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PubMed2000

Gold(III) complexes as potential antitumor agents: solution chemistry and cytotoxic properties of some selected gold(III) compounds.

Gold(III) complexes generally exhibit interesting cytotoxic and antitumor properties, but until now, their development has been heavily hampered by their poor stability under physiological conditions. To enhance the stability of the gold(III) center, we prepared a number of gold(III) complexes with multidentate ligands - namely [Au(en)(2)]Cl(3), [Au(dien)Cl]Cl(2), [Au(cyclam)](ClO(4))(2)Cl, [Au(terpy)Cl]Cl(2), and [Au(phen)Cl(2)]Cl - and analyzed their behavior in solution. The solution properties of these complexes were monitored by visible absorption spectroscopy, mass spectrometry, and chloride-selective potentiometric measurements; the electrochemical properties were also studied by cyclic voltammetry and coulometry. Since all the investigated compounds exhibited sufficient stability under physiological conditions, their cytotoxic properties were tested in vitro, via the sulforhodamine B assay, on the representative human ovarian tumor cell line A2780, either sensitive or resistant to cisplatin. In most cases the investigated compounds showed relevant cell-killing properties with IC(50) values falling in the 0.2-10 microM range; noticeably most investigated gold(III) complexes were able to overcome, to a large extent, resistance to cisplatin when tested on the corresponding cisplatin-resistant cell line. The cytotoxic properties of the free ligands were also determined under the same solution conditions. Ethylenediamine, diethylenetriamine, and cyclam were virtually nontoxic (IC(50) values > 100 microM) so that the relevant cytotoxic effects observed for [Au(en)(2)]Cl(3) and [Au(dien)Cl]Cl(2) could be quite unambiguously ascribed to the presence of the gold(III) center. In contrast the phenanthroline and terpyridine ligands turned out to be even more cytotoxic than the corresponding gold(III) complexes rendering the interpretation of the cytotoxicity profiles of the latter complexes less straightforward. The implications of the present findings for the development of novel gold(III) complexes as possible cytotoxic and antitumor drugs are discussed.

Antineoplastic Agents↗
PubMed1997

Comparison of the gold reduction and stripping processes at platinum, rhodium, iridium, gold and glassy carbon micro- and macrodisk electrodes.

The gold AuIII + 3e(-)-->Au0 reduction and Au0-->AuIII + 3e- oxidation stripping processes in dilute aqua regia electrolyte (0.1 M HCl + 0.32 M HNO3) were examined at platinum, rhodium, iridium, gold and glassy carbon disk electrodes. After ascertaining that the preferred material was platinum, the effect of electrode size was evaluated by using nine different platinum disk electrodes having diameters ranging from 2 to 2000 microns. The optimum analytical response was obtained with a 50 microns diameter platinum disk electrode. With this electrode diameter, a sharp symmetrical gold stripping peak was obtained and the deposition process occurred predominantly under conditions of radial diffusion so that stirring of the solution was not required. In contrast, larger sized platinum electrodes produced a broader, asymmetric stripping response for the gold oxidation peak, whereas electrodes of smaller diameter provided poorer signal-to-noise ratios. The limit of detection and limit of quantification were calculated to be 4.4 x 10(-7) M (86 ppb) and 13.1 x 10(-7) M (258 ppb), respectively, at the 50 microns diameter platinum disk electrode under conditions of linear sweep stripping voltammetry at a scan rate of 200 mV s-1 and a 140 s deposition time. The optimum electrode gave a very well defined gold oxidation signal with negligible background current when applied to the determination of gold in a gold ore sample.

Electrochemistry↗
PubMed2005

Contact allergy to gold in patients with gold-plated intracoronary stents.

An increasingly common and effective method for the treatment of atherosclerotic disease in the coronary arteries is percutaneous transluminal coronary angioplasty (PTCA) and stenting. The stents are made of different metals. An increased rate of restenosis when using gold-plated stents has been shown. Contact allergy to gold is common in many countries. Recently, a study has shown an increased rate of contact allergy to nickel among patients with restenosis and a nickel-containing stent. The aims of our study were to investigate whether there was an increased rate of contact allergy to gold among patients with gold-plated stents and if this increased the risk of restenosis. 22 patients who had received a gold-plated stent were patch tested. An age- and sex-matched population of 88 patients, previously patch tested because of a suspected contact dermatitis, served as controls. In the stent group, 10/22 (45.5%) had a contact allergy to gold, in the control group 18/88 (20.5%); the difference is statistically significant (P = 0.04). There was no significant difference regarding frequency of restenosis. Our study indicates that there is a risk of sensitizing the patient when implanting a gold-plated stent. Further studies are needed to confirm these results and to evaluate whether there is an increased risk of restenosis.

Adult↗
PubMed1997

Reinstitution of gold after gold induced proteinuria.

OBJECTIVE: To assess the benefits and risks to patients who resumed gold after discontinuation of gold because of proteinuria. METHODS: We conducted a review of records of all patients who had resumed gold after discontinuing treatment because of proteinuria. RESULTS: Eight patients developed proteinuria > or = 500 mg/dl while receiving 50 mg weekly doses in the first year of treatment. Proteinuria took a minimum of 4 mo to resolve. No patient had a recurrence of proteinuria when gold was resumed at a lower dosage of 25 mg every 1-2 weeks. This strategy has been successful in 5/8 patients who continue taking gold and are markedly improved compared to pretreatment status after 3-7 years (mean 5 years) of followup. CONCLUSION: The risk of gold induced proteinuria may be dose related and reinstitution of gold at a lower dose is safe in our experience and effective in selected patients.

Aged↗
PubMed2005

SERS of C60/C70 on gold-coated filter paper or filter film influenced by the gold thickness.

SERS of C(60)/C(70) adsorbed on gold nanoparticles coated on filter paper or filter film was studied. As a new SERS substrate, dried gold-coated filter paper or filter film has a high SERS activity, whose enhancement factor can be up to about 10(5), because it avoided the influence of solvents in C(60)/C(70) solution and water in gold hydrosols. The influence of the gold thickness coated on filter paper or filter film to SERS of C(60)/C(70) adsorbed on gold nanoparticles was mainly discussed. It is indicated that the SERS effect of C(60)/C(70) was very sensitive to the distribution and aggregated characteristics of gold nanoparticles, and the SERS intensity of each mode increased at its own proportion, but it integrally tended to saturation when the thickness of colloidal gold coatings increased.

Journal Article↗
PubMed2000

Applications of gold cluster compounds in immunocytochemistry and correlative microscopy: comparison with colloidal gold.

In this review, we discuss the immunocytochemical literature with respect to a comparison between conventional colloidal gold and gold cluster compounds as immunoprobes. The relative advantages and disadvantages of each of these types of particle for immunocytochemical applications are discussed. We present results from our own laboratories and those of others on the comparison of these immunoprobes in selected experimental situations. These results show the use of gold cluster compounds at both light and electron microscope levels. At the ultrastructural level, gold cluster compounds have been used in pre-embedding labelling of cultured cells, and for labelling of ultrathin cryosections and freeze-fracture preparations. Recently, fluorescently tagged gold cluster compounds have become available. Using ultrathin cryosections of human neutrophils as a model system, we demonstrate that a single immunoprobe (i.e. a fluorescently tagged gold cluster compound) is a robust probe for correlative fluorescence and electron microscopy.

Gold Colloid↗
PubMed1998

Metal release from gold-containing jewelry materials: no gold release detected.

Metal release from 13 different gold-containing jewelry alloys stored for 1 and 3 weeks in artificial sweat was analysed. For chemical analysis, inductively-coupled plasma detection (ICP) and atomic absorption spectrophotometry (AA), with flame and with furnace, were used. No release of gold was detected. It is unlikely that skin contact with gold-containing metallic items such as jewelry is responsible for inducing contact allergy to gold or allergic contact dermatitis due to the gold. The patch-test reactivity to gold sodium thiosulfate needs to be explained by some other mechanism(s).

Biological Availability↗
PubMed1986

The neurotoxic effect of gold sodium thiomalate on the peripheral nerves of the rat. Insights into the antiinflammatory actions of gold therapy.

Although gold is one of the few therapeutic agents that has been proven effective in producing remission in patients with rheumatoid arthritis, its mechanism of action is unknown. Since nociceptive afferent and sympathetic efferent fibers of the peripheral nervous system contribute to the pathophysiology of inflammation, and since a known side effect of gold therapy is a polyneuropathy, we tested the hypothesis that gold is toxic to small-diameter peripheral nerve fibers in the rat. We found that prolonged treatment with gold, at the same dosage reported to be effective against adjuvant-induced arthritis in the rat, produced a significant decrease in the numbers of unmyelinated, but not of myelinated, axons. Gold treatment also elevated nociceptive thresholds in both articular and nonarticular structures. These results suggest that gold produces an antiinflammatory effect on arthritis by a neurotoxic effect on the peripheral nerves involved in neurogenic inflammation.

Animals↗
PubMed1991

Application of a novel 1:1 gold(I)-chromophoric thiolate complex as a spectrophotometric probe for the thiol-exchange reactions of anti-arthritic gold drugs in biological fluids.

An oligomeric 1:1 gold(I) complex of the chromophoric thiol 5-mercapto (2-nitrobenzoate) has been synthesized and applied as a spectrophotometric probe for the thiol-exchange reactions of structurally-analogous 1:1 gold(I)-thiolate drugs. For low-molecular-mass thiols, results were consistent with the initial formation of a monomeric mixed-ligand bis-thiolato gold(I) complex followed by further ligand substitution by excess thiol to produce 5-mercapto (2-nitrobenzoate) and a monomeric bis-thiolato gold(I) complex. For human serum albumin, however, the spectrophotometric changes were only consistent with the binding of gold(I) to its single cysteine residue (Cys-34) with the retention of the 5-mercapto (2-nitrobenzoate) ligand on gold(I).

Antirheumatic Agents↗
PubMed2006

Ultrafast cooling of photoexcited electrons in gold nanoparticle-thiolated DNA conjugates involves the dissociation of the gold-thiol bond.

Using UV-visible extinction spectroscopy and femtosecond pump-probe transient absorption spectroscopy, we have studied the effect of femtosecond laser heating on gold nanoparticles attached to DNA ligands via thiol groups. It is found that femtosecond pulse excitation of the DNA-modified nanoparticles at a wavelength of 400 nm leads to desorption of the thiolated DNA strands from the nanoparticle surface by the dissociation of the gold-sulfur bond. The laser-initiated gold-sulfur bond-breaking process is a new pathway for nonradiative relaxation of the optically excited electrons within the DNA-modified gold nanoparticles, as manifested by a faster decay rate of the excited electronic distribution at progressively higher laser pulse energies. The experimental results favor a bond dissociation mechanism involving the coupling between the photoexcited electrons of the nanoparticles and the gold-sulfur bond vibrations over one involving the conventional phonon-phonon thermal heating processes. The latter processes have been observed previously by our group to be effective in the selective photothermal destruction of cancer cells bound to anti-epidermal growth factor receptor-conjugated gold nanoparticles.

DNA↗
PubMed1997

Nickel contamination of gold salts: link with gold-induced skin rash.

Intramuscular chrysotherapy is a well-established treatment for rheumatoid arthritis. Its therapeutic use has been limited by the high incidence of dermatological side-effects. The pathogenic mechanisms of these are unknown, but could include allergic reactions to gold or to nickel contaminating the gold. In order to investigate these mechanisms further, 15 patients, who developed cutaneous eruptions after chrysotherapy, were assessed using skin biopsy and lymphocyte transformation stimulated by gold and nickel salts in vitro. Chrysotherapy induced two main cutaneous eruptions: lichenoid reactions and non-specific dermatitis. Peripheral blood mononuclear cells from patients with lichenoid reaction proliferated to gold salts in vitro, while those who developed non-specific dermatitis responded mainly to nickel. Nickel was a significant contaminant of the gold preparation (sodium aurothiomalate, Myocrisin, Rhone-Poulenc Ltd), amounting to a total of 650 ng after 6 months treatment. We suggest that a significant percentage of skin reactions during chrysotherapy are due to nickel contamination of the gold preparation.

Adult↗
PubMed2005

Gold-tip electrodes--a new "deep lesion" technology for catheter ablation? In vitro comparison of a gold alloy versus platinum-iridium tip electrode ablation catheter.

Gold-tip electrodes. Radiofrequency (RF) catheter ablation is widely used to induce focal myocardial necrosis using the effect of resistive heating through high-frequency current delivery. It is current standard to limit the target tissue-electrode interface temperature to a maximum of 60-70 degrees C to avoid char formation. Gold (Au) exhibits a thermal conductivity of nearly four times greater than platinum (Pt-Ir) (3.17 W/cm Kelvin vs 0.716 W/cm Kelvin), it was therefore hypothesized that RF ablation using a gold electrode would create broader and deeper lesions as a result of a better heat conduction from the tissue-electrode interface and additional cooling of the gold electrode by "heat loss" to the intracardiac blood. Both mechanisms would allow applying more RF power to the tissue before the electrode-tissue interface temperature limit is reached. To test this hypothesis, we performed in vitro isolated liver and pig heart investigations comparing lesion depths of a new Au-alloy-tip electrode to standard Pt-Ir electrode material. Mean lesion depth in liver tissue for Pt-Ir was 4.33+/-0.45 mm (n=60) whereas Au electrode was able to achieve significantly deeper lesions (5.86+/-0.37 mm [n=60; P<0.001]). The mean power delivered using Pt-Ir was 6.95+/-2.41 W whereas Au tip electrode delivered 9.64+/-3.78 W indicating a statistically significant difference (P<0.05). In vitro pig heart tissue Au ablation (n=20) increased significantly the lesion depth (Au: 4.85+/-1.01 mm, Pt-Ir: 2.96+/-0.81 mm, n=20; P<0.001). Au tip electrode again applied significantly more power (P<0.001). Gold-tip electrode catheters were able to induce deeper lesions using RF ablation in vitro as compared to Pt-Ir tip electrode material. In liver and in pig heart tissue, the increase in lesion depth was associated with a significant increase in the average power applied with the gold electrode at the same level of electrode-tissue temperature as compared to platinum material.

Animals↗
PubMed1983

Applications of immunocolloids in light microscopy. II. Demonstration of lectin-binding sites in paraffin sections by the use of lectin-gold or glycoprotein-gold complexes.

A new procedure is presented for the light microscopic demonstration of specific sugar sequences of oligosaccharides in glycoconjugates by lectins combined with the colloidal gold marker system. Tissue sections from aldehyde-fixed and paraffin embedded rat kidney were stained either in a one-step method with lectin directly bound to particles of colloidal gold or in a two-step method using non-labeled lectin and glycoprotein labeled with colloidal gold. In both methods the presence of lectin-binding sites in the tissue sections is revealed by the appearance of a red coloration that is due to the accumulation of gold particles. The high specificity of the technique is combined with a good sensitivity and resolution as demonstrated by a differential plasma membrane staining in renal epithelial cells. The lectin-gold or glycoprotein-gold complexes remain stable for months and produce a permanent nonbleaching staining.

Animals↗
PubMed1992

Localization of immunoreactive tyrosine hydroxylase in the goldfish retina with pre-embedding immunolabeling with one-nanometer colloidal gold particles and gold toning.

The goal of this study was to develop an alternative to silver intensification for visualizing small colloidal gold particles by light and electron microscopy. The isolated goldfish retina was labeled with rabbit antiserum to tyrosine hydroxylase and 1-nm colloidal gold-conjugated goat anti-rabbit IgG. The gold particles were enlarged by toning with gold chloride, followed by reduction in oxalic acid. Dopaminergic interplexiform cells were clearly visible by light microscopy and, in lightly-fixed material treated with detergent, they were labeled in their entirety. Labeling was qualitatively similar, although less extensive, in material fixed and processed for electron microscopy. The labeled processes were apparent in ultra-thin sections viewed at low magnification, but the gold-toned particles were not so large that they obscured subcellular structures. The procedure apparently had no deleterious effects on the tissue, since the ultrastructural preservation was comparable to that seen with other pre-embedding immunolabeling methods. The technique was simple, reliable and, since the gold solutions were so dilute, relatively inexpensive.

Animals↗
PubMed1986

Video microscopy of colloidal gold particles and immuno-gold labelled microtubules in improved rectified DIC and epi-illumination.

Modification of rectified Nomarski differential interference contrast optics (Nikon) and the epi-illumination system (Nikon IGS-cube) improved the detection of colloidal gold particles with analog video enhanced microscopy. Immuno-gold labelled microtubules of Haemanthus endosperm are visualized at a level of detection unmatched in conventional light microscopy. Single gold, or gold silver enhanced particles in suspension viewed with the modified epi-illumination after pressure injection into cells, are well distinguished from other granular cell components. Immuno-gold has also been detected on the surface of chromosomes and the nuclear envelopes in cells during the rapid experimental disassembly of microtubules. Thus, under certain conditions tubulin in a form other than microtubules may be detected. Practical applications of this "optical stain" for non fading immuno-gold 5-40 nm markers are discussed.

Cell Division↗
PubMedDate not supplied

The effect of 3 torque delivery systems on gold screw preload at the gold cylinder-abutment screw joint.

PURPOSE: This study measured the gold screw preload at the gold cylinder-abutment screw joint interface obtained by 3 torque delivery systems. MATERIALS AND METHODS: Using a precalibrated, strain-gauged standard abutment as the load cell, 3 torque delivery systems tested were shown to have significant differences in gold screw preload when a gold cylinder was attached. RESULTS: Mean preloads measured were 291.2 N for hand torque drivers set at 10 Ncm, 340.3 N for electronic torque controllers at low setting/10 Ncm, 384.4 N for electronic torque controllers at high setting/10 Ncm; and 140.8 N for hand-tightening with a prosthetic slot screwdriver. Significant differences in screw preload were also found between operators using a hand torque driver. DISCUSSION: Hand-tightening delivered insufficient preload and cannot be recommended for final gold screw tightening. Different electronic torque controller units set at 10 Ncm induced mean gold screw preloads that ranged from 264.1 N to as high as 501.2 N. CONCLUSION: Electronic torque controllers should be regularly recalibrated to ensure optimal output.

Analysis of Variance↗
PubMed1992

[Gold salt deposits in the conjunctiva in rheumatoid arthritis after gold therapy. A systematic study of 15 biopsies].

Ocular abnormalities have long been recognized as a potential adverse effect of gold therapy in patients with rheumatoid arthritis. Clinical symptoms and ocular tissue lesions possibly related to use of gold therapy were routinely evaluated in eleven patients. There were few clinical manifestations: only one patient had typical accumulation of gold in the anterior crystalloid. In contrast, routine ultrastructural and microprobe studies of conjunctival biopsy specimens disclosed accumulation of gold salts in every case. Gold was visible as aurosomes in the conjunctival macrophages. Aurosomes were seen in patients treated for as little as one month, occurred even with low doses (0.3 g), and were still visible after several years. Duration of accumulation can be roughly estimated on the basis of the morphologic appearance of aurosomes which are lamellar after a few weeks of gold therapy and rod-shaped beyond one month.

Adult↗
PubMed1985

Ploidity and cell cycle progression during treatment with gold chloride, auranofin and sodium aurothiomalate. Studies on a human epithelial cell line and its sub-strains made resistant to the antiproliferative effects of these gold compounds.

The possible influence of gold(III) chloride and the two gold(I)-containing anti-arthritic drugs, auranofin and sodium aurothiomalate, on cellular ploidity and cell cycle progression was investigated on cultured human epithelial cells. Four different cell lines were used: the parent line (HE) and three sub-strains which previously had acquired resistance to the antiproliferative effects of either 350 mumol gold chloride/l culture medium (HEAu350), 2 mumol auranofin/l (HEAF) or 300 mumol sodium aurothiomalate/l (HEMyo). DNA-histograms were obtained by flow cytometry examinations during a 9-days' exposure to either of these gold-containing compounds and concentrations. The HE, HEAF and HEMyo cells had similar ploidities, close to tetraploid. The HEAu350 cells had altered ploidity to distinct tetraploid. The distribution of the resistant cells with the cell cycle phases was not different from that of untreated HE cells. The HE cells, when treated with auranofin or sodium aurothiomalate, accumulated in the G2-phase of the cell cycle. In addition, a new cedecoploid peak appeared. No such changes were observed on gold chloride exposure or in HE controls grown without drug supplement. The effects of auranofin and sodium aurothiomalate on cell cycle progression of the HE cells possibly indicate a tendency to polyploidity, and furthermore that inhibition of cellular mitosis is one mechanism of the antiproliferative effect common to the two drugs.

Auranofin↗