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Dental gold alloys and contact allergy.

Contact allergy to gold as demonstrated by patch testing is very common among patients with eczematous disease and seems to be even more frequent among patients with complaints from the oral cavity. There is a positive correlation between gold allergy and the presence of dental gold. Gold allergy is often found in patients with non-specific stomatitides as well as in those with lichenoid reactions or with only subjective symptoms from the oral cavity. The therapeutic effect of substituting other dental materials for gold alloys is conspicuous in casuistic reports but less impressive in larger patient materials. The amount of dental gold is correlated qualitatively and quantitatively to the blood level of gold and the effects if any of circulating blood gold are unknown. There is clearly a need for prospective studies in the field and gold sodium thiosulfate is considered an important item in the dental series for patch testing.

Dermatitis, Allergic Contact↗

Pseudomonas aeruginosa biofilms react with and precipitate toxic soluble gold.

The interaction between biofilms of Pseudomonas aeruginosa PAO1 and 0.01-5 mM gold chloride was investigated using flow-cells. Scanning confocal laser microscopy (SCLM) of these biofilms revealed the formation of two distinct structural features: (i) confluent areas of uniform thickness and (ii) cell clusters which often emerged as 30-40 micro m, tall narrow pillars (or pedestals) of cells and exopolymeric substance (EPS). When 5-day-old, quasi-steady state biofilms (as indicated by the stability of film thickness and overall structure) were exposed to relatively high AuCl3 (i.e. 0.5-5 mM) for 30 min at 20 degrees C, reduction of the auric ion resulted in the formation of both extracellular and intracellular metallic gold colloids, as revealed by transmission electron microscopy (TEM). Most mineralization occurred on cell surfaces with lesser amounts within cells and little throughout the EPS. Little to no mineralization of gold was seen at 0.01-0.1 mM concentrations. As initial AuCl3 concentrations approached 0.5 mM or greater, more gold particles were seen and cell viability, as determined by a BacLight live/dead viability probe, approached zero. At an intermediate concentration of 0.1 mM, the live:dead ratio increased to 4:1. However, when planktonic cells were exposed to this same 0.1 mM concentration, it resulted in a 4-log reduction in viable counts as determined by plating. The higher resistance of biofilm cells to 0.1 mM gold can be attributed to its binding to the EPS and cell surfaces of the biofilm which ensured a (presumably) low effective cytoplasmic concentration of gold (i.e. no gold crystals were seen in cells by TEM). In addition, SCLM revealed the formation of larger extracellular gold crystals at the substratum (coverslip) level of the biofilms, with a higher proportion of crystals detected beneath pillars (cell cluster structures), suggesting the possibility of unique cell types, more reduced microenvironments at the base of each cluster, or a combination of both. These results suggest that the biomineralization of gold is impacted by biofilm structure.

Biofilms↗

Early versus late gold weight implantation for rehabilitation of the paralyzed eyelid.

OBJECTIVES/HYPOTHESIS: The purpose of this study is to evaluate the outcomes and complications associated with early gold weight implantation for management of the paralyzed eyelid. STUDY DESIGN: A retrospective review of clinical charts was conducted to analyze results and complications in patients who underwent gold weight implantation within 30 days of onset of facial nerve paralysis and to compare these outcomes with those of patients who received gold weights after a traditional waiting period. METHODS: The charts of 67 patients who underwent gold weight implantation during the time period of this study were reviewed. Patients were categorized into "early" or "late" groups based on whether gold weights were implanted before or after 30 days following onset of facial nerve paralysis. Etiology of facial nerve paralysis, degree of paralysis, timing of surgery, and outcomes of the procedure, including degree of lid closure and complication rates, were compared between the two groups. RESULTS: Of the 67 patients, 49.3% underwent gold weight implantation within 30 days of onset of paralysis and 50.7% received gold weights after 30 days. A total of 89.2% of all patients who underwent implantation in this study achieved satisfactory lid closure after the initial procedure. Both early and late implantation groups had statistically similar lid closure and complication rates. CONCLUSIONS: Implantation of gold weights within 30 days of paralysis is as effective for the management of paralytic lagophthalmos as delayed implantation and is not associated with higher complication rates. Early implantation of gold weights should be considered in all patients with paralytic lagophthalmos.

Adolescent↗

Percutaneous absorption of gold sodium thiosulfate used for patch testing.

Contact allergy to gold has been shown to be correlated to wearing of golden jewellery as well as to the presence of dental gold. The prerequisite for sensitization and elicitation of an allergic contact dermatitis to gold is ionization and percutaneous absorption of the allergen. The present study was undertaken with the aim to demonstrate gold in blood after an occlusive patch testing with gold sodium thiosulfate (GSTS). Patients were patch tested with GSTS 0.5, 2.0 and 5.0% in petrolatum. Venous blood was sampled before testing as well as on day 3 (D3) or day 7 (D7). Blood gold levels were analysed by inductively coupled plasma mass spectrometry. In all 66 patients, the blood level of gold was significantly higher in the 2nd blood sample than in the 1st (median 0.34 versus 0.03 micro g/l). The increase was similar in patients allergic and not allergic to gold. There was no difference between gold levels on D3 and on D7 after epicutaneous application. Presumably, other allergens may also be taken up in blood during patch testing.

Adult↗

Labeling of binding sites for beta 2-microglobulin (beta 2m) on nonfibrillar surface structures of mutans streptococci by immunogold and beta 2m-gold electron microscopy.

As little detail is known about the surface structure of streptococci in the mutans group and the relationship of surface structure to host ligand-binding functions, the twofold purpose of this investigation was to examine in detail, by a range of electron microscopic techniques, the surface structures of streptococci in the different species of the mutans group and to investigate the distribution of beta 2-microglobulin (beta 2m)-binding sites on such structures. Strains representing Streptococcus mutans, S. cricetus, S. rattus, S. sobrinus, and four fresh isolates were studied by shadowcasting and histochemical staining of whole-mounted cells as well as by ultrathin and thick sectioning of embedded specimens. beta 2m-binding site distribution was visualized by indirect immunogold electron microscopy and by direct bacterial binding of beta 2m-conjugated gold probes. Shadowcast preparations revealed binding of gold probes to the cell surface of known beta 2m-binding strains but not to their polar fibrillar appendages. These long fibrils, common to all strains, were trypsin and sonication sensitive and stained with lead citrate but not with uranyl acetate or ruthenium red. More gold particles were bound by the indirect technique. For grid-mounted bacteria, the gold was mostly bound in clusters at the periphery of the cells. When gold probes were reacted in suspension with bacteria before mounting onto grids, a more even distribution of the gold was seen, but the bacteria were aggregated. Heating the bacteria eliminated beta 2m-gold binding but had no effect on the morphology of the fibrils. Thick sections of embedded bacteria prereacted with beta 2m-conjugated gold probes were analyzed by stereo imaging. A wispy, uranyl acetate-stained fuzzy layer, distinct from the fibrils seen by shadowcasting and extending up to one cell diameter from the cell wall, contained the gold probes. These findings introduce a concept that binding sites for some salivary ligands on mutans streptococci may be clustered on very delicate, nonfibrillar structures extending much further from the cell wall than previously appreciated. As for beta 2m, which composes part of the human histocompatibility antigens, part of the bacterial surface would be coated at a distance from its body with a protein not necessarily recognized as foreign by the host.

Animals↗

Gold in erythrocytes, whole blood, and plasma during long-term chrysotherapy.

The concentrations of gold in erythrocytes, whole blood, cell-rich plasma, and cell-free plasma were investigated in 17 patients with rheumatoid arthritis undergoing long-term chrysotherapy. Gold estimations were performed with a graphite tube atomic absorption spectrophotometer. Significant quantities of gold were found in isolated erythrocytes of 12 patients. There was no correlation between erythrocyte gold and therapeutic response, plasma gold, and gold in whole blood. Nor did gold in whole blood or plasma show any correlation with therapeutic responses and toxic reaction. However, all patients (3) with toxic reactions had a significantly higher gold concentration in the erythrocytes than the patients without toxic reactions. This result indicates that erythrocyte gold estimations could provide a useful warning of impeding toxic reactions.

Arthritis, Rheumatoid↗

A 10 year follow up of parenteral gold therapy in patients with rheumatoid arthritis.

OBJECTIVES: To study the long term tolerance of parenteral gold and subsequent drug treatment in patients with rheumatoid arthritis, including prediction of outcome and 'survival' of sequential treatments. METHODS: A retrospective cohort study of 376 patients was made, including a detailed screening of 237 patients treated in 1989. Reasons for discontinuing treatment were analysed in life table analyses, which were used to compare patients receiving parenteral gold treatment in 1985 and 1989, and two groups of patients receiving disease modifying antirheumatic drugs after parenteral gold treatment. The causes of discontinuation were followed in sequential treatments. RESULTS: The estimated probability of discontinuation of parenteral gold treatment was 29% after six months and 42%, 55%, 74%, and 92% after 1, 2, 5, and 10 years, respectively. Mucocutaneous side effects were the main cause of discontinuation of parenteral gold treatment during the first three years, while the probability of discontinuation because of inefficacy dominated after four years. Side effects also constituted the main cause of discontinuation of treatments given after parenteral gold treatment during the first three years of follow up. No significant differences were found when comparing the termination rates between the first and the second and subsequent treatments after parenteral gold treatment. The main reasons for discontinuing one treatment could not predict the cause of discontinuation of the next treatment. CONCLUSION: Mucocutaneous side effects dominated initially, while inefficacy was the dominating cause of discontinuation of long term parenteral gold treatment. No serious side effects were registered. The cause of discontinuation of one treatment did not predict the cause of discontinuation of the following drug. Drug 'survival' was the same in both treatments after parenteral gold treatment.

Adolescent↗

Detection of LDL receptor by ligand blotting with chylomicron remnants labelled with colloidal gold.

The LDL receptor plays a pivotal role in the clearance of pro-atherogenic lipoproteins, and LDL receptor deficiency may be the underlying cause of several primary and secondary dyslipidaemic conditions. Intervention strategies are often targeted to increase hepatic LDL receptor expression. It is difficult to quantitate hepatic LDL receptor activity and to monitor changes post-therapy. In order to avoid liver biopsy, human skin fibroblasts or circulating mononuclear cells have often been used as surrogate markers for the hepatic receptor. Fibroblasts, and particularly mononuclear cells, are relatively easy to isolate and can be stored for extensive lengths of time without significant loss of LDL receptor expression. Leucocytes or fibroblasts are normally probed with isotopically or gold-labelled LDL. However, the specific activity of the LDL conjugate is usually too low to enable accurate quantitation of differences, or changes, in LDL receptor expression. In this study, we describe an enhanced colloidal gold-labelling procedure for the detection of LDL receptor binding activity. The binding of colloidal gold-labelled chylomicron remnants to human hepatocytes (HepG2 cells) was compared with that of gold-conjugated LDL. Labelled remnants bound specifically to a cell surface protein with a molecular weight of approximately 130 kDa. Binding was blocked in the presence of unlabelled remnants, LDL, or antiserum specific to the LDL receptor. The binding of gold-labelled remnants was substantially greater than that of gold-labelled LDL. Compared with gold-labelled LDL, we found a much clearer demarcation of remnant binding with hepatocytes incubated in the presence or absence of sterols. Our observations suggest that, because of the greater affinity of the LDL receptor for lipoproteins containing apolipoprotein E, changes in LDL receptor expression might be more readily identified using gold-labelled remnants. We conclude that gold-conjugated chylomicron remnants might provide a useful means of detecting subtle changes in LDL receptor expression.

Apolipoproteins E↗

New frontiers in gold labeling.

Recent advances in gold technology have led to probes with improved properties and performance for cell biologists: higher labeling density, better sensitivity, and greater penetration into tissues. Gold clusters, such as the 1.4-nm Nanogold, are gold compounds that can be covalently linked to Fab' antibody fragments, making small and stable probes. Silver enhancement then makes these small gold particles easily visible by EM, LM, and directly by eye. Another advance is the combination of fluorescent and gold probes for correlative microscopy. Chemical crosslinking of gold particles to many biologically active molecules has made possible many novel probes, such as gold-lipids, gold-Ni-NTA, and gold-ATP.

Gold↗

Effect of physiological media on the stability of surface-adsorbed DNA-dendron-gold nanoparticles.

Plasmid DNA was adsorbed onto 87-nm gold nanoparticles to which were adsorbed a layer of novel cationic dendrons. The behaviour of this DNA-dendron-gold system in cell culture media has been described. Adsorption onto the gold nanoparticles of lipophilic cationic dendrons, with either 8 [(C12)(3)Lys7(NH2)(8)] or 16 [(C12)(3)Lys15(NH2)(16)] free amino groups on their outer surfaces and incorporating a nuclear localization signal peptide (NLS), resulted in positively charged nanoparticles with a corresponding small increase in particle size. Evidence suggested that the interaction between the gold nanoparticles and the dendron was mediated by hydrophobic forces. With an increase in ionic strength, the apparent particle size of the dendron-stabilized-gold particles increased, but at higher salt concentrations than plain gold sols. Addition of plasmid DNA did not markedly reduce the surface potential of the dendron-gold complex but resulted in an approximately 10-20% increase in hydro-dynamic diameter. Increasing ionic strength increased the apparent size of the DNA-dendron-gold particles, up to a maximum diameter of approximately 900 nm. Importantly, in cell culture media the size of the DNA-dendron-gold nanoparticles increased markedly, as surface potential was reduced. The presence of serum components partially ameliorated these effects, possibly due to steric stabilization of the particles. Release of the DNA from the complex was compromised in cell culture media (compared with water). This, coupled with the flocculation of the carrier, demonstrated the importance of testing delivery systems in the presence of relevant physiologically based fluids before cell culture or in-vivo studies.

Adsorption↗

[The effect of an organic gold compound on porphyrin metabolism, with reference to interaction with lead].

Inhibition of the activity of delta-aminolevulinic acid dehydratase by heavy metals such as Cu, Cd and Au has been thought to be related to the inhibition of heme bio-synthesis in the bone marrow. This study investigates the interaction between lead and gold on porphyrin metabolism. Gold thiomalate (Au-T) was injected subcutaneously 10 times into the backs of rabbits in doses of 1, 10 and 100 mg per capita for 30 days. The latter two groups of animals showed mild anemia, but they showed neither reticulocytosis nor increase of free erythrocyte protoporphyrin (FEP). In rabbits administered lead only or lead plus gold thiomalate, however, reticulocytosis and an increase in FEP levels were observed. Therefore, the etiology of anemia may be different between rabbits administered gold thiomalate and rabbits administered lead. Rabbits injected with Au-T showed an increase in urinary coproporphyrin (CP-U) excretion. The maximum concentration of CP-U in the gold groups was about 3 times as high as that in the control group, but the increment was lower than that in the lead group. Rabbits injected with Au-T showed a higher concentration of gold in the kidneys than in other tissues. In those injected lead and Au-T together, concentration of gold in all tissues was higher than in those administered Au-T only. Proteinuria was observed in the rabbits injected Au-T. The increase in CP-U in the gold-injected rabbits was assumed to be related to the increase in gold concentration in the kidneys.

Animals↗

Effects of gold salts on experimental periodontitis. I. Histometric evaluation of periodontal destruction.

Systemic administration of gold salts for treatment of arthritis is thought to limit tissue destruction through alteration of inflammatory cell function. The present study ascertained if gold salts could modify the tissue destruction associated with an experimental marginal periodontitis. Therapeutic levels of serum gold salts were established in four squirrel monkeys (experimental) by intramuscular injection of Myochrisine (gold sodium thiomalate 25 mg/ml) at 5 mg/kg/body weight at 4-day intervals for 12 days. Marginal periodontitis was then induced around mandibular bicuspids by tying plaque retentive ligatures at the gingival margins. Periodontitis was induced around corresponding teeth in four control animals which had not received gold salts. Serum levels of gold salts were maintained in experimental animals, and all animals were killed 2 weeks after induction of periodontitis. Progression of periodontitis was evaluated histometrically on step-serial sections, and the results analyzed statistically. Specimens from gold-receiving animals had significantly smaller areas of infiltrated supracrestal connective tissue, and less loss of connective tissue attachment and coronal alveolar bone. Quantitation of total plaque around the ligatures showed no differences; however, there was less plaque located apical to the ligatures in gold-receiving specimens. Although the study design did not permit identification of the relative importance of cellular or microbial factors, it was concluded that administration of systemic gold salts was associated with significantly less periodontal destruction.

Animals↗

Quantitation of gold in skin in chrysiasis.

Skin, plasma, hair, and nail gold levels were determined in three groups of patients with rheumatoid arthritis comprising: I. Three patients on long term gold therapy exhibiting altered skin pigmentation (chrysiasis); II. Five patients on long term gold therapy exhibiting normal skin pigmentation; III. Two patients starting gold therapy. Group I had higher skin gold levels (50-140 mug/g) than Group II (7.5-13 mug/g) while Group II had minimal levels. Hair and nail gold levels were not much higher than gold levels in non-gold treated individuals. The possible role of skin in the storage or excretion of gold is discussed.

Arthritis, Rheumatoid↗

Inhibition of human phospholipase C by aurothiomalate and (triethylphosphine) gold complexes.

The effect of several gold complexes on the activity of phospholipase C from human blood platelets was studied in vitro. Aurothiomalate and auranofin--2 agents used for the chrysotherapy of rheumatoid arthritis--, gold chloride, (triethylphosphine)gold chloride, and 5 newly synthesized (triethylphosphine)gold complexes dose-dependently inhibited the enzyme with IC50 values between 0.8 mumol/l ((triethylphosphine)gold chloride) and over 100 mumol/l (auranofin). None of the compounds affected phospholipase A2 from human polymorphonuclear leukocytes at concentrations up to 100 mumol/l. Inhibition of phospholipase C by (triethylphosphine)gold chloride, aurothiomalate, and compound 3 was not significantly different at substrate concentrations of 20 and 100 mumol/l phosphatidylinositol, suggesting that these gold complexes do not inhibit phospholipase C by competing with the substrate. After confirming the Ca2+ dependence of the human platelet phospholipase C by demonstrating inhibition by the Ca2+ chelators EDTA and EGTA--but no inhibition by the Zn2+ chelator 1,10-phenanthroline--the inhibition of the enzyme by (triethylphosphine)gold chloride, aurothiomalate, and compound 3 was studied at 3 different concentrations of Ca2+ in the range of 0.2 to 2 mmol/l. Inhibition by (triethylphosphine)gold chloride was not affected by changes of Ca2+, whereas inhibition by aurothiomalate and compound 3 was markedly suppressed by increasing the Ca2+ concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Antirheumatic Agents↗

[Case report and literature analysis of the clinical factors relating to the development of fibrotic changes in gold lung].

A 26-year-old female with gold lung induced by Shiosol (gold thiomalate) administered for her rheumatoid arthritis is presented. Chest X-ray films after treatment with prednisolone hardly improved and showed diffuse fibrotic shadow. We reviewed previously reported cases of gold lung and tried to determine the clinical factors which might affect the development of pulmonary fibrotic changes in gold lung. The cases reported in Japan were classified into two groups according to the improvement of X-ray films after steroid therapy: group A in which the chest X-ray film returned to almost normal, group B these with diffuse fibrotic shadow. No significant difference was observed in the values of %VC and PaO2 admission between the two groups. The total dose of gold received was greater (p less than 0.05) and the duration of gold received was longer (p less than 0.01) in group B than in group A. These findings suggest that the development of pulmonary fibrosis does not depend on the severity of the injury indicated by pulmonary function, but in part on the amount of gold which has been stored in pulmonary macrophages. No statistical difference was shown in the initial dose of steroids between these groups. The duration between the onset of gold lung and the start of steroid therapy were longer in group B than than group A (p less than 0.05). Thus, early diagnosis and treatment with steroids are highly recommended in the clinical management of patients with gold lung.

Adult↗

Autometallographic demonstration of gold in rheumatoid synovial tissue.

A new autometallographic method for the detection of gold was applied to synovial tissue obtained by synovectomy from 30 patients with chronic arthritis. Granules staining for gold were visualized in biopsies from 26 patients previously or currently treated with gold, but not in biopsies from untreated patients. Location of macrophages was confirmed, and in half the biopsies fibroblast-like cells were also stained. Lymphocytes, plasma cells and interstitial tissue were devoid of gold. Granules were seen after treatment with as small an amount as 85 mg gold sodium aurothiomalate. The amount of gold staining varied between the biopsies and seemed to be related to the amount of gold given. Within individual biopsies, the distribution of gold staining was irregular. It is suggested that there may be at least two targets of chrysotherapy in arthritic joints, and that an influence of gold on the immune system may take place, at least in part, via the macrophages. A relationship between the biopsy findings and the clinical course could not be established.

Adolescent↗

Gold and modulation of the immune response.

The effects of gold on immune responses are reviewed. Gold salts used therapeutically can be followed by a decline in serum immunoglobulin levels, and rheumatoid factor titers in rheumatoid arthritis; in pemphigus there is similarly a drop in anti-epithelial antibody titers. Gold inhibits stimulation of immunoglobulin-secreting cells. Gold inhibits the activation of the classical and alternate complement pathways. Gold compounds inhibit numerous cell-mediated immune responses to various mitogens and antigens. Inhibition may be due to the effect of gold on macrophages acting as helper cell in these reactions. Auranofin is a new oral compound which seems to be particularly potent in its immuno-regulatory actions; it differs from other gold compounds in its pharmacokinetics, and in the nature of its ligand. Gold has also been reported to enhance certain immune reactions. The extent of the immuno-regulatory effects of gold in vivo is unknown, and the relation of these effects to its therapeutic actions remains to be clarified.

Animals↗

The effect of gold on copper and zinc in kidney and in metallothionein.

The question as to the increase in copper and zinc contents in metallothionein in response to gold injection was examined. Each rat was injected intraperitoneally once with 0.9% NaCl or gold (5, 10 or 20 mg gold/kg b.w.). After gold injection, 60.1-68.4% of the renal copper content was found in the cytosol. Although the copper contents in cytosol and kidneys of gold-injected rats were higher than those of control rats, they did not increase in response to gold injection. Approx. 61.7-68.5% of the zinc contents in kidneys were detected in cytosol. The distribution profiles of the renal cytosols of gold-injected rats on a Sephadex G-75 column showed that the amount of the increased copper was attributable to the MT fraction. Although the copper content of MT of gold-injected rats were higher than those of control rats, they did not increase in response to gold injection. These results indicate that copper and zinc contents in metallothionein did not increase in response to gold injection.

Animals↗