Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For the treatment of acute poisoning from the inhalation of nickel carbonyl, sodium diethyldithiocarbamate (Dithiocarb) has proved to be a specific antidote; tetraethylthiuram (Antabuse) is effective to a lesser degree; d-penicillamine and dimercaprol (BAL) have limited therapeutic value. For the treatment of nickel eczema and dermatitis, favorable response has been obtained by placing patients on a diet of low nickel content together with the oral administration of Dithiocarb or Antabuse. No specific therapy has been advanced for the treatment of nickel cancer in humans. In experimental animals, Dithiocarb has an inhibitory effect on the production of rat rhabdomyosarcomas induced by the intramuscular implantation of nickel subsulfide, and N-methyl formamide inhibits the growth of transplantable nickel fibromas in rats. It is suggested that for the treatment of tumors arising from the implantations of nickel-containing prostheses in humans, chelation therapy be considered.
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PMID:Chelation therapy in nickel poisoning. 626 8

The common earthworm (Lumbricus terrestris) is being evaluated in our laboratories as a substitute for mice in metal toxicity studies. These two disparate species have enzymes in common, such as catalase, superoxide dismutase and glutathione-S-transferase. Also, worms respond similarly to these rodents for selenium and nickel toxicity. Worms are less sensitive, however, to metal toxicity. In this study earthworms were challenged with three different arsenic compounds: arsenite, arsenate and the vesicant phenyldichloroarsine (PDA). The median lethal dose for each arsenic compound was determined. The order of toxicity of the arsenic compounds to the worms was PDA > arsenite > arsenate (24 h LD50 values were 189.5, 191.0 and 519.4 mumol kg-1, respectively). Individual mammalian dithiol antidotes, namely the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS), meso-dimercaptosuccinic acid (DMSA) or 2,3-dimercapto-1-propanol (BAL), were injected into the worms 5 min after various doses of the arsenic compound were administered. The decreases in acute toxicity values were recorded. All three antidotes protected the worms against arsenic toxicity with varying degrees of effectiveness. The protective action for the inorganic arsenic compounds was in the order DMPS > DMSA > BAL. For the organic arsenical, PDA, the most effective antidote was BAL.
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PMID:Evaluation of three antidotes on arsenic toxicity in the common earthworm (Lumbricus terrestris). 752 93

Two large data bases accumulated from the 1980s at the Finnish Institute of Occupational Health, one with results on urinary chromium and nickel analyses and the other with results on total and hexavalent chromium and nickel, were compiled and analysed in order to clarify the occupational exposure during the 1980s, and to reveal possible trends in the exposure of workers in different jobs. The data were processed in three batches: years 1980-1982, 1983-1985 and 1986-1989. The median values of urinary chromium exceeded the biomonitoring action level, BAL, in metal workers, and the mean values exceeded the BAL in both metal workers and plasma cutters. Among all worker groups the median values of urinary chromium remained quite stable during the study period. The median values of urinary nickel concentration did not exceed the BAL in any worker group studied, but an increasing trend was observed among moulders. In the breathing zone of grinders, the median value of total or trivalent chromium exceeded the occupational exposure limit, OEL. The medial of hexavalent chromium concentration in the breathing zone of metal sprayers and spray painters was higher than the OEL. No decreasing trend in exposure could be observed during the 10-year period in breathing zone air.
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PMID:Occupational exposure to chromium and nickel in the 1980s in Finland. 920 Aug 51

Initiated by numerous factors, acute lung injury is marked by epithelial and endothelial cell perturbation and inflammatory cell influx that leads to surfactant disruption, pulmonary edema, and atelectasis. This syndrome has been associated with a myriad of mediators including cytokines, oxidants, and growth factors. To better understand gene-environmental interactions controlling this complex process, the sensitivity of inbred mouse strains was investigated following acute lung injury that was induced by fine nickel sulfate aerosol. Measuring survival time, protein and neutrophil concentrations in BAL fluid, lung wet-to-dry weight ratio, and histology, we found that these responses varied between inbred mouse strains and that susceptibility is heritable. To assess the progression of acute lung injury, the temporal expression of genes and expressed sequence tags was assessed by complementary DNA microarray analysis. Enhanced expression was noted in genes that were associated with oxidative stress, antiprotease function, and extracellular matrix repair. In contrast, expression levels of surfactant proteins (SPs) and Clara cell secretory protein (ie, transcripts that are constitutively expressed in the lung) decreased markedly. Genome-wide analysis was performed with offspring derived from a sensitive and resistant strain (C57BL/6xA F(1) backcrossed with susceptible A strain). Significant linkage was identified for a locus on chromosome 6 (proposed as Aliq4), a region that we had identified previously following ozone-induced acute lung injury. Two suggestive linkages were identified on chromosomes 1 and 12. Using haplotype analysis to estimate the combined effect of these regions (along with putative modifying loci on chromosomes 9 and 16), we found that five loci interact to account for the differences in survival time of the parental strains. Candidate genes contained in Aliq4 include SP-B, aquaporin 1, and transforming growth factor-alpha. Thus, the functional genomic approaches of large gene set expression (complementary DNA microarray) and genome-wide analyses continue to provide novel insights into the genetic susceptibility of lung injury.
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PMID:Acute lung injury: functional genomics and genetic susceptibility. 1189 92

The authors report the case of a worker in the hard metal industry presenting with asthma due to cobalt and nickel. The diagnosis was supported by the history, positive skin tests and lymphocyte activation as well as elevated levels of the metals in the urine and BAL. Challenge led to a delayed asthmatic reaction occurring 3.5 to 24 hours after exposure. The BAL contained high levels of tungsten and cobalt, the level of the latter doubling 48 hours after exposure. After the provocation test a nasal and broncho-alveolar eosinophilia was observed. The possibility of a delayed hypersensitivity reaction to metals is discussed by the authors.
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PMID:[Occupational asthma due to hard metals hypersensitivity]. 1216 93

The effects of chelating drugs used clinically as antidotes to metal toxicity are reviewed. Human exposure to a number of metals such as lead, cadmium, mercury, manganese, aluminum, iron, copper, thallium, arsenic, chromium, nickel and platinum may lead to toxic effects, which are different for each metal. Similarly the pharmacokinetic data, clinical use and adverse effects of most of the chelating drugs used in human metal poisoning are also different for each chelating drug. The chelating drugs with worldwide application are dimercaprol (BAL), succimer (meso-DMSA), unithiol (DMPS), D-penicillamine (DPA), N-acetyl-D-penicillamine (NAPA), calcium disodium ethylenediaminetetraacetate (CaNa(2)EDTA), calcium trisodium or zinc trisodium diethylenetriaminepentaacetate (CaNa(3)DTPA, ZnNa(3)DTPA), deferoxamine (DFO), deferiprone (L1), triethylenetetraamine (trientine), N-acetylcysteine (NAC), and Prussian blue (PB). Several new synthetic homologues and experimental chelating agents have been designed and tested in vivo for their metal binding effects. These include three groups of synthetic chelators, namely the polyaminopolycarboxylic acids (EDTA and DTPA), the derivatives of BAL (DMPS, DMSA and mono- and dialkylesters of DMSA) and the carbodithioates. Many factors have been shown to affect the efficacy of the chelation treatment in metal poisoning. Within this context it has been shown in experiments using young and adult animals that metal toxicity and chelation effects could be influenced by age. These findings may have a bearing in the design of new therapeutic chelation protocols for metal toxicity.
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PMID:Chelators as antidotes of metal toxicity: therapeutic and experimental aspects. 1630 72

Abstract Nickel, zinc, and copper oxide nanoparticles (NiONP, ZnONP, and CuONP) and their aqueous extracts (AEs) were applied to A549 lung epithelial cells to determine the cytotoxicity, IL-8 production, and activation of transcription factors. Nanoparticles (NPs) and their AEs were also instilled into rat lungs to evaluate acute and chronic inflammatory effects. In vitro AEs had specific effects; for example NiOAE had no effect and ZnOAE affected all parameters measured. NPs themselves all had cytotoxic effects but only ZnONP and CuONP impacted pro-inflammatory endpoints. The inflammatory cells in the BAL were also different from AEs and NPs with ZnONP and CuONP recruiting eosinophils and neutrophils whilst ZnOAE and CuOAE elicited only mild neutrophilic inflammation that had resolved by four weeks. NiONP recruited neutrophils only whilst NiOAE did not cause any inflammation. Understanding differences in the toxic role of the ionic components of metal oxide NPs will contribute to full hazard identification and characterisation.
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PMID:Differential pro-inflammatory effects of metal oxide nanoparticles and their soluble ions in vitro and in vivo; zinc and copper nanoparticles, but not their ions, recruit eosinophils to the lungs. 2133

Most acute and chronic human metal poisonings are due to oral or inhalation exposure. Almost 80% of published animal experiments on chelation in metal poisoning used single or repeated intraperitoneal, intramuscular or intravenous administration of metal and chelator, impeding extrapolation to clinical settings. Intramuscular administration of dimercaptopropanol (BAL) has until now been used in acute arsenic, lead, and mercury poisonings, but repeated BAL administration increased the brain uptake of As, Pb and Hg in experimental animals. Also, diethyl dithiocarbamate (DDC) has been used as antidote in acute experimental animal parenteral Cd poisoning, and both DDC and tetraethylthiuram disulfide (TTD, disulfiram, Antabuse) have been used in nickel allergic patients. However, even one dose of DDC given immediately after oral Cd or Ni increased their brain uptake considerably. The calcium salt of ethylenediamminetetraacetic acid (CaEDTA) but not dimercaptosuccinic acid (DMSA) increased the brain uptake of Pb. In oral Cd or Hg poisoning, early oral administration of DMSA or dimercaptopropane sulfonate (DMPS) increased survival and reduced intestinal metal uptake. Oral administration of Prussian Blue or resins with fixed chelating groups that are not absorbed offer chelation approaches for decorporation after oral exposure to various metals. Diethylenetriaminepentaacetic acid (DTPA) nebulizers for pulmonary chelation after inhalation exposure need further development. Also, combined chelation with more than one compound may offer extensive advances. Solid knowledge on the chemistry of metal chelates together with relevant animal experiments should guide development of chelation procedures to alleviate and not aggravate the clinical status of poisoned patients.
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PMID:A review of pitfalls and progress in chelation treatment of metal poisonings. 2715 Sep 11