Monitoring of selenium in oral cavity argyria - a clinical and microscopic study.

OBJECTIVE: Argyria is generally classified as localized or generalized condition. Distinct pigmentation of the oral mucosa in the vicinity of amalgam fillings is often referred to as amalgam tattoos. Pigmented areas can also be associated with silver-containing corrosion products of dental alloys used for prosthetic restorations. Silver-containing electron dense particles (Ag-EDPs) are frequently found in pigmented areas. We attempted to correlate results of the elemental composition of Ag-EDPs with excerpts from health profiles of our study paticipants. DESIGN/SETTING: Eight patients with diagnosed signs of localized argyria were investigated in this study. Biopsies from distinctly pigmented gingival areas were subjected to histological examination, electron microscopy and x-ray microanalysis. RESULTS: Elemental composition of Ag-EDPs determined by x-ray microanalysis showed mainly silver in combination with sulfur or selenium or a combination of both chalcogens. Elemental analyzes results of Ag-EDPs were analyzed along with excerpts from the patient's clinical records. Two patients with low or undetectable selenium in the Ag-EDPs suffered from autoimmune thyroiditis, Parkinson's disease, bronchial asthma, and allergies to molds, pollen and dust. CONCLUSIONS: We suggest that selenium in Ag-EDPs is a product of the detoxification process for Ag(+) ions in gingival tissue and that it may reflect the availability of endogenous selenium for physiological processes in the human body. Its presence or absence might thus be used as another marker of a patient's health status.

Detection of silver sulfide deposits in the skin of patients with argyria after long-term use of silver-containing drugs.

Five patients with generalized slate-gray discoloration of the skin have been diagnosed histologically as argyria in the last 35 years in the Department of Dermatology and Venereology of Rostock and Halle. Light microscopically, there was visible black pigmentation in histiocytes, fibroblasts, and multinucleated giant cells of the dermis. In the transmission electron microscope (TEM), the authors observed electron-dense deposits inside lysosomes and residual bodies of phagocytes as well as outside the cells in the connective matrix. These deposits were identified by elemental analysis in TEM and electron energy loss spectroscopy (EELS) as well as scanning electron microscope (SEM) and energy dispersive x-ray analysis (EDX) containing silver and sulfur. Therefore, they seem to consist of silver sulfide. Argyria is of low medical relevance and is very rarely induced because of silver-containing drugs. Nevertheless, there are still a lot of silver products on the market, easily available over-the-counter. Therefore, argyria should not be forgotten or missed in the diagnostics of human dermis.

Immunolocalization of HLA-DR and metallothionein on amalgam tattoos.

Despite studies concerning toxic reactions related to amalgam components in the literature, few studies have been devoted to evaluate local noxious effects of amalgam tattoos (AT) on biological tissues. In addition, little is known about activation of inflammatory cells by mucosa-implanted amalgam debris. Tissue reaction to AT depends on the particle size. Human leukocyte antigen DR (HLA-DR) is an activation marker of inflammatory cells associated with antigen presentation. Metallothioneins (MT) are proteins involved with metal detoxication, including mercury and silver. The purpose of the present study was to investigate the immunolocalization of HLA-DR and MT in AT with large or powdered particles. Paraffin-embedded AT tissue blocks were sectioned and subjected to immunohistochemistry for HLA-DR and MT localization. The results demonstrated a dense mononuclear inflammatory infiltrate associated with large and powdered debris and positivity for HLA-DR and MT in inflammatory cells. While blood vessel walls and connective fibers impregnated with powdered particles were negative for HLA-DR, they were positive for MT. In addition, wherever epithelial basement membrane impregnation by powdered amalgam particles was observed, a strong positivity for MT was detected. These findings demonstrate that residual elements of AT still have noxious local effects over tissues.

Generalized argyria after habitual use of AgNO3.

Generalized argyria, the systemic dissemination and tissue deposition of silver-containing particles, is characterized by slate gray discoloration of skin, most pronounced in sun exposed areas. A 33-year-old woman visited our dermatologic clinic complaining of frequent oral ulceration for 10 years and generalized discoloration of her skin for 5 years. She had had her tongue painted with silver nitrate repeatedly 6 years ago for the treatment of oral ulcers. Physical examination showed slate gray discoloration of her skin, most pronounced on the face and neck. The oral mucosa, tongue, sclera, and conjunctiva also had a slightly blue-gray discoloration. Biopsy specimens from the oral mucosa and forearm revealed small brown-black granules scattered in the dermis and basal lamina of eccrine sweat glands, blood vessels, and hair follicles under the light microscope. Tiny black granules were most numerous in the basal laminae of vessels in electron microscopic observation. Energy dispersive X-ray microanalysis (EDXA) confirmed that many of the granules contained silver.

Detection of selenium in generalized and localized argyria: report of four cases with X-ray microanalysis.

Electron microscopic and X-ray microanalytic studies were performed on four cases of argyria; one generalized and three localized. Deposition of electron dense granules was predominantly found on elastic fibers and around basal laminas of secretory portions of eccrine glands, although the amount of deposition was much less in the case of generalized argyria. In all four cases, X-ray microanalysis revealed that the depositions consisted mainly of silver, selenium, and sulfur. The importance of selenium in the detoxification of heavy metals was discussed.

Argyria: microanalytic-morphologic correlation using paraffin-embedded tissue.

Scanning electron microscopes, which have energy dispersive spectroscopy (x-ray microanalysis) capability, can provide accurate identification of the composition of inorganic deposits in tissue. We report a case of florid argyria in which the same deparaffinized 4-micron sections were sequentially examined by light microscopy, scanning electron microscopy, backscattered electron imaging, and x-ray microanalysis to confirm the clinical impression of argyria. We recommend the use of x-ray microanalysis of paraffin-embedded tissue as a simple, rapid and inexpensive means of precise identification of inorganic deposits of heavy elements in tissue sections.

Demonstration of regional blood-brain barrier permeability in human brain.

The brain of a 78-year-old woman with argyria was examined at autopsy. Silver nitrate deposition was observed in circumventricular organs (CVO) and in the paraventricular and supraoptic nuclei of the hypothalamus. These findings parallel animal experiments of other investigators and are the best demonstration so far of regional absence of the blood-brain barrier in humans. These observations demonstrate similarities between humans and other mammals of CVO anatomy, permeability to blood-borne agents, and perhaps neural connections between CVOs and magnocellular nuclei.

Hypoactivity in silver exposed mice.

The functional implications of the presence of silver in the central nervous system are unknown. Since silver is present in the environment and since systemic silver poisoning leads to intraneuronal accumulations of the metal we have evaluated the possible effects of silver on the open field behaviour of mice. Argyric mice have been compared with controls in three experiments, one including long term administration of 0.015% silver nitrate in the drinking water and two in which the reactions of male and female mice to shock doses of silver lactate have been studied. In all experiments the silver treated mice were hypoactive. We suggest that this hypoactivity is due to an influence of silver upon the functional status of the CNS.

Argyria-tissue deposition of silver as selenide.

Generalized argyria was precipitated in a patient by treating gingival erosions with a solution of silver nitrate for several months. High silver concentrations were measured in skin biopsies. treatment with penicillamine did not increase the urinary silver excretion, indicating that silver is deposited in tissues in a chemically stable and apparently inert form. Electron microscopy showed that in the kidney, silver was deposited mainly in the basal membranes as electron-dense particles. These particles were studied by using X-ray emission spectrometry and electron diffraction. the particles consisted of Ag2Se in the low temperature orthorhombic alfaform. The lattice parameters are: a = 0.433 nm, b = 0.693 nm and c = 0.784 nm. This selenide complex seems to be remarkably non-toxic, since the renal function of the patient was unaffected and only negligible reactive changes were observed in kidney biopsies.

Occupational argyria; light and electron microscopic studies and X-ray microanalysis.

Microscopic studies have been performed on skin biopsies from five patients with occupational argyria. Small brown-black granules were present in the dermis on light microscopy and were intensely refractile with dark-field illumination. Electron microscopy showed that the granules were electron-dense, round or oval in shape and varied in size from 30 nm to 100 nm. They were most numerous in relation to the basal lamina of the eccrine sweat glands, but were also present in relation to the basal lamina of the epidermis and dermal elastic fibres. X-ray microanalysis confirmed that many of the granules contained silver and sulphur. However, selenium, mercury, titanium and iron were also identified and it is probable that these elements were deposited in the skin also as a result of occupational exposure.

[Cutaneous argyria: an electron microscopic study of four eases with microanalysis X study of one case (author's transl)]. / Etude en microscopie électronique et en microanalyse X de 4 cas.

This study was done in order to follow the fate of silver in the dermis of chronic argyria. Silver was easily recognizable in the tissue as irregular aggregates of elementary granules round or ovoid in shape, ranging from 30 to 40 mm in size. The microanalysis X showed that the metal was bound with sulfur. In the cases of recent intoxication, the main location of silver was intracellular: the granules were found in the lysosomes as elementary particle or as dense heterogen bodies. In the cases where intoxication had been stopped a long time ago, silver was found either on fibrillar component of the connective tissue or in the basal material of sweat glands. The results show that silver is at first phagocytized by macrophages but this cell is unable to perform complete degradation of the silver salt or metal. Then silver is found on connective fibers where it remains on sulfated glycoproteins.

[Morphology of experimental argyrosis in kidneys]. / Morfológia experimentálnej argyrózy v oblickách.

Prolonged per os administration of silver nitrate solution in rats will result in the development of experimental argyrosis with particles of silver in the kidneys being deposited mainly in the glomerular basal membranes. Apart from that, particles of silver in the glomeruli were also found in the mesangioma and, in minor quantities, in podocytes and endothelial cells. Outside the glomerular structures, silver was found deposited in tubular basal membranes, in the proximal tubule epithelium and minute vessel wals. -- A discussion is presented of the possible mechanisms involved in the development of such deposits, as well as of the relationship between intravital silver depositing and some of the tissues affinity to silver, a property taken advantage of in histological methods.