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PubMed2005

Antimony speciation in terrestrial plants. Comparative studies on extraction methods.

A suitable method for the extraction of antimony species from plant materials prior to IC-HG-AFS analysis is presented. The extraction efficiency with different extraction systems using various aqueous and aqueous/solvent mixtures was initially evaluated by analysing the Virginia Tobacco Leaves Certified Reference Material. The concentration of antimony extracted was compared with the total antimony content in the plant material measured by HG-AFS after focused microwave-acidic digestion using HNO3 and H2O2. The proposed extraction procedures were applied to antimony speciation in several plants from a natural terrestrial environment impacted by mining activities. End-over-end agitation (4 h) followed by sonication (1 h) extraction using 0.1 mol l(-1) citric acid was found to provide the best extraction efficiency while also giving reliable speciation information. Both inorganic and methylantimony species were found in the extractable portion of some terrestrial plants.

Antimony↗
PubMed2005

Determination of antimony in human blood with inductively coupled plasma-mass spectrometry.

A method is presented for the determination of antimony in whole human blood samples with an ICP-MS instrument using a quadrupole mass analyzer. A nitric acid/hydrogen peroxide open digestion procedure was employed for the blood sample treatment and preparation for analysis. The precision and accuracy of the method were evaluated by analyzing several Seronorm trace elements whole blood reference materials. The precision of the method at various antimony levels was better than 4% RSD and the recovery was greater than 92% at all levels. The detection limit, calculated as three times the standard deviation of the blank (3sigma, n= 12), was 0.03 microg L(-1). The method was successfully applied for the determination of antimony in blood samples from school children in rural areas of Kwazulu/Natal, South Africa and adults from Dearborn, Michigan. Blood antimony levels ranged from <0.03 to 3.82 microg L(-1) in children and 1.40 to 4.35 microg L(-1) for adults.

Adult↗
PubMed2003

Treatment of cutaneous leishmaniasis with either topical paromomycin or intralesional meglumine antimoniate.

Ninety-six patients with a clinical and parasitological diagnosis of cutaneous leishmaniasis were recruited to a comparative randomized clinical trial evaluating the efficacy of topical paromomycin vs. weekly intralesional injections of meglumine antimoniate. The patients were randomly divided into two treatment groups: one group was treated with topical paromomycin ointment and the other with intralesional meglumine antimoniate. Treatment was continued in both groups until complete recovery occurred (defined as healing in less than 2 months with no residual scar or relapse for up to 1 year post treatment). Treatment failure was defined as an increase in the number and size of pre-existing lesions or untoward side-effects. The maximum treatment period was 3 months. The patients were followed up for 1 year. The results showed that intralesional meglumine antimoniate led to 41.7% complete recovery, However, topical paromomycin gave a lower cure rate of 16.6% (P < 0.05). Treatment failure was observed in 39.7% of the group receiving intralesional meglumine and in 72.9% of those on topical paromomycin (P < 0.05). This study indicates that intralesional meglumine antimoniate is superior to topical paromomycin in the treatment of cutaneous leishmaniasis.

Administration, Topical↗
PubMed2004

Leishmania major LmACR2 is a pentavalent antimony reductase that confers sensitivity to the drug pentostam.

Arsenicals and antimonials are first line drugs for the treatment of trypanosomal and leishmanial diseases. To create the active form of the drug, Sb(V) must be reduced to Sb(III). Because arsenic and antimony are related metalloids, and arsenical resistant Leishmania strains are frequently cross-resistant to antimonials, we considered the possibility that Sb(V) is reduced by a leishmanial As(V) reductase. The sequence for the arsenate reductase of Saccharomyces cerevisiae, ScAcr2p, was used to clone the gene for a homologue, LmACR2, from Leishmania major. LmACR2 was able to complement the arsenate-sensitive phenotype of an arsC deletion strain of Escherichia coli or an ScACR2 deletion strain of Saccharomyces cerevisiae. Transfection of Leishmania infantum with LmACR2 augmented Pentostam sensitivity in intracellular amastigotes. LmACR2 was purified and shown to reduce both As(V) and Sb(V). This is the first report of an enzyme that confers Pentostam sensitivity in intracellular amastigotes of Leishmania. We propose that LmACR2 is responsible for reduction of the pentavalent antimony in Pentostam to the active trivalent form of the drug in Leishmania.

Amino Acid Sequence↗
PubMed2004

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.

Administration, Topical↗
PubMed1998

Fungal volatilization of arsenic and antimony and the sudden infant death syndrome.

Fungal volatilization of antimony and other group Vb elements has been proposed to have a causal role in the sudden infant death syndrome (SIDS; cot death). The ability of fungi to produce volatile arsenic and antimony compounds in pure culture was examined using Scopulariopsis brevicaulis, reported as an inhabitant of PVC cot mattress covers, and Phaeolus schweinitzii, a wood decay fungus known to be a good volatilizer of arsenic. Volatile arsenic compounds were detected from all cultures grown on arsenic-supplemented media, but antimony volatilization was not reliably detected. Although antimony levels above the baseline sensitivity of the analytical technique were detected in four (out of 24) of the samples analyzed, the concentrations recorded were too low to be reliably interpreted as evidence for volatilization. Our results are discussed in relation to hypotheses regarding the causes of SIDS.

Antimony↗
PubMed2006

Antimony-based antileishmanial compounds prolong the cardiac action potential by an increase in cardiac calcium currents.

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.

Action Potentials↗
PubMed1998

Lack of inhibition of human plasma cholinesterase and red cell acetylcholinesterase by antimony compounds including stibine.

1. The toxic gas hypothesis proposes exposure to stibine (antimony trihydride) generated from microbial contamination of cot mattress materials as a possible cause of unexplained death in infancy (SIDS) as a consequence of cholinesterase inhibition. We have measured the direct effects of antimony compounds including stibine on the activity of plasma cholinesterase, red blood cell acetylcholinesterase (AChE) and mouse neuronal AChE in vitro. 2. Colorimetric assays for the different esterases with potassium antimonyl tartrate or antimony trichloride at concentrations up to 10(-3) M in the presence of substrate concentrations sufficient to produce 80% of the maximum reaction rate produced no inhibition of enzyme activity. Exposure of enzyme preparations to stibine gas at concentrations sufficient to cause denaturation of red cell haemogloblin caused no measurable inhibition of esterase activity. 3. We conclude that stibine gas or soluble antimony compounds are not capable of inhibiting cholinesterase activity at toxicologically relevant concentrations.

Acetylcholinesterase↗
PubMed2003

Distribution of liposome-encapsulated antimony in dogs.

The achievement of complete cure in dogs with visceral leishmaniasis is currently a great challenge, since dogs are the main reservoir for the transmission of visceral leishmaniasis to humans and they respond poorly to conventional treatment with pentavalent antimonials. In order to improve the efficacy of treatment, we developed a novel formulation for meglumine antimoniate based on the encapsulation of this drug in freeze-dried liposomes (LMA). The aim of the present study was to evaluate the biodistribution of antimony (Sb) in dogs following a single intravenous bolus injection of LMA. Four healthy male mongrel dogs received LMA at 3.8 mg Sb/kg body weight and were sacrificed 3, 48 and 96 h and 7 days later. Antimony was determined in the blood, liver, spleen and bone marrow. In the bone marrow, the highest Sb concentration was observed at 3 h (2.8 microg/g wet weight) whereas in the liver and spleen it was demonstrated at 48 h (43.6 and 102.4 microg/g, respectively). In these organs, Sb concentrations decreased gradually and reached levels of 19.1 microg/g (liver), 28.1 microg/g (spleen) and 0.2 microg/g (bone marrow) after 7 days. Our data suggest that the critical organ for the treatment with LMA could be the bone marrow, since it has low Sb levels and, presumably, high rates of Sb elimination. A multiple dose treatment with LMA seems to be necessary for complete elimination of parasites from bone marrow in dogs with visceral leishmaniasis.

Animals↗
PubMed2006

A simple and sensitive analytical method for the determination of antimony in environmental and biological samples.

The results of a study and application of leucocrystal violet for the determination of antimony in parts per million levels is described here. The proposed method is based on the reaction of antimony(III) with acidified potassium iodate to liberate iodine. The liberated iodine selectively oxidizes leucocrystal violet to crystal violet dye. The formed dye shows maximum absorbance at 590 nm. The color system obeys Beer's law in the concentration range from 0.4 - 3.6 microg antimony per 25 ml of final solution. The molar absorptivity and Sandell's sensitivity were found to be 7.32 x 10(5) l mol(-1) cm(-1) and 0.0016 microg cm(-2), respectively. All variables were studied in order to optimize the reaction. The proposed method is satisfactorily applicable for the analysis of antimony in various environmental and biological samples. The method is simple, highly sensitive, accurate and reliable.

Antimony↗
PubMed1981

Continuous intra-arterial pH-monitoring using monocrystalline antimony as sensor. A study in non-heparinized dogs.

Continuous intra-arterial pH-monitoring was performed on anaesthetized and artificially ventilated dogs. The pH sensor consisted of monocrystalline antimony. The sensor was placed on the tip of a catheter, length approximately 35 cm and diameter 0.8 mm. No anticoagulation was undertaken. The pH range studied was 7.01-7.53, the pH being changed by infusion of sodium bicarbonate ro ammonium chloride. Arterial reference blood samples for in vitro blood gas analyses were taken under stable monitoring conditions and analysed with a minimal delay. The millivolt signal from the antimony sensor was found to be a linear function of the pH of the reference blood samples in the intra-arterial pH range studied. The sensitivities of the different antimony sensors were closely correlated but not identical. When the antimony sensor was used completely uncalibrated, the standard deviation of the registered potential corresponds to 0.06 pH units. After single point calibration a standard deviation of 0.03 pH units was obtained. These standard deviations include a suspected influence of minor changes in the partial pressure of oxygen during the experiments.

Ammonium Chloride↗
PubMed1988

Identical 24-hour gastric pH profiles when using intragastric antimony or glass electrodes or aspirated gastric juice.

Intragastric pH was continuously measured over 24 h with a monocrystalline antimony electrode system and was compared with pH measured in simultaneously aspirated gastric juice and with pH measured by using a conventional intragastric glass electrode. There was a marked correlation between the pH readings obtained with the monocrystalline antimony electrode and the pH values measured in aspirated gastric juice (r = 0.92, p less than 0.001) and with the pH readings obtained with the intragastric glass electrode (r = 0.92, p less than 0.001). Both readings of pH with glass electrode and of pH after aspiration can be predicted by readings of pH with antimony electrode by using linear regression lines with slopes close to 1. Intragastric pH measurement is an alternative to aspiration of gastric juice, and the result obtained with an electrode of monocrystalline antimony is comparable to that obtained with a conventional glass electrode.

Antimony↗
PubMed2005

Kinetoplastid membrane protein-11 DNA vaccination induces complete protection against both pentavalent antimonial-sensitive and -resistant strains of Leishmania donovani that correlates with inducible nitric oxide synthase activity and IL-4 generation: evidence for mixed Th1- and Th2-like responses in visceral leishmaniasis.

The emergence of an increasing number of Leishmania donovani strains resistant to pentavalent antimonials (SbV), the first line of treatment for visceral leishmaniasis worldwide, accounts for decreasing efficacy of chemotherapeutic interventions. A kinetoplastid membrane protein-11 (KMP-11)-encoding construct protected extremely susceptible golden hamsters from both pentavalent antimony responsive (AG83) and antimony resistant (GE1F8R) virulent L. donovani challenge. All the KMP-11 DNA vaccinated hamsters continued to survive beyond 8 mo postinfection, with the majority showing sterile protection. Vaccinated hamsters showed reversal of T cell anergy with functional IL-2 generation along with vigorous specific anti-KMP-11 CTL-like response. Cytokines known to influence Th1- and Th2-like immune responses hinted toward a complex immune modulation in the presence of a mixed Th1/Th2 response in conferring protection against visceral leishmaniasis. KMP-11 DNA vaccinated hamsters were protected by a surge in IFN-gamma, TNF-alpha, and IL-12 levels along with extreme down-regulation of IL-10. Surprisingly the prototype candidature of IL-4, known as a disease exacerbating cytokine, was found to have a positive correlation to protection. Contrary to some previous reports, inducible NO synthase was actively synthesized by macrophages of the protected hamsters with concomitant high levels of NO production. This is the first report of a vaccine conferring protection to both antimony responsive and resistant Leishmania strains reflecting several aspects of clinical visceral leishmaniasis.

Animals↗
PubMed1991

Comparison of regimes of treatment of antimony-resistant kala-azar patients: a randomized study.

Three hundred twelve patients with antimony-resistant kala-azar were randomized into three groups. The first group (A) received pentamidine isethionate intravenously three times each week until parasitological cure was achieved. Group B received pentamidine concomitantly with a 20-day regimen of sodium stibogluconate. Group C received pentamidine injections that were followed by 20 days of sodium stibogluconate therapy. All patients became afebrile after 10 injections of pentamidine. Parasitologic cure was achieved in approximately 98% of the patients who had 33 or more injections of this drug. The addition of the antimony compound did not appear to enhance the rate of parasitologic cure. Three patients continued to have parasites after 40 injections of pentamidine. After six months, the rate of parasitologic cure was significantly higher in Group C (pentamidine followed by sodium stibogluconate) than in either Group A or B. Forty patients relapsed after apparent parasitologic cure and were successfully treated with five additional injections of pentamidine, followed by a course of antimony therapy. Minor side effects with pentamidine included an uneasy feeling during intravenous injection (12%), intestinal disturbances (6%), cellulitis (5%), abscess formation (1%), and allergic manifestations (2%). Major reactions to this drug included hyperglycemia (10%; reversible in 6% and irreversible in 4%), and delayed hypoglycemia (8%). Four deaths were associated with the administration of this compound. It is concluded that pentamidine is an effective but toxic drug for the treatment of antimony-resistant kala-azar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1998

[Influence of exposure to mercury, arsenic and antimony on body burden--a biomonitoring study].

Part of the northern Palatinate region in Germany is characterized by elevated levels of mercury, arsenic and antimony in the soil due to the presence of ore sources and former mercury mining activities. Today, the region is characterized by housing and agriculture. In a biomonitoring study, 218 residents (age 1-89 years) were investigated for a putatively increased absorption of these elements from the environment. 76 non-exposed subjects (age 2-84 years) of a region in south lower Saxony (Germany) were chosen as a reference group. Urine and scalp hair samples were obtained as surrogates to determine the internal exposures to mercury, arsenic and antimony. In the northern Palatinate subjects slightly, yet presumably not hazardous, elevated arsenic contents in urine and scalp hair could be correlated to an increased arsenic content in the soil. On the other hand, 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. Urinary mercury contents were correlated with the total amalgam area in both study groups. Mercury contents in scalp hair and arsenic contents in urine were correlated with the consumption of seafood. Surprisingly, the geogenically non-exposed reference subjects showed significantly higher internal exposures to arsenic and antimony in urine and scalp hair. However, data of both groups correspond to normal range reference data described by others.

Adolescent↗
PubMed2004

Antimony toxicity from the use of tartar emetic for the treatment of alcohol abuse.

Antimony is a poisonous element with toxic properties that mimic those of arsenic. Numerous reports describe gastrointestinal complications of vomiting, diarrhea and stomatitis associated with antimony exposure. However, antimony toxicity from the use of tartar emetic as a treatment for alcohol abuse has never been described previously. A 19-y-o man with a history of alcohol abuse ingested a 10 mL bottle of "Soluto Vital" (tartar emetic, 50 mg/mL), produced in Guatemala for treatment of alcohol abuse. He presented 60 min after ingestion with severe vomiting, abdominal cramps, diarrhea, weakness and orthostasis. Initial laboratory evaluations were remarkable for creatinine of 2.5 mg/dL, potassium 6.1 mEq/L, and 60% hematocrit. He was given activated charcoal, iv saline and antiemetics. Over the next 48 h his creatinine normalized to 1.1 mg/dL and the hematocrit returned to 53%; urine had an antimony concentration of 1200 mcg/L (normal = < 10 mcg/L). It is important to recognize that foreign alcohol therapies aversive therapy other than disulfiram may be used, the contents of such a foreign product should be identified.

Adult↗
PubMed2005

Successful treatment of refractory cutaneous leishmaniasis with GM-CSF and antimonials.

Therapeutic failure in the treatment of cutaneous leishmaniasis (CL) occurs in 5% of patients infected by Leishmania braziliensis. This study evaluates the use of topically applied granulocyte macrophage colony-stimulating factor (GM-CSF) combined with the standard dose of antimony to treat refractory cases of CL. Five patients who had received three courses or more of antimony were enrolled in an open-label clinical trial. One to 2 mL of the GM-CSF solution (10 mug/mL in 0.9% saline) was reapplied topically, and dressings were changed three times per week for 3 weeks, associated with standard parenteral antimony (20 mg kg(-1) day(-1) for 20 days). All the patients healed their CL ulcers; 3 healed within 50 days (21, 27, and 44 days) and 2 in 118 and 120 days after beginning therapy. There were no side effects. This study shows that combined topically applied GM-CSF and antimony can be effective and well tolerated in the treatment of relapsed CL.

Administration, Topical↗
PubMedDate not supplied

Comparative and environmental genotoxicity of antimony and arsenic.

Antimony and arsenic compounds are known to have a genotoxic potential. Soil contamination with these elements can be due to the presence of natural ore sources of fahlore (gray copper). As a result, human and animal populations may be highly exposed. The sister chromatid exchange (SCE) test is an adequate tool for the sensitive detection of antimony and arsenic genotoxicity. We used this assay to investigate the coergism of the two elements in vitro to gain data for the assessment of a putative risk from coexposure. The combinative effect of antimony and arsenic in the SCE test appeared subadditive. Additionally, the SCE served to determine the genotoxic potential in extracts of contaminated fahlore soil samples gained under mildly acidic conditions. The genotoxicity observed was very low because antimony and arsenic predominated in the pentavalent, non-genotoxic state, but, the partial antagonism observed in the in vitro experiments could be an additional explanation for the low genotoxicity.

Adult↗