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Blood concentration of essential trace elements and heavy metals in workers exposed to lead and cadmium.

The aim of the study was to determine blood concentration of essential trace elements (Se, Zn, Cu) and toxic metals (Pb, Cd), markers of antioxidant (activities of glutathione peroxidase (GPx), superoxidase dismutase and ceruloplasmin) and prooxidant processes (thiobarbituric acid reactive substances (TBARS)) in workers exposed to Pb and Cd. Forty three male workers of the lead-acid batteries department, aged 25-52 years, and twenty two workers, including 15 women, aged 36-51 years, exposed to Cd in the alkaline batteries department were examined. The reference group consisted of 52 healthy inhabitants of the same region. It was found that Se concentration and GPx activity in both erythrocytes and plasma of Cd exposed workers were significantly lower (p < 0.001) than in the reference group. We found an inverse linear correlation between blood Se and Cd concentrations in the workers exposed to Cd (r = -0.449; p < 0.01). Moreover, the activity of erythrocyte and plasma GPx was shown to be significantly lower in the study group of workers (p < 0.001). It was observed that TBARS concentration in plasma was significantly higher (p < 0.05) in the lead exposed workers than in the group without contact with Pb. Our results indicate that exposure to Pb and Cd affects the antioxidant potential of blood in workers exposed to heavy metals.

Adult↗

Silicon as an essential trace element in animal nutrition.

Within the last decade silicon has been recognized as participating in the normal metabolism of higher animals and as being an essential trace element. Silicon is found to perform an important role in connective tissue, especially in bone and cartilage. Bone and cartilage abnormalities are associated with a reduction in matrix components, resulting in the establishment of a requirement for silicon in collagen and glycosaminoglycan formation. Silicon's primary effect in bone and cartilage is on the matrix, with formation of the organic matrix appearing to be more severely affected by silicon deficiency than the mineralization process. Additional support for silicon's metabolic role in connective tissue is provided by the finding that silicon is a major ion of osteogenic cells and is present in especially high concentrations in the metabolically active state of the cell; furthermore, silicon reaches relatively high levels in the mitochondria of these cells. Further studies also indicate that silicon participates in the biochemistry of the subcellular enzyme-containing structures. Silicon also forms important interrelationships with other elements. Although it is clear from the body of recent work that silicon performs a specific metabolic function, a structural role has also been proposed for it in connective tissue. A relationship established between silicon and ageing probably relates to glycosaminoglycan changes.

Animals↗

Requirements and toxicity of essential trace elements, illustrated by zinc and copper.

Early signs of toxicity of essential trace elements are important. Some trace elements are available over-the-counter (OTC) and/or are present at industrial waste sites. Physicochemically similar trace elements compete for ligands, impairing functions, which is exemplified by the zinc-copper antagonism described long ago by Van Campen, Hill and Matrone, and Klevay. Intestinal absorption of copper is inhibited by zinc. Thus risk of copper deficiency is increased when the molar ratio of zinc to copper (Zn:Cu) is high. As shown by experiments, copper deficiency can occur in humans. Manifestations include decreased erythrocyte copper-zinc superoxide dismutase, increased low-density-lipoprotein cholesterol, decreased high-density-lipoprotein cholesterol, decreased glucose clearance, decreased methionine and leucine enkephalins, and abnormal cardiac function. Calculation of a preliminary reference dose for OTC zinc that assumed high bioavailability and uncertain copper intakes established 9 mg as a safe amount for 60-kg adults.

Animals↗

The NF-kappa B-like site in the TNF-alpha repressor element is essential for its repressor function.

We have previously identified a repressor element in the TNF-alpha promoter (-280 to -172) by deletion analysis. When this 108 bp repressor element was placed in front of a heterologous promoter containing an NF-kappa B binding site, less repression was observed. When this element was dimerized and placed in front of the positive element (-125 to -102) of the TNF-alpha promoter, instead of repression, activation was observed. There is an NF-kappa B-like site in the 108 bp repressor region (-211 to -202) and our gel retardation analysis showed that this site and a known NF-kappa B binding site both could compete for one of the specific protein complexes formed on the 108 bp probe. To test the functionality of this NF-kappa B-like site, we mutagenized the critical GGGG sequence to ATCC. Contrary to our prediction, such a mutation blocked the repressor function of the 108 bp element. This suggests that the NF-kappa B-like site is an essential sequence for the repressor function of the 108 bp repressor element.

Base Sequence↗

[Role of essential trace elements in the disturbance of carbohydrate metabolism].

Zinc and chromium have been well known to be important trace elements in diabetes as a cofactor for insulin, although their real mechanisms in carbohydrate metabolism are not clear. Especially, chromium is considered essential for maintenance of normal glucose tolerance, and a chromium complex occurring in brewer's yeast, termed glucose tolerance factor (GTF), was found to be of outstanding activity. Recently, some essential trace elements such as vanadium and selenium were observed to have several physiological insulin-like effects by a post-insulin receptor kinase mechanism. It is very likely that chromium, manganese, vanadium, and selenium have a favorable effect on carbohydrate metabolism.

Animals↗

[Effects of total parenteral nutrition containing essential trace elements on their concentrations in rats].

Twenty-four rats were equally divided into 4 groups and maintained for 1 week as follows: Group A (normal control) with a synthetic normal diet and distilled water, group B with conventional total parenteral nutrition (TPN), i.e., TPN without essential trace elements (ETE), group C with TPN supplemented with a usual dose of ETE solution (TE-5), and group D with TPN supplemented with 3 times the usual dose of TE-5. Body weight, trace element concentrations in various tissues and certain blood biochemical parameters were determined in these rats. The results were as follows: 1) No significant differences in body weight were observed among the groups. 2) The iron concentrations in plasma and tibia decreased significantly in group B as compared with group A. The addition of TE-5 prevented these decreases, but dose-dependent increases in the concentrations of iron were observed in liver, spleen and kidney (groups C and D). 3) The zinc concentrations in plasma, whole blood, brain, heart, kidney and tibia decreased significantly in group B as compared with group A. The addition of TE-5 prevented these decreases dose-dependently (groups C and D). 4) The copper concentrations in plasma, whole blood, liver, spleen, kidney, testis and tibia decreased significantly in group B as compared with group A. The addition of TE-5 resulted in a tendency for these decreases to diminish (groups C and D). 5) The manganese concentrations of whole blood in group B decreased significantly as compared with group A. The addition of TE-5 caused the manganese concentrations of various tissues in groups C and D to increase significantly as compared with group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Lethal and temperature-sensitive mutations and their suppressors identify an essential structural element in U2 small nuclear RNA.

U2 snRNA is an essential component of the splicing apparatus in eukaryotic cells. Three possible secondary structures for the highly conserved 5' half of U2 snRNA are consistent with U2 phylogenetic sequence variation. To distinguish among these models and to test the function of U2 structural elements, we made greater than 35 mutations in the yeast U2 snRNA gene. Some of the mutations were designed in pairs so that combinations could be made that would restore base-pairing to differentiate helix requirements from primary sequence requirements. The mutations identify an essential stem-and-loop structure adjacent to the branchpoint interaction region. A conserved complementarity to the loop just upstream of the Sm site and an additional conserved stem-loop are dispensable for U2 function, even in the background of a previously identified large internal deletion. Non-Watson-Crick base appositions at the 53-62 base pair in the essential stem lead to a variety of temperature and KCl-sensitive phenotypes, as well as an accumulation of unspliced precursors in vivo. Chemical structure probing of U2 RNA in vivo reveals that the bulk of U2 in a yeast cell adopts a structure in good agreement with that deduced from genetic results. We suggest that this stem-loop is not a binding site for an intrinsic U2 snRNP protein but may interact with other factors during spliceosome assembly or splicing.

Base Sequence↗

A transcriptionally active tRNA gene interferes with nucleosome positioning in vivo.

Incorporation into a positioned nucleosome of a cis-acting element essential for replication in Saccharomyces cerevisiae disrupts the function of the element in vivo [R. T. Simpson, Nature (London) 343:387-389, 1990]. Furthermore, nucleosome positioning has been implicated in repression of transcription by RNA polymerase II in yeast cells. We have now asked whether the function of cis-acting elements essential for transcription of a gene transcribed by RNA polymerase III can be similarly affected. A tRNA gene was fused to either of two nucleosome positioning signals such that the predicted nucleosome would incorporate near its center the tRNA start site and essential A-box element. These constructs were then introduced into yeast cells on stably maintained, multicopy plasmids. Competent tRNA genes were transcribed in vivo and were not incorporated into positioned nucleosomes. Mutated, inactive tRNA genes were incorporated into nucleosomes whose positions were as predicted. This finding demonstrates that the transcriptional competence of the tRNA gene determined its ability to override a nucleosome positioning signal in vivo and establishes that a hierarchy exists between cis-acting elements and nucleosome positioning signals.

Base Sequence↗

Chromium research from a distance: from 1959 to 1980.

More than 50 years of work have led to the recognition of trivalent chromium as an essential element. Shortly after its identification as an essential element in 1959, its interaction with insulin in vitro and in vivo was established, and the site of action identified as the insulin-sensitive cell membrane. Despite other early clinical successes with chromium supplementation, four major problems have influenced the rate of progress since then: 1) chromium analysis; 2) interaction of chromium with other dietary factors; 3) diagnosis of chromium status; and 4) other controversies, such as the carcinogenic potential of chromium (since disproved) and the lack of an effect on glucose tolerance even in chromium deficient organisms (now explained). These controversies have mostly dissipated as new knowledge integrated seemingly irreconcilable facts and opinions. It is now known that chromium may potentiate the action of insulin either by an effect on insulin dependent functions, or by maintaining these functions with less insulin, or by a combination of both. Despite much progress in the last 30 years, major challenges in chromium research remain, such as the development of practical methods for diagnosing chromium deficiency. Of several approaches for solving this problem, the most feasible might be to standardize the urinary chromium response following an insulinogenic challenge, such as an oral load of glucose or of glucose plus fructose (for maximal stimulation) with urine collection before and during the 2-hour test.

Chromium↗

Simultaneous determination of Pt and essential trace elements in plasma by energy dispersive x-ray fluorescence (EDXRF).

Energy dispersive x-ray fluorescence allows the simultaneous determination of platinum and essential trace-elements in plasma and filtered plasma. Pharmacokinetics of platinum and the variations of trace-elements levels with respect to the normal mean values before and during the treatment are reported. Particularly during the treatment we observed that total iron concentration clearly increases in plasma, which suggests a hemolytic effect of the drug. However we can exclude this hypothesis by the simultaneous determination of potassium and rubidium levels, which do not increase as greatly as in hemolysed samples.

Antineoplastic Combined Chemotherapy Protocols↗

In vivo metal substitutions in metal sequestering subcellular compartments: X-ray mapping in cryosections.

Qualitative digital X-ray mapping techniques were employed to determine the distributions of essential and non-essential elements in three invertebrate "models": (1) Pb, Zn, Cd, Cu, Fe in thin cryosections of the hepatopancreas of the terrestrial isopod, Oniscus asellus; (2) Pb, Zn, Cd, Ca in thin cryosections of the chloragogenous tissue of the earthworm, Lumbricus rubellus; and (3) As in air-dried smears and thin cryosections of chloragogen in L. rubellus. Four general conclusions were drawn from the results of these studies: (a) non-essential elements can accumulate, distribute and be compartmentalized because they, or the organo-complexes that they form, act as "mimics" of essential elements with which they share to a greater or lesser extent certain chemical affinities; (b) thermodynamic considerations notwithstanding, the influence of biological factors on the sequestration and fates of certain elements (e.g., arsenic) is profound through modifications of redox states and organo-compound formation; (c) X-ray mapping, combined with anhydrous preparative procedures, yields unbiased information concerning the relative spatial distributions of several elements in structurally heterogeneous sampling "fields", although the morphological characterization of (occasionally unsuspected) subcellular compartments may be constrained by the intrinsic quality of the preparation; and (d) X-ray microanalysis yields codistribution data, when integrated with biochemical information from other sources, which give strong pointers to the identity of binding ligands and of the valence state of sequestered cations.

Animals↗

Concentrations of trace elements in osteoarthritic knee-joint effusions.

Concentrations of the 18 elements, barium (Ba), beryllium (Be), bismuth (Bi), calcium (Ca), cadmium (Cd), cesium (Cs), copper (Cu), lanthanum (La), lithium (Li), magnesium (Mg), molybdenum (Mo), lead (Pb), rubidium (Rb), antimony (Sb), tin (Sn), strontium (Sr), thallium (Tl), and zinc (Zn), were determined in the synovial fluids of osteoarthritic knee joints and in the corresponding sera of 16 patients by inductively coupled plasma-mass spectrometry. Knee-joint effusions have lower elemental concentrations than their corresponding sera. For the essential elements Ca, Cu, Mg, and Zn and for the nonessential and toxic elements Ba, Be, Bi, La, and Sb, this difference was highly significant. Strong positive correlations between concentrations in effusions and sera for the essential elements Cu and Mg and for the nonessential elements Cs, Li, Rb, and Sr could be established. The grade of localized hyperperfusion of the knee region in the blood pool phase of 99mTc HDP bone scan indicating inflammation did not correlate with any elemental concentration determined.

Adult↗

Trace element levels in whole blood and serum from Swedish adolescents.

Blood and serum samples from 372 15-year-old adolescents were collected in two cities in Sweden and analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The objective was to (1) determine the levels of 13 elements in blood and serum from the teenagers; and (2) for each element, investigate the correlation between the concentrations in blood and serum. The concentrations in blood and serum were generally in line with that usually reported for the essential elements Co, Cu, Zn and Se, and generally low for the 'non-essential' elements Cd, Hg, Pb. The median concentrations were in blood and serum, respectively: of Co 0.31 and 0.48 microg/l, Cu 0.92 and 1.0 mg/l, Zn 6.1 and 0.99 mg/l, Se 110 and 100 microg/l, Rb 2.8 and 0.24 mg/l, Hg 1.1 and 0.44 microg/l, Pb 16 and 0.33 microg/l. The median concentration of W in blood was <0.2 microg/l (below the detection limit) and in serum 0.087 microg/l. The median concentrations of Cd, Rh, Pd, Pt and Tl were below the detection limits. Statistically significant correlations were found between the concentrations in blood and serum for Co, Cu, Zn, Se, Rb, W, Hg and Pb. The levels presented in this study constitute baseline levels or levels generally not exceeded in adolescents for 13 elements, including essential, ubiquitous toxic, and rare elements.

Adolescent↗

Essential trace element alterations in amyotrophic lateral sclerosis.

Although trace elements have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) for a long time, new evidence has connected familial ALS with the metalloenzyme copper-zinc superoxide dismutase, thus reinforcing the study of their metabolism. This work presents the results of serum and cerebrospinal fluid levels of copper, zinc, manganese and magnesium, by atomic absorption spectrophotometry. Statistically significant decreased cerebrospinal fluid and serum copper levels were found in patients compared to the control group (20.25 +/- 7.09 vs. 30.86 +/- 16.02 SD micrograms/l and 913.21 +/- 165.55 vs. 1020.17 +/- 197.76 SD micrograms/l) while serum manganese levels were found to be increased in patients (3.59 +/- 0.89 SD micrograms/l) compared to controls (3.03 +/- 1.23 SD micrograms/l). Zinc and magnesium levels were unchanged. Our findings indicate an essential trace element imbalance in the disease.

Adult↗

Lethal mutations in a yeast U6 RNA gene B block promoter element identify essential contacts with transcription factor-IIIC.

The B block promoter element is the primary binding site for the RNA polymerase III transcription initiation factor TFIIIC. It is always located within the transcript coding region, except in the Saccharomyces cerevisiae U6 RNA gene (SNR6), in which the B block lies 120 base pairs downstream of the terminator. We have exploited the unique location of the SNR6 B block to examine the sequence specificity of its interaction with TFIIIC. The in vitro and in vivo effects of all possible single base pair substitutions in the 9-base pair core of the B block were determined. Five mutant alleles are recessive lethal when present at a low copy number; these alleles identify crucial contacts between TFIIIC and the B block promoter element. Transcript analysis reveals that lethal B block substitutions reduce U6 RNA synthesis at least 10-fold in vivo and 20-fold in vitro. One viable B block mutant strain has one-third the wild type amount of U6 RNA and exhibits reduced levels of the U4-U6 RNA complex required for spliceosome assembly. The locations of lethal single and double point mutations leads us to propose that two domains of TFIIIC contact overlapping sites on the B block element.

Alleles↗

Effect of dietary calcium on cadmium absorption and retention in suckling rats.

The effect of calcium supplementation on absorption and retention of cadmium in the suckling period was evaluated in Wistar rat pups of both sexes. Animals were maintained in the litters with the mother rats and supplemented with 1%, 3% or 6% calcium (as CaHPO4 x 2H2O) in cow's milk by artificial feeding from day of birth 6 through 14. All rats were exposed to cadmium (as CdCl2 x H2O) either orally or parenterally. Oral cadmium dose of 0.5 mg/kg body weight a day was administered through nine-day period of calcium supplementation and parenteral cadmium dose was injected subcutaneously in a single dose of 0.5 mg Cd/kg body weight prior to calcium supplementation. On experimental day 10 (at the age of pups of 15 days) all animals were killed and the liver, kidneys, brain and carcass (body without organs and skin) were removed for element analyses. Cadmium and essential elements calcium, zinc and iron were analysed in the tissues by atomic absorption spectrometry. Results showed that after oral exposure cadmium concentrations in all calcium-supplemented groups were significantly decreased in the organs and carcass and that the effect was dose-related. No such effect of calcium was found after parenteral cadmium exposure. Calcium supplementation per se significantly increased calcium concentration in the carcass and had no effect on iron in organs and zinc in carcass. It was concluded that calcium supplementation during the suckling period could be an efficient way of reducing oral cadmium absorption and retention without affecting tissue essential trace element concentrations.

Absorption↗

H1t/GC-box and H1t/TE1 element are essential for promoter activity of the testis-specific histone H1t gene.

The testis-specific linker histone H1t gene is transcribed exclusively in mid to late pachytene primary spermatocytes. Tissue-specific expression of the gene is mediated primarily through elements located within the proximal promoter. Previous work in transgenic animals identified a unique 40-base pair promoter element designated H1t/TE that is essential for spermatocyte-specific expression. The H1t/TE element contains three subelements designated TE2, GC-box, and TE1 based on in vitro footprinting and electrophoretic mobility shift assays. Because GC-box is a consensus site for binding of Sp transcription-factor family members, experiments were performed demonstrating that two Sp family members, Sp1 and Sp3, were present in testis cells from 9-day-old and adult rats and in pachytene primary spermatocytes and early spermatids. A 95- to 105-kDa form of Sp1 is most abundant in the tissues and cell lines examined, but a 60-kDa form of Sp1 is the most abundant species in spermatocytes and early spermatids. Further examination of Sp1 and Sp3 from adult testis, primary spermatocytes, and early spermatids showed that they can bind to the H1t/TE element. In order to determine the contributions of the subelements to H1t transcription, we mutated each of them in H1t promoter luciferase reporter vectors. Mutation of the GC-box and TE1 subelement reduced expression 77% and 49%, respectively, compared with the wild-type H1t promoter in transient expression assays in a testis GC-2spd cell line that was derived from germinal cells. These studies suggest that Sp transcription factors may be involved in transcription of the H1t gene and the GC-box and the TE1 subelement are required for activation of the H1t promoter.

Animals↗