Combination of multifunctional ursolic acid with kinase inhibitors for anti-cancer drug carrier vesicles.

A sterically stabilized unilamellar nanocarrier vesicle (SSV) system containing dipalmitoylphosphatidylcholine, cholesterol, ursolic acid and PEGylated phospholipid has been developed by exploiting the structural advantages of ursolic acid: by spontaneously attaching to the lipid head groups, it induces curvature at the outer side of the bilayers, allowing the preparation of size-limited vesicles without extrusion. Ursolic acid (UA) also interacts with the PEG chains, supporting steric stabilization even when the amount of PEGylated phospholipid is reduced. Using fluorescence immunohistochemistry, vesicles containing ursolic acid (UA-SSVs) were found to accumulate in the tumor in 3 h on xenografted mouse, suggesting the potential use of these vesicles for passive tumor targeting. Further on, mono- and combination therapy with UA and six different kinase inhibitors (crizotinib, erlotinib, foretinib, gefitinib, refametinib, trametinib) was tested on seven cancer cell-lines. In most combinations synergism was observed, in the case of trametinib even at very low concentration (0.001 µM), which targets the MAPK pathway most often activated in human cancers. The coupled intercalation of UA and trametinib (2:1 molar ratio) into vesicles causes further structural advantageous molecular interactions, promoting the formation of small vesicles. The high drug:lipid molar ratio (~0.5) in the novel type of co-delivery vesicles enables their direct medical application, possibly also overcoming the multidrug resistance effect.

Radon and thoron parallel measurements in Hungary.

Hungarian detectors modified and developed at the National Institute of Radiological Sciences (NIRS), Japan were placed at different sites, including homes and underground workplaces in Hungary, in order to gain information on the average radon (222Rn) and thoron (220Rn) concentration levels. Measurements were carried out in dwellings in a village and a manganese mine in Hungary. The radon and thoron concentrations in the dwellings of the village in the summer period were found to be 154 (17-1083) and 98 (1-714) Bq m(-3), respectively. Considering the results of other radon measurements during the winter (814 Bq m(-3)) and summer (182 Bq m(-3)) periods, the thoron concentrations were also expected to be higher in winter. In the manganese mine, radon and thoron were measured at 20 points for 6 months, changing the detectors each month. The averages were 924 (308-1639) and 221 (61-510) Bq m(-3) for radon and thoron, respectively. These results showed significant variance with the date and place of the measurement.

238U, 226Ra, 210Po concentrations of bottled mineral waters in Hungary and their committed effective dose.

Nowadays the consumption of bottled mineral waters has become very popular. The average consumption of these is 0.36 l d(-1) per person in Europe. A considerable segment of the population drinks almost only mineral water as drinking water, which is about 1 l d(-1). As is known, some kinds of mineral waters contain naturally occurring radionuclides in higher concentration than the usual drinking (tap) water. The WHO (1993) legislation concerning the drinking waters does not include the mineral waters. In our work, the concentrations of (226)Ra, (238)U and (210)Po were determined in mineral waters available in Hungary. To determine the (226)Ra concentration the emanation method was used. The (238)U and (210)Po concentrations were determined by alpha spectrometry using semiconductor detector. The dose contribution was calculated using the radionuclide concentrations and the dose conversion factors from the Basic Safety Standard IAEA (1995), for 1 l d(-1) mineral water consumption. In some cases the calculated doses were considerable higher than the limit for drinking waters. Especially for children the doses can be remarkably high.