Evidence for a long-term storage of calcitriol in a patient with 1-alpha hydroxylase deficiency and rickets.
Explore the source record for details and available documents.
25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
Biomedical subjects
J Rungby
Publications and source records attributed to J Rungby.
An experimental study on silver in the nervous system and on aspects of its general cellular toxicity.
Exposure of foetal and adult rats to silver results in a long-lasting deposition of the metal in many structures of the nervous system. A brief anatomical description of the localization of silver deposits as they are visualized by autometallography is provided. The consequences of silver in the nervous system were evaluated by volumetric measurements on developing rat hippocampi which showed that silver induced a decrease in the total volume of hippocampal pyramidal cells. The toxicity of silver at the cellular level was studied in a test-system of cultured macrophages. High doses of silver caused coagulation necrosis, whereas lower concentrations resulted in a cytotoxic and possibly a cytostatic effect without affecting cell structure. The processing of silver which resulted in lysosomal accumulations was affected by the metal itself in a dose-dependent fashion (autointerference). Other basic macrophage functions (protein-production, phagocytosis, migration) were not affected by silver at concentrations which did not cause acute cell death. Biochemically, silver causes an increase in lipid peroxidation, which was evident only in liver tissue. Coagulation necrosis and, to some extent, long-term effects on cell viability could be reversed by inorganic selenium, which was tested as a detoxicant. On the other hand, pre-exposure of animals to selenium greatly enhanced the silver-induced lipid peroxidation. Furthermore, the co-exposure to silver and nickel resulted in a synergistically increased lipid peroxidation.
Animals↗
Evaluation of lysosomal stability in living cultured macrophages by cytofluorometry. Effect of silver lactate and hypotonic conditions.
The ability of living mouse peritoneal macrophages to retain the lysosomotropic photosensitizer acridine orange (AO) within their secondary lysosomes was studied with a novel cytofluorometric method. During exposure to blue light, cellular AO fluorescence turned from a red granular pattern to that of diffuse green. The resulting change in total fluorescence intensity versus time - a primary decline due to red fluorescence bleaching and a secondary recovery due to the spectral shift - was interpreted as the result of leakage of AO from the lysosomal vacuome. The hypothesis that this time course should be affected by changes in lysosomal membrane stability was tested by labilizing the lysosomes by exposure of cultured macrophages to either hypotonic medium or silver lactate. In hypotonic medium, the ability to retain AO decreased continuously. Exposure to low concentrations of silver lactate (10 microM) also decreased AO retention time. We suggest that this method could be used, within appropriate experimental conditions, to evaluate lysosomal membrane stability in living cells.
Acridine Orange↗
Distribution of dietary mercury in a dog. Quantitation and localization of total mercury in organs and central nervous system.
An Alsatian dog which had been fed fish contaminated with methyl mercury for 7 years was examined after its death at the age of 12, 4 years after the exposure to methyl mercury had ceased. Two dogs of the same age and breed served as controls. In the exposed dog, mercury was found in all of the organs examined; the highest concentrations were found in the kidneys, and the lowest in the gastrointestinal tract and skeletal muscles. In the central nervous system (CNS) the mercury was fairly uniformly distributed, with 93% in the inorganic state, whereas the skeletal muscles contained approximately 30% inorganic mercury. This demonstrates time-dependent demethylation and suggests a variation in the rate from one type of tissue to another. At the time of death, the mercury level in the dog was still falling. In the control dogs, detectable amounts (0.01 mg kg-1) of mercury were only found in the kidney and liver. The distribution of mercury was determined by a histochemical method (autometallography) for locating mercury in tissue sections. Sections from autometallography of the central nervous system showed large deposits of mercury in all areas of the cerebral hemispheres, the brainstem and the spinal cord, including nerve cells, astrocytes, microglial cells and vessel walls. The granular layer of the cerebellar hemispheres was especially loaded, while only a few granules were present in the Purkinje cells. In the leptomeninges the vessels and the macrophages were heavily encrusted. High amounts of histochemically demonstrable mercury were observed in the liver, thyroid gland and kidney. In the control dogs, all the organs examined were practically devoid of deposits.
Animals↗
Effects of selenium on toxicity and ultrastructural localization of mercury in cultured murine macrophages.
The effects of selenium on cellular toxicity and histochemical distribution of mercury were examined in a cell culture system of mouse peritoneal macrophages. Selenium protected against the toxicity of mercury in cultures exposed to 4 microM of mercuric chloride. Selenomethionine caused a significant increase in cell survival throughout the experiments, while sodium selenite delayed the toxicity of mercury for a while, after which selenite itself had a toxic effect. The amount of mercury visualized by autometallography was increased in macrophage cultures pre-exposed to sodium selenite or selenomethionine. The additional mercury made visible by this histochemical demonstration was located in the cytoplasm as well as in the lysosomes.
Animals↗
Dose-dependent bimodal effect of low-level lead exposure on the developing hippocampal region of the rat: a volumetric study.
The hippocampal region is known to accumulate experimentally applied and environmentally occurring lead and to be implicated in lead-induced behavioral deficits. With the intention of investigating morphological changes resulting from the lower range of exposures that produce behavioral alterations in laboratory animals, the volumes of hippocampal components were determined in groups of rats exposed from postnatal days 0-21 to different concentrations of lead through the maternal water supply (initially 109 ppm, subsequently replicated with 109, 218, 436 and 872 ppm). Significant effects were found in the mossy fiber zone, the granule cell layer and the commissural-associational zone of the dentate molecular layer of the group exposed to 109 ppm lead and the pyramidal cell layer of regio inferior (CA3) of Ammon's horn in the group exposed to 218 ppm lead. These results provide evidence that lead primarily affects newly formed neuronal components. In contrast to the results of previous studies, which used larger exposures to lead, the components affected in the group exposed to 109 ppm increased in volume. In addition, no significant effects were observed in the groups exposed to 436 and 872 ppm. Based on these findings and additional evidence from the literature, it is concluded that lead has a dose dependent bimodal influence on developing hippocampal components. While the volumetric changes related to lead were of the same magnitude and direction in the initial and replication studies, the absolute volumes of the affected hippocampal components were different. The differences in "baseline" values in the two studies are more likely related to differences in prenatal conditions.
Animals↗
Toxicity and ultrastructural localization of mercuric chloride in cultured murine macrophages.
The effects of mercuric chloride on cell survival, phagocytosis and cell migration were examined in cultured mouse peritoneal macrophages, and the accumulation of mercuric chloride in the cells was visualized by autometallography and evaluated by light and electron microscopy. Macrophages exposed to mercury concentrations from 1.25 microM to 10 microM mercuric chloride showed a concentration- and time-dependent increase in mercuric chloride accumulation, while cells exposed to 20 microM and 40 microM mercury showed an inverse relationship between mercury concentration and the accumulation of mercury. Mercury concentrations above these levels caused cell necrosis. Electron microscopy revealed that mercury was located primarily within lysosomes but also in the nucleus and cytoplasm. Mercury increased the death rate of macrophages in a concentration-dependent manner when cells were treated with mercury concentrations not causing cell necrosis. Further, we found that mercury clearly impaired macrophage random migration and possibly the capability for phagocytosis.
Animals↗
Serum concentrations and accumulation of silver in skin during three months treatment with an anti-smoking chewing gum containing silver acetate.
Silver acetate chewing gum was used for 12 weeks as a smoking deterrent in 21 adults. The effect of silver on serum concentrations, its accumulation in the skin and the risk of developing clinically evident argyria were investigated. Serum concentrations of silver clearly rose after chewing gum use had started, and concentrations quickly returned to normal after use had ceased. In most cases the number of silver granules in skin biopsies, observed by autometallography, increased after the gum had been used for 12 weeks. No one developed clinical signs of argyria. Silver acetate containing remedies can be used as an aid to stop smoking, but the consumption must be monitored to avoid accumulation of larger amounts of silver in the body.
Acetates↗
Silver affects viability and structure of cultured mouse peritoneal macrophages and peroxidative capacity of whole mouse liver.
The effects of silver on cultured mouse peritoneal macrophages were examined by estimation of cell survival and by light and electron microscopy. Addition of silver lactate to the culture medium at final concentrations of 40 and 80 microM resulted in coagulation necrosis and rapid cell death. At lower concentrations cell structure appeared normal. However, the rate of cell death at 20 microM silver lactate was increased as compared to controls. Silver, visualized by physical development/autometallography, was invariably located in lysosomes. The production of malondialdehyde in mouse liver of silver-treated mice as compared to controls was also examined. This lipid peroxidation product had increased to the same amount in animals treated with silver for either 3 days or with only one silver injection 4 h before examination. This study has demonstrated that silver affects viability and structure of cultured macrophages, possibly due to induction of lipid peroxidation, as demonstrated to occur in the liver of silver-exposed mice.
Animals↗
Effects of selenium on toxicity and ultrastructural localization of silver in cultured macrophages.
The effects of selenium on cellular toxicity and histochemical distribution of silver were examined in a cell culture system of mouse peritoneal macrophages. Selenium caused a significant delay in the appearance of coagulation necrosis induced by high silver concentrations and reduced the cytostatic effect of lower doses of silver when long-term toxicity was examined. Furthermore, selenium increased the amount of silver that could be visualized by autometallography. The additional silver made available for this histochemical demonstration was located in the cytosol as well as in lysosomes, the sole localization of silver when selenium was not administered.
Animals↗
Autointerference in silver accumulation in macrophages without affecting phagocytic, migratory or interferon-producing capacity.
Silver accumulation and processing in mouse peritoneal macrophages was studied in vitro by autometallographic visualization of intracellular silver. During the first 24 h of incubation in a medium containing from 5 microM to 20 microM of silver lactate, an inverse relationship between silver concentration in the former and visualizable silver in macrophages was recorded. Later, however, the cells treated with higher silver concentrations accumulated most silver. Cells exposed to silver concentrations above these levels exhibited acute coagulation necrosis and disintegrated within the first 15 min of silver treatment. Macrophages treated with silver lactate concentrations not causing acute cytotoxicity showed no impairment of their phagocytic, migratory or interferon-producing capacities. The significance of autointerference in silver accumulation and processing in macrophages is discussed, and a functional defect in the lysosome/phagosome system is suggested as a basis for the phenomenon.
Animals↗
A quantitative evaluation of the neurotoxic effect of silver on the volumes of the components of the developing rat hippocampus.
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.
Animals↗
Silver-induced lipid peroxidation in mice: interactions with selenium and nickel.
Lipid peroxidation in silver-treated mice was assayed by measuring the malondialdehyde (MDA) content of liver, kidney and brain tissue. After a single intraperitoneal injection of 20 mg/kg silver lactate, lipid peroxidation was significantly increased in the liver 3, 12 and 48 h after exposure whereas MDA levels in kidney and brain were not significantly affected. Pretreatment with 2 mg/kg sodium selenite i.p. for 2 days resulted in an increase in silver-induced lipid peroxidation in the liver. Liver from mice treated with 20 mg/kg silver lactate followed by an injection of 35 micrograms/kg nickel chloride had significantly higher contents of MDA than did livers from mice treated with either silver or nickel alone, suggesting a synergism between silver and other lipid peroxidation-inducing compounds.
Animals↗
Exogenous silver in dorsal root ganglia, peripheral nerve, enteric ganglia, and adrenal medulla.
Following intraperitoneal (i.p.) or oral administration of silver salts, the anatomic distribution of silver in the peripheral nervous system (PNS) has been studied. The structures examined were dorsal root ganglia, peripheral nerve (N. ischiadicus), enteric ganglia, and adrenal medulla. Four days after an i.p. injection of silver lactate, silver deposits were found in these structures. The silver content remained stable during the observation period (45 days). The localization of silver deposits in the orally treated animals was independent of the administered silver salt (silver nitrate or silver lactate). The silver deposits in neurons and chromaffin cells were located in the cytoplasm. In all organs silver was present in large amounts in connective tissue membranes, macrophage-like cells, vascular basal laminae, and supporting cells. Satellite cells of the dorsal root ganglia were always heavily stained, while less stain was present in Schwann cells of the peripheral nerves. Intracellular deposits were invariably located in lysosomes, whereas extracellular grains were found in connective tissue fibers and basement membranes.
Adrenal Medulla↗
Experimental argyrosis: ultrastructural localization of silver in rat eye.
The present paper provides a description of the ultrastructural localization of silver deposits in eyes of adult rats exposed to silver either perorally or intraperitoneally. Silver was found in lysosomes of most cell types, an exception being the neural retina. Extracellularly, silver was present in vascular basal laminae and in connection with connective tissue fibers. Systemic silver intoxication was found to result in a rapid and long-lasting deposition of the metal in the eye.
Animals↗
The silver nitrate prophylaxis of Credé causes silver deposition in the cornea of experimental animals.
Explore the source record for details and available documents.
Animals↗
Selenium accumulation in the oocyte after exposure to sodium selenite.
Explore the source record for details and available documents.
Animals↗
Selenium in the anterior pituitary.
Selenium accumulated in the anterior pituitary of the rat after intraperitoneal injection of NA2Se03. Selenium is bound to a cation (most likely Zn++) and is ultrastructurally located in lysosomes and secretory granules.
Animals↗