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[PMID]: 22941219 [Au] Autor: van Denderen JC; Blom GJ; van der Horst-Bruinsma IE; Dijkmans BA; Nurmohamed MT [Ad] Dirección: Jan van Breemen Research Institute/Reade, Amsterdam, The Netherlands. c.v.denderen@reade.nl [Ti] Título: Elevated liver enzymes in patients with ankylosing spondylitis treated with etanercept. [So] Fuente: Clin Rheumatol;31(12):1677-82, 2012 Dec. [Is] ISSN: 1434-9949 [Cp] País de publicación: Germany [La] Idioma: eng [Ab] Resumen: TNF-alpha blocking agents are very effective in patients with ankylosing spondylitis (AS), but several cases of liver problems have been published. We systematically studied the frequency of this potential side effect in our AS patients treated with etanercept. Consecutive AS patients treated with etanercept for at least 3 months were included. Liver disease was defined as elevated liver enzymes more than 1.5 times the upper normal limit (UNL) and was categorised as probably, possibly, probably not or not related to etanercept treatment. Patients with and without raised liver enzymes were compared for prognostic factors. A total of 105 patients were included. Fifteen patients had elevated liver enzymes more than once. In nine cases, the liver disease was probably (five) or possibly (four) related to etanercept treatment. The liver enzyme elevations were serious (>3× UNL) in six cases and resulted in permanent cessation of etanercept in two cases. The nine patients with liver disease were compared with patients without elevated liver enzymes. No differences were found in age or use of alcohol; however, in patients with liver disease, a higher body mass index and a trend for a higher atherogenic index were observed. Hepatic steatosis was observed in five of six patients with elevated liver enzymes. Elevated serum aminotransferases, probably or possibly related to etanercept treatment, were observed in 9 % of the AS patients. An increased risk for the elevation of liver enzymes was found in patients with a higher body mass index. We recommend regular testing of liver enzymes in patients treated with etanercept. [Mh] Términos MeSH primario: Alanina Transaminasa/sangre Antirreumáticos/efectos adversos Aspartato Aminotransferasas/sangre Inmunoglobulina G/efectos adversos Espondilitis Anquilosante/quimioterapia Factor de Necrosis Tumoral alfa/antagonistas & inhibidores [Mh] Términos MeSH secundario: Adulto Antirreumáticos/uso terapéutico Hígado Graso/sangre Hígado Graso/inducido químicamente Hígado Graso/enzimología Femenino Humanos Inmunoglobulina G/uso terapéutico Hígado/efectos de drogas Hígado/enzimología Masculino Mediana Edad Pronóstico Receptores del Factor de Necrosis Tumoral/uso terapéutico Espondilitis Anquilosante/sangre Espondilitis Anquilosante/enzimología Resultado del Tratamiento [Pt] Tipo de publicación: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nombre de substancia: 0 (Antirheumatic Agents); 0 (Immunoglobulin G); 0 (Receptors, Tumor Necrosis Factor); 0 (Tumor Necrosis Factor-alpha); 185243-69-0 (TNFR-Fc fusion protein); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 121126 [St] Status: MEDLINE [do] DOI: 10.1007/s10067-012-2072-7

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[PMID]: 23133675 [Au] Autor: Parlevliet ET; Wang Y; Geerling JJ; Schröder-Van der Elst JP; Picha K; O'Neil K; Stojanovic-Susulic V; Ort T; Havekes LM; Romijn JA; Pijl H; Rensen PC [Ad] Dirección: Department of General Internal Medicine, Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands. [Ti] Título: GLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice. [So] Fuente: PLoS One;7(11):e49152, 2012. [Is] ISSN: 1932-6203 [Cp] País de publicación: United States [La] Idioma: eng [Ab] Resumen: OBJECTIVE: In addition to improve glucose intolerance, recent studies suggest that glucagon-like peptide-1 (GLP-1) receptor agonism also decreases triglyceride (TG) levels. The aim of this study was to evaluate the effect of GLP-1 receptor agonism on very-low-density lipoprotein (VLDL)-TG production and liver TG metabolism. EXPERIMENTAL APPROACH: The GLP-1 peptide analogues CNTO3649 and exendin-4 were continuously administered subcutaneously to high fat diet-fed APOE*3-Leiden transgenic mice. After 4 weeks, hepatic VLDL production, lipid content, and expression profiles of selected genes involved in lipid metabolism were determined. RESULTS: CNTO3649 and exendin-4 reduced fasting plasma glucose (up to -30% and -28% respectively) and insulin (-43% and -65% respectively). In addition, these agents reduced VLDL-TG production (-36% and -54% respectively) and VLDL-apoB production (-36% and -43% respectively), indicating reduced production of VLDL particles rather than reduced lipidation of apoB. Moreover, they markedly decreased hepatic content of TG (-39% and -55% respectively), cholesterol (-30% and -55% respectively), and phospholipids (-23% and -36% respectively), accompanied by down-regulation of expression of genes involved in hepatic lipogenesis (Srebp-1c, Fasn, Dgat1) and apoB synthesis (Apob). CONCLUSION: GLP-1 receptor agonism reduces VLDL production and hepatic steatosis in addition to an improvement of glycemic control. These data suggest that GLP-receptor agonists could reduce hepatic steatosis and ameliorate dyslipidemia in patients with type 2 diabetes mellitus. [Mh] Términos MeSH primario: Apolipoproteína E3/metabolismo Hígado Graso/metabolismo Péptido 1 Similar al Glucagón/metabolismo Receptores de Glucagón/metabolismo [Mh] Términos MeSH secundario: Animales Apolipoproteína E3/genética Apolipoproteínas B/metabolismo Glucemia/metabolismo Diabetes Mellitus Tipo 2/sangre Dislipidemias/sangre Hígado Graso/terapia Insulina/metabolismo Lipogénesis Hígado/patología Masculino Ratones Ratones Transgénicos Péptidos/química Péptidos/metabolismo Ponzoñas/metabolismo [Pt] Tipo de publicación: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nombre de substancia: 0 (Apolipoprotein E3); 0 (Apolipoproteins B); 0 (Blood Glucose); 0 (Insulin); 0 (Peptides); 0 (Receptors, Glucagon); 0 (Venoms); 0 (glucagon-like peptide-1 receptor); 141732-76-5 (exenatide); 89750-14-1 (Glucagon-Like Peptide 1) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 121107 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0049152

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[PMID]: 23056479 [Au] Autor: Fåk F; Bäckhed F [Ad] Dirección: Sahlgrenska Center for Cardiovascular and Metabolic Research/Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden. fredrik.backhed@wlab.gu.se [Ti] Título: Lactobacillus reuteri prevents diet-induced obesity, but not atherosclerosis, in a strain dependent fashion in Apoe-/- mice. [So] Fuente: PLoS One;7(10):e46837, 2012. [Is] ISSN: 1932-6203 [Cp] País de publicación: United States [La] Idioma: eng [Ab] Resumen: OBJECTIVE: To investigate whether the specific strains of Lactobacillus reuteri modulates the metabolic syndrome in Apoe-/- mice. METHODS: 8 week-old Apoe-/- mice were subdivided into four groups who received either L. reuteri ATCC PTA 4659 (ATCC), DSM 17938 (DSM), L6798, or no bacterial supplement in the drinking water for 12 weeks. The mice were fed a high-fat Western diet with 0.2% cholesterol and body weights were monitored weekly. At the end of the study, oral glucose and insulin tolerance tests were conducted. In addition, adipose and liver weights were recorded along with analyses of mRNA expression of ileal Angiopoietin-like protein 4 (Angptl4), the macrophage marker F4/80 encoded by the gene Emr1 and liver Acetyl-CoA carboxylase 1 (Acc1), Fatty acid synthase (Fas) and Carnitine palmitoyltransferase 1a (Cpt1a). Atherosclerosis was assessed in the aortic root region of the heart. RESULTS AND CONCLUSIONS: Mice receiving L. reuteri ATCC gained significantly less body weight than the control mice, whereas the L6798 mice gained significantly more. Adipose and liver weights were also reduced in the ATCC group. Serum insulin levels were lower in the ATCC group, but no significant effects were observed in the glucose or insulin tolerance tests. Lipogenic genes in the liver were not altered by any of the bacterial treatments, however, increased expression of Cpt1a was found in the ATCC group, indicating increased ß-oxidation. Correspondingly, the liver trended towards having lower fat content. There were no effects on inflammatory markers, blood cholesterol or atherosclerosis. In conclusion, the probiotic L. reuteri strain ATCC PTA 4659 partly prevented diet-induced obesity, possibly via a previously unknown mechanism of inducing liver expression of Cpt1a. [Mh] Términos MeSH primario: Apolipoproteínas E/deficiencia Aterosclerosis/microbiología Aterosclerosis/prevención & control Dieta Alta en Grasa/efectos adversos Lactobacillus reuteri/fisiología Obesidad/microbiología Obesidad/prevención & control [Mh] Términos MeSH secundario: Animales Aterosclerosis/etiología Aterosclerosis/metabolismo Hígado Graso/etiología Hígado Graso/metabolismo Hígado Graso/microbiología Hígado Graso/prevención & control Humanos Inflamación/etiología Inflamación/metabolismo Inflamación/microbiología Resistencia a la Insulina Ratones Obesidad/etiología Obesidad/metabolismo Fenotipo Probióticos/farmacología Especificidad de la Especie [Pt] Tipo de publicación: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nombre de substancia: 0 (Apolipoproteins E) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 121011 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0046837

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[PMID]: 23417420 [Au] Autor: Sellix MT; Murphy ZC; Menaker M [Ad] Dirección: Department of Medicine, Division of Endocrinology and Metabolism, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 693, Rochester, New York 14642, USA. michael_sellix@urmc.rochester.edu [Ti] Título: Excess androgen during puberty disrupts circadian organization in female rats. [So] Fuente: Endocrinology;154(4):1636-47, 2013 Apr. [Is] ISSN: 1945-7170 [Cp] País de publicación: United States [La] Idioma: eng [Ab] Resumen: Circadian clocks have been described in each tissue of the hypothalamo-pituitary-ovarian axis. Although a role for the clock in the timing of ovulation is indicated, the impact of diseases that disrupt fertility on clock function or the clocks' role in the etiology of these pathologies has yet to be fully appreciated. Polycystic ovary syndrome (PCOS) is a particularly devastating endocrinopathy, affecting approximately 10% of women at childbearing age. Common features of PCOS are a polycystic ovary, amenorrhea, and excess serum androgen. Approximately 40% of these women have metabolic syndrome, including hyperinsulinemia, dyslipidemia, and hyperleptinemia. It has been suggested that excess androgen is a critical factor in the etiology of PCOS. We have examined the effects of androgen excess during puberty on the phase of circadian clocks in tissues of the metabolic and hypothalamo-pituitary-ovarian axes. Female period1-luciferase (per1-luc) rats were exposed to androgen (5α-dihydrotestosterone [DHT]) or placebo for 4-6 weeks (short term) or 9-15 weeks (long term). As expected, DHT-treated animals gained more weight than controls and had disrupted estrous cycles. At the end of treatment, tissues, including the liver, lung, kidney, white adipose, cornea, pituitary, oviduct, and ovarian follicles, were cultured, and per1-luc expression in each was recorded. Analysis of per1-luc expression revealed that DHT exposure increased phase distribution of multiple oscillators, including ovarian follicles, liver, and adipose, and altered phase synchrony between animals. These data suggest that excess androgen during puberty, a common feature of PCOS, negatively affects internal circadian organization in both the reproductive and metabolic axes. [Mh] Términos MeSH primario: Andrógenos/farmacología Relojes Circadianos/efectos de drogas Dihidrotestosterona/farmacología Proteínas Circadianas Period/efectos de drogas [Mh] Términos MeSH secundario: Tejido Adiposo/efectos de drogas Tejido Adiposo/metabolismo Animales Peso Corporal/efectos de drogas Relojes Circadianos/fisiología Córnea/efectos de drogas Córnea/metabolismo Modelos Animales de Enfermedad Ciclo Estral/efectos de drogas Ciclo Estral/metabolismo Femenino Hígado/efectos de drogas Hígado/metabolismo Actividad Motora/efectos de drogas Folículo Ovárico/efectos de drogas Folículo Ovárico/metabolismo Proteínas Circadianas Period/metabolismo Síndrome del Ovario Poliquístico/metabolismo Ratas Ratas Transgénicas Maduración Sexual/efectos de drogas [Pt] Tipo de publicación: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL [Nm] Nombre de substancia: 0 (Androgens); 0 (Per1 protein, rat); 0 (Period Circadian Proteins); 521-18-6 (Dihydrotestosterone) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: AIM; IM [Da] Fecha de ingreso para procesamiento: 130325 [St] Status: MEDLINE [do] DOI: 10.1210/en.2012-2066

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[PMID]: 22576023 [Au] Autor: Shigefuku R; Takahashi H; Kobayashi M; Ikeda H; Matsunaga K; Okuse C; Matsumoto N; Maeyama S; Sase S; Suzuki M; Itoh F [Ad] Dirección: Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan. [Ti] Título: Pathophysiological analysis of nonalcoholic fatty liver disease by evaluation of fatty liver changes and blood flow using xenon computed tomography: can early-stage nonalcoholic steatohepatitis be distinguished from simple steatosis? [So] Fuente: J Gastroenterol;47(11):1238-47, 2012 Nov. [Is] ISSN: 1435-5922 [Cp] País de publicación: Japan [La] Idioma: eng [Ab] Resumen: INTRODUCTION: Effective noninvasive tests that can distinguish early-stage nonalcoholic steatohepatitis (NASH) from simple steatosis (SS) have long been sought. Our aim was to determine the possibility of noninvasively distinguishing early-stage NASH from SS. MATERIALS AND METHODS: We used Fick's principle and the Kety-Schmidt equation to determine the hepatic tissue blood flow (TBF) in 65 NASH patients who underwent xenon computed tomography (Xe-CT). We calculated the lambda value (LV), i.e., Xe gas solubility coefficient, in liver and blood. We assessed the histological severity of fatty changes and fibrosis on the basis of Brunt's classification. Liver biopsy revealed SS in 9 patients and NASH in 56 patients. NASH stages 1 and 2 were classified as early-stage NASH (Ea-NASH; 38 patients) and stages 3 and 4 as advanced-stage NASH (Ad-NASH; 18 patients). We evaluated the differences in LV and TBF among the 3 groups. RESULTS: LV was significantly lower in the Ad-NASH group than in the SS and Ea-NASH groups. Portal venous TBF (PVTBF) was significantly lower in the Ea-NASH group than in the SS group, and PVTBF was lower in the Ad-NASH group than in the Ea-NASH group. Total hepatic TBF (THTBF) was significantly different between the SS and Ea-NASH groups and between the SS and Ad-NASH groups. CONCLUSIONS: In conclusion, measurements of TBF and LV are useful for evaluating the pathophysiological progression of NASH. In addition, these measurements can facilitate the differential diagnosis of SS and Ea-NASH, which may not be distinguishable by other means. [Mh] Términos MeSH primario: Hígado Graso/diagnóstico Hígado/fisiopatología Tomografía Computarizada por Rayos X/métodos [Mh] Términos MeSH secundario: Adulto Anciano Diagnóstico Diferencial Hígado Graso/fisiopatología Femenino Humanos Hígado/irrigación sanguínea Masculino Mediana Edad Flujo Sanguíneo Regional Índice de Severidad de la Enfermedad Solubilidad Xenón/química Adulto Joven [Pt] Tipo de publicación: CLINICAL TRIAL; JOURNAL ARTICLE [Nm] Nombre de substancia: 7440-63-3 (Xenon) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 121119 [St] Status: MEDLINE [do] DOI: 10.1007/s00535-012-0581-4

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[PMID]: 22569763 [Au] Autor: Ikegami T; Hyogo H; Honda A; Miyazaki T; Tokushige K; Hashimoto E; Inui K; Matsuzaki Y; Tazuma S [Ad] Dirección: Division of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami-machi, Inashiki-gun, Ibaraki 300-0395, Japan. [Ti] Título: Increased serum liver X receptor ligand oxysterols in patients with non-alcoholic fatty liver disease. [So] Fuente: J Gastroenterol;47(11):1257-66, 2012 Nov. [Is] ISSN: 1435-5922 [Cp] País de publicación: Japan [La] Idioma: eng [Ab] Resumen: BACKGROUND: This study is a post-hoc analysis of a subset of patients who participated in our multi-institutional case-control study that evaluated the effects of pitavastatin in patients with non-alcoholic fatty liver disease (NAFLD) with hypercholesterolemia. METHODS: Serum samples of fifteen patients with biopsy-proven NAFLD with dyslipidemia were investigated. Serum markers of lipid metabolism were quantified by liquid chromatography-mass spectrometry (LC-MS)/MS. These data were then compared with those of 36 sex- and age-matched healthy controls. In addition, changes in these markers produced by treatment with pitavastatin were evaluated. RESULTS: Serum non-cholesterol sterols, reflecting intestinal cholesterol absorption, were significantly lower in the NAFLD patients compared to the controls, and the cholesterol synthesis marker, the ratio of lathosterol to cholesterol, was not significantly different between the two groups. Serum proportions of liver X receptor α (LXRα) ligand oxysterols (ratios to cholesterol) were significantly elevated in the NAFLD patients compared to the controls. The sum of oxysterols relative to cholesterol and the homeostasis model assessment as an index of insulin resistance (HOMA-IR) were significantly correlated. The marker representing cholesterol synthesis was significantly suppressed by pitavastatin treatment, from 3 months after initiation of the treatment, and the suppression remained significant during the observation period. The markers representing cholesterol absorption were unchanged at 3 months, but had significantly increased at 12 months. Serum oxysterol levels relative to cholesterol maintained high values and did not change significantly during the 12-month period of treatment. CONCLUSIONS: We speculate that serum LXRα ligand oxysterol levels (relative to cholesterol) could be surrogate markers of insulin resistance, and that high oxysterol levels in the circulation may play an important role in the development of hepatic and peripheral insulin resistance followed by NAFLD. [Mh] Términos MeSH primario: Hígado Graso/fisiopatología Hipercolesterolemia/quimioterapia Receptores Nucleares Huérfanos/sangre Quinolinas/uso terapéutico [Mh] Términos MeSH secundario: Adulto Marcadores Biológicos/sangre Estudios de Casos y Controles Colesterol/sangre Cromatografía Liquida Hígado Graso/quimioterapia Femenino Humanos Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico Resistencia a la Insulina Metabolismo de los Lípidos/efectos de drogas Masculino Mediana Edad Estudios Prospectivos Espectrometría de Masas en Tándem Adulto Joven [Pt] Tipo de publicación: CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nombre de substancia: 0 (Biological Markers); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (Orphan Nuclear Receptors); 0 (Quinolines); 0 (liver X receptor); 57-88-5 (Cholesterol); M5681Q5F9P (pitavastatin) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 121119 [St] Status: MEDLINE [do] DOI: 10.1007/s00535-012-0585-0

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[PMID]: 23104131 [Au] Autor: Bhargava P; Li C; Stanya KJ; Jacobi D; Dai L; Liu S; Gangl MR; Harn DA; Lee CH [Ad] Dirección: Department of Genetics and Complex Diseases, Division of Biological Sciences, Harvard School of Public Health, Boston, MA, USA. [Ti] Título: Immunomodulatory glycan LNFPIII alleviates hepatosteatosis and insulin resistance through direct and indirect control of metabolic pathways. [So] Fuente: Nat Med;18(11):1665-72, 2012 Nov. [Is] ISSN: 1546-170X [Cp] País de publicación: United States [La] Idioma: eng [Ab] Resumen: Parasitic worms express host-like glycans to attenuate the immune response of human hosts. The therapeutic potential of this immunomodulatory mechanism in controlling the metabolic dysfunction that is associated with chronic inflammation remains unexplored. We demonstrate here that administration of lacto-N-fucopentaose III (LNFPIII), a Lewis(X)-containing immunomodulatory glycan found in human milk and on parasitic helminths, improves glucose tolerance and insulin sensitivity in diet-induced obese mice. This effect is mediated partly through increased interleukin-10 (Il-10) production by LNFPIII-activated macrophages and dendritic cells, which reduces white adipose tissue inflammation and sensitizes the insulin response of adipocytes. Concurrently, LNFPIII treatment upregulates nuclear receptor subfamily 1, group H, member 4 (Fxr-α, also known as Nr1h4) to suppress lipogenesis in the liver, conferring protection against hepatosteatosis. At the signaling level, the extracellular signal-regulated kinase (Erk)-activator protein 1 (Ap1) pathway seems to mediate the effects of LNFPIII on both inflammatory and metabolic pathways. Our results suggest that LNFPIII may provide new therapeutic approaches to treat metabolic diseases. [Mh] Términos MeSH primario: Tejido Adiposo Amino Azúcares Inflamación Redes y Vías Metabólicas Polisacáridos Receptores Citoplasmáticos y Nucleares [Mh] Términos MeSH secundario: Tejido Adiposo/crecimiento & desarrollo Tejido Adiposo/patología Amino Azúcares/administración & dosificación Amino Azúcares/inmunología Amino Azúcares/metabolismo Animales Células Dendríticas/metabolismo Diabetes Mellitus Experimental/patología Diabetes Mellitus Experimental/terapia Dieta Alta en Grasa Hígado Graso/inmunología Hígado Graso/metabolismo Hígado Graso/terapia Células Hep G2 Humanos Inflamación/inmunología Inflamación/patología Inflamación/terapia Resistencia a la Insulina/inmunología Interleucina-10/metabolismo Hígado/metabolismo Hígado/patología Macrófagos/metabolismo Redes y Vías Metabólicas/inmunología Ratones Ratones Obesos/inmunología Ratones Obesos/metabolismo Polisacáridos/administración & dosificación Polisacáridos/inmunología Polisacáridos/metabolismo Receptores Citoplasmáticos y Nucleares/inmunología Receptores Citoplasmáticos y Nucleares/metabolismo Transducción de Señal [Pt] Tipo de publicación: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nombre de substancia: 0 (Amino Sugars); 0 (Polysaccharides); 0 (Receptors, Cytoplasmic and Nuclear); 0 (farnesoid X-activated receptor); 0 (lacto-N-fucopentaose III); 130068-27-8 (Interleukin-10) [Em] Mes de ingreso: 1304 [Cu] Fecha actualización por clase: 130503 [Lr] Fecha última revisión: 130503 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 121108 [St] Status: MEDLINE [do] DOI: 10.1038/nm.2962

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[PMID]: 23119079 [Au] Autor: Marino JS; Iler J; Dowling AR; Chua S; Bruning JC; Coppari R; Hill JW [Ad] Dirección: Department of Physiology and Pharmacology, Center for Diabetes and Endocrine Research, University of Toledo Medical Center, Toledo, Ohio, United States of America. [Ti] Título: Adipocyte dysfunction in a mouse model of polycystic ovary syndrome (PCOS): evidence of adipocyte hypertrophy and tissue-specific inflammation. [So] Fuente: PLoS One;7(10):e48643, 2012. [Is] ISSN: 1932-6203 [Cp] País de publicación: United States [La] Idioma: eng [Ab] Resumen: Clinical research shows an association between polycystic ovary syndrome (PCOS) and chronic inflammation, a pathological state thought to contribute to insulin resistance. The underlying pathways, however, have not been defined. The purpose of this study was to characterize the inflammatory state of a novel mouse model of PCOS. Female mice lacking leptin and insulin receptors in pro-opiomelanocortin neurons (IR/LepR(POMC) mice) and littermate controls were evaluated for estrous cyclicity, ovarian and adipose tissue morphology, and body composition by QMR and CT scan. Tissue-specific macrophage infiltration and cytokine mRNA expression were measured, as well as circulating cytokine levels. Finally, glucose regulation during pregnancy was evaluated as a measure of risk for diabetes development. Forty-five percent of IR/LepR(POMC) mice showed reduced or absent ovulation. IR/LepR(POMC) mice also had increased fat mass and adipocyte hypertrophy. These traits accompanied elevations in macrophage accumulation and inflammatory cytokine production in perigonadal adipose tissue, liver, and ovary. These mice also exhibited gestational hyperglycemia as predicted. This report is the first to show the presence of inflammation in IR/LepR(POMC) mice, which develop a PCOS-like phenotype. Thus, IR/LepR(POMC) mice may serve as a new mouse model to clarify the involvement of adipose and liver tissue in the pathogenesis and etiology of PCOS, allowing more targeted research on the development of PCOS and potential therapeutic interventions. [Mh] Términos MeSH primario: Adipocitos/metabolismo Modelos Animales de Enfermedad Inflamación/genética Síndrome del Ovario Poliquístico/genética [Mh] Términos MeSH secundario: Adipocitos/patología Tejido Adiposo/metabolismo Tejido Adiposo/patología Animales Glucemia/metabolismo Femenino Expresión Génica Humanos Hipertrofia Inflamación/metabolismo Interleucina-1beta/sangre Interleucina-1beta/genética Interleucina-1beta/metabolismo Interleucina-6/sangre Interleucina-6/genética Interleucina-6/metabolismo Hígado/metabolismo Hígado/patología Imagen por Resonancia Magnética Masculino Ratones Ratones Noqueados Ovario/metabolismo Ovario/patología Ovulación/genética Síndrome del Ovario Poliquístico/sangre Síndrome del Ovario Poliquístico/metabolismo Embarazo Receptor de Insulina/genética Receptor de Insulina/metabolismo Receptores de Leptina/genética Receptores de Leptina/metabolismo Reacción en Cadena de la Polimerasa de Transcriptasa Inversa Tomografía Computarizada por Rayos X [Pt] Tipo de publicación: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nombre de substancia: 0 (Blood Glucose); 0 (Interleukin-1beta); 0 (Interleukin-6); 0 (Receptors, Leptin); EC 2.7.10.1 (Receptor, Insulin) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 121102 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0048643

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[PMID]: 22854109 [Au] Autor: Tsuchiya H; Ebata Y; Sakabe T; Hama S; Kogure K; Shiota G [Ad] Dirección: Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Misasagi Nakauchi-cho 5, Yamashina-ku, Kyoto, 607-8414, Japan. tsuchiya@mb.kyoto-phu.ac.jp [Ti] Título: High-fat, high-fructose diet induces hepatic iron overload via a hepcidin-independent mechanism prior to the onset of liver steatosis and insulin resistance in mice. [So] Fuente: Metabolism;62(1):62-9, 2013 Jan. [Is] ISSN: 1532-8600 [Cp] País de publicación: United States [La] Idioma: eng [Ab] Resumen: OBJECTIVE: Excess iron deposition in tissues leads to increased oxidative stress. The clinical observation that non-alcoholic fatty liver disease (NAFLD) is frequently associated with hepatic iron overload (HIO) indicates that iron-induced oxidative stress may be related to NAFLD pathology. Decreased expression of hepcidin, a hepatic hormone that suppresses dietary iron absorption in the duodenum, is frequently observed in NAFLD patients and has been postulated to be a cause of HIO. MATERIALS/METHODS: Because dietary fat and fructose intake play roles in the onset of NAFLD, we fed C57BL/6J mice a high-fat, high-fructose (HFHFr) diet for 16 weeks to study the relationship between hepatic iron content and NAFLD. RESULTS: Within 4 weeks after the start of the experiment, the mice exhibited significant increases in hepatic free fatty acid (FFA) content, serum insulin levels, and the homeostasis model assessment of insulin resistance. Interestingly, hepatic iron content and oxidative stress significantly increased with the HFHFr diet 2 weeks earlier than hepatic FFA accumulation and decreased insulin sensitivity. Moreover, hepatic hepcidin expression was significantly downregulated, as is also observed in NAFLD patients, but much later than the onset of HIO. CONCLUSIONS: Accordingly, our data demonstrated that HIO may have a pathogenic role in the onset of liver steatosis and insulin resistance. Moreover, distinct mechanisms, in addition to hepcidin, may underlie NAFLD-related HIO. These data suggest that the HFHFr diet can be used for establishing a suitable model to study the precise mechanism of HIO in NAFLD patients. [Mh] Términos MeSH primario: Péptidos Catiónicos Antimicrobianos/metabolismo Grasas en la Dieta/administración & dosificación Hígado Graso/metabolismo Fructosa/administración & dosificación Resistencia a la Insulina/fisiología Sobrecarga de Hierro/etiología [Mh] Términos MeSH secundario: Alanina Transaminasa/sangre Animales Péptidos Catiónicos Antimicrobianos/genética Aspartato Aminotransferasas/sangre Dieta Alta en Grasa Modelos Animales de Enfermedad Ácidos Grasos no Esterificados/metabolismo Hígado Graso/sangre Hígado Graso/etiología Insulina/sangre Sobrecarga de Hierro/metabolismo Masculino Ratones Ratones Consanguíneos C57BL ARN/química ARN/genética Organismos Libres de Patógenos Específicos [Pt] Tipo de publicación: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nombre de substancia: 0 (Antimicrobial Cationic Peptides); 0 (Dietary Fats); 0 (Fatty Acids, Nonesterified); 0 (Insulin); 0 (hepcidin); 30237-26-4 (Fructose); 63231-63-0 (RNA); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 121211 [St] Status: MEDLINE

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MEDLINE

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[PMID]: 22841522 [Au] Autor: Polyzos SA; Kountouras J; Papatheodorou A; Patsiaoura K; Katsiki E; Zafeiriadou E; Zavos C; Anastasiadou K; Terpos E [Ad] Dirección: Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece. stergios@endo.gr [Ti] Título: Helicobacter pylori infection in patients with nonalcoholic fatty liver disease. [So] Fuente: Metabolism;62(1):121-6, 2013 Jan. [Is] ISSN: 1532-8600 [Cp] País de publicación: United States [La] Idioma: eng [Ab] Resumen: OBJECTIVE: Clinical data regarding Helicobacter pylori (Hp) infection in nonalcoholic fatty liver disease (NAFLD) are limited. The aim was the evaluation of Hp infection in patients with NAFLD and its association with disease severity. METHODS: 28 patients with biopsy-proven NAFLD (15 with simple nonalcoholic fatty liver [NAFL], 13 with nonalcoholic steatohepatitis [NASH]) and 25 matched healthy controls were recruited. Blood samples for anti-Hp Immunoglobulin G (IgG) and standard biochemical tests were obtained after overnight fasting, and (13)C urea breath test was performed before liver biopsy in NAFLD group. RESULTS: Higher rates of anti-Hp IgG (P=.038) were observed in NAFLD compared to control group. Only two NAFLD patients neither were Hp IgG seropositive nor did they have a history of eradication treatment compared to 11 control subjects (P=.002). Both Hp infection (assessed by history of Hp eradication treatment and/or Hp IgG seropositivity) (P=.034) and log(HOMA-IR) (P=.007) could independently predict NAFLD in logistic regression analysis. There were similar rates of Hp IgG seropositivity or positivity in (13)C urea breath test or their combination between NAFL and NASH patients. There were no significant differences in steatosis grade, fibrosis stage, lobular or portal inflammation, or ballooning, when NAFLD patients were divided according to Hp IgG seropositivity or (13)C urea breath test positivity. CONCLUSIONS: Hp infection may represent one more hit contributing to the pathogenesis of NAFL, though not to the progression from NAFL to NASH. These results warrant further validation. If confirmed, eradicating Hp infection may have certain therapeutic perspectives in NAFLD treatment. [Mh] Términos MeSH primario: Hígado Graso/microbiología Infecciones por Helicobacter/metabolismo Helicobacter pylori/aislamiento & purificación [Mh] Términos MeSH secundario: Adulto Alanina Transaminasa/sangre Aspartato Aminotransferasas/sangre Proteína C-Reactiva/metabolismo Distribución de Chi-Cuadrado Estudios Transversales Hígado Graso/sangre Hígado Graso/patología Femenino Infecciones por Helicobacter/sangre Infecciones por Helicobacter/microbiología Humanos Inmunoglobulina G/sangre Masculino Factor de Necrosis Tumoral alfa/sangre gamma-Glutamiltransferasa/sangre [Pt] Tipo de publicación: JOURNAL ARTICLE [Nm] Nombre de substancia: 0 (Immunoglobulin G); 0 (Tumor Necrosis Factor-alpha); 9007-41-4 (C-Reactive Protein); EC 2.3.2.2 (gamma-Glutamyltransferase); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase) [Em] Mes de ingreso: 1305 [Sb] Subgrupo de revista: IM [Da] Fecha de ingreso para procesamiento: 121211 [St] Status: MEDLINE

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