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[Hygienic evaluation and the effects of toxic factors in the work environment of copper-processing plants].

The study embraces the shops: metallurgic, electrolysis, production of sulfuric acid and shop 100. Tests are performed on the environmental pollution by dust, sulfur dioxide, chlorine, aerosols of sulfuric acid, carbon monoxide, nitric oxide and dioxide, hydrogen chloride, arsenic (II) oxide (III), selenium, tellurium and metal aerosols: lead, copper, cadmium and zinc. The total concentrations of chemical noxae, generating multicomponent mixtures with one-way effect on the work place, are reckon, and estimation in the Bulgarian Institute of Hygiene and Occupational Health and the Ministry of public health methods. In the same shop is comprised a representative group of workers with paraclinical tests: GOT and GPT activity, content of copper and zinc in blood. The assessment made on the work conditions and the changes already found in the workers lead to a discussion for optimizing the conditions in the new shops for copper production.

Air Pollutants, Occupational↗

Selenium-containing tRNA(Glu) and tRNA(Lys) from Escherichia coli: purification, codon specificity and translational activity.

In response to low (approximately 1 microM) levels of selenium, Escherichia coli synthesizes tRNA(Glu) and tRNA(Lys) species that contain 5-methylaminomethyl-2-selenouridine (mnm5Se2U) instead of 5-methylaminomethyl-2-thiouridine (mnm5S2U). Purified glutamate- and lysine-accepting tRNAs containing either mnm5Se2U (tRNA(SeGlu), tRNA(SeLys] or mnm5S2U (tRNA(SGlu), tRNA(SLys] were prepared by RPC-5 reversed-phase chromatography, affinity chromatography using anti-AMP antibodies and DEAE-5PW ion-exchange HPLC. Since mnm5Se2U, like mnm5S2U, appears to occupy the wobble position of the anticodon, the recognition of glutamate codons (GAA and GAG) and lysine codons (AAA and AAG) was studied. While tRNA(SGlu) greatly preferred GAA over GAG, tRNA(SeGlu) showed less preference. Similarly, tRNA(SGlu) preferred AAA over AAG, while tRNA(SeLys) did not. In a wheat germ extract--rabbit globin mRNA translation system, incorporation of lysine and glutamate into protein was generally greater when added as aminoacylated tRNA(Se) than as aminoacylated tRNA(S). In globin mRNA the glutamate and lysine codons GAG and AAG are more numerous than GAA and AAA, thus a more efficient translation of globin message with tRNA(Se) might be expected because of facilitated recognition of codons ending in G.

Cell-Free System↗

Biochemical and genetic analysis of Salmonella typhimurium and Escherichia coli mutants defective in specific incorporation of selenium into formate dehydrogenase and tRNAs.

Mutation of a single gene, referred to as selA1 in Salmonella typhimurium and as selD in Escherichia coli, results in the inability of these organisms to insert selenium specifically into the selenopolypeptides of formate dehydrogenase and into the 2-selenouridine residues of tRNAs. The mutation does not involve transport of selenite into the cell or reduction of selenite to selenide since both mutant strains synthesize selenocysteine and selenomethionine from added selenite and incorporate these selenoamino acids non-specifically into numerous proteins of the bacterial cells. Complementation of the mutation in S. typhimurium with the selD gene from E. coli indicates functional identity of the selA1 and selD genes. Although the selA1 gene maps at approximately 21 min on the S. typhimurium chromosome and the selD gene at approximately 38 min on the E. coli chromosome, only a single gene in wild-type S. typhimurium hybridized to the E. coli selD gene probe. Transformation of the mutant Salmonella strain with a plasmid bearing the E. coli selD gene restored formate dehydrogenase activity, 75Se incorporation into formate dehydrogenase seleno-polypeptides and [75Se]seleno-tRNA synthesis. Transformation with an additional plasmid carrying an E. coli formate dehydrogenase selenopolypeptide-lacZ gene fusion showed that the selD gene allowed readthrough of the UGA codon and synthesis of beta-galactosidase in the Salmonella mutant.

Aldehyde Oxidoreductases↗

Study on the interaction of Se and erythrocyte membrane--protective effect of Se on the erythrocyte membranes.

During the ageing of erythrocyte membrane, the spectrin content, Na,K-ATPase activity as well as the lipid fluidity are obviously decreased. However, supplementation of a trace amount of Na2SeO3 in the medium could prevent the dissociation of spectrin from membrane and delay the changes of Na,K-ATPase activity and lipid fluidity. The effectiveness is proportional to Se concentration within the range of 0.1-1.0 ppm. Similar effect of supplementation of Se on the intact erythrocytes during ageing has been also observed. The protective action of Se on biomembranes is generally interpreted in terms of the activity of Se-containing glutathione peroxidase (GSHPx). However, GSHPx mainly distributes in the cytoplasma of erythrocytes, therefore it seems that the protective action of supplemented Se on the isolated erythrocyte membrane might not be related to the activity of GSHPx.

Erythrocyte Aging↗

Biochemical abnormalities in patients with multiple chemical sensitivities.

Patients with MCS show numerous physiological and biochemical abnormalities and are generally sicker than a control group of allergic patients. Associated with MCS are mitral valve prolapse, hypothyroidism, autoimmune thyroiditis, specific abnormalities of amino acid and essential fatty acid metabolism, and diminished activity of ESOD and EGPx. Equally prevalent among MCS patients and controls are deficiencies of magnesium and Vitamin B6. Since patients with MCS feel sick almost all of the time, it is likely that some of these abnormalities contribute to their general level of ill health, if not to their sensitivities. It is also possible that these various abnormalities are caused by some unidentified fundamental metabolic or neuroendocrine disturbance that is common to states of hypersensitivity. A provocative finding is the high frequency with which impaired anti-oxidant levels were detected. Erythrocyte activity of SOD was low in 89% and EGPx was low in 48% of MCS patients. Furthermore, 41% showed impaired excretion of essential amino acids, despite a high protein diet, and leucocyte vitamin C was low in the 5 patients not taking vitamin C supplements. Anti-oxidant deficiences may certainly contribute to hypersensitivity to environmental pollutants and toxic chemicals. In fact, treatment with anti-oxidants, including selenium, vitamin C, copper, zinc, and sulfur-containing amino acids was associated with major clinical improvement in 14 (25%) of the patients in the MCS group and with limited relief of symptoms in another 10 (18%). In all patients in whom ESOD or EGPx were repeated, improvement in levels was observed following treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hybridoma cultivation in defined serum-free media: growth-supporting substances. V. Trace elements.

The effects of selenium and manganese on growth of hybridomas in serum-free medium were studied. The optimum growth-supporting concentration of Na2SeO3 was about 50 nM. Omission of selenite resulted in decreased growth (60-70% of the number of cells growing with selenite when cultivated for 3 days). The optimum growth-supporting concentration of MnCl2 was 0.5 nM. The number of hybridoma cells growing 3 days without MnCl2 represented about 80% of the cell number obtained by cultivation with MnCl2. Compounds of other trace elements did not display growth-stimulating activity, when tested in short-term culture, perhaps with the exception of lithium at relatively very high concentrations (about 0.2-0.6 mM).

Animals↗

Antagonism between selenium and humic acid.

In this work, two groups of experiments have been done by using mice and luminous bacteria. The results show that there exists an antagonism in toxicity between selenium and humic acid (HA) extracted from the drinking water in Kaschin Beck disease regions. In order to study the chemical mechanism of the antagonism, gel filtration and X-ray photoelectron spectroscopy techniques have been used to study the chemical bonding of the synthetic HA-Se in solution. The relationship between Se and HA in the cause of Kaschin Beck disease is discussed.

Animals↗

Growth of human hepatoma cells lines with differentiated functions in chemically defined medium.

A human hepatoma cell line, HuH-7, which was established from a hepatocellular carcinoma, was found to replicate continuously in a chemically defined medium when the medium was supplemented with Na2SeO3. The cells grew better in this medium than in serum-containing medium without any adaptation period. Other established human hepatoma and hepatoblastoma cell lines, HuH-6 cl-5, PLC/PRF/5, huH-1, and huH-4, also grew in the defined medium. Although HLEC-1 cells failed to proliferate continuously with Na2SeO3 alone, they grew if a cell-free conditioned medium from HuH-7 cells was added to the medium. These cell lines, except the HLEC-1 cell line, produced the following human plasma proteins among those examined: albumin, prealbumin, alpha 1-antitrypsin, ceruloplasmin, fibrinogen, fibronectin, haptoglobin, hemopexin, beta-lipoprotein, alpha 2-macroglobulin, beta 2-microglobulin, transferrin, lipoprotein, alpha 2-macroglobulin, beta 2-microglobulin, transferrin, Complement Components 3 and 4, and alpha 1-fetoprotein. Beside plasma proteins, the media from HuH-7, HuH-6 cl-5, PLC/PRF/5, and huH-1 contained anti-carcinoembryonic antigen-reactive proteins, and those from PLC/PRF/5, huH-1, and huH-4 medium contained hepatitis B surface antigen. These proteins were detected during periods of serial cultivation over 9 months under the above culture conditions. The hepatoma cell lines grown in the fully defined synthetic medium may provide a new approach for investigating the growth and metabolism of human hepatoma cells in vitro.

Blood↗

Effect of selenium dioxide on the testes of rat.

Selenium dioxide was administered (ip) to albino male rats (200 +/- 5 g) in increasing doses (2, 6 and 10 micrograms/rat, daily) for 90 days. Histologic and histometric study showed that there was dose dependent injury to testes. No cellular deformation was observed following 2 micrograms-dose; whereas 6 micrograms-dose caused significant damage of gametogenic cells. At a dose of 10 micrograms, there was a significant testicular degeneration along with testicular atrophy.

Animals↗

Selenium and kidney deposits in experimental argyria. Electron microscopy and microanalysis.

The conjugate effects of selenium and silver salts were studied in experimental renal argyria. Microanalysis has led to the localization of products of chemical reactions to Se and Ag in tissue sections. After prolonged treatment with Ag salts alone, there was Ag and S deposits in basal membranes. When Se and Ag were used together, the formation of these deposits in glomerular basal membranes was accelerated spectacularly. Electron probe microanalysis has shown that Se replaces S in silver deposits. Compared to its effect on other metals, Se was shown to have a complex action, characterized primarily by its toxic effect, favoring the appearance of symptoms of argyria.

Animals↗

Pseudopterygium from exposure to selenium dioxide.

Pseudopterygium and symblepharon developed in a patient exposed to selenium dioxide gas. Previously, a case of pseudopterygium had been reported after exposure to seleniferous acid. This cicatricial condition can be distinguished from the pterygium by eccentric location, the lid scarring, and the absence of pterygium in the other eye. This pseudopterygium recurred despite 11 operations. Full-thickness mucous membrane grafts wee used to separate the lid from the globe.

Adult↗

Scanning ion microscopy mapping of basement membrane elements and arterioles in the kidney after selenium-silver interaction.

The effects of selenium and silver salts was studied by scanning ionic microscopy during experimental argyria mapping of the different basement membrane elements. The ionic microscope (IMS 4F) was equipped with a high resolution spectrometer giving high spatial resolution on the image obtained. After long-term treatment with silver salt alone, silver and sulphur deposits were observed in the membranes. After administration of selenium and silver salt, it was possible to map nitrogen, sulphur, selenium and silver to the glomerular basement membrane as well as to the wall of the kidney arterioles. In the latter, sulphur, selenium and silver were localized only in the elastic laminae of the walls. This process of precipitation of silver deposits in the membrane can be interpreted as process of selenium "detoxification" of the organism.

Animals↗

[Inhibition of the protein kinase C-alpha gene overexpression in rat preneoplastic liver by selenium].

Effect of selenium on the protein kinase c-alpha (PKC-alpha) gene expression was observed in the preneoplastic lesions in liver of S.D. rat Solt-Farber model. Overexpression of PKC-alpha was found in preneoplastic liver but not in partially hepatectomized liver. Administration of 4PPm Na2SeO3 in water 2 weeks before i.p injection of DEN (200 ng/kg bw) for 8 weeks reduced the PKC-alpha gene overexpression in preneoplastic liver and the formation of hyperplastic foci, alpha-GT-altered foci and preneoplastic lesions.

Animals↗

Selenium-induced thyroid dysfunction.

Administration of the anti-oxidative trace element selenium is currently being evaluated for its benefits in patients with inflammatory diseases. However, little is known about the risks of selenium. We report on a patient in whom, along with standard therapy, administration of large intravenous doses of selenite for sepsis secondary to pneumonia resulted in development of marked hypothyroidism. In addition, severe iodine deficiency was noted, and supplementation with iodine led to normalisation of thyroid function.

Aged↗

Toxicity and oxidative stress of different forms of organic selenium and dietary protein in mallard ducklings.

Concentrations of over 100 ppm (mg/kg) selenium (Se) have been found in aquatic plants and insects associated with irrigation drainwater and toxicity to fish and wildlife. Composition of diet for wild ducklings can vary in selenium-contaminated environments. Earlier studies have compared toxicities and oxidative stress of Se as selenite to those of seleno-DL-methionine (DL) in mallards (Anas platyrhynchos). This study compares DL, seleno-L-methionine (L), selenized yeast (Y) and selenized wheat (W). Day-old mallard ducklings received an untreated diet (controls) containing 75% wheat (22% protein) or the same diet containing 15 or 30 ppm Se in the above forms except for 30 ppm Se as W. After 2 weeks, blood and liver samples were collected for biochemical assays and Se analysis. All forms of selenium caused significant increases in plasma and hepatic glutathione peroxidase activities. Se as L at 30 ppm in the diet was the most toxic form, resulting in high mortality (64%) and impaired growth (>50%) in survivors and the greatest increase in ratio of oxidized to reduced hepatic glutathione (GSH). Se as both L and DL decreased the concentrations of hepatic GSH and total thiols. Se as Y accumulated the least in liver (approximately 50% of other forms) and had less effect on GSH and total thiols. In a second experiment, in which the basal diet was a commercial duck feed (22% protein), survival was not affected by 30 ppm Se as DL, L, or Y and oxidative effects on GSH metabolism were less pronounced than with the wheat diet.

Animal Feed↗

Hepatic selenium concentration in pigs with microangiopathy (mulberry heart disease)--an animal model for the study of oxidative damage.

The significance of selenium deficiency was investigated in pigs that died suddenly of microangiopathy (MAP, mulberry heart disease). Hepatic selenium concentration (mean +/- SD) in pigs with MAP (1.04 +/- 0.47 micrograms/g dry weight) was lower than in healthy pigs (1.23 +/- 0.53 micrograms/g). The lowest hepatic selenium values were found in pigs with MAP and in 22.2% of MAP pigs hepatic selenium concentration was below 0.5 microgram/g which reflects selenium deficiency. Thus, pigs with a low selenium status are at risk of MAP. The low selenium status together with vitamin E deficiency increases oxidative stress and thus contributes to the development of oxidative damage.

Animals↗

Selenium redox cycling in the protective effects of organoselenides against oxidant-induced DNA damage.

The biological role of selenium is a subject of intense current interest, and the antioxidant activity of selenoenzymes is now known to be dependent upon redox cycling of selenium within their active sites. Exogenously supplied or metabolically generated organoselenium compounds, capable of propagating a selenium redox cycle, might therefore supplement natural cellular defenses against the oxidizing agents generated during metabolism. We now report evidence that selenium redox cycling can enhance the protective effects of organoselenium compounds against oxidant-induced DNA damage. Phenylaminoethyl selenides were found to protect plasmid DNA from peroxynitrite-mediated damage by scavenging this powerful cellular oxidant and forming phenylaminoethyl selenoxides as the sole selenium-containing products. The redox properties of these organoselenoxide compounds were investigated, and the first redox potentials of selenoxides in the literature are reported here. Rate constants were determined for the reactions of the selenoxides with cellular reductants such as glutathione (GSH). These kinetic data were then used in a MatLab simulation, which showed the feasibility of selenium redox cycling by GSH in the presence of the cellular oxidant, peroxynitrite. Experiments were then carried out in which peroxynitrite-mediated plasmid DNA nick formation in the presence or absence of organoselenium compounds and GSH was monitored. The results demonstrate that GSH-mediated redox cycling of selenium enhances the protective effects of phenylaminoethyl selenides against peroxynitrite-induced DNA damage.

Antioxidants↗