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PubMed2005

Retrospective study of 151 patients with cutaneous leishmaniasis treated with meglumine antimoniate.

We retrospectively analyzed a series of 151 cases of cutaneous leishmaniasis treated between 1967 and 1982. One-hundred-and-thirty-nine (92%) patients presented with active lesions and were treated with daily doses of meglumine antimoniate: 81 adults received a 5-ml vial IM and 58 children received 1 to 5 ml. Forty-five (32.4%) patients underwent continuous treatment with meglumine antimoniate for 25 to 116 days without rest intervals, and 94 (67.6%) intermittent treatment with 2 to 5 series of meglumine antimoniate. Intermittent series could include schedules of daily IM applications for 10 to 25 days each and intervals varying from 10 to 60 days. Antimony dose was calculated for 66 (47.5%) patients and ranged from 3.9 to 28.7 Sb5+/kg/day. Of these, 35 patients received > or =10 mg and 31 patients < 10 mg Sb5+/kg/day. Median time of healing was longer for lesions on the legs and feet -- 67.5 days versus 48.7 days (p < 0.001) for other sites. However, there were no significant differences in the median time of healing between adults and children, intermittent and continuous regimens or high and low antimony doses. Fifty-one patients were reassessed 5 to 14 years after treatment and showed no evidence of disease. These results support further investigation (clinical trials) on treatment using low doses of antimony.

Adolescent↗
PubMed2005

Pharmacokinetic and parasitological evaluation of the bone marrow of dogs with visceral leishmaniasis submitted to multiple dose treatment with liposome-encapsulated meglumine antimoniate.

The aim of the present study was to evaluate the impact of a multiple dose regimen of a liposomal formulation of meglumine antimoniate (LMA) on the pharmacokinetics of antimony in the bone marrow of dogs with visceral leishmaniasis and on the ability of LMA to eliminate parasites from this tissue. Dogs naturally infected with Leishmania chagasi received 4 intravenous doses of either LMA (6.5 mg antimony/kg body weight, N = 9), or empty liposomes (at the same lipid dose as LMA, N = 9) at 4-day intervals. A third group of animals was untreated (N = 8). Before each administration and at different times after treatment, bone marrow was obtained and analyzed for antimony level (LMA group) by electrothermal atomic absorption spectrometry, and for the presence of Leishmania parasites (all groups). There was a significant increase of antimony concentration from 0.76 microg/kg wet organ (4 days after the first dose) to 2.07 microg/kg (4 days after the fourth dose) and a half-life of 4 days for antimony elimination from the bone marrow. Treatment with LMA significantly reduced the number of dogs positive for parasites (with at least one amastigote per 1000 host cells) compared to controls (positive dogs 30 days after treatment: 0 of 9 in the LMA group, 3 of 9 in the group treated with empty liposomes and 3 of 8 in the untreated group). However, complete elimination of parasites was not achieved. In conclusion, the present study showed that multiple dose treatment with LMA was effective in improving antimony levels in the bone marrow of dogs with visceral leishmaniasis and in reducing the number of positive animals, even though it was not sufficient to achieve complete elimination of parasites.

Animals↗
PubMed2003

Speciation of antimony using chromosorb 102 resin as a retention medium.

The selective retention of the Sb(III) chelate with ammonium pyrrolidine dithiocarbamate (APDC) on a column of Chromosorb 102 resin from a buffered sample solution including Sb(V) was used for the determination of Sb(III). The retained antimony was eluted with acetone. The retention of the Sb(III)-iodide compounds with sodium iodide on the Chromosorb 102 resin column from the same solution after reducing Sb(V) to Sb(III) by iodide in acidic solution was used to preconcentrate the total antimony. The retained antimony was eluted with 0.25 mol l(-1) HNO3. The antimony in the effluent was determined by flame atomic-absorption spectrometry. Also, the total antimony was determined directly by graphite-furnace atomic absorption spectrometry. The Sb(V) concentration could be calculated by the difference. The recoveries were > or = 95%. The detection limits of a combination of the column procedure and flame AAS for antimony were 6 - 61 microg l(-1) and comparable to 4 microg l(-1) for a direct GFAAS measurement. The relative standard deviations were <6%. The procedure was applied to the determination of Sb(III) and Sb(V) in spiked tap water, waste-water samples and a certified copper metal with the satisfactory results.

Antimony↗
PubMed1980

Redox substoichiometry in neutron activation analysis. Determination of antimony in metallic tin.

Redox substoichiometry in neutron activation analysis has been applied to the determination of antimony content in metallic tin of chemical grade. The substoichiometric separation is based on the extraction of unreacted antimony(III) with an excess of N-benzoyl-N-phenylhydroxylamine (BPHA) after the substoichiometric oxidation of antimony(III) with potassium bromate, such as arsenic(III), could be prevented by the addition of large amounts of antimony(III) carrier before substoichiometric oxidation. Only about one hour is required for the antimony analysis of metallic tin, excluding the irradiation period of sample. The antimony content of 1.22 +/- 0.14 microgram tin (10 mg) was determined without separation of the matrix element.

Antimony↗
PubMed1984

Lung retention of antimony and arsenic in hamsters after the intratracheal instillation of industrial dust.

Airborne factory dust (with a volume median diameter of 5.0 micron and a geometric standard deviation of 2.1 micron) from a Swedish copper smeltery contained antimony (Sb) (1.6 weight %) and arsenic (As) (19 weight %). The dust was neutron activated and intratracheally instilled in hamsters. In vivo measurements of lung clearance were undertaken of the radionuclides 76As, 122Sb, and 124Sb. Comparison was made with pure substances of antimony trioxide (Sb2O3) and arsenic trioxide (As2O3). Two phases were recognized in the clearance curves. The approximate half-time for the initial phase was 13 h for As2O3, 20 h for arsenic dust, about 40 h for Sb2O3, and about 30 h for antimony dust. The second phase had an approximate half-time of 20-40 d for Sb2O3 and antimony dust. Because of the short physical half-life of 76As, the second phase of the lung clearance was not possible to follow for AS2O3 and arsenic dust. The observed differences in clearance were primarily related to the solubility of the dust particles in saline, while particle size seemed to be less important in this instillation experiment. The low solubility of antimony in factory dust combined with a long biological half-time may be of importance in explaining the observed lung accumulation of antimony in exposed workers. The greater solubility and shorter biological half-time restricted the lung retention of arsenic.

Animals↗
PubMed1977

Fundamental aspects of antimony thin film electrodes for pH measurement.

This report concerns the investigation of the sensitivity, temperature dependence, accuracy, and the standard electrode potential EO of an antimony thin film pH electrode which was prepared with electron beam evaporation techniques. The air-formed oxide film on antimony thin film electrodes has been proved by both the cathodic reduction method and electron spectroscopy for chemical analysis (ESCA). The antimony thin film electrode responded rapidly to pH changes and its sensitivity was slightly changed depending on the buffer composition. The accuracy of this electrode was compared with that of the glass electrode. Temperature had some influence on the function of this electrode. The standard electrode potential of this electrode was discussed together with that of other forms of antimony electrodes. The structure and thickness of the surface oxide on antimony thin film electrodes was confirmed by cathodic reduction and ESCA. It was clear that the surface oxide governs the electrode reactions. Possible applications of the antimony thin film electrode are discussed stating some limitations in the use.

Antimony↗
PubMed1998

[Biological monitoring of persons in areas with increased soil mercury, arsenic and antimony content].

Part of the northern Palatinate region in Germany is characterised by elevated levels of mercury, arsenic and antimony in the soil due to the presence of ore sources and former mercury mining activities. In a biomonitoring study, roughly 200 residents of this region were investigated for a putative increased absorption of these elements. Urine and scalp hair samples were examined. The results did not show a correlation between the mercury and antimony contents in the soil of the housing area and those in urine and hair. On the other hand, slightly but presumably non-hazardous, elevated arsenic contents in urine and scalp hair could be correlated to an increased arsenic content in the soil. According to multiple regression analysis this increase also correlated with the consumption of poultry, eggs and vegetables kept and cultivated respectively in grounds contaminated with arsenic. In urine, sex differences could be seen for antimony: male probands showing significantly higher mean urinary antimony levels than female probands. Urinary mercury contents were correlated with the amalgam area. Similarly, scalp hair of men contained significantly higher levels of arsenic and antimony in comparison to women. Mercury contents in scalp hair were correlated with the consumption of seafood. Children aged 2 to 6 years had significantly lower levels of mercury, arsenic and antimony in urine than the adult subjects. Thus, an elevated health hazard to these children by e.g. intake of contaminated soil is not expected.

Adolescent↗
PubMed2000

Antimony accumulation in Achillea ageratum, Plantago lanceolata and Silene vulgaris growing in an old Sb-mining area.

Preliminary data of a biogeochemical survey concerning antimony transfer from soil to plants in an abandoned Sb-mining area are presented. Achillea ageratum, Plantago lanceolata and Silene vulgaris can strongly accumulate antimony when its extractable fraction in the soil is high (139-793 mg/kg). A. ageratum accumulates in basal leaves (1367 mg/kg) and inflorescences (1105 mg/kg), P. lanceolata in roots (1150 mg/kg) and S. vulgaris in shoots (1164 mg/kg). In these plant species, the efficiency of antimony accumulation decreases when the antimony availability in the soil is high. In A. ageratum and S. vulgaris, the death of the epigeal target part at the end of the growing season contributes to a reduction of the antimony load in the plant. A study to test the use of these species as bioindicators of antimony availability in soil is suggested by our results.

Journal Article↗
PubMed2001

Monitoring of total antimony and its species by ICP-MS and on-line ion chromatography in biological samples from patients treated for leishmaniasis.

Results from a study are reported in which patients with leishmaniasis were monitored by whole blood, blood plasma, urine, and hair analysis, before, during, and after intramuscular administration of N-methyl meglumine antimoniate. Quadrupole ICP-MS was used for the detection of antimony and on-line ion chromatography for the separation of its species. After typically 30 consecutive daily injections of 5 mg antimony per kg of body weight, Sb concentrations of up to 250 microg L(-1) in whole blood and plasma, and 60 mg of Sb per gram of creatinine in urine, were measured 24 h after drug administration. Antimony in hair samples of these patients showed concentrations of up to 24 microg g(-1). Speciation studies of Sb5+ and Sb3+ in drug, urine, and plasma samples were performed by ion chromatography using a Hamilton PRP-100X anion exchange column and EDTA (2 or 20 mM, pH 4.7) as the mobile phases. Repeatability of elution time and peak area measurements for a 0.125 ng spike were <1.2% and <3.5%, respectively. Method detection limits for both species, using a 1:10 diluted urine or plasma sample, were typically 1.6 microg L(-1). The procedure was capable of separating the very intense drug peak from its inorganic species, thus permitting the first studies on the bio-transformation of N-methyl meglumine antimoniate to Sb5+ and Sb3+ in the human body.

Adult↗
PubMed2004

Dual action of antimonial drugs on thiol redox metabolism in the human pathogen Leishmania donovani.

Despite extensive use of antimonial compounds in the treatment of leishmaniasis, their mode of action remains uncertain. Here we show that trivalent antimony (Sb(III)) interferes with trypanothione metabolism in drug-sensitive Leishmania parasites by two inherently distinct mechanisms. First, Sb(III) decreases thiol buffering capacity by inducing rapid efflux of intracellular trypanothione and glutathione in approximately equimolar amounts. Second, Sb(III) inhibits trypanothione reductase in intact cells resulting in accumulation of the disulfide forms of trypanothione and glutathione. These two mechanisms combine to profoundly compromise the thiol redox potential in both amastigote and promastigote stages of the life cycle. Furthermore, we demonstrate that sodium stibogluconate, a pentavalent antimonial used clinically for the treatment for leishmaniasis, induces similar effects on thiol redox metabolism in axenically cultured amastigotes. These observations suggest ways in which current antimony therapies could be improved, overcoming the growing problem of antimony resistance.

Animals↗
PubMed1997

Pentostam induces resistance to antimony and the preservative chlorocresol in Leishmania donovani promastigotes and axenically grown amastigotes.

An axenic amastigote culture system was utilized to directly assess the stage-specific antileishmanial effects of antimony on amastigotes of Leishmania donovani devoid of the macrophage host cell. Pentostam, which contains antimony in the form of sodium stibogluconate and the preservative chlorocresol, was used. Cell density was quantified by measuring the activity of the stable enzyme ornithine decarboxylase. Dose-response curve analyses show that Leishmania promastigotes are susceptible to Pentostam, with the 50% inhibitory concentration (IC50) being 104 microg/ml, while amastigotes are more susceptible, with the IC50 being 24 microg/ml. Promastigotes and amastigotes are also susceptible to chlorocresol, with IC50s being 1.27 and 1.82 microg/ml, respectively. Given that promastigotes are insensitive to antimony, these results suggest that the increased susceptibility of amastigotes to Pentostam is due to the stage-specific activity of sodium stibogluconate. To further study this phenomenon, spontaneous resistance to Pentostam was induced in L. donovani promastigotes by increasing the concentration of Pentostam in the growth medium in a stepwise fashion. Two mutants, Ld1S.04 and Ld1S.20, grew at 0.4 and 2.0 mg of Pentostam per ml, respectively. Promastigotes of these mutants were 11 and 21 times, respectively, more resistant to Pentostam than the wild type. Amastigotes were 40 and 148 times, respectively, more resistant than the wild type. The mutants were also chlorocresol resistant; promastigotes were 6 and 9 times, respectively, more resistant than the wild type, and amastigotes were 14 and 35 times, respectively, more resistant than the wild type. These data show that resistance to Pentostam induced in antimony-insensitive promastigotes is manifested in amastigotes as resistance both to pentavalent antimony and to chlorocresol. The axenic amastigote system is a unique tool which enables direct evaluation of the activity of antileishmanial compounds on the amastigote devoid of its host cell.

Animals↗
PubMed1998

Effects of antimonial therapy on serum zinc, copper and iron concentrations in patients with cutaneous Leishmaniasis in Turkey.

The effects of cutaneous leishmaniasis (CL) infections on total content of the essential trace elements and alterations of these elements content during antimonial therapy, serum iron (Fe), copper (Cu) and zinc (Zn), were determined in 40 patients with CL. 32 healthy subjects were selected as control group. Pentavalent antimonial compounds (Glucantime) were given intramuscularly (20 mg/kg/day) for three weeks in patients group. Serum Cu and Zn levels were determined by flame atomic absorption spectrometry and Fe levels were determined by colorimetrically. Before antimonial therapy; Cu levels were found significantly higher. However, Zn and Fe levels were found significantly lower in the patients group than those of controls. Cu levels were found tended to decrease, while Zn and Fe levels tended to increase during antimonial therapy. There was a negative correlation between serum Cu and Zn levels in CL patients (r = -0.322, p < 0.05). The findings showed that CL affects the essential trace element content and these changes began to disappear during antimonial therapy.

Adolescent↗
PubMed1990

Antimony and glass pH electrodes can be used interchangeably in 24-hour studies of gastric acidity.

Antimony and glass pH electrodes show almost identical experimental errors in continuously measuring buffer solutions at constant temperature over 24 hr. These errors are lower than the nominal quantization error of the instruments and are not properly described by the 24-hr drift determination. The addition of food particles to the solutions can induce severe reading artifacts. The longer response time reported in vitro of antimony electrodes when moving from pH 1 to pH 7 (3.4 sec vs 0.8 sec with glass electrodes) is irrelevant during in vivo pH-metry studies, because we found that the greatest absolute difference between raw fast acquired (4-6 sec) consecutive pH readings of two commonly used devices was 0.7 pH units in circadian profiles obtained from 413 subjects with various clinical conditions. In our in vivo studies, gastric acidity was monitored continuously with two side-by-side minielectrodes, which were variously combined (antimony-glass, A-G; antimony-antimony A1-A2; glass-glass, G1-G2) and applied on groups of 27 subjects matched for clinical condition. The 24-hr pH means and the 24-hr [H+] means calculated from the acidity profiles obtained with the three electrode combinations, lie on the identity line in each group. Using the Bland-Altman technique for assessing measurement agreement, the differences between the 24-hr pH means and the 24-hr [H+] means obtained with the three combined systems are similar (P = .903 and P = 0.824, respectively) and their 95% confidence limits are comprised within the range (+/-) of the reading error of the measuring systems (namely, +/- 0.3 pH units and +/- 12 mmol/liter in terms of [H+]).(ABSTRACT TRUNCATED AT 250 WORDS)

Antimony↗
PubMedDate not supplied

Short term treatment of visceral leishmaniasis of the Old World with low dose interferon gamma and pentavalent antimony.

Eight adult patients with visceral leishmaniasis acquired in mediterranean countries were treated in a prospective study with a combined immunomodulating and antiparasitic regimen consisting of low-dose interferon-gamma (IFN-gamma) and pentavalent antimony. The clinical outcome, hematological and parasitological parameters, the duration of treatment and number of treatment cycles as well as the cumulative dose of pentavalent antimony applied, have been evaluated. The combined treatment led to complete resolution of symptoms and parasitological cure in all cases of visceral leishmaniasis without major side effects. Combined treatment resulted in a significant reduction of duration of treatment (19 vs. 31 days, p < 0.02) and cumulative dose of pentavalent antimony (11.67 vs. 19.30 g, p < 0.02) compared to historical controls (n = 6). No relapses occurred after a median follow-up of 9 months (range: 2-28 months). We conclude that combination therapy is tolerated well and is highly effective in patients with visceral leishmaniasis. The addition of IFN-gamma to standard therapy with pentavalent antimony may reduce the cumulative dose of antimonial drugs, shortens the treatment period and probably reduces the number of relapses.

Adult↗
PubMed2002

Hydride generation for the direct determination of trace and ultra-trace level of arsenic and antimony in waters using derivative atomic absorption spectrometry.

A new method is developed for the direct determination of trace and ultra-trace level of arsenic and antimony in waters by hydride generation derivative atomic absorption spectrometry (DHGAAS). The signal model and fundamentals of DHGAAS are described. The effects of atomization temperature, argon flow rate, acidity and concentration of KBH(4)and KI were investigated and analytical conditions were optimized. The sensitivities for arsenic and antimony were increased 36.4 and 27.6 times better than those of conventional hydride generation atomic absorption spectrometry (HGAAS). For a 2 mV min(-1) sensitivity range setting, the characteristic concentration was 0.003 microg L(-1) for arsenic and 0.004 microg L(-1)for antimony, and the detection limits (3sigma) were 0.015 micro g L(-1) for arsenic and 0.020 microg L(-1) for antimony. The proposed method was applied to the determination of arsenic and antimony in several water samples with satisfactory results.

Antimony↗
PubMed1985

Visceral leishmaniasis unresponsive to antimonial drugs. I. Clinical and immunological studies.

Ten Kenyan patients with visceral leishmaniasis, unresponsive to sodium stibogluconate at a dose of 16 to 20 mg Sb/kg/day given for 30 to 98 days, have been studied clinically and immunologically and compared with 57 antimony-responsive patients. Pulmonary tuberculosis and previous treatment with antimonial drugs were the only factors which were more common in unresponsive patients. The degree of immunosuppression and rate of recovery of immunoreactivity did not differ between antimony-responsive and -unresponsive patients. Only one patient had never been treated before (primary unresponsiveness). In the other nine patients secondary unresponsiveness occurred after one or more treatment courses, suggesting that the parasite developed resistance to antimony. Antimony-unresponsiveness in visceral leishmaniasis is a serious problem numerically, clinically and economically. A plea is made that the initial treatment of visceral leishmaniasis should be adequate in dose and duration.

Antimony Sodium Gluconate↗
PubMed1997

Arsenic and antimony: comparative approach on mechanistic toxicology.

A chemico-toxicological similarity between arsenic and antimony exists and their toxicology is often seen. Indeed, both elements possess several common properties, e.g. they are clastogenic but not mutagenic in the trivalent state and they have a carcinogenic potential: trivalent arsenicals are known to be human carcinogens and antimony(III) oxide (by inhalation) has been shown to cause lung cancer in female rats. For years, arsenic has been known to be environmentally toxic. Elevated human exposure to this element, mostly caused by the intake of contaminated tap water, is associated with increased incidences of cancer at various sites. It is still not clear how arsenic compounds exert their genotoxic effect. It may be connected with an inhibition of DNA repair or the induction of oxidative stress. Little work has been done on the toxicology of antimony as it is less widely present in the environment. There is evidence that in mammals antimony, unlike arsenic, is not detoxified via methylation but it still remains unclear what mechanism is responsible for antimony's genotoxicity. In general, there is little information known about this element to accurately determine its impact on human health. Thus, the aim of this paper is to review current knowledge for future risk assessment and further scientific work.

Animals↗
PubMed2000

Antimony biomethylation by Scopulariopsis brevicaulis: characterization of intermediates and the methyl donor.

The filamentous fungus Scopulariopsis brevicaulis biomethylates inorganic antimony(III) compounds to trimethylstibine, that can be detected in culture headspace gases. Dimethylantimony and trimethylantimony species have been detected in the medium of these cultures, but the origin of these species was controversial. We now show that the dimethylantimony species is a true intermediate on the pathway to trimethylstibine (rather than arising from trimethylstibine oxidation or as an analytical artifact) because no dimethylantimony species are formed on trimethylstibine oxidation, as determined by using HG-GC-AAS. Furthermore, the dimethylantimony and trimethylantimony species can be separated, by using anion exchange chromatography, and so the dimethylantimony species is not an analytical artifact, formed during the hydride generation process. The antimony biomethylation mechanism was further probed by measuring incorporation of the methyl group, from 13CD3-L-methionine and CD3-D-methionine, into methylantimony species and, for comparison, into methylarsenic species. The percentage incorporation of the labeled methyl group into methylarsenic and methylantimony species was not significantly different. The incorporation from 13CD3-L-methionine was 54% and 47% for antimony and arsenic, respectively. The incorporation from CD3-D-methionine was 20% and 16% for antimony and arsenic, respectively. It appears that the biomethylation of arsenic and antimony occur by very similar, perhaps identical, mechanisms.

Anions↗