ISOLATION OF ANTIPROLIFERATIVE COMPOUNDS FROM CENTAUREA JACEA L.

Antiproliferative screening of 53 Asteraceae species against human tumour cell lines demonstrated a high cell proliferation inhibitory activity of the Centaurea species native to Middle and Eastern Europe. The highest activity was recorded for C. jacea, whose chloroform extract, prepared from different plant parts, significantly inhibited the growth of HeLa (57-86 %), MCF7 (44-64 %) and A431 (43-69 %) cells in 10 µg/ml concentrations. This species is a perennial herb occurring widespread in Europe. Its anti-tumour constituents have not been investigated earlier. Previous studies revealed the presence of flavones, flavonols, sesquiterpenes and cinnamic alcohol glucosides. The aim of the present work was the isolation and identification of the antiproliferative compounds from the aerial parts of C. jacea using bioactivity guided fractionations. The chloroform extract was chromatographed by CC on silica gel and polyamide, and further separated by CPC, PLC and RP-HPLC, to yield 10 pure compounds. Structure determinations were carried out by means of UV, MS and NMR spectroscopy and the comparison of the spectral data with literature values. The results allowed the identification of the flavonoid apigenin, axillarin, centaureidin, cirsiliol and isokaempferide, the sesquiterpene 4’-acetylcnicin, one new dibenzylbutyrolactone-type lignane, and three aliphatic glucose diesters, including the new natural product 1-beta-isobutanoyl-2-angeloylglucose. All compounds were isolated for the first time from this species. The isolated compounds were evaluated for their tumour cell inhibitory activity on HeLa, MCF7 and A431 cells and it was found that besides the extremely active centaureidin (IC50 0.0819–0.3540 microM), cirsiliol, isokaempferide, apigenin and 4’-acetylcnicin also exerted remarkable effects. Acknowledgements: This work was supported by grant OTKA K72771

Studies of mefloquine bioavailability and kinetics using a stable isotope technique: a comparison of Thai patients with falciparum malaria and healthy Caucasian volunteers.

1 A mefloquine hydrochloride tablet (250 mg base equivalent to 4.8 +/- 0.6 mg kg-1; mean +/- s.d.) and deuterium labelled mefloquine hydrochloride solution (250 mg base) were given to six adult male Thai patients with acute falciparum malaria and six healthy Swiss adult male volunteers (equivalent to 3.5 +/- 0.1 mg kg-1). 2 The relative bioavailability of the tablet formulation derived from comparison of the areas under the plasma concentration-time curves was similar in both groups; 87 +/- 11% and 89 +/- 10% (mean +/- s.d.). 3 The rate of drug absorption appeared to be similar in the two groups but peak plasma mefloquine concentrations were approximately three times higher in the Thai patients (1004 +/- 276 ng ml-1 for the tablet and 1085 +/- 280 ng ml-1 for the suspension) compared with the Swiss volunteers (319 +/- 73 ng ml-1 for the tablet, and 369 +/- 121 ng ml-1 for the suspension). 4 Estimates of the oral clearance CLpo of unlabelled mefloquine were significantly lower (17.5 +/- 4.4 ml h-1 kg-1) in the Thai patients compared with 28.8 +/- 3.5 ml h-1 kg-1 in the Swiss volunteers; P less than 0.05). Terminal elimination half-lives were significantly shorter in the patients (10.3 +/- 2.5 days) than in the volunteers (16.7 +/- 1.9 days; P less than 0.005). Differences of a similar magnitude were observed when comparing the pharmacokinetic parameters derived from the deuteromefloquine plasma concentrations. 5 Both genetic and disease related factors are likely to account for the large pharmacokinetic differences between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS

An ethico-legal framework for social data science

This paper presents a framework for research infrastructures enabling ethically sensitive and legally compliant data science in Europe. Our goal is to describe how to design and implement an open platform for big data social science, including, in particular, personal data. To this end, we discuss a number of infrastructural, organizational and methodological principles to be developed for a concrete implementation. These include not only systematically tools and methodologies that effectively enable both the empirical evaluation of the privacy risk and data transformations by using privacy-preserving approaches, but also the development of training materials (a massive open online course) and organizational instruments based on legal and ethical principles. This paper provides, by way of example, the implementation that was adopted within the context of the SoBigData Research Infrastructure