No abstract

Poly(L-lactic acid) microspheres loaded with holmium-166 acetylacetonate ( 166 Ho-PLLA-MS) are a novel microdevice for intra-arterial radioembolization in patients with unresectable liver malignancies. The neutron activation in a nuclear reactor, in particular the gamma heating, damages the 166 Ho-PLLA-MS. The degree of damage is dependent on the irradiation characteristics and irradiation time in a particular reactor facility. The aim of this study was to standardize and objectively validate the activation procedure in a particular reactor. The methods included light-and scanning electron microscopy (SEM), particle size analysis, differential scanning calorimetry, viscometry, thermal neutron flux measurements and energy deposition calculations. Seven hours-neutron irradiation results in sufficient specific activity of the 166 Ho-PLLA-MS while structural integrity is preserved. Neutron flux measurements and energy deposition calculations are required in the screening of other nuclear reactors. For the evaluation of microsphere quality, light microscopy, SEM and particle size analysis are appropriate techniques.

No abstract

In this work it is demonstrated that the susceptibility of diamagnetic substances, such as water and agarose gel, can easily be tuned to the susceptibility of air by the addition of a proper amount of strongly paramagnetic ions, in this case 16.6 ؎ 0.1 mM holmium(III). The resultant air-equivalent substances are shown to allow the creation of objects that do not disturb the static magnetic field of the scanner and hence do not invoke susceptibility artifacts, regardless of the objects' shape, size, and orientation with respect to B 0 , and regardless of the pulse sequence being used. The addition of the proper amount of holmium(III) to aqueous solutions and gels is further shown to exert a negligible influence on the chemical shift and to cause a moderate increase of the relaxation rates 1/T 1 and 1/T 2 . The results indicate the potential of air-equivalent substances for many purposes, including construction of artifact-free test objects; experimental setups and accessory devices; investigation of systems that contain air cavities, gas bubbles, etc.; and monitoring of system-related and object-induced field disturbances.

. Nitric oxide donor induces temporal and dose-dependent reduction of gene expression in human endothelial cells. Am J Physiol Heart Circ Physiol 287: H1977-H1986, 2004. First published July 8, 2004 doi:10.1152/ ajpheart.00323.2004.-The present study tested the hypothesis that acute increases in nitric oxide (NO) exert substantial influences on gene transcription in endothelial cells (ECs) via guanylyl cyclase (GC). Human umbilical veins ECs (HUVECs) were exposed to 0.1, 1, and 10 mM of sodium nitroprusside (SNP) for 4 h and to 1 mM SNP or 250 M of (Z)-1[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]-diazen-1-ium-1,2-diolate (DETA-NONOate) for 2, 4, 8, and 24 h. Also, cells were exposed to DETA-NONOate in the presence and absence of the GC inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ; 10 M) for 4 h. RNA was isolated, reverse transcribed, Cy3 and Cy5 labeled, and analyzed using cDNA microarrays. Increasing doses of SNP predominantly depressed gene expression in HUVECs. Gene function was related to growth, adhesion, and cell structure. DETA-NONOate evoked a wave of expression changes (maximum at 4 h), with a remarkable downregulation of the transcription factors MSX1, RELB, and Egr-1. Both SNP-and DETANONOate-induced gene expression had faded after 24 h, despite continued elevation of cGMP in the medium. Coadministration of ODQ decreased many, but not all, of the transcriptional responses to DETA-NONOate. NO pronouncedly depressed EC gene expression, in particular of transcription factors. The observation that many, but not all, transcriptional changes induced by NO could be inhibited by inhibition of GC indicates the presence of GC-independent NO actions on gene expression. Thus EC gene expression responds to NO; however, the transcriptional response fades during prolonged exposure. This could allow the EC to respond to increased shear, without vigorous changes in gene expression. microarray; nitrate tolerance; guanylate cyclase; Egr-1; V-Rel avian reticuloendotheliosis viral oncogene homolog B SUBSTANTIAL EVIDENCE is now available on the actions of nitric oxide (NO) in the vasculature (4). The, by now already classical, paradigm is that NO, released from endothelial cells (ECs) in response to shear stress, acts on vascular smooth muscle cells (VSMCs) by activating soluble guanylyl cyclase (GC), resulting in cGMP formation and vasodilation (4). In addition, NO affects multiple other processes in VSMCs, i.e., inhibits proliferation (41) and modulates expression of genes with vasoactive function (19). NO also affects EC function in an autocrine fashion and thereby inhibits adhesion, inflammation, and generation of proliferative stimuli. Indeed, exogenously applied NO can affect transcription of adhesion molecules, such as ICAM-1 and E-selectin (23) and VEGF (11) in ECs that are activated with IL-1␤ or TNF-␣. Interestingly, there is a large body of data available to support that NO actions in physiological settings are short lived, because of acute desensitization (5, 14) and slower adaptations of the GC ...