Biomedical subjects

G Danscher

Publications and source records attributed to G Danscher.

At least 37 records · Page 2Linked to original sources

PubMed2001

The positive effects of zinc on skeletal strength in growing rats.

The aim of the present study was to assess the skeletal effects of alimentary zinc depletion and supplementation in an animal model of intact, growing rats. The study was planned as a dose-response study. Thirty-six male Wistar rats, 4 weeks old, were divided into three groups of 12 rats each. The rats had free access to a semisynthetic diet with different amounts of zinc added. Group 1 was given a zinc-free diet containing 2 mg zinc/kg, group 2 was given a normal-zinc diet containing 47 mg zinc/kg; and group 3 was given a zinc-supplemented diet containing 60 mg zinc/kg. All animals were killed 4 weeks after initiation of the experiment and the right femora were removed. The biomechanical effects were measured at the following skeletal sites: femoral diaphysis; femoral neck; and distal femoral metaphysis. In addition, static histomorphometry was performed at the middiaphyseal region. Biomechanical testing revealed a significant zinc-induced increase in bone strength at all sites investigated. It also showed that zinc influenced bone strength in a dose-dependent manner except at the distal metaphysis, where there was no significant difference between the group fed normal-zinc diet and the group fed a hyper-zinc diet. Zinc also improved the rates of growth in the rats. The body weights and length of femora increased dose-dependently. Static histomorphometry showed that zinc exerted its main effect on the periosteal envelope, thereby increasing bone area, tissue area, and axial moment of inertia. We conclude that alimentary zinc supplementation in growing rats induces an increase of bone strength in both the femoral neck and the femoral diaphysis. These results further support the view that zinc has a positive effect on bone metabolism which mimics that of growth hormone (GH) or insulin-like growth factor 1 (IGF-1).

Animals↗

PubMed2001

Autometallographic tracing of bismuth in human brain autopsies.

For decades, drugs containing bismuth have been used to treat gastrointestinal disorders. Although a variety of adverse effects, including neurological syndromes, have been recorded, the biological/toxicological effects of bismuth ions are far from disclosed. Until recently, only quantitative assessments were possible, but resent research has made histochemical tracing of bismuth possible. The technique involves silver enhancement of bismuth crystallites by autometallography (AMG). In the present study, the localization of bismuth was traced by AMG in sections of paraffin-embedded brain tissue obtained by autopsy from 6 patients suffering from bismuth intoxication in a period ranging from 1975 through 1977. Tissue was analyzed at light and electron microscopical levels, and the presence of bismuth further confirmed by proton-induced x-ray emission (PIXE). Clinical data and bismuth concentrations in blood, cerebellum, and thalamus were measured by atomic absorption spectrophotometry (AAS) and are reported here. Histochemical analyses demonstrate that bismuth accumulated in neurons and glia cells in the brain regions examined (neocortex, cerebellum, thalamus, hippocampus). Cerebellar blood vessels stained most intensely. The PIXE and AAS data correlated with the histochemical staining patterns and intensities. At the ultrastructural level, bismuth was found to accumulate intracellularly in lysosomes and extracellularly in the basement membranes of some vessels.

Aged↗

PubMed2000

Release of synaptic zinc is substantially depressed by conventional brain slice preparations.

Research on synaptically-released zinc is frequently done in vitro with acute brain slice preparations. We show here the in vitro hippocampal slice preparation has two major pitfalls for zinc research. First, up to 50% of the synaptic zinc is lost during slice cutting and/or the first 10 min of slice incubation, with the losses being most pronounced on the edges of the slice. Second, the release of the remaining zinc from a slice is substantially depressed (up to 50%) at the low temperatures (32 degrees C) typically used for brain slice studies. In concert, these effects reduce zinc release about 75% in vitro, compared to in vivo. Implications for research on synaptically-released zinc are discussed.

Animals↗

PubMed2000

Zinc-enriched (ZEN) terminals in mouse spinal cord: immunohistochemistry and autometallography.

The general distribution of zinc-enriched (ZEN) terminals in mouse spinal cord was investigated at light microscopic level by means of zinc transporter-3 immunohistochemistry (ZnT3(IHC)) and zinc selenium autometallography (ZnSe(AMG)). Staining for ZnT3(IHC) corresponded closely to the ZnSe(AMG) staining. Both appeared as dense grains of variable sizes and densities in the gray matter with a characteristic segmental laminar pattern. The white matter was unstained but contained rows of stained terminals radiating from the gray matter. In the dorsal horn, laminae I, III and IV were heavily stained, whereas lamina II appeared as the least stained area in the gray matter. Moderate staining was seen in laminae V and VI. In the ventral horn, large ZnT3(IHC) and ZnSe(AMG) grains, known from previous papers to represent ZEN terminals, were observed related in particular to motor neuronal somata and big dendrites. These ZEN terminals in the ventral horn were in general larger than those in the dorsal horn. This is the first description of the pattern of ZEN terminals in mouse spinal cord.

Animals↗

PubMed2000

Zinc-enriched boutons in rat spinal cord.

The rat spinal cord reveals a complex pattern of zinc-enriched (ZEN) boutons. As a result of in vivo exposure to selenide ions, nanosized clusters of zinc selenide are created in places where zinc ions are present, including the zinc-containing synaptic vesicles of ZEN boutons. The clusters can be silver enhanced by autometallographic (AMG) development. A description of the ZEN bouton patterns is presented and discussed. The distribution of ZEN boutons could indicate that these terminal systems have a differentiated influence on sensory and motor systems.

Animals↗

PubMed2000

Zinc-enriched (ZEN) terminals in mouse olfactory bulb.

The present study was designed to localize zinc-enriched (ZEN) terminals in mouse olfactory bulb by means of ZnT3 immunocytochemistry (ICC) and zinc autometallography (AMG). The immunocytochemical staining of ZnT3 was closely correlated with the AMG pattern. ZEN terminals were defined as terminals showing both ZnT3 immunoreactivities and AMG granules. At the light microscopic level, dense staining patterns for ZnT3 immunoreactivity were seen in the granule cell layer and the olfactory glomerular layer. At the ultrastructural level, ZEN terminals were restricted to presynaptic terminals with single or multiple postsynaptic thickenings. The postsynaptic profiles contacting ZEN terminals appeared to be dendrites or somata of granule cells in the granule cell layer and periglomerular cells and mitral/tufted (M/T) cells in the olfactory glomerular layer. This suggests that two main sources of ZEN terminals are present in mouse olfactory bulb: (1) centrifugal fibres making asymmetrical synapses with granule cells and periglomerular cells, and (2) olfactory receptor terminals contacting dendritic profiles of M/T cells or periglomerular cells. The close correlation between ZEN terminals and the glutamatergic system is discussed.

Animals↗

PubMed2000

Evidence that synaptically-released zinc contributes to neuronal injury after traumatic brain injury.

Prior evidence indicates that synaptically-released zinc enters postsynaptic neurons in toxic excess during ischemia and seizures. In addition, prevention of this zinc translocation has been shown to be neuroprotective in both ischemia and seizures. Here we show evidence that the same translocation of zinc from presynaptic boutons into postsynaptic neurons occurs after mechanical injury to the brain. Specifically, using a rat model of traumatic brain injury, we show that trauma is associated with (i) loss of zinc from presynaptic boutons (ii) appearance of zinc in injured neurons, and (iii) neuroprotection by intraventricular administration of a zinc chelator just prior to brain impact. The possible use of zinc chelators for neuroprotection after head trauma is considered.

Aminoquinolines↗

PubMed2000

Histochemically-reactive zinc in amyloid plaques, angiopathy, and degenerating neurons of Alzheimer's diseased brains.

Excess brain zinc has been implicated in Alzheimer's neuropathology. Here we evaluated that hypothesis by searching the brains of Alzheimer's patients for abnormal zinc deposits. Using histochemical methods, we found vivid Zn2+ staining in the amyloid deposits of dense-core (senile) plaques, in the amyloid angiopathy surrounding diseased blood vessels, and in the somata and dendrites of neurons showing the characteristic neurofibrillary tangles (NFT) of Alzheimer's. In contrast, brains from age-matched, non-demented subjects showed only occasional staining for Zn2+ in scattered neurons and possible plaques. A role of abnormal zinc metabolism in Alzheimer's neuropathology is suggested.

Aged↗

PubMed2000

Tissue uptake of bismuth from shotgun pellets.

Shotgun pellets containing bismuth have been suggested to be less environmentally toxic than those containing other metals. We sought to find if bismuth from shotgun pellets embedded within an animal enters the tissues of that animal. Five bismuth-containing shotgun pellets were placed intraperitoneally into adult mice. Four or 9 weeks later the tissue distribution of bismuth was examined histologically using silver lactate autometallography. Bismuth was seen in the nervous system of the mice, either in cells with processes outside the nervous system or in cells not protected by the blood-brain barrier. Bismuth was also seen in the kidney, liver, spleen, and lung. The amount of bismuth within tissues varied widely between animals at both time intervals. Bismuth from shotgun pellets enters the tissues of mice, with some mice taking up more bismuth than others. Some animals wounded with bismuth pellets are therefore likely to accumulate large amounts of potentially toxic bismuth in their tissues.

Animals↗

PubMed2000

Zinc-rich synaptic boutons in human temporal cortex biopsies.

The distribution of zinc-rich synaptic boutons in biopsies of the temporal cortex from epileptic patients who had undergone surgery is described. Unfixed cryostat sections were exposed to H(2)S vapour to precipitate endogenous zinc, which was subsequently shown by silver enhancement. In the temporal cortex, the stain for zinc was arranged in bands: stain was heavy in layers II and VI, moderate-to-heavy in layers I, III and V, and low in layer IV. The white matter was virtually devoid of staining. At the electron microscope level, labelling was found in synaptic boutons that made asymmetric synaptic contacts. Immunohistochemical staining for glutamate receptor subunits GluR2/3 was observed in cell bodies in layers II, III, V and VI, coincident with the layers that showed heavy staining for zinc. Immunostaining for glutamate receptor subunit GluR1 was prominent in non-pyramidal neurons in deep cortical layers. These results support findings in other mammals and indicate that the human neocortex may contain an extensive system of zinc-rich cortico-cortical connections. This system may be altered in pathological conditions.

Biopsy↗

PubMed2000

Histochemical differentiation of autometallographically traceable metals (Au, Ag, Hg, Bi, Zn): protocols for chemical removal of separate autometallographic metal clusters in Epon sections.

Nano-sized clusters of gold atoms, or alternatively silver, mercury, bismuth, or zinc sulphide/selenide molecules, can be autometallographically silver-enhanced by being placed in a developer containing reducing molecules and silver ions, i.e. an autometallographic developer. A specific recipe has been worked out for each autometallographically traceable metal, and in cases where two or more autometallographic catalysts are present in the same section it is feasible to distinguish one from the other by chemical removal of one or the other of the metals. In the present study we present protocols that allow differentiation and control of specificity of the established autometallographically detectable metals. It is recommended to implement a multi-element analysis, e.g. proton-induced X-ray emission on a few samples to secure the histochemical data.

Animals↗

PubMed2000

Bismuth autometallography: protocol, specificity, and differentiation.

We provide a detailed protocol of the autometallographic bismuth technique and evaluate the specificity of the technique. We show by the multi-element technique "proton-induced X-ray microanalysis" (PIXE) that the autometallographic grains contain silver, bismuth, and sulfur, proving that autometallography can be used for specific tracing of bismuth bound as bismuth sulfide clusters in tissue sections from Bi-exposed animals or humans. In sections from animals exposed concurrently to selenium and bismuth, the autometallographic grains also contain selenium. This demonstrates that, if present in excess in the organisms, selenium will bind to exogenous bismuth, creating bismuth selenide clusters. As a further possible control for specificity and as a tool for differentiating among autometallographically detectable metals in sections containing more than one, we describe how bismuth sulfide clusters can be removed from Epon-embedded tissue sections by potassium cyanide.

Animals↗

PubMed1999

Effects of pesticide exposure on time to pregnancy: results of a multicenter study in France and Denmark. ASCLEPIOS Study Group.

The aim of this study was to determine whether there was a relation between male exposure to pesticides and the amount of time needed to conceive (time to pregnancy) for farmers and agricultural workers in France and Denmark. The authors used retrospective studies to compare the time to pregnancy of couples in which the man was exposed to pesticides during the year before the birth of their youngest child with that of couples in which the man was not exposed. In 1995 and 1996, the authors studied 362 French rural workers (142 exposed to pesticides and 220 not exposed), 449 Danish farmers (326 conventional farmers exposed to pesticides and 123 nonexposed organic farmers), and 121 Danish greenhouse workers exposed to pesticides. The fecundability ratio for exposure to pesticides (Cox model, before and after adjustment for confounding factors) did not differ from 1 in any of the three populations. In France, the adjusted fecundability ratio was 1.17 (95% confidence interval (CI) 0.89-1.55) for exposed and nonexposed agricultural workers. In Denmark, it was 1.09 (95% CI 0.82-1.43) for exposed and nonexposed farmers and 0.83 (95% CI 0.69-1.18) for greenhouse workers and nonexposed farmers. Thus, this study found no relation between fertility (time to pregnancy) and male exposure to pesticides.

Adult↗

PubMed1999

Chelation of intracellular zinc ions affects human sperm cell motility.

The effects of two different zinc chelators, diethyldithiocarbamate (DEDTC) and calcium ethylenediaminetetraacetic acid (EDTA), in full semen samples and 'swim-up' samples were investigated. DEDTC, which crosses cell membranes, and EDTA, which does not cross cell membranes, were added to semen samples in different concentrations. Sperm cell motility parameters were assessed by computer-assisted semen analysis (CASA). It was found that very small concentrations (0.01 mM) of DEDTC immobilized the sperm cells within 80 min, while EDTA had no depressing effect at the concentrations used. In full semen samples EDTA enhanced straight line velocity (VSL) at concentrations of 1.0 and 0.5 mM; this effect was not found at higher concentrations. It is suggested that intracellular mitochondrial zinc ions play a crucial role for sperm cell motility, while loosely bound or free zinc ions in the seminal plasma exert a secondary role on human sperm cell motility.

Adult↗

PubMed1999

Autometallographic mercury correlates with degenerative changes in dorsal root ganglia of rats intoxicated with organic mercury.

Organic mercury intoxication in rats produces degenerative changes in the dorsal root ganglia and dorsal nerve roots. In a previous study of rats treated with organic mercury (2 mg/kg ) for 19 days, significant losses of ganglion cells (especially A-cells) and myelinated axons were observed in dorsal nerve roots and there was qualitative evidence of glial cell proliferation and the formation of Nageotte bodies (1). In the present study, the autometallographic silver-enhancement technique, for tracing inorganic mercury bound to sulphide or selenide (AMG-Hg), was applied to tissue sections of dorsal root ganglia and dorsal nerve roots of the same rats used in the earlier study. Satellite cells and macrophages that surrounded ganglion cells and formed Nageotte bodies were heavily labelled by coarse deposits of AMG-Hg, while the labelling of ganglion cells was less pronounced. A-cells were consistently labelled, while B-cells were only occasionally labelled. In the dorsal nerve roots, only a few AMG-Hg deposits could be seen in macrophages. At the ultrastructural level, AMG-Hg was observed within lysosomes of target cells. It is concluded that AMG-Hg is primarily located in glial cells and that the pattern of deposition of AMG-Hg is the same as that for the morphological changes observed in rats intoxicated with organic mercury.

Animals↗

PubMed1999

Detection of pathological zinc accumulation in neurons: methods for autopsy, biopsy, and cultured tissue.

It has been repeatedly shown that synaptically released zinc contributes to excitotoxic neuronal injury in ischemia, epilepsy, and mechanical head trauma. Such zinc-induced injury leaves an unmistakable "footprint" in the injured neurons, allowing an easy and unambiguous postmortem diagnosis. This footprint is the presence of weakly bound, histochemically reactive zinc in the cytoplasm of the perikaryon and proximal dendrites. Such staining appears to be a necessary and sufficient marker for zinc-induced neuronal injury. Here we show how to prepare and stain tissue from biopsy, autopsy, or experimental animal sources for maximal contrast and visibility of zinc-injured neurons.

Animals↗

PubMed1999

Objectives, designs and populations of the European Asclepios study on occupational hazards to male reproductive capability.

The main objective of the Asclepios program was to examine occupational risk factors for the male reproductive system. The program focused on occupational exposure to fungicides (farmers, greenhouse workers, and vineyard workers), styrene (laminators in the reinforced plastics industry) and inorganic lead (battery workers, foundry workers, and lead smelters). Questionnaire studies of time to pregnancy were combined with longitudinal and cross-sectional studies of semen quality. The 8 data-collecting centers addressed 6553 male workers and contributed time-to-pregnancy values on the 3077 most recent pregnancies. Data collection was by interview or self-collection. The average response rate across all exposures and centers was 69.8%. The Asclepios project is the first international multicenter research project on environmental risks to male reproductive function. A protocol for epidemiologic research on occupational risk factors to the male reproductive system was developed, and links between epidemiologic and experimental units were established. The majority, but not all, of the studies was completed within the given time frame.

Adult↗

PubMed1999

Mercury accumulations in brains from populations exposed to high and low dietary levels of methyl mercury. Concentration, chemical form and distribution of mercury in brain samples from autopsies.

Autopsy samples from 17 Greenlanders and 12 Danes were analysed for total and organic mercury by atomic absorption spectrophotometry, and for cellular localisation by autometallography. The concentration of total mercury in the Greenlanders (median: 174 micrograms Hg/kg wet weight brain tissue, range 59-4782, highest in cerebellum: 492) was found to be significantly higher than in the Danish group (3.7 micrograms Hg/kg w.w., range 1.2-11.8). Furthermore, the total concentration of mercury was positively correlated to age (rho = 0.56, p < 0.05), and the fraction of methyl mercury was negatively correlated to age (rho = -0.66, p < 0.01) among the Greenlanders. This suggests an age dependent accumulation of total mercury and a slow transformation of methyl mercury to inorganic mercury in the brain. The autometallographically demonstrable mercury was primarily located in glia cells.

Adult↗