Garcinia Glycosides is a candidate drug obtained by structural modification of Gambogic Acid (GA), which was acquired through High Throughput Screening(HTS). As Garcinia Glycosides is an effective but insoluble anti-t...Garcinia Glycosides is a candidate drug obtained by structural modification of Gambogic Acid (GA), which was acquired through High Throughput Screening(HTS). As Garcinia Glycosides is an effective but insoluble anti-tumor drug, the aim of this study was to obtain a solid dispersion form Garcinia Glycosides by using solvent-melt method so that improve the solubility and dissolution rate. The solid dispersion was characterized by High Performance Liquid Chromatography (HPLC), infrared spectroscopy and evaluated the intestinal absorption of the drug by rat in situ single pass intestinal perfusion. The results showed the increase of solubility, dissolution velocity and absorption compared to other forms. This indicated that solid dispersion could greatly improve the relative bioavailability of Garcinia Glycosides in vivo.展开更多
AIM To review the clinical impact of machine perfusion(MP) of the liver on biliary complications post-transplantation, particularly ischaemic-type biliary lesions(ITBL). METHODS This systematic review was performed in...AIM To review the clinical impact of machine perfusion(MP) of the liver on biliary complications post-transplantation, particularly ischaemic-type biliary lesions(ITBL). METHODS This systematic review was performed in accordance with the Preferred Reporting Systematic Reviews and MetaAnalysis(PRISMA) protocol. The following databases were searched: PubMed, MEDLINE and Scopus. The keyword "liver transplantation" was used in combination with the free term "machine perfusion". Clinical studies reporting results of transplantation of donor human livers following ex situ or in situ MP were analysed. Details relating to donor characteristics, recipients, technique of MP performed and post-operative biliary complications(ITBL, bile leak and anastomotic strictures) were critically analysed.RESULTS Fifteen articles were considered to fit the criteria for this review. Ex situ normothermic MP was used in 6 studies, ex situ hypothermic MP in 5 studies and the other 4 studies investigated in situ normothermic regional perfusion(NRP) and controlled oxygenated rewarming. MP techniques which have per se the potential to alleviate ischaemia-reperfusion injury: Such as hypothermic MP and NRP, have also reported lower rates of ITBL. Other biliary complications, such as biliary leak and anastomotic biliary strictures, are reported with similar incidences with all MP techniques. There is currently less clinical evidence available to support normothermic MP as a mitigator of biliary complications following liver transplantation. On the other hand, restoration of organ to full metabolism during normothermic MP allows assessment of hepatobiliary function before transplantation, although universally accepted criteria have yet to be validated.CONCLUSION MP of the liver has the potential to have a positive impact on post-transplant biliary complications, specifically ITBL, and expand extended criteria donor livers utilisation.展开更多
AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis(TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior...AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis(TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior was investigated in an in situ single-pass intestinal perfusion(SPIP) assay in rats. RESULTS: The intestinal absorption of TAMC was much more than that of a single compound or a mixture of compounds(jatrorrhizine, palmatine, and berberine). Promotion of absorption by the bicyclic monoterpenoids(borneol or camphor) was higher than by the monocyclic monoterpenes(menthol or menthone), and promotion by compounds with a hydroxyl group(borneol or menthol) was higher than those with a carbonyl group(camphor or menthone). The apparent permeability coefficient(Papp) of TAMC was increased to 1.8-fold by verapamil, while it was reduced to one half by thiamine. The absorption rate constant(Ka) and Papp of TAMC were unchanged by probenecid and pantoprazole. CONCLUSION: The intestinal absorption characteristics of TAMC might be passive transport, and the intestinum tenue was the best absorptive site. In addition, TAMC might be likely a substrate of P-glycoprotein(P-gp) and organic cation transporters(OCT), rather than multidrug resistance protein(MRP) and breast cancer resistance protein(BCRP). Compared with a single compound and a mixture of compounds, TAMC was able to be absorbed in the blood circulation effectively.展开更多
文摘Garcinia Glycosides is a candidate drug obtained by structural modification of Gambogic Acid (GA), which was acquired through High Throughput Screening(HTS). As Garcinia Glycosides is an effective but insoluble anti-tumor drug, the aim of this study was to obtain a solid dispersion form Garcinia Glycosides by using solvent-melt method so that improve the solubility and dissolution rate. The solid dispersion was characterized by High Performance Liquid Chromatography (HPLC), infrared spectroscopy and evaluated the intestinal absorption of the drug by rat in situ single pass intestinal perfusion. The results showed the increase of solubility, dissolution velocity and absorption compared to other forms. This indicated that solid dispersion could greatly improve the relative bioavailability of Garcinia Glycosides in vivo.
基金supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trustthe University of Birmingham
文摘AIM To review the clinical impact of machine perfusion(MP) of the liver on biliary complications post-transplantation, particularly ischaemic-type biliary lesions(ITBL). METHODS This systematic review was performed in accordance with the Preferred Reporting Systematic Reviews and MetaAnalysis(PRISMA) protocol. The following databases were searched: PubMed, MEDLINE and Scopus. The keyword "liver transplantation" was used in combination with the free term "machine perfusion". Clinical studies reporting results of transplantation of donor human livers following ex situ or in situ MP were analysed. Details relating to donor characteristics, recipients, technique of MP performed and post-operative biliary complications(ITBL, bile leak and anastomotic strictures) were critically analysed.RESULTS Fifteen articles were considered to fit the criteria for this review. Ex situ normothermic MP was used in 6 studies, ex situ hypothermic MP in 5 studies and the other 4 studies investigated in situ normothermic regional perfusion(NRP) and controlled oxygenated rewarming. MP techniques which have per se the potential to alleviate ischaemia-reperfusion injury: Such as hypothermic MP and NRP, have also reported lower rates of ITBL. Other biliary complications, such as biliary leak and anastomotic biliary strictures, are reported with similar incidences with all MP techniques. There is currently less clinical evidence available to support normothermic MP as a mitigator of biliary complications following liver transplantation. On the other hand, restoration of organ to full metabolism during normothermic MP allows assessment of hepatobiliary function before transplantation, although universally accepted criteria have yet to be validated.CONCLUSION MP of the liver has the potential to have a positive impact on post-transplant biliary complications, specifically ITBL, and expand extended criteria donor livers utilisation.
基金supported by China Pharmaceutical University Training Programs of Innovation for Undergraduates(No.02640390)
文摘AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis(TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior was investigated in an in situ single-pass intestinal perfusion(SPIP) assay in rats. RESULTS: The intestinal absorption of TAMC was much more than that of a single compound or a mixture of compounds(jatrorrhizine, palmatine, and berberine). Promotion of absorption by the bicyclic monoterpenoids(borneol or camphor) was higher than by the monocyclic monoterpenes(menthol or menthone), and promotion by compounds with a hydroxyl group(borneol or menthol) was higher than those with a carbonyl group(camphor or menthone). The apparent permeability coefficient(Papp) of TAMC was increased to 1.8-fold by verapamil, while it was reduced to one half by thiamine. The absorption rate constant(Ka) and Papp of TAMC were unchanged by probenecid and pantoprazole. CONCLUSION: The intestinal absorption characteristics of TAMC might be passive transport, and the intestinum tenue was the best absorptive site. In addition, TAMC might be likely a substrate of P-glycoprotein(P-gp) and organic cation transporters(OCT), rather than multidrug resistance protein(MRP) and breast cancer resistance protein(BCRP). Compared with a single compound and a mixture of compounds, TAMC was able to be absorbed in the blood circulation effectively.
