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Platelet and cell interactions on gold sputter-deposited polymeric surfaces.

Surface treatment as gold sputter-deposited treatment onto various polymeric surfaces has been investigated to improve the cell-, tissue- and blood-compatibility. Surface treated samples were characterized by measurement of contact angle goniometer and electron spectroscopy for chemical analysis (ESCA). The contact angles on the gold-coated polymeric surfaces decreased from 95-65 degrees to around 50 degrees, i.e., increased hydrophilicity due to incorporation of gold thin layer. From the results of ESCA analysis of the modified polymeric surfaces, surface modification by the gold-sputter method was successfully performed. Morphology of the adhered platelets on the gold-coated polymeric surfaces showed lesser activating than control, and the number of adhered platelets surface modified samples decreased with decreasing water contact angle. Fibroblast cell adhesion and growth on the gold-coated polymeric surfaces were more active than those of control. It seems that surface wettability and surface chemistry of gold play important roles for platelet adhesion and cell adhesion, spreading and growth.

3T3 Cells↗

Development of gold stents for the treatment of intracranial aneurysms: an experimental study in a canine model.

BACKGROUND AND PURPOSE: Gold has often been used in medicine because of its radiopacity and flexibility. To perform stent-supported coil embolization of intracranial aneurysms, we prepared a gold stent and examined its flexibility, radiopacity, and thrombogenic properties in comparison with a stainless steel device implanted in vitro and in vivo. METHODS: Gold stents were prepared by plating gold on stainless steel stents as a template. Their mechanical properties and trackability in vitro were determined and compared with those of stainless steel stents of the same design. Twenty gold stents and two stainless steel stents were implanted in canine external carotid, vertebral, and renal arteries, as a muscle branch of the maxillary arteries, to examine their performance in vivo. RESULTS: The gold stent exhibited much less radial force and greater flexibility than the stainless steel stent. It also demonstrated superior trackability and radiopacity in the experimental endovascular procedures in canines. Histologic examination showed good patency of the stented artery with slight endothelial hypertrophy. CONCLUSION: Although there is still room for more radial strength, less influence on intimal hypertrophy, a more suitable flexibility, and a smoother surface, the superior trackability and radiopacity of gold stents seem to support use of this device for the endovascular treatment of intracranial aneurysms.

Animals↗

[Immunogenic properties of the colloidal gold].

We studied the capacity of colloidal gold for enhancing specific and nonspecific immune response in laboratory animals (rabbits, rats, and mice) immunized with antigens of various nature. The antibody titers obtained with colloidal gold as a carrier were higher as compared to the standard immunization techniques (free antigen or Freund's adjuvant). Application of colloidal gold increased nonspecific immune responses as well: lysozyme concentration in the blood, activity of the complement system proteins, as well as phagocytic and bactericidal activities. The obtained antibodies were tested by immunodot assay using gold markers. Immunization of the animals with colloidal gold conjugates with haptens as well as complete antigens was shown to induce formation of highly active antibodies without using other antigens such as complete Freund's adjuvant. In addition, antigen quantities for animal immunization with colloidal gold was by one order of magnitude lower as compared to the complete Freund's adjuvant immunization. This fact can point to direct adjuvant activity of colloidal gold.

Actins↗

[Gold compounds and D-penicillamine for therapy of rheumatoid arthritis].

Rheumatoid arthritis is a severe disease and it is difficult to prevent the progression of disease. Gold compounds (injectable gold and oral gold) and D-penicillamine (D-PA) have the possibility to retard joint destruction and to slow radiological progression. These drugs are called Disease Modifying Antirheumatic Drugs (DMARD), and they should be tried in cases resisting conventional NSAID's therapy. They are effective in more than 60% in severe rheumatoid patients but they also have many side effects, e.g. eczema, skin rash, renal dysfunction, aplastic anemia. Laboratory checks should be carried out once a month during the first six month, and every 2 or 3 months thereafter. To compare injectable gold with D-PA, discontinuation due to inefficacy of D-PA is higher than with injectable gold, but side effects of injectable gold is greater. Oral gold is less effective than the other 2 drugs, but has a lower rate of side effects.

Arthritis, Rheumatoid↗

[Gold-silver technic--a new immunohistochemical method for detecting cell membrane antigens].

The gold-silver technique is presented as a new method for immunohistochemical labelling of cell membrane antigens. At first, membrane antigens of mouse lymphocytes, human leukaemic cells, and experimental brain tumour cells are labelled by immunoglobulin- or anti-immunoglobulin-gold complexes. Secondarily, gold colloid particles are made visible in the light microscope by means of subsequent precipitation of metallic silver around the colloid particles according to the principle of photographic development. The gold-silver reaction can be used after direct or indirect gold-labelling of cell membrane antigens. The technique is suitable for both vital and prefixed cells. Labelling of membrane antigens of vital and prefixed cells, however, results in a different pattern of the gold-silver grains. The gold-silver method is easy and quickly to perform, sensitive and not expensive.

Animals↗

Inhibitory effects of gold sodium thiomalate on DNA polymerase alpha.

The usefulness of gold compounds in the therapy of rheumatoid arthritis is well established, however, the pharmacological mechanisms of the compounds are still unclear. In this report, effects of gold compounds on DNA synthesis were examined. Gold sodium thiomalate inhibited DNA synthesis in the HeLa "nuclei system" as well as in the enzyme reaction using DNA polymerase alpha. More precisely, gold sodium thiomalate inhibited the activity of DNA polymerase alpha using activated DNA, poly[d(A-T)] or poly[d(G-C)] for the template, but did not inhibit the activity of DNA polymerase I with each template. The compound had also no inhibitory effect on DNA polymerase beta or gamma. On the other hand, auranofin inhibited the incorporation of [3H]thymidine into HeLa DNA but did not inhibit DNA synthesis in the HeLa "nuclei system". The inhibition of DNA polymerase alpha activity by gold sodium thiomalate was competitive with poly(dA).oligo(dT) for template but noncompetitive with dTTP. Thus, gold sodium thiomalate is a potent and specific inhibitor of DNA polymerase alpha and this inhibitory effect could play an important role in the therapeutic and pharmacological effects of gold sodium thiomalate.

Auranofin↗

Location and identification of colloidal gold particles on the cell surface with a scanning electron microscope and energy dispersive analyzer.

The use of colloidal gold particles for locating cell surface components by scanning electron microscopy (SEM) has been restricted due to difficulties in the identification of these gold particles under SEM. It is shown here how the gold particles bound to cell surfaces can be located and identified under SEM using the secondary electron imaging (SEI) mode with an energy dispersive X-ray microanalyzer (EDS). This enables reliable identification of gold particles and good quality micrographs of the cells to be achieved at the same time. The distribution of receptors for two lectins, concanavalin A (ConA) and wheat germ agglutinin (WGA), on the surface of cultured Raji cells and human erythrocytes is presented as an example. Raji cells and erythrocytes were fixed with glutaraldehyde, post-fixed with a glutaraldehyde-tannic acid mixture and then incubated with ConA- or WGA-coated gold particles. After dehydration and critical point drying, the specimen filters were mounted on copper stubs and coated with carbon. The cells were examined on a JEOL TEMSCAN 100CX II electron microscope. The gold particles could be identified with the EDS analyzer, which was able to detect the Au spectrum when the electron beam was focused on single gold particles using a magnification of 100,000 or more. High-resolution photographs of the same cells were obtained up to the same magnification of 100,000.

Cell Line↗

[Use of colloidal gold in ultrastructural cytochemistry].

Colloid gold stabilized by macromolecules with various binding characteristics proved to be usable in transmission electron microscopy: Nucleic acids localization was studied in tissue cultures after embedding by techniques autoimmune serum-protein A--gold and RNase--gold. Technique with serum autoantibodies against double-stranded DNA resulted in marking condensed chromatin. Further experiments with ultrastructural localization of other autoimmune components seemed to be perspective and of diagnostic importance. Technique with RNase--gold complex marked especially ribosomes, nucleolus and interchromatin nuclear spaces. Herpes virus, rotavirus and enterovirus were identified in negative contrast by the technique antivirus serum--protein A--gold. A higher warrant of evidence achieved by the method may be used in virologic diagnosis. A small amount of tubulin was found in isolated permeabilized nuclei of Xenopus laevis by a direct immunocytochemical method with complex monoclonal IgG against tubulin-gold. Binding of complex of triiodothyronine-bovine serum albumin--gold on the cytoplasmic membrane of LEP cells in a short term tissue culture showed a possibility of tracing non-peptidic hormones binding on specific receptors.

Animals↗

Platelet-derived growth factor labeled to colloidal gold for use as a mitogenic receptor probe.

Studies by others utilizing 125I-PDGF have indicated that target cells express a high affinity surface receptor for PDGF. We have bound purified platelet-derived growth factor (PDGF) to gold colloid particles to explore the interaction of PDGF with mouse 3T3 cells. The gold-PDGF complex consists of approximately 26 PDGF molecules electrostatically absorbed to gold colloid (approximately 14.1 nm). The gold-PDGF complex induced mitogenic stimulation similar to unbound PDGF, although a 5 to 6 fold greater amount of complexed PDGF was required for the same effect. Incubation of the gold-PDGF complex with 3T3 cells for 4 h at 4 degrees C revealed that 98% of the membrane binding was randomly distributed on the cell surface with respect to coated pits, with each cell binding 7000 to 11000 complexes. Addition of a 20-fold excess of unlabeled PDGF reduced surface binding of the gold-PDGF complex by 87% (1230 probes/cell). Warming to 37 degrees C followed by time-interval fixation permitted visualization of endocytosis of the complexes in coated vesicles (1-3 min), internalization (3-15 min) and lysosomal accumulation (15-60 min). Pretreatment of cultures with monensin (2 h, 10 microM) abolished receptor binding, internalization and subsequent mitogenesis of the gold-PDGF complex. These studies support the suggestion that PDGF requires a surface receptor to elicit mitogenesis.

Animals↗

Chronic interstitial nephritis associated with gold therapy.

A patient suffered chronic interstitial nephritis after receiving large quantities of gold salts for rheumatoid arthritis. Gold deposits were seen with transmission electron microscopy and confirmed by microprobe x-ray analysis both within renal tubular epithelial cells and interstitial macrophages and free within the renal interstitium. Clinical resolution of renal failure followed discontinuation of therapy with gold salts. Probable mechanisms of injury to renal tubular epithelial cells include uptake of gold by tubular epithelial cells and incorporation of gold into mitochondria, with subsequent cellular injury; interstitial deposits probably occur after necrosis of tubular epithelial cells, with release of gold into the interstitium and resultant inflammation. Thus, chronic interstitial nephritis can be added to the patterns of renal injury seen after gold therapy for rheumatoid arthritis.

Arthritis, Rheumatoid↗

Gold therapy in arthritis treatment.

The purpose of this article is to familiarize primary care providers with the use of gold salts in the treatment of rheumatoid arthritis. Gold salts used carefully can be very effective in controlling the disease when used in conjunction with other anti-inflammatory medicines. Side effects of gold therapy can be potentially dangerous; but used cautiously, gold can be of great value in the treatment of rheumatoid arthritis. The dosage schedule of gold salts described in this article is the current method of administering gold salts. The side effects--dermatological, hematological, and renal are described, and the parameters that need to be followed are also included. The flow sheet in the article can be used by health care providers as a part of the medical record in which lab results and amount of gold can be kept current. The article also emphasizes that a nurse practitioner should be aware of the emotional and financial status of the patient.

Arthritis, Rheumatoid↗

Inhibition of complement by gold sodium thiomalate.

The effect of gold sodium thiomalate on C3 and factor B activation by monosodium urate monohydrate (MSUM) and zymosan was studied using a quantitative immunoelectrophoretic assay for complement activation. C3 and factor B conversion by the classical pathway activator MSUM, was inhibited 50% and 100% by 3.2 x 10(-4)M and 10(-3)M gold sodium thiomalate, respectively. C3 and factor B conversion by the alternative pathway activator, zymosan, was much less susceptible to inhibition by gold. Gold at 10(-3)M, inhibited alternative pathway activation by only 30%. A 50% inhibition would have required 10(-2)M gold. There was no significant inhibition of complement activation through either pathway by less than 10(-4)M gold. Sodium thiomalate alone showed no inhibition. Studies using other crystals and immune complexes were confirmatory. Thus, there was no appreciable inhibition of the complement system at concentrations of gold attainable in the serum of patients receiving chrysotherapy. The in vivo significance of these findings is unknown.

Complement C3↗

Effect of auranofin dose regimen change upon cell-associated gold in rheumatoid arthritic patients.

We examined whether changes in auranofin dose regimen in rheumatoid arthritis (RA) patients affect cell-associated and/or serum gold levels. In 7 RA patients, a reduction in daily dosage of auranofin from 3 mg bid to 3 mg qd was correlated with a marked reduction (81%-95%) in cell-associated gold, whereas a return to the 3 mg bid dose level resulted in a reinstatement of cell-associated gold. These changes in cell-associated gold were not reflected in alterations of serum gold levels. This apparent lack of change in serum gold level as opposed to cell-associated gold suggests that this phenomenon warrants further investigation.

Anti-Inflammatory Agents↗

Gold coating of respiratory cilia for scanning electron microscopy.

The optimal thickness of gold coating of cilia for scanning electron microscopy was studied using respiratory mucosa obtained from pigs. We tested 8 different coating times, from 10 seconds to 4 minutes, which resulted in gold layer thicknesses varying from 16 +/- 1 nm to 100 +/- 3 nm. The thickness of the gold layer with a coating time of 60 seconds and voltage of 2.5 kV was 43 +/- 5 nm. This thickness of gold layer gave good image quality without causing any electric charging. With thinner gold films, the amount of electric charging increased. When the coating time was longer, the gold layer was thicker but image quality did not improve. The thicknesses of the gold layers were measured using transmission electron microscopy (TEM).

Animals↗

Surface treatment of gold alloys for resin adhesion.

This in vitro study compared three methods of surface treating gold alloys to improve resin adhesion. The tensile bond strengths and modes of failure between specimen pairs cemented with a chemically adhesive resin were recorded. Heat-treated gold alloy specimens were significantly more resistant to bond failure under tensile loading than were either alumina-blasted or tin-plated gold specimens. There was no statistically significant difference in bond failure between alumina-blasted and tin-plated gold specimens. The surface treatment altered the mode of failure from adhesive and/or adhesive-cohesive for alumina-blasted and tinplated gold specimens to cohesive (within the resin) for heat-treated gold specimens. Three case reports are presented to illustrate clinical applications of heat-treated gold alloys.

Adult↗

Physical and biological interface dose effects in tissue due to X-ray-induced release of secondary radiation from metallic gold surfaces.

Dose enhancement up to more than a factor of 100 was found in an environment of tissue-equivalent polymethylmethacrylate (PMMA) close to the surface of a thin metallic gold foil. The enhancement factors were determined for heavily filtered X rays (40 to 120 kV tube potential) under backscatter conditions, using thin-film radiation detectors with sub-micrometer resolution. The secondary electrons were found to range up to some 10 microm in tissue-equivalent material. Correspondingly, enhanced biological effects could be shown in vitro, using monolayers of C3H 10T1/2 mouse embryo fibroblasts exposed in intimate contact with the gold surface. The decay of the survival curves of cells irradiated on gold was significantly steeper than for those obtained from irradiation between PMMA disks with the same dose, also giving biological evidence for significantly enhanced doses at the gold interface. The shape of the inactivation curves resembled those for high-LET radiation, lacking a pronounced shoulder at the lower doses. Quantitatively, doses of e.g. 50 mGy (80 kV X rays) in homogeneous PMMA caused about 35% cell killing and 200 mGy about 80% when the cells were irradiated at the gold surface. From a comparison of these inactivation numbers with those found for irradiation between PMMA disks, biological dose enhancement factors for the cell system considered ranged up to about a factor of 50. In addition to cell inactivation, the in vitro irradiations of C3H 10T1/2 cells adjacent to the gold surface resulted in increased rates of oncogenic transformation. A dose of 100 mGy 80 kV X rays (measured in homogeneous PMMA) caused a frequency at an inserted gold surface comparable to that obtained with a dose of about 4.5 Gy of 60Co gamma rays in homogeneous PMMA.

Animals↗

Antiarthritic synergism of combined oral and parenteral chrysotherapy. II. Increased inhibition of activated leukocyte oxygen burst by combined gold action.

We have observed an antiarthritic effect of combined chrysotherapy in adjuvant arthritis. Since superoxide radicals (O2-) are potent mediators of rheumatoid inflammation, we studied the combined effect of auranofin (AF) and injectable golds on luminol-dependent chemiluminescence (LDCL) and O2- generation by cytochrome-c reduction of activated leukocytes by different receptor-mediated stimuli: phorbol myristic acetate, 10(-6) M; f-Met-Leu-Phe, 10(-6) M; and poly-L-histidine, 10(-5) M. AF, 0.6 and 0.9 micrograms Au/ml, inhibited 34 and 58% of O2- generation, respectively; the addition to AF of 0.3 micrograms Au/ml of gold thiosulfate (GTS) increased this inhibition to 84 and 97% of the oxygen burst. Similar synergistic potentiation inhibition was obtained by LDCL. When the inhibition of O2- generation by the combined action of AF and GTS was compared with AF + gold sodium thiomalate (GTM), only GTS showed an activation on AF's inhibition of the oxygen burst of human leukocytes. The ligand thiosulfate in equimolar concentrations to GTS had a statistically significant (P less than 0.01) inhibitory effect on AF's blockade of O2- generation during the first 5 min of the interaction with the PMNs; thiomalate had no effect. Sequential pretreatment of PMNs with AF and GTS on O2- generation revealed that for synergism of combined gold action to take place, the cell membrane had to be subjected first to the action of oral gold or to the simultaneous combined action of oral and parenteral gold.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

The subcellular distribution of gold in monkey liver, kidney and spleen, in vivo.

1. The subcellular distribution of gold in the livers, kidney cortex and the spleens of rhesus monkeys was determined at 2, 10 and 20 days after the administration of sodium (195Au)-aurothiomalate. The serum gold levels were also determined over the period of study. 2. With the continued decrease in the serum gold levels from day 1 to day 20, a continued increase in the tissue levels of the organs studied was observed. The corresponding subcellular fractions of the tissues also showed continued increases in the radioactive concentrations of gold. 3. Gold was found to localise in all the organelles of the cells in the liver, kidney cortex and the spleen, though in varying amounts. The largest increases in the concentrations of gold from day 2 to day 20 were found in the lysosomal bodies of liver and kidney. The concentrations in the kidney cortex increased from approximately five times those in the liver or the spleen on day 2 to about eight times those on day 20.

Animals↗