Browsing by Author "Pizarro, Margarita"
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- ItemEffect of losartan on early liver fibrosis development in a rat model of nonalcoholic steatohepatitis(WILEY, 2007) Ibanez, Patricio; Solis, Nancy; Pizarro, Margarita; Aguayo, Gloria; Duarte, Ignacio; Miquel, Juan Francisco; Accatino, Luigi; Arrese, MarcoBackground and aim: Nonalcoholic steatohepatitis (NASH) is a metabolic disorder of the liver that may evolve into fibrosis or cirrhosis. Recent studies have shown reduction of experimental liver fibrosis with the use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor antagonists. The aim of this study was to determine whether losartan can influence the early phase of fibrogenesis in an animal model of NASH.
- ItemEffects of Japanese herbal medicine inchin-ko-to on endotoxin-induced cholestasis in the rat(MEXICAN ASSOC HEPATOLOGY, 2009) Pablo Arab, Juan; Ramirez, Carolina; Munoz, Pablo; Pizarro, Margarita; Solis, Nancy; Riquelme, Arnoldo; Arrese, MarcoBackground/Objective. Inchin-ko-to (ICKT) is an herbal medicine used in Japan to treat jaundice and liver fibrosis. We investigated the effect of oral ICKT supplementation on endotoxin-induced cholestasis in the rat. Material and methods. Lipopolysaccharide (LPS) injection (1 mg/kg body weight i.p.) was used as a model of sepsis-induced cholestasis. Bite flow, biliary bile salt secretion, biliary glutathione secretion and protein expression of the main hepatobiliary transporters Na(+)-taurocholate-cotransporting peptide (Ntcp), multidrug resistance protein 2 (Mrp2) and bile salt export pump (Bsep) were analyzed by conventional techniques in ICKT treated and non-treated animals. Results. Injection of LIDS induced a significant decrease of bite ftow (-24%), biliary bite salts (-40%) and glutathione excretion (-70%) as well as a significant decrease in Ntcp (-90%) and Mrp2 (-80%) protein levels. ICKT supplementation partially prevented the effects of LIPS determining a less intense reduction in bile flow (-10%), a normalization of glutathione excretion as well as a significant increase in Mrp2 protein levels to 60% of the levels observed in control animals. ICKT administration did not modify the effects of LPS on BS secretion or Ntcp protein levels. Conclusion. Our data show that oral. supplementation of ICKT partially prevents LPS-induced cholestasis by increasing Mrp2 protein levels and biliary glutathione excretion thus increasing bite salt-independent ftow.
- ItemEvaluación de docentes clínicos de Postgrado: desarrollo y propiedades psicométricas del instrumento MEDUC-PG14(2015) Pizarro Rojas, Margarita Alicia; Solís, Nancy; Rojas, Viviana; Díaz, Luis Antonio; Padilla, Oslando; Letelier Saavedra, Luz María; Aizman, Andrés; Sarfatis Feige, Alberto; Olivos, Trinidad; Soza, Alejandro; Delfino, Alejandro; Latorre, Gonzalo; Ivanovic-Zuvic, Danisa; Hoyl, Trinidad; Bitrán Carreño, Marcela; Arab Verdugo, Juan Pablo; Riquelme Pérez, Arnoldo; Pizarro, Margarita; Solís, Nancy; Rojas, Viviana; Díaz, Luis Antonio; Padilla, Oslando; Letelier Saavedra, Luz María; Aizman, Andrés; Sarfatis Feige, Alberto; Olivos, Trinidad; Soza, Alejandro; Delfino, Alejandro; Latorre, Gonzalo; Ivanovic-Zuvic, Danisa; Hoyl, Trinidad; Bitrán Carreño, Marcela; Arab Verdugo, Juan Pablo; Riquelme Pérez, Arnoldo
- ItemEvaluation of the educational environment in medical specialty programs(SOC MEDICA SANTIAGO, 2012) Herrera, Cristian A.; Olivos, Trinidad; Roman, Jose Antonio; Larrain, Antonia; Pizarro, Margarita; Solis, Nancy; Sarfatis, Alberto; Torres, Patricio; Padilla, Oslando; Le Roy, Catalina; Riquelme, ArnoldoBackground: The Postgraduate Hospital Education Environment Measure (PHEEM) questionnaire, is a valid and reliable instrument to measure the educational environment (EE) in postgraduate medical education. Aim: To evaluate the EE perceived by the residents of a postgraduate training program using the PHEEM. Material and Methods: The PHEEM was applied in 2010-2011 in 35 specialty programs. We calculated their individual results and compared means of both global and individual domain scores of the PHEEM, by gender, university of origin and nationality. Cronbach's alpha coefficients and D study (Generalizability theory) were performed for reliability. Results: Three hundred eighteen residents were surveyed (75.7% of the total universe). The mean score of the PHEEM was 105.09 +/- 22.46 (65.7% of the maximal score) which is considered a positive EE. The instrument is highly reliable (Cronbach's alpha = 0.934). The D study found that 15 subjects are required to obtain reliable results (G coefficient = 0.813). There were no significant differences between gender and university of origin. Foreigners evaluated better the EE than Chileans and racism was not perceived. The programs showed a safe physical environment and teachers with good clinical skills. The negative aspects perceived were a lack of information about working hours, insufficient academic counseling, and scanty time left for extracurricular activities. Conclusions: This questionnaire allowed us to identify positive aspects of the EE, and areas to be improved in the specialty programs. The PHEEM is a useful instrument to evaluate the EE in Spanish-speaking participants of medical specialty programs. (Rev Med Chile 2012; 140: 1554-1561).
- ItemExperience of continuing online education in gastroenterology for non specialist medical doctors(SOC MEDICA SANTIAGO, 2019) Isbej, Lorena; Uribe, Javier; Carrasco, Olga; Villarroel, Isaac; Pizarro, Margarita; Isabel Jiron, Maria; Sanhueza, Edgar; Alvarez Lobos, Manuel; Hernandez Rocha, Cristian; Rollan, Antonio; Monsalve, Ximena; Antonio Diaz, Luis; Alejandra Cerda, Maria; Kramer, Tomas; Munizaga, Fernando; Riquelme, ArnoldoBackground: Continuing education is essential for health professions and online courses can be a good way for professional development. Aim: To describe the experience with online courses for continuing education in hepatology and gastroenterology and to analyze their educational impact. Material and Methods: A three years' experience in courses on liver diseases and digestive tract is described. Their curricular design, methodology, and the educational impact was analyzed using the four levels of the Kirkpatrick's model. Results: On average, there were 321 students per course (2015-2017). 94% were Chilean and 6% from abroad (20 countries). In the educational impact analysis, in level 1 "reaction": 93% said that the course fulfilled their expectations and 92% would recommend it. In level 2 "learning": 42% approved the courses. Level 3 "behavior" was not evaluated and level 4 "organizational change" highlighted that the traditional face-to-face continuing education model of Chilean Gastroenterology Society (SChG) changed to full distance model in these three courses, with 1284 students from South America, Asia and Europe, in a 3-years-period. Additionally, these programs were included in the Medical Society of Santiago (SMS) continuing education agenda. Conclusions: The alliance between the SMS and the SChG generated on line courses that meet the educational needs of physicians and medical students, with excellent results and student perception.
- ItemFarnesoid X Receptor Critically Determines the Fibrotic Response in Mice but Is Expressed to a Low Extent in Human Hepatic Stellate Cells and Periductal Myofibroblasts(ELSEVIER SCIENCE INC, 2009) Fickert, Peter; Fuchsbichler, Andrea; Moustafa, Tarek; Wagner, Martin; Zollner, Gernot; Halilbasic, Emina; Stoeger, Ulrike; Arrese, Marco; Pizarro, Margarita; Solis, Nancy; Carrasco, Gonzalo; Caligiuri, Alessandra; Sombetzki, Martina; Reisinger, Emil; Tsybrovskyy, Oleksiy; Zatloukal, Kurt; Denk, Helmut; Jaeschke, Hartmut; Pinzani, Massimo; Trauner, MichaelThe nuclear bile acid receptor, farnesoid X receptor (FXR), may play a pivotal role in liver fibrosis. We tested the impact of genetic FXR ablation in four different mouse models. Hepatic fibrosis was induced in wild-type and FXR knock-out mice (FXR-/-) by CCl4 intoxication, 3,5-diethoxycarbonyl-1,4-dihydrocollidine feeding, common bile duct ligation, or Schistosoma mansoni (S.m.)-infection. In addition, we determined nuclear receptor expression levels (FXR, pregnane X receptor (PXR), vitamin D receptor, constitutive androstane receptor (CAR), small heterodimer partner (SHP)) in mouse hepatic stellate cells (HSCs), portal myofibroblasts (MFBs), and human HSCs. Cell type-specific FXR protein expression was determined by immunohistochemistry in five mouse models and prototypic human fibrotic liver diseases. Expression of nuclear receptors was much lower in mouse and human HSCs/MFBs compared with total liver expression with the exception of vitamin D receptor. FXR protein was undetectable in mouse and human HSCs and MFBs. FXR loss had no effect in CCl4-intoxicated and S. m.-infected mice, but significantly decreased liver fibrosis of the bitiary type (common bile duct ligation, 3,5-diethoxycarbonyl-1,4-dihydrocoUidine). These data suggest that FXR loss significantly reduces fibrosis of the biliary type, but has no impact on non-cholestatic liver fibrosis. Since there is no FXR expression in HSCs and MFBs in liver fibrosis, our data indicate that these cells may not represent direct therapeutic targets for FXR ligands. (Am J Pathol 2009, 175;2392-2405; DOI: 10.2353/ajpath.2009.090114)
- ItemMild hypothermia does not affect liver regeneration after partial hepatectomy in mice(WILEY, 2009) Pablo Arab, Juan; Pizarro, Margarita; Solis, Nancy; Sun, Hongdan; Thevananther, Sundararajah; Arrese, MarcoThe use of mild hypothermia has been suggested to be therapeutically useful in treating acute liver failure. It is not known if hypothermia influences liver regeneration.
- ItemMineralocorticoid 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.
- ItemOverexpression 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.
- ItemOverexpression 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, MarcoBackground: 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.
- 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.