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Pesquisa : A12.200.087 [Categoria DeCS]
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[PMID]:29175453
[Au] Autor:Zhang Y; Lickteig AJ; Csanaky IL; Klaassen CD
[Ad] Endereço:School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, PR China. Electronic address: youcai.zhang@tju.edu.cn.
[Ti] Título:Activation of PPARα decreases bile acids in livers of female mice while maintaining bile flow and biliary bile acid excretion.
[So] Source:Toxicol Appl Pharmacol;338:112-123, 2018 01 01.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Fibrates are hypolipidemic drugs that act as activators of peroxisome proliferator-activated receptor α (PPARα). In both humans and rodents, females were reported to be less responsive to fibrates than males. Previous studies on fibrates and PPARα usually involved male mice, but little has been done in females. The present study aimed to provide the first comprehensive analysis of the effects of clofibrate (CLOF) and PPARα on bile acid (BA) homeostasis in female mice. Study in WT male mice showed that a 4-day CLOF treatment increased liver weight, bile flow, and biliary BA excretion, but decreased total BAs in both serum and liver. In contrast, WT female mice were less susceptible to these CLOF-mediated responses observed in males. In WT female mice, CLOF decreased total BAs in the liver, but had little effect on the mRNAs of hepatic BA-related genes. Next, a comparative analysis between WT and PPARα-null female mice showed that lack of PPARα in female mice decreased total BAs in serum, but had little effect on total BAs in liver or bile. However, lack of PPARα in female mice increased mRNAs of BA synthetic enzymes (Cyp7a1, Cyp8b1, Cyp27a1, and Cyp7b1) and transporters (Ntcp, Oatp1a1, Oatp1b2, and Mrp3). Furthermore, the increase of Cyp7a1 in PPARα-null female mice was associated with an increase in liver Fxr-Shp-Lrh-1 signaling. In conclusion, female mice are resistant to CLOF-mediated effects on BA metabolism observed in males, which could be attributed to PPARα-mediated suppression in females on genes involved in BA synthesis and transport.
[Mh] Termos MeSH primário: Ácidos e Sais Biliares/metabolismo
Bile/metabolismo
Fígado/metabolismo
PPAR alfa/fisiologia
[Mh] Termos MeSH secundário: Animais
Colesterol/metabolismo
Colesterol 7-alfa-Hidroxilase/genética
Clofibrato/farmacologia
Feminino
Íleo/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Bile Acids and Salts); 0 (PPAR alpha); 97C5T2UQ7J (Cholesterol); EC 1.14.14.23 (Cholesterol 7-alpha-Hydroxylase); EC 1.14.14.23 (Cyp7a1 protein, mouse); HPN91K7FU3 (Clofibrate)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


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[PMID]:29331654
[Au] Autor:Xu Y; Mao X; Qin B; Peng Y; Zheng J
[Ad] Endereço:Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China.
[Ti] Título:In vitro and in vivo metabolic activation of rhein and characterization of glutathione conjugates derived from rhein.
[So] Source:Chem Biol Interact;283:1-9, 2018 Mar 01.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Rhein (RH), 4,5-dihydroxyanthrauinone-2-carboxylic acid, is found in rhubarb (Dahuang), a traditional herbal medicine. RH has reportedly demonstrated multiple pharmacologic properties. Previous studies have also shown that RH induced hepatotoxicity, but the mechanisms of the adverse effect remain unknown. The major objective of the present study was to study the metabolic pathways of RH in order to identify potential reactive metabolites. One mono-hydroxylation metabolite (M1) was detected in urine and bile of rats given RH. M1 was also observed in rat and human liver microsomal incubations after exposure to RH. A total of three (GSH) conjugates (M2, M3 and M5) were detected in bile of rats treated with RH. We concluded that M2-M3 were directly derived from parent compound RH through spontaneous reaction with GSH. M5 was derived from M1 by reaction with GSH, which required cytoslic GSTs. M5 was further metabolized to the corresponding NAC conjugate (mercapturic acid) and was excreted in urine. P450 2C9 was mainly involved in the oxidation of RH.
[Mh] Termos MeSH primário: Antraquinonas/metabolismo
Glutationa/química
[Mh] Termos MeSH secundário: Acetilcisteína/química
Animais
Antraquinonas/química
Antraquinonas/farmacologia
Antraquinonas/urina
Bile/química
Bile/efeitos dos fármacos
Bile/metabolismo
Cromatografia Líquida de Alta Pressão
Sistema Enzimático do Citocromo P-450/genética
Sistema Enzimático do Citocromo P-450/metabolismo
Seres Humanos
Masculino
Microssomos Hepáticos/efeitos dos fármacos
Microssomos Hepáticos/metabolismo
Ratos
Ratos Sprague-Dawley
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/genética
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthraquinones); 0 (Recombinant Proteins); 9035-51-2 (Cytochrome P-450 Enzyme System); GAN16C9B8O (Glutathione); WYQ7N0BPYC (Acetylcysteine); YM64C2P6UX (rhein)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180115
[St] Status:MEDLINE


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[PMID]:29324798
[Au] Autor:Gookin JL; Mathews KG; Cullen J; Seiler G
[Ad] Endereço:Department of Clinical Sciences, College of Veterinary Medicine and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, United States of America.
[Ti] Título:Qualitative metabolomics profiling of serum and bile from dogs with gallbladder mucocele formation.
[So] Source:PLoS One;13(1):e0191076, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mucocele formation is characterized by secretion of abnormally thick mucus by the gallbladder epithelium of dogs that may cause obstruction of the bile duct or rupture of the gallbladder. The disease is increasingly recognized and is associated with a high morbidity and mortality. The cause of gallbladder mucocele formation in dogs is unknown. There is a strong breed predisposition and affected dogs have a high incidence of concurrent endocrinopathy or hyperlipidemia. These observations suggest a significant influence of both genetic and metabolic factors on disease pathogenesis. In this study, we investigated a theory that mucocele formation is associated with a syndrome of metabolic disruption. We surmised that a global, untargeted metabolomics approach could provide unique insight into the systemic pathogenesis of gallbladder mucocele formation and identify specific compounds as candidate biomarkers or treatment targets. Moreover, concurrent examination of the serum and hepatic duct bile metabolome would enable the construction of mechanism-based theories or identification of specific compounds responsible for altered function of the gallbladder epithelium. Abnormalities observed in dogs with gallbladder mucocele formation, including a 33-fold decrease in serum adenosine 5'-monophosphate (AMP), lower quantities of precursors required for synthesis of energy transporting nucleotides, and increases in citric acid cycle intermediates, suggest excess metabolic energy and a carbon surplus. Altered quantities of compounds involved in protein translation and RNA turnover, together with accumulation of gamma-glutamylated and N-acetylated amino acids in serum suggest abnormal regulation of protein and amino acid metabolism. Increases in lathosterol and 7α-hydroxycholesterol suggest a primary increase in cholesterol synthesis and diversion to bile acid formation. A number of specific biomarker compounds were identified for their ability to distinguish between control dogs and those that formed a gallbladder mucocele. Particularly noteworthy was a significant decrease in quantity of biologically active compounds that stimulate biliary ductal fluid secretion including adenosine, cAMP, taurolithocholic acid, and taurocholic acid. These findings support the presence of significant metabolic disruption in dogs with mucocele formation. A targeted, quantitative analysis of the identified serum biomarkers is warranted to determine their utility for diagnosis of this disease. Finally, repletion of compounds whose biological activity normally promotes biliary ductal secretion should be examined for any therapeutic impact for resolution or prevention of mucocele formation.
[Mh] Termos MeSH primário: Bile/metabolismo
Sangue
Doenças da Vesícula Biliar/metabolismo
Metabolômica
Mucocele/metabolismo
[Mh] Termos MeSH secundário: Animais
Cães
Feminino
Doenças da Vesícula Biliar/sangue
Masculino
Mucocele/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191076


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[PMID]:29229136
[Au] Autor:Wang Q; Wang B; Saxena V; Miles L; Tiao J; Mortensen JE; Nathan JD
[Ad] Endereço:Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
[Ti] Título:The gut-liver axis: impact of a mouse model of small-bowel bacterial overgrowth.
[So] Source:J Surg Res;221:246-256, 2018 Jan.
[Is] ISSN:1095-8673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The mechanisms by which intestinal bacteria impact liver diseases remain poorly understood. The aim of this study was to develop a mouse model of small-bowel bacterial overgrowth and to determine its impact on hepatobiliary injury. MATERIALS AND METHODS: A jejunal self-filling blind loop (SFBL) was created in C57BL/6 mice. Three weeks after surgery, the mice were euthanized, and bacterial cultures of luminal content of the loop and extraintestinal tissues were performed. Liver and jejunum were collected for histological grading of inflammation and injury. Serum liver biochemistry assays were performed. Hepatobiliary transporter mRNA expression in liver was measured by quantitative real-time polymerase chain reaction. Bile and blood were collected for measurement of total bile acids, phospholipid, and cholesterol. Mice undergoing jejunal transection and reanastomosis and laparotomy only served as control groups. RESULTS: SFBL induced a dramatic increase in intraluminal bacterial counts, mesenteric lymph node bacterial translocation, and evidence of jejunal and hepatobiliary injury. Significant reductions in hepatic expression of hepatobiliary transporters involved in biliary canalicular export and basolateral uptake were observed in SFBL mice. SFBL resulted in a significant increase in biliary total bile acid concentration, decreases in bile phospholipid and cholesterol output, and an increase in the bile acid/phospholipid ratio. CONCLUSIONS: We have developed a reproducible mouse model of small-bowel bacterial overgrowth with evidence of liver inflammation, altered hepatobiliary transporter expression, and alterations in bile composition. This model may help to elucidate the mechanisms by which gut-derived bacterial factors impact the liver and contribute to the exacerbation of liver diseases and biliary injury.
[Mh] Termos MeSH primário: Translocação Bacteriana
Síndrome da Alça Cega/complicações
Modelos Animais de Doenças
Doenças do Jejuno/complicações
Hepatopatias/microbiologia
[Mh] Termos MeSH secundário: Animais
Bile/metabolismo
Síndrome da Alça Cega/metabolismo
Hepatopatias/metabolismo
Masculino
Proteínas de Membrana Transportadoras/metabolismo
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Membrane Transport Proteins)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE


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[PMID]:28873632
[Au] Autor:Corte-Real J; Desmarchelier C; Borel P; Richling E; Hoffmann L; Bohn T
[Ad] Endereço:Department of Population Health, Luxembourg Institute of Health (LIH), 1A-B, rue Thomas Edison, L-1445 Strassen, Luxembourg; Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology (LIST), 41 rue du Brill, L-4422 Belvaux, Luxembourg; Food Chemistry and
[Ti] Título:Magnesium affects spinach carotenoid bioaccessibility in vitro depending on intestinal bile and pancreatic enzyme concentrations.
[So] Source:Food Chem;239:751-759, 2018 Jan 15.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Magnesium may reduce carotenoid bioavailability by forming insoluble complexes with bile salts/fatty acids, inhibiting micelle formation. Here, we investigated whether altering bile/pancreatin concentration influenced potential negative effects of magnesium on carotenoid bioaccessibility. Spinach (4g) was digested in vitro with added magnesium (0, 200, 400mg/L) and canola oil/coffee creamer, at varying bile extract (1 or 8mM) and pancreatin (100 or 990mg/L) concentrations. Bioaccessibility was determined for ß-carotene, lutein, and total carotenoids via HPLC. Additionally, lipolysis, particle size, and zeta potential of the micellar fractions were investigated. Increasing magnesium concentrations negatively affected carotenoid bioaccessibility (p<0.001), lipolysis, particle size and zeta potential. The impact of magnesium on carotenoid bioaccessibility was modulated mainly by bile concentration, with samples digested with 1mM of bile being more susceptible to inhibitory effects of magnesium than those digested with 8mM (p<0.001). Thus, magnesium was found to potentially interfere with carotenoid bioaccessibility at various physiologically plausible conditions.
[Mh] Termos MeSH primário: Pâncreas/enzimologia
Spinacia oleracea
[Mh] Termos MeSH secundário: Bile
Disponibilidade Biológica
Carotenoides
Magnésio
beta Caroteno
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
01YAE03M7J (beta Carotene); 36-88-4 (Carotenoids); I38ZP9992A (Magnesium)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170907
[St] Status:MEDLINE


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[PMID]:29031685
[Au] Autor:Rees DO; Crick PJ; Jenkins GJ; Wang Y; Griffiths WJ; Brown TH; Al-Sarireh B
[Ad] Endereço:Swansea University Medical School, ILS1 Building, Singleton Park, Swansea SA2 8PP, UK; Department of Surgery, Morriston Hospital, Swansea, SA6 6NL, UK.
[Ti] Título:Comparison of the composition of bile acids in bile of patients with adenocarcinoma of the pancreas and benign disease.
[So] Source:J Steroid Biochem Mol Biol;174:290-295, 2017 Nov.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Bile acids have been implicated in the development of gastrointestinal malignancies. Both the specific nature of individual bile acids and their concentration appear key factors in the carcinogenic potency of bile. Using liquid chromatography mass spectrometry (LC-MS) we performed quantitative profiling of bile extracted directly from the common bile duct in 30 patients (15 patients with pancreatic cancer and 15 patients with benign disease). Separation and detection of bile acids was performed using a 1.7µm particle size reversed-phase C LC column at a flow rate of 200µL/min with negative electrospray ionization MS. A significant difference (p=0.018) was seen in the concentration of unconjugated cholic acid in the malignant group (0.643mmol/L) compared to the benign group (0.022mmol/L), with an overall significant difference (p=0.04) seen in the level of total unconjugated bile acids in the malignant group (1.816mmol/L) compared to the benign group (0.069mmol/L). This finding may offer the possibility of both understanding the biology of cancer development in the pancreas, as well as offering a potential diagnostic avenue to explore. However, a larger study is necessary to confirm the alterations in bile acid profiles reported here and explore factors such as diet and microbial populations on the bile acid profiles of these patient groups.
[Mh] Termos MeSH primário: Adenocarcinoma/metabolismo
Ácidos e Sais Biliares/análise
Bile/química
Colecistite/metabolismo
Neoplasias Pancreáticas/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
Seres Humanos
Masculino
Meia-Idade
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bile Acids and Salts)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171017
[St] Status:MEDLINE


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[PMID]:28946128
[Au] Autor:Ding LQ; Qiu TY; Liu ZX; Chen LX; Oppong MB; Zhang DQ; Zhang BL; Bai G; Qiu F
[Ad] Endereço:Tianjin Key Laboratory of TCM Chemistry and Analysis, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
[Ti] Título:Systematic characterization of the metabolites of paeonol in rats using ultra performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry with an integrative strategy.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1065-1066:70-78, 2017 Oct 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Paeonol, an active constituent in the root bark of Paeonia suffruticosa Andrews, is used to treat inflammation, headache and other diseases in clinic. Though the data on pharmacological researches of paeonol abounds, its metabolic profile is not so clear. It is essential to systematically characterize the in vivo metabolites in order to better understand its mechanism of action. In this study, ultra performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q/TOF-MS) with an integrative strategy was developed for analysis of paeonol metabolites. As a result, based on seven reference substances isolated or synthesized, twenty-five metabolites were detected and identified in urine, feces, bile and plasma of rats after oral administration of paeonol. To the best of our knowledge, 14 of these metabolites have not been reported previously. In addition, the dominating metabolic fates were oxidation, demethylation, hydrogenation, glucuronic acid and sulfate conjugations, and hydrogenation of paeonol was reported for the first time. This research provides scientific and reliable support for full understanding of the metabolic profiling of paeonol.
[Mh] Termos MeSH primário: Acetofenonas/análise
Acetofenonas/química
Cromatografia Líquida de Alta Pressão/métodos
Espectrometria de Massas por Ionização por Electrospray/métodos
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Acetofenonas/metabolismo
Animais
Bile/química
Fezes/química
Masculino
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetophenones); 3R834EPI82 (paeonol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE


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[PMID]:28837403
[Au] Autor:Holth TF; Storset A; Ribeiro AL; Ólafsdóttir Á; Halldórsson HP; Hylland K
[Ad] Endereço:a Department of Biosciences , University of Oslo , Blindern , Oslo , Norway.
[Ti] Título:Environmentally realistic exposure to weathered North Sea oil: Sublethal effects in Atlantic cod (Gadus morhua) and turbot (Scophthalmus maximus).
[So] Source:J Toxicol Environ Health A;80(16-18):895-906, 2017.
[Is] ISSN:1528-7394
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:With increasing oil and gas activities and transport in the Arctic, there is a need to understand how operational or accidental releases of substances affect marine organisms from a pristine environment. The aim of the current study was to describe and compare the responses of two marine fish species, Atlantic cod (Gadus morhua) and turbot (Scophthalmus maximus), following exposure to three levels (low, medium, high) of the water-soluble fraction of a North Sea crude oil for 16 days. The exposure system simulated environmental exposure by allowing clean seawater to percolate through gravel covered in weathered oil before being introduced to aquaria. Both polycyclic aromatic hydrocarbon (PAH) metabolite bile concentrations and cytochrome P4501A (CYP1A) levels and activity increased markedly in comparison with controls in both species, but there were no significant differences between the three exposures. Turbot possessed 4-5-fold higher concentrations of two PAH bile metabolites compared to Atlantic cod by day 8. In contrast, hepatic CYP1A activity in cod was consistently 2-6-fold higher than in turbot with increasing differences over the experimental period. Baseline DNA strand breaks in lymphocytes and kidney cells were low in both species, but was elevated for all treatments by day two. There were no marked indications of the treatments affecting immune functions in either species. This investigation demonstrated that there may be significant differences in responses between species receiving identical exposures and that DNA strand breaks in lymphocytes and kidney cells are sensitive to confinement stress. Data also indicate that some species, such as turbot, may adapt to treatments within days and weeks.
[Mh] Termos MeSH primário: Exposição Ambiental/efeitos adversos
Linguados/metabolismo
Gadus morhua/metabolismo
Petróleo/toxicidade
Água do Mar/química
Poluentes Químicos da Água/toxicidade
[Mh] Termos MeSH secundário: Animais
Hidrocarboneto de Aril Hidroxilases/metabolismo
Bile/química
Contaminação de Alimentos/análise
Leucócitos Mononucleares/efeitos dos fármacos
Leucócitos Mononucleares/metabolismo
Fígado/efeitos dos fármacos
Fígado/metabolismo
Mar do Norte
Hidrocarbonetos Aromáticos Policíclicos/toxicidade
Explosão Respiratória/efeitos dos fármacos
Alimentos Marinhos/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Petroleum); 0 (Polycyclic Aromatic Hydrocarbons); 0 (Water Pollutants, Chemical); EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170825
[St] Status:MEDLINE
[do] DOI:10.1080/15287394.2017.1352195


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[PMID]:28796833
[Au] Autor:Pereira P; Aho V; Arola J; Boyd S; Jokelainen K; Paulin L; Auvinen P; Färkkilä M
[Ad] Endereço:Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
[Ti] Título:Bile microbiota in primary sclerosing cholangitis: Impact on disease progression and development of biliary dysplasia.
[So] Source:PLoS One;12(8):e0182924, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The etiopathogenesis and risk for development of biliary neoplasia in primary sclerosing cholangitis (PSC) are largely unknown. Microbes or their metabolites have been suggested to play a role. To explore this potential microbial involvement, we evaluated the differences in biliary microbiota in PSC patients at an early disease stage without previous endoscopic retrograde cholangiography (ERC) examinations, advanced disease stage, and with biliary dysplasia or cholangiocarcinoma. DESIGN: Bile samples from the common bile duct were collected from 46 controls and 80 patients with PSC during ERC (37 with early disease, 32 with advanced disease, and 11 with biliary dysplasia). DNA isolation, amplification, and Illumina MiSeq sequencing were performed for the V1-V3 regions of the bacterial 16S rRNA gene. RESULTS: The most common phyla found were Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria, and Actinobacteria. The most common families were Prevotellaceae, Streptococcaceae, Veillonellaceae, Fusobacteriaceae, and Pasteurellaceae, and the most common genera were Prevotella, Streptococcus, Veillonella, Fusobacterium, and Haemophilus. The bacterial communities of non-PSC subjects and early stage PSC patients were similar. Alpha diversity was lower in patients with biliary dysplasia/cholangiocarcinoma than in other groups. An increase in Streptococcus abundance was positively correlated with the number of ERC examinations. Streptococcus abundance was also positively correlated with an increase in disease severity, even after controlling for the number of ERC examinations. CONCLUSIONS: Our findings suggest that the aetiology of PSC is not associated with changes in bile microbial communities, but the genus Streptococcus may play a pathogenic role in the progression of the disease.
[Mh] Termos MeSH primário: Bactérias/isolamento & purificação
Bile/microbiologia
Colangite Esclerosante/microbiologia
Microbiota
[Mh] Termos MeSH secundário: Adulto
Bactérias/genética
Sistema Biliar/microbiologia
Sistema Biliar/patologia
Colangite Esclerosante/patologia
DNA Bacteriano/genética
DNA Bacteriano/isolamento & purificação
Progressão da Doença
Feminino
Seres Humanos
Masculino
Meia-Idade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Bacterial)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182924


  10 / 22489 MEDLINE  
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[PMID]:28734749
[Au] Autor:Ceballos L; Canton C; Cadenazzi G; Larsen K; Virkel G; Moreno L; Fairweather I; Lanusse C; Alvarez L
[Ad] Endereço:Centro de Investigación Veterinaria de Tandil (CIVETAN), UNCPBA-CICPBA-CONICET, Facultad de Ciencias Veterinarias, UNCPBA, Campus Universitario, 7000 Tandil, Argentina. Electronic address: ceballos@vet.unicen.edu.ar.
[Ti] Título:Understanding the main route of drug entry in adult Fasciola hepatica: Further insights into closantel pharmacological activity.
[So] Source:Exp Parasitol;181:23-29, 2017 Oct.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Closantel (CLS) is highly effective against adult liver flukes after its oral or subcutaneous (sc) administration in ruminants. Trans-tegumental diffusion and oral ingestion are the two potential routes available for the entry of drugs into Fasciola hepatica. The work reported here contributes to improve the understanding of CLS pharmacology. The main goals of were: I) to determine the pattern of in vivo CLS accumulation into adult F. hepatica and relevant tissues in CLS-treated sheep; II) to investigate the influence of the physicochemical composition of the incubation medium on the CLS diffusion process into adult F. hepatica; III) to assess the ovicidal activity of CLS against F. hepatica eggs; and IV) to investigate the in vivo effect of CLS treatment on glutathione S-transferases activity in adult liver flukes exposed to CLS. Fourteen healthy sheep were each orally infected with 75 F. hepatica metacercariae. Sixteen (16) weeks after infection, animals were treated with CLS by oral (n = 6, 10 mg/kg) or sub-cutaneous (sc) (n = 6, 5 mg/kg) route. At 12, 24 and 36 h post-treatment, animals were sacrificed (n = 2) and samples of blood, bile and adult F. hepatica were collected. In addition, flukes recovered from non-treated sheep (n = 2) were ex vivo incubated (60 min) in the presence of CLS in either RPMI or bile as incubation medium. CLS concentration was measured by HPLC. The ovicidal activity of CLS was investigated using eggs obtained from the bile of untreated sheep. Finally, glutathione S-transferase activity in F. hepatica recovered from untreated and CLS-treated sheep was assessed. In the in vivo studies, the highest CLS concentrations were measured in plasma and adult liver flukes. A positive correlation was observed between CLS concentration in plasma and in F. hepatica. Results obtained in the current work indicate that the in vivo accumulation of CLS into adult liver flukes occurs mainly by the oral route. After ex vivo incubation, the uptake of CLS by the parasite was markedly diminished in the presence of bile compared with that observed in the presence of RPMI as incubation medium. CLS lacks ovicidal activity at therapeutically relevant concentrations. Lastly, CLS significantly increased glutathione S-transferase activity in flukes recovered at 12 h (oral treatment) and 24 h (sc treatment), compared to the control liver flukes.
[Mh] Termos MeSH primário: Anti-Helmínticos/farmacologia
Fasciola hepatica/metabolismo
Fasciolíase/veterinária
Salicilanilidas/farmacologia
Doenças dos Ovinos/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Oral
Animais
Anti-Helmínticos/administração & dosagem
Anti-Helmínticos/sangue
Anti-Helmínticos/farmacocinética
Bile/metabolismo
Ductos Biliares/parasitologia
Fasciola hepatica/efeitos dos fármacos
Fasciola hepatica/enzimologia
Fasciolíase/tratamento farmacológico
Fasciolíase/metabolismo
Glutationa Transferase/metabolismo
Infusões Subcutâneas/veterinária
Fígado/metabolismo
Masculino
Óvulo/efeitos dos fármacos
Distribuição Aleatória
Salicilanilidas/administração & dosagem
Salicilanilidas/sangue
Salicilanilidas/farmacocinética
Ovinos
Doenças dos Ovinos/metabolismo
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthelmintics); 0 (Salicylanilides); EC 2.5.1.18 (Glutathione Transferase); EUL532EI54 (closantel)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170724
[St] Status:MEDLINE



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