>Posted-Date: Mon, 13 May 1996 15:20:09 -0700 >Date: Mon, 13 May 1996 15:19:34 -0700 (PDT) >From: Camilla Cracchiolo <[log in to unmask]> >To: "Ronald F. Vetter" <[log in to unmask]> >Subject: Re: Ag+ and blood/brain barrier (fwd) Here are some abstracts passed on to me. You might find them interesting. I, Ron, thank: Camilla Cracchiolo, RN [log in to unmask] Here are reports of two women with argyria (silver poisoning) with demonstrable silver in the CNS. Silver crosses the BBB in rodents and is apparently neurotoxic. These references indicate that humans are probably no different. Prior to modern antibiotics, silver (as well as other heavy metals like arsenic and mercury) were used as antimicrobials. Perhaps the older literature has some discussions of the neurotoxicity of silver treatments. Dietl HW. Anzil AP. Mehraein P. Brain involvement in generalized argyria. Clinical Neuropathology. 3(1):32-6, 1984 Jan-Feb. Abstract Cutaneous argyria was diagnosed in a 59-year-old woman. Manic depressive psychosis developed at about the same or a short time thereafter. The patient died 6 years later from a ruptured aortic aneurysm. At autopsy silver deposits were seen in skin, mucous membranes, heart, kidney, and liver. In the central nervous system the leptomeninges and choroid plexuses contained silver granules. In addition, silver granules were visualized in the walls of many intraparenchymal vessels, particularly of the basal ganglia, hypothalamus, substantia nigra, and cerebellum. Progressive glial changes and cellular gliosis were evident in many areas of the brain. With the electron microscope the deposition of silver granules in basal membrane structures of the choroid plexus and intracerebral vasculature was amply confirmed. Furthermore, silver deposition was seen in brain parenchymal cells inside bodies of apparently lysosomal nature. The silver content of various brain regions was determined by absorption spectrophotometry. Landas S. Fischer J. Wilkin LD. Mitchell LD. Johnson AK. Turner JW. Theriac M. Moore KC. Demonstration of regional blood-brain barrier permeability in human brain. Neuroscience Letters. 57(3):251-6, 1985 Jun 24. Abstract 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. Rungby J. Slomianka L. Danscher G. Andersen AH. West MJ. A quantitative evaluation of the neurotoxic effect of silver on the volumes of the components of the developing rat hippocampus. Toxicology. 43(3):261-8, 1987 Mar. Abstract The volumes of the components of the hippocampus of rats subjected to subcutaneous injections of silver during the first 4 postnatal weeks were compared to those of littermate controls. Of the 14 components measured, only the pyramidal cell layer was found to be significantly smaller in the treated animals. These findings indicate that the perikaria of the pyramidal cells are either the first elements in the developing hippocampus to show signs of silver toxicity or that they are the selective sites of silver neurotoxicity. The volumetric approach is shown to be a sensitive means by which small localized neurotoxic effects can be detected. Rungby J. Danscher G. Hypoactivity in silver exposed mice. Acta Pharmacologica et Toxicologica. 55(5):398-401, 1984 Nov. Abstract 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. Rungby J. Danscher G. Localization of exogenous silver in brain and spinal cord of silver exposed rats. Acta Neuropathologica. 60(1-2):92-8, 1983. Abstract Exogenous silver in brain and spinal cord sections from rats treated with Protargol, silver lactate or silver nitrate was visualized by physical development. The silver penetrated the blood-brain barrier and accumulated in neurones and glia. The distribution of silver in the CNS was heterogeneous. Even with low doses and short survival periods, silver was found to accumulate in large motoneurones in the brain stem and spinal cord and neurones in the cerebellar nuclei. Silver was only found in di- and telencephalic structures after extensive exposure. Silver distribution following oral silver lactate and silver nitrate treatment differed in that silver nitrate resulted in a relatively high content of silver in glia whereas deposition occurred preferentially in neurones following silver lactate treatment. Electron-microscopical studies showed that silver was located intracellularly in the lysosomes and extracellularly in basement membranes and elastic fibres of the vessels. Danscher G. Stoltenberg M. Juhl S. How to detect gold, silver and mercury in human brain and other tissues by autometallographic silver amplification. Neuropathology & Applied Neurobiology. 20(5):454-67, 1994 Oct. ron 1936, dz PD 1984 Ronald F. Vetter <[log in to unmask]> http://www1.ridgecrest.ca.us/~rfvetter/