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PubMed1982

Prior gold therapy does not influence the adverse effects of D-penicillamine in rheumatoid arthritis.

One hundred fourteen patients with definite or classic rheumatoid arthritis were followed prospectively between January 1976 and April 1981 to monitor their toxicity pattern to D-penicillamine. The influence of previous sodium aurothiomalate therapy on the toxicity pattern of D-penicillamine is described. There was no significant difference in overall outcome of the patients treated with D-penicillamine with respect to adverse effects, whether they had previous gold toxicity, previous gold therapy but no toxicity, or no previous gold therapy. The time from gold toxicity to the start of D-penicillamine therapy was greater in those who did not develop D-penicillamine toxicity compared with those who did. This difference just reached statistical significance. Total gold salt received had no effect on eventual outcome of D-penicillamine treatment, and the toxicity pattern of D-penicillamine in those patients who had previous gold therapy was similar to those patients who had never received gold therapy.

Adolescent↗
PubMed2006

Fabrication of a gold microelectrode for amperometric detection on a polycarbonate electrophoresis chip by photodirected electroless plating.

A novel method of photoresist-free micropatterning coupled with electroless gold plating is described for the fabrication of an integrated gold electrode for electrochemical detection (ED) on a polycarbonate (PC) electrophoresis microchip. The microelectrode layout was photochemically patterned onto the surface of a PC plate by selective exposure of the surface coated without photoresist to 254 nm UV light through a chromium/quartz photomask. Thus, the PC plate was selectively sensitized by formation of reactive chemical moieties in the exposed areas. After a series of wet chemistry reactions, the UV-exposed area was activated with a layer of gold nanoparticles that served as a seed to catalyze the electroless plating. The gold microelectrode was then selectively plated onto the activated area by using an electroless gold plating bath. Nonselective gold deposition on the unwanted areas was eliminated by sonication of the activated PC plate in a KSCN solution before electroless plating, and the adhesion of the plated electrodes to the PC surface was strengthened with thermal annealing. Compared with the previously reported electroless plating technique for fabrication of microelectrodes on a microchip, the present method avoided the use of a membrane stencil with an electrode pattern to restrict the area to be wet-chemically sensitized. The CE with integrated ED (CE-ED) microchip was assembled by thermal bonding an electrode-plated PC cover plate to a microchannel-embossed PC substrate. The novel method allows one to fabricate low-cost, electrode-integrated, complete PC CE-ED chips with no need of a clean room. The fabricated CE-ED microchip was demonstrated for separation and detection of model analytes, including dopamine (DA) and catechol (CA). Detection limits of 0.65 and 1.03 microM were achieved for DA and CA, respectively, and theoretical plate number of 1.4 x 10(4) was obtained for DA. The plated gold electrode can be used for about 4 h, bearing usually more than 100 runs before complete failure.

Catechols↗
PubMed1993

Uptake and recovery of gold by immobilized persimmon tannin.

Some attempts were made to recover gold from aqueous systems using immobilized persimmon tannin. This adsorbent adsorbed gold from solutions containing hydrogen tetrachloroaurate (III) with high efficiency, whereas there was minimal adsorption from solutions containing gold(I) sodium thiomalate and sodium dicyanoaurate(I). The adsorption of gold was rapid, and was affected by the pH of the solution, temperature, external gold concentration and amount of adsorbent. Adsorbed gold was easily desorbed with 1 mol dm-3 thiourea solution, indicating that immobilized persimmon tannin can be repeatedly re-used for the recovery of gold using adsorption-desorption cycles.

Adsorption↗
PubMed2007

Visible-laser desorption/ionization on gold nanostructures.

In this report, we describe the visible-laser desorption/ionization of biomolecules deposited on gold-coated porous silicon and gold nanorod arrays. The porous silicon made by electrochemical etching was coated with gold using argon ion sputtering. The gold nanorod arrays were fabricated by electrodepositing gold onto a porous alumina template, and the subsequent partial removal of the alumina template. A frequency-doubled/tripled Nd : YAG laser was used to irradiate the gold nanostructured substrate, and the desorbed molecular ions were mass-analyzed by a time-of-flight mass spectrometer. The desorption/ionization of biomolecules for both substrates was favored by the use of the 532-nm visible-laser, which is in the range of the localized surface plasmon resonance of the gold nanostructure. The present technique offers a potential analytical method for low-molecular-weight analytes that are rather difficult to handle in the conventional matrix-assisted laser desorption/ionization (MALDI) mass spectrometry.

Adsorption↗
PubMed1993

Site of action for the inhibition by gold sodium thiomalate of rabbit platelet activation.

The inhibitory action of the gold-based drug gold sodium thiomalate was investigated in rabbit platelets. Gold sodium thiomalate at concentrations of 0.25-13 x 10(-4) M inhibits collagen-, ADP-, and 9,11,dideoxy-11 alpha,9 alpha-epoxymethanoprostaglandin F2 alpha (U46619)-induced aggregation as well as collagen- and U46619-induced serotonin release. This inhibition occurs in both Tyrodes-albumin or Tyrodes-gelatin buffer systems. Preincubation of gold sodium thiomalate with platelets resulted in less inhibition as the time of preincubation increased. The inhibitory effect of gold sodium thiomalate could be removed by washing the platelets. Other sulfhydryl-reacting compounds, such as D-penicillamine, thiomalic acid, 5,5'-dithiobis-2-nitrobenzoic acid, and 6,6'-dithiodinicotinic acid, were all capable of inhibiting collagen-induced aggregation and serotonin release. Evidence is presented that gold sodium thiomalate interferes with the activation of rabbit platelets by several activators, that this action of gold sodium thiomalate is similar to the action of other sulfhydryl-reacting agents, that this inhibition is likely occurring at the membrane, and that the action of the drug is not dependent on the presence of albumin.

Animals↗
PubMed1991

Membrane routing during exocytosis and endocytosis in neuroendocrine neurones and endocrine cells: use of colloidal gold particles and immunocytochemical discrimination of membrane compartments.

The hypothesis that the retrieval of membranes of neurohypophysial neurosecretory granules (NSG) and small electron-lucent microvesicles occurs by different routes was tested by incubating neurohypophysial neurosecretosomes with colloidal gold particles of various sizes. Neurosecretosomes derived from normal Long Evans rats and incubated in media of normal ionic composition endocytosed a few small (less than 25 nm) gold particles into 40-50 nm electron-lucent microvesicles. After depolarisation, more small gold particles were found in microvesicles, and small and large (greater than 25 nm) gold particles in vacuoles. Oxytocin-containing neurosecretosomes derived from Brattleboro rats, which contain 160 nm-diameter NSG, endocytosed gold particles in a pattern indistinguishable from that of neurosecretosomes from Long Evans rats. However, neurosecretosomes derived from defective vasopressin neurones of Brattleboro rats, which contain microvesicles, small vacuoles, and a few 100 nm dense-cored vesicles, but no 160 nm NSG, endocytosed only small colloidal gold particles. Early after depolarisation the gold particles were present only in microvesicles, but later some could be found in vacuoles and lysosome-like structures. Immunogold cytochemistry using a polyclonal antiserum raised against microvesicle-rich neurosecretosomes derived from Brattleboro rats labelled microvesicles in the posterior pituitary strongly, NSG weakly, and vacuoles to a variable extent. These data together indicate that, after exocytosis, the membranes of NSG are recaptured as large vacuoles. Microvesicles are exocytosed and endocytosed separately.

Animals↗
PubMed1985

Retrograde tracing of neural pathways with a protein gold complex. II. Electron microscopic demonstration of projections and collaterals.

This paper describes a sensitive method for tracing neural connections at the electron microscopic (EM) level using a new compound produced through the coupling of colloidal gold particles to a wheat germ agglutinin horseradish peroxidase conjugate (the WGA*HRP-gold complex). Visualization of retrogradely labeled cells at the EM level was achieved either directly by gold particles scanning or after silver enhancement. By using different sizes of gold particles individually coupled to WGA*HRP and injected in different brain areas EM detection of multiple retrograde labeling was possible. Thus retrogradely labeled cells were first identified at the light microscopic level through HRP histochemistry with tetramethylbenzidine as a chromogen and then examined under the electron microscope after osmication and embedding. Gold particles were readily identified as electron dense, round dots in spherical grey vesicles. Identification of different sizes of gold particles often localized in the same vesicle established that the protein-gold complex can be used to study collateralisation of parental axons.

Animals↗
PubMed1989

Variability in gold bead density in cells. Quantitative immunocytochemistry.

Variability in gold bead distribution between individual cells was demonstrated in both pituitary melanotrophic cells immunocytochemically reacted for ACTH and in neurohypophysial terminals reacted for oxytocin-neurophysin. Gold beads were confined to the secretory granules compartment of both tissues. Density of gold beads in melanotrophic cells reacted for ACTH varied from 100-480 gold beads/microns 2. A much narrower range of gold beads distribution (460-900 gold beads/microns 2) was observed in axons of the neurohypophysis reacted with anti-oxytocin-neurophysin. These results indicate that the labeling density varies from cell to cell (as well as axon terminals) within morphologically homogeneous populations. Thus, it may reflect certain physiological differences between cells. A suggestion is being made that mean gold bead density coefficient of variation should be calculated by comparison between individual cells.

Adrenocorticotropic Hormone↗
PubMed1976

A multicentre controlled trial of the effects of different dosage of gold therapy, followed by a maintenance dosage.

In a combined clinical trial with gold in patients with rheumatoid arthritis (RA) 95 patients were treated with a high initial dosage of 2,500 mg aurothioglucose in 21 weeks. Afterwards 48 of these patients received a maintenance dosage of gold and 47 patients placebo injections. Another group of 101 patients received 1,000 mg gold in 21 weeks. Finally a maintenance dose of gold was administered to 49 of these patients, to the other 52 patients placebo injections were administered. For the treatment of RA a high dosage of a gold compound offers no advantage over a low dosage. After a high dosage one can expect a significantly higher number of side effects. The development of toxicity does not influence the ultimate results. A second course of gold has hardly any benificial effect. Prolonged administration of gold is usually well-tolerated; whether it has substantial and sustained therapeutic value remains dubious. Progression of radiological abnormalities can be observed at the same moment that signs and other symptoms of the disease show improvement.

Adult↗
PubMed2001

Occupational exposure to airborne mercury during gold mining operations near El Callao, Venezuela.

OBJECTIVE: The National Institute for Occupational Safety and Health (NIOSH) recently conducted a cross-sectional study during gold mining operations near El Callao, Venezuela. The purpose of the study was to assess mercury exposures and mercury-related microdamage to the kidneys. The study consisted of concurrent occupational hygiene and biological monitoring, and an examination of the processing techniques employed at the different mining facilities. Mercury was used in these facilities to remove gold by forming a mercury-gold amalgam. The gold was purified either by heating the amalgam in the open with a propane torch or by using a small retort. METHODS: Thirty-eight workers participated in this study. Some participants were employed by a large mining company, while others were considered "informal miners" (self-employed). Mercury exposure was monitored by sampling air from the workers' breathing zones. These full-shift air samples were used to calculate time-weighted average (TWA) mercury exposure concentrations. A questionnaire was administered and a spot urine sample was collected. Each urine sample was analyzed for mercury, creatinine, and N-acetyl-beta-D-glucosaminidase (NAG). RESULTS: The range for the 8-h TWA airborne mercury exposure concentrations was 0.1 to 6,315 micrograms/m3, with a mean of 183 micrograms/m3. Twenty percent of the TWA airborne mercury exposure measurements were above the NIOSH recommended exposure limit (REL) of 50 micrograms/m3, and 26% exceeded the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV) of 25 micrograms/m3. The mean urine mercury concentration was 101 micrograms/g creatinine (microgram/g-Cr), and the data ranged from 2.5 to 912 micrograms/g-Cr. Forty-two percent of the study participants had urine mercury concentrations that exceeded the ACGIH biological exposure index (BEI) of 35 micrograms/g-Cr. Urinary NAG excretion is considered a biological marker of preclinical, nonspecific microdamage to the kidney's proximal tubule cells. The mean urine NAG concentration was 3.6 International Units/g-Cr (IU/g-Cr) with a range of 0.5 to 11.5 IU/g-Cr. Three workers had urine NAG levels in excess of the reference values. Correlation analyses found statistically significant correlations between airborne mercury exposure and urine mercury level (P = 0.01), and between urine mercury level and urine NAG excretion (P = 0.01). In addition, the airborne mercury exposure data and urine mercury data were segregated by job tasks. A Wilcoxon rank sum test revealed significant correlations between tasks and mercury exposure (P = 0.03), and between tasks and urine mercury level (P = 0.02). CONCLUSIONS: The tasks with the highest mean airborne mercury exposures were "burning the mercury-gold amalgam" and "gold refining/smelting". Recommendations were provided for improving the retort design to better contain mercury, for ventilation in the gold shops, and for medical surveillance and educational programs.

Acetylglucosaminidase↗
PubMed2006

Solid phase extraction of gold(III) on Amberlite XAD-2000 prior to its flame atomic absorption spectrometric determination.

A solid phase extraction method for the determination of gold(III) at trace levels by flame atomic absorption spectrometer (FAAS) was developed. The method was based on retention of gold as chloro complexes through the Amberlite XAD-2000. The effect of some analytical parameters including hydrochloric acid concentration, sample volume, sample and eluent flow rates, eluent volume, eluent concentration and interfering ions on the recovery of gold(III) was investigated. The retention of gold(III) from 1.5 mol l(-1) HCl solution and the recovery of gold with 0.07 mol l(-1) NH3 solution were quantitative (>or=95%). The relative standard deviation (RSD) was calculated as 3.2% (n = 10). The detection limit for gold was 2 microg l(-1). The accuracy was checked with the determination of gold spiked an artificial seawater and a pure copper samples.

Adsorption↗
PubMed2006

Metal-enhanced fluorescence from gold surfaces: angular dependent emission.

The first observation of Metal-Enhanced Fluorescence (MEF) from large gold colloids is presented. Gold colloids, 40 and 200 nm diameter, were deposited onto glass substrates in a homogeneous fashion. The angular-dependent fluorescence emission of FITC-HSA, adsorbed onto gold colloids, was measured on a rotating stage which was used to evaluate MEF at all spatial angles. The emission intensity of FITC-HSA was found to be up to 2.5-fold brighter than the emission on bare glass substrates at an angle of 270 degrees. This is explained by the Radiating Plasmon Model, whereby the combined system, composed of the fluorophore and the metal colloids, emits with the photophysical characteristics of the fluorophore, after the excitation and the partial radiationless energy transfer between the excited states of the fluorophore and the surface plasmons of the gold colloids. The fluorescence enhancement was found to be higher with 200 nm gold colloids as compared to 40 nm colloids due to the increased contribution of the scattering portion of the 200 nm gold colloid extinction spectrum. These observations suggest that gold colloids could be used in MEF applications, offering more stable surfaces than the commonly used silvered surfaces, for applications requiring longer term storage and use.

Colloids↗
PubMed1983

Parenteral gold in the treatment of rheumatoid arthritis.

For over 50 years, gold therapy has played an important role in the treatment of rheumatoid arthritis. Since 1932, many clinicians and investigators have confirmed the beneficial effects of the water-soluble gold salts, aurothioglucose and gold sodium thiomalate. Gold therapy is indicated for patients with active disease who are not responsive to conservative therapy. To minimize patient risks, contraindications must be considered, and careful clinical and laboratory monitoring must be performed under close supervision by the physician during therapy. Side effects may include vasomotor reactions, dermatitis, stomatitis, leukopenia, proteinuria, nephrosis, and thrombocytopenia. During therapy, one of six patients may have an adverse reaction requiring suspension or termination of therapy. Of the five tolerating gold, one will not benefit, three may have marked improvement, and one may have a remission. The usual recommended dosage schedule is intramuscular injection of 25 to 50 mg of gold salt at weekly intervals until a total of 1,000 mg has been achieved. At this level, gold injections may be spaced biweekly, triweekly, and then monthly for an indefinite period.

Arthritis, Rheumatoid↗
PubMed1983

Liposomes containing colloidal gold are a useful probe of liposome-cell interactions.

A method is described for the preparation of liposomes containing colloidal gold as an electron-dense marker to trace liposome-cell interactions. Since gold sols would precipitate at the high concentrations necessary for loading a large proportion of liposomes, gold sols were formed within preformed liposomes which had encapsulated gold chloride. The optimal conditions for encapsulating the marker were ascertained for liposomes prepared by the method of reverse-phase evaporation. Gold sols formed rapidly at ambient temperature and without organic solvent, and produced homogeneous populations of gold granules inside liposomes. Most vesicles contained the marker, allowing us to determine unambiguously the intracellular fate of liposomes and their contents. The in vitro experiments showed that gold-liposomes were internalized by African green monkey kidney cells in a manner similar to receptor-mediated endocytosis of well-characterized ligands. Preliminary in vivo studies also indicated that liposomes were endocytosed by Kupffer cells via the coated vesicle pathway.

Animals↗
PubMed1986

Effects of ligands on gold inhibition of selenium glutathione peroxidase.

Gold inhibits selenium-dependent glutathione peroxidase (GSH Px) in vitro. Chrysotherapy has been used for over five decades without complete understanding of its pharmacodynamics. This study shows that gold is potentially an inhibitor of GSH Px in vivo. Reported are conditions for assay of GSH-Px activity showing that the inhibition by gold species can be reversed. The study demonstrates the high affinity of gold for the selenohydryl-active site of GSH Px relative to the affinities of other physiological ligands; GSH Px was inhibited to a greater extent by a small molecular-weight fraction isolated from kidneys of gold-treated rats than by the fraction isolated from kidneys of rats not treated with gold. The data provide a new perspective on the action of gold-containing drugs in vivo.

Animals↗
PubMed1989

Direct neuronal and macroglial versus indirect macrophagic labeling in transplants of fetal neural tissue incubated with gold particles.

In a recent light microscopic study based on the transplantation of fetal cells previously incubated with gold-loaded Sendai viruses, S. C. Ardizzoni, A. Michaels, and G. W. Arendash (1988, Science 239: 635-637) proposed that fetal neurons could migrate out into an adult host brain. This result was puzzling in view of several previous contradictory studies, and the light microscopic identification of labeled cells as neurons could be questioned. The present study was therefore undertaken to replicate this study but using electron microscopy to definitely identify migrating gold-labeled elements. Analysis was performed in a model of thalamic transplantation in which previous labeling studies, using thymidine or horseradish peroxidase, had failed to demonstrate any neuronal migration. Gold particles combined with wheat germ agglutinin peroxidase were used to label the fetal tissue prior to transplantation. Fetal cells did incorporate the protein gold complex, and the gold particles were visualized in transplants up to at least 2.5 months after grafting. Electron microscopy analysis reveals that the gold particles are internalized and retained in the lysosomes of grafted neurons and glial cells. In no transplant could labeled grafted neurons be observed intermingled with host neurons, outside the limits of the transplant. In contrast, heavily labeled macrophages were observed surrounding the transplants and sometimes migrating away from the transplant-host interface into the host tissue. These macrophages, presumably of host origin, can be recognized at the light microscopic level by their yellowish staining, a cellular characteristic already noted by Ardizzoni et al. for gold-labeled migrating elements.

Animals↗
PubMed1984

Immuno-gold labeling for flow cytometric analysis.

Colloidal gold particles coated with goat anti-mouse immunoglobulin antibodies were used to analyse surface antigens on various cell types by flow cytometry. The gold-labeled cells showed an increasing signal amplification in the 90 degree light scatter with increasing wavelength of the incident laser light, reaching a more than 10-fold amplification at 632.8 nm. This wavelength was provided by a 0.5 mW helium-neon laser. The magnitude of the signal amplification due to the gold label as well as the specificity of the label was sufficient for quantitative discrimination between positive and negative cells. Cell viability was not affected by the gold label. Mouse spleen cells were labeled with various combinations of FITC- and gold-conjugated antibodies. It was found that the gold and fluorescent labels did not interfere with each other. Colloidal gold may thus be used as an additional label for multiparameter cell analysis and sorting. Biparametric cell analysis/sorting of surface antigen-labeled cells (label versus low-angle scatter) becomes possible even with a low energy helium-neon laser.

Animals↗
PubMed1986

Receptor-mediated endocytosis of GnRH analogs: differential processing of gold-labeled agonist and antagonist derivatives.

The hypothalamic decapeptide, GnRH, stimulates LH and FSH release from pituitary gonadotrophs. Many synthetic peptide analogs, both agonist (GnRH-A) and antagonist (GnRH-AT), have been developed which bind specifically to the GnRH receptor. We have utilized highly potent GnRH-A and GnRH-AT analogs labeled with 18 nm colloidal gold to analyze ultrastructurally the events of binding and interiorization of these specific ligands by gonadotrophs in vitro. To examine internalization of GnRH-A-gold, gonadotrophs were cooled to 4 degrees C and equilibrated with the ligand for 1 h. Next, the cells were either fixed immediately or warmed to 37 degrees C for various times (5, 15 and 30 min) and prepared for electron microscopy. For GnRH-AT-gold, which binds slowly at 4 degrees C, the ligand was incubated with gonadotrophs at 37 degrees C for 15, 30 and 60 min, and the cells were processed for electron microscopy at each time point. In both cases, control gonadotrophs were also incubated in an excess of GnRH-A and GnRH-AT, respectively, in the presence of the gold-conjugated ligands. The results indicated that GnRH-A-gold was bound and rapidly internalized via a receptor-mediated endocytic pathway. GnRH-AT-gold was also bound but showed only limited entry into gonadotrophs; the percentage of intracellular GnRH-AT-gold in gonadotrophs was the same as in other pituitary cells contaminating the gonadotroph fraction and did not increase with time. In the gonadotroph, binding of the specific antagonist ligand to GnRH receptors does not stimulate its interiorization, in contrast to the rapid endocytosis and processing of the agonist ligand. These data suggest that specific ligand internalization requires prior receptor activation, and that GnRH-AT which does not activate the receptor remains bound at the cell surface for a prolonged period.

Animals↗