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PubMedDate not supplied

Successful treatment of non-healing cases of cutaneous leishmaniasis, using a combination of meglumine antimoniate plus allopurinol.

Cutaneous leishmaniasis (CL) is endemic in many countries. It has been recognized as a major public health problem in Iran. The pentavalent antimonials are the first line drugs for the treatment of CL. Recently strains resistant to these drugs have been reported. Allopurinol (AL) has also been suggested for treatment of CL. The efficacy of combination of AL and meglumine antimoniate (MA) in treatment of non-healing cases of CL was evaluated. Non-healing cases of CL have been treated with combination of AL (20 mg/kg for 30 days) and meglumine antimoniate (60 mg/kg per day for 20 days). Twenty-six patients with lupoid leishmaniasis, 6 patients with chronic leishmaniasis and 5 patients who had unhealed leishmaniasis due to leishmanization were accepted for the study. All of the patients except two responded well to treatment, no side effects have been observed and a two year follow up showed no recurrence. A combination of AL and MA increase the antileishmanial effects of antimoniate. We suggest this combination therapy for non-healing and resistant cases of CL.

Adolescent↗
PubMed1987

Antimony accumulation in hair during treatment of leishmaniasis.

We used instrumental neutron activation analysis (INAA) to determine antimony in small quantities of hair from individuals living in an area of endemic leishmaniasis. The groups studied were 12 patients undergoing treatment with N-methylglucamine antimoniate, 34 patients who had received such treatment a year ago, and 17 control subjects (untreated) who were living in the same area. Patients receiving treatment showed mean and median (12.13, 2.9 micrograms/g) values for antimony in hair that significantly exceeded those in either controls (1.01, 0.4 microgram/g) or patients one year after treatment (1.54, 1.0 microgram/g). We conclude that INAA can be useful in monitoring and differentiating such exposure to antimony in patients under treatment.

Antimony↗
PubMed2000

Effects of trivalent antimony on human erythrocyte glutathione-S-transferases.

Trivalent antimony (SB3+) in the form of potassium antimony tartrate was found to be an inhibitor of glutathione-S-transferases (GST) from human erythrocytes with a 50% inhibition concentration (IC50) of 0.05 mM. The inhibition was, however, incomplete with 15-20% of the GST activity remaining unaffected. In comparison, ethacrynic acid, a known inhibitor of GST, was tenfold more potent and affected close to 100% inhibition. Pentavalent antimony (SB5+) in the form of sodium stibogluconate had no effect on GST. Group V metalloids such as arsenite was slightly inhibitory, and arsenate was noninhibitory. When compared with five heavy metals, the inhibitory potency followed the order of SB3+ > Hg2+, Cu2+ > Cd 2+ > Cr3+ > Fe2+ x SB3+ inhibition of GST was competitive against the substrate 1-chloro-2,4-dinitrobenzene (CDNB) with an apparent Ki of 0.018 mM. Increasing the glutathione (GSH) concentration, however, produced a biphasic response: at concentrations below 1 mM, GSH was noncompetitive against SB3+, but at 1 mM and higher it was apparently competitive. A concurrent study of interactions between GSH, CDNB, and SB3+ showed that there was a significant nonenzymatic conjugation of CDNB at high GSH concentrations, which was suppressed by SB3+. The presence of albumin (500 mg/dL), or up to 5 mM N-acetylcysteine, cysteine, or ethylenediamine tetraacetic acid (EDTA) did not protect GST from the inhibitory effect of SB3+. The ability of erythrocyte GST to conjugate CDNB, which was measured directly by the formation of dinitrophenyl-glutathione (DNP-glutathione), was reduced by approximately 20 and 33%, respectively, in the presence of 2 and 10 mM SB3+, and nearly abolished with the addition of 0.2 mM ethacrynic acid. Based on these inhibition characteristics and the preferential accumulation of SB3+ in mammalian erythrocytes, it may be deduced that in the case of high antimonial intake, for example, during therapeutic treatment of Leishmaniasis, SB3+ levels in erythrocytes may be high enough to depress GST activity, which might compromise the ability of erythrocytes to detoxify electrophilic xenotbiotics.

Antimony↗
PubMed1995

Mortality in a cohort of antimony smelter workers.

Animal studies show that antimony may cause lung cancer and heart and lung disease in rodents. In exposed humans, ECG abnormalities and heart and lung disease have been reported. This mortality study of 1,014 men employed between 1937 and 1971 in a Texas antimony smelter consisted primarily of workers of Spanish ancestry (n = 928, 91.5%). Hispanics are known to smoke at much lower rates than non-Hispanics, and their lung cancer and heart disease mortality is generally low. When ethnic-specific Texas lung cancer death rates were used for comparison, mortality from lung cancer among antimony workers was elevated (SMR) 1.39, 90% CI 1.01-1.88), and we observed a significant positive trend in mortality with increasing duration of employment. When ischemic heart disease death rates from three different Spanish-surnamed populations were used for comparison, the rate ratios for mortality from ischemic heart disease were 0.91 (90% CI 0.84-1.09), 1.22 (90% CI 0.78-1.89), and 1.49 (90% CI 0.84-2.63). Pneumoconiosis/ other lung disease death rates for Spanish-surnamed men were unavailable and so calculation of rate ratios used white males as a comparison population (SMR 1.22; 90% CI 0.80-1.80). These data suggest some increased mortality from lung cancer and perhaps nonmalignant respiratory heart disease in workers exposed to antimony. However, conclusions are limited by possible confounders and the difficulty of identifying appropriate referent groups.

Adult↗
PubMed2002

Genotoxic risk and oxidative DNA damage in workers exposed to antimony trioxide.

The growing use of antimony (Sb) compounds in industry and the consequent increase in the number of exposed workers make it important to carry out a health risk assessment. The main goal of this study was to assess the genotoxicity of Sb(2)O(3) in occupationally exposed workers. Genotoxicity was evaluated by the sister chromatid exchange (SCE) and micronucleus tests, and the enzyme (Fpg)-modified comet assay. In addition, antimony exposure levels were established by environmental monitoring with personal air samplers. We studied 23 male workers assigned to different fire retardant treatment tasks in the car upholstery industry and a control group of 23 healthy nonexposed males. The exposed workers were divided into two groups on the basis of their tasks and the work cycle: Group A comprised finishing and intermediate inspection operators who directly handled a mixture containing Sb(2)O(3); Group B were jet operators, not directly exposed to the compound. Environmental monitoring detected low Sb exposure levels but significant differences between the two groups, with Group A having the higher exposure level. Cytogenetic analyses showed no difference between exposed workers and controls for micronuclei and SCE. The enzyme-modified comet assay showed a probable relation between moderate levels of oxidative DNA damage and exposure to antimony, with a significantly higher proportion of workers in Group A having oxidative DNA damage compared to controls. The results support the theory that oxidative DNA damage is involved in the genotoxicity of antimony and indicate the need for further research in this field.

Adult↗
PubMed1987

Biological assessment of exposure to antimony and lead in the glass-producing industry.

The oxide of trivalent antimony is used in the glass-producing industry as a refining agent and as a glass colouring. The batch contains up to 2% Sb2O3, a substance which has shown carcinogenic properties in animal experiments. The internal levels of antimony and lead in blood (SbB and PbB) as well as the excretion with the urine (SbU and PbU) were determined by hydrid and electrothermal atomic absorption (HY-AAS and ET-AAS), respectively. In addition, measurements of airborne Sb2O3-concentrations were performed. The 109 volunteers were employed in four different fields: melting area, batch bunker, glass-washing area, and transport/maintenance. Differences between the concentrations of antimony and lead in blood and urine with respect to the fields of activity were evaluated statistically. The highest values of airborne Sb2O3, with up to 840 micrograms/m3 (TWA), were detected in the batch bunker. Correspondingly, significantly enhanced SbU-values from 1.5 to 15.7 micrograms/l (median: 5.0 micrograms/l) were found in specimens collected from the batch mixers. In the same group, the lead excretion (PbU) with values from 9 to 110 micrograms/l (median: 43 micrograms/l) was also found to be the highest. Due to the fast renal excretion of antimony, the determination of SbU is useful for biological monitoring.

Adult↗
PubMedDate not supplied

Visceral leishmaniasis during pregnancy treated with meglumine antimoniate.

Data on the efficacy and safety of pentavalent antimony in the treatment of visceral leishmaniasis during pregnancy are scanty. A case of visceral leishmaniasis in a 39-year-old woman in the second trimester of pregnancy is reported here. The patient was hospitalized in poor condition with high fever and pancytopenia which had lasted for 6 weeks. A bone marrow aspirate revealed numerous amastigotes and serodiagnosis for Leishmania was positive at a high titer. The patient was successfully treated with meglumine antimoniate at a daily dose of 850 mg of antimony for 20 days. She delivered at term a healthy female baby who remains in good condition at 18 months of age. Thus a dose of 850 mg of antimony, which is lower than that presently recommended, seems to be effective and non toxic to the fetus when administered at the second trimester of pregnancy.

Adult↗
PubMed2004

Failure to remove true sentinel nodes can cause failure of the sentinel node biopsy technique: evidence from antimony concentrations in false-negative sentinel nodes from melanoma patients.

We have recently found that antimony (originating from the technetium 99m antimony trisulfide colloid, used for preoperative lymphoscintigraphy) can be measured in tissue sections from archival paraffin blocks of sentinel nodes (SNs) by means of inductively coupled plasma mass spectrometry (ICP-MS) to confirm that removed nodes are true SNs. We performed a retrospective analysis of antimony concentrations in all our false-negative (FN) SNs to determine whether errors in lymphadenectomy (i.e., failure to remove true SNs) may be a cause of FN SN biopsies (SNBs). Among 27 patients with an FN SNB, metastases were found on histopathologic review of the original slides or additional sections in 7 of 23 patients for which they were available; however, antimony concentrations were low in 5 of 20 presumptive SNs. Our results suggest that an FN SNB can occur because of failure to remove the true SN as well as histopathologic misdiagnosis.

Antimony↗
PubMed1997

New approach for elucidating the oxygen sensitivity and calibration of the antimony electrode.

The biomedical use of the polycrystalline antimony pH electrode is hampered by oxygen dependence and low pH resolution (0.1 pH). Although, the pH resolution is improved by using highly purified crystallographically oriented monocrystalline antimony (COMA), the oxygen effect on the electrode remains. In an in vitro examination of the COMA electrode it was found that the oxygen dependence is similar to that of polycrystalline antimony, i.e. nonlinear with an increase in sensitivity below 10 kPa. These findings imply that the oxygen tension in the vicinity of a COMA pH electrode, has to be known or controllable for the pH reading to be at all valid especially at low oxygen levels, such as is often seen in biomedical applications. A calibration procedure using a zero oxygen solution is used in order to obtain absolute pH readings in a measurement solution of pre-set or known oxygen levels. Furthermore, the nonlinear oxygen sensitivity of the antimony electrode suggests that the underlying electrochemical reactions are other than those described by corrosion theory.

Antimony↗
PubMed1995

Disposition of antimony and aminosidine in dogs after administration separately and together: implications for therapy of leishmaniasis.

The pharmacokinetic behaviour of aminosidine (15 mg kg-1) and antimony (25.65 mg kg-1 as N-methylglucamine antimoniate), administered subcutaneously either separately or together was studied on four dogs. The results demonstrated that antimony (Sb) did not significantly modify the kinetics of aminosidine (AM) but that the kinetic behaviour of the metal was markedly influenced by the antibiotic, as shown by the differences in mean residence time (MRT), elimination rate constant (Kel) and area under the curve (AUC) with and without the antibiotic (MRT[Sb] = 243.8 +/- 29.5 minutes, MRT[Sb+AM] = 1067.9 +/- 199.2 minutes; Kel[Sb] = 0.008 +/- 0.001 min-1, Kel[Sb+AM] = 0.0015 +/- 0.0003 min-1; AUC[Sb] = 21,024.6 +/- 4448.5 micrograms min ml-1, AUC[Sb+AM] = 130,478.5 +/- 30,481.7 micrograms min ml-1). The persistence of high serum concentrations of antimony when it was administered with aminosidine suggests that the therapeutic doses commonly used should be reduced and that the interval between administration should be increased to avoid the metal reaching toxic concentrations.

Animals↗
PubMedDate not supplied

Electrocardiographic alterations during treatment of mucocutaneous leishmaniasis with meglumine antimoniate and allopurinol.

The electrocardiographic (ECG) changes in Bolivian patients with mucocutaneous leishmaniasis, treated with meglumine antimoniate and allopurinol, were evaluated. Electric changes due to the antimonial compound appeared in 45% of the patients, and consisted of repolarization alteration, principally affecting the T wave and the S-T segment. The changes disappeared within 2 months following the end of the antimonial treatment. In patients with associated Chagas disease and leishmaniasis, antimonial therapy did not aggravate the ECG changes characteristic of Chagasic cardiopathy.

Adolescent↗
PubMed2006

Antimony content of macrofungi from clean and polluted areas.

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)).

Antimony↗
PubMed2003

Cobalt and antimony: genotoxicity and carcinogenicity.

The purpose of this review is to summarise the data concerning genotoxicity and carcinogenicity of Co and Sb. Both metals have multiple industrial and/or therapeutical applications, depending on the considered species. Cobalt is used for the production of alloys and hard metal (cemented carbide), diamond polishing, drying agents, pigments and catalysts. Occupational exposure to cobalt may result in adverse health effects in different organs or tissues. Antimony trioxide is primarily used as a flame retardant in rubber, plastics, pigments, adhesives, textiles, and paper. Antimony potassium tartrate has been used worldwide as an anti-shistosomal drug. Pentavalent antimony compounds have been used for the treatment of leishmaniasis. Co(II) ions are genotoxic in vitro and in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal dust, of which occupational exposure is linked to an increased lung cancer risk, is proven to be genotoxic in vitro and in vivo. Possibly, production of active oxygen species and/or DNA repair inhibition are mechanisms involved. Given the recently provided proof for in vitro and in vivo genotoxic potential of hard metal dust, the mechanistic evidence of elevated production of active oxygen species and the epidemiological data on increased cancer risk, it may be advisable to consider the possibility of a new evaluation by IARC. Both trivalent and pentavalent antimony compounds are generally negative in non-mammalian genotoxicity tests, while mammalian test systems usually give positive results for Sb(III) and negative results for Sb(V) compounds. Assessment of the in vivo potential of Sb2O3 to induce chromosome aberrations (CA) gave conflicting results. Animal carcinogenicity data were concluded sufficient for Sb2O3 by IARC. Human carcinogenicity data is difficult to evaluate given the frequent co-exposure to arsenic. Possible mechanisms of action, including potential to produce active oxygen species and to interfere with DNA repair systems, still need further investigation.

Animals↗
PubMed1996

Assessment of a possible genotoxic environmental risk in sheep bred on grounds with strongly elevated contents of mercury, arsenic and antimony.

A part of Northern Palatinate country (Germany) was formerly influenced by mercury mining. Today, in many cases agricultural and housing areas are placed onto or near to former dump grounds of rubble. In the soil of these areas the concentration of mercury, arsenic and antimony was found ranging from basic natural contents up to strongly elevated levels. In a biomonitoring project, sheep bred on grounds contaminated with mercury (range 1-435 mg Hg/kg dry matter), arsenic (range 17-147 mg As/kg dry matter) and antimony (range 2-15 mg Sb/kg dry matter) were taken as example on the uptake of these elements from the environment and for possible effects of this exposure. Significantly elevated mercury levels were found in wool of one collective of exposed sheep (0.107 mg/kg mean vs. 0.048 mg/kg mean, p < 0.001, U-test). Surprisingly, the arsenic content of wool taken from sheep bred in the urban referential area was approx. 10 times higher than that of the sheep bred on the grounds contaminated with arsenic (0.57 mg/kg mean vs. 0.051 mg/kg mean, p < 0.001, U-test). In general, element concentrations in the examined blood samples were low and the differences between the collectives were small: mercury was found in concentrations ranging from 0.9 microgram/l up to 2.0 micrograms/l (means), arsenic and antimony were generally found in concentrations below 1 microgram/l. Neither in the alkaline elution technique nor in the sister chromatid exchange (SCE) analysis significant increases in the rate of DNA-damaging effects between the different sheep collectives were detected. This indicates that the transfer rate of genotoxic compounds of mercury, arsenic or antimony from the environment is too low to register effects with AFE and SCE although the soil was highly contaminated.

Animals↗
PubMed1998

An assessment of the genetic toxicology of antimony trioxide.

Antimony trioxide (Sb2O3, CAS 1309-64-4) has been examined in a range of in vitro and in vivo genotoxicity assays. Negative results were obtained with the Salmonella/microsome assay and the L5178Y mutation assay, but a positive response was observed in the in vitro cytogenetic assay using isolated human peripheral lymphocytes. However, in vivo, antimony trioxide was non-clastogenic in the mouse bone marrow micronucleus assay, following oral gavage administration for 1, 7, 14 or 21 days at dose levels of up to 5000 mg/kg (single dose) or 1000 mg/kg (repeat dose). A negative result was also obtained in the in vivo rat liver DNA repair (unscheduled DNA synthesis) assay following a single oral gavage administration of doses up to 5000 mg/kg. These data show no genotoxicity for antimony trioxide in vivo and do not confirm a previous report of clastogenicity in the mouse on repeated dosing. It is concluded that antimony trioxide is not genotoxic in vivo and does not present a genotoxic hazard to humans.

Animals↗
PubMed2000

The gas-phase on-line formation of antimony oxide trihalides, SbOX3 where X = F and Cl and their identifications by infrared spectroscopy.

Antimony oxide trihalides, SbOX3 molecules, where X = F or Cl have been produced, by means of an on-line process, using antimony trichloride, SbOCl3 as starting material passed over heated silver oxide at 230 degrees C. The antimony oxide trichloride SbOCl3 formed is then reacted with sodium fluoride, NaF at 550 degrees C to produce antimony oxide trifluoride, SbOF3. The products have been characterized by the IR spectra of their vapors. Low resolution gas-phase Fourier transform infrared spectra show strong bands centered at 1272 and 1217 cm(-1), assigned to nu1(a1), the O=Sb stretching fundamental of SbOF3 and SbOCl3, respectively. Both observed bands show typical PQR-type structure with a strong Q-head.

Antimony↗
PubMed2002

Chemical vapor generation for sample introduction into inductively coupled plasma atomic emission spectroscopy: vaporization of antimony(III) with bromide.

A new method for antimony determination in soils is proposed. It is based on the chemical vapor generation of Sb(III) with bromide, after a reaction in sulfuric acid media and transport of the gaseous phase into an inductively coupled plasma for atomic emission spectrometry. The experimental variables influencing the method were delimited by experimental design and the most important were finally optimized by the modified Simplex method. In optimized conditions the method involves the reaction of 579 microl concentrated sulfuric acid with 120 microl 5% w/v KBr and 250 microl antimony solution. Measurement of antimony emission intensity at 217.581 nm provides a method with an absolute detection limit of 3.5 ng and a precision (RSD) of 5.8% for the injection of five replicates of 175 ng Sb(III) (250 microl of 0.7 microg ml(-1) solution). The interference of common anions and cations on the antimony signal was evaluated. A 21% Sb(III) volatilization efficiency was calculated from the mean of six experiments at optimum conditions. The accuracy of the methodology was checked by the analysis of one standard reference soil after acid decomposition heating in a microwave oven.

Antimony↗
PubMed2002

Flow analysis-hydride generation-Fourier transform infrared spectrometry. A new analytical technique for the simultaneous determination of antimony, arsenic and tin.

The combination of flow analysis (FA), hydride generation (HG) and Fourier transform infrared (FTIR) spectrometry is proposed as a novel and powerful analytical technique for the individual and simultaneous determination of antimony, arsenic and tin in aqueous samples. The analytes were transformed into the volatile hydride form by on-line reaction with sodium tetrahydroborate in acidic medium. The gaseous analyte hydrides [M(n)H(m), (g)] generated, were transported by means of a carrier gas stream inside the IR gas cell and the corresponding FTIR spectrum was acquired in a continuous mode. The 1893, 1904 and 2115 cm(-1) bands of the SbH3, SnH4, and AsH3 were selected for the determination of antimony, tin and arsenic, respectively. The limit of detection (3sigma) obtained by using a short-path (10 cm) IR gas cell were 0.25, 0.30 and 1.2 mg l(-1) for the determination of antimony, tin and arsenic, respectively; while the precision (relative standard deviation, RSD, n 5) found from a standard solution containing 50 mg l(-1) of each element was, in all cases, less than 0.3%. However, the use of a long-path (7.25 m) IR gas cell improved the figures of merit (sensitivity, limits of detection and quantification) nearly 60-fold. The effect of the main experimental and instrumental variables, such as acidic media, sodium tetraborohydrate concentration, nitrogen flow rate, nominal resolution and the scan accumulation on the analytical signals of the antimony, tin and arsenic hydrides, were studied. Further, the potential of the proposed technique for the simultaneous determination of these elements was tested, analyzing synthetic samples containing different amounts of Sb, Sn and As.

Antimony↗