Browsing by Author "Lagos, Carlos"
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Item Clinical, Biochemical, and Genetic Characteristics of “Nonclassic” Apparent Mineralocorticoid Excess Syndrome(Oxford University Press, 2019) Tapia-Castillo, Alejandra; Baudrand, Rene; Vaidya, Anand; Campino, Carmen; Allende, Fidel; Valdivia, Carolina; Vecchiola, Andrea; Lagos, Carlos; Fuentes, Cristóbal; Solari, Sandra; Martínez-Aguayo, Alejandro; García, Hernán; Carvajal, Cristian; Fardella, CarlosContext Classical apparent mineralocorticoid excess (AME) is a rare recessive disorder, caused by severe 11β-hydroxysteroid dehydrogenase type 2 enzyme (11β-HSD2) deficiency. AME manifests as low-renin pediatric hypertension, hypokalemia and high cortisol/cortisone (F/E) ratio. Objective To evaluate nonclassic AME (NC-AME) due to partial 11β-HSD2 insufficiency and its association with hypertension, mineralocorticoid receptor (MR) activation, and inflammatory parameters. Design Cross-sectional study. Setting Primary care cohort. Participants We recruited 127 adolescents and adults. Subjects with secondary hypertension were excluded. We measured clinical, biochemical, renal, vascular, and inflammatory variables. Sequencing of HSD11B2 gene was performed in all subjects. Main Outcome Measure NC-AME. Results Serum F/E ratio was positively associated with systolic blood pressure (BP), microalbuminuria, and high-sensitivity C-reactive protein (hs-CRP). Serum cortisone correlated with MR activation parameters even when adjusted for age, body mass index, and sex: lower cortisone with higher potassium excretion (partial r = −0.29, P = 0.002) and with lower plasma renin activity (PRA) (partial r = 0.29, P = 0.001). Consistently, we identified 9 in 127 subjects (7.1%) with high F/E ratios (first quartile) and low cortisone (last quartile), suggestive of NC-AME. These subjects had higher systolic BP, 141.4 ± 25.7 mm Hg vs 127.3 ± 18.1 mm Hg, P = 0.03; lower PRA, 0.36 ± 0.19 ng/L*s vs 0.64 ± 0.47 ng/L*s, P < 0.0001; and greater potassium excretion, microalbuminuria, hs-CRP, and plasminogen activator inhibitor. We only found in 2 out of 9 subjects with NC-AME heterozygous mutations in the HSD11B2 gene. Conclusions These findings suggest a spectrum of partial 11β-HSD2 insufficiency in a primary care cohort without the classic phenotype and genotype of AME. NC-AME may represent a phenotype of MR activation and cardiovascular risk, suggesting that these subjects could be treated with MR antagonists.Publication NLC-Based Rifampicin Delivery System: Development and Characterization for Improved Drug Performance Against Staphylococcus aureus(2025) Carrasco, Javiera; Sandoval, Felipe; Schuh, Christina; Lagos, Carlos; Morales, Javier; Arriagada, Francisco; Ortiz, AndreaBackground/Objectives: Rifampicin is a typical antibiotic used for the treatment of Staphylococcus aureus (S. aureus) infections; however, its clinical utility is limited by poor aqueous solubility, chemical instability, and increasing bacterial resistance. Nanostructured lipid carriers (NLCs) offer a promising strategy to improve drug solubility, stability, and antimicrobial performance. Methods: In this study, rifampicin-loaded NLC (NLC-RIF) was developed using a hot homogenization with a low energy method and characterized in terms of particle size, polydispersity index, zeta potential, encapsulation efficiency, colloidal stability, and drug loading. Results: In vitro release studies under sink conditions demonstrated a biphasic release pattern, best described by the Korsmeyer-Peppas model, suggesting a combination of diffusion and matrix erosion mechanisms. Antimicrobial activity against S. aureus revealed a substantial increase in potency for NLC-RIF, with an IC50 of 0.46 ng/mL, approximately threefold lower than that of free rifampicin. Cytotoxicity assays in HepG2 cells confirmed over 90% cell viability across all tested concentrations. Conclusions: These findings highlight the potential of NLC-RIF as a biocompatible and effective nanocarrier system for enhancing rifampicin delivery and antibacterial activity.Item Serum Cortisol and Cortisone as Potential Biomarkers of Partial 11β-Hydroxysteroid Dehydrogenase Type 2 Deficiency(2018) Carvajal, Cristian; Tapia, Alejandra; Valdivia, Carolina; Allende, Fidel; Solari, Sandra; Lagos, Carlos; Campino, Carmen; Martínez, Alejandro; Vecchiola, Andrea; Pinochet, Constanza; Godoy, Claudia; Iturrieta, Virginia; Baudrand, Rene; Fardella, CarlosBackground: Pathogenic variations in HSD11B2 gene triggers the apparent mineralocorticoid excess syndrome (AME). There is scarce information regarding the phenotypes of subjects carrying heterozygous pathogenic variants in HSD11B2 gene. We investigated if serum cortisol/cortisone (F/E) ratio and cortisone are useful for identifying partial 11βHSD2 deficiency in those heterozygous subjects. Methods: We studied two patients diagnosed with AME and their families carrying either D223N or R213C mutation. We also evaluated 32 healthy control subjects (13 children and 19 adults) to obtain normal references ranges for all measured variables. Case 1: A boy carrying D223N mutation in HSD11B2 gene and Case 2: A girl carrying R213C mutation. We assessed serum F/E ratio and cortisone by HPLC-MS/MS, aldosterone, plasma-renin-activity(PRA), electrolytes, and HSD11B2 genetic analyses. Results: The normal values (median [interquartile range]) in children for serum F/E and cortisone (µg/dl) were 2.56 [2.21-3.69] and 2.54 [2.35-2.88], and in adults were 4.42 [3.70-4.90] and 2.23 [1.92-2.57], respectively. Case 1 showed a very high serum F/E 28.8 and low cortisone 0.46 µg/dl. His mother and sister were normotensives and heterozygous for D223N mutation with high F/E (13.2 and 6.0, respectively) and low cortisone (2.0 and 2.2, respectively). Case 2 showed a very high serum F/E 175 and suppressed cortisone 0.11 µg/dl. Her parents and sister were heterozygous for the R213C mutation with normal phenotype, but high F/E and low cortisone. Heterozygous subjects showed normal aldosterone, PRA, but lower fractional excretion of sodium and urinary Na/K ratio than controls. Conclusion: Serum F/E ratio and cortisone allow to identify partial 11βHSD2 deficiencies, as occurs in heterozygous subjects, who would be susceptible to develop arterial hypertension.