Browsing by Author "Jarufe Cassis, Nicolas Patricio"

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    Ezetimibe prevents cholesterol gallstone formation in mice
    (2008) Zuñiga, Silvia Eugenia; Molina, Héctor; Azócar, Lorena; Amigo Boker, Ludwig Peter; Nervi Oddone, Flavio; Pimentel Muller, Fernando Ernesto; Jarufe Cassis, Nicolas Patricio; Arrese Jimenez, Marco Antonio; Lammert, Frank; Miquel Poblete, Juan Francisco
    Background: Intestinal cholesterol absorption may influence gallstone formation and its modulation could be a useful therapeutic strategy for gallstone disease (GSD). Ezetimibe (EZET) is a cholesterol-lowering agent that specifically inhibits intestinal cholesterol absorption. Aims: To test whether EZET can prevent gallstone formation in mice. Methods/Results: Gallstone-susceptible C57BL/6 inbred mice were fed control and lithogenic diets with or without simultaneous EZET administration. Lithogenic diet increased biliary cholesterol content and secretion, and induced sludge or gallstone formation in 100% of the animals. EZET administration reduced intestinal cholesterol absorption by 90% in control animals and by 35% in mice receiving the lithogenic diet. EZET prevented the appearance of cholesterol crystals and gallstones. In addition, mice fed the lithogenic diet plus EZET exhibited a 60% reduction in biliary cholesterol saturation index. Of note, EZET treatment caused a significant increase in bile flow (+50%, P < 0.01) as well as bile salt, phospholipid and glutathione secretion rates (+60%, +44% and +100%, respectively, P < 0.01), which was associated with a moderately increased expression of hepatic bile salt transporters. In addition, relative expression levels of Nieman-Pick C1 like 1 (NPC1L1) in the enterohepatic axis in humans were assessed. Expression levels of NPC1L1 were 15-to 30-fold higher in the duodenum compared with the liver at transcript and protein levels, respectively, suggesting preferential action of EZET on intestinal cholesterol absorption in humans. Conclusions: In a murine model of GSD, EZET prevented gallstone formation by reducing intestinal cholesterol absorption and increasing bile salt-dependent and -independent bile flow. EZET could be useful in preventing GSD disease in susceptible patients.
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    Trasplante hepático: Evolución, curva de aprendizaje y resultados después de los primeros 300 casos
    (2019) Quezada González, José Luis; Cancino, Alejandra; Arrese Jimenez, Marco Antonio; Wolff, Rodrigo; Benitez Gajardo, Carlos Esteban; Pattillo Silva, Juan Carlos; Gana Ansaldo, Juan Cristobal; Concha Pinto, Mario Rodrigo; Cortinez Fernandez, Luis Ignacio; Vera Alarcón, María Magdalena; Miranda, Paula; Rubilar, Francisco; Troncoso, Andrés; Briceno Valenzuela, Eduardo Andres; Dib Marambio, Martin Javier; Jarufe Cassis, Nicolas Patricio; Martínez, Jorge; Guerra Castro, Juan Francisco
    Liver transplantation (LT) is an option for people with liverfailure who cannot be cured with other therapies and for some people with liver cancer. Aim: To describe, and analyze the first 300 LT clinical results, andto establish our learning curve. Material and Methods: Retrospective cohortstudy with data obtained from a prospectively collected LT Program database.We included all LT performed at a single center from March 1994 to September2017. The database gathered demographics, diagnosis, indications for LT, surgicalaspects and postoperative courses. We constructed a cumulative summation testfor learning curve (LC-CUSUM) using 30-day post-LT mortality. Mortality at 30days, and actuarial 1-, and 5-year survival rate were analyzed. Results: A total of281 patients aged 54 (0-71) years (129 women) underwent 300 LT. Ten percentof patients were younger than 18 years old. The first, second and third indicationsfor LT were non-alcoholic steatohepatitis, chronic autoimmune hepatitis andalcoholic liver cirrhosis, respectively. Acute liver failure was the LT indication in51 cases (17%). The overall complication rate was 71%. Infectious and biliarycomplications were the most common of them (47 and 31% respectively). TheLC-CUSUM curve shows that the first 30 patients corresponded to the learningcurve. The peri-operative mortality was 8%. Actuarial 1 and 5-year survival rateswere 82 and 71.4%, respectively. Conclusions: Outcome improvement of a LTprogram depends on the accumulation of experience after the first 30 transplantsand the peri-operative mortality directly impacted long-term survival.