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Microdialysis, a sampling method for pharmacokinetics⁻pharmacodynamics (PK⁻PD) modeling in preclinical and clinical studies, is a convenient in vivo sampling technique. Geniposide (GE), an iridoid glycoside compound, is the major active ingredient of Gardenia jasminoides Ellis fruit which has an anti-inflammatory effect. In this study, an articular cavity microdialysis sampling system for adjuvant arthritic (AA) rats was established to study the effect of GE on the release of prostaglandin E₂ (PGE₂) in AA rats induced by Freund's complete adjuvant (FCA). An UHPLC-MS/MS method was developed to determine the concentrations of GE and PGE₂ in the dialysate. Through the determination of drug concentrations and PGE₂ efficacy levels in the dialysate, the developed methods were successfully applied to set up concentration⁻time and effect⁻time profiles followed by PK⁻PD modeling of GE's effect on decreasing PGE₂ release after oral administration of GE. The effect was well described by the developed PK⁻PD modeling, indicating that GE may play an anti-inflammatory role via decreasing AA-induced elevated PGE₂ levels. In the selection of suitable endogenous small molecules as effect markers, the establishment of AA rat joint-cavity microdialysis is an attractive technique for rational PK⁻PD studies.
Pubmed ID: 29695042
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A second-generation retrovirus producer lines for the generation of helper free ecotropic and amphotropic retroviruses. The lines are based on the 293T cell line (a human embryonic kidney line transformed with adenovirus E1a and carrying a temperature sensitive T antigen co-selected with neomycin). The unique feature of this cell line is that it is highly transfectable with either calcium phosphate mediated transfection or lipid-based transfection protocols-- up to 50% or higher of cells can be transiently transfected. The lines were created by placing into 293T cells constructs capable of producing gag-pol, and envelope protein for ecotropic and amphotropic viruses. The lines offered advantages over previous stable systems in that virus can be produced in just a few days. Academic and non-profit laboratories may obtain the Phoenix cells from either Allele Biotechnology or the National Gene Vector Bank. The vectors may be obtained from Addgene. They are no longer distributing these reagents from the lab.
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