Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC/Q-TOF MS)was used to characterize ornidazole metabolites in human bile after intravenous doses.A liquid chromatography tandem mas...Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC/Q-TOF MS)was used to characterize ornidazole metabolites in human bile after intravenous doses.A liquid chromatography tandem mass spectrometry(LC–MS/MS)assay was developed for the determination of the bile level of ornidazole.Bile samples,collected from four patients with T-tube drainage after biliary tract surgery,were prepared by protein precipitation with acetonitrile before analysis.A total of 12 metabolites,including 10 novel metabolites,were detected and characterized.The metabolites of ornidazole in human bile were the products of hydrochloride(HCl)elimination,oxidative dechlorination,hydroxylation,sulfation,diastereoisomeric glucuronation,and substitution of NO_(2) or Cl atom by cysteine or N-acetylcysteine,and oxidative dechlorination followed by further carboxylation.The bile levels of ornidazole at 12 h after multiple intravenous infusions were well above its minimal inhibitory concentration for common strains of anaerobic bacteria.展开更多
Vanishing bile duct syndrome(VBDS) is a group of rare disorders characterized by ductopenia,the progressive destruction and disappearance of intrahepatic bile ducts leading to cholestasis.Described in association with...Vanishing bile duct syndrome(VBDS) is a group of rare disorders characterized by ductopenia,the progressive destruction and disappearance of intrahepatic bile ducts leading to cholestasis.Described in association with medications,autoimmune disorders,cancer,transplantation,and infections,the specific mechanisms of disease are not known.To date,only 4 cases of VBDS have been reported in human immunodeficiency virus(HIV) infected patients.We report 2 additional cases of HIV-associated VBDS and review the features common to the HIV-associated cases.Presentation includes hyperbilirubinemia,normal liver imaging,and negative viral and autoimmune hepatitis studies.In HIV-infected subjects,VBDS occurred at a range of CD4+ T-cell counts,in some cases following initiation or change in antiretroviral therapy.Lymphoma was associated with two cases;nevirapine,antibiotics,and viral co-infection were suggested as etiologies in the other cases.In HIV-positive patients with progressive cholestasis,early identification of VBDS and referral for transplantation may improve outcomes.展开更多
Based on the principle of fluid mechanics a mathematical model of the oval gallbladder’smoving boundaries was obtained by CT,radio contrast radiography and B mode echography.Weadopted for the first time in this field...Based on the principle of fluid mechanics a mathematical model of the oval gallbladder’smoving boundaries was obtained by CT,radio contrast radiography and B mode echography.Weadopted for the first time in this field,the finite element method to calculate the transient flow fieldwithin the human gallbladder in vivo and successfully made out the distribution of bile flow withinthe cyst,known as Newtonian fluid and axisymmetric flow.Thus we completed the poineering ofthe bile flow study within the gallbladder,and confirmed the way of the cholelithogenesis withinthe cyst.Theoretically the vortex flow is proved to be the mechanical factor in the formation ofgallbladder stone and several conclusions were drawn from this study:(1)near the axis of thecontacting gallbladder exists an accelerated bile out-flow column;(2)near the central cross-section ofthe flow field there exist two opposed vortex areas,the one which near the axis rotatescounterwise and flows faster;(3)a gross similarity exists between the law of attenuation of bile flowvelocity and the gallbladder contraction;(4)chololithogenesis within the cyst is related to the vortex inthe flow field.展开更多
AIM To evaluate a culture system for bile acidformation in primary human hepatocytes incomparison with HepG2 cells.METHODS Hepatocytes were isolated fromnormal human liver tissue and were cultured inserum-free William...AIM To evaluate a culture system for bile acidformation in primary human hepatocytes incomparison with HepG2 cells.METHODS Hepatocytes were isolated fromnormal human liver tissue and were cultured inserum-free William’s E medium.The medium wascollected and renewed every 24 h.Bile acids andtheir precursors in media were finally analysed bygas chromatography-mass spectrometry.RESULTS Cholic acid(CA)andchenodeoxycholic acid(CDCA)conjugated withglycine or taurine accounted for 70% and 25% oftotal steroids.A third of CDCA was alsoconjugated with sulphuric acid.Dexamethasoneand thyroid hormone alone or in combination didnot significantly effect bile acid formation.Theaddition of cyclosporin A(10 μmol/L)inhibited thesynthesis of CA and CDCA by about 13% and30%,respectively.CONCLUSION Isolated human hepatocytes inprimary culture behave as in the intact liver byconverting cholesterol to conjugated CA andCDCA.This is in contrast to cultured HepG2 cells,which release large amounts of bile acidprecursors and unconjugated bile acids into themedium.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81173117).
文摘Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC/Q-TOF MS)was used to characterize ornidazole metabolites in human bile after intravenous doses.A liquid chromatography tandem mass spectrometry(LC–MS/MS)assay was developed for the determination of the bile level of ornidazole.Bile samples,collected from four patients with T-tube drainage after biliary tract surgery,were prepared by protein precipitation with acetonitrile before analysis.A total of 12 metabolites,including 10 novel metabolites,were detected and characterized.The metabolites of ornidazole in human bile were the products of hydrochloride(HCl)elimination,oxidative dechlorination,hydroxylation,sulfation,diastereoisomeric glucuronation,and substitution of NO_(2) or Cl atom by cysteine or N-acetylcysteine,and oxidative dechlorination followed by further carboxylation.The bile levels of ornidazole at 12 h after multiple intravenous infusions were well above its minimal inhibitory concentration for common strains of anaerobic bacteria.
基金Supported by The Intramural Research Programs of the National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Diseases
文摘Vanishing bile duct syndrome(VBDS) is a group of rare disorders characterized by ductopenia,the progressive destruction and disappearance of intrahepatic bile ducts leading to cholestasis.Described in association with medications,autoimmune disorders,cancer,transplantation,and infections,the specific mechanisms of disease are not known.To date,only 4 cases of VBDS have been reported in human immunodeficiency virus(HIV) infected patients.We report 2 additional cases of HIV-associated VBDS and review the features common to the HIV-associated cases.Presentation includes hyperbilirubinemia,normal liver imaging,and negative viral and autoimmune hepatitis studies.In HIV-infected subjects,VBDS occurred at a range of CD4+ T-cell counts,in some cases following initiation or change in antiretroviral therapy.Lymphoma was associated with two cases;nevirapine,antibiotics,and viral co-infection were suggested as etiologies in the other cases.In HIV-positive patients with progressive cholestasis,early identification of VBDS and referral for transplantation may improve outcomes.
文摘Based on the principle of fluid mechanics a mathematical model of the oval gallbladder’smoving boundaries was obtained by CT,radio contrast radiography and B mode echography.Weadopted for the first time in this field,the finite element method to calculate the transient flow fieldwithin the human gallbladder in vivo and successfully made out the distribution of bile flow withinthe cyst,known as Newtonian fluid and axisymmetric flow.Thus we completed the poineering ofthe bile flow study within the gallbladder,and confirmed the way of the cholelithogenesis withinthe cyst.Theoretically the vortex flow is proved to be the mechanical factor in the formation ofgallbladder stone and several conclusions were drawn from this study:(1)near the axis of thecontacting gallbladder exists an accelerated bile out-flow column;(2)near the central cross-section ofthe flow field there exist two opposed vortex areas,the one which near the axis rotatescounterwise and flows faster;(3)a gross similarity exists between the law of attenuation of bile flowvelocity and the gallbladder contraction;(4)chololithogenesis within the cyst is related to the vortex inthe flow field.
基金the Swedish Medical Research Council(03X-4793 and 03X-7890)
文摘AIM To evaluate a culture system for bile acidformation in primary human hepatocytes incomparison with HepG2 cells.METHODS Hepatocytes were isolated fromnormal human liver tissue and were cultured inserum-free William’s E medium.The medium wascollected and renewed every 24 h.Bile acids andtheir precursors in media were finally analysed bygas chromatography-mass spectrometry.RESULTS Cholic acid(CA)andchenodeoxycholic acid(CDCA)conjugated withglycine or taurine accounted for 70% and 25% oftotal steroids.A third of CDCA was alsoconjugated with sulphuric acid.Dexamethasoneand thyroid hormone alone or in combination didnot significantly effect bile acid formation.Theaddition of cyclosporin A(10 μmol/L)inhibited thesynthesis of CA and CDCA by about 13% and30%,respectively.CONCLUSION Isolated human hepatocytes inprimary culture behave as in the intact liver byconverting cholesterol to conjugated CA andCDCA.This is in contrast to cultured HepG2 cells,which release large amounts of bile acidprecursors and unconjugated bile acids into themedium.
