Browsing by Author "Amigo Boker, Ludwig Peter"

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    El ácido nicotínico aumenta el transporte celular de colesterol de las lipoproteínas de alta densidad en pacientes con hipoalfalipoproteinemia
    (2015) Figueroa, Catalina; Droppelmann Droppelmann, Katherine Ann; Quinones, Verónica; Amigo Boker, Ludwig Peter; Mendoza, Camila; Serrano Larrea, Valentina; Véjar, Margarita; Maiz Gurruchaga, Manuel Alberto; Rigotti Rivera, Attilio
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    Apolipoprotein A-I deficiency does not affect biliary lipid secretion and gallstone formation in mice
    (2011) Amigo Boker, Ludwig Peter; Quiñones, Verónica; Leiva Mendoza, Andrea Alejandra; Busso, Dolores; Zanlungo Matsuhiro, Silvana; Nervi, Flavio; Rigotti Rivera, Attilio
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    Biliary aminopeptidase-N and the cholesterol crystallization defect in cholelithiasis
    (British Medical Journal Publishing Group, 1995) Núñez, L.; Amigo Boker, Ludwig Peter; Mingrone, G.; Rigotti Rivera, Attilio Gianpietro; Puglielli, L.; Raddatz Echavarría, Alejandro; Pimentel González, Eduardo Fernando; Greco, A.; González, S.; Garrido Negri, Jorge; Miquel Poblete, Juan Francisco; Nervi Oddone, Flavio; Pontificia Universidad Católica de Chile. Departamento de Gastroenterología y Centro para la Prevención y tratamiento del Cáncer Digestivo; Institute of Clinical Medicine, Universita Cattolica del Sacro Cuore, Rome, Italy
    Several biliary proteins have cholesterol crystallisation promoting activity. One of these glycoproteins is aminopeptidase-N, a canalicular ectoenzyme. This study attempted to localise aminopeptidase-N along the biliary tree, to assess its concentration in a series of 98 patients subjected to abdominal surgery, 40 of them without gap stones, and to correlate its concentration with cholesterol crystal formation time of gall bladder bile. Aminopeptidase-N was isolated from purified native biliary vesicles. A specific polyclonal rabbit anti-aminopeptidase-N antibody was prepared for quantitative immunoblotting and for immunolocalisation. Tissue was obtained from liver biopsy specimens and from gall bladders removed at surgery because of gall stone disease. Aminopeptidase-N was immunolocalised to the apical membranes of hepatocytes and to the apical pole of ductular and gall bladder mucosal cells. The nucleation time of gall bladder bile was mean (SD) 4 (3) days in the gall stone group, compared with 21 (18) days in the control group (p < 0.001). Total absolute biliary protein and aminopeptidase-N concentrations were similar in both the control and gall stone patients. There was a reciprocal significant correlation, however, between the nucleation time and the relative aminopeptidase-N concentration (r = -0.35, p < 0.01) only in the gall stone group of patients, This study shows that this apical transmembrane ectoenzyme with cholesterol crystallisation promoting activity is present along the biliary tree and the hepatocyte. These findings support the concept that high concentrations or qualitative changes of biliary aminopeptidase-N contribute to cholesterol gall stone formation.
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    Cholesterol saturation, not proteins or cholecystitis, is critical for crystal formation in human gallbladder bile
    (W. B. Saunders Co., 1998) Miquel Poblete Juan Francisco; Nuñez, Liliana; Amigo Boker, Ludwig Peter; González Bombardiere, Sergio Javier; Raddatz Echavarría, Alejandro; Rigotti Rivera, Attilio Gianpietro; Nervi Oddone, Flavio
    Biliary proteins are promoters of cholesterol crystallization in artificial model bile. However, their pathogenic importance for cholesterol precipitation in native gallbladder bile (GB) is uncertain. The aim of this study was to evaluate the significance of biliary lipids and proteins on cholesterol crystal detection time (ChCDT) of GB in patients with gallstones. Methods: ChCDT and concentrations of lipids, albumin, mucins, aminopeptidase N, alpha 1-acid glycoprotein, haptoglobin, and immunoglobulins (Igs) were measured in GB of 92 patients, 52 of whom had cholesterol gallstones. Results: ChCDT was markedly reduced in gallstone patients. Compared with patients without gallstones, they had a significant increase in cholesterol saturation and total protein, albumin, mucin, and IgG biliary concentrations. In univariate analysis, ChCDT of GB was significantly correlated with cholesterol saturation and total lipid, protein, Ig, aminopeptidase N, and alpha 1-acid glycoprotein concentrations. However, stepwise logistic regression analysis showed that only cholesterol saturation independently correlated to ChCDT. Gallbladder inflammation correlated with the concentration of Igs, but subtraction of IgG from GB did not modify the ChCDT. Conclusions: Biliary cholesterol transport and saturation, but not proteins, appear critical for the cholesterol crystallization abnormality observed in native bile from patients with gallstones.
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    Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis
    (2014) Busso, Dolores; Mascareno, L.; Salas, F.; Berkowitz Fiebich, Loni; Santander, N.; Quiroz Vallverdu, Alonso Ingmar; Amigo Boker, Ludwig Peter; Valdés Stromilli, Gloria; Rigotti Rivera, Attilio
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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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    Fecal bile acid excretion and messenger RNA expression levels of ileal transporters in high risk gallstone patients
    (2009) Herrera Sepúlveda, Jorge Gabriel; Amigo Boker, Ludwig Peter; Benítez, Carlos; Zanlungo Matsuhiro, Silvana; Miquel P., Juan Francisco; Nervi, Flavio; Husche, Constanze; Lütjohann, Dieter
    Abstract Background Cholesterol gallstone disease (GS) is highly prevalent among Hispanics and American Indians. In GS, the pool of bile acids (BA) is decreased, suggesting that BA absorption is impaired. In Caucasian GS patients, mRNA levels for ileal BA transporters are decreased. We aimed to determine fecal BA excretion rates, mRNA levels for ileal BA transporter genes and of regulatory genes of BA synthesis in Hispanic GS patients. Results Excretion of fecal BA was measured in seven GS females and in ten GS-free individuals, all with a body mass index < 29. Participants ingested the stool marker Cr2O3 (300 mg/day) for 10 days, and fecal specimens were collected on the last 3 days. Chromium was measured by a colorimetric method, and BA was quantitated by gas chromatography/mass spectroscopy. Intake of calories, nutrients, fiber and cholesterol were similar in the GS and GS-free subjects. Mean BA excretion levels were 520 ± 80 mg/day for the GS-free group, and 461 ± 105 mg/day for the GS group. Messenger RNA expression levels were determined by RT-PCR on biopsy samples obtained from ileum during diagnostic colonoscopy (14 GS-free controls and 16 GS patients) and from liver during surgery performed at 8 and 10 AM (12 GS and 10 GS-free patients operated on for gastrointestinal malignancies), all with a body mass index < 29. Messenger RNA level of the BA transporter genes for ileal lipid binding protein, multidrug resistance-associated protein 3, organic solute transporter alpha, and organic solute transporter beta were similar in GS and GS-free subjects. Messenger RNA level of Cyp27A1, encoding the enzyme 27α-hydroxylase, the short heterodimer partner and farnesoid X receptor remained unchanged, whereas the mRNA level of Cyp7A1, the rate limiting step of BA synthesis, was increased more than 400% (p < 0.01) in the liver of GS compared to GS-free subjects. Conclusion Hispanics with GS have fecal BA excretion rates and mRNA levels of genes for ileal BA transporters that are similar to GS-free subjects. However, mRNA expression levels of Cyp7A1 are increased in GS, indicating that regulation of BA synthesis is abnormal in Hispanics with GS.
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    Impaired biliary cholesterol secretion and decreased gallstone formation in apolipoprotein E-deficient mice fed a high-cholesterol diet
    (2000) Amigo Boker, Ludwig Peter; Quiñones, Verónica; Mardones, Pablo; Zanlungo Matsuhiro, Silvana; Miquel Poblete, Juan Francisco; Nervi Oddone, Flavio; Rigotti Rivera, Attilio Gianpietro
    Background & aimsBecause apolipoprotein E (apoE) is a key cholesterol transport molecule involved in the hepatic uptake of chylomicron cholesterol, it may play a critical role in controlling bile cholesterol elimination and cholesterol gallstone formation induced by dietary cholesterol. To test this hypothesis, we studied biliary lipid secretion and gallstone formation in apoE-deficient mice fed cholesterol-rich diets.MethodsBile lipid outputs and gallstone sequence events were analyzed in apoE-deficient mice fed a high-cholesterol diet or a lithogenic diet compared with control animals.ResultsA high-cholesterol diet increased biliary cholesterol secretion and gallbladder bile cholesterol concentration in wild-type mice; the increase in bile cholesterol secretion was significantly attenuated in apoE-deficient mice. ApoE knockout mice fed a high-cholesterol lithogenic diet had a markedly lower frequency of gallbladder bile cholesterol crystal and gallstone formation than wild-type mice, which was most likely a result of the decreased cholesterol saturation index found in gallbladder bile of apoE-deficient mice.ConclusionsThese results show that apoE expression is an important factor for regulating both biliary secretion of diet-derived cholesterol as well as diet-induced cholesterol gallstone formation in mice.
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    Metabolic Effects of Cholecystectomy : Gallbladder Ablation Increases Basal Metabolic Rate through G-Protein Coupled Bile Acid Receptor Gpbar1-Dependent Mechanisms in Mice
    (2015) Cortés Mora, Víctor Antonio; Amigo Boker, Ludwig Peter; Zanlungo Matsuhiro, Silvana; Galgani Fuentes, José; Robledo, Fermín; Arrese Jiménez, Marco; Bozinovic Kuscevic, Francisco; Nervi, Flavio