The major impetus behind the rise in energy drink popularity among adults is their ability to heighten mental alertness, improve physical performance and supply energy. However, accompanying the exponential growth in energy drink usage have been recent case reports and analyses from the National Poison Data System, raising questions regarding the safety of energy drinks. Most of the safety concerns have centered on the effect of energy drinks on cardiovascular and central nervous system function. Although the effects of caffeine excess have been widely studied, little information is available on potential interactions between the other active ingredients of energy drinks and caffeine. One of the active ingredients often mentioned as a candidate for interactions with caffeine is the beta-amino acid, taurine. Although taurine is considered a conditionally essential nutrient for humans and is thought to play a key role in several human diseases, clinical studies evaluating the effects of taurine are limited. However, based on this review regarding possible interactions between caffeine and taurine, we conclude that taurine should neutralize several untoward effects of caffeine excess. In agreement with this conclusion, the European Union's Scientific Committee on Food published a report in March 2003 summarizing its investigation into potential interactions of the ingredients in energy drinks. At the cardiovascular level, they concluded that "if there are any interactions between caffeine and taurine, taurine might reduce the cardiovascular effects of caffeine." Although these interactions remain to be further examined in humans, the physiological functions of taurine appear to be inconsistent with the adverse cardiovascular symptoms associated with excessive consumption of caffeine-taurine containing beverages.

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Benzbromarone is a uricosuric drug and has been shown to be metabolized predominantly by cytochrome P450(CYP)2C9 in vitro findings. This study aims to investigate the influence of the CYP2C9 genotype on plasma levels of benzbromarone and 6-hydroxybenzbromarone, as well as uric acid lowering effects. A single oral dose pharmacokinetic and pharmacodynamic trial of benzbromarone (100 mg) was performed in 20 healthy volunteers, which included 15 with CYP2C9*1/*1, 4 with CYP2C9*1/*3, and 1 with CYP2C9*3/*3. The oral clearance of benzbromarone in the CYP2C9*1/*1 genotype and CYP2C9*1/*3 genotype was 58.8±25.2 L/hr/kg (mean±SD) and 51.3±7.9 L/hr/kg, respectively, whereas 8.58 L/hr/kg in the CYP2C9*3/*3 genotype. The metabolic ratio (6-hydroxybenzbromarone/benzbromarone) in urine was 38.6±10.7 in the CYP2C9*1/*1 genotype, 35.4±12.4 in the CYP2C9*1/*3 genotype and 12.9 in the CYP2C9*3/*3 genotype. Although benzbromarone significantly increased the urinary excretion and reduced the plasma concentration of uric acid, there were no significant differences in its effects for different CYP2C9 genotypes. These results suggest a critical role for CYP2C9 in the metabolism of benzbromarone in humans and a possible risk of toxicity in the CYP2C9*3 homozygote by lowering clearance of the drug. Further studies are required to assess the clinical impact of CYP2C9 on the metabolism of benzbromarone.

BackgroundCalculus Bovis (:C.Bovis) is one of the most precious and commonly-used medicinal materials in Japan and China. As the natural occurrence is very rare, a source of supply for C. Bovis is far behind the actual need and great efforts have been taken for some substitutes of natural C. Bovis. Unfortunately, very little information is available on the quality and/or clinical efficacy of medication based on C. Bovis. To ensure sustainable use of traditional therapeutic agents derived from C. Bovis, we felt that several issues needed to be addressed: 1) the source of the C. Bovis materials and quality control; 2) the role of taurine in the efficacy of C. Bovis.MethodsNine samples of natural C. Bovis and its substitutes were collected. ICP-MS was used for elemental analysis and the characterization was performed by principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA) as multivariate approaches. The efficacy of C. Bovis was evaluated for morphology, viability and beating pattern on cultured cardiac myocytes and/or fibroblasts.ResultsPCA and multi-elemental focus was effective in discriminating C. Bovis samples derived from different habitats. A satisfactory classification using SIMCA was obtained among Australia C. Bovis, other habitats and the substitutes. Australian samples had better batch uniformity than other habitats and were composed of fewer elements. We have used Australian C. Bovis for assessment on its bioactive compounds. Rat cardiac cells incubated with C. Bovis extract (0.01-0.1mg/ml) maintained normal morphology, viability and beating pattern. Cardiac myocytes and fibroblasts treated for 48 h with CA (0.5mM) or DCA (0.1mM) caused cell injury, as reflected by changes in appearance and a reduction of viability detected by the MTS assay. In cardiomyocytes, 0.5 h exposure of CA (0.5mM) markedly decreased the velocity ratio of beating, whereas the simultaneous addition of 1 mM taurine largely prevented the decrease.ConclusionsThe multi-elemental focus provided some references for the quality control and the efficacy of C. Bovis. Taurine partly attenuated the harmful actions of bile acids. It is plausible that the relationship between taurine and the bile acids contributes to therapeutic effect of C. Bovis.

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We aimed to establish a methodology for identifying Paeonia samples based on metallomic analysis. We prepared 66 batches of samples (16 batches of crude drugs and 50 batches of cultivars, comprising 64 batches of Paeonia lactiflora and 2 batches of P. veitchii) collected from Japan and China (Inner Mongolia and elsewhere) between 1996 and 2008. P. lactiflora samples were genetically classified into white peony root (WPR) type and red peony root (RPR) type. Up to 47 elements were measured by inductively coupled plasma-mass spectrometry, and RPR type crude drug samples contained up to five times as much calcium as the others. Principal component analysis (PCA) of the multi-element fingerprints obtained suggested that P. veitchii, which grows wild, were distinguishable from the other cultivated P. lactiflora samples. This was confirmed perfectly by soft independent modeling of class analogy (SIMCA). The PCA of the fingerprints of P. lactiflora crude drug samples also suggested that it was possible to classify them by production area (Japan, Inner Mongolia, and China excluding Inner Mongolia) and genetic type (RPR and WPR types). They were also classified 100 % to the predicted class by SIMCA in both cases. These analyses were successful among the samples whose collection dates varied. This simple metallomic method is an efficient approach for verifying the complex origin of Paeoniae Radix.

Calculus Bovis (C. Bovis) is a commonly used animal-derived therapeutic preparation. To meet the increasing clinical demand for the preparation, two artificial substitutes for Bos Taurus have been introduced in China: artificial C. Bovis and in vitro cultured C. Bovis. However, information on their efficacy and safety is inadequate. Therefore, we investigated the biological differences between the commonly used natural preparation and its two substitutes, with the aim of not only identifying the differences but also providing a procedure to distinguish between the different preparations.In the study, we prepared 9 natural C. Bovis, 2 artificial C. Bovis, and 2 in vitro cultured C. Bovis preparations for evaluation. Differences were noted between the three preparations relative to their effect on viability of cardiac fibroblasts from 1-day-old Wistar rats. Although natural C. Bovis had no effect on cell viability, 1-h treatment of the cells with 0.25 mg/ml of the substitutes significantly reduced cell viability, as detected by the MTS assay. Based on liquid chromatography and inductively coupled plasma mass spectrometry, the preparations also differed in composition. Indeed, the substitutes contained more taurine, cholic acid, iron, magnesium, and calcium than the natural preparations. They also differed spectroscopically.The present results reveal significant biological differences between natural C. Bovis and two of its substitutes. Since the substitutes appear to contain more taurine, cholic acid, and elements, these constituents may serve as markers to distinguish between natural C. Bovis and its substitutes.

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