High doses of ionising radiation damage the heart by an as yet unknown mechanism. A concern for radiological protection is the recent epidemiological data indicating that doses as low as 100-500 mGy may induce cardiac damage. The aim of this study was to identify potential molecular targets and/or mechanisms involved in the pathogenesis of low-dose radiation-induced cardiovascular disease. The vascular endothelium plays a pivotal role in the regulation of cardiac function and is therefore a potential target tissue. We report here that low-dose radiation induced rapid and time-dependent changes in the cytoplasmic proteome of the human endothelial cell line EA.hy926. The proteomes were investigated at 4 and 24 h after irradiation at two different dose rates (Co-60 gamma ray total dose 200 mGy; 20 mGy/min and 190 mGy/min) using 2D-DIGE technology. Differentially expressed proteins were identified, after in-gel trypsin digestion, by MALDI-TOF/TOF tandem mass spectrometry, and peptide mass fingerprint analyses. We identified 15 significantly differentially expressed proteins, of which 10 were up-regulated and 5 down-regulated, with more than ±1.5-fold difference compared with unexposed cells. Pathways influenced by the low-dose exposures included the Ran and RhoA pathways, fatty acid metabolism and stress response.
High doses of ionising radiation significantly increase the risk of cardiovascular disease (CVD), the vascular endothelium representing one of the main targets. Whether radiation doses lower than 500 mGy induce cardiovascular damage is controversial. The aim of this study was to investigate radiation-induced expression changes on protein and microRNA (miRNA) level in primary human coronary artery endothelial cells after a single 200 mGy radiation dose (Co-60). Using a multiplex gel-based proteomics technology (2D-DIGE), we identified 28 deregulated proteins showing more than ±1.5-fold expression change in comparison with non-exposed cells. A great majority of the proteins showed up-regulation. Bioinformatics analysis indicated "cellular assembly and organisation, cellular function and maintenance and molecular transport" as the most significant radiation-responsive network. Caspase-3, a central regulator of this network, was confirmed to be up-regulated using immunoblotting. We also analysed radiation-induced alterations in the level of six miRNAs known to play a role either in CVD or in radiation response. The expression of miR-21 and miR-146b showed significant radiation-induced deregulation. Using miRNA target prediction, three proteins found differentially expressed in this study were identified as putative candidates for miR-21 regulation. A negative correlation was observed between miR-21 levels and the predicted target proteins, desmoglein 1, phosphoglucomutase and target of Myb protein. This study shows for the first time that a low-dose exposure has a significant impact on miRNA expression that is directly related to protein expression alterations. The data presented here may facilitate the discovery of low-dose biomarkers of radiation-induced cardiovascular damage.
The structure of TiO2 hydrates is studied by X-ray
diffraction, atomic force microscopy (AFM),
and transmission electron microscopy (TEM). The samples prepared
by NH4OH precipitation
from an aqueous TiCl4 solution are amorphous or partially
crystalline. They consist of a mixture
of distorted anatase and brookite crystallites, each having a diameter
of 20 nm. The sample
prepared by thermal hydrolysis from a titanium oxide sulfate solution
was totally crystalline,
composed only of distorted anatase crystallites with a diameter of 15
nm. Primary particles
can be oriented in chainlike structures. The crystallinity and the
crystal shape reveal the sample
history. The applicability of the AFM and TEM measurements for
structural investigations of
the powder specimens concerned is briefly discussed.
Acoustic emissions were detected, both during the roller compaction of the microcrystalline cellulose powder and from single tablets after compaction by a single-punch tablet machine, via air using a microphone with a flat frequency response up to 20 kHz. Both of the compaction units were instrumented for the measurement of applied compressive force. The microcrystalline cellulose roller compacted using compressive forces below 30 kN showed a quite normal compaction behaviour but the product compacted at this force split into two and turned to yellow by its edges. This "capping" phenomenon was indicated by an enhancement of acoustic emission in the region of about 17-23 kHz. Acoustic emissions from single tablets after compaction by a single-punch tablet machine seemed to appear as wave packets consisting in very many frequency components that may, in addition, be time-varying. However, some small peaks werc found probably being characteristic of these transient sounds.Acoustic emission techniques have been developed for the prediction of failure in engineering structures and in geologic materials [l], based on the fact that strain release gives a raise to acoustic emission as well as to plastic deformation in solid state materials.These techniques have been applied for the monitoring of the compaction of pharmaceutical powders, i. e. drugs and excipients. Rue et al.[2] fitted a piezoclcctric transducer to the take off chute of a single-punch tablet machine which was instrumented for the measurement of applied compressive force during compaction, and took the acoustic emission signals of a spray-dried paracetamol 1573 Copyright 0 1995 by Marcel Dekker, Inc Drug Dev Ind Pharm Downloaded from informahealthcare.com by University of Sydney on 01/05/15 For personal use only. Drug Dev Ind Pharm Downloaded from informahealthcare.com by University of Sydney on 01/05/15 For personal use only.
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