-
Blood Sep 1949
Topics: Antimony; Multiple Myeloma; Neoplasms
PubMed: 18134771
DOI: No ID Found -
International Journal of Environmental... Jun 2017This study investigated antimony exposure among employees in industries in Taiwan and evaluated whether their immunologic markers were associated with antimony exposure....
This study investigated antimony exposure among employees in industries in Taiwan and evaluated whether their immunologic markers were associated with antimony exposure. We recruited 91 male workers and 42 male office administrators from 2 glass manufacturing plants, 1 antimony trioxide manufacturing plants, and 2 engineering plastic manufacturing plants. Air samples were collected at worksites and administrative offices, and each participant provided specimens of urine, blood, and hair to assay antimony levels. We also determined white blood cells, lymphocyte, and monocyte, IgA, IgE, and IgG in blood specimens. The mean antimony concentration in the air measured at worksites was much higher in the antimony trioxide plant (2.51 ± 0.57 mg/m³) than in plastic plants (0.21 ± 0.06 mg/m³) and glass plants (0.14 ± 0.01 mg/m³). Antimony levels in blood, urine, and hair measured for participants were correlated with worksites and were higher in workers than in administrators. The mean serum IgG, IgA, and IgE levels were lower in workers than in administrators ( < 0.001). Serum IgA and IgE levels in participants were negatively associated with antimony levels in air samples of workplaces, and in blood, urine, and hairs of participants. Serum IgG and IgE of all participants were also negatively associated with antimony levels in their hairs. In conclusion, the antimony exposure is greater for workers employed in the five industrial plants than for administrators. This study suggests serum IgG, IgA, and IgE levels are negatively associated with antimony exposure.
Topics: Adult; Air Pollutants; Antimony; Biomarkers; Hair; Humans; Male; Metallurgy; Occupational Exposure; Taiwan
PubMed: 28672853
DOI: 10.3390/ijerph14070689 -
The Science of the Total Environment Mar 2022The mining of deposits containing metals like antimony (Sb) causes serious environmental issues that threaten human health and ecological systems. However, information...
The mining of deposits containing metals like antimony (Sb) causes serious environmental issues that threaten human health and ecological systems. However, information on the effect of Sb on freshwater sediment microorganisms and the mechanism of microbial Sb resistance is still very limited. This was the first attempt to explore microbial communities in river sediments impacted by accidental Sb spill. Metagenomic analysis revealed the high relative abundance of Proteobacteria and Actinobacteria in all the studied river sediments, showing their advantage in resistance to Sb pollution. Under Sb stress, microbial functions related to DNA repair and ion transport were enhanced. Increase in heavy metal resistance genes (HMRGs), particularly Sb transport-related arsB gene, was observed at Sb spill-impacted sites. HMRGs were significantly correlated with ARGs and MGEs, and the abundant MGEs at Sb spill-impacted sites might contribute to the increase in HMRGs and ARGs via horizontal gene transfer. Deinococcus, Sphingopyxis and Paracoccus were identified as potential tolerant genera under Sb pressure and might be related to the transmission of HMRGs and ARGs. This study can add new insights towards the effect of accidental metal spill on sediment microbial community.
Topics: Anti-Bacterial Agents; Antimony; Genes, Bacterial; Humans; Metagenomics; Metals, Heavy; Microbiota; Rivers
PubMed: 34923019
DOI: 10.1016/j.scitotenv.2021.152484 -
Clinical Infectious Diseases : An... May 2021Antimonial drugs have long been the mainstay to treat visceral leishmaniasis. Their use has been discontinued in the Indian subcontinent because of drug resistance, but...
BACKGROUND
Antimonial drugs have long been the mainstay to treat visceral leishmaniasis. Their use has been discontinued in the Indian subcontinent because of drug resistance, but they are still clinically useful elsewhere. The goal of this study was to find markers of antimony resistance in Leishmania donovani clinical isolates and validate experimentally their role in resistance.
METHODS
The genomes of sensitive and antimony-resistant clinical isolates were sequenced. The role of a specific gene in contributing to resistance was studied by CRISPR-Cas9-mediated gene editing and intracellular drug sensitivity assays.
RESULTS
Both gene copy number variations and single nucleotide variants were associated with antimony resistance. A homozygous insertion of 2 nucleotides was found in the gene coding for the aquaglyceroporin AQP1 in both resistant isolates. Restoring the wild-type AQP1 open reading frame re-sensitized the 2 independent resistant isolates to antimonials. Alternatively, editing the genome of a sensitive isolate by incorporating the 2-nucleotide insertion in its AQP1 gene led to antimony-resistant parasites.
CONCLUSIONS
Through genomic analysis and CRISPR-Cas9-mediated genome editing we have proven the role of the AQP1 mutations in antimony clinical resistance in L. donovani.
Topics: Antimony; Antiprotozoal Agents; Aquaglyceroporins; DNA Copy Number Variations; Drug Resistance; Humans; Leishmania donovani; Leishmaniasis, Visceral; Mutation
PubMed: 32827255
DOI: 10.1093/cid/ciaa1236 -
Chemosphere Jan 2021Antimony (Sb) is a highly toxic heavy metal, and the amount of Sb in the soil is increasing due to anthropogenic activities. Recently, biochar (BC) has been used for...
Antimony (Sb) is a highly toxic heavy metal, and the amount of Sb in the soil is increasing due to anthropogenic activities. Recently, biochar (BC) has been used for remediation of Sb-contaminated soil, therefore, understanding the effect of BC-induced changes in soil microbial on the change of Sb speciation will help to elucidate the mechanism of BC in immobilization/mobilization of Sb in contaminated soils. Sb-contaminated soil with 10 wt % of Wheat straw-derived BC (SBC) and fruit (apple) tree-derived BC (FBC) and control was incubated for 130 days. Changes of soil bacterial community composition and Sb oxidation gene induced by BC were explored during the incubation. Dynamic change of Sb speciation was assessed by the citric acid extraction. The redundancy analysis (RDA) and spearman analysis (PCA) was used to analyze the relationship between Sb immobilization/mobilization and change of soil bacterial community induced by BC. The soil properties change induced by BC affected soil bacterial community composition, and Sb mobilization was strongly related to the change of soil bacterial community composition. The relative abundance of Sb oxidation gene increased in the soil amended by BC, which proved that oxidation of Sb(III) after 20 d incubation with SBC and 50 d incubation with FBC incubation. It is noteworthy that the application of BC has a potential mobilizing risk for Sb and both the change of soil bacteria and soil chemical properties play an important role in Sb mobilization. The possible risks induced by BC should be considered before applying the BC to Sb contaminated soil.
Topics: Antimony; Charcoal; Soil; Soil Microbiology; Soil Pollutants
PubMed: 32822942
DOI: 10.1016/j.chemosphere.2020.127795 -
The Journal of Infectious Diseases Nov 2004Cutaneous leishmaniasis (CL) requires 2-6 months to heal. In an effort to reduce this healing time, we studied topically applied granulocyte-macrophage... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Antimony plus recombinant human granulocyte-macrophage colony-stimulating factor applied topically in low doses enhances healing of cutaneous Leishmaniasis ulcers: a randomized, double-blind, placebo-controlled study.
Cutaneous leishmaniasis (CL) requires 2-6 months to heal. In an effort to reduce this healing time, we studied topically applied granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjunct to antimonial therapy. Ten patients received antimony plus topical GM-CSF, and 10 patients received antimony plus placebo (saline). GM-CSF was diluted for topical use and was applied 3 times weekly for 3 weeks (1-2 microg/cm2/lesion). The mean +/- SD healing time was 43 +/- 14 days in the GM-CSF group and was 104+/-79 days in the placebo group (P=.043). Ten (100%) of 10 patients in the GM-CSF group healed within 60 days, compared with 5 (50%) of 10 patients in the placebo group. Two of the patients in the placebo group required retreatment with antimony. In conclusion, topically applied GM-CSF is effective in the management of CL.
Topics: Administration, Topical; Adolescent; Adult; Antimony; Antiprotozoal Agents; Brazil; Double-Blind Method; Drug Therapy, Combination; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leishmaniasis, Cutaneous; Male; Middle Aged; Recombinant Proteins; Time Factors; Treatment Outcome
PubMed: 15499535
DOI: 10.1086/424848 -
MSphere Apr 2018Antimonials (Sb) were used for decades for chemotherapy of visceral leishmaniasis (VL). Now abandoned in the Indian subcontinent (ISC) because of resistance, this drug...
Antimonials (Sb) were used for decades for chemotherapy of visceral leishmaniasis (VL). Now abandoned in the Indian subcontinent (ISC) because of resistance, this drug offers a unique model for understanding drug resistance dynamics. In a previous phylogenomic study, we found two distinct populations of : the core group (CG) in the Gangetic plains and ISC1 in the Nepalese highlands. Sb resistance was only encountered within the CG, and a series of potential markers were identified. Here, we analyzed the development of resistance to trivalent antimonials (Sb) upon experimental selection in ISC1 and CG strains. We observed that (i) baseline Sb susceptibility of parasites was higher in ISC1 than in the CG, (ii) time to Sb resistance was higher for ISC1 parasites than for CG strains, and (iii) untargeted genomic and metabolomic analyses revealed molecular changes along the selection process: these were more numerous in ISC1 than in the CG. Altogether these observations led to the hypothesis that CG parasites are preadapted to Sb resistance. This hypothesis was experimentally confirmed by showing that only wild-type CG strains could survive a direct exposure to the maximal concentration of Sb The main driver of this preadaptation was shown to be , a gene involved in Sb sequestration and amplified in an intrachromosomal amplicon in all CG strains characterized so far. This amplicon emerged around 1850 in the CG, well before the implementation of antimonials for VL chemotherapy, and we discuss here several hypotheses of selective pressure that could have accompanied its emergence. The "antibiotic resistance crisis" is a major challenge for scientists and medical professionals. This steady rise in drug-resistant pathogens also extends to parasitic diseases, with antimony being the first anti- drug that fell in the Indian subcontinent (ISC). Leishmaniasis is a major but neglected infectious disease with limited therapeutic options. Therefore, understanding how parasites became resistant to antimonials is of commanding importance. In this study, we experimentally characterized the dynamics of this resistance acquisition and show for the first time that some populations of the ISC were preadapted to antimony resistance, likely driven by environmental factors or by drugs used in the 19th century.
Topics: Antimony; Antimony Potassium Tartrate; Antiprotozoal Agents; Drug Resistance; Genetic Variation; Genomics; Humans; India; Leishmania donovani; Leishmaniasis, Visceral; Metabolomics; Nepal; Protozoan Proteins
PubMed: 29669889
DOI: 10.1128/mSphere.00548-17 -
Molecular Pharmacology Apr 2006Antimonial agents are a mainstay for the treatment of leishmaniasis, a group of protozoal diseases that includes visceral leishmaniasis, or Kala Azar. Chemotherapy with...
Antimonial agents are a mainstay for the treatment of leishmaniasis, a group of protozoal diseases that includes visceral leishmaniasis, or Kala Azar. Chemotherapy with trivalent potassium antimony tartrate (PAT) and, more importantly, pentavalent antimony-carbohydrate complexes, such as sodium stibogluconate (SSG), has been reported to prolong the QT interval and produce life-threatening arrhythmias. PAT is chemically related to As2O3, which alters cardiac excitability by inhibition of human ether a-go-go related gene (hERG) trafficking and an increase of cardiac calcium currents. In this study, we report that PAT does not block hERG currents on short-term exposure but reduces current density on long-term exposure (IC50, 11.8 microM) and inhibits hERG maturation on Western blots (IC50, 62 microM). Therapeutic concentrations of 0.3 microM PAT increase cardiac calcium currents from -4.8 +/- 0.7 to -7.3 +/- 0.5 pA/pF at 10 mV. In marked contrast, pentavalent SSG, the drug of choice for the treatment of leishmaniasis, did not affect hERG/IKr or any other cardiac potassium current at therapeutic concentrations. However, both cardiac sodium and calcium currents were significantly increased on long-term exposure to 30 microM SSG in isolated guinea pig ventricular myocytes. We propose that the increase in calcium currents from -3.2 +/- 0.3 to -5.1 +/- 0.3 pA/pF at 10 mV prolongs APD90 from 464 +/- 35 to 892 +/- 64 ms. Our data suggest that conversion of Sb(V) into active Sb(III) in patients produces a common mode of action for antimonial drugs, which define a novel compound class that increases cardiac risk not by a reduction of hERG/IKr currents but-for the first time-by an increase in cardiac calcium currents.
Topics: Action Potentials; Antimony; Antiprotozoal Agents; Calcium; Cell Line; Ether-A-Go-Go Potassium Channels; Humans; Leishmaniasis, Visceral; Long QT Syndrome; Myocardium; Torsades de Pointes
PubMed: 16418337
DOI: 10.1124/mol.105.019281 -
Chemosphere Sep 2006Species of macrofungi (mushrooms) were collected from clean areas and analyzed for their antimony content. These were compared to species collected from extremely...
Species of macrofungi (mushrooms) were collected from clean areas and analyzed for their antimony content. These were compared to species collected from extremely polluted areas in the vicinity of a lead smelter and on mine and slag dumps. Antimony content was determined using long-term instrumental neutron activation analysis (INAA). Ectomycorrhizal and terrestrial saprobic macrofungi were examined. Antimony content of macrofungi from the clean areas was mostly less than 100 microg kg(-1) (dry mass). The highest concentrations (units of mg kg(-1)) were found in various species of the ectomycorrhizal genera Chalciporus and Suillus. Antimony contents of macrofungi growing in the polluted areas were considerably higher. The highest content was found in a single collection of Chalciporus piperatus (1,423 mg kg(-1)).
Topics: Antimony; Environmental Pollutants; Fungi; Species Specificity
PubMed: 16529796
DOI: 10.1016/j.chemosphere.2006.01.060 -
Tropical Medicine & International... Dec 2009To evaluate the levels of antimony in plasma and skin of patients being treated with pentavalent antimonials (Glucantime) and their relationship with side effects.
OBJECTIVE
To evaluate the levels of antimony in plasma and skin of patients being treated with pentavalent antimonials (Glucantime) and their relationship with side effects.
METHODS
We evaluated 19 patients treated endovenously at the conventional dose (20 mg Sb(v)/kg/day), two at a smaller dose (5 mg Sb(v)/kg/day) and three treated intralesionally (up to 4.0 ml/week). During treatment, patients underwent periodic blood exams and were interviewed weekly about the incidence of adverse symptoms. The levels of antimony in plasma and skin samples were determined by Inductively Coupled Plasma with Mass Spectrometry (ICP-MS).
RESULTS
The patients under conventional treatment presented a mean initial antimony plasma concentration of 3.39 microg/l; at the end of treatment, these levels were 0.21 before Glucantime application and 125.8 mg after Glucantime application. The mean antimony level in their skin at the end of the treatment was 9.24 microg/g. The main adverse symptoms were arthralgia and myalgia; laboratory results showed mainly lymphocytosis and eosinophilia.
CONCLUSIONS
We found some significant correlations between antimony concentrations, adverse symptoms and laboratory alterations, strengthening the hypothesis of a dose-dependent relationship between antimony concentration in plasma and skin and side effects.
Topics: Adult; Antimony; Antiprotozoal Agents; Dose-Response Relationship, Drug; Female; Humans; Leishmaniasis, Cutaneous; Male; Mass Spectrometry; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Skin; Treatment Outcome
PubMed: 19954451
DOI: 10.1111/j.1365-3156.2009.02408.x