Differential distribution of and similar biochemical responses to different species of arsenic and antimony in Vetiveria zizanioides.

Vetiver grass (Vetiveria zizanioides L. Nash) has a great application potential to the phytoremediation of heavy metals pollution. However, few studies explored the bioavailability and distribution of different speciations of As and Sb in V. zizanioides. This study aimed to clarify the allocation and accumulation of two inorganic species arsenic (As(III) and As(V)) and antimony (Sb(III) and Sb(V)) in V. zizanioides, to understand the self-defense mechanisms of V. zizanioides to these metal(loids) elements. Thus, an experiment was conducted under greenhouse conditions to identify distribution of As and Sb in plant roots and shoots. Antioxidant enzymes (superoxide dismutase, SOD) and changes of subcellular structures were tested to evaluate metal(loids) tolerance capacities of V. zizanioides. This study demonstrated that V. zizanioides had higher capacity to accumulate Sb than As. For Sb absorption, Sb(III) content is significantly higher than Sb(V) in tissues of V. zizanioides under all concentration levels, despite the oxidation of Sb(III) on the nutrient solution surface. Additional Sb was mainly accumulated in plant roots due to Sb immobilization by transforming it into precipitates. As was more easily transferred to aerial tissues and had low accumulation rates, probably due to its restricted uptake rather than restricted transport. In many cases, two inorganic species of As and Sb showed almost same biotoxicity to V. zizanioides estimated from its biomass, SOD activity, and MDA content as well as functional groups. In summary, the results of this study provide new insights into understanding allocation, accumulation and phytotoxicity effects of arsenic and antimony in V. zizanioides. Schematic diagram of distribution of and biochemical responses to As(III), As(V), Sb(III), and Sb(V) in tissue of V. zizanioides.

Antimony symplastic and apoplastic absorption, compartmentation, and xylem translocation in Brassica parachinensis L. under antimonate and antimonite.

Antimony (Sb) excess accumulation in edible parts of crops causes potential risks to human health. However, knowledge about the mechanisms of its accumulation within vegetable plants is still not well known. Here, we investigated the physiological processes of Sb involved in symplastic and apoplastic absorption, compartmentation by roots, and translocation in xylem in Brassica parachinensis L. exposed to antimonate (SbV) and antimonite (SbIII) forms. The results showed that plants treated with SbIII emerged to be more toxic than SbV as proved by the lower biomass and the higher concentrations of malonaldehyde (MDA) and hydrogen peroxide (H2O2) in plant tissues, especially at high dosages. The Sb concentration showed more in shoots but less in roots treated with SbV than with SbIII. The total Sb accumulation was higher under the SbV treatment than the SbIII treatment, mainly due to the higher accumulation in shoots. Additionally, the Sb concentration in symplastic flow of roots was higher exposed to SbV than SbIII, while no differences were found for the Sb concentration in apoplastic flow between them. Moreover, the Sb concentration in cell walls of roots was higher exposed to SbIII than SbV, especially at high levels. Furthermore, the Sb concentration in xylem was higher exposed to SbV than SbIII, and a greatly positive correlation was observed between the Sb concentrations in xylem and shoots. Overall, these findings revealed that vegetable plants accumulated more SbV than SbIII in edible parts mainly due to xylem translocation rather than root absorption.

Fraction and mobility of antimony and arsenic in three polluted soils: A comparison of single extraction and sequential extraction.

Co-contamination of arsenic (As) usually occurs with antimony (Sb) in Sb mine ores. However, the mobility and bio-availability of Sb and As in different types of mine impacted soils have received relatively little attention. This study aimed to investigate the fraction, mobility and removal of Sb and As in three types of polluted soils using environmentally friendly and cost-effective extractants. In the present study, lightly polluted (L), moderately polluted (M), and 3) highly polluted (H) soils were collected from the Xikuangshan (XKS) mine area in Hunan, China. Toxicity risk assessment, fraction and extraction of Sb and As were performed to evaluate Sb and As mobility and availability. According to the speciation fractions, the percent of residual Sb was larger than As in all studied soils, which suggested that As is far more mobile than Sb. Sb and As extractabilities from selected polluted soils were compared and ranked as: citric acid > tartaric acid > EDTA > HCl > Na2HPO4 > CaCl2. Citric acid showed the highest extractabilities for both Sb and As (up to 24% for total Sb and 41% for total As respectively). Moreover, obvious alteration of Sb and As fractionations in three types of soils were observed after chemical extractions. The mobility of Sb and As increased after extraction by citric acid and tartaric acid, suggesting that these organic acids can make soil trace metals more bio-available and that, Sb/As polluted soils can be remediated via phytoextraction.

As and Sb are more labile and toxic to water spinach (Ipomoea aquatica) in recently contaminated soils than historically co-contaminated soils.

Elevated concentrations of As and Sb impact environmental quality and human health. In this study total and bioavailable As and Sb were measured from recently and historically contaminated soils and the phytotoxicity of these soils was evaluated with Ipomoea aquatica (35-d exposure from germination) using biomass, length of plant tissues and photosynthetic efficiency. As and Sb were both present within the soil (co-contaminated). The bioavailable As and Sb in soils were determined by a Sequential Extraction Procedure (SEP) and compared to total soil concentrations and bioaccumulation in the edible parts of I. aquatica. For both As and Sb, bioavailable concentrations increased proportionally with the total soil concentrations and greater bioavailability in recently contaminated soil was observed. Tissue dry mass and length drastically reduced with increasing total and SEP-bioavailable As and Sb soil concentrations. The total soil concentration was a less sensitive measure of the phytotoxicity of As and Sb than the bioavailable fraction. Shoot length was inhibited by 50% (EC50) at bioavailable As concentrations of 80-96 mg kg-1 in both recently and historically contaminated soils; however, bioavailable Sb EC50 for shoot length was achieved at lower bioavailable concentrations, 96 (42-219) and 12 (7-19) mg kg-1 in recently contaminated soils and historically contaminated soils, respectively. Shoot biomass was inhibited by 50% (EC50) at bioavailable As concentrations of 11 (4-30) and 49 (37-65) mg kg-1 in recently and historically contaminated soils, respectively whereas this occurred at much lower bioavailable Sb concentrations, 2-5 mg kg-1 in both recently and historically contaminated soils. Aging is important in contaminated soils, it decreases the lability of As and Sb and hence their bioavailability to agricultural plants, thus posing a lower risk of exposure of these metalloids to humans through agricultural plants grown in contaminated soils.

In vitro and in vivo pharmacodynamics of three novel antileishmanial lead series.

OBJECTIVES: Three new chemical series (bicyclic nitroimidazoles, aminopyrazoles and oxaboroles) were selected by Drugs for Neglected Diseases initiative as potential new drug leads for leishmaniasis. Pharmacodynamics studies included both in vitro and in vivo efficacy, cross-resistance profiling against the current antileishmanial reference drugs and evaluation of their cidal activity potential. METHODS: Efficacy against the reference laboratory strains of Leishmania infantum (MHOM/MA(BE)/67/ITMAP263) and L. donovani (MHOM/ET/67/L82) was evaluated in vitro on intracellular amastigotes and in vivo in the early curative hamster model. Cidal activity was assessed over a period of 15 days in an in vitro 'time-to-kill' assay. Cross-resistance was assessed in vitro on a panel of L. infantum strains with different degrees of resistance to either antimony, miltefosine or paromomycin. RESULTS: All lead compounds showed potent and selective in vitro activity against the Leishmania strains tested and no cross-resistance could be demonstrated against any of the current antileishmanial drugs. Cidal activity was obtained in vitro for all series within 15 days of exposure with some differences noted between L. donovani and L. infantum. When evaluated in vivo, all lead compounds showed high efficacy and no adverse effects were observed. CONCLUSIONS: The new lead series were shown to have cidal pharmacodynamic activity. The absence of cross-resistance with any of the current antileishmanial drugs opens possibilities for combination treatment to reduce the likelihood of treatment failures and drug resistance.

Influence of arbuscular mycorrhizal fungi on antimony phyto-uptake and compartmentation in vegetables cultivated in urban gardens.

1. CONTEXT: Urban areas are often contaminated with various forms of persistent metal (loid) and emerging contaminants such as antimony (Sb). Thus, in the context of urban agriculture where sustainable practices such as biofertilizers application (arbuscular mycorrhizal fungi, AMF) could improve nutrient transfer from the soil to the vegetables, the effect of AMF on metal (loid) mobility and human bioaccessibility is still poorly known. 2. METHODS: The role of AMF in Sb uptake by lettuce and carrot grown in artificial substrate spiked with different Sb chemical species was investigated. Plants were grown under hydroponic conditions and half of the treatments received a concentrated spore solution to obtain mycorrhized and non-mycorrhized plants. Three weeks before harvest, plants were exposed to 10 mg.L-1 of either Sb2O3 or KSbO-tartrate (KSb). 3. RESULTS: The presence of AMF significantly increased its accumulation in carrots (all organs) with higher accumulation in roots. In lettuce, accumulation appeared to be dependent on the Sb chemical species. Moreover, it was observed for the first time that AMF changed the human bioaccessible fraction of Sb in edible organs. 4. IMPLICATIONS: The present results highlight a possible risk of Sb transfer from soil to edible plants cultivated in soil naturally containing AMF propagules, or when AMF are added as biofertilizers. After validating the influence of soil environment and AMF on Sb behavior in the field, these results should be considered in health risk assessments.

Polarity-sensitive nanocarrier for oral delivery of Sb(V) and treatment of cutaneous leishmaniasis.

There is a great need for orally active drugs for the treatment of the neglected tropical disease leishmaniasis. Amphiphilic Sb(V) complexes, such as 1:3 Sb-N-octanoyl-N-methylglucamide complex (SbL8), are promising drug candidates. It has been previously reported that SbL8 forms kinetically stabilized nanoassemblies in water and that this simple dispersion exhibits antileishmanial activity when given by oral route to a murine model of visceral leishmaniasis. The main objective of the present work was to interfere in the structural organization of these nanoassemblies so as to investigate their influence on the oral bioavailability of Sb, and ultimately, optimize an oral formulation of SbL8 for the treatment of cutaneous leishmaniasis. The structural organization of SbL8 nanoassemblies was manipulated through addition of propylene glycol (PG) to the aqueous dispersion of SbL8. The presence of 50% (v/v) PG resulted in the loss of hydrophobic microenvironment, as evidenced by fluorescence probing. However, nanostructures were still present, as demonstrated by dynamic light scattering, small-angle X-ray scattering, and atomic force microscopy (AFM). A remarkable property of these nanoassemblies, as revealed by AFM analysis, is the flexibility of their supramolecular organization, which showed changes as a function of the solvent and substrate polarities. The formulation of SbL8 in 1:1 water:PG given orally to mice promoted significantly higher and more sustained serum levels of Sb, when compared to SbL8 in water. The new formulation, when given as repeated doses (200 mg Sb/kg/day) to BALB/c mice infected with Leishmania amazonensis, was significantly more effective in reducing the lesion parasite burden, compared to SbL8 in water, and even, the conventional drug Glucantime(®) given intraperitoneally at the same dose. In conclusion, this work introduces a new concept of polarity-sensitive nanocarrier that was successfully applied to optimize an oral formulation of Sb(V) for treating cutaneous leishmaniasis.

Antimony (SbIII) reduces growth, declines photosynthesis, and modifies leaf tissue anatomy in sunflower (Helianthus annuus L.).

The role of antimony (Sb)--a non-essential trace metalloid--in physiological processes running in crops is still poorly understood. Present paper describes the effect of Sb tartrate (SbIII) on growth, Sb uptake, photosynthesis, photosynthetic pigments, and leaf tissue organization in young sunflower plants grown in hydroponics. We found that growth of below- and aboveground part was reduced with increasing concentration of Sb in the medium. Although Sb was mostly taken up by sunflower roots and only small part (1-2%) was translocated to the shoots, decline in photosynthesis, transpiration, and decreased content of photosynthetic pigments were observed. This indicates that despite relatively low mobility of Sb in root-shoot system, Sb in shoot noticeably modifies physiological status and reduced plant growth. Additionally, leaf anatomical changes indicated that Sb reduced the size of intercellular spaces and made leaf tissue more compact.

Arsenic (As), antimony (Sb), and lead (Pb) availability from Au-mine Technosols: a case study of transfer to natural vegetation cover in temperate climates.

Soils from old Au-mine tailings (La Petite Faye, France) were investigated in relation to the natural vegetation cover to evaluate the risk of metals and metalloids (Pb, As, Sb) mobilizing and their potential transfer to native plants (Graminea, Betula pendula, Pteridium aquilinum, Equisetum telmateia). The soils are classified as Technosols with high contamination levels of As, Pb, and Sb. The single selective extractions tested to evaluate available fraction (CaCl2, acetic acid, A-Rhizo, and DTPA) showed low labile fractions (<5 % of bulk soil contents), but still significant levels were observed (up to 342.6 and 391.9 mg/kg for As and Pb, respectively) due to the high contamination levels of soils. Even at high soil contaminations (considered as phytotoxic levels for plants), translocation factors for native plants studied are very low resulting in low concentrations of As, Sb, and Pb in their aerial part tissues. This study demonstrates the important role of (1) native plant cover in terms of "stabilization" of these contaminants, and (2) the poor effectiveness of extraction procedures used for this type of soil assemblages, i.e., rich in specific mineral phases.

Uptake of different forms of antimony by wheat and rye seedlings.

PURPOSE: The objectives of the research were to study how antimony (Sb) chemical form present in the growth medium can affect Sb uptake by plants and estimate effects of Sb on wheat and rye seedlings, in particular, assess variations in concentrations of nutrients resulting from bioaccumulation of Sb. METHODS: Seedlings were (1) germinated in media spiked with Sb(III) or Sb(V) and then transferred to clean water, and (2) germinated in Sb-free medium and then grown in water enriched with Sb. Variations of Sb concentrations in the seedlings were studied, and effects of Sb bioaccumulation on plant development and concentrations of macro- and trace elements in the plants were assessed. RESULTS: Rye was capable of accumulating more Sb than wheat. This resulted in necrosis of the rye leaves. During germination in Sb-rich medium rye and wheat accumulated Sb differently. When the seedlings germinated in Sb-amended medium were then grown in clean water, Sb concentration in all plant parts decreased. Plant concentrations of Sb increased significantly when seedlings germinated in Sb-free medium were transferred to Sb-spiked water. However, with time saturation with Sb in the plants was observed. The bioaccumulation of Sb led to significant variations in concentrations of various elements in different plant parts. CONCLUSIONS: Wheat and rye seedlings were capable of identifying different Sb forms and demonstrated certain differences in the ability to uptake Sb and survive under high external Sb concentrations. An increase of Sb in the plants caused important variations in the concentrations of many essential nutrients.

Disposition of antimony in rhesus monkeys infected with Leishmania braziliensis and treated with meglumine antimoniate.

Antimony (Sb) disposition and toxicity was evaluated in Leishmania braziliensis-infected monkeys (Macaca mulatta) treated with a 21-d course of low (LOW) or standard (STD) meglumine antimoniate (MA) dosage regimens (5 or 20 mg Sb(V)/kg body weight/d im). Antimony levels in biological matrices were determined by inductively coupled plasma mass spectrometry (ICPMS), while on-line ion chromatography coupled to ICPMS was used to separate and quantify Sb species in plasma. Nadir Sb levels rose steadily from 19.6 ± 4 and 65.1 ± 17.4 ng/g, 24 h after the first injection, up to 27.4 ± 5.8 and 95.7 ± 6.6 ng/g, 24 h after the 21st dose in LOW and SDT groups, respectively. Subsequently, Sb plasma levels gradually declined with a terminal elimination phase half-life of 35.8 d. Antimony speciation in plasma on posttreatment days 1-9 indicated that as total Sb levels declined, proportion of Sb(V) remained nearly constant (11-20%), while proportion of Sb(III) rose from 5% (d 1) to 50% (d 9). Plasma [Sb]/erythrocyte [Sb] ratio was >1 until 12 h after dosing and reversed thereafter. Tissue Sb concentrations (posttreatment days 55 and 95) were as follows: >1000 ng/g in thyroid, nails, liver, gall bladder and spleen; >200 and <1000 ng/g in lymph nodes, kidneys, adrenals, bones, skeletal muscles, heart and skin; and <200 ng/g in various brain structures, thymus, stomach, colon, pancreas. and teeth. Results from this study are therefore consistent with view that Sb(V) is reduced to Sb(III), the active form, within cells from where it is slowly eliminated. Localization of Sb active forms in the thyroid gland and liver and the pathophysiological consequences of marked Sb accumulation in these tissues warrant further studies.

Methylated metal(loid) species in humans.

While the metal(loid)s arsenic, bismuth, and selenium (probably also tellurium) have been shown to be enzymatically methylated in the human body, this has not yet been demonstrated for antimony, cadmium, germanium, indium, lead, mercury, thallium, and tin, although the latter elements can be biomethylated in the environment. Methylated metal(loid)s exhibit increased mobility, thus leading to a more efficient metal(loid) transport within the body and, in particular, opening chances for passing membrane barriers (blood-brain barrier, placental barrier). As a consequence human health may be affected. In this review, relevant data from the literature are compiled, and are discussed with respect to the evaluation of assumed and proven health effects caused by alkylated metal(loid) species.

Prolonged absorption of antimony(V) by the oral route from non-inclusion meglumine antimoniate-beta-cyclodextrin conjugates.

The orally active composition comprising meglumine antimoniate (MA) and beta-cyclodextrin (beta-CD) differs markedly from conventional drug-CD complexes, since it combines a water-soluble drug and a hydrophilic CD. In order to obtain insights into the mechanism(s) responsible for the improved oral delivery of the drug, physicochemical and pharmacokinetic studies were carried out. The composition investigated here was prepared at a 7:1 antimony(Sb)/beta-CD molar ratio, a condition that improves its solubility in water and allows the oral administration of a high dose of Sb in large animals. It was characterized by circular dichroism, (1)H-NMR, ESI-MS and photon correlation spectroscopy. Pharmacokinetic data were obtained in Beagle dogs after oral administration of the composition at 100 mg Sb/kg. (1)H-NMR and ESI-MS data supported the formation of non-inclusion complexes between MA and beta-CD. Sub-micron assemblies were also evidenced that slowly dissociate and presumably release the MA drug, upon reconstitution of the composition in water. Pharmacokinetic studies of MA and MA/beta-CD in dogs showed a prolongation of the serum mean residence time of Sb from 4.1 to 6.8 h, upon complexation of MA with beta-CD. Evidence was also obtained that Sb remains essentially under the form of pentavalent Sb-meglumine complex, following gastro-intestinal absorption from the MA/beta-CD composition. In conclusion, the present data support the model that the sustained drug release property of 7:1 MA/beta-CD composition resulted in the prolongation of MA absorption by the oral route and, consequently, in the increase of the drug mean residence time in serum.

Factors affecting sentinel lymph node detection failure in breast cancer patients using intradermal injection of the tracer.

OBJECTIVE: The standard method for axillary lymph node staging in early breast cancer is sentinel lymph node biopsy. In some patients the sentinel lymph node can not be localized during surgery and these patients have to undergo standard axillary lymph node dissection. In this study we have evaluated the predictors of sentinel lymph node localization failure using (99m)Tc-antimony sulfide colloid and intradermal injection combined with blue dye technique. MATERIAL AND METHODS: 202 consecutive patients with early stage breast cancer (clinically stage I or II) were retrospectively evaluated. Patients whose sentinel lymph node was localized during surgery were compared to those with localization failure considering several variables. RESULTS: Sentinel lymph node was successfully located on the pre-operative lymphoscintigraphy images in 180 patients (89%). Both univariate and multivariate analyses showed that only sentinel lymph node non-visualization by pre-operative lymphoscintigraphy, experience of the surgeon, and axillary lymph node involvement are associated with sentinel node localization failure during surgery. CONCLUSIONS: This study shows the importance of pre-operative lymphoscintigraphy in order to identify the group of patients with possible localization failure during surgery and warning the surgeon beforehand. We also recommend that all surgeons pass the learning curve of sentinel lymph node biopsy before routinely performing this procedure.

Metabolism of tellurium, antimony and germanium simultaneously administered to rats.

Recently, tellurium (Te), antimony (Sb) and germanium (Ge) have been used as an alloy in phase-change optical magnetic disks, such as digital versatile disk-random access memory (DVD-RAM) and DVD-recordable disk (DVD-RW). Although these metalloids, the so-called "exotic" elements, are known to be non-essential and harmful, little is known about their toxic effects and metabolism. Metalloid compounds, tellurite, antimonite and germanium dioxide, were simultaneously administered to rats. Their distributions metabolites were determined and identified by speciation. Te and Sb accumulated in red blood cells (RBCs): Te accumulated in RBCs in the dimethylated form, while Sb accumulated in the inorganic/non-methylated form. In addition, trimethyltelluronium (TMTe) was the urinary metabolite of Te, whereas Sb in urine was not methylated but oxidized. Ge was also not methylated in rats. These results suggest that each metalloid is metabolized via a unique pathway.

False-negative sentinel node biopsy because of obstruction of lymphatics by metastatic melanoma: the value of ultrasound in conjunction with preoperative lymphoscintigraphy.

The aim of this study was to describe how metastatic melanoma obstructing lymphatic flow to sentinel nodes can result in a false-negative sentinel node biopsy and to show that the use of ultrasound in conjunction with preoperative lymphoscintigraphy can avoid this potential diagnostic pitfall. A series of three patients in whom metastatic melanoma obstructed lymphatic flow to sentinel nodes is reported. In these patients, lymphoscintigraphy failed to identify nodes containing metastatic disease. This resulted in a false-negative sentinel node biopsy result in two patients. A sentinel node biopsy was not carried out in the third patient, but the same dilemma was encountered. These cases provide further insights into the dynamics of lymphatic flow and suggest possible reasons for occasional inaccuracy of sentinel node biopsy. They also highlight the advantages of using ultrasound to assess lymph nodes in any node fields to which lymphatic drainage occurs from a primary tumour site.

Comparison of arsenic and antimony contents in tissues and organs of brown trout caught from the river Presa polluted by ancient mining practices and from the river Bravona in Corsica (France): a survey study.

The present study evaluates the concentrations of arsenic (As) and antimony (Sb) in the intestine, liver, muscle, gonads, gills, and kidney of Salmo trutta subsp. from the Presa River in Corsica (France; n = 10), which crosses an abandoned arsenic mine, and from the Bravona River (reference site; n = 10). Both metalloids were analyzed by means of ICP-MS. The relationships between fish size (length and weight) and metalloid concentrations in their tissues were investigated by linear regression analysis. In all fish samples concentrations of As and Sb (expressed as micrograms per gram fresh weight) were highest in the kidney. Lowest Sb concentrations were found in the muscle, whereas lowest As concentrations were found in the gonads of S. trutta. Two organotropisms were revealed: one for As-kidney (21.4656) > intestine (3.9535) > gills (3.0404) > liver (1.1743) > muscle (0.9976) > gonads (0.8081); and the other for Sb-kidney (0.70067) > gills (0.6181) > intestine (0.2576) > gonads (0.1673) > liver (0.9625) > muscle (0.0753). Results of linear regression analysis in most cases showed a significant negative correlation between metalloid concentration and fish size. Highly significant (p < 0.05) negative correlations were found between fish length and As concentration in the gonads, as well as between fish length and Sb concentrations in the gills. Arsenic concentrations in female fish were significantly higher than those in males in the kidney, gonads, gills, and liver. The same results were found for Sb, except in the liver, where the tendency was reversed.

Plant uptake of trace elements on a Swiss military shooting range: uptake pathways and land management implications.

Over 400tons of Pb enters Swiss soils annually at some 2000 military shooting ranges (MSRs). We measured elements in the leaves of 10 plant species and associated rhizospheric soil on the stop butt of a disused MSR. The geometric mean concentrations of Pb, Sb, Cu, Ni in rhizospheric soils were 10,171mg/kg, 5067mg/kg, 4125mg/kg and 917mg/kg. Some species contained Pb, Cu and Ni, above concentrations (30mg/kg, 25mg/kg and 50mg/kg) shown to be toxic to livestock. Most contaminants in leaves resulted from surface deposition. However, at soil Pb concentrations >60,000mg/kg, Equisetum arvense and Tussilago farfara took up >1000mg/kg Pb into the leaves. These plants are not hyperaccumulators, having <100mg/kg Pb in leaves at lower soil concentrations. Removal of soil with more than 30,000 Pb, from which one could smelt this metal to offset remediation costs, followed by revegetation, would minimise dust and hence leaf-borne contaminants.

Bioavailability of arsenic and antimony in soils from an abandoned mining area, Glendinning (SW Scotland).

The mobility and bioavailability of As and Sb in relation to soil-biota transfer were evaluated at a former Sb mining and smelting site (Glendinning, SW Scotland, UK). The study specifically assessed the accumulation of As and Sb in different environmental components (soil, plants and earthworms) across mining area to estimate risk factors for the biota. Total concentrations and fractions of As and Sb in soils were determined. The latter using both a single solute and a non-specific stepwise sequential extraction (CISED) method. Mineralogical information was gathered from XRD and SEM analysis used to identify element distribution patterns. Pseudo-total (aqua-regia) levels of As and Sb in the soils varied between 50-17,400 mg kg(-1) and 10-1,200 mg kg(-1), respectively. Both elements are predominantly associated with Fe (or Al) oxides/hydroxides, by adsorption around silicate grains, representing a potentially bioavailable fraction. Antimony was also associated with sulphide phases. The highest values of As and Sb in biota were recorded in the earthworms (960 mg kg(-1) and 27 mg kg(-1), respectively). Bioconcentration factors for both elements were below 1 and the highest for earthworms. Total and leached As levels in soils and biota were positively and significantly correlated, but only for Sb in earthworms and grass. Bioavailability of As in the biota, was shown to be limited by pH. In spite of the considerably high As and Sb contents of the soil the plant contamination remained comparably low, but still exceeded background values.

Effects of fluconazole on the pharmacokinetics and pharmacodynamics of antimony in cutaneous leishmaniasis-infected hamsters.

Pentavalent antimony (Sb(V)) compounds are the drugs of choice for the treatment of all forms of leishmaniasis. For 20 years there has been an interest in antifungal azoles for treating leishmaniasis, with variable success. In the current study, we examined the effects of co-administration of fluconazole (FLZ) on the pharmacokinetics and pharmacodynamics of Sb(V) in cutaneous leishmaniasis-infected hamsters. Hamsters were divided into four groups. All hamsters were injected with 0.1 mL of 1x10(8)promastigotes/mL into the right foot on Day 1. Treatment was started 5 days after the infection. The antimony group received 80 mg/kg/day of Pentostam intramuscularly whilst the FLZ group received FLZ 20 mg/kg/day orally for 14 days. The combination group received both Pentostam and FLZ at the above mentioned doses for 14 days. Animals in the control group received no treatment. The infected footpads were measured on Days 1 and 14. A pharmacokinetic study was conducted on Days 1 and 14 of treatment, representing single- and multiple-dose pharmacokinetics, respectively. Blood samples were collected at different time intervals up to 24h. Sb(V) was determined using flameless atomic absorption spectrophotometry. Pharmacokinetic parameters were calculated using a non-compartmental analysis. In the single-dose study, there was no statistically significant difference in any of the pharmacokinetic parameters of Sb(V) when given alone or with FLZ. However, on Day 14 a significant increase in peak plasma concentration (C(max)) (three-fold) and area under the concentration-time curve (AUC) (four-fold) of antimony was observed when Sb(V) was co-administered with FLZ. A statistically significant prolongation of the terminal half-life from 1.63 to 8.67 h (P<0.05) was also observed. A significant reduction in clearance was detected. However, FLZ had no effect on the pharmacodynamics of Sb(V) as measured by footpad sizes. In conclusion, FLZ did not improve the therapeutic effect of Sb(V) when given concomitantly despite the significant increase in blood concentration and prolongation of the elimination half-life of Sb(V).