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Infrared gold alloy brazing on titanium and Ti-6Al-4V alloy surfaces and its application to removable prosthodontics.

PURPOSE: This study investigated the area size of the flow of a gold braze alloy on commercially pure titanium and Ti-6Al-4V alloy plates, and elemental composition at the interface was determined. In the second part of this study, the tensile strengths of titanium plates brazed using a gold alloy were investigated. MATERIALS AND METHODS: Chips of Type IV gold alloy and silver braze alloys were melted onto commercially pure titanium and Ti-6Al-4V surfaces in a dental infrared radiation unit. Flow area of each braze alloy was measured using a digital image analyzer. Tensile specimens (n = 5) were also prepared by infrared brazing using the braze alloys. Five specimens for each combination of the two titanium plates and the two braze alloys were subjected to tensile loading using a Universal testing machine. Electronprobe microanalysis of x-rays at cross-section of the brazed joints to determine elemental composition across the interface, as well as scanning electron microscopic observation at the fracture surfaces, were also conducted. RESULTS: The braze alloys flowed well and spread over the Ti and Ti-6Al-4V plates. Braze alloy type significantly influenced flow, and the gold alloy flowed less on the titanium materials. The mean tensile strengths of Ti and Ti-6Al-4V plates brazed using the gold braze alloy were 219 MPa and 417 MPa, respectively. The fracture surfaces of Ti-6Al-4V specimens with the gold braze alloy exhibited typical ductile behavior. Ti with the same braze alloy showed brittle surfaces. A greater concentration of Cu was found at the Ti with gold braze interface. CONCLUSION: The flow and the tensile strength of the gold alloy coating on titanium surface by means of an infrared brazing is adequate for dental use.

Alloys↗

Interferon-gamma secreted from peripheral blood mononuclear cells as a possible diagnostic marker for allergic contact dermatitis to gold.

10% of patch-tested patients have a positive reaction to gold. Most lack clinical symptoms, but allergic contact dermatitis (ACD) to gold is increasing. In this study, 77 dermatological outpatients were divided into 3 groups depending on epicutaneous patch test outcomes: a group positive to gold (EPI+), a group negative to gold (EPI-), and a group with irritant reactions to gold (EPI-IR). Lymphocytes were stimulated in vitro with gold sodium thiosulfate. Proliferation was assessed using the lymphocyte transformation test (LTT), and cytokine secretion was assessed using a multibead array (Luminex; Linco Research Inc., St. Charles, MO, USA), in order to evaluate whether an in vitro method with high diagnostic accuracy could be devised. The EPI+ group showed a significantly increased secretion of interferon (IFN)-gamma, interleukin (IL)-2, and IL-13 and also showed a significantly higher stimulation indexes for LTT, compared to the other 2 subject groups. Sensitivity and specificity were calculated for all methods individually and combined, but IFN-gamma assessment alone was the most accurate method for identifying ACD to gold, with sensitivity and specificity of 81.8% and 82.1%, respectively. This method also identified 87.5% of the EPI-IR subjects as non-allergic. Therefore, assessment of secretion of IFN-gamma should be a valuable complement to patch test for diagnosing gold allergy.

Adult↗

Colloidal gold and biotin-avidin conjugates as ultrastructural markers for neural antigens.

The use of two new reagents, biotin-avidin conjugates and colloidal gold particles, for ultrastructural immunocytochemistry has been reviewed, and their potential for immunocytochemistry in the central nervous system has been discussed. Although these compounds have been used very little in the C.N.S. in the past, with their high sensitivity, versatility, and potential for simultaneous localization of two antigens with two electron dense markers, these reagents may prove very useful for answering a number of neural questions. Colloidal gold adsorbed to immunoglobulins can be used for light microscopic observation, and owing to its high electron density and ability to readily adsorb to immunoglobulins, protein A, and antigen-carrier complexes, it also serves as an excellent immunomarker at the ultrastructural level. Several procedures have been described for the use of pre- and post-embedding immunostaining with colloidal gold particles. Different size gold particles, adsorbed to different antibodies can be used for pre- and post-embedding staining of different antigens in the same tissue. While at the light microscopic level only the large particles are visible as a pink haze, a fluorescent step can be added to allow easy identification and characterization of neurones labelled with any size colloidal gold, even if the pink colour of the gold is not visible. These same sections can subsequently be studied ultrastructurally. Unlike enzymatic methods, gold particles have less tendency to obscure ultrastructure. Biotin can be easily conjugated to immunoglobulins and, due to its high affinity for avidin (10(15) M-1) which has four biotin binding sites, can be localized with avidin markers, or biotin-avidin-marker complexes. Some procedures such as the avidin-biotin-peroxidase complex are extremely sensitive. Biotin and avidin can be bound to a number of different markers including peroxidase, colloidal gold, and ferritin. Photomicrographs from our hypothalamic work have been used to illustrate the histological results of some of the procedures described.

Animals↗

Association of different HLA antigens with various toxic effects of gold salts in rheumatoid arthritis.

An association of gold induced proteinuria with HLA-D(R)3 has been reported. To investigate other possible relationships between gold toxicity and HLA antigens we studied 85 patients with rheumatoid arthritis (RA) divided into four subgroups: patients with gold induced interstitial pneumonitis, mucocutaneous lesions, proteinuria, and patients without gold toxicity. The HLA frequencies in patient groups and 283 healthy controls were compared in different pairwise combinations. Gold induced pneumonitis was associated with HLA-B40 and Dw1. An association between gold induced proteinuria and HLA-Dw3 was also seen. The increased prevalence of Dw4 in RA was observed only in the control patient group without gold induced side effects. The frequencies of HLA-B7 and Dw2 were decreased in all patient groups compared with the control population. These results further support the view of the heterogeneity of RA as manifested by the unique HLA associations with resistance and susceptibility to gold induced side effects characterising different subgroups.

Adult↗

Stabilization of gold nanoparticles by hydrophobically-modified polycations.

Surface-modified gold nanoparticles have pronounced benefits in the biomedical field due to their significant interaction with delivery materials. In the present study we used hydrophobically-modified polycations (i.e., N-acylated chitosan) to stabilize gold nanoparticles. Aliphatic hydrophobic groups, having carbon chains of different lengths, were first grafted onto the backbone of chitosan by N-acylation with fatty-acid chlorides in order to increase its hydrophobicity. Gold nanoparticles stabilized with native chitosan and N-acylated chitosan were prepared by the graft-onto approach. Chemical modification and its quantification were studied by Fourier-transform infrared (FT-IR) spectroscopy. Further, the stabilized gold nanoparticles were characterized by different physico-chemical techniques such as UV-Vis, FT-IR, TEM, TGA and DLS. Spectral studies of gold nanoparticles show the backbone and the side chain functional groups of chitosan were not cleaved during the conjugation process. TEM observations revealed that the modified chitosan gold nanoparticles were well dispersed and spherical in shape with average size around 10-12 nm in triply-distilled water at pH 7.4, whereas the native chitosan gold nanoparticles appeared as clusters with 9.9 nm as average diameter and were dispersed only in dilute HCl. The size of modified chitosan gold nanoparticles varied depending on the length of grafting molecules.

Biocompatible Materials↗

Effect of gold sodium thiomalate and its thiomalate component on the in vitro expression of endothelial cell adhesion molecules.

Endothelial adhesion molecules play an important role in the tissue recruitment of leukocytes in inflammatory conditions such as rheumatoid arthritis. We have investigated the effect of the antirheumatic drug gold sodium thiomalate on adhesion molecule protein and mRNA expression in cultured human endothelial cells. Gold sodium thiomalate inhibited cytokine (TNF, IL-1, IL-4)-stimulated expression of vascular cell adhesion molecule-1 and E-selectin but not intercellular adhesion molecule-1 on endothelial cells. Gold sodium thiomalate also suppressed TNF-stimulated increases in vascular cell adhesion molecule-1 and E-selectin mRNA levels but had no effect on intercellular adhesion molecule-1 mRNA. Thiomalate (mercaptosuccinate), but not gold thioglucose or D-penicillamine, mimics the effect of gold sodium thiomalate at equimolar concentrations. We propose that the inhibition of vascular cell adhesion molecule-1 and E-selectin expression by gold sodium thiomalate is due to its thiomalate and not its gold component. Gold sodium thiomalate has a direct effect on endothelial adhesion molecule expression, and this may contribute to its antiinflammatory activity.

Animals↗

Adsorption of horseradish peroxidase, ovomucoid and anti-immunoglobulin to colloidal gold for the indirect detection of concanavalin A, wheat germ agglutinin and goat anti-human immunoglobulin G on cell surfaces at the electron microscopic level: a new method, theory and application.

A method is described for the adsorption of selected macromolecules to colloidal gold which is then used as an electron dense marker for the indirect detection of specific cell surface molecules. Membrane bound concanavalin A, which binds specific sugars on horseradish peroxidase, and wheat germ agglutinin, which binds specific sugars on ovomucoid are detected indirectly with gold labeled horseradish peroxidase and ovomucoid, respectively. Goat anti-human IgM on blood lymphocytes is detected with gold labeled rabbit anti-goat IgG. In the preparation of colloidal gold labeled proteins, the problems of flocculation of colloidal gold by proteins and nonadsorption of proteins to colloidal gold, are solved through a combination of concentration of protein and pH variable adsorption isotherms, which allows one to determine the conditions for adsorption of proteins to colloidal gold. Adsorption is pH dependent, the pH conditions correlating with the isoelectric point(s) of the major protein fraction(s); adsorption is influenced by interfacial tension, solubility and by the electrical charge on the molecules. Colloidal gold is inexpensive and preparation of a useful label is rapid, reproducible and the results easily quantitated from electron micrographs.

Animals↗

A double-immunostaining procedure using colloidal gold, ferritin, and peroxidase as markers for simultaneous detection of two hypophysial hormones with the electron microscope.

For simultaneous ultrastructural localization of intracellular peptides, protein A-gold techniques or immuno-gold techniques have generally been applied. The present study reports a double immunostaining procedure for simultaneous visualization of two hypophysial hormones (prolactin and corticotropin) on a single ultrathin section of the pars distalis of an amphibian. Prolactin and corticotropin antisera were respectively raised in guinea pigs and rabbits and were applied simultaneously to ultrathin sections. Antigenic binding sites were detected under the electron microscope using differently labeled species-specific secondary antisera raised in goats or sheep. Three labels (gold particles, ferritin, peroxidase) were checked for double labeling. The combinations investigated were: 1) two gold preparations or IgG-gold labeled with different-sized gold particles; 2)IgG-gold and IgG-ferritin; 3) IgG-gold and IgG-PAP (peroxidase-antiperoxidase). The double-immunostaining procedures described here have proved useful in the simultaneous ultrastructural localizations of two intracellular antigens on a single tissue section. These procedures constitute a basis for the development of triple immunostaining methods.

Adrenocorticotropic Hormone↗

Morphometric analysis of gold particles in low-label cell compartments.

Quantitative estimation of the binding of gold-conjugated ligands to various cell organelles has become a commonly used method to quantify the amount of ligand-binding sites associated with those organelles. However, often a small percentage of organelles is labeled or the density of gold labeling is low. We have defined the "gold-labeled region" as a zone that has a boundary defined by the localization of the outermost gold particles. Such a phenomenon was recently observed in a study of the internalization of gold-labeled native surfactant into lamellar bodies of cultured pulmonary type II cells. We estimated the size and density of gold-labeled regions in lamelar bodies using a simple stereological approach and demonstrated that the low percentage of gold-labeled organelles can be explained as a result of the probability of random selecting through the labeled areas. Our method, which permits use of transmission electron microscopy to calculate the true parameters of gold-labeled regions, can significantly facilitate analyses of ligand binding to various cell compartments.

Animals↗

Rheumatoid arthritis, gold therapy, contact allergy and blood cytokines.

OBJECTIVE: To study the clinical and biochemical effects of a low starting dose for gold therapy in rheumatoid arthritis patients with a contact allergy to gold. METHODS: Serum cytokines were assayed before and 24 h after the first injection of gold sodium thiomalate (GSTM). RESULTS: Contact allergy to gold was found in 4 of 19 patients. Compared to gold-negative patients (starting dose: 10 mg GSTM), there was a larger increase in serum TNFalpha (p < 0.05), sTNF-R1 (NS), and IL-1 ra (p < 0.05) in gold-allergic patients. CONCLUSIONS: Cytokines are released in blood by GSTM in RA patients with gold allergy. To minimize the risk of acute adverse reactions the starting dose of GSTM should be lowered to 5 mg. Alternatively, patients should be patch-tested before gold therapy; in test-positive cases, 5 mg is recommended as the first dose.

Adult↗

Evaluation of alternative alloys to type III gold for use in fixed prosthodontics.

A study was done to evaluate the fit of castings made from commercially available alloys promoted by their manufacturers as cheaper alternatives to type III gold for use in fixed prosthodontics. Two nickel-chromium alloys, two silver-palladium alloys, two gold-silver-palladium alloys, a 50% gold alloy, and a type III conventional gold alloy (used as a basis of comparison) were evaluated. After optimum conditions for waxing, investing, and casting were determined experimentally, four crowns (two full crowns and two three quarter crowns) were cast from each alloy. The castings were cleaned by pickling or sandblasting and placed on their respective dies. Only one casting was made from each die. Ten judges were asked to evaluate the marginal fit and completeness of each casting on its die. The judges rated each casting and the ratings were converted into rankings. Type III gold and Forticast tied and were ranked first; Paliney CB was ranked second; Alborium and Albacast tied and ranked third; Aurolite CB was ranked fourth; and Jelenko Experimental and Howmedica III tied and ranked fifth. It was found that the nickel-chromium alloys produced castings that had a tight fit and showed marginal discrepancies even under conditions designed to yield maximum expansion of the investment. These nonprecious metal castings were judged inferior in terms of fit when compared with castings made from noble metal-and precious metal-containing alloys. Existing investments and techniques were adequate for all castings except those made from the nonprecious alloys. It was concluded that low (approximately lambda 50%) gold alloys and palladium-silver-gold alloys that are commerically available can be used as substitutes for type III gold alloy without any loss inthe quality of casting fit.

Chromium Alloys↗

Lysosomal gold accumulations in pulmonary macrophages.

Although soluble gold has been widely used in the treatment of rheumatoid arthritis, little is known about the distribution of gold deposits in extra-articular tissues. In the synovial lining cells and articular cartilage, the morphology of lysosomes containing gold, the aurosomes, is well documented. Because gold may cause pulmonary injury, the morphology and distribution of gold deposits in pulmonary tissue should be recognized. We found morphologically typical aurosomes with electron-dense membranes and granules, giving the spectrum of gold in electron microprobe analysis, in the interstitial and alveolar macrophages in the open lung biopsies of 3 patients who had received gold treatment but not in 12 patients who had not received gold treatment. In contrast to previous studies, aurosomes were not found in the endothelial cells.

Arthritis, Rheumatoid↗

Gold sodium thiomalate toxicity in cadmium-sensitive and cadmium-resistant Chinese hamster ovary cells.

Gold sodium thiomalate was incubated with one cadmium-sensitive cell line and two cadmium-resistant variants. The resistant lines have been reported to synthesize metallothionein (MT) in response to both cadmium and zinc, whereas the sensitive line does not. All cell lines showed a dose-dependent inhibition of growth as a result of gold sodium thiomalate treatment. However, daily comparisons of cell numbers indicate that the cadmium-resistant lines actually increase in number at the highest gold concentrations, whereas numbers of cells in the nonresistant line decrease. MT biosynthesis was measured by monitoring the incorporation of [35S )cysteine into low molecular weight protein. None of the cells synthesized MT in response to gold. When incubated with both zinc and gold, MT was synthesized by both of the cadmium resistant lines; however, the amount of MT synthesized was reduced in the presence of gold which appears to inhibit the uptake of [35S]cysteine by all the cell lines. Although MT is synthesized in the presence of zinc and gold sodium thiomalate, the MT does not have a significant effect on the ability of these cells to withstand high concentrations of gold.

Animals↗

Allergic contact dermatitis to gold.

Gold is a relatively common allergen that appears to induce dermatitis about the face and eyelids, as well as at sites of direct cutaneous contact. In this study, 355 patients with suspected contact dermatitis were evaluated; 17 (4.8%) were found to be allergic to gold. Fifteen of these 17 patients were re-evaluated at > 2 months after patch testing. When contact with gold jewelry was discontinued, 7 of 15 (46.7%) of the gold-allergic patients reported that their dermatitis cleared. In 3 of 7 patients (42.9%), discontinuing contact with gold jewelry was the only modification to their behavior; whereas in 4 of 7 (57.1%), discontinuing contact with gold jewelry and other documented allergens was necessary to affect resolution. Despite continuous contact with gold (jewelry and/or dental appliances), 7 of 15 (46.7%) of our patients had complete clearing of their symptoms by avoiding other documented allergens. None of our patients required the removal of dental gold.

Adult↗

Longterm therapy of psoriatic arthritis: intramuscular gold or methotrexate?

OBJECTIVE: To compare the efficacy and toxicity of methotrexate (MTX) and intramuscular (im) gold in the treatment of psoriatic arthritis (PsA). METHODS: Medical records from all patients with PsA attending the gold and MTX clinics at the Vancouver Mary Pack Arthritis Centre between 1971 and 1995 were reviewed. The odds of a clinical response (defined as at least a 50% reduction in active joint count from initial to last visit or for at least 6 months) and the relative risk of discontinuing therapy associated with treatment (MTX or im gold) were calculated after controlling for significant baseline covariates, using logistic regression and Cox regression analyses, respectively. The frequency of side effects and the reasons for treatment cessation were also compared between treatment groups. RESULTS: Eighty-seven patients received 111 treatment courses: 43 of MTX and 68 of im gold. The likelihood of a clinical response was 8.9 times greater (95% CI 1.8; 44.0) with MTX than im gold. Patients were 5 times more likely (95% CI 2.4; 10.4) to discontinue therapy with im gold than with MTX. No major toxicity occurred and frequency of side effects was similar for both treatments. Patients with a longer duration of PsA prior to initiation of study treatment were less likely to achieve a clinical response. CONCLUSION: MTX and im gold are safe and well tolerated in the treatment of PsA. In our experience. MTX was superior to im gold in the likelihood of achieving a clinical response and in permitting an individual to continue longterm treatment. Our data suggest that earlier treatment may be associated with a better response.

Administration, Oral↗

Preclinical tolerance and pharmacokinetic assessment of MU-Gold, a novel chemotherapeutic agent, in laboratory dogs.

MU-Gold, tetrakis (trishydroxymethyl) phosphine gold(I) chloride, a novel gold compound, has cytotoxic effects against human androgen-dependent and -independent prostatic, gastric, and colonic carcinoma in cell culture and against malignant lymphoma in rodent models. A pilot study was conducted to evaluate the tolerance and pharmacokinetic properties of MU-Gold in normal dogs in anticipation of clinical trials in cancer-bearing dogs. MU-Gold (10 mg/kg) was administered by i.v. injection to three purpose-bred dogs. Serum was collected from all dogs for measurement of gold levels via atomic absorption spectrometry. In addition, complete blood counts and biochemical profiles were monitored for Dogs 2 and 3 every 7 days for 30 days. A two-compartment i.v. bolus model with first-order kinetics, mean elimination half-life of approximately 40 hours, and mean volume of distribution of 0.6 L/kg was established. Serum gold concentrations ranging from 10 to 50 mcg/ml were sustained for 2 to 3 days with no clinically significant toxicities observed. Based on in vitro results in earlier studies and preliminary pharmacokinetic data collected in the present study, Phase I clinical trials should be conducted to define the optimal dosage, dose-limiting toxicities, and other characteristics of MU-Gold that will be used to design Phase II clinical trials.

Animals↗

Injectable gold dermatitis and proteinuria: retreatment with auranofin.

Seven female patients with classical rheumatoid arthritis (RA), treated successfully with injectable gold salts (Fosfocrisolo ICI, 0.10 g/week, with a serum gold concentration of 200-400 mcg/dl), experienced severe gold side-effects after 3 to 20 months of therapy, requiring their withdrawal from gold despite the good results in both clinical and laboratory findings. Four patients showed mucocutaneous side-effects (2 dermatitis and 2 stomatitis) and three a moderate or severe proteinuria. Renal biopsy was performed in these patients, with a histological picture of membranous glomerulonephritis referable to gold therapy. Remission inducing drug (R.I.D.) therapy being mandatory in patients with a chronic progressive disease, and in view of the previous efficacy of gold salts, the patients were put on oral gold, Auranofin being administered 3 mg b.i.d. Both the mucocutaneous side-effects and the proteinuria ameliorated within 2 to 6 months, and the remission of the disease was maintained. The chemical and pharmacokinetic differences between the above two gold compounds are discussed.

Adult↗

Determination of gold in animal tissue by graphite furnace atomic absorption spectrophotometry.

Historically, compounds that contain gold have been used to treat conditions such as rheumatoid arthritis in humans. However, understanding of the metabolic fate of gold in biological tissues has been limited by lack of sensitive quantitative methods of analysis. We addressed this problem by developing a graphite furnace atomic absorption (GFAA) spectrophotometric method to measure trace amounts of gold. This method was validated on small samples of beef liver, kidney, and bone. The samples were digested in micro-Kjeldahl flasks with a mixture of sulfuric, perchloric, and nitric acids; the residue was treated with aqua regia and extracted into methylisobutyl ketone (MIBK); levels of gold were then measured by GFAA. All the reagents were of an ultra-pure grade and were monitored for gold content. We established that the linear range of quantitation was from 1 to 2500 ppb. Multiple extractions with MIBK were not necessary to recover all the gold, and, in most cases, use of ultra-pure acids was not necessary. A scan of the extracts by inductively coupled argon plasma atomic emission spectrophotometry revealed no appreciable concentration of elements that would be most likely to interfere with the determination of gold. Average recoveries of gold ranged from 102 to 111%, and the overall coefficient of variation was 5.5%.

Animals↗