A comprehensive platform for quality control of botanical drugs (PhytomicsQC): a case study of Huangqin Tang (HQT) and PHY906

<p>Abstract</p> <p>Background</p> <p>Establishing botanical extracts as globally-accepted polychemical medicines and a new paradigm for disease treatment, requires the development of high-level quality control metrics. Based on comprehensive chemical and biological fingerprints correlated with pharmacology, we propose a general approach called PhytomicsQC to botanical quality control.</p> <p>Methods</p> <p>Incorporating the state-of-the-art analytical methodologies, PhytomicsQC was employed in this study and included the use of liquid chromatography/mass spectrometry (LC/MS) for chemical characterization and chemical fingerprinting, differential cellular gene expression for bioresponse fingerprinting and animal pharmacology for <it>in vivo </it>validation. A statistical pattern comparison method, Phytomics Similarity Index (PSI), based on intensities and intensity ratios, was used to determine the similarity of the chemical and bioresponse fingerprints among different manufactured batches.</p> <p>Results</p> <p>Eighteen batch samples of Huangqin Tang (HQT) and its pharmaceutical grade version (PHY906) were analyzed using the PhytomicsQC platform analysis. Comparative analysis of the batch samples with a clinically tested standardized batch obtained values of PSI similarity between 0.67 and 0.99.</p> <p>Conclusion</p> <p>With rigorous quality control using analytically sensitive and comprehensive chemical and biological fingerprinting, botanical formulations manufactured under standardized manufacturing protocols can produce highly consistent batches of products.</p

Decrease in TTP pools mediated by 5-bromo-2'-deoxyuridine exposure in a human glioblastoma cell line

The antitumor and radiosensitizing properties of 5-bromo-2'-deoxyuridine (BUdR) appear to be due, in part, to its incorporation into cellular DNA. To optimize conditions for incorporation of 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdUMP) into DNA, we investigated the metabolism of BUdR to its DNA precursor form, the 5'-triphosphate BrdUTP, in the U251 human glioblastoma cell line. The results demonstrated that BrdUTP accumulated rapidly in this cell line, achieving steadystate values within 2 hr of drug addition. The level of BrdUTP accumulation was proportional to the amount of exogenous BUdR up to a concentration of 100 [mu]M, without apparent saturation. Exposure of glioblastoma cells to BUdR was associated with substantial selective decreases in both the cellular dCTP and TTP pools, the extent of which was dependent on the exogenous BUdR concentration. In the absence of exogenous BUdR, BrdUTP was eliminated rapidly from cells with an initial half-life of approximately 15 min. As the cellular BrdUTP level declined, the dCTP and TTP levels increased to control values. Incorporation of BrdUMP into DNA appeared linear with time as long as the cellular BrdUTP level remained constant. This incorporation was not enhanced by the addition of 5-fluoro-2'-deoxyuridine (FUdR), a potent inhibitor of thymidylate synthetase, which at a concentration of 10 nM had no effect on TTP pools in this cell line. Thus, the decrease in cellular TTP pools mediated by BrdUTP allows the halogenated pyrimidine to enhance its own incorporation into DNA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30144/1/0000521.pd

Improving accuracy of major depression age-of-onset reports in the US National Comorbidity Survey

This paper describes a series of questions designed to improve the accuracy of age-of-onset reports in the US National Comorbidity Survey (NCS) and empirically evaluates the impact of these questions on reports about age of onset of major depressive episodes. The logic underlying the series of question is traced to cognitive psychological research on autobiographical memory. Data are presented showing that the new question series yielded more substantively plausible age-of-onset reports than those obtained a decade earlier in the Epidemiologic Catchment Area (ECA) Study. The test–retest consistency of age-of-onset reports was also higher in the NCS than the ECA. Despite these improvements, considerable inconsistency in age-of-onset reports remains in the NCS test-retest data. The paper closes with a discussion of potentially promising future directions to improve retrospective age-of-onset reports in new psychiatric epidemiological surveys. Copyright © 1999 Whurr Publishers, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34219/1/55_ftp.pd