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A low-dose antimony treatment in 159 patients with American cutaneous leishmaniasis: extensive follow-up studies (up to 10 years).

The efficacy of an antimony regimen at the dose of 20 mg/kg/day for a 3-4-week period is well established in the treatment of American cutaneous leishmaniasis. Several drug side effects, however, have been described and the search for more suitable regimens is advisable. In the present paper, the effect of a low dose (5 mg/kg/day for 30 days) of antimony was evaluated in 159 individuals from endemic regions of Rio de Janeiro State, Brazil, an area of Leishmania (V.) braziliensis transmission. Patients presented typical cutaneous lesions and parasites were demonstrated in all cases. One hundred forty-three patients were available for evaluation and of these, 120 (84%) were cured by the end of therapy. Twenty-three patients (16%) were considered treatment failures. Side effects were observed in only six patients (4%). Extensive follow-up (up to 10 years) disclosed no relapses or mucosal lesions. The results show that a low dose of antimony is less toxic, more appropriate, especially in children and elderly people, and has the same final result as that obtained with larger doses.

Adolescent↗

Response of cutaneous leishmaniasis (chiclero's ulcer) to treatment with meglumine antimoniate in Southeast Mexico.

Cutaneous leishmaniasis, known as chiclero's ulcer in southeastern Mexico, is characterized by a predominantly single, painless, ulcerated lesion, without lymphangitis or adenopathy. When located on the ear, it tends to become chronic, causing destruction of the pinna and disfigurement. It is caused predominantly by Leishmania (L.) mexicana. Although pentavalent antimonials (Sb5+) are the mainstay of leishmanial therapy and have been used for more than 50 years, dosage regimens have been repeatedly modified and the best one has not been fully identified. The main purpose of the present study was to investigate the response of chiclero's ulcer to treatment with meglumine antimoniate. One hundred five patients were treated with meglumine antimoniate at a daily dose of 1 ampule per day (425 mg of Sb5+) until healing. The lesions healed after a mean of 25 days (range = 5-60 days).

Adolescent↗

Comparison of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis and L. (V.) guyanensis in Brazil: therapeutic response to meglumine antimoniate.

We conducted a quasi-experimental study to compare the response to meglumine antimoniate in patients with localized cutaneous leishmaniasis from two endemic areas of Brazil that were infected by two Leishmania species. Sixty-one were infected by Leishmania (Viannia) braziliensis (group B) and 57 by L. (V.) guyanensis (group G). All had a parasitologically proven diagnosis and were treated with 20 mg of pentavalent antimonial (SbV)/kg/day given intravenously or intramuscularly for 20 days. Main outcomes were diagnosed using clinical criteria three months after treatment and patients were followed for six months. Intention-to-treat analysis showed a higher failure rate in group G (relative risk [RR] = 1.5, 95% confidence interval [CI] = 1.1-2.0, chi2 = 7.44, P = 0.006). The analysis using an explanatory approach including 52 patients from group B and 49 from group G, who were regularly treated and followed for six months, showed a low cure rate (50.8% in group B and 26.3% in group G) with a greater risk of failure in the latter group (RR = 1.7, 95% CI = 1.2-2.5, chi2 = 8.56, P = 0.003). The effect of the etiologic agent remained significant after adjusting for age, disease duration, and site and number of lesions that were identified as predictors of failure in a logistic regression model. We concluded that Leishmania species constitute an important factor in predicting the outcome of cutaneous leishmaniasis treated with a pentavalent antimonial.

Adolescent↗

Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus antimony.

Mucosal leishmaniasis is characterized by an intense inflammatory reaction and tissue damage with few parasites in the lesion. On the basis of previous observations that suggest a possible role of tumor necrosis factor alpha (TNF-alpha) in the pathology of this disease, an open-label study was performed to evaluate the efficacy of the treatment with an inhibitor of TNF-alpha (pentoxifylline) associated to antimony therapy in 10 patients with refractory mucosal leishmaniasis. Patients were treated with pentavalent antimony (20 mg per kilogram of body weight per day) plus orally administered pentoxifylline 400 mg 3 times daily for 30 days. Nine of 10 patients fulfilled the criteria for cure: they experienced complete reepithelization of the mucosal tissue 90 days after therapy and displayed no evidence of relapse at 1 year of follow-up. The TNF-alpha levels before therapy (776 +/- 342 pg/mL) fell to 94 +/- 57 pg/mL (P < 0.05) within 60 days after therapy. Our results indicate that pentoxifylline plus antimony therapy should be considered in all patients with mucosal leishmaniasis that is refractory to treatment.

Administration, Oral↗

[An experimental study on effects of antimony on anti-oxidase system on liver mitochondria in mice].

OBJECTIVE: To explore the mechanisms of toxic liver damage caused by antimony. METHODS: Experimental mice were injected peritoneally 40 mg/kg of antimony trioxide daily for 28 days to observe the effects of it on the anti-oxidase system in their liver mitochondria. RESULTS: Activities of aspartate aminotransferase and alanine aminotransferase increased obviously in the experimental animals, and those of superoxide dismutase and glutathione peroxidase in liver mitochondria lowered, as compared to those in the control animals with statistical significance. Content of malonyl dialdehyde in the liver mitochondria was 47.27 +/- 1.21 mumol/L in the experimental animals, significantly higher than that in controls. CONCLUSION: It suggested that the mechanism of liver damage caused by antimony associated with injury to the ability of anti-oxidation and lipid peroxidation in the liver mitochondria.

Animals↗

Particle size analysis of (99m)Tc-labeled and unlabeled antimony trisulfide and rhenium sulfide colloids intended for lymphoscintigraphic application.

UNLABELLED: Colloidal particle size is an important characteristic to consider when choosing a radiopharmaceutical for mapping sentinel nodes in lymphoscintigraphy. METHODS: Photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) were used to determine the particle size of antimony trisulfide and rhenium sulfide colloids, and membrane filtration (MF) was used to determine the radioactive particle size distribution of the corresponding (99m)Tc-labeled colloids. RESULTS: Antimony trisulfide was found to have a diameter of 9.3 +/- 3.6 nm by TEM and 18.7 +/- 0.2 nm by PCS. Rhenium sulfide colloid was found to exist as an essentially trimodal sample with a d(v(max1)) of 40.3 nm, a d(v(max2)) of 438.6 nm, and a d(v) of 650-2200 nm, where d(v) is volume diameter. (99m)Tc-antimony trisulfide by MF showed that more than 96% of radioactive particles were smaller than 100 nm; however, (99m)Tc-rhenium sulfide showed that more than 21% were smaller than 100 nm. These radioactive colloids were used with seven different membrane compositions and found not to adsorb significantly to any of them. CONCLUSION: MF was validated as a simple and reliable technique to estimate the percentage radioactive particle size distribution.

Antimony↗

Electrothermal atomization of arsenic, antimony and thallium using a graphite atomizer with refractory metal platforms.

The electrothermal atomization of the volatile elements arsenic, antimony and thallium from a refractory metal platform consisting of a tungsten coil and/or a refractory metal foil with the dimensions of a conventional graphite platform was studied. Several combinations of refractory metal platforms were investigated, as follows: W platform; Ta platform; W coil; W coil on a W platform and W coil on a Ta platform. The best combination for these elements as regards both thermal stabilization and sensitivity is the W coil on a Ta platform. Thermal stabilization is also achieved with a W coil on a W platform. The presence of Pd-containing chemical modifier favors the thermal stabilization of the analytes. The sufficient amount is 2 micrograms of Pd. The maximal temperatures of pyrolysis are higher (arsenic, antimony) or equal (thallium) to those when using different chemical modifiers, added as solutions. It may be concluded, that the refractory metal platforms act as "built-in modifiers". They are suitable for the determination of arsenic, antimony and thallium in samples of complex matrix composition where high thermal stability of the analytes during the pyrolysis step is required.

Air Pollutants↗

Fractionation and redox speciation of antimony in agricultural soils by hydride generation--atomic fluorescence spectrometry and stability of Sb(III) and Sb(V) during extraction with different extractant solutions.

This stability of Sb(III) and Sb(V) species was studied during single extraction from soils by water. EDTA, diluted H2SO4 and H3PO4, and oxalic acid/oxalate solutions, with and without ascorbic acid, were used as stabilizing reagent of both Sb species. Antimony redox speciation in soil extracts was performed by selective hydride generation-atomic fluorescence spectrometry. Simulated extraction procedures (without soil) showed that, except in oxalate medium, Sb(III) was oxidized to Sb(V), and this reaction was avoided with ascorbic acid. Recovery studies from a spiked agricultural soil showed that no oxidation but sorption of Sb(III) occurred during the extraction process in water and H2SO4 medium, and quantitative oxidation in EDTA and oxalate medium. With ascorbic acid, this oxidation was totally avoided in EDTA and partially avoided in oxalate solution. A new sequential extraction procedure was proposed and applied to the fractionation and redox speciation of antimony in agricultural soils, using EDTA + ascorbic acid, pH 7 (available under complexing and moderately reducible conditions); oxalic acid/oxalate + ascorbic acid (extractable in reducible conditions) and HNO3 + HCl + HF (residual fraction). The proposed extraction scheme can provide information about the availability and mobility of antimony redox species in agricultural soils.

Agriculture↗

Sir Thomas Oliver (1853-1942) and the health of antimony workers.

Imported antimony sulphide ore has been processed in the north-east of England on Tyneside since 1864, first at Gateshead and then at Willington Quay, until the process closed in 2000. The health of antimony workers was a concern of Sir Thomas Oliver (1853-1942) who was distinguished in the field of occupational medicine, particularly in connection with diseases due to lead exposure. Antimony appears to have fascinated him but he underestimated its toxic effects on the process workers in concluding that they were healthy and that there were no industrial hygiene problems in the process. Subsequent investigations have presented a much less satisfactory picture although in recent times the factory atmosphere had been transformed so that Oliver's view had probably come true.

Antimony↗

Comparison of generic to branded pentavalent antimony for treatment of new world cutaneous leishmaniasis.

The cost of generic pentavalent antimony (generic stibogluconate) is approximately one-sixth that of branded pentavalent antimony (stibogluconate in the form of Pentostam or meglumine antimoniate in the form of Glucantime. We compared generic stibogluconate to Pentostam and Glucantime for the treatment of cutaneous leishmaniasis patients in Bolivia and Colombia. For all 114 patients, the per-protocol cure rates were 83-91% and the intent-to-treat cure rates were 75-83%. The highest values were in the generic stibogluconate group. The incidence of pancreatic enzyme abnormalities was 48-88% and the incidence of liver enzyme abnormalities was 48-87%. The lowest incidences were in the generic stibogluconate group. The efficacy and tolerance of inexpensive generic stibogluconate appears comparable to branded formulations for the treatment of cutaneous leishmaniasis in these endemic regions.

Adolescent↗

Anthropogenic impacts on the biogeochemistry and cycling of antimony.

Antimony is a potentially toxic trace element with no known biological function. Antimony is commonly enriched in coals, and fossil fuel combustion appears to be the largest single source of anthropogenic Sb to the global atmosphere. Abundant in sulfide minerals, its emission to the atmosphere from anthropogenic activities is linked to the mining and metallurgy of non-ferrous metals, especially Pb, Cu, and Zn. In particular, the geochemical and mineralogical association of Sb with Pb minerals implies that, like Pb, Sb has been emitted to the environment for thousands of years because of Pb mining, smelting, and refining. In the US alone, there are more than 400 former secondary lead smelting operations and worldwide there are 133 Pb-Zn smelters in operation today. Antimony is used in creating and improving dozens of industrial and commercial materials including various alloys, ceramics, glasses, plastics, and synthetic fabrics, making waste incineration another important source of Sb to the environment. Enrichments of Sb in atmospheric aerosols, plants, soils, sediments, as well as alpine and polar snow and ice suggest that Sb contamination is extensive, but there are very few quantitative studies of the geographic extent, intensity, and chronology of this contamination. There is an urgent need to quantify the extent of human impacts and how these have changed with time. The decreasing inventories of anthropogenic Sb with time in peat cores from Switzerland and Scotland suggest that the atmospheric Sb flux may be declining, but there have been too few studies to make any general conclusions. In fact, some studies of sediments and biomonitors in central Europe show little decline in Sb concentrations during the past decades. There is an obvious need for reliable data from well dated archives such as polar snow and ice, peat bogs, and sediments. The air concentrations, extent of enrichment, particle size distribution, and rate of deposition of Sb in urban areas is cause for concern. The natural processes which controlled the Sb flux to the atmosphere in the pre-anthropogenic past are poorly understood. The cumulative amount of anthropogenic Sb in soils has not yet been quantified. The long-term fate of Sb in soils, including weathering and mobilization, has only started to be investigated. However, the limited data available suggests that, in some locations at least, anthropogenic Sb in soils may be more mobile than anthropogenic Pb. Further study of this problem is needed, as well as the chemical speciation of Sb in soil-water-plant-sediment systems, and the implications which this has for human and ecosystem health.

Air Pollutants↗

[Determination of trace arsenic and mercury in antimony concentrates by hydride generation atomic fluorescence spectrometry].

A method for the determination of trace arsenic and mercury in antimony concentrates by hydride generation atomic fluorescence spectrometry was investigated. The method of dissolving sample and the effect of concomitant ion were studied. It was found that aqua regia can be used to dissolve the sample completely, with maximum quantities of dissolved arsenic and mercury. The interference of chemical elements in antimony concentrates was avoided by adding thiourea-Vc. The matrix of antimony was vaporized with tartaric acid during sample pre-treatment. Trace arsenic and mercury were determined in real samples. The detection limits of 0.220 ng x mL(-1) and 0.002 ng x mL(-1) were obtained, the relative standard deviations(RSD% = 11) are 1.47% and 0.52%, and the recoveries are 94.0%-103.0% and 98.7%-102.8% for As and Hg respectively. This method has proved rapid, accurate and highly sensitive.

Antimony↗

[Cellular adsorption and absorption of antimony (III) by Mycobacterium smegmatis].

Adsorption studies of Sb (III) as the antimonyl (125Sb) tartrate complex using acidified, non-proliferative suspensions of Mycobacterium smegmatis show that the uptake of Sb by the biomass increases with the external concentration of antimony ([Sb]) and decreases, at given concentration, with increasing pH. Measurements of Sb uptake in the cells under growth conditions in liquid culture indicate that the cellular concentration factor of antimony is of the order of 10 when the concentration of antimony in the medium is 10 microM, i.e., close to the minimum inhibitory concentration.

Absorption↗

Penicillamine as an adjuvant to antimonial therapy of schistosomiasis: effect on liver function tests in rabbits and on antischistosomal activity.

Earlier work has shown that penicillamine reduces the acute toxicity of antimonyl potassium tartrate (APT) as well as the abnormal ECG changes it induces. In the present study, the possible protective effect of penicillamine on the hepatic toxicity of APT was investigated. Tests of liver function showed changes in the level of serum aspartate and alanine aminotransferase and of alkaline phosphatase, and in the beta-/alpha-lipoprotein ratio, in response to antimony treatment. The changes were significantly reduced by penicillamine, though the effect depended on the dose. Penicillamine was found to give the best overall protection without affecting the antischistosomal efficacy of the antimonial when a 1:2 APT/penicillamine ratio was used. The findings provide further evidence of the potential usefulness of penicillamine in the antimonial treatment of schistosomiasis.

Alanine Transaminase↗

The effects of drugs on Onchocerca volvulus. 2. The antimonial preparations TWSb and MSbE.

Antimonial preparations (Pentostam, Neostibosan, stibophen, and tartar emetic) have occasionally been used in the treatment of onchocerciasis without very promising results. The advent of the preparations TWSb (stibocaptate) and MSbE (Friedheim) of allegedly reduced toxicity made it desirable to test them against Onchocerca volvulus.The action of both preparations on the parasites was found to vary from one patient to another, ranging from complete elimination of all parasites in a few cases to no detectable action in others. A microfilaricidal action was detectable in many patients, particularly after treatment with TWSb, which was used at higher doses than MSbE. A lethal or sterilizing action on some or all adult female worms was observed in some patients. However, toxic reactions to the drugs were common and distressing, and often it was necessary to stop treatment on this account. Anorexia, nausea, vomiting and prostration were the most common manifestations, and there was one fatality from coincident yellow fever, which may well have been aggravated by antimony treatment.The uncertain action of these preparations on O. volvulus and the toxic manifestations that accompany their use render them unsuitable for the treatment of onchocerciasis, and it is probable that the effects of antimony on O. volvulus are produced only at or above the normal level of human tolerance.

Animals↗

Comparative trials of antimonial drugs in urinary schistosomiasis.

Chemotherapeutic trials in urinary schistosomiasis are described and discussed. Their design and conduct were based on recommended statistical techniques, now generally accepted as the most appropriate approach to the assessment of antischistosomal drugs.Randomization produced comparable host groups in whom multiple parasitic infection and radiological urinary tract damage were common. Treatment was with one of three antimonial compounds given at equivalent metallic dosage daily.Antimony sodium tartrate (AST) and antimony dimercaptosuccinate (TWSb) were equally efficient curatively but both produced many side-effects. Sodium antimonylgluconate (TSAG) was four-fifths as effective but tolerance was superior. Estimations of urinary antimony excretion showed that tissue retention of the metal was related to cure-rates and side-effects. It was concluded that none of the drugs were suitable for mass chemotherapy.More new non-toxic schistosomicides are urgently needed and for their assessment, the setting-up of multicentre trials, following international agreement on technical methods, is suggested.

Adult↗

Technetium-99m antimony colloid for bone-marrow imaging.

Technetium-99m antimony colloid was prepared in our laboratory for bone-marrow imaging. Optimal production of colloid particles of size range 1-13 nm was achieved by the use of polyvinylpyrrolidone of mol. wt. 44,000. Electron microscopy was used to size the particles. Studies in rabbits showed exclusive concentration in the subendothelial dendritic phagocytes of the bone marrow. Pseudopods from these cells were found to traverse interendothelial junctions and concentrate colloid from the sinusoids. Imaging studies of bone marrow in rabbits showed the superiority of the Tc-99m antimony colloid over the much larger colloidal particles of Tc-99m sulfur colloid. Tissue distribution studies in the rat confirmed that bone-marrow uptake of Tc-99m antimony colloid was greater than that of Tc-99m sulfur colloid, although blood clearance was much slower.

Animals↗

Subacute toxicity of pentavalent antimony compounds in rats.

A subacute toxicity study of pentavalent antimony (Sb) compounds, sodium stibogluconate (SSG) and meglumine antimoniate (MA) was carried out in rats. Three groups of 10 rats each were treated with saline (control group), 300 mg Sb kg-1 d-1 or 900 mg Sb kg-1 d-1 of SSG for 30 d. A parallel study of similar type was conducted for MA. Compared with controls, drug-treated rats showed an impairment of feeding habits and retardation of weight gain (P less than 0.01) during the treatment period. In both SSG- and MA-treated rats there was a dose-related reduction in haemoglobin concentration (P less than 0.001), and hematocrit (P less than 0.001). Red cell count was reduced in SSG-treated rats only. Both drugs, however, significantly raised the white cell count (P less than 0.05). These changes were more pronounced with SSG them with MA. There was no change in MCV, MCH and MCHC. SSG, 900 mg Sb kg-1 d-1, significantly raised AST (P less than 0.005), ALT (P less than 0.01) and alkaline phosphatase activity (P less than 0.01). SSG-treated rats also had raised BUN (P less than 0.01) and creatinine (P less than 0.001), but no significant change in bilirubin levels. MA significantly raised AST (P less than 0.01), ALT (P less than 0.01), BUN (P less than 0.001) and serum creatinine levels (P less than 0.001), but had no appreciable effect on bilirubin and alkaline phosphatase levels. Both SSG and MA decreased blood glucose levels (P less than 0.01) and induced proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗