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Effects of extreme hyperinsulinaemia on serum levels of trace metals, trace metal binding proteins, and electrolytes in normal females.

In order to assess the possible effects of insulin on serum concentrations of trace metals (iron, copper, zinc) and trace metal binding proteins (ferritin, transferrin, coeruloplasmin), five normal females were studied with the hyperinsulinaemic-euglycaemic clamp technique. A 0.1 U/kg insulin bolus was administered, followed by an insulin infusion at a rate of 10 mU/kg/min for 12-16 h. Insulin levels of 1500-2000 microU/ml (9.21-12.28 nmol/l) were attained. When iron levels in serum were assayed colorimetrically, there appeared to be a progressive rise in the mean concentration during the course of the insulin infusion. Direct analysis of serum samples by atomic absorption spectrophotometry also showed that the level of non-haeme iron increased 3-fold in the serum of the subject with the lowest concentration of this metal at the start of the study. In contrast with the results for serum iron, the levels of ferritin, total iron binding capacity (transferrin), zinc, copper and coeruloplasmin were not altered in any subject during the insulin infusion or at 24 h following discontinuation of the infusion. Within 4 h of institution of the hyperinsulinaemic clamp significant reductions in serum levels of potassium, phosphorus, cholesterol, total protein and albumin were noted. As the insulin infusion progressed, the urea nitrogen, uric acid and bicarbonate levels fell as well. These observations suggest that supraphysiologic hyperinsulinaemia of 12-16 h duration may alter serum levels of iron, but not serum levels of zinc, copper or trace metal binding proteins in some individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Lack of correlation between trace metal staining and trace metal content of the rat hippocampus following colchicine microinjection.

Following the intrahippocampal injection of colchicine, the trace metal staining with Timm's method is shown to change in the hippocampus. The histochemical examinations were supplemented with atomic absorption spectrophotometric measurement of the trace metals (Zn, Fe, Cu). It was found that intrahippocampal colchicine treatment induces the temporary disappearance of the trace metal staining of the pyramidal cells of the regio superior, while there is a considerable reduction in the staining in the granular cells of the area dentata and in their mossy fibre terminals. Simultaneously, in contrast with the histochemical results, quantitative studies on the trace metal levels showed that colchicine does not lead to evacuation of the trace metals from the hippocampal formation. The combined atomic absorption and trace metal staining investigations prove that there is no correlation between the trace metal staining and the quantitative amounts of the trace metals.

Animals

Control of the growth of leukemic cells (L1210) through manipulation of trace metals.

Trace metals have a role in the activity of the enzyme ribonucleotide reductase (RR) which is essential for the synthesis of DNA and the growth of lymphocytes. Manipulation of the intracellular metals of leukemic cells has been proposed for the therapeutic control of cell growth. We studied the effects of prolonged metal deprivation (Fe, Cu, Zn) on cell growth and RR activity of murine leukemic lymphocytes in culture in metal-depleted media. Intracellular metals, cell growth and RR activity were decreased in related and interdependent ways. A metal-chelator (deferoxamine, DFX) had similar effect. In all cases these effects were reversible by metal supplementation. We conclude that it is possible to control RR activity and growth of leukemic cells in vitro by exposing them to a metal-poor environment (eg. through the action of a chelator). These effects are not permanent, but might be beneficial if integrated with more conventional measures (chemotherapy).

Animals

Genetic trace metal disturbances.

Genetic trace metal disturbances can be at three levels. Trace metals play an important role in the metabolism of genetic macromolecules and the information transfer system. Deficiency or excess of trace metals caused either by dietary or genetic factors will affect the normal functioning of the whole organism. The roles of trace metals in carcinogenesis/mutagenesis and ageing are typical of this category. The second level of genetic trace metal disturbances affect the metabolic pathway of the trace metal itself. Biochemical derangement resulting from genetic defects cause aberrant metabolism of the element and thus disease symptoms. Diseases caused by abnormal metabolism of copper, zinc, iron, and molybdenum are discussed. Trace metal disturbances can also be the result of other genetic diseases. This aspect of genetic trace metal disturbances is least investigated. However, information should be important for improving the existing treatment protocol for the more common inborn errors of metabolism, such as phenylketonuria.

Animals

Toxic trace metals in food. I. A new voltammetric procedure for toxic trace metal control of wines.

A new highly sensitive and particularly reliable analytical procedure for the precise determination of the most relevant toxic trace metals cadmium, lead and copper in wine is presented. It consists of a simple and convenient sample pretreatment by UV irradiation (1,5 h, 500-W-Hg-lamp) to release the toxic trace metals bound by organic substances and subsequent voltammetry (DPASV) of cadmium and lead simultaneously at a mercury film electrode (MFE) formed in situ on a vitreous carbon carrier and of copper on a gold electrode. Particular emphasis has been placed on the efficient exclusion of interference due to contamination. Only special wines, with more than 10% of sugar, require substitution of UV irradiation by a wet digestion also described. The procedure may be easily expanded to include the determination of mercury and zinc.

Electrodes

Toxic trace metals in food. II. A comparative study of the levels of toxic trace metals in wine by differential pulse anodic stripping voltammetry and electrothermal atomic absorption spectrometry.

A new high-performance analytical procedure for the determination of the toxic trace metals cadmium, lead and copper in wines by differential pulse anodic-stripping voltammetry (DPASV) subsequent to UV irradiation of the sample is compared with the hitherto more common application of electrothermal atomic absorption spectrometry (AAS). In this manner also mutually the accuracy attainable with both alternatives has been established. The particularly favourable potentialities of the new voltammetric approach for toxic metal control of wines are demonstrated by the investigation of a typical selection of 36 wines from recent vintages and common vine types of the German and some European wine cultivating regions.

Cadmium

Trace metals: essential nutrients or toxins.

Trace metals play important roles in biological processes, both as essential components and toxins. Monitoring body status of trace metals thus has become an important function of many clinical, industrial, and government laboratories. Deficiencies of some essential trace metals are seen occasionally, but of most importance is the area of metal toxicity resulting from environmental, occupational, accidental, or iatrogenic exposure. Major questions persist about which specimen best reflects body status, and in this regard each metal has different requirements. Blood is used most widely, urine has a few applications, and hair can be used, although external contamination is an ever-present problem. Tissue is by far the best specimen but is not easily obtained. Contamination of specimens during collection and processing must be controlled. Of the instrumental techniques available, atomic absorption spectrometry has been used most widely, particularly with electrothermal and atomization approaches.

Chemistry, Clinical

Trace metal abnormalities in adults during hyperalimentation.

Trace metal deficiencies are now a well-documented complication of total parenteral nutrition (TPN). Zinc deficiency may present in a variety of ways including acrodermatitis skin lesions, impaired immunity, poor growth or impaired wound healing, and mental disturbances. Copper deficiency presents a more uniform picture of hematologic abnormalities, usually anemia with leukopenia and neutropenia. Chromium and selenium deficiencies occur much less frequently, but well-documented cases have been reported. We currently recommended regular monitoring and supplementation of these four trace metals during TPN administration. This article describes the clinical abnormalities that may develop when deficiencies of trace metals occur during TPN administration, and we present recommendations for trace metal supplementation during TPN administration.

Chromium

Trypanosoma lewisi: effects of trace metal contaminants on immunological responses.

The effects of trace metal contaminants (lead, cadmium, and mercury) on the immunologic responses of rats infected with Trypanosoma lewisi were investigated to determine whether chronic exposures to subclinical levels of these metals have adverse effects on the host's ability to respond to an infective agent.Earlier and higher levels of parasitemia were detected in animals exposed to cadmium, lead, and mercury. The variability in length of trypanosome cells in metal-exposed animals became constant at a later time and persisted for a longer time, indicating a delay in antibody synthesis. Serum levels of IgG and IgM were increased in infected animals exposed to trace metals; however, lower levels were observed when compared with infected control animals. Animals exposed only to trace metals showed decreases in serum levels of IgG and IgM. In contact sensitivity to dinitrofluorobenzene (DNFB), animals exposed to trace metals demonstrated no significant difference in sensitization when compared with those infected and exposed to trace metals.

Animals

Determination of subnanogram per cubic meter concentrations of metals in the air of a trace metal clean room by impaction graphite furnace atomic absorption and laser excited atomic fluorescence spectrometry.

Air, drawn by vacuum through a jet, was impacted against the inside surface of an atomic absorption graphite electrothermal atomizer (ETA). The amounts of the particles thus collected were determined at the ng m-3 level by graphite furnace atomic absorption or at the pg m-3 level by laser excited atomic fluorescence. The overall reproducibility of two sets of measurements, made 7 months apart, was 23%, with no significant difference between the two sets of data, based on Student's "t" test at the 95% confidence level. Short-term reproducibility varied from 13% to 34% depending upon the air concentration of the metal. The method shows promise for monitoring long-term effectiveness of the filtering systems in trace metal clean rooms. It was not possible to test for accuracy, due to the low concentrations involved, but accuracy was expected to be within a factor of 2 or 3 of the actual value, based on theoretical aspects of impaction.

Air

Aquatic insects and trace metals: bioavailability, bioaccumulation, and toxicity.

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physicochemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.

Animals

Effect of essential trace metals on bone metabolism in weanling rats: comparison with zinc and other metals' actions.

The effect of essential trace metals on bone metabolism was investigated in the femoral diaphysis of weanling rats. Oral administration of zinc (1.53-306 mumol/100 g body weight) for 3 days produced significant increases in alkaline phosphatase activity and DNA content. These biochemical indices were also increased by oral administration of chromium (III), cobalt, copper, manganese, and nickel with the dose of 1.53 mumol/100 g. With the dose of 15.3 mumol/100 g of above all metals, except zinc, the enzyme activity was significantly decreased in comparison with control, while DNA content was not decreased significantly. Moreover, the effect of zinc on alkaline phosphatase activity and DNA content was not enhanced by simultaneous administration of other metals (1.53 mumol/100 g). The present study indicates that, of the essential trace metals, zinc can effectively stimulate the bone growth and calcification with comparatively higher dose levels. This suggests a nutritional significance of zinc on bone growth.

Alkaline Phosphatase

Plasma trace metals during total parenteral alimentation.

The plasma concentrations of the trace metals zinc and copper were studied prospectively in 13 patients with gastrointestinal diseases treated with parenteral alimentation (TPA) for periods of from 8 days to 7 1/2 weeks. Plasma copper levels fell rapidly and consistently in all patients, with an overall rate of - 11 mug per 100 ml per week. Zinc concentrations declined in 10 of 13 patients at a more gradual rate. Analysis of the standard parenteral alimentation fluids revealed zinc content equivalent to 50% of the daily requirement and a negligible content of copper. From combined analysis of plasma zinc, hair zinc, and taste acuity, there is evidence that increased utilization or redistribution within the body may effect plasma concentrations in some patients. Neither an increase in urinary excretion nor a primary decrease in plasma binding proteins appeared to be a major factor in lowering plasma trace metal concentrations. These findings indicate that a marked decrease in plasma copper is regular and a decline in plasma zinc is common during TPA using fluids unsupplemented with trace metals. Supplementation of parenteral alimentation fluids with the trace metals zinc and copper is recommended.

Adolescent