The aim of this study is to evaluate the efficacy of total saponins of Dioscorea(TSD), an extract of the Chinese herbal Bi Xie, on hyperuricemia and to elucidate the underlying mechanisms. The rat hyperuricemia mode...The aim of this study is to evaluate the efficacy of total saponins of Dioscorea(TSD), an extract of the Chinese herbal Bi Xie, on hyperuricemia and to elucidate the underlying mechanisms. The rat hyperuricemia model was established by administration of adenine. Thirty-two rats were randomly allocated into 4 groups: model group, low/high-dose TSD-treated groups, and allopurinol-treated group. Meanwhile, 8 rats were used as normal controls. Serum uric acid(UA), blood urea nitrogen(BUN), serum creatinine(Scr), and organic anion transporting polypeptide 1A1(OATP1A1) levels were measured. Comparison between the model group and treatment(allopurinol and TSD) groups showed the serum UA levels were significantly decreased in treatment groups. TSD had similar effects to allopurinol. It was found that the OATP1A1 protein expression levels in treatment groups were higher than in model group and normal controls. And different from the allopurinol-treated groups, TSD-treated group had elevated OATP1A1 expression levels in the stomach, liver, small intestine and large intestine tissues. It was suggested that TSD may facilitate the excretion of UA and lower UA levels by up-regulating OATP1A1 expression.展开更多
Gadoxetic acid- or gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI) achieves excellent lesion detection and characterization for both hypervascular hepatocellula...Gadoxetic acid- or gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI) achieves excellent lesion detection and characterization for both hypervascular hepatocellular carcinoma(HCC) in arterial phase imagingand hypovascular early HCC(small well-differentiated HCC of the vaguely nodular type) in hepatobiliary phase imaging, and has become an indispensable imaging modality in the treatment of HCC. Early HCCs have been detected more frequently since the introduction of EOB-MRI into daily clinical practice. Early HCC is known to progress to conventional hypervascular HCC, and many risk factors have been identified for the hypervascularization of early HCC including the diameter of the tumor, presence of fat, and imaging findings of EOB-MRI. The rate of the development of hypervascular HCC was previously reported to be high in patients with chronic liver disease and early HCC. The presence of early HCC is regarded as a predictor for the recurrence of HCC following hepatic resection. On the other hand, although early HCC itself is currently not regarded as a target lesion for hepatic resection, early HCC at high risk of hypervascularity needs to be treated by local ablation therapy. If concomitant early HCC with progressed HCC is at high risk of hypervascularization and the functional liver reserve of a patient is sufficient, its simultaneous treatment at the time of hepatic resection for progressed HCC is recommended. Further studies on larger numbers of patients are needed before this strategy is adopted.展开更多
Bilirubin,a major end product of heme breakdown,is an important constituent of bile,responsible for its characteristic colour.Over recent decades,our understanding of bilirubin metabolism has expanded along with the p...Bilirubin,a major end product of heme breakdown,is an important constituent of bile,responsible for its characteristic colour.Over recent decades,our understanding of bilirubin metabolism has expanded along with the processes of elimination of other endogenous and exogenous anionic substrates,mediated by the action of multiple transport systems at the sinusoidal and canalicular membrane of hepatocytes.Several inherited disorders characterised by impaired bilirubin conjugation(Crigler-Najjar syndrome typeⅠand typeⅡ,Gilbert syndrome)or transport(Dubin-Johnson and Rotor syndrome)result in various degrees of hyperbilirubinemia of either the predominantly unconjugated or predominantly conjugated type.Moreover,disrupted regulation of hepatobiliary transport systems can explain jaundice in many acquired liver disorders.In this review,we discuss the recent data on liver bilirubin handling based on the discovery of the molecular basis of Rotor syndrome.The data show that a substantial fraction of bilirubin conjugates is primarily secreted by MRP3 at the sinusoidal membrane into the blood,from where they are subsequently reuptaken by sinusoidal membrane-bound organic anion transporting polypeptides OATP1B1 and OATP1B3.OATP1B proteins are also responsible for liver clearance of bilirubin conjugated in splanchnic organs,such as the intestine and kidney,and for a number of endogenous compounds,xenobiotics and drugs.Absence of one or both OATP1B proteins thus may have serious impact on toxicity of commonly used drugs cleared by this system such as statins,sartans,methotrexate or rifampicin.The liverblood cycling of conjugated bilirubin is impaired in cholestatic and parenchymal liver diseases and this impairment most likely contributes to jaundice accompanying these disorders.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81072806,and No.81373500)Natural Science Foundation of Guangdong Province(No.S2012010009277)Traditional Chinese Medicine Bureau of Guangdong Province(No.20141046)
文摘The aim of this study is to evaluate the efficacy of total saponins of Dioscorea(TSD), an extract of the Chinese herbal Bi Xie, on hyperuricemia and to elucidate the underlying mechanisms. The rat hyperuricemia model was established by administration of adenine. Thirty-two rats were randomly allocated into 4 groups: model group, low/high-dose TSD-treated groups, and allopurinol-treated group. Meanwhile, 8 rats were used as normal controls. Serum uric acid(UA), blood urea nitrogen(BUN), serum creatinine(Scr), and organic anion transporting polypeptide 1A1(OATP1A1) levels were measured. Comparison between the model group and treatment(allopurinol and TSD) groups showed the serum UA levels were significantly decreased in treatment groups. TSD had similar effects to allopurinol. It was found that the OATP1A1 protein expression levels in treatment groups were higher than in model group and normal controls. And different from the allopurinol-treated groups, TSD-treated group had elevated OATP1A1 expression levels in the stomach, liver, small intestine and large intestine tissues. It was suggested that TSD may facilitate the excretion of UA and lower UA levels by up-regulating OATP1A1 expression.
文摘Gadoxetic acid- or gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI) achieves excellent lesion detection and characterization for both hypervascular hepatocellular carcinoma(HCC) in arterial phase imagingand hypovascular early HCC(small well-differentiated HCC of the vaguely nodular type) in hepatobiliary phase imaging, and has become an indispensable imaging modality in the treatment of HCC. Early HCCs have been detected more frequently since the introduction of EOB-MRI into daily clinical practice. Early HCC is known to progress to conventional hypervascular HCC, and many risk factors have been identified for the hypervascularization of early HCC including the diameter of the tumor, presence of fat, and imaging findings of EOB-MRI. The rate of the development of hypervascular HCC was previously reported to be high in patients with chronic liver disease and early HCC. The presence of early HCC is regarded as a predictor for the recurrence of HCC following hepatic resection. On the other hand, although early HCC itself is currently not regarded as a target lesion for hepatic resection, early HCC at high risk of hypervascularity needs to be treated by local ablation therapy. If concomitant early HCC with progressed HCC is at high risk of hypervascularization and the functional liver reserve of a patient is sufficient, its simultaneous treatment at the time of hepatic resection for progressed HCC is recommended. Further studies on larger numbers of patients are needed before this strategy is adopted.
基金Supported by The Project(Ministry of Health,Czech Republic)for Development of Research Organization 00023001(IKEM,Prague,Czech Republic),Institutional support
文摘Bilirubin,a major end product of heme breakdown,is an important constituent of bile,responsible for its characteristic colour.Over recent decades,our understanding of bilirubin metabolism has expanded along with the processes of elimination of other endogenous and exogenous anionic substrates,mediated by the action of multiple transport systems at the sinusoidal and canalicular membrane of hepatocytes.Several inherited disorders characterised by impaired bilirubin conjugation(Crigler-Najjar syndrome typeⅠand typeⅡ,Gilbert syndrome)or transport(Dubin-Johnson and Rotor syndrome)result in various degrees of hyperbilirubinemia of either the predominantly unconjugated or predominantly conjugated type.Moreover,disrupted regulation of hepatobiliary transport systems can explain jaundice in many acquired liver disorders.In this review,we discuss the recent data on liver bilirubin handling based on the discovery of the molecular basis of Rotor syndrome.The data show that a substantial fraction of bilirubin conjugates is primarily secreted by MRP3 at the sinusoidal membrane into the blood,from where they are subsequently reuptaken by sinusoidal membrane-bound organic anion transporting polypeptides OATP1B1 and OATP1B3.OATP1B proteins are also responsible for liver clearance of bilirubin conjugated in splanchnic organs,such as the intestine and kidney,and for a number of endogenous compounds,xenobiotics and drugs.Absence of one or both OATP1B proteins thus may have serious impact on toxicity of commonly used drugs cleared by this system such as statins,sartans,methotrexate or rifampicin.The liverblood cycling of conjugated bilirubin is impaired in cholestatic and parenchymal liver diseases and this impairment most likely contributes to jaundice accompanying these disorders.