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Sublethal concentrations of diverse gold compounds inhibit mammalian cytosolic thioredoxin reductase (TrxR1).

UNLABELLED: Thioredoxin reductase (TrxR) reduces thioredoxin (Trx), thereby contributing to cellular redox balance, facilitating the synthesis of deoxy-ribose sugars for DNA synthesis, and regulating redox-sensitive gene expression. Auranofin is a gold compound that potently inhibits TrxR. This inhibition is one suspected mechanism of auranofin's therapeutic benefit in the treatment of rheumatoid arthritis. The use of other gold compounds to treat cancer or inflammatory disease may rely on their ability to inhibit TrxR. In the current study, we tested the hypothesis that a variety of gold compounds may inhibit TrxR. METHODS: We exposed rat-TrxR1 to auranofin, gold sodium thiomalate, sodium aurothiosulfate, triphenyl phosphine gold chloride, or gold acetate, and measured TrxR activity ex vivo. We then compared TrxR1 inhibitory levels of gold compounds to those that inhibited mitochondrial activity of THP1 monocytes and OSC2 epithelial cells, estimated by succinate dehydrogenase activity. RESULTS: All gold compounds inhibited TrxR1 at concentrations ranging from 5 to 4000 nM (50% inhibitory concentration). The oxidation state of gold did not correlate with inhibitory potency, but ligand configuration was important. Au(I)-phosphine compounds (triphenyl phosphine gold chloride and auranofin) were the most potent inhibitors of TrxR. All TrxR1 inhibitory concentrations were sublethal to mitochondrial activity in both THP1 and OSC2 cells. CONCLUSIONS: Diverse types of gold compounds may be effective inhibitors of TrxR1 at concentrations that do not suppress cellular mitochondrial function. Inhibition may be optimized to some degree by altering the ligand configuration of the compounds. These results support future study of a variety of Au compounds for therapeutic development as inhibitors of TrxR1.

Animals↗

Mammalian sensitivity to elemental gold (Au degrees).

There is increasing documentation of allergic contact dermatitis and other effects from gold jewelry, gold dental restorations, and gold implants. These effects were especially pronounced among females wearing body-piercing gold objects. One estimate of the prevalence of gold allergy worldwide is 13%, as judged by patch tests with monovalent organogold salts. Eczema of the head and neck was the most common response of individuals hypersensitive to gold, and sensitivity can last for at least several years. Ingestion of beverages containing flake gold can result in allergic-type reactions similar to those seen in gold-allergic individuals exposed to gold through dermal contact and other routes. Studies with small laboratory mammals and injected doses of colloidal gold showed increased body temperatures, accumulations in reticular cells, and dose enhancement in tumor therapy; gold implants were associated with tissue injuries. It is proposed that Au degrees toxicity to mammals is associated, in part, with formation of the more reactive Au+ and Au3+ species.

Animals↗

Comparative studies on electrogenerated chemiluminescence of luminol on gold nanoparticle modified electrodes.

Comparative studies on the electrogenerated chemiluminescence (ECL) behavior of luminol on various electrodes modified with gold nanoparticles of different size were carried out in neutral solution by conventional cyclic voltammetry (CV). The results demonstrated that the gold nanoparticle modified electrodes could generate strong luminol ECL in neutral pH conditions. The catalytic performance of gold nanoparticle modified electrodes on luminol ECL depended not only on the gold nanoparticles but also on the substrate. Gold electrode and glassy carbon electrode were the most suitable substrates for the self-assembly of gold nanoparticles. Moreover, the gold nanoparticle modified gold and glassy carbon electrode had satisfying stability and reproducibility and did not need tedious pretreatment of electrode surface before each measurement. It was also found that luminol ECL behavior depended on the size of gold nanoparticles. The most intense ECL signals were obtained on a 16-nm-diameter gold nanoparticle modified electrode. The modified electrode prepared by the self-assembly method exhibited much better catalytic effect on luminol ECL than that prepared by the electrically deposited method. The ECL behavior of luminol on a gold nanoparticle self-assembled gold electrode was also investigated by other transient-state electrochemical techniques, such as chronoamperometry, differential pulse voltammetry, normal pulse voltammetry, and square wave voltammetry. The strongest ECL intensity was obtained under square wave voltammetric condition.

Journal Article↗

Gold and Clarke Questionnaires Identify Different People With Insulin-Treated Diabetes and Impaired Awareness of Hypoglycaemia in Almost 60% of Cases: A Post Hoc Analysis From the Hypo-METRICS Study.

AIMS: Gold and Clarke questionnaires are used to identify impaired awareness of hypoglycaemia (IAH) and severe hypoglycaemic event (SHE) risk in people with diabetes (pwD). We explored their overlap, including Clarke's Hypoglycaemia Awareness Status (Clarke-HAS) subfactor, and subsection differences in SHE incidence (Gold, Clarke, overlap). MATERIALS AND METHODS: This post hoc analysis of the Hypo-METRICS study recruited pwD on insulin (type 1: T1D; type 2: T2D) with &#x2265;&#x2009;1 hypoglycaemic event in the previous 3 months. IAH was defined as Gold &#x2265;&#x2009;4, Clarke &#x2265;&#x2009;4, Clarke-HAS &#x2265;&#x2009;2. RESULTS: Gold and Clarke were completed by 232 pwT1D and 285 pwT2D (age: 47 vs. 62&#x2009;years, p&#x2009;<&#x2009;0.001; HbA1c: 56&#x2009;mmol/mol (7.3%) vs. 57&#x2009;mmol/mol (7.4%), p&#x2009;=&#x2009;0.03). IAH prevalence in T1D vs. T2D was 21% vs. 26% (p&#x2009;=&#x2009;0.1), 14% vs. 18% (p&#x2009;=&#x2009;0.2), and 41% vs. 48% (p&#x2009;=&#x2009;0.2) according to Gold, Clarke and Clarke-HAS. The overlap between Gold &#x2265;&#x2009;4, Clarke &#x2265;&#x2009;4 was 40% (T1D: 45%; T2D: 37%); between Gold &#x2265;&#x2009;4, Clarke-HAS &#x2265;&#x2009;2 it was 45% (T1D: 43%; T2D: 47%). The overlap between Gold &#x2265;&#x2009;4, Clarke &#x2265;&#x2009;4 was 41% vs. 39% in CGM vs. non-CGM users (T1D: 50% vs. 35%; T2D: 32% vs. 40%); between Gold &#x2265;&#x2009;4, Clarke-HAS &#x2265;&#x2009;2 it was 39% vs. 53% (T1D: 38% vs. 54%; T2D: 40% vs. 53%). In the IAH sample, SHE rate was lower in people found with IAH by Gold vs. Clarke, 9% vs. 53%, and in those assessed by Gold-Clarke overlap vs. Clarke, 20% vs. 53% (all p&#x2009;<&#x2009;0.001). CONCLUSIONS: Gold and Clarke show moderate consistency (37%-54%) in identifying IAH in insulin-treated diabetes, with/without CGM use, each associated with different SHE rates, indicating the two questionnaires measure different, independent aspects of IAH.

Humans↗

[Does parenteral gold inhibit roentgen progression of chronic polyarthritis?].

The retardation of radiological progression is one of the most important characteristics of a disease-modifying effect of an antirheumatic drug. For the following overview 10 trials were identified dealing with x-ray progression under treatment with parenteral gold. Nine of these trials were randomised parallel studies, one was a retrospective long-term observational study, all had a control group, in five this control group was treated with placebo, in two trials parenteral gold was compared with another DMARD (auranofin and methotrexate, respectively), in two trials different doses of gold were compared and in two trials the radiological progression during the first 6 months was compared with the following treatment period (in one of these trials gold was compared with methotrexate as well). The duration of treatment and follow-up was up to 1 year in two trials, up to 2 years in six, and over 2 years in only two studies. There is a great number of limitations in these studies: for instance, there was a large number of withdrawals who were not followed, x-rays were available for evaluation only in a relatively small proportion of treated patients in five studies, in six studies the disease duration was over 2 years at baseline, which limits the evaluability of x-ray progression for technical reasons. In one study juxta articular osteoporosis and joint swelling were evaluated; but these parameters are very difficult to evaluate in a multicenter study because of the different quality of the films. In spite of all limitations and reservations with the studies reviewed the published results indicate a reduction of radiological progression with parenteral gold treatment of rheumatoid arthritis patients: in the placebo-controlled studies outcome in the gold group was significantly better than in the placebo group. The study of the Empire Rheumatism Council failed to show a significant difference compared to the control group after 30 months, but the patients had been treated sufficiently only for 5 months. The study of Cats indicated a better outcome in the group of patients with a high gold dose, which is confirmed by the retrospective analysis of Luukkainen. In a comparison between 113 patients treated with parenteral gold and 119 patients treated with auranofin for 1 year Larsen found a significantly smaller progression in the patients treated with parenteral gold. In a patient population of 73 and 53 the difference between methotrexate and parenteral gold was too small to be detectable, but the progression curve was significantly flattened after the first 6 months, indicating a treatment effect. In a macroradiographic study the erosion surface area increased during the first 6 months of gold treatment, it did not change during the second 6 months, and decreased during the third 6 months together with healing of erosions. In conclusion, the studies reviewed in this paper indicate a disease-modifying potency of parenteral gold treatment, especially when the treatment is started early and sufficiently dosed.

Animals↗

Comparison of gold levels and distribution in guinea pig serum.

Serum levels after oral administration of 30 mg/kg of sodium aurothiomalate (Myocrisin), triethylphosphine gold chloride, or triphenylphosphine gold chloride to guinea pigs indicated that all were orally absorbed. However, the serum gold level of triethylphosphine gold chloride was three to four times that of Myocrisin or triphenylphosphine gold chloride and was comparable with the serum level produced when the same dose of Myocrisin was injected intramuscularly. A comparative time-course study between intramuscular administration of Myocrisin and oral administration of triethylphosphine gold chl;ride indicated that during the first 24 hours after intramuscular injection of Myocrisin, a large fraction of the gold was not protein-bound, whereas all detectable gold in serum after oral administration of triethylphosphine gold chloride was protein-bound. Gold levels in the separated protein fractions indicate that the gamma-globulin level after oral administration of triethylphosphine gold chloride is approximately three times higher after 24 hours than with intramuscular Myocrisin.

Administration, Oral↗

Selective adsorption: a new method for purification of protein A-gold complexes.

Protein gold complexes are prepared by adding gold colloids to cytochemically active proteins in solution. The gold particles of the colloid form complexes with the protein spontaneously, but some of the protein remains uncomplexed. Currently, when protein A-gold complexes are prepared, the uncomplexed protein. A is separated from the complex by ultracentrifugation, which is a lengthy procedure and requires special equipment. This report describes a simple and rapid method for removing uncomplexed protein A from freshly-prepared "crude" protein A-gold at the laboratory bench. In this method, larger gold particles of 15-nm diameter are added to a crude protein A-gold preparation made with smaller particles (e.g.,6nm diameter). The 15-nm particles adsorb uncomplexed protein A preferentially, but do not form complexes with already-formed 6-nm protein A-gold. The adsorbed protein A, attached to the 15-nm particles, can then be sedimented in a bench centrifuge, leaving the purified 6-nm protein A-gold complexes in the supernatant. The stability, immunocytochemical activity, and degree of aggregation of the protein A-gold complexes prepared by this method are comparable to protein A-gold complexes prepared by ultracentrifugation. The method is simple to perform, avoids lengthy purification procedures, and yields complexes with reproducible labelling characteristics.

Centrifugation↗

A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: results of the METGO study.

OBJECTIVE: To evaluate the efficacy and safety of adding intramuscular (IM) gold to the treatment regimen of patients with rheumatoid arthritis (RA) who have a suboptimal response to methotrexate (MTX). METHODS: A randomized, double-blind, double-observer, placebo-controlled multicenter trial of 48 weeks was conducted. Sixty-five RA patients who had a suboptimal response to >/=12 weeks of MTX therapy were randomly assigned to receive weekly IM gold or placebo in addition to MTX. Gold was administered according to a standard protocol developed for the study. The primary outcome measure was the percentage of patients who met the American College of Rheumatology (ACR) 20% improvement criteria (achieved an ACR20 response) at week 48. Secondary outcomes included the percentages of patients achieving ACR50 and ACR70 responses, the individual criteria that make up the primary outcome, quality of life, direct and indirect health care costs, intraarticular steroid use, and adverse events, among other measures. Statistical analyses were based on an intent-to-treat strategy. RESULTS: Sixty-one percent of patients receiving gold achieved an ACR20 response compared with 30% of patients receiving placebo (chi(2) = 6.04, P = 0.014; logistic regression odds ratio 3.64 [95% confidence interval 1.3, 10.4], P = 0.016). Twenty-six percent of patients receiving gold achieved an ACR50 response compared with 4% of patients receiving placebo (P = 0.017), and 21% of patients receiving gold achieved an ACR70 response compared with 0% of patients receiving placebo (P = 0.011). From both clinical and cost-effectiveness perspectives, gold was the preferred and dominant strategy. Study treatment was discontinued in 23 patients (14 in the placebo group compared with 9 in the gold group; P = 0.022) due to loss to followup, adverse events, or lack of efficacy. CONCLUSION: In RA patients with a suboptimal response to MTX, adding weekly IM gold causes significant clinical improvement. Adverse events were minor, and IM gold-related adverse events led to discontinuation in only 11% of the gold group over 48 weeks.

Antirheumatic Agents↗

SEM/EDS evaluation of porcelain adherence to gold-coated cast titanium.

The adhesion between titanium and dental porcelain is related to the diffusion of oxygen to the reaction layer formed on cast-titanium surfaces during porcelain firing. The diffusion of oxygen could be suppressed by coating the titanium surface with a thin gold layer. This study characterized the effects of gold coating on titanium-ceramic adhesion. ASTM grade II CP titanium was cast into a MgO-based investment (Selevest CB, Selec). The specimen surfaces were air abraded with 110-microm Al(2)O(3) particles. Gold coating was applied on titanium surfaces by three methods: gold-paste (Deck Gold NF, Degussa-Ney) coating and firing at 800 degrees C for three times, single gold-paste coating and firing followed by sputter coating (40 mA, 500 s), and sputter coating (40 mA, 1000 s). Surfaces only air abraded with Al(2)O(3) particles were used as controls. An ultra-low-fusing dental porcelain (Vita Titankeramik, Vident) was fused on titanium surfaces. Specimen surfaces were characterized by SEM/EDS and XRD. The titanium-ceramic adhesion was evaluated by a biaxial flexure test (N = 8), and area fraction of adherent porcelain (AFAP) was determined by EDS. Numerical results were statistically analyzed by one-way ANOVA and the Student-Newman-Keuls test at alpha = 0.05. SEM fractography showed a substantial amount of porcelains remaining on the gold-sputter-coated titanium surfaces. A new Au(2)Ti phase was found on gold-coated titanium surface after the firing. Significantly higher (p <.05) AFAP values were determined for the gold-sputter-coated specimens compared to the others. No significant differences were found among the other groups and the control. Results suggested that gold coatings used in this study are not effective barriers to completely protect titanium from oxidation during the porcelain firing, and porcelain adherence to cast titanium can be improved by gold-sputter coating used in the present study.

Dental Porcelain↗

Longterm experience with oral gold in rheumatoid arthritis and psoriatic arthritis.

Oral gold (auranofin) has been used in 31 patients, 20 with active rheumatoid arthritis and 11 with active psoriatic arthritis. In rheumatoid arthritis the oral gold treatment was compared to parenteral gold treatment in a patient blind trial for two years. The psoriatic arthritis cases were incorporated in an open trial. Auranofin 6 mg once daily reduced significantly the activity in rheumatoid arthritis and in psoriatic arthritis. The beneficial effect obtained with auranofin at a dose of 6 mg/day during the first year of treatment could not be maintained by 3 mg/day in the second year. Auranofin compared to parenteral gold had a distinct advantage of better systemic tolerability, although parenteral gold was found to be more potent. There was no greater risk for toxic skin reaction to oral gold in psoriatic arthritis than in rheumatoid arthritis. The overall conclusion of this longterm study is that oral gold (auranofin) 6 mg once daily, although slightly less effective than parenteral gold, can be considered to be the first choice of gold treatment for rheumatoid arthritis and psoriatic arthritis, because the compliance, which is a reflection of a combination of tolerance and efficacy, for oral gold therapy was, in our hands, undoubtedly superior to parenteral gold.

Adult↗

Safety of gold in stapes surgery.

Gold prostheses in middle ear surgery were found to have a higher extrusion rate than prostheses made from titanium. Incidences of deafness after insertion of a gold piston into the vestibule during stapes surgery have been observed. The aim of this study was to find out to what degree gold cations can diffuse from the prosthesis piston into the perilymph. For this, gold prostheses were incubated in artificial perilymph for four months, after which the gold content of the perilymph was analysed. As gold exhibits a special behaviour in complex fluids like the perilymph, a new analysing method was developed. The results show that gold does leak out of the pistons, that it can be reliably measured and that the amount of gold reaching the perilymph depends on the contact area. As the amount of gold measured in the perilymph stays far below the toxic level, it is very unlikely that the gold cations diffusing from a stapes prosthesis into the perilymph have a toxic effect on the inner ear hair cells. Inflammatory or allergic reactions to gold induced by direct tissue contact, however, cannot be excluded.

Animals↗

The surface free energy of dental gold-based materials.

OBJECTIVE: A gold composite material (Captek) has been developed which is claimed to resist plaque deposition. This study's aim was to compare the surface free energy (SFE) of this composite material with that of a type III casting gold. METHODS: Contact angle measurements, using the Wilhelmy technique, were made on four bar-shaped samples of each material, using five test liquids (diiodomethane, ethylene glycol, formamide, glycerol and water) and four measurements per sample per liquid. For each material, the dispersive, Lewis acid and Lewis base components of SFE (gamma(S)D, gamma(S)+, gamma(S)-, respectively) were estimated by least squares analysis and also by a Bayesian method. RESULTS: The gold composite material and the type III casting gold did not differ significantly in their gamma(S)D values (95% confidence interval for gold composite minus type III gold, -5.0 to +2.7). Both materials had low gamma(S)+ values in common with most solids. The gold composite had a significantly lower Lewis base component of SFE than the type III gold-8.4 mN/m for the former material compared to 19.1 mN/m for the latter (95% confidence interval for gold composite minus type III gold, -16.4 to -4.9). The difference between materials could be related to the lack of non-precious metals and the structure of the gold composite material. CONCLUSIONS: It is hypothesized that difference in gamma(S)- components of SFE may be an important parameter in predicting bacterial adhesion and plaque resistance. Methods that only determine SFE as a single parameter may be unable to differentiate adequately between dental restorative materials.

Bayes Theorem↗

Gold complexes inhibit mitochondrial thioredoxin reductase: consequences on mitochondrial functions.

The effects of gold(I) complexes (auranofin, triethylphosphine gold and aurothiomalate), gold(III) complexes ([Au(2,2'-diethylendiamine)Cl]Cl(2), [(Au(2-(1,1-dimethylbenzyl)-pyridine) (CH(3)COO)(2)], [Au(6-(1,1-dimethylbenzyl)-2,2'-bipyridine)(OH)](PF(6)), [Au(bipy(dmb)-H)(2,6-xylidine)](PF(6))), metal ions (zinc and cadmium acetate) and metal complexes (cisplatin, zinc pyrithione and tributyltin) on mitochondrial thioredoxin reductase and mitochondrial functions have been examined. Both gold(I) and gold(III) complexes are extremely efficient inhibitors of thioredoxin reductase showing IC(50) ranging from 0.020 to 1.42 microM while metal ions and complexes not containing gold are less effective, exhibiting IC(50) going from 11.8 to 76.0 microM. At variance with thioredoxin reductase, auranofin is completely ineffective in inhibiting glutathione peroxidase and glutathione reductase, while gold(III) compounds show some effect on glutathione peroxidase. The mitochondrial respiratory chain is scarcely affected by gold compounds while the other metal complexes and metal ions, in particular zinc ion and zinc pyrithione, show a more marked inhibitory effect that is reflected on a rapid induction of membrane potential decrease that precedes swelling. Therefore, differently from gold compounds, the various metal ions and metal complexes exert their effect on different targets indicating a lower specificity. It is concluded that gold compounds are highly specific inhibitors of mitochondrial thioredoxin reductase and this action influences other functions such as membrane permeability properties. Metal ions and metal complexes markedly inhibit the activity of thioredoxin reductase although to an extent lower than that of gold compounds. They also inhibit mitochondrial respiration, decrease membrane potential and, finally, induce swelling.

Animals↗

A study on the sizes and concentrations of gold nanoparticles by spectra of absorption, resonance Rayleigh scattering and resonance non-linear scattering.

Liquid phase gold nanoparticles with different diameters and colors can be prepared using sodium citrate reduction method by controlling the amounts of sodium citrate. The mean diameters of gold nanoparticles are measured by transmission electron microscope (TEM). Gold nanoparticles with different sizes have specific absorption spectra. When the diameters of nanoparticles is between 12 and 41 nm, the maximum absorption peaks locate at 520-530 nm and there are red shifts gradually with the increase of diameters of gold nanoparticles. And when the size of gold nanoparticle is constant, the absorbance is proportional to the concentration of gold. Obvious resonance Rayleigh scattering (RRS) and the resonance non-linear scattering such as second-order scattering (SOS) and frequency-doubling scattering (FDS) appear at the same time as well, and the maximum scattering peaks are located at 286 nm (RRS), 480 nm (SOS) and 310 nm (FDS), respectively. When the concentration of gold is constant, absorbance and the intensities of RRS, SOS and FDS (I(RRS), I(SOS) and I(FDS)) have linear relationships with the diameters of gold nanoparticles. When the diameter of gold nanoparticle is constant, the absorbance and I(RRS), I(SOS), I(FDS) are directly proportional to the concentrations of gold nanoparticles. Therefore, it is very useful for studying the liquid phase gold nanoparticles by investigating the absorption, RRS, SOS and FDS spectra.

Color↗

Oral manifestations of gold allergy.

BACKGROUND: Sensitization to gold in a large group of patients suspected of clinical allergy to this metal has not been reported. OBJECTIVE: Two hundred patients with symptoms of persistent oral mucosal or cutaneous lesions that were possibly related to allergy to constituents of gold alloys or gold jewelry were patch tested to determine the frequency of sensitization. METHODS: Patch testing was performed with the European standard series and a series of dental materials including three different salts of gold. A persistent papular reaction to gold-(tri)chloride was considered a positive reaction. RESULTS: In 17 patients (8.5%, all women, mean age 50.2 years) persistent papular patch test reactions to both 0.5% and 1.0% gold(tri)chloride were observed. In five of seven patients with oral lichen planus (OLP) and in one of six patients with the burning mouth syndrome, gold in the dentures was replaced. Particularly in patients with OLP, a significant but variable improvement was observed. In all cases in which gold was replaced and improvement occurred, the patients were sensitized to 0.5% gold(tri)chloride. One patient with allergic contact stomatitis and one patient with allergic contact dermatitis healed completely after gold had been replaced. CONCLUSION: Sensitization to gold should be considered as a possible cause of allergic contact dermatitis and allergic contact stomatitis as well as a pathogenic or triggering factor in OLP.

Burning Mouth Syndrome↗

Effects of gold nanoparticle and electrode surface properties on electrocatalytic silver deposition for electrochemical DNA hybridization detection.

In this paper we report the catalytic effects of various gold nanoparticles for silver electrodeposition on indium tin oxide (ITO)-based electrodes, and successfully apply this methodology for signal amplification of the hybridization assay. The most widely used gold nanoparticle-based hybridization indicators all promote silver electrodeposition on the bare ITO electrodes, with decreasing catalytic capability in order of 10 nm gold, DNA probe-10 nm gold conjugate, streptavidin-5 nm gold, and streptavidin-10 nm gold. Of greater importance, these electrocatalytic characteristics are affected by any surface modifications of the electrode surfaces. This is illustrated by coating the ITO with an electroconducting polymer, poly(2-aminobenzoic acid)(PABA), as well as avidin molecules, which are promising immobilization platforms for DNA biosensors. The catalytic silver electrodeposition of the gold nanoparticles on the PABA-coated ITO surfaces resembles that on the bare surfaces. With avidin covalently bound to the PABA, it is interesting to note that the changes in electrocatalytic performance vary for different types of gold nanoparticles. For the streptavidin-5 nm gold, the silver electrodeposition profile is unaffected by the presence of the avidin layer, whereas for both the 10 nm Au and DNA probe-10 nm gold conjugate, the deposition profiles are suppressed. The streptavidin-5 nm gold is employed as the hybridization indicator, with avidin-modified (via PABA) ITO electrode as the immobilization platform, to enable signal amplification by the silver electrodeposition process. Under the conditions, this detection strategy offers a signal-to-noise ratio of 20. We believe that this protocol has great potential for simple, reproducible, highly selective and sensitive DNA detection on fully integrated microdevices in clinical diagnostics and environmental monitoring applications.

DNA↗

Detection of gold particles in the neck skin after lightning stroke with evaporation of an ornamental chain.

A German couple was struck by lightning. Both patients survived this event. Whereas the husband was unconscious for only a few minutes, his wife fell into coma for 24 h. The lightning stroke entered the body of the woman behind the left ear and left it at the left shoe. The stroke caused a partial evaporation of a gold ornamental chain on the neck, resulting in a tattoo of the neck skin. A biopsy of the skin 6 months after the event showed the accumulation of gold particles of different size in the dermis down to the subcutaneous fatty tissue. In semithin sections, histiocytes, multinucleated foreign giant cells, and fibroblasts were visible with uptaken metallic particles. In transmission electron microscopy, gold globules of up to 30 microm in diameter were visible outside the cells in the collageneous matrix of the connective tissue besides smaller metallic particles up to 5 nm inside lysosomes and residual bodies of phagocytic cells. Four different kinds of gold particles could be differentiated: globules, granular irregular particles, tubules, and tanglelike tracks. In scanning electron microscopy, gold particles were demonstrated by backscatter detection in the connective tissue of subcutis, where the EDX elemental analysis showed strong signals of aurum (Au), copper (Cu), and argentum (Ag). The detected metals were quantified by AAS as 70% gold, 21% silver, and 9% copper, which demonstrates the composition of gold alloy of the neck chain of the patient. Tanglelike tracks and elongated gold deposits represent crystals of gold salts, as detected by electron diffraction and polarization microscopy. Attempts to remove the gold particles from the skin to remove the tattoo should not be undertaken because the gold is deep and widespread.

Adult↗

Distribution pattern of inhaled ultrafine gold particles in the rat lung.

The role of alveolar macrophages in the fate of ultrafine particles in the lung was investigated. Male Wistar-Kyoto rats were exposed to ultrafine gold particles, generated by a spark generator, for 6 h at a concentration of 88 microg/m3 (4 x 10(6)/cm3, 16 nm modal mobility diameter). Up to 7 days, the animals were serially sacrificed, and lavaged cells and lung tissues were examined by transmission electron microscopy. The gold concentration/content in the lung, lavage fluid, and blood was estimated by inductively coupled plasma-mass spectrometry. Gold particles used were spherical and electron dense with diameters of 5-8 nm. The particles were individual or slightly agglomerated. By inductively coupled plasma-mass spectrometry analysis of the lung, 1945 +/- 57 ng (mean +/- SD) and 1512 +/- 184 ng of gold were detected on day 0 and on day 7, respectively, indicating that a large portion of the deposited gold particles was retained in the lung tissue. In the lavage fluid, 573 +/- 67 ng and 96 +/- 29 ng were found on day 0 and day 7, respectively, which means that 29% and 6% of the retained gold particles were lavageable on these days. A low but significant increase of gold (0.03 to 0.06% of lung concentration) was found in the blood. Small vesicles containing gold particles were found in the cytoplasm of alveolar macrophages. In the alveolar septum, the gold particles were enclosed in vesicles observed in the cytoplasm of alveolar type I epithelial cells. These results indicate that inhaled ultrafine gold particles in alveolar macrophages and type I epithelial cells are processed by endocytotic pathways, though the uptake of the gold particles by alveolar macrophages is limited. To a low degree, systemic particle translocation took place.

Animals↗