Browsing by Author "Nervi Oddone, Flavio"

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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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    Diet as a risk factor for cholesterol gallstone disease
    (2004) Cuevas Marín, Ada Marisa; Miquel Poblete, Juan Francisco; Reyes Soto, María Soledad; Zanlungo Matsuhiro, Silvana; Nervi Oddone, Flavio
    Cholesterol gallstone disease is a common condition in western populations. The etiology is multifactorial with interaction of genetic and environmental factors. Obesity, aging, estrogen treatment, pregnancy and diabetes are consistently associated to a higher risk. A number of dietary factors have been involved in the pathogenesis of cholelithiasis. In this article we summarize several studies that have evaluated the role of diet as a potential risk factor for gallstone formation, including energy intake, cholesterol, fatty acids, fiber, carbohydrates, vitamins and minerals, and alcohol intake. Consumption of simple sugars and saturated fat has been mostly associated to a higher risk, while fiber intake and moderate consumption of alcohol, consistently reduce the risk. The association between cholesterol intake and gallstone disease has been variable in different studies. The effects of other dietary factors are less conclusive; additional studies are therefore necessary to clarify their relevance in the pathogenesis of gallstone disease. Recent discoveries of the role of orphan nuclear receptors in the regulation of fatty acid and hepatic cholesterol metabolism and excretion open new perspectives for a better understanding of the role of dietary constituents on cholesterol gallstone formation. KEY TEACHING POINTS: The etiology of cholesterol gallstone disease is multifactorial with interaction between genome and environment. It has been postulated that dietary constituents are important determinants for the formation of lithogenic bile. Intake of high energy, simple sugar and saturated fat favors gallstone formation. Fiber and moderate consumption of alcohol reduce the risk. The role of orphan nuclear receptors in the regulation of hepatic cholesterol metabolism and excretion open new leads for understanding the role of dietary constituents on cholesterol gallstone formation.
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    Diminishing benefits of urban living for children and adolescents' growth and development
    (Nature Portfolio, 2023) Berrios Carrasola, Ximena; Echeverría Errázuriz, Guadalupe; Ferreccio Readi, Fresia Catterina; Margozzini Maira, Paula Andrea; Miquel Poblete, Juan Francisco; Nervi Oddone, Flavio; Rigotti Rivera, Attilio Gianpietro; Valdivia Cabrera, Gonzalo Sergio; Mishra, A.; Zhou, B.; Rodríguez-Martínez, A.; Bixby, H.; Singleton, R. K.; Carrillo-Larco, R. M.; Sheffer, K. E.; Paciorek, C. J.; Bennett, J. E.; Lhoste, V.; Lurilli, M. L.; Di Cesare, M.
    Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1,2,3,4,5,6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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    Enfermedad vesicular inaparente o microlitiasis en pacientes con pancreatitis aguda: Una situación clínica frecuente
    (1997) Miquel Poblete, Juan Francisco; Prado Sanhueza, María Alejandra; Asahi Kodama, Harumi Paz; Ibáñez Anrique, Luis Alberto; Guzmán Bondiek, Sergio; Cruz Olivos, Francisco; Rollan Rodríguez, Antonio Rafael; Nervi Oddone, Flavio
    Background: Patients with acute pancreatitis (AP) and a normal gallbladder by standard echographic evaluation may have "occult" gallbladder disease or microlithiasis with recurrent episodes of AP. Aim: To conduct a prospective evaluation of patients with the diagnosis of non-biliary AP in order to detect "occult" gallbladder disease and to compare its clinical presentation with that of biliary AP. Patients and methods: Patients admitted with the diagnosis of AP to a clinical hospital were included in the study. According to an abdominal ultrasound study, patients were classified as having or not cholelithiasis. A duodenal biliary drainage was performed in 15 patients with AP and without gallbladder stones. Results: Patients without cholelithiasis had recurrent AP more often than patients with biliary AP (53 and 33% respectively). Excessive alcohol ingestion did not rule out the possibility of biliary etiology. In 6 patients, the analysis of duodenal bile showed cholesterol crystals, and cholecystectomy confirmed the existence of gallbladder disease in 5. All of them remained asymptomatic during a follow-up period of four years. One patient refused surgery, with subsequent development of gallstones and recurrent episodes of AP. In other 4 patients, gallbladder disease was confirmed by percutaneous gallbladder puncture or during cholecystectomy. No recurrence of AP were observed during the follow-up. Conclusions: Microlithiasis or "occult" gallbladder disease accounts for at least 67% of the original "non-biliary" AP. Duodenal bile analysis is a useful and necessary technique for the evaluation of patients with "non-biliary" acute pancreatitis'. Careful clinical and echographic follow-up of this subgroup of patients with AP is mandatory.
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    Epidemiology and Molecular Pathology of Gallbladder Cancer
    (2001) Lazcano-Ponce, Eduardo; Miquel Poblete, Juan Francisco; Muñoz, Nubia; Herrero, Rolando; Ferrecio, Catterina; Wistuba Oyarzún, Ignacio; Alonso de Ruiz, Patricia; Aristi Urista, Gerardo; Nervi Oddone, Flavio
    Gallbladder cancer is usually associated with gallstone disease, late diagnosis, unsatisfactory treatment, and poor prognosis, We report here the worldwide geographical distribution of gallbladder cancer, review the main etiologic hypotheses, and provide some comments on perspectives for prevention. The highest incidence rate of gallbladder cancer is found among populations of the Andean area, North American Indians, and Mexican Americans. Gallbladder cancer is up to three times higher among women than men in all populations. The highest incidence rates in Europe are found in Poland, the Czech Republic, and Slovakia. Incidence rates in other regions of the world are relatively low. The highest mortality rates are also reported from South America, 3.5-15.5 per 100,000 among Chilean Mapuche Indians, Bolivians, and Chilean Hispanics. Intermediate rates, 3.7 to 9.1 per 100,000, are reported from Peru, Ecuador, Colombia, and Brazil. Mortality rates are low in North America, with the exception of high rates among American Indians in New Mexico (11.3 per 100,000) and among Mexican Americans.", "The main associated risk factors identified so far include cholelithiasis (especially untreated chronic symptomatic gallstones), obesity, reproductive factors, chronic infections of the gallbladder, and environmental exposure to specific chemicals. These suspected factors likely represent promoters of carcinogenesis. The main limitations of epidemiologic studies on gallbladder cancer are the small sample sizes and specific problems in quantifying exposure to putative risk factors. The natural history of gallbladder disease should be characterized to support the allocation of more resources for early treatment of symptomatic gallbladder disease in high-risk populations. Secondary prevention of, gallbladder cancer could be effective if supported by cost-effective studies of prophylactic cholecystectomy among asymptomatic gallstone patients in high-risk areas."]
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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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    Hepatic cholesterol transport from plasma into bile: implications for gallstone disease
    (2004) Zanlungo Matsuhiro, Silvana; Rigotti Rivera, Attilio Gianpietro; Nervi Oddone, Flavio
    Purpose of reviewThe transhepatic traffic of cholesterol from plasma lipoproteins into the bile is critical for overall cholesterol homeostasis and its alterations may lead to cholesterol gallstone formation. This review summarizes recent progress in understanding the key hepatic cholesterol metabolism-related proteins and pathways that influence biliary secretion of cholesterol.Recent findingsIn cholesterol-fed apolipoprotein E knockout mice, the availability of dietary cholesterol for biliary disposal is decreased and diet-induced gallstone formation is impaired. Scavenger receptor class B type I is relevant for cholesterol transport from plasma HDL into the bile in chow-fed mice, however its expression is not critical for biliary cholesterol secretion and gallstone formation in lithogenic diet-fed mice. Intrahepatic cholesterol transport proteins (e.g. sterol carrier protein-2, Niemann Pick type C-1 protein) also determine liver cholesterol available for biliary secretion in mice. Genetic manipulation of canalicular ATP-binding cassette transporter G5 and G8 expression in mice has established their essential role for biliary cholesterol secretion.SummaryRecent studies have underscored that different proteins involved in hepatic cholesterol transport regulate the availability of cholesterol for biliary secretion. These advances may provide new avenues for prevention and treatment of various disease conditions linked to abnormal cholesterol metabolism.
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    Hypoadiponectinemia and its Association with Liver Fibrosis in Morbidly Obese Patients
    (2010) Nazal Ortiz, Leyla María; Riquelme Pérez, Arnoldo Javier; Solís López, Nancy De Las Mercedes; Pizarro Rojas, Margarita Alicia; Escalona Pérez, Alex Gamaliel; Burotto Pichun, Mauricio Emanuel; Méndez, Juan Ignacio; Saint-Jean, Catalina; Concha Bustos, María José; Giovanni, Stefano; Awruch Diego Ariel; Morales Soto, Arturo Javier; Baudrand Biggs, Rene Felipe; Carrasco Avino, Gonzalo; Domínguez De Landa, María Angelica; Padilla Pérez, Oslando; Espinoza, Manuel; Miquel, Juan Francisco; Nervi Oddone, Flavio; Arrese Jiménez, Marco Antonio
    Reduced serum levels of adiponectin have been associated with insulin resistance and non-alcoholic fatty liver disease (NAFLD). However, the relationship between serum adiponectin levels and hepatic histology in NAFLD is controversial. The aim of this study was to explore associations between plasma adiponectin concentrations and liver histology in morbidly obese patients.", "We conducted a case-control study including obese patients undergoing bariatric surgery and normal controls. Anthropometric, standard biochemical variables as well as plasma adiponectin and leptin levels were determined. Liver biopsy was performed in all patients at the time of surgery.", "Seventy morbidly obese patients (mean BMI, 40.6 +/- 5.6 kg/m(2)) met the inclusion criteria and were compared with 69 controls (mean BMI, 22.8 +/- 1.6 kg/m(2), p = 0.0001). Thirty patients (43%) had NAFLD and 20 (28%) of them fulfilled the histological criteria for steatohepatitis. Obesity was associated with increased leptin and decreased adiponectin levels. NAFLD patients exhibited decreased levels of serum adiponectin compared with matched controls [median (Q1-Q3), 3.9 (3.2-4.3) vs. 8.6 (6.5-9.2) mu g/mL, p < 0.0001]. In univariate analysis, age, gender, type 2 diabetes mellitus, BMI, HOMA-IR, aspartate aminotransferase (AST), alanine aminotransferase, serum glucose, and adiponectin levels were independently associated with hepatic fibrosis. In multivariate analysis, AST [OR = 1.082 (1.000-1.170)], age [OR = 1.119 (1.023-1.225)], and serum adiponectin levels [OR = 0.529 (0.299-0.936)] were significantly associated with the presence of liver fibrosis.", "NAFLD patients have lower plasma adiponectin concentrations than control subjects. Low adiponectin levels are associated with more severe liver histology. Serum adiponectin may be useful to estimate the severity of liver damage in obese patients with NAFLD.
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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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    Microlithiasis and cholesterolosis in idiopathic acute pancreatitis
    (W. B. Saunders Co., 1992) Miquel Poblete, Juan Francisco; Rollan Rodríguez, Antonio Rafael; Guzmán Bondiek, Sergio; Nervi Oddone, Flavio
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    Plasminogen activator inhibitor type 1 serum levels and 4G/5G gene polymorphism in morbidly obese Hispanic patients with non-alcoholic fatty liver disease
    (Elsevier España, 2011) Espino Espino, Alberto Antonio; Villagran Torres, Andrea Alejandra; Vollrath Reyes, Valeska Yolanda; Hanckes Mayo, Maria Paulina; Salas Ocaranza, Roberto Ignacio; Farah Samaan, Andrea Catherina; Solis, Nancy; Pizarro Rojas, Margarita Alicia; Escalona Perez, Alex Gamaliel; Boza Wilson, Camilo; Perez, Gustavo; Carrasco, Gonzalo; Padilla, Orlando; Francisco Miguel, Juan; Nervi Oddone, Flavio; Chavez Tapia, Norberto C.; Arab Verdugo, Juan Pablo; Alvarez Lobos, Manuel Marcelo; Arrese Jimenez, Marco Antonio; Riquelme Perez, Arnoldo Javier
    Background. The plasminogen activator inhibitor type-1 (PAI-1) has been implicated in the regulation of fibrinolysis and extracellular matrix components. The single base pair guanine insertion/deletion polymorphism (4G/5G) within the promoter region of the PAI-1 gene influences PAI-1 synthesis and may modulate hepatic fibrogenesis. Aim. To evaluate the influence of PAI-1 serum levels and 4G/5G polymorphism on the risk of liver fibrosis associated to non-alcoholic fatty liver disease (NAFLD) in morbidly obese patients. Material and methods. Case-control study of 50 obese patients undergoing bariatric surgery and 71 non-obese subjects matched by age and sex. Anthropometric and biochemical measurements were performed, including PAI-1 serum levels. Genomic DNA was obtained to assess the presence of 4G/5G polymorphism. Results. BMI, insulinemia, triglycerides, HOMA-IR, hypertension and diabetes were significantly higher in obese patients compared to control subjects. PAI-1 serum levels observed in obese patients were significantly lower (10.63 +/- 4.82) compared to controls (14.26 +/- 11.4; p < 0.05). No differences were observed in the PAI-1 4G/5G promoter genotypes frequencies (p = 0.12). No differences were observed in PAI-1 plasma levels among obese patients with liver fibrosis (10.64 +/- 4.35) compared to patients without liver fibrosis (10.61 +/- 5.2; p = 0.985). PAI-1 4G/5G promoter genotypes frequencies were similar in patients with or without liver fibrosis associated to NASH (p = 0.6). Conclusions. Morbidly obese patients had significantly Lower PAI-1 serum levels with similar PAI-1 4G/5G genotypes frequencies compared to non-obese subjects. The frequency of 4G/5G genotypes in Chilean Hispanic healthy subjects was similar to that described in other populations. No association was found between PAI-1 serum levels or 4G/5G genotype with liver fibrosis in obese patients.
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    The ABCs of biliary cholesterol secretion and their implication for gallstone disease
    (2003) Zanlungo Matsuhiro, Silvana; Miquel Poblete, Juan Francisco; Rigotti Rivera, Attilio Gianpietro; Nervi Oddone, Flavio
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    The molecular and metabolic basis of biliary cholesterol secretion and gallstone disease
    (2003) Zanlungo Matsuhiro, Silvana; Nervi Oddone, Flavio
    This article presents an up to date of selected aspects of the molecular mechanisms of cholesterol metabolism most likely involved in cholesterol gallstones disease, a highly prevalent disease in the Western world. The etiology of cholesterol cholelithiasis is considered to be multifactorial, with interaction of genetic and environmental factors. The production of supersaturated bile by the liver of cholesterol is a key early metabolic event underlying cholesterol lithogenesis. Regulation of hepatic cholesterol trafficking within the hepatocyte appears essential for the production of cholesterol supersaturated bile. Impaired sorting of metabolically active hepatic free cholesterol to the bile acid biosynthetic or lipoprotein production pathways leads to an increased availability of cholesterol for preferential channeling of cholesterol to the canalicular membrane and further secretion into bile. Many of these intrahepatic cholesterol trafficking steps are under genetic control and might be influenced by a variety of environmental factors. This review summarizes recent discoveries related to transhepatic cholesterol flux and biliary lipid secretion, which have provided new insights to the regulation of hepatic cholesterol metabolism as related to gallstone disease.
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    The old enigma of diets, oils, and stones
    (2005) Miquel Poblete, Juan Francisco; Zanlungo Matsuhiro, Silvana; Nervi Oddone, Flavio