancalari, Rodrigo; Bolte, Lillian; Avalos, Carolina; Loureiro, Carolina; Carvajal, Cristian A.; Avila, Alejandra; Perez, Viviana; Inostroza, Andrea; Fardella, Carlos E.Primary aldosteronism is an important cause of secondary hypertension and is suspected in adults with an aldosterone/renin ratio >= 25. The normal aldosterone/renin ratio is unknown in children. The aim was to establish serum aldosterone, plasma renin activity, and aldosterone/renin ratio values in a healthy pediatric population. A cross-sectional study was performed in 211 healthy normotensive children (4 to 16 years old). Two subgroups of normotensive children were obtained: with hypertensive parents (NH) (n=113) and normotensive parents (n=98). Blood samples for measuring serum aldosterone, plasma renin activity, aldosterone/renin ratio, and DNA were collected. In subjects with aldosterone/renin ratio >= 25, the chimeric CYP11B1/CYP11B2 gene was investigated by long-extension PCR. Results are expressed as median [Q(1)-Q(3)]. NH and normotensive parents groups were similar in serum aldosterone (6.5 [3.6 to 9.0] ng/dL versus 6.5 [2.9 to 9.7] ng/dL; P=0.968) and plasma renin activity (2.3 [1.6 to 3.1] versus 2.4 [1.7 to 3.7] ng/mL per hour; P=0.129). The aldosterone/renin ratio was higher in the NH group, but this difference did not reach statistical significance (2.8 [1.9 to 4.1] versus 2.5 [1.4 to 4.0], P=0.104). In one subject of the NH group, the chimeric CYP11B1/CYP11B2 gene was detected. We demonstrated that normal aldosterone/renin ratio values in a healthy pediatric population without NH were lower than those reported for an adult normotensive population. (Hypertension. 2010;56:391-396.)
- ItemBirth weight is inversely associated with blood pressure and serum aldosterone and cortisol levels in children(WILEY, 2012) Martinez Aguayo, Alejandro; Aglony, Marlene; Bancalari, Rodrigo; Avalos, Carolina; Bolte, Lillian; Garcia, Hernan; Loureiro, Carolina; Carvajal, Cristian; Campino, Carmen; Inostroza, Andrea; Fardella, CarlosContext Low birth weight has been independently associated with adult hypertension, and renin-angiotensin system (RAS) plays a role in this connection.
- ItemCitosine-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
- ItemFrequency of Familial Hyperaldosteronism Type 1 in a Hypertensive Pediatric Population Clinical and Biochemical Presentation(LIPPINCOTT WILLIAMS & WILKINS, 2011) Aglony, Marlene; Martinez Aguayo, Alejandro; Carvajal, Cristian A.; Campino, Carmen; Garcia, Hernan; Bancalari, Rodrigo; Bolte, Lillian; Avalos, Carolina; Loureiro, Carolina; Trejo, Pamela; Brinkmann, Karin; Giadrosich, Vinka; Mericq, Veronica; Rocha, Ana; Avila, Alejandra; Perez, Viviana; Inostroza, Andrea; Fardella, Carlos E.Familial hyperaldosteronism type 1 is an autosomal dominant disorder attributed to a chimeric CYP11B1/CYP11B2 gene (CG). Its prevalence and manifestation in the pediatric population has not been established. We aimed to investigate the prevalence of familial hyperaldosteronism type 1 in Chilean hypertensive children and to describe their clinical and biochemical characteristics. We studied 130 untreated hypertensive children (4 to 16 years old). Blood samples for measuring plasma potassium, serum aldosterone, plasma renin activity, aldosterone/renin ratio, and DNA were collected. The detection of CG was performed using long-extension PCR. We found 4 (3.08%) of 130 children with CG who belonged to 4 unrelated families. The 4 patients with CG had very high aldosterone/renin ratio (49 to 242). In addition, we found 4 children and 5 adults who were affected among 21 first-degree relatives. Of the 8 affected children, 6 presented severe hypertension, 1 presented prehypertension, and 1 presented normotension. High serum aldosterone levels (> 17.7 ng/dL) were detected in 6 of 8 subjects (range: 18.6 to 48.4 ng/dL) and suppressed plasma renin activity (<= 0.5 ng/mL per hour) and high aldosterone/renin ratio (> 10) in 8 of 8 children (range: 49 to 242). Hypokalemia was observed in only 1 of 8 children. We demonstrated that the prevalence of familial hyperaldosteronism type 1 in a pediatric hypertensive pediatric population was surprisingly high. We found a high variability in the clinical and biochemical characteristics of the affected patients, which suggests that familial hyperaldosteronism type 1 is a heterogeneous disease with a wide spectrum of presentations even within the same family group. (Hypertension. 2011;57:1117-1121.). Online Data Supplement
- ItemHigher 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
- ItemIncreased 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.
- ItemInsulin 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
- ItemOverexpression of hepatic 5 alpha-reductase and 11 beta-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue is associated with hyperinsulinemia in morbidly obese patients(W B SAUNDERS CO-ELSEVIER INC, 2011) Baudrand Biggs Rene Felipe; Domínguez Ruiz-tagle, José Miguel; Carvajal, Cristian A.; Riquelme, Arnoldo; Campino, Carmen; Macchiavello, Stefano; Bozinovic, Milan; Morales, Mauricio; Pizarro, Margarita; Solis, Nancy; Escalona, Alex; Boza, Camilo; Arrese, Marco; Fardella, Carlos E.11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) converts cortisone to cortisol, mainly in the liver and visceral adipose tissue (VAT), and has been implicated in several metabolic disorders. The absence of systemic hypercortisolism in central obesity could be due to increased inactivation of cortisol to its tetrahydrometabolites by the hepatic enzymes 5 alpha-and 5 beta-reductases. Our aim was to assess the expression of the reductases in the liver and of 11 beta-HSD1 in the liver and VAT in morbidly obese patients and to analyze their association with clinical, anthropometric, and biochemical parameters. Hepatic and VAT samples were obtained during bariatric surgery. 5 alpha- and 5 beta-reductases, 11 beta-HSD1, and 18S expression was measured using real-time polymerase chain reaction. Anthropometric and biochemical variables were analyzed. Forty-one patients were recruited (age, 41.8 +/- 10.6 years; body mass index, 42.1 +/- 6.6 kg/m(2); 71% women). The expression of hepatic 5 alpha- and 5 beta-reductases was positively correlated (r = +0.53, P = .004), and their expression levels were correlated with hepatic 11 beta-HSD1 expression (r = +0.61, P < .001 for 5 alpha-reductase and r = +0.50, P < .001 for 5 beta-reductase). Hepatic 5 alpha-reductase was associated with insulin (r = +0.34, P = .015). Visceral adipose tissue 11 beta-HSD1 expression was associated with glucose (r = +0.37, P = .025) and insulin (r = +0.54, P = .002). Our results showed that 5 alpha-reductase and VAT 11 beta-HSD1 expressions were associated with insulinemia. These findings suggest that overexpression of 5 alpha-reductase, through a higher inactivation of cortisol in the liver, could have a protective role in preserving hepatic sensitivity to insulin. The overexpression of liver reductases in obesity could be an adaptive response to an increase in cortisol production by the liver and visceral 11 beta-HSD1 to avoid systemic hypercortisolism. (C) 2011 Elsevier Inc. All rights reserved.
- ItemPolymorphisms 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.