ArticleLiterature Review

Use of gold implants as a treatment of pain related to canine hip dysplasia - A review. Part 1: Background and current state of research regarding the effects of implanting gold in tissue

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Gold-bead implantation as a method of pain treatment in dogs suffering from osteoarthritic disease is receiving increasing attention in veterinary medicine. For the present article, publications from veterinary books and journals were collected and evaluated, together with related articles in human medicine. After providing an overview of the historical use of gold and gold compounds, the technique of implanting this noble metal is introduced. The reasons for establishing the terms gold acupuncture and gold (bead) implantation are described, considering the question whether and what kind of methodological differences exist behind these terms. Next, previous publications concerning the effects of gold implantation in tissue are summarised. In 2002 it was proven that gold ions are released from the surface of gold implants by a process termed dissolucytosis. Subsequent publications further investigated details about the interaction between gold ions and tissue as well as the distribution pattern of bio-released ions. Gold compounds were previously used for chrysotherapy in human medicine until medication with fewer side effects became established. The anti-inflammatory and immuno-modulatory properties of gold compounds were used to treat rheumatoid arthritis. Current research aims to ascertain whether the anti-inflammatory and immuno-modulating effects of gold compounds are imitated by gold ions released from gold implants at a local level. In conclusion, the present review summarises important findings about the effects of gold implanted in tissue. However, further research is necessary to estimate the limitations and benefits of this auromedication.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

Article
Gold bead implantation/gold acupuncture is becoming increasingly used in veterinary medicine as a method of pain treatment in cases of osteoarthritic diseases. Part one of the overview dealing with the use of gold implants as a treatment of canine hip joint dysplasia (cHD) introduced the method of implanting gold in tissue and publications which investigated the subsequent effects of implantation. This article focuses on publications concerning the clinical effectiveness of gold implantation within the scope of pain therapy in cHD. Due to the study design, a classification using evidence-based levels (EbL) was carried out. Three double-blind, placebo-controlled randomised studies (EbL II) were considered together with three retrospective studies on own patients (EbL IV) and five case studies (EbL IV). While the case and retrospective studies reported impressive therapeutic success in treating cHD-incurred pain with gold implantation, a pain-reducing effect through gold implantation was only demonstrated in one of the three double-blind studies. The two remaining EbL II studies found no differences between the placebo-group and the group of dogs treated with gold implantation. In one of these two studies, kinematic and kinetic gait analyses were used for objective evaluation of the effects of the treatment. Thus, the only study that carried out an objective evaluation of the therapeutic result of gold implantation came to the conclusion that the method is ineffective. For a concluding assessment of gold implantation in the case of cHD, gait analysis studies investigating the effects of gold implantation in comparison to a standard treatment with nonsteroidal anti-inflammatory drugs are currently lacking.
Article
Full-text available
Inflammatory changes associated with periarticular pure gold bead implants were studied in dogs involved in a clinical trial investigating motor dysfunction and chronic pain owing to hip joint dysplasia and osteoarthritis. Gold beads were percutaneously implanted via a needle into different locations surrounding the greater trochanter of the femur. Nine dogs with implants were necropsied. In all examined animals, characteristic histologic lesions were observed in the tissue surrounding the gold implants--namely, a fibrous capsule composed of concentric fibroblasts intermixed with a variable number of inflammatory cells and a paucicellular innermost layer of collagen with a few fibrocyte-like cells in empty lacunae. Lymphocytes dominated the inflammatory infiltrate, with rarely observed macrophages present in close proximity to the implant site. No giant cells were observed. Immunohistochemistry showed mixed populations of lymphocytes, both CD3 positive (T cells) and CD79a positive (B cells), which in some cases formed lymphoid follicles. Diffuse inflammatory changes were present to a minor extent in the perimysium and surrounding fascia. The inflammation observed in dogs is similar to that observed with gold implants in humans. It is possible that the clinically beneficial effect of gold beads for chronic osteoarthritis depends on sustained localized inflammation with localized release of soluble mediators. The encapsulation of the implant by a paucicellular and poorly vascularized fibrous capsule may help prevent an exaggerated inflammatory reaction by sequestering the gold bead from the surrounding tissue.
Article
Full-text available
Recent experimental research has shown that metallic gold releases charged gold atoms when placed intracerebrally and that the liberated gold ions affect inflammation in the brain. The observations suggest that metallic gold can be used as a safe suppressor of inflammation in the central nervous system.
Article
Full-text available
Thirty-eight dogs with hip dysplasia were studied to evaluate the use of gold wire implants at acupuncture points around the hip joints. They were assigned at random into two groups of 19. In the treated group, gold wire was inserted through hypodermic needles at electrically found acupuncture points around both hips. In the control group, the areas were prepared in the same way but had only the skin pierced at sites which were not acupuncture points, with a needle of the same size as that used in the treated group. Over a period of six months the dogs were studied repeatedly by two veterinarians and by the dogs' owners who were unaware of the treatments the dogs had received; they assessed the dogs' locomotion, hip function and signs of pain. Radiographs were taken at the beginning and end of the study. Although the data collected from both groups by the veterinarians and the owners showed a significant improvement of locomotion and reduction in signs of pain (P=0.036 for the veterinary evaluation and locomotion and P=0.0001 and P=0.0034 for the owners' evaluation of locomotion and pain, respectively), there were no statistically significant differences between the treated and control groups (P=0.19 and P=0.41, P=0.24, respectively).
Article
Full-text available
For some years, the implantation of small pieces of gold has been used as an unauthorised remedy for osteoarthritis and pain. The aim of the present study was to evaluate whether gold ions are released from gold implants. Pieces of pure gold were placed in the connective tissue of skin, bone and brains of anaesthetised animals. Ten days to several months later the animals were anaesthetised and killed by transcardial perfusion. Tissue blocks containing the gold pieces were cut, and the sections were silver-enhanced by autometallography. It was found that gold ions are released from the implanted gold and diffuse out into the surrounding tissue. The gold-containing cells in connective tissues were macrophages, mast cells and fibroblasts. In the brain, gold accumulated in astrocytes and neurons. Proton-induced X-ray emission spectroscopy analysis of the tissue surrounding gold implants confirmed that gold ions are liberated. The findings suggest that the gold implant technique, on a local scale, mimics systemic treatment with a gold-containing drug.
Article
Full-text available
Seventy-eight dogs with pain due to hip dysplasia were studied in a controlled, double-blind clinical trial to evaluate gold bead implantation as a pain-relieving treatment. The dogs were randomly assigned to two groups, 36 in the gold implantation group and 42 in the placebo group. Both groups were treated equally regarding anaesthesia, hair clipping and penetration of the skin with the same type of needle. The gold implantation group had small pieces of 24 carat gold inserted through needles at five different acupuncture points and the placebo group had the skin penetrated at five non-acupuncture points so as to avoid any possible effect of stimulating the acupuncture points. A certified veterinary acupuncturist marked the points, and two surgeons performed the implantations according to a randomisation code made in advance. After 14 days, three months and six months, the owners assessed the overall effect of the treatments by answering a questionnaire, and the same veterinarian examined each dog and evaluated its degree of lameness by examining videotaped footage of it walking and trotting. The treatment was blinded for both the owners and the veterinarian. There were significantly greater improvements in mobility and greater reductions in the signs of pain in the dogs treated with gold implantation than in the placebo group. The veterinarian's and the owners' assessments corresponded well.
Article
Full-text available
This review concerns the importance of length and time on physicochemical interactions between living tissue and biomaterials that occur on implantation. The review provides information on material host interactions, materials for medical applications and cell surface interactions, and then details the extent of knowledge concerning the role(s) that surface chemistry and topography play during the first stage of implant integration, namely protein adsorption. The key points are illustrated by data from model in vitro studies. Host implant interactions begin nanoseconds after first contact and from then on are in a state of flux due to protein adsorption, cell adhesion and physical and chemical alteration of the implanted material. The many questions concerning the conformational form and control of bound proteins and how this may impact on cell adhesion in the first instance and later on cell signalling and implant integration can be answered by systematic investigations using model materials. Only then we will be in a more informed position to design new materials for use in the body.
Article
Full-text available
The present study demonstrates that cultured macrophages are able to liberate gold ions from metallic gold surfaces, a process suggested to be called "dissolucytosis", in a way analogous to the release taking place when metallic implants are placed in a body. Using the ultra-sensitive autometallographic (AMG) technique, we demonstrate that murine macrophages grown on a surface of metallic gold liberate gold ions. Ultra-structural AMG reveals that the gold ions are located in an ultra-thin membrane-like structure, "the dissolution membrane", intervened between the macrophages and the metal surface. The presence of AMG silver enhanced gold nanoparticles in the dissolution membrane proves that the release of charged gold atoms takes place extracellularly. The dissolution membrane is most likely secreted and chemically controlled by the "dissolucytes", here macrophages, and the membrane is essential for the dissolution of metal implants and particles, which cannot be phagocytosed. Our findings support the notion that whenever a metallic gold surface is attacked by dissolucytes, gold ions are liberated and taken up by surrounding cells. As gold ions can suppress the inflammatory process, it is reasonable to expect that when dissolucytosis takes place in the living organism the liberated gold ions will cause local immunosuppression.
Article
Full-text available
Insertions of orthopedic implants are traumatic procedures that trigger an inflammatory response. Macrophages have been shown to liberate gold ions from metallic gold. Gold ions are known to act in an antiinflammatory manner by inhibiting cellular NF-kappaB-DNA binding and suppressing I-kappa B-kinase activation. The present study investigated whether gilding implant surfaces augmented early implant osseointegration and implant fixation by its modulatory effect on the local inflammatory response. Ion release was traced by autometallographic silver enhancement. Gold-coated cylindrical porous coated Ti6Al4V implants were inserted press-fit in the proximal part of tibiae in nine canines and control implants without gold inserted contralateral. Observation time was 4 weeks. Biomechanical push-out tests showed that implants with gold coating had approximately 50% decrease in mechanical strength and stiffness. Histomorphometrical analyses showed gold-coated implants had a decrease in overall total bone-to-implant contact of 35%. Autometallographic analysis revealed few cells loaded with gold close to the gilded implant surface. The findings demonstrate that gilding of implants negatively affects mechanical strength and osseointegration because of a significant effect of the released gold ions on the local inflammatory process around the implant. The possibility that a partial metallic gold coating could prolong the period of satisfactory mechanical strength, however, cannot be excluded.
Article
Full-text available
Traumatic brain injury results in loss of neurons caused as much by the resulting neuroinflammation as by the injury. Gold salts are known to be immunosuppressive, but their use are limited by nephrotoxicity. However, as we have proven that implants of pure metallic gold release gold ions which do not spread in the body, but are taken up by cells near the implant, we hypothesize that metallic gold could reduce local neuroinflammation in a safe way. Bio-liberation, or dissolucytosis, of gold ions from metallic gold surfaces requires the presence of disolycytes i.e. macrophages and the process is limited by their number and activity. We injected 20-45 mum gold particles into the neocortex of mice before generating a cryo-injury. Comparing gold-treated and untreated cryolesions, the release of gold reduced microgliosis and neuronal apoptosis accompanied by a transient astrogliosis and an increased neural stem cell response. We conclude that bio-liberated gold ions possess pronounced anti-inflammatory and neuron-protective capacities in the brain and suggest that metallic gold has clinical potentials. Intra-cerebral application of metallic gold as a pharmaceutical source of gold ions represents a completely new medical concept that bypasses the blood-brain-barrier and allows direct drug delivery to inflamed brain tissue.
Article
According to reports from the US and Europe degenerative arthropathies, as hip dysplasia and other painful hip processes, can successfully be treated by implanting gold particles into the depth of acupuncture points. A presently discussed hypothesis claims the pathologically negative charge in the joint area to be neutralized and reduced to a normal degree by the implanted gold. Three dogs are presented as successfully treated with this method. One can well imagine that this method could also seem promising in suitable cases within human medicine.
Article
Beschrieben wird der Fall einer falsch angewandten Goldakupunktur bei einer Deutschen Dogge, die fatale Störungen des Allgemeinbefindens zur Folge hatte. Da eine Heilung des Tieres nicht möglich war, bestand die homöopathische Behandlung allein in der Unterdrückung der Aurumsymptomatik. Die abschließende Bewertung aus homöopathischer Sicht wird ergänzt durch eine Einschätzung desselben Falles aus der Perspektive der traditionellen chinesischen Veterinärmedizin auf Seite 48. Summary The article describes the case of wrong therapy of gold acupuncture on a German Dogge with fatal disorders regarding its general health. The complete recovery of the dog was not possible and thus homeopathic treatment was the only possibility of suppressing the Aurum symptomatic. Additionally an evaluation from the homeopathic point of view and Traditional Chinese Veterinary Medicine is offered.
Article
Background In veterinary medicine, the implantation of pure gold beads in acupuncture points has been a common procedure for 30 years. In 1973, Dr. Young reported on the efficacy in dogs suffering from epilepsy. Dr. Durkes used this method on dogs with hip dysplasia. In the meantime, a great number of veterinarians has worked with gold implants to treat various symptoms. Although there have been many successful case reports, the exact mechanism behind these findings has yet to be elucidated.Objectives It is assumed that electric activity originating from the 24 carat gold implants inserted into muscles in the proximity of the treated joint could be responsible for the analgetic effect. This may seem feasible, although experts know that 24 ct gold does not consist of 100 % pure gold. It rather always contains so-called ”accompanying side elements” like silver, iron, copper, lead, bismuth etc. needed to stabilize the material. Pure 24 ct gold consists of 99.95 % gold and 0.05 % „acconpanying side elements”. The aim of this study is to investigate the role these accompanying elements play in the therapeutic effect of gold implants.Methods The postulated importance of the „accompanying side elements” in the induction of an electric field inside an acidic environment as resembled by damaged and inflamed body tissue was the initiation to start the experimental measurements on a specially prepared, in-vitro acidic veal model. A portable measuring instrument was used and 6 measuring sets of an electric field between two 24 ct pure gold electrodes were recorded followed by the same procedure between a 24 ct gold and a pure silver 925 electrode, both unmoved and in motion.ResultsAfter insertion of the electrodes into the veal models, an electric potential could be detected between two 24 ct gold electrodes (pure gold to pure gold) even in the unmoved experiment. When the electrodes were moved, the electric potential increased significantly. Electrodes in the combination pure gold to pure silver 925 showed a higher indicated value even when unmoved, and also increased in motion.ConclusionA common therapy for dogs with pain due to hip dysplasia is the insertion of pure gold implants around the painful joint. After implantation, the animals show less pain and soon will be able to move like before. This effect is undoubtedly due to the gold implantation and can be reproduced. The described measurements allow the conclusion that accompanying side elements within the gold implants will, in an acidic environment, produce an electric potential which in turn will inactivate pain mediators such as serotonin and histamine. The described effect will improve in motion.
Article
Vor 90 Jahren wurde Gold erstmals von Robert Koch in der Annahme einer mykobakteriellen Verursachung der rheumatoiden Arthritis in Analogie zur Tuberkulose intravenös als Zyan-Gold-Verbindung eingesetzt. Schnell wurde klar, dass diese ursprüngliche Rationale nicht für die positiven Wirkungen von Gold verantwortlich ist, und seit dieser Zeit bemühen sich die Wissenschaftler um die Aufklärung des Wirkungsmechanismus von Gold in der Therapie rheumatischer Erkrankungen. Nahezu in jedem Bereich des Immunsystems wurden inhibierende Wirkungen des Goldes nachgewiesen, wobei unklar ist, ob es einen gemeinsamen Nenner dieser Wirkungen gibt oder aber ob Goldverbindungen parallele Wirkungsmechanismen beinhalten, die unabhängig voneinander aktiv sind. Jedoch erscheint auch anhand jüngster Studien die Reaktivität von Goldverbindungen mit Thiol-Gruppen ein entscheidender Faktor zu sein. Bei der Analyse der Wirkungen von Gold auf die unterschiedlichen Phasen der Immunreaktion spielt vermutlich Gold gleich am Anfang, nämlich bei der Aufnahme von Antigenen in antigenpräsentierende Zellen eine wesentliche Rolle. So wird Gold insbesondere von Makrophagen aufgenommen und lagert sich dort in den Lysosomen der Makrophagen ab. Hier entstehen die sog. Aureosomen, wobei Gold I nach Loslösung von seinem Trägermolekül die Antigenprozessierung hemmt. Hier spielen insbesondere Peptidantigene eine wichtige Rolle, die schwefelhaltige Aminosäuren beinhalten, wie Cystein und Methionin, so dass die T-Zell-Erkennung solcher Peptide gehemmt wird. Auch auf der molekularen Ebene konnte zwischenzeitlich gezeigt werden, dass Gold die NF-Kappa B-Bindungsaktivität unterdrückt sowie die Aktivierung der I-Kappa B-Kinase behindert. Vermutlich durch diesen Mechanismus kommt es anschließend zu einer verminderten Produktion pro-inflammatorischer Enzyme, insbesondere von TNF-α, Interleukin-1 und Interleukin-6. Auf der nachfolgenden T-Zell-Ebene führt Gold vermutlich über eine Hochregulation der mRNA für Interleukin-4 zu einer Verschiebung der T-Zell-Subpopulationen in Richtung Th2. Zudem wird die Aktivierung der B-Zellen vermutlich ebenfalls über einen T-Zell-vermittelten Mechanismus behindert. Auf der Effektorebene kann Gold einen weiteren Einfluss auf proteolytische Enzyme durch Interaktion mit Disulfidbrücken ausüben. Weiterhin zeigen die destruktiven synovialen Fibroblasten bei in vitro-Studien toxische Deformierungen und Lysezeichen, so dass möglicherweise auch in dieser Phase Gold wirksam ist. Zusammenfassend ist Gold weiterhin eines der faszinierendsten antirheumatischen Pharmaka mit einem außerordentlich vielfältigen Wirkungsspektrum. Durch weitere Analyse molekularer Mechanismen, insbesondere im Bereich der Signaltransduktion, dürften in absehbarer Zeit neue fundamentale Erkenntnisse über seine Wirkung entwickelt werden, die sicher auch Rückschlüsse auf die Wirksamkeit anderer Antirheumatika erlauben und zum Pathogeneseverständnis der rheumatoiden Arthritis beitragen werden. Gold was first used 90 years ago by Robert Koch for the treatment of tuberculosis based on the assumption that rheumatoid arthritis was caused by microbacteria. It soon became clear that this would not explain the action of gold in rheumatoid arthritis, and since then scientists have been struggling to elucidate the mechanisms of gold‘s action in the treatment of rheumatic diseases. In nearly every area of immunology inhibiting actions of gold could be documented; however, it is still unclear if there is a common denominator or if there are parallel modes of actions which are independent of each other. In any case, also based on recent studies the reactivity of gold compounds with thiol groups appears to the predominant factor. Analyzing the actions of gold in the different phases of an immune reaction suggested that gold plays an important role already in the initiation, namely the uptake and presentation of foreign antigens. Thus, gold is taken up by the macrophages and stored in the lysosomes which are called aureosomes where gold inhibits antigen processing. Especially peptide antigens, which contain sulfur such as cysteine and methionine, are important. Moreover, it could be shown that gold supresses NF-kappa B binding activity as well as the activation of the I-kappa B-kinase. This mechanism results in a subsequently reduced production of pro-inflammatory cytokines, most notably TNF-α, interleukin-1 and interleukin-6. On the subsequent T-cell level, gold has been shown to induce an upregulation of IL-4mRNA, resulting in a shift of the T-cell population to the Th2 phenotype. Moreover, the activation of T-cells is inhibited. On the effector level, gold inhibits proteolytic enzymes and can result in the destruction of synovial fibroblasts. In conclusion, gold remains one of the most fascinating antirheumatic drugs with multiple modes of actions.    The future analysis of molecular mechanisms, especially with regard to signal transduction, will lead to new fundamental knowledge of gold action, possible allowing a further understanding of the pathogenesis of rheumatoid arthritis.
Article
Background Various implants are used to treat lagophthalmos in facial paralysis. The implantation of gold or platinum eyelid weights (lid loading) is being used increasingly. Histological changes have not yet been systematically examined in the implant capsule during explantation of the eyelid weight. Material und methods Of 26 explanted implants, 18 implants in 17 patients were followed-up using light microscopy from 1997 to 2004. We semi-quantitatively evaluated the density of the inflammatory infiltrate and recorded the occurrence of foreign bodies in the tissue. The inflammatory infiltrate was also immunohistochemically examined to characterize cellular composition. Results In the semi-quantitative examination of inflammatory infiltration density, 60% of the gold implants showed a moderately dense or dense inflammatory infiltrate, while there was moderately dense infiltration in only 12.5% of the platinum implants. The immunohistochemical examination revealed a mixed lymphocytic inflammatory infiltrate which tended to a preponderance of B lymphocytes (humoral response). This is typical of unspecific chronic inflammation. Conclusions Both gold and platinum are suitable for treating lagophthalmos, however, platinum has a higher density and better biocompatibility than gold.
Article
Metal complexes have shown interesting preclinical and clinical results as antitumor drugs and platinum compounds are well established in current cancer chemotherapy. However, the platinum based treatment of tumoral diseases is massively hampered by severe side effects and resistance development. Consequently, the development of novel metallodrugs with a pharmacological profile different from that of the platinum drugs is in the focus of modern medicinal chemistry and drug design.Among the non-platinum antitumor drugs, gold complexes have recently gained considerable attention due to their strong antiproliferative potency. In many cases the cell growth inhibiting effects could be related to anti-mitochondrial effects making gold species interesting drug candidates with a mode of action different from that of the platinum agents. The spectrum of gold complexes described as antiproliferative compounds comprises a broad variety of different species including many phosphine complexes as well as gold in different oxidation states.This presentation gives an overview of the relevant medicinal chemistry of known gold complexes with in vitro and in vivo tumor growth inhibiting properties.
Article
Electroacupuncture (EA) applied to both legs of the rat for 30 min (1session) raised the average tail flick latency to 89% above the control level. Repeated electroacupuncture for 6 sessions, with 30 min between successive sessions, resulted in a gradual decline in the hypoalgesic effect. The time-course of the development and disappearance of acupuncture tolerance was studied. A bidirectional cross-tolerance between electroacupuncture and morphine points to the similarity between the underlying mechanisms of electroacupuncture hypoalgesia and morphine analgesia.
Article
The purpose of this study was to evaluate both, clinically and with electroencephalographic (EEG) recordings, the effect of gold wire implants in acupuncture points in dogs with uncontrolled idiopathic epileptic seizures. Fifteen dogs with such diagnosis were enrolled in the study. A first EEG recording was performed in all dogs under anaesthesia with xylazine (1 mg/kg) and propofol (6 mg/kg) before the treatment protocol, and a second EEG was performed 15 weeks later. Relative frequency power, intrahemispheric coherence available through EEG, number of seizures and seizure severity were compared before and after treatment using a Wilcoxon signed-rank test. There were no significant statistical differences before and after treatment in relative power or in intrahemispheric coherence in the EEG recording. However, there was a significant mean difference in seizure frequency and seizure severity between control and treatment periods. After treatment, nine of the 15 dogs (60%) had at least a 50% reduction in seizures frequency during the 15 weeks established as follow-up of this treatment.
Article
The aurocyanide anion, Au(CN) (2) (-) , is a human metabolite of several anti-rheumatic gold complexes containing monovalent gold (I) bound to a sulphur ligand. This article reviews some of the chemical and pharmacological properties of this intriguing metabolite, and reports its anti-arthritic and anti-inflammatory activity in rats. Au(CN) (2) (-) is generated from the therapeutic gold complexes by small amounts of hydrogen cyanide, HCN, produced from thiocyanate, SCN(-), by myeloperoxidase (MPO) an enzyme in neutrophils which normally produces hypochlorite, OCl(-). Thus, Au(CN) (2) (-) is formed at sites of inflammation where activated neutrophils are present. This includes atherosclerotic lesions as well as inflamed joints. MPO also oxidises Au(CN) (2) (-) to Au(III) complexes such as Au(CN) (4) (-) .Au(CN) (2) (-) is normally a very stable monovalent gold complex. In a biological context, only low concentrations are ever present at both extracellular and intracellular sites. However, Au(CN) (2) (-) produced locally may facilitate the cellular uptake and hence the therapeutic and toxic effects of gold drugs. Au(CN) (2) (-) may also be involved in a redox cycle where Au(CN) (2) (-) is oxidised to Au(CN) (4) (-) which is, in turn, reduced back to Au(CN) (2) (-) by endogenous thiols. There are still many questions to be resolved concerning Au(CN) (2) (-) including its intrinsic toxicity and the extent to which it may contribute to the overall anti-arthritic activities of the gold-thiolates from which it is formed in vivo.
Article
To describe a technique to treat paralytic lagophthalmos and exposure keratitis with gold weight implants covered by levator aponeurosis. The authors studied a case series of 29 patients who underwent surgical treatment for paralytic lagophthalmos using the technique of gold weight implantation covered by the aponeurosis of the levator palpebrae superioris muscle between June 1997 and December 2006. None had undergone previous surgical treatment. All patients sustained their implants; there were no cases of extrusion, dislocation, or infection. Patients had significant improvement of symptoms, especially exposure keratopathy, with lagophthalmos dimensions decreased from 4 to 5 mm preoperatively to 0.5 mm after surgery. Excellent results were obtained by recessing the levator palpebrae superioris muscle aponeurosis with relaxing incisions and advancing it to overly the gold weight implant completely. Visibility of the implant in the pretarsal upper eyelid surface was minimized, extrusion was avoided, and good eyelid position was obtained.
Article
By causing long-term stimulation, gold wire implantation at acupoints has been used empirically to prolong the effects of acupuncture. This study shows that subcutaneous gold wire implantation at acupoints has long-term effects on bone regeneration in the rat ulna bone defect model.
Article
Brain injury represents a major health problem and may result in chronic inflammation and neurodegeneration. Due to antiinflammatory effects of gold, we have investigated the cerebral effects of metallic gold particles following a focal brain injury (freeze-lesion) in mice. Gold particles 20-45 microm in size or the vehicle (placebo) were implanted in the cortical tissue followed by a cortical freeze-lesioning. At 1-2 weeks post-injury, brains were analyzed by using immunohistochemistry and markers of inflammation, oxidative stress and apoptosis. This study shows that gold treatment significantly reduces the cerebral levels of tumor necrosis factor alpha (TNFalpha), oxidative DNA damage (as judged by 8-oxoguanine levels), and pro-apoptotic markers (cleaved caspase-3, cytochrome c leakage), when compared to those of controls. The data presented here points toward gold particles as a tool to modulate the cerebral response to injury.
Article
Gold bead implantation is an experimental area of study in the acupuncture field dealing with chronic diseases. Special acupuncture techniques are required to implant the gold beads successfully in the proper location. Gold beads are used to treat degenerative joint disease, osteochondritis, osteochondritis dessicans, ventral spondylosis, and seizures.
Article
Experiments have been conducted to investigate a possible mechanism which might explain why aurothiomalate (Autm), a gold complex used in the treatment of rheumatoid arthritis, is active in vivo but not in vitro, by testing the hypothesis that Autm is converted to aurocyanide by activated polymorphonuclear leukocytes (PMN) which generate cyanide from thiocyanate, an anion which is present in plasma at concentrations ranging from 20 to 200 microM. Two-stage experiments were conducted in which PMN, in the first stage, were activated by opsonized zymosan in the presence of Autm both with and without thiocyanate. Then, in the second stage, the effect of the drugs on superoxide (O2-) production stimulated by a further addition of zymosan was measured. Autm at concentrations of 10 and 100 microM decreased O2- production if thiocyanate was present, but not if it was absent. By contrast, preformed aurocyanide at 10 and 100 microM decreases O2- production by PMN stimulated by opsonized zymosan both in the presence and absence of thiocyanate. Changes in the ultraviolet spectra of the supernatants of PMN indicated that aurocyanide was formed by activated PMN in the presence of thiocyanate but not in its absence.
Article
Nuclear factor kappa B (NF-kappa B) is a transcription factor that is critical for the inducible expression of multiple cellular and viral genes. DNA binding activity is essential for its function. Here, we report that gold compounds, especially aurothioglucose (AuTG), have a strong inhibitory effect on NF-kappa B-DNA binding. Our finding also reveals that Zn2+ is a necessary component of NF-kappa B for its DNA binding activity and that gold ion can efficiently block NF-kappa B-DNA binding, presumably through oxidation of the cysteins associated with zinc. This redox mechanism may provide an explanation for the observed efficacy of gold compounds in the treatment of rheumatoid arthritis.
Article
There is considerable evidence that the anti-rheumatic gold complexes are activated by their conversion to aurocyanide. In order to understand the mechanism of production of aurocyanide, we investigated the involvement of myeloperoxidase in the reaction. This haem enzyme of neutrophils and monocytes uses hydrogen peroxide to oxidise chloride and thiocyanate to hypochlorous acid and hypothiocyanite, respectively. When aurothiomalate (10 microM) was incubated with thiocyanate (200 microM), hydrogen peroxide (100 microM) and myeloperoxidase (20 nM), it was transformed to a product that was spectrally identical to authentic aurocyanide. Aurothiomalate was quantitatively converted to aurocyanide in about 10 min at pH 6.0 and in 40 min at pH 7.4. Aurocyanide formation occurred after myeloperoxidase had used all the hydrogen peroxide available to produce hypothiocyanite. Thus, the cyanide must have formed from the slow decomposition of hypothiocyanite. The rate of aurocyanide production was increased in the presence of 100 mM chloride, which indicates that hypochlorous acid accelerates the formation of cyanide. Hypochlorous acid (100 to 400 microM) reacted non-enzymatically with thiocyanate (200 microM) and aurothiomalate (10 microM) to produce aurocyanide. Thus, aurocyanide is produced by two processes, involving both the formation of hypothiocyanite and hypochlorous acid. Aurocyanide is an effective inhibitor of the respiratory burst of neutrophils and monocytes and the proliferation of lymphocytes. Therefore, aurothiomalate may attenuate inflammation by acting as a pro-drug which is reliant on neutrophils and monocytes to produce hypothiocyanite. When the hypothiocyanite decays to hydrogen cyanide, the pro-drug is converted to aurocyanide which then suppresses further oxidant production by these inflammatory cells.
Article
Biomimetic pathways for the oxidation of [Au(CN)(2)](-), a gold metabolite, and further cyanation of the gold(III) products to form Au(CN)(4)(-) were investigated using 13C NMR and UV-Visible spectroscopic methods. Hypochlorite ion, an oxidant released during the oxidative burst of immune cells, was employed. The reaction generates mixed dicyanoaurate(III) complexes, trans-[Au(CN)(2)X(2)](-), where X(-) represents equilibrating hydroxide and chloride ligands, and establishes the chemical feasibility of dicyanoaurate oxidation by OCl(-) to gold(III) species. This oxidation reaction suggests a new procedure for synthesis of H[Au(CN)(2)Cl(2)]. Reaction of trans-[Au(CN)(2)X(2)](-) (X(-)=Cl(-) and Br(-)) or [AuCl(4)](-) with HCN in aqueous solution at pH 7.4 leads directly to [Au(CN)(4)](-) without detection of the anticipated [Au(CN)(x)X(4-x)](-)intermediates, which is attributed to the cis- and trans-accelerating effects of the cyanides. The reduction of [Au(CN)(4)](-) by glutathione and other thiols is a complex, pH-dependent process that proceeds through two intermediates and ultimately generates [Au(CN)(2)](-). These studies provide further insight into the possible mechanisms of an immunogenically generated gold(I)/gold(III) redox cycle in vivo.
Article
Gold sodium thiosulfate (GSTS) is reputed to be the most reliable gold antigen, but control studies are still required. Although Koreans have more varied sources of contact with gold, such as herbal medicines with gold coatings and indwelling gold acupuncture needles, no epidemiological studies have been performed. This study examined the frequency and sources of contact allergy to gold in South Korea by a multicenter study. Patch testing with 0.5% GSTS in pet. was conducted in 255 eczema patients and 58 control subjects. Results were observed at 21 days (D) to ensure there were no undetected late reactions in 54 observed patients and 47 controls. 8 (3.1%) of the 255 patients reacted positively to GSTS, including 1 with a late reaction. 1 of the 58 controls showed a positive reaction to GSTS on D4 with a negative reaction on D14. Clinical relevance was lacking in the patients with positive reactions. Unexpectedly, the above particular sources of gold contact gave rise to few allergic reactions in our patients.
Article
Despite increasing sales of gold supplements, and claims of benefits for neurological and glandular conditions, gold has received little attention in modern medical literature except as a drug for rheumatoid arthritis. Historically, however, gold had a reputation as a "nervine," a therapy for nervous disorders. A review of the historical literature shows gold in use during the 19th century for conditions including depression, epilepsy, migraine, and glandular problems such as amenorrhea and impotence. The most notable use of gold was in a treatment for alcoholism developed by Keeley (1897). In the modern medical literature, gold-containing medicines for rheumatoid arthritis are known to have occasional neurotoxic adverse effects. There are also a few studies suggesting a role for gold as a naturally occurring trace element in the reproductive glands. One small recent study demonstrated a possible positive effect of gold on cognitive ability. There is a need for more experimental and clinical research of the neuropharmacology and neurochemistry of gold, and for the exploration of gold's possible role as a trace element.
Article
Therapy of rheumatoid arthritis (RA) is typically characterized by the sequential use of disease-modifying anti-rheumatic drugs (DMARDs). This study aimed to reveal treatment patterns with traditional DMARDs and their changes during the two decades before the recent introduction of new DMARDs. A total of 593 RA patients were followed from their first presentation to our clinic throughout the course of their disease; 222 patients received their first DMARD therapy while under our care. More than 2,300 patient years of therapy were analysed for the efficacy [using C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as surrogates] and duration of drug therapy of consecutive DMARDs. Before 1985, 65-90% of initial DMARDs were gold compounds, but their use decreased continuously thereafter. Antimalarial (AM) drugs were important initial DMARDs in new patients at all times, whereas sulphasalazine (SSZ) and methotrexate (MTX) gained increasing significance after 1985 (the first DMARD was MTX in up to 29% of new patients). Penicillamine (DPA), azathioprine (AZP), cyclosporin (CyA) and combination therapies were not usually employed initially, but were reserved for the later course of the disease. Gender, age and rheumatoid factor were not different between patients receiving different DMARDs. The baseline acute-phase response was higher in patients treated with MTX (mean CRP 3.5 mg/dl) than in those treated with SSZ (CRP 2.4 mg/dl; P < 0.05) or AM (CRP 2.1 mg/dl; P < 0.05), suggesting that MTX was used preferentially in patients with high disease activity. On the other hand, once AM or SSZ had been discontinued, MTX was the most common subsequent DMARD (in 31 and 56% respectively). Comparison of first DMARDs with subsequent ones revealed that first DMARDs were more effective: the acute-phase response decreased most prominently during first therapies (CRP reduction was 1.28 mg/dl during first courses and 0.35 mg/dl during fourth or later courses; P < 0.01); and retention rates were significantly longer for first compared with subsequent therapies (median of 24.5 months for first and 18.6 months for fourth or subsequent therapies; P < 0.001). MTX was the most commonly employed DMARD therapy for RA and was used increasingly as first therapy in newly diagnosed RA. Patients with high disease activity were given MTX therapy more often than other DMARDs, while those with low activity were more likely to receive SSZ or AM, and MTX on failure of these drugs. First DMARDs in new patients were retained longer than subsequent DMARDs, apparently because they are more effective.
Article
Nitric oxide (NO) is a destructive mediator produced by activated chondrocytes. The aim of the present study was to investigate the effect of disease-modifying anti-rheumatic drugs (DMARDs) on interleukin-1beta (IL-1beta)-induced NO production in chondrocyte cultures, and in human osteoarthritic cartilage. Aurothiomalate, hydroxychloroquine, methotrexate and leflunomide inhibited IL-1beta-induced inducible NO synthase (iNOS) expression and NO production in immortalized H4 chondrocytes, while penicillamine and sulfasalazine had no effect. This can be explained by the fact that the four effective DMARDs also suppressed IL-1beta-induced activation of nuclear factor kappa B (NF-kappaB), which is a crucial transcription factor for iNOS. Aurothiomalate and hydroxychloroquine also inhibited IL-1beta-induced NO production in OA cartilage whereas methotrexate and leflunomide had no effect. Aurothiomalate and hydroxychloroquine suppressed IL-1beta-induced NO production in chondrocyte cultures and in OA cartilage. The results suggest an additional anti-inflammatory mechanism for aurothiomalate and hydroxychloroquine and indicates their possible therapeutic value in the treatment of osteoarthritis (OA).
Article
More than 15 years have passed since stent technology was introduced by Sigwart et al. [U. Sigwart, J. Puel, V. Mirkovitch, F. Joffe, et al. Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. N. Engl. J. Med. 316 (1987) 701-706.] among interventional cardiologists. Recently drug eluting stents have assumed dominance in the interventional world as positive trial results revealed their efficacy for preventing restenosis. Stent design, delivery-vehicle materials, and drug properties affect the function of these stents. Stainless steel stents with tubular and multicellular design have proven superior to coil or hybrid stent models. This chapter describes stents which have subtle influences of modular design, metal coverage, strut thickness, strut shape, surface smoothness, and coating materials like an alloy composition.
Article
Acupuncture has been used in China and other Asian countries for the past 3000 yr. Recently, this technique has been gaining increased popularity among physicians and patients in the United States. Even though acupuncture-induced analgesia is being used in many pain management programs in the United States, the mechanism of action remains unclear. Studies suggest that acupuncture and related techniques trigger a sequence of events that include the release of neurotransmitters, endogenous opioid-like substances, and activation of c-fos within the central nervous system. Recent developments in central nervous system imaging techniques allow scientists to better evaluate the chain of events that occur after acupuncture-induced stimulation. In this review article we examine current biophysiological and imaging studies that explore the mechanisms of acupuncture analgesia.
Article
The primary objective of this double-blind, randomised, controlled trial was to determine if implanting gold beads at five acupuncture points around the knee joint improves 1-year outcomes for patients with osteoarthritis (OA) of the knee. Participants were 43 adults aged 18-80 years with pain and stiffness from non-specific OA of the knee for over a year. The intervention was blinded implantation of gold beads at five acupuncture points around the affected knee through a hypodermic needle, or needle insertion alone. Primary outcome measures were knee pain, stiffness and function assessed by the patient at 0, 1, 3, 6, 9 and 12 months and knee score and knee function assessed by an orthopaedic surgeon at 0, 6 and 12 months. Within the first month, three patients dropped out. The remaining 21/19 patients in the intervention/control groups generally improved, but there was no statistically significant difference between the groups. The improvement was shown in the patients' self-assessment scores that decreased from randomisation until 1 year later (intervention/control group, medians): pain -1.92/-2.18 (P = 0.95, F test, general linear mixed model); stiffness -0.93/-0.43 (P = 0.11); function -7.23/-3.36 (P = 0.63). The surgeon's scores also generally improved, i.e. increased: knee score +16.4/+8.2 (P = 0.65); knee function +10.5/+5.8 (P = 0.79). In the protocol-based subgroup analysis, the 15 intervention patients of the 32 patients who had a positive response to the initial conventional acupuncture had greater relative improvements in self-assessed outcomes. The treatment was well tolerated. This 1-year pilot study indicates that extraarticular gold bead implantation is a promising treatment modality for patients with OA of the knee. The new treatment should be tested in a larger trial including only patients who respond positively to initial conventional acupuncture.
Article
Several important contributions of electroanalytical techniques over the past 20 years for investigating three major biological processes at the single cell level: vesicular exocytosis, oxidative stress, and nitric oxide metabolism in brain have been reported. It is evident that molecular electrochemistry at microelectrodes enhances the understanding of central processes of cellular biology including cellular metabolism either at a single cell stage or in living tissues. Since cells have highly variable metabolism even among single genetic lines, studies performed at the single cell level allow delineating precisely the extent and limits of these variabilities.