Browsing by Author "Lagos, Carlos F."

Now showing 1 - 9 of 9
  • No Thumbnail Available
    Item
    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.
  • Thumbnail Image
    Item
    2D-QSAR and 3D-QSAR/CoMSIA Studies on a Series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-Phenylethan-1-ol with Human β₃-Adrenergic Activity
    (2017) Apablaza H., Gastón E.; Montoya, Luisa; Morales Verdejo, César Aarón; Mellado, Marco; Cuellar Fritis, Mauricio Alcides; Lagos, Carlos F.; Soto Delgado, Jorge; Chung, Hery; Pessoa Mahana, Carlos David; Jaime Mella
  • Thumbnail Image
    Item
    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
  • No Thumbnail Available
    Item
  • Thumbnail Image
    Item
    Design, synthesis, biological evaluation and binding mode modeling of benzimidazole derivatives targeting the cannabinoid receptor type 1
    (2015) Espinosa Bustos, Christian Marcelo; Lagos, Carlos F.; Romero Parra, Javier Hernán; Zárate Méndez, Ana María; Mella Raipán, Jaime Alberto; Pessoa Mahana, Hernán; Recabarren Gajardo, Gonzalo; Iturriaga Vásquez, Patricio; Tapia Apati, Ricardo; Pessoa Mahana, Carlos David
  • Thumbnail Image
    Item
    PCSK9 conjugated liposomes for targeted delivery of paclitaxel to the cancer cell: a proof-of-concept study
    (ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2022) Charbe, Nitin Bharat; Lagos, Carlos F.; Ortiz, Cristian Andres Vilos; Tambuwala, Murtaza; Palakurthi, Sushesh Srivatsa; Zacconi, Flavia C. M.
    Ligand-based targeting of the receptors that are overexpressed explicitly on cancer cells represents an effective drug delivery approach to enhance the chemotherapeutic efficacy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) which is a serine protease enzyme primarily produced by the liver cells, can potentially be used as a targeting ligand. PCSK9 binds to the LDL-r on hepatocytes' surface, leading to endocytosis and endosomal degradation. High LDL-r expression, which is believed to meet the higher demand of the cholesterol and phospholipids to build proliferating cancer cell membrane, ensures selective uptake of the PCSK9 conjugated liposomes. In the present work, the PCSK9 conjugated liposomal system was developed to deliver paclitaxel (PTX) to cancer cells. The protein was conjugated by EDC and NHS in a two-step coupling reaction to the li-posomes containing COOH-PEG2000-COOH lipid. Conjugation was confirmed by NMR, and liposomes were further characterized by SEM and zeta sizer. PCSK9-conjugated liposomes showed high encapsulation efficiency of 69.1% with a diameter of 90.0 & PLUSMN; 4.9 nm. Long-term stability (30 days) study (Zeta potential:-9.88) confirmed excellent constancy and significant drug retention (58.2%). Invitro cytotoxicity and targeting effi-ciency was explored using MTS assay in human embryonic kidney cells (HEK293), liver hepatocellular cells (HEPG2), and a human colon cancer cell line (HCT116) for 24 h. PCSK9 conjugated liposomes exhibited significantly higher growth inhibition than the unconjugated (control) liposomes in HCT116 cell line (p < 0.001). The novel PCSK9 conjugated liposomes presented potent and precise in vitro anticancer activity and, therefore, are suggested for the first time as a promising targeted delivery system for cancer treatment.
  • No Thumbnail Available
    Item
    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.
  • Thumbnail Image
    Item
    Structure-activity relationships studies on weakly basic N-arylsulfonylindoles with an antagonistic profile in the 5-HT6 receptor
    (2017) Mella, Jaime; Villegas, Francisco; Morales Verdejo, César Aarón; Lagos, Carlos F.; Recabarren Gajardo, Gonzalo
  • Thumbnail Image
    Item
    Usefulness and Pitfalls in Sodium Intake Estimation : Comparison of Dietary Assessment and Urinary Excretion in Chilean Children and Adults
    (2016) Campino Johnson, María del Carmen; Hill, Caroline; Baudrand Biggs, René; Martínez Aguayo, Alejandro Gregorio; Aglony Imbarack, Marlene Elizabeth; Carrasco, Carmen A.; Ferrada, Clarita; Loureiro Pérez, Carolina Andrea; Vecchiola Cárdenas, Andrea Paola; Bancalari, Rodrigo; Grob Lunecke, Francisca Andrea; Carvajal, Cristian A.; Lagos, Carlos F.; Valdivia, Carolina; Tapia-Castillo, Alejandra; Fuentes Zúñiga, Cristóbal Andrés; Mendoza, Carolina; García Bruce, Hernán; Uauy, Ricardo; Fardella B., Carlos; Campino Johnson, María del Carmen; Hill, Caroline; Baudrand Biggs, René; Martínez Aguayo, Alejandro Gregorio; Aglony Imbarack, Marlene Elizabeth; Carrasco, Carmen A.; Ferrada, Clarita; Loureiro Pérez, Carolina Andrea; Vecchiola Cárdenas, Andrea Paola; Bancalari, Rodrigo; Grob Lunecke, Francisca Andrea; Carvajal, Cristian A.; Lagos, Carlos F.; Valdivia, Carolina; Tapia-Castillo, Alejandra; Fuentes, Cristóbal A.; Mendoza, Carolina; García Bruce, Hernán; Uauy, Ricardo; Fardella B., Carlos