Search

Background: Phytosterolemia is a rare autosomal recessive lipid storage disease. It is caused by mutations of ABCG5 and ABCG8 genes and characterized by the increased plasma levels of plant sterols. The common clinical manifestations include tendon and tuberous xanthomas and premature coronary heart disease; it has occasionally been associated with hematologic abnormalities. Aims: We report a phytosterolemia patient presenting exclusively with macrothrombocytopenia and stomatocytic hemolysis and discuss its clinical significance. Case Report: The patient, aged 31 years, was born of a consanguineous marriage. He had epistaxis from childhood and underwent splenectomy because of thrombocytopenia, anemia and splenomegaly at the age of 9 years. His blood film showed prominent stomatocytes and macroplatelets. High performance liquid chromatography showed a grossly elevated level of phytosterols in the blood. The patient was confirmed to be a homozygote of missense mutation R419H in ABCG5. Conclusion: We describe a phytosterolemia patient whose clinical manifestations were macrothrombocytopenia, stomatocytic hemolysis and splenomegaly, without the common features of this disorder. Our results suggest that blood cells could be a target for the toxic effect of plasma plant sterols, which should be measured in patients with unexplained stomatocytosis and/or macrothrombocytopenia in order to determine if they have phytosterolemia. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A new method for the screening of compounds with hypoglycemic effect from traditional Chinese medicines employing high-performance liquid chromatography and lipase-linked magnetic microspheres has been proposed. We hypothesized that the interaction of traditional Chinese medicine extracts with lipase-linked magnetic microspheres should decrease the concentration of compounds with hypoglycemic effect. Using this approach, the potential lipase inhibitors in Folium Mori extract were investigated. First, lipase was immobilized on magnetic microspheres by a chemical method. Then, by comparing the chromatograms of samples before and after the interaction with lipase-linked magnetic microspheres, seven compounds of Folium Mori extract were identified. It was found that protocatechuic acid, chlorogenic acid, protocatechualdehyde, rutin, isoquercitrin, astragalin, and dicaffeoylquinic acid B had evident combination with lipase-linked magnetic microspheres. Their hypoglycemic effects were verified in streptozocin-induced diabetic mice. In the present study, astragalin was verified to improve the glucose tolerance and lower the level of glucose in streptozocin-induced diabetic mice, which indicated that astragalin might be a new highly efficient lipase inhibitor. Based on these significant results, this method could be a convenient approach to screen potential lipase inhibitors from traditional Chinese medicines. Meanwhile, it also could be expanded to screen other active compounds in traditional Chinese medicines. [ABSTRACT FROM AUTHOR]

An in vivo study of efavirenz metabolites in rats and human patients with ultra high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry combined with MetabolitePilotMT software is reported for the first time. Considering the polarity differences between the metabolites, solid-phase extraction and protein precipitation were both applied as a part of the sample preparation method. The structures of the metabolites and their fragment ions were identified or tentatively characterized based on the accurate mass and MS2 data. As a result, a total of 15 metabolites, including 11 from rat samples and 13 from human samples, were identified or tentatively characterized. Two metabolites and several new metabolism pathways are reported for the first time. This study provides a practical approach for identifying complicated metabolites through the rapid and reliable ultra high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry technique, which could be widely used for the investigation of drug metabolites. [ABSTRACT FROM AUTHOR]

Abstract: A new method employing HPLC, LC–MS, liposomes and cell membranes for the screening of bioactive compounds in traditional Chinese medicines (TCMs) has been proposed. We hypothesized that exposure of the TCM extracts to liposome membranes or cell membranes should decrease the concentration of membrane-permeable compounds in the solution. Using this approach, the permeability of the compounds in Radix Salviae Miltiorrhizae was investigated. By comparing chromatograms of samples prepared both before and after interaction with liposome membranes, erythrocyte membranes and cardiac myocyte membranes, 12 permeable compounds of Radix Salviae Miltiorrhizae were identified, and they were proven to be biologically active, with the exception of vanillic acid. There was a good correlation between the liposome model and the erythrocyte membranes, which was determined by comparing the binding degree of the permeable compounds (n =0.9059). Additionally, it was found that dihydrotanshinone I, cryptotanshinone, tanshinone I, tanshinone IIA combined specifically with cardiac myocyte membranes, which might indicate a useful approach for revealing the cardiovascular effects of Radix Salviae Miltiorrhizae. Based on these results, this method could be a novel approach for identifying potentially bioactive components in other TCMs. [Copyright &y& Elsevier]

Abstract: A new method for the screening of membrane-permeable compounds in traditional Chinese medicines (TCMs), using ultrafiltration and HPLC analysis, has been proposed. We hypothesized that exposure of a TCM extract to a liposome membrane, the concentration of membrane-permeable compounds in the solution should decrease. Using this approach, the permeability of compounds in Flos Lonicerae Japonicae (Japanese honeysuckle) was investigated. By comparing chromatograms of samples prepared before and after interaction with a liposome membrane, eight permeable compounds of Flos Lonicerae Japonicae were identified, and all of them were proven to be biologically active. Based on the significance of these results, this method could be a novel approach for identifying potentially bioactive components in other TCMs. [ABSTRACT FROM AUTHOR]

Abstract: A sensitive and specific method for the determination of bifendate in human plasma was developed, based on high-performance liquid chromatography (HPLC)–mass spectrometry (MS). The samples were extracted from plasma with diethyl ether, followed by separation and evaporation after addition of internal standard diazepam. The residue was reconstituted in methanol and injected into the HPLC–MS. Chromatography was performed on an Inertsil ODS column with a mobile phase consisting of methanol–distilled water (70/30, v/v) at a flow rate of 0.3mL/min. Quantitative analysis was achieved by MS detection, using a mass spectrometer equipped with an electrospray ionization interface (ESI) and operated in selected ion monitoring (SIM) and positive-ionization mode using target ions at m/z 419 for bifendate and m/z 285 for internal standard, respectively. The linearity was confirmed in the concentration range of 2–200ng/mL in human plasma and the precision of this assay was not more than 6.79% over the entire concentration range. The method was sensitive and repeatable enough to be used in pharmacokinetic and bioavailability studies. [Copyright &y& Elsevier]