Pharmazie
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Stachydrine ((2S)-1,1-dimethylpyrrolidinium-2-carboxylic acid) may be regarded as an essential active principle of the aerial parts of Leonurus japonicus Houtt. (Leonuri herba, yimucao; Chin. Ph., DAB) which are used in TCM and Kampo for the treatment of various gynaecological and cardiovascular disorders. Medically and botanically closely related Lamioideae drugs are the fruits of L. japonicus (Leonuri fructus, chongweizi; Chin. ⋯ These measurements of 12 drug samples revealed stachydrine contents (w/w) of 0.2 to 1.0% for the L. japonicus aerial parts, 0.6 to 1.5 % for the L. cardiaca aerial parts, 6.7% for the antiarrhythmic refined extract of L. cardiaca, and 0.3% for the aerial parts of Leonotis leonurus, while both L. japonicus and L. cardiaca fruits contained, on average, 0.2 %. Furthermore, stachydrine was found for the first time as a constituent of L. japonicus and L. cardiaca fruits as well as Leonotis leonurus. Methodically, instrumental HPTLC may be a powerful tool for quality assurance for stachydrine containing plants and herbal drugs, especially for industrial routine protocols.
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Pyrrolizidine alkaloids (PAs) can show a hazardous potential for men and animals. They can act as cancerogenic, mutagenic, teratogenic and fetotoxic agents. One pathway of a human intoxication is its occurence as contaminants in food and feed. ⋯ Milk can contain PAs in case the milk producing animals have access to contaminated feed. In this context it is of special interest whether the PA content of contaminated silage remains stable during the ensiling procedure or show a more or less high level of decomposition. We could show that ensiling will not lead to PA-free silage.
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Delay in the initiation of appropriate antifungal therapy is associated with substantial morbidity and mortality. The aim of this study was to derive a risk score system for the development of invasive fungal infections in an intensive care unit (ICU). We retrospectively evaluated 1812 patients who stayed in the ICU for > or = 4 days, used univariate and multivariable logistic regression to identify potential risk factors associated with invasive fungal infections (IFI), and created a risk score system. ⋯ The percentages of patients with ICU-IFI in the low, intermediate, and high risk groups were 5.2%, 31.6%, and 63.2% in the derivation cohort and 4.2%, 30.1%, and 66.7% in the validation cohort, respectively. A new risk score was developed to predict ICU-IFI and was validated in an independent cohort. The new risk score may help clinicians identify patients who are at high risk of developing ICU-IFI and increase their odds of survival.
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Recently published data indicate that CYP2C19*2 allele is the major determinant of metabolic bioactivation of clopidogrel and thereby variability of antiplatelet effect of clopidogrel in white or black patients undergoing elective coronary stent placement. The conclusion may not be fully generalized or extrapolated to the Chinese people due to significantly higher frequencies of the CYP2C19*2 or *3 variant alleles. We sought to investigate whether the CYP2C19*2 or *3 alleles affects platelet reactivity of clopidogrel in Chinese stroke patients. ⋯ In addition, in the patients who were carriers of 2 mutant allele (mutant homozygotes, CYP2C19*2/*2, *2/*3 or *3/*3,), MPA were also significantly different compared with wildtype homozygous patients [35.7% (IQR, 21.0 to 78.1%) versus 23.6% (IQR, 14.0 to 35.4%, respectively; P = 0.039]. By multivariable linear regression, CYP2C19*2 or *3 loss-of-function alleles were independently associated with ADP-induced MPA measurements (partial R2 = 0.138, P = 0.001). CYP2C19*2 or *3 allele does link to increased MPA and clopidogrel response.
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Randomized Controlled Trial
ABCB1 gene polymorphisms, ABCB1 haplotypes and ABCG2 c.421c > A are determinants of inter-subject variability in rosuvastatin pharmacokinetics.
A randomized cross-over pharmacokinetic study of rosuvastatin calcium (single dose: 5 mg, 10 mg and 20 mg; multiple doses: 10mg once daily for 7 days) was conducted in 12 healthy Chinese volunteers. Plasma concentrations of rosuvastatin were determined by an LC-ESI-MS-MS method. Single-nucleotide polymorphisms (SNPs) in ABCB1, ABCG2, SLCOB1, CYP2C9 and CYP3A5 were determined by TaqMan (MGB) genotyping assay. ⋯ There were no significant effects on single-dose and steady-state pharmacokinetics of rosuvastatin by CYP2C9*3 (1075A > C), CYP3A5*3 g.6986A > G, ABCG2 c.34G > A, SLCO1B1 c.521 T > C, c.388 A > G, g.11187 G > A, c.571 T > C and c.597 C > T. In addition, no difference in rosuvastatin pharmacokinetics was observed among subjects of different genders. We conclude that ABCB1 C1236T, G2677T/A and C3435T polymorphism, ABCB1 haplotypes and ABCG2 c.421C > A are determinants of inter-subject variability in rosuvastatin pharmacokinetics in healthy Chinese volunteers, and potentially affect the efficacy and toxicity of statin therapy.