[Diffuse pneumopathy with digital vasculitis in rheumatoid arthritis. Probable role of gold].
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Gold injected under the form of anti-rheumatoid polyarthritis soluble solutions provokes, as observed by electron microscope, a deposit of crystalline micro-needles in different tissues, like in cells of adrenal and suprarenal glands, in Leydig cells of the testicles, in isolated thyrocytes and in thyroid endothelial cells. They are present as bundles, often of incurvated type, of high electron-density, present in lysosomes, which contain moreover a hyaline, emptied vesicle. These structures are named "aurosomes". The microanalysis, using the MS 46 (Cameca) and the Camebax (MBX) demonstrates that these crystalline structures are composed by gold associated with sulphur, and not with phosphate.
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A novel method for fabrication of a diphtheria potentiometric immunosensor has been developed by means of self-assembling compound nanoparticles to a thiol-containing sol-gel network. A cleaned gold electrode was first immersed in a 3-mercaptopropyltrimethoxysilane (MPS) sol-gel solution to assemble a silica sol-gel monolayer. The silane entities were then polymerized into a two-dimensional sol-gel network (2D network) by dipping into aqueous NaOH. The second silane layer was formed by re-immersion in the MPS sol-gel solution overnight. The compound nanoparticles (nanocompounds) containing gold nanoparticles and silver nanoparticles were then chemisorbed on to the thiol groups of the second silane layer. Finally, diphtheria antibody (anti-Diph) was adsorbed on to the surface of the compound nanoparticles. The modified process was characterized by cyclic voltammetry (CV). Detection is based on the change in the potentiometric response before and after the antigen-antibody reaction. A direct potentiometric response to diphtheria antigen (Diph) was obtained from the immobilized diphtheria antibody. The potentiometric response of the resulting immunosensor was rapid and the linear range was from 22 to 800 ng mL-1 with the linear regression equation DeltaE=-79.5+69.4 log [Diph] and a detection limit of 3.7 ng mL-1 (at 3delta). Up to 19 successive assay cycles with retention of sensitivity were achieved for probes regenerated with 0.2 mol L-1 glycine-hydrochloric acid (Gly-HCl) buffer solution. Moreover, analytical results from several serum samples obtained using the developed technique were in satisfactory agreement with those given by the ELISA method, implying a promising alternative approach for detecting diphtheria antigen in clinical diagnosis.
Crystalline bacterial cell surface layers (S-layers) composed of identical protein units have been used as binding templates for well-organized arrangements of nanoparticles. Isolated S-layer proteins were recrystallized into monomolecular arrays on solid substrates (such as silicon wafers and SiO2-coated grids) and in suspension forming so-called self-assembly products. These S-layer assemblies were studied by atomic force microscopy and transmission electron microscopy (TEM). The orientation of the S-layer lattice, exhibiting anisotropic surface properties, on the solid surface and on the self-assembly products, was compared with the orientation on the bacterial cell. On both bacterial cells and SiO2 surfaces the outer face of the S-layer protein was exposed. On the self-assembly products occasionally the inner face was also visible. Metal- and semiconductor nanoparticles 2 to 10 nm in mean diameter were covalently or electrostatically bound to the solid-supported S-layers and self-assembly products. TEM studies reveal that upon activation of carboxyl groups in the S-layer lattice with 1-ethyl-3,3'(dimethylaminopropyl)carbodiimide (EDC), a close-packed monolayer of 4-nm amino-functionalized CdSe nanoparticles could be covalently established on the S-layer lattice. Because of electrostatic interactions, anionic citrate-stabilized Au nanoparticles (5 nm in diameter) formed a superlattice at those sites where the inner face of the S-layer lattice was exposed. In contrast, cationic semiconductor nanoparticles (such as amino-functionalized CdSe particles) formed arrays on the outer face of the solid-supported S-layer lattices.
Several years ago we showed that prostaglandins (PGs) are potent radioprotective agents. To investigate further the potential use of these compounds we employed quantitative measures of murine hair loss and regrowth to assess the effects of PG administration before multi-dose fractionated radiation exposures. We compared these results with findings utilizing the thiol compounds WR-2721 or WR-1065, the "gold standard" laboratory radioprotectors. Three weeks after systemic administration of 16-16 dm PGE2 (Upjohn Company) or WR-2721, given 1 h before each dose of 2-4.5 Gy per fraction for 10-15 fractions, regrowing hair counts increased up to 100% compared to irradiated-only skin sites. The thiol compound effects were slightly superior to the PG effects in these studies. Local applications of 16-16 dm PGE2 or WR-1065 given 15 min before each radiation fraction also enhanced post-radiation hair regrowth, although systemic administration of either agent was more effective than the topical route. We also evaluated possible protective effects of PGs given before doxorubicin, measuring murine hair loss 1 week after parenteral injections of the drug. Five daily doses of doxorubicin, 0.1 mg/25 g animal, reduced the number of hairs in a 4.42 mm2 area of skin from 241 +/- 5 (controls) to 144 +/- 3. Misoprostol (G.D. Searle & Co.), 25 micrograms/mouse, applied locally 2 h before each dose of doxorubicin, resulted in 213 +/- 8 residual hairs. We conclude that clinical use of these compounds may provide significant protection of hair follicles and possibly other normal tissues (skin; oral, rectal, and bladder mucosa) lying within a radiation field or in patients treated with chemotherapeutic agents. Further assessment of possible tumor protection effects are needed, however.
Relative potencies for 30 compounds scheduled for carcinogenic testing in the 2-year rodent bioassays were estimated based on comparisons with a wide variety of bioassay data for benzo[a]pyrene, nicotine, cisplatin, aflatoxin B1, and cyclophosphamide. Potential for oncogenic transformation of each of the compounds was estimated from short-term bioassays. Promoting strength was assigned on the basis of comparisons of the product of relative potency and test dose with the distribution of similar products obtained for 67 common compounds in the data-base of Gold et al. A potency class for promotion was assigned on the basis of whether the potency-adjusted test dosage was > 2 sigma below the mean, > 1 sigma below the mean, within +/- sigma of the mean, > sigma above the mean, or > 2 sigma above the mean, as determined from the 67 compounds. The underlying hypothesis is that a weak test dose may have a low probability of revealing a potential carcinogen, whereas a strong dose may have a high probability of producing false-positive results. Predictions are therefore directed at the central 68% of the log-normal frequency distribution according to the assumption that +/- sigma represents the ideal test dose.
Fifteen patients, eight males and seven females, suffering from classic or definite rheumatoid arthritis were treated for 1 year with Auranofin, a new gold salt active by the oral route, different from parenteral gold as far as dosage, mechanism of action and toxicity are concerned. Patients received a dosage of 3 mg twice daily, equivalent to 0.85 mg of elemental gold, in order to evaluate the therapeutic efficacy and tolerability of this new compound. Subjective and objective parameters were monitored during the trial and serum gold levels were assayed every 2 months by atomic absorption spectrophotometry. Our study, which is on-going, shows the therapeutic efficacy of Auranofin which seems better tolerated than parenteral gold salts and will probably become a widely used drug in the long-term treatment of rheumatoid arthritis.
This technique describes a simple and practical approach to the fabrication of collarless metal-ceramic restorations. Instead of making a duplicate die from the master die, this technique conserves time by blocking out the undercut using impression modeling compound on the master die. The use of gold powder does not require special equipment and produces a precise porcelain abutted margin on the shoulder. Excluding the labial gold collar from the shoulder enhances the esthetic appearance of the restoration. This approach is effective with gold-based and silver-palladium alloys as materials for the metal-ceramic framework. The marginal fit of 10 collarless meta-ceramic crowns cemented on silver plated dies were evaluated by measuring sectioned specimens with a scanning electron microscope. The average gap at the porcelain butt margin was observed to be 30 to 50 mu (Fig. 10).
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The reactivity in solution of two recently characterized gold(III) complexes, AuCl3(Hpm) and AuCl2(pm), has been investigated in view of their potential use as anti-cancer agents. In water, both compounds undergo relatively fast hydrolysis of the bound chlorides without loss of the heterocycle ligand; the process is much faster within a physiological buffer. When the two gold(III) complexes react with proteins like albumin or transferrin, reduction of gold(III) to gold(I) and/or hydrolysis is observed. On the other hand, both complexes bind rapidly and tightly to either polynucleotides or calf thymus DNA, with gold remaining in the +3 oxidation state. Circular dichroism investigations reveal a large perturbation of DNA conformation upon gold(III) binding; preferential binding to GC sequences is shown. Cytotoxicity studies on a number of tumor cell lines demonstrate a good activity of these gold(III) complexes compared to cisplatin. However, quick hydrolysis and/or reduction of these compounds under physiological conditions may represent a severe limitation to their use.
Norgaman has been examined by anodic rotating disc electrode voltammetry in buffered media over the range of pH from 0-11.5. The best medium is 0.1 mol 1(-1) sulphuric acid in which the anodic wave is well defined at lower rotation speeds. The compound does not show obedience to the Levich relationship at platinum and gold electrodes. Rapid determination of the compound is not possible due to the adsorption of the oxidation product. Electrode mechanism for the reaction has been elucidated.
Adverse reactions produced by sulfhydryl compounds with active thiol groups have generally formed a distinctive pattern in man when they are viewed as a class. It has been reported that cutaneous SH-induced drug eruptions have a wide variety of clinical presentations; histologically, they show a pattern of eosinophilic necrosis and/or satellite necrosis similar to that seen in cutaneous graft vs host reactions. In the present experiments, guinea pigs were sensitized with cephalothin (CET) and thiol compounds such as tiopronin (TP), D-penicillamine, gold sodium thiomalate or thiomalate, using a method similar to that described previously. In lymphocyte stimulation tests, lymph node cells from the sensitized animals responded positively to spleen cells pulsed with each thiol compound. Intracutaneous tests revealed some positive reactions to each thiol compound; there was a tendency to produce a tuberculin type reaction with indurated erythema rather than the Jones-Mote type seen in CET-induced reactions. The dose-requirements for positive intracutaneous tests and generalized rash (GR) due to thiol compounds were lower than for CET, which required relatively large doses. Histologically, infiltration of basophilic cells was prominent in the skin lesions induced by intracutaneous tests with CET and in those of CET-induced GR. On the other hand, intracutaneous tests with TP following the induction of TP-induced GR revealed eosinophilic degeneration of epidermal cells, which was similar to the eosinophilic necrosis seen in cutaneous GVHR. Intracutaneous tests after the induction of CET-GR did not show any eosinophilic changes in the epidermal cells. These findings are reminiscent of the characteristics of eruptions induced by thiol compounds in man, which differ from the eruptions induced by CET.
Reaction of (C6H3-2-AsPh2-n-Me)Li (n = 5 or 6) with [AuBr(AsPh3)] at -78 degrees C gives the corresponding cyclometallated gold(I) complexes [Au2[(mu-C6H3-n-Me)AsPh2]2] [n = 5, (1); n = 6, (9)]. 1 undergoes oxidative addition with halogens and with dibenzoyl peroxide to give digold(II) complexes [Au2X2[(mu-C6H3-5-Me)AsPh2]2] [X = Cl (2a), Br (2b), I (2c) and O2CPh (3)] containing a metal-metal bond between the 5d9 metal centres. Reaction of 2a with AgO2CMe or of 3 with C6F5Li gives the corresponding digold(II) complexes in which X = O2CMe (4) and C6F5 (6), respectively. The Au-Au distances increase in the order 4 < 2a < 2b < 2c < 6, following the covalent binding tendency of the axial ligand. Like the analogous phosphine complexes, 2a-2c and 6 in solution rearrange to form C-C coupled digold(I) complexes [Au2X2[mu-2,2-Ph2As(5,5-Me2C6H3C6H3)AsPh2]] [X = Cl (5a), X = Br (5b), X = I (5c) and C6F5 (7)] in which the gold atoms are linearly coordinated by As and X. In contrast, the products of oxidative additions to 9 depend markedly on the halogens. Reaction of 9 with chlorine gives the gold(I)-gold(III) complex, [ClAu[mu-2-Ph2As(C6H3-6-Me)]AuCl[(6-MeC6H3)-2-AsPh2]-kappa2As,C] (10), which contains a four-membered chelate ring, Ph2As(C6H3-6-Me), in the coordination sphere of the gold(III) atom. When 10 is heated, the ring is cleaved, the product being the digold(I) complex [ClAu[mu-2-Ph2As(C6H3-6-Me)]Au[AsPh2(2-Cl-3-Me-C6H3)]] (11). Reaction of 9 with bromine at 50 degrees C gives a monobromo digold(I) complex (12), which is similar to 11 except that the 2-position of the substituted aromatic ring bears hydrogen instead halogen. Reaction of 9 with iodine gives a mixture of a free tertiary arsine, (2-I-3-MeC6H3)AsPh2 (13), a digold diiodo compound (14) analogous to 11, and a gold(I)-gold(III) zwitterionic complex [I2Au(III)[(mu-C6H3-2-AsPh2-6-Me)]2Au(I)] (15) in which the bridging units are arranged head-to-head between the metal atoms. The structures of 2a-2c and 4-15 have been determined by single-crystal X-ray diffraction analysis. The different behaviour of 1 and 9 toward halogens mirrors that of their phosphine analogues; the 6-methyl substituent blocks C-C coupling of the aryl residues in the initially formed oxidative addition product. In the case of 9, the greater lability of the Au-As bond in the initial oxidative addition product may account for the more complex behaviour of this system compared with that of its phosphine analogue.
The purpose of this study was to modify the gold chloride procedure for studies of total innervation in corneal whole mounts to provide a decrease in nonspecific background staining and to eliminate the progressively deteriorating stain quality of standard gold chloride techniques. Modifications included use of cryoprotective agents, mechanical removal of Descemet's membrane-endothelium complex prior to fixation, treatment with alpha amylase, and halting the reduction of gold chloride to metallic gold using Kodak rapid fixer with hardener. Rat corneas were stored at -70 C in O.C.T. compound. The Descemet's membrane-endothelium complex was removed after thawing, and corneas were fixed in 4% NaPO4-buffered paraformaldehyde with 8% sucrose. Fixed corneas were incubated in NaPO4-buffered saline containing alpha amylase, placed in 100% lemon juice, then in 1% gold chloride solution, transferred to glacial acidic acid, placed in rapid fixer, rinsed in NaPO4-buffered saline, and dehydrated in graded alcohols. Flat mounts of whole corneas were examined using contralateral corneas as controls. Freezing corneas in O.C.T. compound, removal of the Descemet's membrane-endothelium complex, and treatment with alpha amylase reduced non-specific background staining compared to controls. Treatment with Kodak rapid fixer prevented the deterioration of staining quality for at least 8 months. These improvements allow the gold chloride technique to be used with immunohistochemical procedures where the reaction products would be obscured by background staining.