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  1 / 1968 MEDLINE  
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[PMID]:28466561
[Au] Autor:Li W; Amet T; Xing Y; Yang D; Liangpunsakul S; Puri P; Kamath PS; Sanyal AJ; Shah VH; Katz BP; Radaeva S; Crabb DW; Chalasani N; Yu Q
[Ad] Endereço:Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN.
[Ti] Título:Alcohol abstinence ameliorates the dysregulated immune profiles in patients with alcoholic hepatitis: A prospective observational study.
[So] Source:Hepatology;66(2):575-590, 2017 08.
[Is] ISSN:1527-3350
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Alcoholic hepatitis (AH) develops in only a small proportion of heavy drinkers. To better understand the mechanisms underlying this disparity, we conducted a study to define the relationship between AH development and dysregulated immune responses that might be ameliorated by alcohol abstinence. Sixty-eight AH patients, 65 heavy drinking controls without liver disease (HDC), and 20 healthy controls were enrolled and followed up to 12 months. At baseline, HDC and healthy controls had no significant differences in their plasma levels of 38 inflammatory cytokines/chemokines measured using multiplex immunoassays. However, compared to HDC, AH patients had higher baseline levels of 11 cytokines/chemokines (tumor necrosis factor alpha, interleukin 6 [IL-6], IL-8, interferon gamma-induced protein 10, IL-4, IL-9, IL-10, fibroblast growth factor 2, IL-7, IL-15, and transforming growth factor alpha) but lower levels of the anti-inflammatory macrophage-derived chemokine. AH patients also had more activated yet dysfunctional immune cells as monocytes, T cells, and B cells expressed higher levels of cluster of differentiation 38 (CD38) and CD69 but low levels of human leukocyte antigen DR, CD80, and CD86 at baseline. In addition, CD4 T cells produced less interferon-gamma in response to T-cell stimulation. Up-regulated IL-6, IL-8, CD38, and CD69 and down-regulated macrophage-derived chemokine, human leukocyte antigen DR, CD86, and CD80 correlated positively and negatively, respectively, with disease severity. Longitudinal analysis indicated that levels of IL-6, IL-8, CD38, and CD69 were reduced, whereas levels of macrophage-derived chemokine, human leukocyte antigen DR, CD80, and CD86 were increased in abstinent AH patients. All of the cellular immune abnormalities were reversed by day 360 in abstinent AH patients; however, plasma levels of tumor necrosis factor alpha, IL-8, IL-10, fibroblast growth factor 2, and IL-7 remained higher. CONCLUSION: AH patients were in a highly immune-dysregulated state, whereas HDC showed little evidence of immune activation; alcohol abstinence reversed most, but not all, of the immunological abnormalities. (Hepatology 2017;66:575-590).
[Mh] Termos MeSH primário: Abstinência de Álcool
Citocinas/sangue
Hepatite Alcoólica/imunologia
Imunidade Celular/fisiologia
[Mh] Termos MeSH secundário: Adulto
Biomarcadores/sangue
Estudos de Casos e Controles
Quimiocinas/sangue
Progressão da Doença
Ensaio de Imunoadsorção Enzimática
Feminino
Citometria de Fluxo
Hepatite Alcoólica/fisiopatologia
Seres Humanos
Interleucina-6/sangue
Interleucina-8/sangue
Masculino
Meia-Idade
Estudos Prospectivos
Medição de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Biomarkers); 0 (Chemokines); 0 (Cytokines); 0 (Interleukin-6); 0 (Interleukin-8)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1002/hep.29242


  2 / 1968 MEDLINE  
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[PMID]:29324766
[Au] Autor:Marot A; Dubois M; Trépo E; Moreno C; Deltenre P
[Ad] Endereço:Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
[Ti] Título:Liver transplantation for alcoholic hepatitis: A systematic review with meta-analysis.
[So] Source:PLoS One;13(1):e0190823, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The rate of alcohol relapse among patients who underwent liver transplantation for alcoholic hepatitis (AH) is not precisely known. AIM: Synthesize the available evidence on liver transplantation for AH to assess alcohol relapse and 6-month survival. METHODS: Meta-analysis of trials evaluating liver transplantation for AH, either clinically severe or diagnosed on the explant. RESULTS: Eleven studies were included. The pooled estimate rate for alcohol relapse was 0.22 (95% CI = 0.12-0.36) in overall analysis with high heterogeneity between studies (I2 = 76%), 0.20 (95% CI = 0.07-0.43) in the subgroup analysis including patients with clinically severe AH (I2 = 84%), 0.14 (95% CI = 0.08-0.23) among patients with clinically severe AH in sensitivity analysis excluding the discrepant studies that did not use stringent selection criteria for liver transplantation (I2 = 0%), and 0.15 (95% CI = 0.07-0.27) for recurrent harmful alcohol consumption among patients with clinically severe AH (I2 = 3%). The risk of alcohol relapse was not different between AH transplanted patients and patients with alcoholic cirrhosis who underwent elective liver transplantation in sensitivity analysis excluding the discrepant studies (OR = 1.68, 95%CI = 0.79-3.58, p = 0.2, I2 = 16%). The pooled estimate rate for 6-month survival was 0.85 (95% CI = 0.77-0.91, I2 = 49%), and 0.80 among patients transplanted for clinically severe AH (95% CI = 0.69-0.88, I2 = 30%). AH transplanted patients had similar 6-month survival to patients with alcoholic cirrhosis who underwent elective liver transplantation (OR = 2.00, 95% CI = 0.95-4.23, p = 0.07, I2 = 0%). CONCLUSION: Using stringent selection criteria, 14% of patients with clinically severe AH have alcohol relapse after liver transplantation. The percentage of alcohol relapse of AH transplanted patients is similar than that of patients who underwent elective liver transplantation.
[Mh] Termos MeSH primário: Alcoolismo/complicações
Hepatite Alcoólica/cirurgia
Transplante de Fígado
[Mh] Termos MeSH secundário: Abstinência de Álcool
Procedimentos Cirúrgicos Eletivos
Seres Humanos
Recidiva
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190823


  3 / 1968 MEDLINE  
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[PMID]:28741287
[Au] Autor:Lucey MR
[Ad] Endereço:Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, WI.
[Ti] Título:Redefining Successful Treatment of Severe Alcoholic Hepatitis.
[So] Source:Hepatology;66(6):1722-1723, 2017 12.
[Is] ISSN:1527-3350
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Hepatite Alcoólica
Transplante de Fígado
[Mh] Termos MeSH secundário: Seres Humanos
Índice de Gravidade de Doença
[Pt] Tipo de publicação:JOURNAL ARTICLE; COMMENT
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180125
[Lr] Data última revisão:
180125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1002/hep.29398


  4 / 1968 MEDLINE  
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[PMID]:28459138
[Au] Autor:Louvet A; Labreuche J; Artru F; Bouthors A; Rolland B; Saffers P; Lollivier J; Lemaître E; Dharancy S; Lassailly G; Canva-Delcambre V; Duhamel A; Mathurin P
[Ad] Endereço:Service des Maladies de l'appareil digestif, Hôpital Huriez, Lille, France.
[Ti] Título:Main drivers of outcome differ between short term and long term in severe alcoholic hepatitis: A prospective study.
[So] Source:Hepatology;66(5):1464-1473, 2017 11.
[Is] ISSN:1527-3350
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Understanding the mechanisms of outcome according to the time frame can help optimize the therapeutic development in severe alcoholic hepatitis. We assessed short-term and long-term survival in severe alcoholic hepatitis based on baseline disease severity, extent of therapeutic improvement, long-term influence of alcohol relapse, and their interaction. Data and alcohol consumption were prospectively recorded in 398 patients treated with corticosteroids in the short term (from corticosteroid initiation to 6 months) and long term (from 6 months to maximum follow-up time). Cumulative incidence rate of first alcohol relapse was 25.2%, 33.7%, and 35.2% at 1, 3, and 5 years, respectively. Alcohol relapse (≥30 g/day) was not associated with mortality (P = 0.24) during the short-term period (1,606 patient-months at risk), but the Lille (P < 0.0001) and Model for End-Stage Liver Disease (P < 0.0001) scores were independent prognostic factors. In patients who were alive at 6 months (median follow-up, 42 months; interquartile range 11-88), corresponding to 10,413 patient-months at risk, alcohol consumption (≥30 g/day) was associated with mortality (hazard ratio, 3.9; P < 0.0001). Additional analysis with abstinent patients as a reference showed a dose effect of alcohol on the hazard ratio of death: 2.36 (P = 0.052) for 1-29 g/day, 3.2 (P = 0.003) for 30-49 g/day, 3.51 (P < 0.0001) for 50-99 g/day, and 5.61 (P < 0.0001) for ≥ 100 g/day. The baseline Model for End-Stage Liver Disease score was not predictive of long-term outcome, while Lille score (P = 0.02) and alcohol relapse (P < 0.0001) were independent prognostic factors. CONCLUSION: This study shows that new therapeutic development for severe alcoholic hepatitis must target liver injury in the short term and alcohol consumption in the long term; thus, health agencies can endorse future study designs adapted to the time frame of factors influencing mortality; with this in mind, drug-targeting mechanisms involved in liver injury should only be tested for the short-term period. (Hepatology 2017;66:1464-1473).
[Mh] Termos MeSH primário: Hepatite Alcoólica/mortalidade
[Mh] Termos MeSH secundário: Corticosteroides/uso terapêutico
Adulto
Consumo de Bebidas Alcoólicas
Feminino
França/epidemiologia
Hepatite Alcoólica/tratamento farmacológico
Seres Humanos
Masculino
Meia-Idade
Estudos Prospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenal Cortex Hormones)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180122
[Lr] Data última revisão:
180122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1002/hep.29240


  5 / 1968 MEDLINE  
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[PMID]:27775820
[Au] Autor:Das S; Maras JS; Hussain MS; Sharma S; David P; Sukriti S; Shasthry SM; Maiwall R; Trehanpati N; Singh TP; Sarin SK
[Ad] Endereço:Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
[Ti] Título:Hyperoxidized albumin modulates neutrophils to induce oxidative stress and inflammation in severe alcoholic hepatitis.
[So] Source:Hepatology;65(2):631-646, 2017 02.
[Is] ISSN:1527-3350
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Albumin is a potent scavenger of reactive oxygen species (ROS). However, modifications in albumin structure may reduce its antioxidant properties and modulate its immune-regulatory functions. We examined alterations in circulating albumin in severe alcoholic hepatitis (SAH) patients and their contribution to neutrophil activation, intracellular stress, and alteration in associated molecular pathways. Albumin modifications and plasma oxidative stress were assessed in SAH patients (n = 90), alcoholic cirrhosis patients (n = 60), and healthy controls (n = 30) using liquid chromatography/mass spectrometry and spectrophotometry. Activation and intracellular ROS were measured in healthy neutrophils after treatment with purified albumin from the study groups. Gene expression of SAH neutrophils was analyzed and compared to gene expression from healthy neutrophils after stimulation with purified albumin from SAH patient plasma. SAH-albumin showed the highest albumin oxidative state (P < 0.05) and prominent alteration as human nonmercaptalbumin 2 (P < 0.05). Plasma oxidative stress (advanced oxidative protein product) was higher in SAH versus alcoholic cirrhosis patients and healthy controls (P < 0.05). Neutrophil gelatinase-associated lipocalin, myeloperoxidase, and intracellular ROS levels were highest in SAH-albumin-treated neutrophils (P < 0.05). Genes associated with neutrophil activation, ROS production, intracellular antioxidation, and leukocyte migration plus genes for proinflammatory cytokines and various toll-like receptors were overexpressed in SAH neutrophils compared to healthy neutrophils (P < 0.05). Expression of the above-mentioned genes in SAH-albumin-stimulated healthy neutrophils was comparable with SAH patient neutrophils, except for genes associated with apoptosis, endoplasmic reticulum stress, and autophagy (P < 0.05). CONCLUSIONS: In patients with SAH, there is a significant increase in albumin oxidation, and albumin acts as a pro-oxidant; this promotes oxidative stress and inflammation in SAH patients through activation of neutrophils. (Hepatology 2017;65:631-646).
[Mh] Termos MeSH primário: Hepatite Alcoólica/sangue
Hepatite Alcoólica/patologia
Estresse Oxidativo/fisiologia
Espécies Reativas de Oxigênio/sangue
[Mh] Termos MeSH secundário: Adulto
Cromatografia Líquida
Estudos Transversais
Feminino
Seres Humanos
Lipocalina-2/metabolismo
Testes de Função Hepática
Masculino
Espectrometria de Massas
Meia-Idade
Ativação de Neutrófilo
Reação em Cadeia da Polimerase em Tempo Real/métodos
Valores de Referência
Índice de Gravidade de Doença
Estatísticas não Paramétricas
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (LCN2 protein, human); 0 (Lipocalin-2); 0 (Reactive Oxygen Species)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180121
[Lr] Data última revisão:
180121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1002/hep.28897


  6 / 1968 MEDLINE  
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[PMID]:28373772
[Au] Autor:Dhanda AD; Sinha A; Hunt V; Saleem S; Cramp ME; Collins PL
[Ad] Endereço:Ashwin D Dhanda, Matthew E Cramp, Institute of Translational and Stratified Medicine, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth PL6 8BU, United Kingdom.
[Ti] Título:Infection does not increase long-term mortality in patients with acute severe alcoholic hepatitis treated with corticosteroids.
[So] Source:World J Gastroenterol;23(11):2052-2059, 2017 Mar 21.
[Is] ISSN:2219-2840
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIM: To determine whether infection in patients with acute severe alcoholic hepatitis (AAH) treated with corticosteroids is associated with increased mortality. METHODS: Consecutive patients with AAH were treated with steroids and recruited to the study. Clinically relevant infections (body temperature > 38 °C or < 36 °C for more than 4 h, ascitic neutrophil count > 0.25 ×10 /L, consolidation on chest radiograph or clinically relevant positive microbiological culture of bodily fluid) were recorded prospectively. Clinical and laboratory parameters were recorded and survival at 90 d and 6 mo was determined. Univariate analysis of factors associated with 90-d mortality was performed and significant variables included in a multivariate analysis. RESULTS: Seventy-two patients were included in the final analysis (mean age 47.9 years, 26% female, mean discriminant function 53.0). Overall mortality in the group occurred in 15 (21%), 23 (32%) and 31 (43%) at day 28, day 90 and 1 year respectively. 36 (50%) had a clinically relevant infection during their hospitalisation (23 after initiation of steroids). The median time to development of incident infection after commencement of steroids was 10 d. The commonest site of infection was ascites (31%) and bacteraemia (31%) followed by urinary tract (19%) and respiratory tract (8%). Forty-one separate organisms were isolated in 33 patients; the most frequent genus was Escherichia (22%) and Enterococcus (20%). Infection was not associated with 90-d or 1 year mortality but was associated with higher creatinine, model for end-stage liver disease and Lille score. Baseline urea was the only independent predictor of 90-d mortality. CONCLUSION: Clinically relevant infections are common in patients with AAH but are not associated with increased 90-d or 1 year mortality.
[Mh] Termos MeSH primário: Infecções Bacterianas/complicações
Glucocorticoides/uso terapêutico
Hepatite Alcoólica/tratamento farmacológico
Hepatite Alcoólica/mortalidade
[Mh] Termos MeSH secundário: Doença Aguda
Adulto
Idoso
Infecções Bacterianas/sangue
Infecções Bacterianas/microbiologia
Creatinina/sangue
Doença Hepática Terminal/diagnóstico
Feminino
Seguimentos
Hepatite Alcoólica/sangue
Hepatite Alcoólica/complicações
Seres Humanos
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Prognóstico
Estudos Prospectivos
Fatores de Risco
Índice de Gravidade de Doença
Ureia/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Glucocorticoids); 8W8T17847W (Urea); AYI8EX34EU (Creatinine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE
[do] DOI:10.3748/wjg.v23.i11.2052


  7 / 1968 MEDLINE  
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[PMID]:28350851
[Au] Autor:Lowe PP; Gyongyosi B; Satishchandran A; Iracheta-Vellve A; Ambade A; Kodys K; Catalano D; Ward DV; Szabo G
[Ad] Endereço:Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
[Ti] Título:Alcohol-related changes in the intestinal microbiome influence neutrophil infiltration, inflammation and steatosis in early alcoholic hepatitis in mice.
[So] Source:PLoS One;12(3):e0174544, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Alcohol-induced intestinal dysbiosis disrupts homeostatic gut-liver axis function and is essential in the development of alcoholic liver disease. Here, we investigate changes in enteric microbiome composition in a model of early alcoholic steatohepatitis and dissect the pathogenic role of intestinal microbes in alcohol-induced liver pathology. MATERIALS AND METHODS: Wild type mice received a 10-day diet that was either 5% alcohol-containing or an isocaloric control diet plus a single binge. 16S rDNA sequencing defined the bacterial communities in the cecum of alcohol- and pair-fed animals. Some mice were treated with an antibiotic cocktail prior to and throughout alcohol feeding. Liver neutrophils, cytokines and steatosis were evaluated. RESULTS: Acute-on-chronic alcohol administration induced shifts in various bacterial phyla in the cecum, including increased Actinobacteria and a reduction in Verrucomicrobia driven entirely by a reduction in the genus Akkermansia. Antibiotic treatment reduced the gut bacterial load and circulating bacterial wall component lipopolysaccharide (LPS). We found that bacterial load suppression prevented alcohol-related increases in the number of myeloperoxidase- (MPO) positive infiltrating neutrophils in the liver. Expression of liver mRNA tumor necrosis factor alpha (Tnfα), C-X-C motif chemokine ligand 1 (Cxcl1) and circulating protein monocyte chemoattractant protein-1 (MCP-1) were also reduced in antibiotic-treated alcohol-fed mice. Alcohol-induced hepatic steatosis measured by Oil-Red O staining was significantly reduced in antibiotic treated mice. Genes regulating lipid production and storage were also altered by alcohol and antibiotic treatment. Interestingly, antibiotic treatment did not protect from alcohol-induced increases in serum aminotransferases (ALT/AST). CONCLUSIONS: Our data indicate that acute-on-chronic alcohol feeding alters the microflora at multiple taxonomic levels and identifies loss of Akkermansia as an early marker of alcohol-induced gut dysbiosis. We conclude that gut microbes influence liver inflammation, neutrophil infiltration and liver steatosis following alcohol consumption and these data further emphasize the role of the gut-liver axis in early alcoholic liver disease.
[Mh] Termos MeSH primário: Fígado Gorduroso/genética
Microbioma Gastrointestinal/genética
Hepatite Alcoólica/genética
Inflamação/genética
Infiltração de Neutrófilos/genética
[Mh] Termos MeSH secundário: Animais
Antibacterianos/administração & dosagem
Antibacterianos/farmacologia
Bactérias/classificação
Bactérias/efeitos dos fármacos
Bactérias/genética
Depressores do Sistema Nervoso Central/administração & dosagem
Depressores do Sistema Nervoso Central/toxicidade
Etanol/administração & dosagem
Etanol/toxicidade
Fígado Gorduroso/induzido quimicamente
Fígado Gorduroso Alcoólico/etiologia
Fígado Gorduroso Alcoólico/genética
Feminino
Microbioma Gastrointestinal/efeitos dos fármacos
Expressão Gênica/efeitos dos fármacos
Hepatite Alcoólica/etiologia
Inflamação/induzido quimicamente
Fígado/efeitos dos fármacos
Fígado/metabolismo
Fígado/patologia
Camundongos Endogâmicos C57BL
Infiltração de Neutrófilos/efeitos dos fármacos
RNA Ribossômico 16S/genética
Reação em Cadeia da Polimerase Via Transcriptase Reversa
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Central Nervous System Depressants); 0 (RNA, Ribosomal, 16S); 3K9958V90M (Ethanol)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170329
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0174544


  8 / 1968 MEDLINE  
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[PMID]:28274894
[Au] Autor:Chang YY; Liu YC; Kuo YH; Lin YL; Wu YS; Chen JW; Chen YC
[Ad] Endereço:Department of Microbiology and Immunology, School of Medicine, Chung-Shan Medical University, Taichung 402, Taiwan; Clinical Laboratory, Chung-Shan Medical University Hospital, Taichung 402, Taiwan. Electronic address: cyy0709@csmu.edu.tw.
[Ti] Título:Effects of antrosterol from Antrodia camphorata submerged whole broth on lipid homeostasis, antioxidation, alcohol clearance, and anti-inflammation in livers of chronic-alcohol fed mice.
[So] Source:J Ethnopharmacol;202:200-207, 2017 Apr 18.
[Is] ISSN:1872-7573
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia camphorata is a functional fungus in Taiwan and owns several pharmacological functions. Antrosterol, a bioactive constitute of sterols in edible Antrodia camphorata submerged whole broth, can protect liver from CCl damage via enhancing antioxidant and anti-inflammatory capacities. AIM OF THE STUDY: The aim of this study was to investigate the hepatoprotection of antrosterol (named as EK100) against alcohol consumption. MATERIALS AND METHODS: A Lieber-DeCarli regular EtOH diet (EtOH liquid diet, 5% (v/v) alcohol) was applied to induce alcoholic liver damage. Mice were randomly divided into 5 groups: (1) Control: control liquid diet; (2) EtOH: EtOH liquid diet; (3) EK100_1X: EtOH liquid diet and 1mg EK100 (Antrosterol)/Kg body weight (bw); (4) EK100_5X: EtOH liquid diet and 5mg EK100/Kg bw; (5) EK100_10X: EtOH liquid diet and 10mg EK100/Kg bw. At the end of experiment, the livers were collected for histo-pathological analyses, RNA and protein extraction, and enzymatic activities. RESULTS: Antrosterol reduced serum/liver lipids of alcohol-diet fed mice which highly related to upregulated fatty acid ß-oxidation and downregulated lipogenesis, and increased fecal lipid/bile-acid outputs. Antrosterol enhanced hepatic antioxidant capabilities in alcohol-diet fed mice while it also lowered serum alcohol level, as well as increased alcohol dehydrogenase (ADH) and catalase (CAT) activities and decreased CYP2E1 protein expression in livers of alcohol-diet fed mice. Besides, antrosterol lowered hepatic inflammation and fibrosis related gene expressions, as well as serum AST/ALT values and TNF-α/IL-1ß contents in alcohol-diet fed mice. CONCLUSION: Based on the results, hepatoprotection of antrosterol is mostly attributed to its regulations of lipid homeostasis, antioxidant capability, alcohol metabolism, and anti-inflammation.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacologia
Antioxidantes/farmacologia
Antrodia/química
Depressores do Sistema Nervoso Central/farmacocinética
Etanol/farmacocinética
Hepatite Alcoólica/prevenção & controle
Metabolismo dos Lipídeos/efeitos dos fármacos
Esteróis/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Depressores do Sistema Nervoso Central/sangue
Citocinas/metabolismo
Dieta
Etanol/sangue
Ácidos Graxos/metabolismo
Crescimento/efeitos dos fármacos
Hepatite Alcoólica/metabolismo
Hepatite Alcoólica/patologia
Fígado/metabolismo
Fígado/patologia
Testes de Função Hepática
Masculino
Camundongos
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Antioxidants); 0 (Central Nervous System Depressants); 0 (Cytokines); 0 (Fatty Acids); 0 (Sterols); 0 (antrosterol); 3K9958V90M (Ethanol)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170310
[St] Status:MEDLINE


  9 / 1968 MEDLINE  
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[PMID]:28225807
[Au] Autor:Cho YE; Im EJ; Moon PG; Mezey E; Song BJ; Baek MC
[Ad] Endereço:Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
[Ti] Título:Increased liver-specific proteins in circulating extracellular vesicles as potential biomarkers for drug- and alcohol-induced liver injury.
[So] Source:PLoS One;12(2):e0172463, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Drug- and alcohol-induced liver injury are a leading cause of liver failure and transplantation. Emerging evidence suggests that extracellular vesicles (EVs) are a source of biomarkers because they contain unique proteins reflecting the identity and tissue-specific origin of the EV proteins. This study aimed to determine whether potentially hepatotoxic agents, such as acetaminophen (APAP) and binge alcohol, can increase the amounts of circulating EVs and evaluate liver-specific EV proteins as potential biomarkers for liver injury. The circulating EVs, isolated from plasma of APAP-exposed, ethanol-fed mice, or alcoholic hepatitis patients versus normal control counterparts, were characterized by proteomics and biochemical methods. Liver specific EV proteins were analyzed by immunoblots and ELISA. The amounts of total and liver-specific proteins in circulating EVs from APAP-treated mice significantly increased in a dose- and time-dependent manner. Proteomic analysis of EVs from APAP-exposed mice revealed that the amounts of liver-specific and/or hepatotoxic proteins were increased compared to those of controls. Additionally, the increased protein amounts in EVs following APAP exposure returned to basal levels when mice were treated with N-acetylcysteine or glutathione. Similar results of increased amounts and liver-specific proteins in circulating EVs were also observed in mice exposed to hepatotoxic doses of thioacetamide or d-galactosamine but not by non-hepatotoxic penicillin or myotoxic bupivacaine. Additionally, binge ethanol exposure significantly elevated liver-specific proteins in circulating EVs from mice and alcoholics with alcoholic hepatitis, compared to control counterparts. These results indicate that circulating EVs in drug- and alcohol-mediated hepatic injury contain liver-specific proteins that could serve as specific biomarkers for hepatotoxicity.
[Mh] Termos MeSH primário: Doença Hepática Induzida por Substâncias e Drogas/diagnóstico
Vesículas Extracelulares/metabolismo
Hepatite Alcoólica/diagnóstico
Fígado/metabolismo
[Mh] Termos MeSH secundário: Adulto
Animais
Aspartato Aminotransferases/sangue
Bilirrubina/sangue
Biomarcadores/metabolismo
Doença Hepática Induzida por Substâncias e Drogas/metabolismo
Feminino
Células Hep G2
Hepatite Alcoólica/metabolismo
Seres Humanos
Masculino
Camundongos
Meia-Idade
Proteômica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); EC 2.6.1.1 (Aspartate Aminotransferases); RFM9X3LJ49 (Bilirubin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170223
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0172463


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[PMID]:28207552
[Au] Autor:Huang A; Chang B; Sun Y; Lin H; Li B; Teng G; Zou ZS
[Ad] Endereço:aCenter of Noninfectious Liver Diseases, Beijing 302 Hospital bInstitute of Alcoholic Liver Disease, Beijing 302 Hospital, Beijing, China.
[Ti] Título:Disease spectrum of alcoholic liver disease in Beijing 302 Hospital from 2002 to 2013: A large tertiary referral hospital experience from 7422 patients.
[So] Source:Medicine (Baltimore);96(7):e6163, 2017 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Alcohol consumption in China has substantially increased over the last 3 decades and the number of patients with alcoholic liver disease (ALD) is rising at an alarming rate. However, accurate and representative data on time trends in its hospitalization rates are not available. The aim of this study is to assess the current status and burden of ALD in China by analyzing the data from a large tertiary referral hospital, Beijing 302 Hospital.Data were retrospectively recorded from patients diagnosed as ALD in Beijing 302 Hospital from 2002 to 2013. The disease spectrum and biochemical parameters of each patient were collected.The patients with ALD accounted for 3.93% (7422) of all patients (188,902) with liver diseases between 2002 and 2013. The number of patients hospitalized with ALD increased from 110 in 2002 to 1672 in 2013. The ratio of patients hospitalized with ALD to all patients hospitalized with liver diseases was rising almost continuously and increased from 1.68% in 2002 to 4.59% in 2013. Most patients with ALD were male. Age distribution of ALD hospitalization showed that the highest rate was in 40- to 49-year-old group in subjects. Notably, the annual proportion of severe alcoholic hepatitis (SAH) increased 2.43 times from 2002 to 2013. We found the highest levels of mean corpuscular volume, the aspartate aminotransferase/alanine aminotransferase ratio, total bilirubin, international normalized ratio, and alkaline phosphatase in SAH patients, while serum levels of hemoglobin, albumin, and cholinesterase were significantly decreased in SAH group. Among these ALD, the SAH patient population has the worst prognosis. Alcoholic cirrhosis (ALC) is the most common ALD, and annual admissions for ALC increased significantly during the analyzed period.The number of hospitalized patients with ALD and the annual hospitalization rate of ALD were increasing continuously in Beijing 302 Hospital from 2002 to 2013. More attention should be paid to develop population-based effective strategy to control ALD.
[Mh] Termos MeSH primário: Hepatopatias Alcoólicas/epidemiologia
Hepatopatias Alcoólicas/fisiopatologia
Centros de Atenção Terciária/estatística & dados numéricos
[Mh] Termos MeSH secundário: Adulto
Distribuição por Idade
Alcoolismo/complicações
China
Feminino
Hepatite Alcoólica/epidemiologia
Hepatite Alcoólica/fisiopatologia
Seres Humanos
Cirrose Hepática Alcoólica/epidemiologia
Cirrose Hepática Alcoólica/fisiopatologia
Hepatopatias Alcoólicas/etiologia
Testes de Função Hepática
Masculino
Meia-Idade
Estudos Retrospectivos
Índice de Gravidade de Doença
Distribuição por Sexo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170315
[Lr] Data última revisão:
170315
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170217
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000006163



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