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Effects of dissolucytotic gold ions on recovering brain lesions

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Abstract

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.

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References

  • Aktas O, Waiczies S, Zipp F (2007) Neurodegeneration in autoimmune demyelination: recent mechanistic insights reveal novel therapeutic targets. J Neuroimmunol 184:17–26

    Article  CAS  PubMed  Google Scholar 

  • Amatore C, Arbault S, Bouton C, Drapier JC, Ghandour H, Koh AC (2008) Real-time amperometric analysis of reactive oxygen and nitrogen species released by single immunostimulated macrophages. Chembiochem 9:1472–1480

    Article  CAS  PubMed  Google Scholar 

  • Back T, Schüler OG (2004) The natural course of lesion development in brain ischemia. Acta Neurochir Suppl 89:55–61

    CAS  PubMed  Google Scholar 

  • Barker RA, Widner H (2004) Immune problems in central nervous system cell therapy. NeuroRx 1:472–481

    Article  PubMed  Google Scholar 

  • Bendayan M (1980) Use of the protein A-gold technique for the morphological study of vascular permeability. J Histochem Cytochem 28:1251–1254

    CAS  PubMed  Google Scholar 

  • Brunk UT, Dalen H, Roberg K, Hellquist HB (1997) Photo-oxidative disruption of lysosomal membranes causes apoptosis of cultured human fibroblasts. Free Radic Biol Med 23:616–626

    Article  CAS  PubMed  Google Scholar 

  • Burkhardt D, Stephens RW, Ghosh P, Taylor TK (1978) Inhibition of synovial fluid lysosomal glycosidases by anti-arthritic gold preparations. Agents Actions 8:251–257

    Article  CAS  PubMed  Google Scholar 

  • Chew LJ, Takanohashi A, Bell M (2006) Microglia and inflammation: impact on developmental brain injuries. Ment Retard Dev Disabil Res Rev 12:105–112

    Article  PubMed  Google Scholar 

  • Choi M, Driscoll CF (2004) Fabrication of a custom eyelid implant prosthesis: a clinical report. J Prosthodont 13:101–103

    Article  PubMed  Google Scholar 

  • Danscher G (1981) Localization of gold in biological tissue. A photochemical method for light and electron microscopy. Histochemistry 71:81–88

    Article  CAS  PubMed  Google Scholar 

  • Danscher G (1991) Histochemical tracing of zinc, mercury, silver and gold. Prog Histochem Cytochem 23:273–285

    CAS  PubMed  Google Scholar 

  • Danscher G (2002) In vivo liberation of gold ions from gold implants. Autometallographic tracing of gold in cells adjacent to metallic gold. Histochem Cell Biol 117:447–452

    Article  CAS  PubMed  Google Scholar 

  • Danscher G (2010) Medicament and method of treatment of patients with heavy metals. United States Patent 7,655,261 B2, 2 Feb 2010

  • Danscher G, Nørgaard JOR (1983) Light microscopic visualization of colloidal gold on resin-embedded tissue. J Histochem Cytochem 31:1394–1398

    CAS  PubMed  Google Scholar 

  • Danscher G, Nørgaard JOR (1985) Ultrastructural autometallography: a method for silver amplification of catalytic metals. J Histochem Cytochem 33:706–710

    CAS  PubMed  Google Scholar 

  • Danscher G, Stoltenberg M (2006) Autometallography (AMG). Silver enhancement of quantum dots resulting from 1) metabolism of toxic metals in animals and humans, 2) in vivo, in vitro and immersion created zinc-sulphur/zinc-selenium nanocrystals, 3) metal ions liberated from metal implants and particles. Prog Histochem Cytochem 41:57–140

    Article  CAS  PubMed  Google Scholar 

  • Danscher G, Hansen HJ, Møller-Madsen B (1984) Energy dispersive X-ray analysis of tissue gold after silver amplification by physical development. Histochemistry 81:283–285

    Article  CAS  PubMed  Google Scholar 

  • Davies M, Lloyd JB, Beck F (1971) The effect of trypan blue, suramin and aurothiomalate on the breakdown of 125 I-labelled albumin within rat liver lysosomes. Biochem J 121:21–26

    CAS  PubMed  Google Scholar 

  • Debons AF, Das KC, Fuhr B, Siclari E (1982a) Inhibition by hypophysectomy of the hyperphagia and obesity following gold thioglucose. Physiol Behav 29:695–699

    Article  CAS  PubMed  Google Scholar 

  • Debons AF, Siclari E, Das KC, Fuhr B (1982b) Gold thioglucose-induced hypothalamic damage, hyperphagia, and obesity: dependence on the adrenal gland. Endocrinology 110:2024–2029

    Article  CAS  PubMed  Google Scholar 

  • Faulk WP, Taylor GM (1971) An immunocolloid method for the electron microscope. Immunochemistry 8:1081–1083

    Article  CAS  PubMed  Google Scholar 

  • Felson DT, Anderson JJ, Meenan RF (1990) The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses. Arthritis Rheum 33:1449–1461

    Article  CAS  PubMed  Google Scholar 

  • Fleming CJ, Salisbury EL, Kirwan P, Painter DM, Barnetson RS (1996) Chrysiasis after low-dose gold and UV light exposure. J Am Acad Dermatol 34:349–351

    Article  CAS  PubMed  Google Scholar 

  • Giulian D, Corpuz M, Chapman S, Mansouri M, Robertson C (1993) Reactive mononuclear phagocytes release neurotoxins after ischemic and traumatic injury to the central nervous system. J Neurosci Res 36:681–693

    Article  CAS  PubMed  Google Scholar 

  • Habal MB (1979) Current status of biomaterial’s clinical applications in plastic and reconstructive surgery. Biomater Med Devices Artif Organs 7:229–241

    CAS  PubMed  Google Scholar 

  • Hashimoto K, Whitehurst CE, Matsubara T, Hirohata K, Lipsky PE (1992) Immunomodulatory effects of therapeutic gold compounds. Gold sodium thiomalate inhibits the activity of T cell protein kinase C. J Clin Invest 89:1839–1848

    Article  CAS  PubMed  Google Scholar 

  • Hashizume H, Seo N, Ito T, Takigawa M, Yagi H (2008) Promiscuous interaction between gold-specific T cells and APCs in gold allergy. J Immunol 181:8096–8102

    CAS  PubMed  Google Scholar 

  • Holgate CS, Jackson P, Cowen PN, Bird CC (1983) Immunogold-silver staining: new method of immunostaining with enhanced sensitivity. J Histochem Cytochem 31:938–944

    CAS  PubMed  Google Scholar 

  • Hostýnek JJ (1997) Gold: an allergen of growing significance. Food Chem Toxicol 35:839–844

    Article  PubMed  Google Scholar 

  • Inglese M, Mancardi GL, Pagani E, Rocca MA, Murialdo A, Saccardi R, Comi G, Filippi M (2004) Brain tissue loss occurs after suppression of enhancement in patients with multiple sclerosis treated with autologous haematopoietic stem cell transplantation. J Neurol Neurosurg Psychiatry 75:643–644

    CAS  PubMed  Google Scholar 

  • Larsen A, Stoltenberg M, Danscher G (2007) In vitro liberation of charged gold atoms: autometallographic tracing of gold ions released by macrophages grown on metallic gold surfaces. Histochem Cell Biol 128:1–6

    Article  CAS  PubMed  Google Scholar 

  • Larsen A, Kolind K, Pedersen DS, Doering P, Pedersen MO, Danscher G, Penkowa M, Stoltenberg M (2008) Gold ions bio-released from metallic gold particles reduce inflammation and apoptosis and increase the regenerative responses in focal brain injury. Histochem Cell Biol 130:681–692

    Article  CAS  PubMed  Google Scholar 

  • Liu B, Hong JS (2003) Neuroprotective effect of naloxone in inflammation-mediated dopaminergic neurodegeneration. Dissociation from the involvement of opioid receptors. Methods Mol Med 79:43–54

    CAS  PubMed  Google Scholar 

  • McGirr EE, Browne CD, Champion GD, Day RO, Sambrook PN (1984) Aurothioglucose in rheumatoid arthritis. Outcome of treatment in patients intolerant of sodium aurothiomalate. Med J Aust 141:349–351

    CAS  PubMed  Google Scholar 

  • Merchant B (1998) Gold, the noble metal and the paradoxes of its toxicology. Biologicals 26:49–59

    Article  CAS  PubMed  Google Scholar 

  • Mhatre AN, Li Y, Feng L, Gasperin A, Lalwani AK (2004) SDHB, SDHC, and SDHD mutation screen in sporadic and familial head and neck paragangliomas. Clin Genet 66:461–466

    Article  CAS  PubMed  Google Scholar 

  • Møller-Madsen B, Mogensen SC, Danscher G (1984) Ultrastructural localization of gold in macrophages and mast cells exposed to aurothioglucose. Exp Mol Pathol 40:148–154

    Article  PubMed  Google Scholar 

  • Møller-Madsen B, Danscher G, Uldbjerg N, Allen JG (1987) Autometallographic demonstration of gold in human fetal liver and placenta. Rheumatol Int 7:47–48

    Article  PubMed  Google Scholar 

  • Ogura T, Takaoka M, Yamauchi T, Oishi T, Mimura Y, Hashimoto M, Asano N, Yamamura M, Otsuka F, Makino H, Ota Z, Takahashi K (1996) Changes in urinary enzyme activity and histochemical findings in experimental tubular injury induced by gold sodium thiomalate. J Med 27:41–55

    CAS  PubMed  Google Scholar 

  • Pantano P, Mainero C, Caramia F (2006) Functional brain reorganization in multiple sclerosis: evidence from fMRI studies. J Neuroimaging 16:104–114

    Article  PubMed  Google Scholar 

  • Pedersen MO, Larsen A, Pedersen DS, Stoltenberg M, Penkova M (2009a) Metallic gold treatment reduces proliferation of inflammatory cells, increases expression of VEGF and FGF, and stimulates cell proliferation in the subventricular zone following experimental traumatic brain injury. Histol Histopathol 24:573–586

    CAS  PubMed  Google Scholar 

  • Pedersen MO, Larsen A, Pedersen DS, Stoltenberg M, Penkowa M (2009b) Metallic gold reduces TNFα expression, oxidative DNA damage and pro-apoptotic signals after experimental brain injury. Brain Res 1271:103–113

    Article  CAS  PubMed  Google Scholar 

  • Pedersen MO, Larsen A, Stoltenberg M, Penkowa M (2010) Bio-released gold ions modulate expression of neuroprotective and hematopoietic factors after brain injury. Brain Res 1307:1–13

    Article  CAS  PubMed  Google Scholar 

  • Persellin RH, Ziff M (1966) The effect of gold salt on lysosomal enzymes of the peritoneal macrophage. Arthritis Rheum 9:57–65

    Article  CAS  PubMed  Google Scholar 

  • Rasmussen S, Wang Y, Kivisäkk P, Bronson RT, Meyer M, Imitola J, Khoury SJ (2007) Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing—remitting experimental autoimmune encephalomyelitis. Brain 130:2816–2829

    Article  PubMed  Google Scholar 

  • Richards DG, McMillin DL, Mein EA, Nelson CD (2002) Gold and its relationship to neurological/glandular conditions. Int J Neurosci 112:31–53

    Article  PubMed  Google Scholar 

  • Roach TI, Slater SE, White LS, Zhang X, Majerus PW, Brown EJ, Thomas ML (1998) The protein tyrosine phosphatase SHP-1 regulates integrin-mediated adhesion of macrophages. Curr Biol 8:1035–1038

    Article  CAS  PubMed  Google Scholar 

  • Schiønning JD, Poulsen EH, Møller-Madsen B, Danscher G (1992) Autometallographic detection of gold in dorsal root ganglia of rats treated with sodium aurothiomalate. Exp Mol Pathol 56:239–247

    Article  PubMed  Google Scholar 

  • Sennerby L, Kälebo P, Thomsen P, Albrektsson T (1993) Influence of indomethacin on the regeneration of cortical bone within titanium implants in rabbits. Biomaterials 14:156–158

    Article  CAS  PubMed  Google Scholar 

  • Stierhof YD, Humbel BM, Schwarz H (1991) Suitability of different silver enhancement methods applied to 1 nm colloidal gold particles: an immunoelectron microscopic study. J Electron Microsc Tech 17:336–343

    Article  CAS  PubMed  Google Scholar 

  • Stoll G, Jander S, Schroeter M (1998) Inflammation and glial responses in ischemic brain lesions. Prog Neurobiol 56:149–171

    Article  CAS  PubMed  Google Scholar 

  • Svedman C, Ekqvist S, Möller H, Björk J, Pripp CM, Gruvberger B, Holmström E, Gustavsson CG, Bruze M (2009) A correlation found between contact allergy to stent material and restenosis of the coronary arteries. Contact Dermat 60(3):158–164

    Article  Google Scholar 

  • Tanigawa N, Sawada S, Kobayashi M (1995) Reaction of the aortic wall to six metallic stent materials. Acad Radiol 2:379–384

    Article  CAS  PubMed  Google Scholar 

  • Tozman EC, Gottlieb NL (1987) Adverse reactions with oral and parenteral gold preparations. Med Toxicol 2:177–189

    CAS  PubMed  Google Scholar 

  • Traber KE, Okamoto H, Kurono C, Baba M, Saliou C, Soji T, Packer L, Okamoto T (1999) Anti-rheumatic compound aurothioglucose inhibits tumor necrosis factor-alpha-induced HIV-1 replication in latently infected OM10.1 and Ach2 cells. Int Immunol 11:143–150

    Article  CAS  PubMed  Google Scholar 

  • Vernon-Roberts B (1979) Action of gold salts on the inflammatory response and inflammatory cell function. J Rheumatol Suppl 5:120–129

    CAS  PubMed  Google Scholar 

  • Whitney NP, Eidem TM, Peng H, Huang Y, Zheng JC (2009) Inflammation mediates varying effects in neurogenesis: relevance to the pathogenesis of brain injury and neurodegenerative disorders. J Neurochem 108(6):1343–1359

    Article  CAS  PubMed  Google Scholar 

  • Yamaguchi K, Ushijima H, Hisano M, Inoue Y, Shimamura T, Hirano T, Müller WE (2001) Immunomodulatory effect of gold sodium thiomalate on murine acquired immunodeficiency syndrome. Microbiol Immunol 45:549–555

    CAS  PubMed  Google Scholar 

  • Yang JP, Merin JP, Nakano T, Kato T, Kitade Y, Okamoto T (1995) Inhibition of the DNA-binding activity of NF-kappa B by gold compounds in vitro. FEBS Lett 361:89–96

    Article  CAS  PubMed  Google Scholar 

  • Yanni G, Nabil M, Farahat MR, Poston RN, Panayi GS (1994) Intramuscular gold decreases cytokine expression and macrophage numbers in the rheumatoid synovial membrane. Ann Rheum Dis 53:315–322

    Article  CAS  PubMed  Google Scholar 

  • Yoshida S, Kato T, Sakurada S, Kurono C, Yang JP, Matsui N, Soji T, Okamoto T (1999) Inhibition of IL-6 and IL-8 induction from cultured rheumatoid synovial fibroblasts by treatment with aurothioglucose. Int Immunol 11:151–158

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors acknowledge the technical assistance of Mrs. Karin Wiedemann and Mr. Albert Meier.

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Correspondence to Gorm Danscher.

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Danscher, G., Larsen, A. Effects of dissolucytotic gold ions on recovering brain lesions. Histochem Cell Biol 133, 367–373 (2010). https://doi.org/10.1007/s00418-010-0681-2

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