Investigating sub-2 µm particle stationary phase supercritical fluid chromatography coupled to mass spectrometry for chemical profiling of chamomile extracts.

Roman and German chamomile are widely used throughout the world. Chamomiles contain a wide variety of active constituents including sesquiterpene lactones. Various extraction techniques were performed on these two types of chamomile. A packed-column supercritical fluid chromatography-mass spectrometry method was designed for the identification of sesquiterpenes and other constituents from chamomile extracts with no derivatization step prior to analysis. Mass spectrometry detection was achieved by using electrospray ionization. All of the compounds of interest were separated within 15 min. The chamomile extracts were analyzed and compared for similarities and distinct differences. Multivariate statistical analysis including principal component analysis and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to differentiate between the chamomile samples. German chamomile samples confirmed the presence of cis- and trans-tonghaosu, chrysosplenols, apigenin diglucoside whereas Roman chamomile samples confirmed the presence of apigenin, nobilin, 1,10-epioxynobilin, and hydroxyisonobilin.

Genome-wide association study reveals a complex genetic architecture underpinning-induced CYP3A4 enzyme activity.

Atypical cytochrome P450 3A4 (CYP3A4) enzyme activity-induced and inhibited-is thought to be the driver of numerous poor or adverse therapeutic responses to up to 50 % of all commonly prescribed drugs. We carried out a genome-wide association study to identify common genetic variants associated with variation in induced CYP3A4 activity. A total of 310 twins were included in this study. Each participant had already completed a 14 days course of St John's Wort to induce CYP3A4, which was quantified through the metabolic ratio of exogenous 3-hydroxyquinine to quinine. We failed to detect any genome-wide significant associations (P < 1 × 10(-8)) with variation in induced CYP3A4 activity although several genomic regions were highlighted which may play minor roles. We report the first GWAS of variation in induced CYP3A4 activity and our preliminary results indicate a complex genetic architecture underpinning induced CYP3A4 enzyme activity.

A novel dietary intervention to optimize vitamin E intake of pregnant women to 15 mg/day.

Associations have been reported between suboptimal maternal vitamin E intake during pregnancy and childhood asthma. This pilot study conducted in 2008/2009 investigated the feasibility and acceptability of a food-based randomized controlled trial in pregnant women to optimize dietary vitamin E intake to 15 mg/day. A food-based intervention using "food exchanges" to individually optimize dietary vitamin E intake to 15 mg/day was developed and included in an advice booklet. Forty-three pregnant women with a personal/partner history of asthma were recruited at 12 weeks gestation and randomized to food-based intervention or a control group until 20 weeks gestation. A registered dietitian assessed the vitamin E intake of 22 women and provided tailored advice on food-based exchanges to optimize their intake to 15 mg/day. The 21 control women were not given dietary advice. The food-based intervention was completed by 19 women and increased mean vitamin E intake: food diary data, 7.13 mg/day (95% confidence interval: 5.63 to 18.6) to 17.4 mg/day (95% confidence interval: 14.4 to 20.5) (P<0.001). This pilot study demonstrates the feasibility and acceptability of a food-exchange-based intervention to optimize dietary vitamin E intake during pregnancy. Additional work is required to determine whether this intervention, if sustained for the rest of pregnancy, reduces the likelihood of childhood asthma. The methodology used in the design of this novel food-based intervention could be transferred to other nutrients.

Genetic epidemiology of induced CYP3A4 activity.

AIM: The cytochrome P450 3A4 (CYP3A4) enzyme is implicated in the metabolism of more than 50% of all prescribed medications and its activity - including induced or inhibited activity - is deemed to be a crucial determinant of interindividual variability in drug disposition, poor therapeutic efficacy, and adverse response to medication. METHODS: We used the classical twin model in conjunction with an induction experiment to uncover the relative contribution of genetic and environmental factors to interindividual variation in induced CYP3A4 activity. A total of 367 healthy twins participated in the study. Each volunteer was administered a potent inducer of CYP3A4 (St John's Wort) for 14 days and the activity of CYP3A4 was quantified through the metabolism of the exogenously administered probe drug quinine sulfate. RESULTS: Baseline and induced CYP3A4 activity were highly variable with a seven-fold and 11-fold difference among our population, respectively. Alcohol consumption, BMI, and smoking were significantly associated with induced CYP3A4 activity, collectively explaining 20% of the variation (P<1×10(-4)). The narrow-sense heritability of induced CYP3A4 activity was estimated at 66%, whereas the remainder of the variation was attributed to unique environmental factors. CONCLUSION: To our knowledge, this is the first genetic epidemiological study of induced CYP3A4 activity. Our results motivate further research to identify common and rarer genetic variants that underpin the heritable component of variation in induced CYP3A4 activity.

Prediction of variability in CYP3A4 induction using a combined 1H NMR metabonomics and targeted UPLC-MS approach.

The activity of Cytochrome P450 3A4 (CYP3A4) enzyme is associated with many adverse or poor therapeutic responses to drugs. We used (1)H NMR-based metabonomics to identify a metabolic signature associated with variation in induced CYP3A4 activity. A total of 301 female twins, aged 45--84, participated in this study. Each volunteer was administered a potent inducer of CYP3A4 (St. John's Wort) for 14 days and the activity of CYP3A4 was quantified through the metabolism of the exogenously administered probe drug quinine sulfate (300 mg). Pre- and postintervention fasting urine samples were used to obtain metabolite profiles, using (1)H NMR spectroscopy, and were analyzed using UPLC--MS to obtain a marker for CYP3A4 induction, via the ratio of 3-hydroxyquinine to quinine (3OH-Q:Q). Multiple linear regression was used to build a predictive model for 3OH-Q:Q values based on the preintervention metabolite profiles. A combination of seven metabolites and seven covariates showed a strong (r = 0.62) relationship with log(3OH-Q:Q). This regression model demonstrated significant (p < 0.00001) predictive ability when applied to an independent validation set. Our results highlight the promise of metabonomics for predicting CYP3A4-mediated drug response.

Evaluation of Chinese medicinal herbs fingerprinting by HPLC-DAD for the detection of toxic aristolochic acids.

Aristolochic acids are known to contribute to various renal disorders; therefore, expanding the availability of analytical methodology to detect these compounds is important in order to assess the quality of Chinese herbal medicines in which they can be found. Twelve medicinal herbal samples were procured from various sources and extracted in duplicate prior to a "fingerprint" analysis using conventional HPLC-DAD. Multivariate analysis was performed on the entire chromatographed fingerprints. The resulting output was a partial least-square discriminant analysis model, which was able to evaluate the potential presence of aristolochic acids I and II as well as providing an individual herbal "fingerprint". The results of this study provide evidence that the presence of aristolochic acids contained within certain herbal extractions could be detected using a simple method, although some limitations apply to this method for quality control, since newly detected samples for aristolochic acid (positives) will need further confirmation with purity checks or MS hyphenation.

Assessment of Chinese medicinal herb metabolite profiles by UPLC-MS-based methodology for the detection of aristolochic acids.

In this study, aristolochic acid in different herbal medicines containing a mixture of varying herb species was identified through fingerprint pattern similarities. Aristolochic acid I and II are nephrotoxic compounds naturally present in the Aristolochia plant species that are commonly used in Chinese herbal medicines. Twenty-four commercially available herbal formulations were extracted into an aqueous solution and injected into a UPLC-MS system. All the samples were analysed by multiple reaction monitoring (MRM) to check for the presence of aristolochic acids I and II. The same samples were then fingerprinted using two different gradient methods and the chromatograms deconvoluted into retention time (RT) and masses for the chemicals present taking concentration into account. Statistical analysis of this data revealed that samples were highly heterogeneous, and that the main differences between the preparations were concentrations of polar compounds. A model was constructed where the samples could be separated into two groups differentiated by the presence of the two forms of aristolochic acid.

Opiate addiction and the entanglements of imperialism and patriarchy in Manchukuo, 1932-45.

In the Japanese colonial state of Manchukuo, opiate addiction was condemned by officials and critics alike. But the state-sponsored creation of a monopoly, opium laws, and rehabilitation programs failed to reduce rates of addiction. Further, official media condemnation of opiate addiction melded with local Chinese-language literature to stigmatise addiction, casing a negative light over the state's failure to realise its own anti-opiate agenda. Chinese writers were thus transfixed in a complex colonial environment in which they applauded measures to reduce harm to the local population while levelling critiques of Japanese colonial rule. This paper demonstrates how the Chinese-language literature of Manchukuo did not simply parrot official politics. It also delegitimised Japanese rule through opiate narratives that are gendered, consistently negative, and more critical of the state than might be expected in a colonial literature.