Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1974
... Cuu-S' irtiftirtio >< "> B aa ai | ... more ... Cuu-S' irtiftirtio >< "> B aa ai | " ^ ^ ^ 2 ^ S t 6 -s < s '" ". ^ S3" oooo Q o S g +1+1+1+1 MS .5 .a ^ ^ " 0 '^. S a 'S 3 S" i-06 t-i-1 1 0 SS i S saaa o'o ... S ri +l +( +i +i oooo SSM,2 o a. dd co eo bu ^ (Ji t" 2 s 0 22 '3 M CO ^ <f CO+1 +1 +1 +f si t-M t" COi in 10 tu l ' *f t-t0 M sdddd hOJ +l ...
... Is there concordance among patients and doctors? Alejandra Palma 1 , Ignacia del Río 1a , Pil... more ... Is there concordance among patients and doctors? Alejandra Palma 1 , Ignacia del Río 1a , Pilar Bonati 1b , Laura Tupper 2 , Luis Villarroel 3 , Patricia Olivares 4c , Flavio Nervi 1,5 . ... J Pall Med 2006; 9: 293-303. [ Links ]. 13. ...
In recent years, the Chilean population has suffered significant lifestyle changes associated wit... more In recent years, the Chilean population has suffered significant lifestyle changes associated with the rapid socioeconomic development of the country. These changes can induce a significant increase in the prevalence of some chronic diseases, such as obesity, dyslipidemia, and diabetes mellitus. We aimed to assess diabetes mellitus, obesity, and hypercholesterolemia trends in a Chilean urban population followed between 1993 and 2001. A total of 1584 adults, living in Santiago, the capital of Chile, were randomly enrolled in a cross-sectional epidemiologic study in 1993. The same population was re-evaluated in 2001, recruiting 964 individuals from the original sample. Prevalences of diabetes mellitus, obesity, and hypercholesterolemia were determined according to standard criteria. We tested the significance of the differences between the observed prevalence of diabetes mellitus, obesity, and hypercholesterolemia in the 964 subjects evaluated in 2001 compared with the expected prevalence according to population aging based in data from 1993. In 1993, 3.8% of the sample population had diabetes mellitus, 21.8% had obesity, and 37.3 % exhibited hypercholesterolemia. In 2001, the observed prevalence of diabetes mellitus, obesity, and hypercholesterolemia was 10.1%, 32%, and 58%, respectively. The latter percentages were significantly higher than the expected prevalence according to the aging of the population (6.5% for diabetes mellitus, 27.7% for obesity, and 47.7 for hypercholesteromia). Our findings indicate that Chilean population has suffered an accelerated increase in the prevalence of diabetes mellitus, obesity, and hypercholesterolemia, due to the ongoing epidemiological transition that will lead to an enormous public health burden in the near future.
1. Hepatology. 1990 Sep;12(3 Pt 2):134S-141S; discussion 141S-142S. Secretion of biliary lipids f... more 1. Hepatology. 1990 Sep;12(3 Pt 2):134S-141S; discussion 141S-142S. Secretion of biliary lipids from the hepatocyte. Marzolo MP, Rigotti A, Nervi F. Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile. ...
1Departamento de Medicina Interna. 2Departamento de Gastroenterología. 3Departamento de Anatomía ... more 1Departamento de Medicina Interna. 2Departamento de Gastroenterología. 3Departamento de Anatomía Patológica. 4Departamento de Dermatología. 5Centro de Información Toxicológica. CITUC Pontificia Universidad Católica de Chile. Recibido: 7 de abril de ...
El DNA mitocondrial humano tiene características únicas que lo hacen muy apropiado para estudios ... more El DNA mitocondrial humano tiene características únicas que lo hacen muy apropiado para estudios microevolutivos. Posee una alta frecuencia de mutaciones (5 a 10 veces mayor que el DNA nuclear), no sufre recombinación génica y tiene una transmisión unidireccional ...
Introducción Definiciones Principios básicos de la Medicina Paliativa Control de síntomas Caquexi... more Introducción Definiciones Principios básicos de la Medicina Paliativa Control de síntomas Caquexia-Anorexia Compromiso de Conciencia Constipación Delirium Depresión y Ansiedad Diarrea Disnea Dolor Fatiga Náuseas y Vómitos Retención urinaria e Incontinencia de ...
Biliary cholesterol represents one of the two major excretory pathways for sterol elimination fro... more Biliary cholesterol represents one of the two major excretory pathways for sterol elimination from the body and plays a central role in cholesterol gallstone formation. Biliary cholesterol originates from a precursor pool of preformed and newly synthesized free cholesterol. Although it has been suggested that newly synthesized and preformed biliary cholesterol are secreted by independent pathways, the specific cellular and molecular mechanisms are unknown. We used male Wistar rats to study the time-course of the appearance of newly synthesized cholesterol, phosphatidylcholine and protein into bile. The specific role of sterol carrier protein-2 (SCP-2) in the transport of newly synthesized biliary cholesterol was evaluated by an in vivo antisense oligonucleotide approach. In contrast to [14C]phosphatidylcholine and [35S]proteins, the time-course of [14C]cholesterol appearance into bile was rapid, and microtubule- and Golgi-independent. In vivo SCP-2 antisense treatment reduced and de...
The presence of acyl-CoA synthetase (EC 6.2.1.3) in peroxisomes and the subcellular distribution ... more The presence of acyl-CoA synthetase (EC 6.2.1.3) in peroxisomes and the subcellular distribution of beta-oxidation enzymes in human liver were investigated by using a single-step fractionation method of whole liver homogenates in metrizamide continuous density gradients and a novel procedure of computer analysis of results. Peroxisomes were found to contain 16% of the liver palmitoyl-CoA synthetase activity, and 21% and 60% of the enzyme activity was localized in mitochondria and microsomal fractions respectively. Fatty acyl-CoA oxidase was localized exclusively in peroxisomes, confirming previous results. Human liver peroxisomes were found to contribute 13%, 17% and 11% of the liver activities of crotonase, beta-hydroxyacyl-CoA dehydrogenase and thiolase respectively. The absolute activities found in peroxisomes for the enzymes investigated suggest that in human liver fatty acyl-CoA oxidase is the rate-limiting enzyme of the peroxisomal beta-oxidation pathway, when palmitic acid is...
We studied the effect of a bean diet on biliary lipid secretion, serum cholesterol concentration,... more We studied the effect of a bean diet on biliary lipid secretion, serum cholesterol concentration, and hepatic cholesterol metabolism in the rat. Rats fed a bean diet for 10-12 days had increased biliary cholesterol output and molar percentage by 300% and 200%, respectively, compared to rats fed an isocaloric and isoprotein casein diet. Biliary phospholipid output increased 180%. Bile flow and biliary bile salt output remained in the normal range. Total serum and VLDL cholesterol concentration significantly decreased 27% and 50%, respectively, in the rats fed the bean diet. Hepatic cholesterogenesis was increased 170% in the bean-fed animals. The relative contribution of newly synthesized hepatic cholesterol to total biliary cholesterol increased 200%, and that of endogenous origin only 50%. These results suggested that newly synthesized hepatic cholesterol was preferentially channelled to the biliary cholesterol secretory pathway in bean-fed rats. Although hepatic cholesteryl ester ...
Bile acids (BAs) regulate energy expenditure by activating G-protein Coupled Bile Acid Receptor G... more Bile acids (BAs) regulate energy expenditure by activating G-protein Coupled Bile Acid Receptor Gpbar1/TGR5 by cAMP-dependent mechanisms. Cholecystectomy (XGB) increases BAs recirculation rates resulting in increased tissue exposure to BAs during the light phase of the diurnal cycle in mice. We aimed to determine: 1) the effects of XGB on basal metabolic rate (BMR) and 2) the roles of TGR5 on XGB-dependent changes in BMR. BMR was determined by indirect calorimetry in wild type and Tgr5 deficient (Tgr5-/-) male mice. Bile flow and BAs secretion rates were measured by surgical diversion of biliary duct. Biliary BAs and cholesterol were quantified by enzymatic methods. BAs serum concentration and specific composition was determined by liquid chromatography/tandem mass spectrometry. Gene expression was determined by qPCR analysis. XGB increased biliary BAs and cholesterol secretion rates, and elevated serum BAs concentration in wild type and Tgr5-/- mice during the light phase of the diurnal cycle. BMR was ~25% higher in cholecystectomized wild type mice (p <0.02), whereas no changes were detected in cholecystectomized Tgr5-/- mice compared to wild-type animals. XGB increases BMR by TGR5-dependent mechanisms in mice.
The plasminogen activator inhibitor type-1 (PAI-1) has been implicated in the regulation of fibri... more 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. 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. 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. 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 low...
Cholesterol has evolved to fulfill sophisticated biophysical, cell signaling and endocrine requir... more Cholesterol has evolved to fulfill sophisticated biophysical, cell signaling and endocrine requirements of animal systems. At a cellular level, cholesterol is found in membranes, where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signaling functions. At an organismal level, cholesterol is the precursor for all steroid hormones, including gluco- and mineralo-corticoids, sex hormones and vitamin D, all of which regulate carbohydrate, sodium, reproductive and bone homeostasis, respectively. This sterol is also the precursor for bile acids, which are important for intestinal absorption of dietary lipids as well as energy and glucose metabolic regulation. Importantly, complex mechanisms maintain cholesterol within physiological ranges and the disregulation of these mechanisms results in embryonic or adult diseases, caused by either exces...
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1974
... Cuu-S' irtiftirtio >< "> B aa ai | ... more ... Cuu-S' irtiftirtio >< "> B aa ai | " ^ ^ ^ 2 ^ S t 6 -s < s '" ". ^ S3" oooo Q o S g +1+1+1+1 MS .5 .a ^ ^ " 0 '^. S a 'S 3 S" i-06 t-i-1 1 0 SS i S saaa o'o ... S ri +l +( +i +i oooo SSM,2 o a. dd co eo bu ^ (Ji t" 2 s 0 22 '3 M CO ^ <f CO+1 +1 +1 +f si t-M t" COi in 10 tu l ' *f t-t0 M sdddd hOJ +l ...
... Is there concordance among patients and doctors? Alejandra Palma 1 , Ignacia del Río 1a , Pil... more ... Is there concordance among patients and doctors? Alejandra Palma 1 , Ignacia del Río 1a , Pilar Bonati 1b , Laura Tupper 2 , Luis Villarroel 3 , Patricia Olivares 4c , Flavio Nervi 1,5 . ... J Pall Med 2006; 9: 293-303. [ Links ]. 13. ...
In recent years, the Chilean population has suffered significant lifestyle changes associated wit... more In recent years, the Chilean population has suffered significant lifestyle changes associated with the rapid socioeconomic development of the country. These changes can induce a significant increase in the prevalence of some chronic diseases, such as obesity, dyslipidemia, and diabetes mellitus. We aimed to assess diabetes mellitus, obesity, and hypercholesterolemia trends in a Chilean urban population followed between 1993 and 2001. A total of 1584 adults, living in Santiago, the capital of Chile, were randomly enrolled in a cross-sectional epidemiologic study in 1993. The same population was re-evaluated in 2001, recruiting 964 individuals from the original sample. Prevalences of diabetes mellitus, obesity, and hypercholesterolemia were determined according to standard criteria. We tested the significance of the differences between the observed prevalence of diabetes mellitus, obesity, and hypercholesterolemia in the 964 subjects evaluated in 2001 compared with the expected prevalence according to population aging based in data from 1993. In 1993, 3.8% of the sample population had diabetes mellitus, 21.8% had obesity, and 37.3 % exhibited hypercholesterolemia. In 2001, the observed prevalence of diabetes mellitus, obesity, and hypercholesterolemia was 10.1%, 32%, and 58%, respectively. The latter percentages were significantly higher than the expected prevalence according to the aging of the population (6.5% for diabetes mellitus, 27.7% for obesity, and 47.7 for hypercholesteromia). Our findings indicate that Chilean population has suffered an accelerated increase in the prevalence of diabetes mellitus, obesity, and hypercholesterolemia, due to the ongoing epidemiological transition that will lead to an enormous public health burden in the near future.
1. Hepatology. 1990 Sep;12(3 Pt 2):134S-141S; discussion 141S-142S. Secretion of biliary lipids f... more 1. Hepatology. 1990 Sep;12(3 Pt 2):134S-141S; discussion 141S-142S. Secretion of biliary lipids from the hepatocyte. Marzolo MP, Rigotti A, Nervi F. Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile. ...
1Departamento de Medicina Interna. 2Departamento de Gastroenterología. 3Departamento de Anatomía ... more 1Departamento de Medicina Interna. 2Departamento de Gastroenterología. 3Departamento de Anatomía Patológica. 4Departamento de Dermatología. 5Centro de Información Toxicológica. CITUC Pontificia Universidad Católica de Chile. Recibido: 7 de abril de ...
El DNA mitocondrial humano tiene características únicas que lo hacen muy apropiado para estudios ... more El DNA mitocondrial humano tiene características únicas que lo hacen muy apropiado para estudios microevolutivos. Posee una alta frecuencia de mutaciones (5 a 10 veces mayor que el DNA nuclear), no sufre recombinación génica y tiene una transmisión unidireccional ...
Introducción Definiciones Principios básicos de la Medicina Paliativa Control de síntomas Caquexi... more Introducción Definiciones Principios básicos de la Medicina Paliativa Control de síntomas Caquexia-Anorexia Compromiso de Conciencia Constipación Delirium Depresión y Ansiedad Diarrea Disnea Dolor Fatiga Náuseas y Vómitos Retención urinaria e Incontinencia de ...
Biliary cholesterol represents one of the two major excretory pathways for sterol elimination fro... more Biliary cholesterol represents one of the two major excretory pathways for sterol elimination from the body and plays a central role in cholesterol gallstone formation. Biliary cholesterol originates from a precursor pool of preformed and newly synthesized free cholesterol. Although it has been suggested that newly synthesized and preformed biliary cholesterol are secreted by independent pathways, the specific cellular and molecular mechanisms are unknown. We used male Wistar rats to study the time-course of the appearance of newly synthesized cholesterol, phosphatidylcholine and protein into bile. The specific role of sterol carrier protein-2 (SCP-2) in the transport of newly synthesized biliary cholesterol was evaluated by an in vivo antisense oligonucleotide approach. In contrast to [14C]phosphatidylcholine and [35S]proteins, the time-course of [14C]cholesterol appearance into bile was rapid, and microtubule- and Golgi-independent. In vivo SCP-2 antisense treatment reduced and de...
The presence of acyl-CoA synthetase (EC 6.2.1.3) in peroxisomes and the subcellular distribution ... more The presence of acyl-CoA synthetase (EC 6.2.1.3) in peroxisomes and the subcellular distribution of beta-oxidation enzymes in human liver were investigated by using a single-step fractionation method of whole liver homogenates in metrizamide continuous density gradients and a novel procedure of computer analysis of results. Peroxisomes were found to contain 16% of the liver palmitoyl-CoA synthetase activity, and 21% and 60% of the enzyme activity was localized in mitochondria and microsomal fractions respectively. Fatty acyl-CoA oxidase was localized exclusively in peroxisomes, confirming previous results. Human liver peroxisomes were found to contribute 13%, 17% and 11% of the liver activities of crotonase, beta-hydroxyacyl-CoA dehydrogenase and thiolase respectively. The absolute activities found in peroxisomes for the enzymes investigated suggest that in human liver fatty acyl-CoA oxidase is the rate-limiting enzyme of the peroxisomal beta-oxidation pathway, when palmitic acid is...
We studied the effect of a bean diet on biliary lipid secretion, serum cholesterol concentration,... more We studied the effect of a bean diet on biliary lipid secretion, serum cholesterol concentration, and hepatic cholesterol metabolism in the rat. Rats fed a bean diet for 10-12 days had increased biliary cholesterol output and molar percentage by 300% and 200%, respectively, compared to rats fed an isocaloric and isoprotein casein diet. Biliary phospholipid output increased 180%. Bile flow and biliary bile salt output remained in the normal range. Total serum and VLDL cholesterol concentration significantly decreased 27% and 50%, respectively, in the rats fed the bean diet. Hepatic cholesterogenesis was increased 170% in the bean-fed animals. The relative contribution of newly synthesized hepatic cholesterol to total biliary cholesterol increased 200%, and that of endogenous origin only 50%. These results suggested that newly synthesized hepatic cholesterol was preferentially channelled to the biliary cholesterol secretory pathway in bean-fed rats. Although hepatic cholesteryl ester ...
Bile acids (BAs) regulate energy expenditure by activating G-protein Coupled Bile Acid Receptor G... more Bile acids (BAs) regulate energy expenditure by activating G-protein Coupled Bile Acid Receptor Gpbar1/TGR5 by cAMP-dependent mechanisms. Cholecystectomy (XGB) increases BAs recirculation rates resulting in increased tissue exposure to BAs during the light phase of the diurnal cycle in mice. We aimed to determine: 1) the effects of XGB on basal metabolic rate (BMR) and 2) the roles of TGR5 on XGB-dependent changes in BMR. BMR was determined by indirect calorimetry in wild type and Tgr5 deficient (Tgr5-/-) male mice. Bile flow and BAs secretion rates were measured by surgical diversion of biliary duct. Biliary BAs and cholesterol were quantified by enzymatic methods. BAs serum concentration and specific composition was determined by liquid chromatography/tandem mass spectrometry. Gene expression was determined by qPCR analysis. XGB increased biliary BAs and cholesterol secretion rates, and elevated serum BAs concentration in wild type and Tgr5-/- mice during the light phase of the diurnal cycle. BMR was ~25% higher in cholecystectomized wild type mice (p <0.02), whereas no changes were detected in cholecystectomized Tgr5-/- mice compared to wild-type animals. XGB increases BMR by TGR5-dependent mechanisms in mice.
The plasminogen activator inhibitor type-1 (PAI-1) has been implicated in the regulation of fibri... more 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. 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. 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. 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 low...
Cholesterol has evolved to fulfill sophisticated biophysical, cell signaling and endocrine requir... more Cholesterol has evolved to fulfill sophisticated biophysical, cell signaling and endocrine requirements of animal systems. At a cellular level, cholesterol is found in membranes, where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signaling functions. At an organismal level, cholesterol is the precursor for all steroid hormones, including gluco- and mineralo-corticoids, sex hormones and vitamin D, all of which regulate carbohydrate, sodium, reproductive and bone homeostasis, respectively. This sterol is also the precursor for bile acids, which are important for intestinal absorption of dietary lipids as well as energy and glucose metabolic regulation. Importantly, complex mechanisms maintain cholesterol within physiological ranges and the disregulation of these mechanisms results in embryonic or adult diseases, caused by either exces...
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