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PubMed2004

In vivo inflammatory and wound healing effects of gold electrode voltammetry for MEMS micro-reservoir drug delivery device.

The in vivo biocompatibility and biofouling of gold electrodes for a microelectromechanical systems drug delivery device were investigated in a rodent model. The role of the applied voltage and gold electrolysis products in modulating the inflammatory response (biocompatibility), and the temporal adhesion of cellular populations onto macroscopic gold film electrodes (biofouling) were analyzed in reference to two controls, devices to which voltage was not applied (uncorroded) or voltage was applied to inert platinum electrodes (electrical controls). Voltammetry was applied to the gold surfaces once (day 4, 7, 14, 21, 28, 35, 42, or 49), while voltage of identical magnitude was applied to the electrical controls. An inflammatory response characterized by a rapid decrease of leukocyte concentration to control levels was observed 48 h following voltage application with no significant cell concentration difference (p > 0.05) between the corroded devices and electrical controls. The histological evaluation of the direct implant fibrous capsule showed comparable thickness of voltage applied and control specimens. The gold corrosion peak current showed no significant difference (p > 0.05) among peak values at all time points. It was concluded that gold electrode corrosion was biocompatible and its electrochemical performance was not hindered by fibrous capsule formation.

Animals↗
PubMed2006

Forming microstructured alkanethiol self-assembled monolayers on gold by laser ablation.

A process to form microstructured alkanethiol self-assembled monolayers (SAMs) on gold is described. It is well known that alkanethiols spontaneously form homogenous SAMs on gold surfaces. By means of laser ablation, the exposed areas of alkanethiol monolayers can be removed from the gold surface. Free gold is obtained which can react further with second and third thiols. By this technique, structured alkanethiol SAMs are obtained reliably and easily. In a rather narrow window of pulse intensities, in our example 120 MW/cm2 +/- 10% from a frequency-doubled Nd: YVO4 laser with 6-ns pulsewidth operating at a repetition rate of 20 kHz, ablation of alkanethiol monolayers is obtained without causing any damage to the gold substrate. Examples are presented where lines down to 10 microm in width were laser ablated into an SAM formed either from a hydrophilic or a hydrophobic alkanethiol and filled with a monolayer of a second alkanethiol of opposite hydrophilicity. The patterned structures were examined by optical and fluorescence microscopy as well as by lateral force microscopy. The presented method enables the preparation of microstructured SAMs on gold and probably on a wide variety of other substrates.

Alkanes↗
PubMed1986

Thrombocytopenia associated with gold therapy: a drug-induced autoimmune disease?

We studied 13 patients with rheumatoid arthritis (RA) and gold-induced thrombocytopenia. Platelet-specific autoantibodies of the IgG and often also of the IgM class were detected by immunofluorescence on the patient's platelets and in ether eluates from these platelets. In nine patients we also detected autoantibodies in the serum. The antibodies were unreactive with platelets from patients with Glanzmann's disease in most cases, and were not EDTA dependent. Thus, they had the serological characteristics of true autoantibodies. The reaction of the antibodies with platelets was not influenced by the addition of extra gold. By atomic absorption spectrophotometry we found that the ether eluates, which were often strongly reactive with donor platelets, were free of gold. This indicated that the autoantibodies in the thrombocytopenic patients were not dependent on gold for their reaction. The possibility is raised that gold treatment of rheumatoid arthritis patients induces or enhances the formation of platelet-specific autoantibodies, and that gold-induced thrombocytopenia is a drug-induced autoimmune disease.

Arthritis, Rheumatoid↗
PubMed1993

Gold in the dermis following chrysotherapy: histopathology and microanalysis.

Paraffin-embedded sections of skin from patients with rheumatoid arthritis treated with gold who had developed skin rashes were examined by light microscopy and scanning electronmicroscopy with microanalysis. Sparse, small, brown or black granules in plump, often elongated cells in the dermis were shown to contain gold by energy dispersive X-ray microanalysis. These cells expressed some macrophage markers. The amount of gold present showed some correlation with the total gold dose. Gold was not confined to lesional skin. In one case where uninvolved skin was examined, more gold was found there than in lesional skin.

Aged↗
PubMed1981

Colloidal gold markers and probes for routine application in microscopy.

Colloidal gold can be used as an electron-dense cytochemical probe for direct or indirect labelling techniques. Gold markers can be prepared in a size range of 5-150 nm, and show size-dependent shape characteristics and absorption spectra. Size and shape distribution increases with mean particle diameter, with appreciable overlapping between populations of different mean size. Using radio isotope-binding assays, spectrophotometric analysis and an innovative rapid microtitration technique, the effect of pH, ionic strength and protein concentration on gold-protein interaction has been studied. Efficient adsorption of protein to gold occurs at, or near, the pI of the protein. The amount of protein needed to effect stabilization is both a function of pH and of ionic strength, but does not reflect the amount of protein binding for all proteins. There is evidence for multilamellar adsorption of proteins to gold, which is discussed in context of the bioactivity, and stability of the probe. A working protocol for the routine reproducible manufacture of protein-gold probes is given, making use of the microtitration assay.

Colloids↗
PubMed1983

Gold-containing drugs and the control of proteolytic enzymes.

1 NaAuCl4 and aurothioglucose inhibited trypsin in free solution without the need of a carrier molecule. 2 NaAuCl4, aurothioglucose, aurothiomalate, auranofin and chloro-triethyl phosphine) gold all inhibited the trypsin-like neutral protease on the surfaces of Ehrlich ascites tumour cell membranes equally well. 3 Crude cathepsin preparations were activated by low concentrations of dithiothreitol and also by aurothioglucose, due to the displacement of an inhibitor. 4 Thiol-activated cathepsins were inhibited by each of the gold derivatives. The gold could be withdrawn from the enzyme by incremental additions of thiols such as reduced glutathione and cysteine with regeneration of enzymic activity. 5 Lineweaver-Burk plots of kinetic data indicated that gold acted as a non competitive inhibitor of cathepsins. 6 A naturally occurring inhibitor of cathepsins was extracted from cartilage. The mechanism of inhibition was again shown to be a thiol-disulfide exchange, the disulphide being provided by the inhibitor and the thiol being provided by the enzyme. 7 The role of gold in the attempted control of proteolysis in the rheumatoid arthritis is briefly discussed in terms of reversible exchange reactions involving gold thiols, disulphides and cartilage inhibitors of proteolytic enzymes.

Aminopeptidases↗
PubMed1996

Comparison of gold versus platinum electrodes on myocardial lesion size using radiofrequency energy.

During radiofrequency (RF) catheter ablation of arrhythmias, temperatures that approach 100 degrees C cause a coagulum to form on the ablation electrode that results in an increase in electrical impedance and prevents further energy delivery. Since gold has nearly four times the thermal conductivity as platinum, the metal commonly used, it was postulated that gold tip electrodes could deliver more power and produce deeper lesions because of its greater heat dissipation from the electrode-tissue interface to the circulating blood. To test this hypothesis, RF energy was applied to fresh bovine ventricular myocardium using 6 French catheters with 2-mm long distal electrodes made from gold or platinum. Similar studies were also conducted using 7 French catheters with 4-mm long distal electrodes. Maximum lesion depth was defined as that produced with the level of energy just below that causing an impedance rise. A maximum lesion depth of 6.2 +/- 0.7 mm (mean +/- SD) was obtained with the gold 2-mm electrode and 4.7 +/- 0.5 mm with the platinum electrode (P = 0.003). The 4-mm gold electrode produced a maximum lesion depth of 7.2 +/- 1.4 mm, while a catheter with a 4-mm platinum electrode caused a maximum lesion depth of 5.8 +/- 0.7 mm (P = 0.05). We conclude that deeper lesions should be able to be made when RF energy is delivered to a gold rather than platinum tip electrode.

Animals↗
PubMed1999

The flare-up reactions after systemic provocation in contact allergy to nickel and gold.

In a controlled double-blind experimental study, patients with contact allergy to nickel or gold were exposed systemically to their contact allergen. Nickel sulfate was given orally, gold sodium thiomalate intramuscularly, and placebo by both routes. Clinical reactions including body temperature were followed and 7 plasma cytokines and acute phase reactants were assayed before and 24 h after provocation. Clinical flare-up, with reactivation of healing patch tests and/or toxicoderma-like reactions, was observed in patients receiving their specific allergen. A transient fever was noted in patients allergic to gold when exposed to gold, not in others. There was a significant increase in plasma tumour necrosis factor-alpha, soluble tumour necrosis factor receptor 1, interleukin-1 receptor antagonist, and neutrophil gelatinase associated lipocalin in patients allergic to gold when exposed to gold allergen. Furthermore, in patients allergic to nickel exposed to nickel allergen there was a highly significant increase in plasma soluble tumour necrosis factor receptor 1. Interferon-gamma, interleukin-4, and C-reactive protein did not increase in any of the patient groups. Clinical reactions during flare-up in contact allergy are accompanied by release in the blood of several cytokines. This release is not a consequence of a toxic effect or bound to a particular allergen. Instead, the cytokine release should be considered a general phenomenon characteristic of the flare-up in contact allergy.

Acute-Phase Proteins↗
PubMed1982

Corrosion of gold alloys and titanium in artificial saliva.

Two types of gold alloys and one type of pure titanium have been submitted to corrosion in artificial saliva for periods of up to about 2 months. The release of copper, gold or silver from the gold alloys as well as titanium from the titanium matrix was measured with nuclear tracer technique. The physical/chemical state of the corrosion products of gold alloys referring to the ionic state or presence in particulate form has been examined retaining the particulate matter on a glass filter. Copper was observed to be mainly present in the ionic state. Considerable amounts of gold were observed to be retained on the glass filter explained by the presence of gold in particular form or as a component of a dispersed colloidal phase. The estimation of the release of titanium was registered by the tracer nuclide 46Sc assuming particulate matter to be deteriorated from the titanium surface.

Chemical Phenomena↗
PubMed1985

Auranofin treatment of rats: adaptation to intestinal adverse effects and observations on the cytosolic distribution of gold in the intestines, liver and kidneys.

The possibility of development of adaptation to intestinal adverse effects of auranofin (AF), a gold-containing anti-arthritic drug, was investigated in rats. Groups of 6 rats received orally 0.0, 2.5 or 10.0 mg AF/kg daily for one week, and 20.0 mg AF/kg daily the next week. During the first week all animals had normal stools. During the second week, those on 0.0 or 2.5 mg AF/kg the preceding week developed persistent loose stools, whereas those on 10.0 mg AF/kg the preceding week did not. At the end of the second week, no differences in the intestinal cytosolic gold concentrations were detected, which could be related to the dose regimen or the loose stools. Gel filtration profiles of gold from intestinal, liver and kidney cytosols following AF treatment, were compared with gold profiles following in vitro incubation of AF with cytosols obtained from non-treated rats. In the in vivo situation, but not in vitro, gold peaked with proteins of mol. wt. about 10,000 in the small intestine and kidneys. Up to 20% of the cytosolic gold was recovered in these fractions in the small intestine. These proteins eluted slightly different from metallothionein on gel filtration. The cellular mechanisms involved in the demonstrated adaptation to intestinal adverse effects from AF, are not clear, judged from the present study.

Animals↗
PubMed2005

Attenuation of stress-elicited brain catecholamines, serotonin and plasma corticosterone levels by calcined gold preparations used in Indian system of medicine.

Problems associated with mental health have increased tremendously in modern times. The search for effective and safe alternatives should, therefore, be pursued vigorously. Forced immobilization is one of the best explored models of stress in rats and the role of corticosterone, serotonin (5-HT) and catecholamines, i.e. norepinephrine, epinephrine, dopamine is well documented. We investigated the therapeutic potential of two gold preparations (Ayurvedic Swarna Bhasma and Unani Kushta Tila Kalan) in restraint induced stress at different time points of 1 hr, 2 hr and 4 hr. We pretreated rats with two gold preparations, Ayurvedic Swarna Bhasma and Unani Kushta Tila Kalan (25 mg/kg, orally for 10 days) prior to restraint stress. Brain catecholamine, serotonin and plasma corticosterone levels were determined following 1, 2 and 4 hr restraint stress, using HPLC and also plasma corticosterone using luminescence spectrophotometry. Gold preparations restored restraint stress-induced elevation in levels of brain catecholamines (norepinephrine, epinephrine and dopmine), 5-HT and plasma corticosterone to near normal levels. Gold, widely used in modern medicine for the treatment of rheumatoid arthritis, is highly valued for various medicinal uses in Indian systems of medicine. Traditional gold preparations are attributed with tonic/rejuvenating and antioxidant properties. Our earlier studies revealed interesting analgesic, immunostimulant, adaptogenic and glycogen sparing properties in these preparations, but their effects in stress and depression have not been investigated yet. Significant restoration of altered values to near normal levels suggest potentials for gold preparations in stress and depression.

Animals↗
PubMed1990

The effect of gold coating agents on residual stress in alloy-ceramic specimens.

The use of gold coating agents has been claimed to reduce residual stress in alloy-ceramic composites. The purpose of this study was to evaluate the efficacy of gold coating agents in preventing cracking of bonded porcelain. Residual stress in alloy-ceramic specimens could be increased by decreasing the coefficient of thermal expansion (alpha) of the porcelain. Vitadur-N porcelain (jacket crown type, low alpha) was mixed in increasing proportions with VMK porcelain (high alpha) to prepare five test blends with decreasing values for alpha. For each test blend, alpha was measured by means of a vitreous silica dilatometer, and varied from 13.6 x 10(-6)/K to 11.0 x 10(-6)/K. The test blends were fused around spherical specimens of a substrate alloy, Option (alpha = 14.0 x 10(-6)/K), both with and without the use of three gold coating agents, Wilkote, Spectra-Seal and Deck-Gold (normal). The composite spheres were examined under 20 x magnification after 24 hours and again after eight weeks for evidence of cracking. There was no significant difference in the failure rate of the alloy-ceramic specimens with or without any of the gold coating agents. In a bonding porcelain, alpha can be lowered in a controlled manner by the addition of varying amounts of jacket crown porcelain. Cracking of the ceramic coating occurred at and above an alpha mismatch of 1.8 x 10(-6)/K. Gold coating agents have an insignificant effect on residual stress in alloy-ceramic specimens.

Crowns↗
PubMedDate not supplied

Effects of gold and silver backings on the dose rate around an 125I seed.

Measurements of the effect of either gold or silver backing on the dose rate around an 125I seed were performed using a Therados RFA7 dosimetry system and a small diode detector which was 2.5 mm in diameter and 0.06 mm thick. It was found that the presence of the gold or silver backing modifies the diode response on the side of the 125I seed away from the backing. The effect depends on the backing material and the distance from the seed. There is a small increase close to the gold backing but a decrease further away. This decrease at distances greater than 10 mm from the seed is uniformly 10%, the same as found when the seed is backed by air. There is an increase of up to 25% observed with silver backing the seed and this increase remains significant more than 30 mm from the seed. When the response increases, the results are hard to interpret quantitatively because of variations in the diode response per unit dose with photon energy and extreme sensitivity to geometric changes. Nonetheless, except for the increase at close distances with the gold, the results are in agreement with EGS4 Monte Carlo photon transport simulations which are for a simplified geometry and account for x-ray fluorescence from the K-shell. Furthermore, the increase in the gold-backed case is qualitatively explained by Williamson's Monte Carlo calculations which take into account the L-shell fluorescent x-rays from gold.

Brachytherapy↗
PubMedDate not supplied

The effect of lead, gold, and silver backings on dose near 125I seeds.

Brachytherapy for ocular melanoma uses 125I seeds backed by a gold shield. Conflicting results are reported in the literature on the effect of the gold on dose close to the seeds. In this work, a small lucite jig was constructed such that the seed-to-detector separation remained fixed as high-Z materials of lead, silver, and gold were moved in and out of position behind the seed. The jig was clamped in place in the water filled tank of a beam scanning system. The response of two p-type silicon diodes was measured at several distances from the seed with and without the high-Z backings. The response with the high-Z backing relative to water, found to be the same for each diode and the same for lead and gold, decreased from about 1.01 at 1.5 mm to about 0.92 at 20 mm. It has been suggested in the literature that L-shell fluorescent x rays of approximately 10 keV from the gold backing might contribute significantly to the dose within 7 mm of the seed. To test this, the response with the gold backing relative to water was measured with an aluminum cap of 1-mm wall thickness covering the diode. The cap transmits about 70% of the 125I influence but is essentially infinitely thick to 10-keV photons. The relative response (gold/water) was the same with and without the cap showing that the contribution of 10-keV x rays is negligible. Compared to water, the silver backing was found to enhance the diode response by about 14% between 5 to 10 mm from the seed.

Biophysical Phenomena↗
PubMed1987

Long-term treatment of rheumatoid arthritis with sulphasalazine, gold, or penicillamine: a comparison using life-table methods.

Life-table analysis was applied to the records of 317 patients with rheumatoid arthritis (RA) treated with sulphasalazine (SAS), 201 treated with sodium aurothiomalate (gold), and 163 with penicillamine. They comprised all those treated in our department with these drugs between January 1973 and July 1984. Risks of treatment termination for all reasons were similar for each drug at five years (gold 92%, penicillamine 83%, SAS 81%). The risk of treatment termination due to inefficacy was less for gold (29.5%) than for penicillamine (38.1%) or sulphasalazine (41.2%). Adverse effects, however, led to withdrawal of gold in 57%, penicillamine in 41.2%, and SAS in 37%; the most effective drugs appeared most toxic. Serious adverse effects were much more common in association with gold (17.4%) and penicillamine (12.3%) than with SAS (1.6%). Sulphasalazine appears as well tolerated over long periods in RA as gold or penicillamine and is associated with fewer serious adverse effects; of these drugs, it might therefore be considered the agent of first choice.

Actuarial Analysis↗
PubMed1993

Gold induced nephropathy in rheumatoid arthritis and HLA class II genes.

OBJECTIVES: To elucidate the role of HLA-DRB, -DQA, and -DQB genes in patients with rheumatoid arthritis (RA) who developed gold induced nephropathy. METHODS: Southern blot analysis of HLA-DRB, -DQA, and -DQB genes was performed on DNA from 27 patients with RA with gold induced nephropathy, 37 patients with RA who were treated with gold but did not develop nephropathy, and 122 ethnically matched normal subjects. RESULTS: The 4.7 kb DQA1/Taq I band associated with DQA1*0501 and DR3 and DR5 was found in 16 (59%) patients with gold induced nephropathy compared with five (14%) patients without gold induced nephropathy. CONCLUSION: It is concluded that HLA-DQA region genes may be an important susceptibility factor for the development of gold induced nephropathy in patients with RA.

Arthritis, Rheumatoid↗
PubMed2002

Long term efficacy and safety of cyclosporin versus parenteral gold in early rheumatoid arthritis: a three year study of radiographic progression, renal function, and arterial hypertension.

OBJECTIVE: To compare the three year safety and efficacy of cyclosporin and parenteral gold in the treatment of early, active, severe rheumatoid arthritis (RA), and to study the reversibility of cyclosporin associated renal dysfunction in patients who discontinued cyclosporin treatment. METHODS: The patients continued to receive cyclosporin or parenteral gold in an 18 month open extension to an 18 month randomised, parallel group study. The main efficacy variable was blinded evaluation of radiographic progression of joint damage. Safety variables included serum creatinine, calculated creatinine clearance, and blood pressure. RESULTS: Radiographic progression during follow up was similar in both groups. About 60% of the patients in the intention to treat groups (n=272) and about half of the patients in the completer groups (n=114) had definite radiographic progression in joint damage (increases >6 in the Larsen-Dale score), and about one in three also had substantial progression (>18 increase in Larsen-Dale score). Both systolic and diastolic blood pressure were significantly increased in the cyclosporin group compared with the gold group, and 12/139 (9%) versus 3/139 (2%) (p=0.03) had notably raised blood pressure. The mean serum creatinine increased by 28% at the treatment end point in the cyclosporin group as compared with 7% in the gold group. The mean calculated creatinine clearance was reduced by 16% and increased by 1% in the cyclosporin and gold groups, respectively, at the end of the study. At the final follow up visit after discontinuation of cyclosporin (at least three months after treatment was stopped) the mean serum creatinine was increased by 15% and creatinine clearance reduced by 16%. Sustained increases in serum creatinine at this post-treatment end point were mostly seen in patients with a raised serum creatinine during treatment of at least 50%. CONCLUSION: Three year changes in radiographic damage during cyclosporin and parenteral gold were similar in patients with early, active RA. Abnormal renal function and raised blood pressure were often seen in the cyclosporin treated patients.

Activities of Daily Living↗
PubMedDate not supplied

Influence of previous gold toxicity on subsequent development of penicillamine toxicity.

The incidence of penicillamine toxicity was determined in 250 patients who had never previously received gold, 76 patients who had received gold without toxic reaction, and 79 patients with a previous history of gold toxicity. The results suggest that there may be a higher incidence of penicillamine toxicity in patients who have previously shown toxic reactions. The interval between stopping the gold and starting the penicillamine did not influence incidence of toxicity. The development of a rash during gold treatment does not seem to influence the development of a rash during penicillamine treatment, but patients who have had proteinuria or bone-marrow depression during gold treatment may have an increased likelihood of developing a similar side effect with penicillamine.

Arthritis, Rheumatoid↗