Determining the effect of Huangqi on the pharmacokinetics of six different alkaloids from Fuzi in rats by LC-MS / 药学学报

This study aimed to investigate the influence of combinating Huangqi with Fuzi on the pharmacokinetics of six Aconitum alkaloids, i.e. aconitine (AC), hypaconitine (HA), mesaconitine (MA), benzoylaconine (BAC), benzoylhypaconine (BHA) and benzoylmesaconine (BMA). The plasma concentrations of the drugs were determined by LC-MS for dose response and time dependent curves. The pharmacokinetic parameters were calculated by DAS 3.3, and SPSS 12.0 was used to analyze the differences of main pharmacokinetic parameters between the two groups. Comparing with Fuzi group, the AUC0-t and AUC0-∞ of six alkaloids in Fuzi-Huangqi group was significantly decreased, the CLz/Fof six alkaloids except HA was significantly increased; the Cmax was decreased and the tmax was prolonged in 3 monoester alkaloids, and the apparent volume of distribution of BMA and MA (Vz/F) increases. These data indicated that Huangqi can inhibit the absorption of aconite alkaloids, induce the distribution of aconite alkaloids to the whole body, and accelerate the elimination of aconite alkaloids. The animal experiment scheme in this study has been approved by the Experimental Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine.

Pharmacokinetics study of brucine and strychnine in rat liver microsomes under different chemical environments / 中草药

Objective To study the enzyme kinetics of brucine (BRU) and strychnine (STR), total alkaloids, and monomers active components of BRU and STR in extracts of Strychnos nux-vomica in rat liver microsomes, and investigate metabolic differences between BRU and STR monomer, total alkaloids, and BRU and STR in extracts in rat liver microsomes. Methods The contents of BRU and STR in the monomers, total alkaloids, and extracts in the metabolic system in vitro were measured by LC-MS/MS method, and the kinetic parameters of the enzyme were calculated. Results Compared with monomer group, Km and Vmax value of BRU and STR in total alkaloids and extracts of S. nux-vomica were obviously decreased; Compared with total alkaloids, Km and Vmax value of BRU and STR monomers in S. nux-vomica were obviously increased. The CLint of BRU among total alkaloids and monomer extracts groups had no significantly difference; And the CLint of STR in three groups was successively decreased. Conclusion Total alkaloids, BRU and STR in S. nux-vomica extracts, and BRU and STR monomer can be metabolized by the liver microsomes, and the pharmacokinetical parameters of BRU and STR in all groups have significant differences in metabolism.

Investigation epidemiology and sub-clinical infection of hepatitis E in voluntary blood donors in south Zhejiang / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the southern region of Zhejiang hepatitis E virus (HEV) infection.</p><p><b>METHODS</b>A cluster sampling strategy was used to sample all blood donors from February to October in 2008 in Wenzhou blood center. Their blood was tested for IgG and IgM antibody against HEV. Reverse transcriptase-polymerase chain reaction(RT-PCR) and sequencing were applied to detect its genotype and sequence homology in HEV IgM-positive specimen.</p><p><b>RESULTS</b>The prevalence of anti-HEV IgG in 3044 cases of blood donors was 33.28%. IgG increased with age. There are certain increase in positive rates between the 20-year-old group and over 40 years of age group from 21.16% to 50.36%. The positive rate of IgM was 0.92%. The ratio of infection among different age group was the highest in the age range from 31 to 40 years and up to 1.90%. IgG and IgM through their negative and positive analysis of samples found in their group with donors age, sex and blood type does not significantly related to each other. Nucleic acids were found in three cases through PCR amplification in all 28 cases of HEV IgM positive samples. The total positive rate was one-thousandth, of which two cases for gene 4, 1 cases of infection for gene 1.</p><p><b>CONCLUSION</b>The results indicate that there was a certain percentage of HEV virus in voluntary blood donors in south Zhejiang.</p>

Primary evaluation of anti-HEV diagnostic reagent by experimental infection animal model with hepatitis E virus / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate anti-HEV diagnostic kits by experimental infecting rhesus monkeys with HEV.</p><p><b>METHODS</b>Eight rhesus monkeys were infected with genotype 1 and 4 HEV separately. The alanine aminotransferase (ALT) level of all monkeys were detected before and after the process of infection. HEV RNA in stool specimens was tested by reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Anti-HEV IgG in serum was detected by GL-IgG and WT-IgG.</p><p><b>RESULTS</b>HEV RNA presented in the stool of all the 8 monkeys after infection. The ALT level of 1 monkey infected with genotype 1 HEV and 2 monkeys infected with genotype 4 HEV appeared abnormally after infection. Tested by GL-IgG, 2 of the 4 monkeys infected with genotype 1 HEV and 1 of 4 monkeys infected with genotype 4 HEV seroconverted to anti-HEV IgG. However, when tested by WT-IgG, all the infected monkeys seroconverted to anti-HEV IgG. The anti-HEV IgG tested by WT-IgG was positive during the whole observation period,and the anti-HEV IgG measured by GL-IgG only remained 12 weeks after infection. Detected by GL-IgG and WT-IgG, seropositive conversion of the anti-HEV IgG happened almost at the same time.</p><p><b>CONCLUSION</b>Both GL-IgG and WT-IgG could detect the anti-HEV IgG of experimentally infected rhesus monkeys but the WT-IgG had a higher sensitivity for detection of anti-HEV IgG than</p>

Significance of serological markers and virological marker for hepatitis E in rhesus monkey model / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the serological markers and biological marker in the diagnosis of hepatitis E infection in a rhesus monkey model.</p><p><b>METHODS</b>86 rhesus monkeys had been infected with different doses of HEV. Hence, they were taken sequential blood samples at intervals up to 86 weeks for 4 hepatitis E virus (HEV) specific antibody assays (E2-IgM, E2-IgG, GL-IgG, and YES-IgG), and nucleic acid assay.</p><p><b>RESULTS</b>All the animals produced E2-IgG and all but one also produced E2-IgM and excreted the virus in stool, whereas positive rate of GL-IgG and YES IgG were low and correlated with virus level. Hepatitis occurred over a period of 4 weeks (between 3 an 7 weeks) after infection. Virological marker occurred mainly during incubation period and declined rapidly after onset of hepatitis. Seroconversion of E2-IgM occurred before onset of hepatitis in 70% monkeys and declined rapidly up to 50% of peak value after 4 weeks. E2-IgM seroconversion was closely paralleled by E2-IgG; however, E2-IgG persisted in all animals for the entire duration of experiment of up to 86 weeks. Production of GL-IgG and YES-IgG was delayed by one week after the E2 antibodies, these antibodies showed a transient occurrence and seroprevalence declined to 50% of the peak value over a period of 12 weeks.</p><p><b>CONCLUSION</b>E2-IgM might be used as a suitable acute hepatitis E marker, and E2-IgG as a suitable epidemiological marker. The seroconversion or titer elevation of GL-IgG and YES-IgG antibodies probably used to confirm the infection. The viral markers are optional for early diagnosis.</p>

Distribution of hepatitis B virus genotypes and its clinical significance in Guangxi / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To understand the distribution of hepatitis B virus genotype in Guangxi and its clinical significance.</p><p><b>METHODS</b>Nested polymerase chain reaction (nPCR) was used for amplification of HBV DNA in sera of asymptomatic carrier (ASC) of hepatitis B virus (HBV) and patients with different liver diseases from southern and northern Guangxi. Specimens from 161 subjects were positive for HBV DNA and HBV genotype was determined by using restriction fragment length polymorphism analysis, direct sequencing or cloning sequencing.</p><p><b>RESULTS</b>The prevalence of genotype A was 3.7% in all samples and that of genotype B, C and D was 21.7%, 72.7% and 1.2%, respectively. No other genotypes (such as genotype E, F, G, H) were found. The prevalence of genotype C showed an increasing trend in ASC, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) group; in contrast, the prevalence of genotype B showed an opposite trend, although no statistically significant difference was observed, except between ASC and HCC (P=0.05). The HBeAg positive rate was higher, and the anti-HBe positive rate was lower in patients with chronic genotype C infection than in those with genotype B (P<0.05 for both). Liver function test (ALT) abnormality was more severe in genotype C group than in genotypes A and B groups having acute or chronic infection (P<0.01 for all comparisons). The prevalence of genotype C in southern Guangxi was higher than that in northern Guangxi. In contrast, the prevalence of genotype B in southern Guangxi was lower than that in northern Guangxi.</p><p><b>CONCLUSIONS</b>1. The predominant HBV genotypes in Guangxi were genotypes B and C. The major genotype in southern Guangxi was genotype C; while that in northern Guangxi was genotype B, which implied that the distribution of HBV genotype C was consistent with the incidence of HCC in Guangxi. 2. Genotype C maybe associated with development of severe liver diseases including HCC. 3. Genotype A,D and B+C were mostly found in acute, hepatitis and chronic hepatitis group.</p>

Serial pathologic changes in livers of Tree shrews and Macaca assamensises infected with human Hepatitis B virus / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To serially observe the pathologic changes in livers of tree shrews and macaca assamensises infected with HHBV.</p><p><b>METHODS</b>10 adult tree shrews and 28 macaca assamensises were inoculated with HBV rich human sera. The liver of the animals were regularly biopsied. The liver samples were examined histopathologically by HE staining. Some samples were stained for HBsAg by immunohistochemistry (IH), and HBV DNA by in situ hybridization (ISH).</p><p><b>RESULTS</b>HBsAg in 80% of tree shrews infected with HHBV can be detected by IH, HBV DNA in 50% of those can be found by ISH.The positive rates of HBsAg in macaca assamensises' livers were 25% by IH, none HBV DNA was detected.</p><p><b>CONCLUSION</b>The tree shrew model seems to be applicable for the research of human hepatitis B.</p>

Human hepatitis B virus infection of tree shrews and Macaca assamensis in vivo / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To examine sensitivity of the tree shrews and Macaca assamensis to human hepatitis B virus (HHBV) by serologic methods.</p><p><b>METHODS</b>Totally 233 tree shrews and 28 Macaca assamensis were inoculated with human sera containing HBV. After inoculation, the sera were collected weekly from them and HBV markers were detected with HBV ditecting ELISA kits.</p><p><b>RESULTS</b>Ninety percent of the tree shrews developed acute infection, among them, 44.4 % persisted for over one year, 33.3% of them developed chronic infection persisted for 2 years and one month; the persistence of HBV in Macaca assamensis was much shorter.</p><p><b>CONCLUSION</b>These data clearly indicated that tree shrew may be used as an animal model for study of chronic HBV infection, whereas, Macaca assamensis, showed only a transient sensitivity to HHBV.</p>