ABSTRACT
The efflux of gold from red blood cells (RBCs) exposed to 10-100 microM auranofin [the second generation chrysotherapy agent, triethylphosphine-(2,3,4,6-tetra-O-acetyl-1-beta-D-glucopyranosato -S-)gold(I)] was studied. RBCs in whole blood were allowed to accumulate gold, and then were placed in fresh plasma or buffered saline solution. In plasma, the kinetics of efflux were first order in gold with an apparent rate constant of 0.81 +/- 0.18 hr-1. Serum albumin, in plasma or added to a buffered solution, shifted the equilibrium between intra- and extracellular gold in favor of the latter (compared to saline solution). [14C]Glutathione, generated by in situ labeling, also effluxed and associated with the albumin and gold, providing the first direct evidence that the albumin-gold-glutathione complex (AlbSAuSG) may be a circulating metabolite of auranofin formed after both of the original ligands of auranofin are displaced.
Subject(s)
Albumins/metabolism , Auranofin/metabolism , Erythrocytes/metabolism , Glutathione/metabolism , Gold/metabolism , Auranofin/pharmacology , Binding Sites , Cells, Cultured , Chromatography, Gel , Humans , KineticsABSTRACT
We evaluated 44 patients with suspected spinal tumors or previous laminectomies with gadolinium-DTPA MR imaging in order to characterize the enhancement in normal, postoperative, and neoplastic intraspinal tissue. Using the signal intensity of CSF as an internal control, we calculated the percentage increase in signal intensity from pre- to postgadolinium studies. Tumors (astrocytoma, ependymoma, schwannoma) enhanced 70-350%; epidural scar, normal epidural venous plexus, and dorsal root ganglion enhanced up to 200%. Contrast enhancement does not per se distinguish neoplastic from normal tissue. Enhancement with gadolinium-DTPA appeared to increase the conspicuousness of intramedullary tumors but not intraosseous metastases. We believe that gadolinium-enhanced MR imaging is a valuable adjunct to routine MR imaging in the evaluation of intraspinal neoplastic processes and may be useful in delineating normal and postoperative structures in the spinal canal.
Subject(s)
Magnetic Resonance Imaging , Organometallic Compounds , Pentetic Acid , Spinal Cord Neoplasms/diagnosis , Spinal Neoplasms/diagnosis , Contrast Media , Gadolinium DTPA , Humans , Laminectomy , Spinal Cord Neoplasms/surgery , Spinal Neoplasms/surgeryABSTRACT
Thiols (RSH = 2,3,4,6-tetra-O-acetyl-beta-1-D-thioglucose, beta-1-D-thioglucose, and glutathione) can displace either the albumin or the triethylphosphine from the protein-gold complex, AlbSAuPEt3. The albumin is displaced in preference to triethylphosphine, but irreversible oxidation of the latter eventually shifts the equilibria toward Et3PO and AlbSAuSR. Albumin disulfide bonds are the probable oxidants. Neither O2 nor oxidized glutathione substantially enhanced the rate or extent of Et3PO formation. The labilization of the phosphine in AlbSAuPEt3 is attributed to a strong trans effect of the albumin thiolate, Cys-34. The 31P NMR chemical shifts of various thiolato(triethylphosphine)gold(I) complexes are correlated directly with the affinity of the thiols for gold and inversely with their pKSH values. Deacetylated auranofin (1-thio-beta-D-glucopyranosato-S) (triethylphosphine)gold(I) reacts with the mercaptalbumin and oxidized mercaptalbumin (putatively AlbSOH) forms of bovine serum albumin to form AlbSAuPEt3 with displacement of the thioglucose ligand.
Subject(s)
Gold/metabolism , Phosphines/metabolism , Serum Albumin, Bovine/metabolism , Sulfhydryl Compounds/pharmacology , Kinetics , Magnetic Resonance SpectroscopyABSTRACT
The ratio of intensity (RI) of the plasma lipid methyl proton NMR resonance from two Carr-Purcell-Meiboom-Gill spectra acquired with a short (2.4 msec) and long (120 msec) pulse delay time is proposed to provide a potentially more sensitive and less variable marker of human malignancy than the linewidth parameter previously suggested (E.T. Fossel, J.M. Carr, and J. McDonagh (1986) N. Engl. J. Med. 315, 1369-1376). Linewidth and transverse (T2) relaxation data are presented which demonstrate that the observed correlation between methyl and methylene lipid linewidth and the methyl RI parameter arises from a combination of T2 differences and the relative amounts that fast- and slow-relaxing components contribute to the composite methyl resonance.
