Effect of soy extract administration on losartan pharmacokinetics in healthy female volunteers.

BACKGROUND: osartan is metabolized by CYP2C9 and CYP3A4 to an active metabolite, E-3174, which has greater antihypertensive activity than the parent compound. Soy extract has been shown to be an activator of CYP2C9 and CYP3A4 in vitro. Coadministration of soy extract and losartan may therefore alter the pharmacokinetics of losartan and E-3174. OBJECTIVE: To determine whether, when losartan was used in combination with soy extract, a significant pharmacokinetic interaction would be observed in healthy female volunteers. METHODS: Eighteen healthy Chinese female volunteers were recruited. In an open-label, 2-phase study, losartan 50 mg was given to each subject, with and without soy extract. Plasma concentrations of losartan and E-3174 were determined by liquid chromatography-tandem mass spectrometry for 12 and 24 hours, respectively. On day 8 through day 21 of the study, following a 7-day washout period, each subject consumed two 1000-mg Genistein Soy Complex tablets orally after meals, twice daily, for 14 days. On day 22, all volunteers received losartan 50 mg and blood samples were collected again. RESULTS: All subjects completed the study, without adverse drug effects. Over the 14-day pretreatment period, soy extract did not significantly influence the pharmacokinetics of losartan or E-3174. The ratio of the area under the curve of the drug and metabolite after losartan administration, with and without soy extract ingestion, was 0.21 +/- 0.05 and 0.23 +/- 0.05 (mean +/- SD), respectively. The difference was not statistically significant (p = 0.22). CONCLUSIONS: Our data indicate that a significant interaction between soy extract and losartan is unlikely to occur in females.

Cloning and expression of Vibrio harveyi OmpK* and GAPDH* genes and their potential application as vaccines in large yellow croakers Pseudosciaena crocea.

Vibrio harveyi is a causative agent of vibriosis in the large yellow croaker Pseudosciaena crocea and causes severe losses to the aquaculture industry in China. The vaccines based on the outer membrane proteins (OMPs) of the pathogens are considered to be the optimum intervention for this disease. In this study, two V. harveyi OMP genes, OmpK* and glyceraldehyde-3-phosphate dehydrogenase (GAPDH*), were cloned, sequenced, and characterized. The recombinant proteins (r-OmpK and r-GAPDH) were expressed by the prokaryotic expression vector pET-30a(+) and purified with nickel-nitrilotriacetic acid affinity chromatography. Western blots showed that rabbit antisera against purified r-OmpK and r-GAPDH specifically reacted with the native OMP of V. harveyi. Large yellow croakers were immunized with r-OmpK and r-GAPDH. Specific antibody titer assessed by enzyme-linked immunosorbent and phagocytosis assays demonstrated that specific and innate immunity was stimulated in response to the OMPs of V. harveyi. Challenge results indicated that vaccination of large yellow croakers with r-OmpK and r-GAPDH increased relative survival (37.7% and 40.0%, respectively) against wild V. harveyi.

Expression, characterization and immunogenicity of a major outer membrane protein from Vibrio alginolyticus.

Vibrio alginolyticus is one of the Vibrio pathogens common to humans and marine animals. During infection and induction of the host immune response, outer membrane proteins of bacteria play an important role. In this study, an outer membrane protein gene (ompW) was cloned from V. alginolyticus and expressed in Escherichia coli. The 645 bp open reading frame (ORF) encodes a protein of 214 amino acid residues with a predicted molecular weight of 23.3 kDa. The amino acid sequence showed a high identity with that of Photobacterium damselae (96.2%) and Vibrio parahaemolyticus (94.4%). The alignment analysis indicated that OmpW was highly conserved. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the gene was over-expressed in E. coli BL21(DE3). Western blot analysis revealed that the expressed protein had immunoreactivity. The recombinant protein was purified by affinity chromatography on Ni-NTA Superflow resin. Large yellow croaker vaccinated with the purified OmpW showed significantly increased antibody to OmpW, which could resist the infection by V. alginolyticus. A specific antibody was detected by enzyme-linked immunosorbent assay. This study suggested that the conserved OmpW could be an effective vaccine candidate against infection by V. alginolyticus.

Characterization of the 5'-to-5'linked adult alpha- and beta-globin genes from three sciaenid fish species (Pseudosciaena crocea, Sciaenops ocellatus, Nibea miichthioides).

Recently, we cloned the adult alpha-globin genes from large yellow croaker Pseudosciaena crocea, cuneate drum Nibea miichthioides and red drum Sciaenops ocellatus. All these alpha-globins have a unique Gly insertion at the 47th residue. In this paper, the three sciaenid globin complexes were identified and compared in detail. Linkage analysis indicated that the sciaenid alpha- and beta-globin genes were oriented head-to-head relative to each other. The sciaenid intergenic regions between the linked alpha- and beta-globin genes were the smallest in reported fish globin gene complexes to date. Classical promoter elements were condensed and the CCAAT box unstable duplication was found in these regions. The promoter function of the intergenic region from large yellow croaker was tested by transient expression of EGFP in Vero cells. We also described a method for studying luciferase reporter gene transient expression in primary fish erythrocytes. We used the method to assess the promoter strength of the three intergenic regions between the sciaenid alpha- and beta-globin genes.