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Effects of potassium antimony tartrate on rat erythrocyte phosphofructokinase activity.

In an earlier study, we observed a marked accumulation of antimony in erythrocytes of rats administered potassium antimony tartrate (Sb) in drinking water. This observation has raised concerns of possible adverse effects on the hematological systems. A study was therefore carried out to investigate the effects of Sb on phosphofructokinase (PFK), a rate-limiting enzyme of erythrocyte glycolysis. Preincubation of PFK with Sb caused a marked inhibition of the enzyme with 95% loss of activity at 5 mM. In comparison, 5 mM sodium arsenite, a known enzyme inhibitor, reduced PFK activity by only 38%. Increasing the concentrations of fructose-6-phosphate (F6P) or magnesium had no effects on the inhibitory potency of Sb. Varying the concentrations of ATP and Sb produced a complex effect on PFK activity. At 1 mM ATP, 0.2 mM Sb was required for 50% inhibition (IC50) of PFK but only 0.05 mM Sb was required for the same inhibition when the concentration of ATP was reduced to 0.2 mM. Glutathione (2-10 mM) and hemoglobin (8-40 micronM partially protected the enzyme from the Sb effect, with the protection being more effective at low antimony concentrations. When Sb was added to assay mixtures after initiation of a PFK reaction with physiological concentrations of ATP (0.2 mM) and F6P (0.1 mM), PFK activity was approximately 50% inhibited by 0.5 mM Sb and completely inhibited by 5 mM Sb. In contrast, glucose utilization in whole blood was only 16% lower over an 8 hour incubation period in the presence of 5 mM Sb. It is concluded that while PFK is markedly inhibited by Sb under in vitro assay conditions, glycolysis in erythrocytes is not significantly affected except at very high Sb concentrations. The weak effect of Sb on glycolysis in erythrocytes may be due in part to the protective effect of hemoglobin and, to a lesser extent, glutathione on PFK.

Animals↗

Radionuclide lymphoscintigraphy with technetium 99m antimony sulfide colloid to identify lymphatic drainage of cutaneous melanoma at ambiguous sites in the head and neck and trunk.

Frequently the primary lesion of high-risk cutaneous melanoma (level III, greater than or equal to 1.5mm; greater than or equal to 1.0 mm with ulceration) is in an ambiguous lymphatic drainage site on the trunk, pelvic and shoulder girdles, and head and neck area. Lymphoscintigrams were performed by a circumferential intradermal injection of the biopsy site using technetium 99m (99mTc) antimony sulfide colloid in a total dose of 0.2 to 0.6 mCi in a volume of 0.1 to 0.5 ml. Imaging was done with a large-field gamma camera with high-resolution parallel hole collimator. Technetium 99m antimony sulfide colloid is an ideal agent for lymphoscintigrams because of small particle size (3-30 micron), which permits early migration into the interstitial space and lymphatics and rapid pickup by lymph nodes. Although it is a gamma emmitter with high activity, it has a short half-life and does not induce tissue necrosis. It does not localize the site of lymph node metastases, but indicates only the drainage pattern. Images were obtained at 1, 5, 10, 15, 30, and 60 minutes, respectively, and then three times every hour. Surgery was usually performed 24 hours later. The majority of patients had lesions with ambiguous drainage sites: head and neck (4 of 5 patients) and trunk (9 of 13 patients). The drainage by scan was to unpredictive sites in 72%, and resulted in a change of treatment planning by location and extent of ablation with node dissection in 9 of 18 patients. Ambiguous dissection sites included: (1) question of preauricular dissection with parotidectomy versus posterior auricular and cervical dissection for selected scalp lesions; (2) low-neck with or without axillary dissection for upper chest and shoulder lesions; and (3) axillary versus groin dissections for midflank lesions at zone of ambiguity between axilla and groin. It was concluded that preoperative 99mTc antimony sulfide lymphoscintigraphy is a highly useful planning technique in determining the appropriate lymphatic drainage basin for dissection in selected melanoma patients.

Adult↗

Determination of antimony in drinking waters by an inexpensive, reproducible hydride generator for atomic spectroscopy.

A method for determining antimony in drinking waters is described. In order to prevent a substantial error caused by the different oxidation states of antimony, Sb(V) is reduced to Sb(III) with potassium iodide-ascorbic acid. Covalent hydride is generated with a home made device by adding NaBH4. The hydride is then atomized in a flame-heated silica tube and atomic absorption is measured spectrophotometrically. The optimal conditions for this determination are discussed and interference effects are described. Results obtained by determining linearity range (0-200 ng), detection (LOD) and quantitation (LOQ) limits (LOD = 0.347 ng/ml, LOQ = 1.158 ng/ml), precision (instrumental CV 4.08% and method CV 7.74%) and accuracy performed by recovery assays (96.1%) show that the method is useful for antimony determination at the concentration usually present in drinking water.

Antimony↗

Altered Ca2+ mobilization during excitation-contraction in cultured cardiac myocytes exposed to antimony.

Industrial exposure and pharmaceutical use of antimony compounds have been linked to altered cardiovascular function and pathology. Antimony compounds induce hypotension, bradycardia, and cardiac arrhythmias, all of which can arise from aberrations in myocyte regulation of intracellular free calcium concentration ([Ca2+]i). To determine if trivalent antimony affects [Ca2+]i during excitation-contraction, we developed an in vitro cardiac myocyte model that was exposed for 24 hr to potassium antimonyl tartrate (PAT) at 0-10 microM. Control myocytes received sodium potassium tartrate. Concentrations of up to 10 microM PAT were without effect on total DNA and protein content of cultures, indicating that PAT exposures were not overtly toxic. However, spontaneous beating rates of myocytes were significantly reduced by 5 and 10 microM PAT. Myocytes were paced by electric field stimulation at 0.5 Hz, and the effect of PAT on [Ca2+]i transients during excitation-contraction was monitored with fura-2. PAT (2-8 microM) significantly reduced systolic [Ca2+]i in a concentration-dependent fashion, but was without effect on diastolic [Ca2+]i or on the first derivative of the transient rise (d[Ca2+]i/dt). Myocytes from control cells responded to epinephrine (10(-8)-10(-5) m) in concentration-dependent fashion with elevated systolic [Ca2+]i and an increase in the rate of decay of transients. In PAT-exposed myocytes, the systolic response was blunted while the decay rate was enhanced. PAT-exposed cells also exhibited a reduced basal [Ca2+]i when depolarized by 90 mm KCl and a reduced caffeine-releasable Ca2+ pool of the sarcoplasmic reticulum. Both control and PAT-treated cells responded to ryanodine in a comparable fashion. Results indicate that a nonlethal exposure to PAT reduces Ca2+ availability during excitation-contraction. Decreased influx of Ca2+ across the sarcolemma and enhanced removal of Ca2+ appear to be responsible.

Animals↗

Mercury-resistant plasmids in bacteria from a mercury and antimony deposit area.

Most bacterial cells (Pseudomonas, Acinetobacter) obtained from the soil at the Khaidarkan mercury and antimony mine (Kirghiz USSR) contain R plasmids with mercury (HgCl2) resistance determinants. The plasmids have a large molecular mass (about 100 MD, though smaller ones also occur), and at least some of them are transmissive. Many of the Hgr bacteria also display an elevated antimony (SbCl3) resistance, though this trait was not shown to be plasmid-dependent. There are practically no Hgr plasmids in bacteria taken from the soil at different distances from the mine: the saturation of bacteria with Hgr plasmids is maintained by selective pressure only in the area with a high enough toxin concentration. In the same mercury and antimony deposit area Hgr plasmids were also found in Escherichia coli isolates from the gut of Mus musculus mice and Bufo viridis toads. At least some of the bacterial plasmids obtained from animals also carry antibiotic-resistance determinants (Tcr, Cmr, Smr). These plasmids are also transmissive. They display internal instability and lose their resistance determinants after a conjugation transfer to other E. coli strains.

Acinetobacter↗

The influence of carbon dioxide, bicarbonate and other buffers on the potential of antimony microelectrodes.

Antimony microelectrodes were calibrated at 37 degrees C in phosphate buffers, in different bicarbonate solutions at various CO2-partial pressures and in buffers like TRIS1, TES2, MES3 and malonic acid. By use of the latter buffers (with exception of malonic acid) the most reliable calibration curves were obtained ("normal values"). The usual calibration in 67 mmol/l standard phosphate buffers turned out to be unacceptable because the obtained mV-values were too high (negative) in comparison to all other buffers. Different calibration curves resulted from the use of pure bicarbonate solution whether the pH-values were changed by variation of pCO2 or of the bicarbonate concentration. Low bicarbonate concentrations in combination with low pCO2 gave mV-values which were too low relative to the other buffers. Both the increase of pCO2 as well as of the bicarbonate concentration caused a shift of the potential of the antimony electrodes toward "normal values". In solutions containing other buffers the influence of bicarbonate and pCO2 became negligible with increasing buffer concentration. Decreasing oxygen partial pressure was found to cause an increase of the potential of the antimony electrodes. The influence of liquid junction potentials at the reference electrode is discussed.

Antimony↗

Comparison of clastogenic effects of antimony and bismuth as trioxides on mice in vivo.

Comparison of the clastogenic effects of antimony and bismuth used as trioxides, when administered orally by gavaging to laboratory bred male mice, showed that the former was more strongly clastogenic than the latter. Three doses of each chemical (400, 666.67, and 1000 mg/kg body wt), corresponding to 1/50, 1/30, and 1/20 of oral LD50 of antimony trioxide, were fed daily to sets of mice up to 21 d. Animals were sacrificed on day 7, 14, and 21 of the experiment. Chromosomal aberrations and mitotic index were studied from bone marrow cells following a colchicine-air drying Giemsa schedule. The frequencies of chromosomal aberrations induced by both chemicals were directly proportional to the dose used and the duration of exposure, indicating their cumulative effects on the organism. The highest dose of antimony, given for the longest period was, however, lethal. Effects on germ cells, as shown by screening for sperm head abnormalities, were not significant.

Animals↗

Synthesis and characterization of aspartic acid complexes of antimony and bismuth triiodide.

New bioinorganic complexes of the aspartic acid with the antimony or bismuth triiodide were synthesized by a direct solid-solid reaction at room temperature. The formula of the complex is MI(3)[OOCCH(2)CH(NH(2))CO](2.5) x 2.5H(2)O (M = Sb, Bi). The complex may be a dimer with bridge structure. The crystal structure of the complexes belongs to a triclinic system. The lattice parameters are a = 0.9883 nm, b = 1.4284 nm, c = 2.0114 nm, alpha = 94.46 degrees , beta = 99.76 degrees and gamma = 100.1 degrees for the complex of antimony and a = 0.9756 nm, b = 1.4560 nm, c = 1.9875 nm, alpha = 94.18 degrees , beta = 97.25 degrees and gamma = 101.16 degrees for the complex of bismuth. The infrared spectra and thermal analyses can demonstrate the complex formation between the aspartic acid and the antimony or bismuth ion.

Antimony↗

Comparison of the effectiveness of two topical paromomycin treatments versus meglumine antimoniate for New World cutaneous leishmaniasis.

The randomized, controlled study compared the therapeutic efficacy and safety of two paromomycin-containing topical preparations with the gold treatment standard, meglumine antimoniate, and with each other in 120 Ecuadorian patients with ulcerated lesions. The two paromomycin treatment comparisons were double-blinded. Group 1 (n = 14) received 15% paromomycin plus 12% methylbenzonium chloride (PR-MBCL) dissolved in a soft white paraffin base, applied twice daily for 30 days. Group 2 (n = 40) was also treated for 30 days with 15% paromomycin plus 10% urea (PR-U) dissolved in the same paraffin base. Group 3 (n = 40) received 20mg/kg/day of IM meglumine antimoniate (MA) for 10 days as per Ecuadorian Ministry of Public Health recommendations at the time of the study. The 10-day treatment was completed by 90% of the MA group compared to 72.5% of the PR-MBCL (X2 = 4.0, P = 0.045) and 75% of the PM-U (X2 = 3.1, P > 0.05) groups whose treatment regime lasted 20 days longer than the MA treatment. Post-treatment lesion burning, redness, inflammation, and soreness were more common in the two paromomycin groups compared to MA group (P < 0.05). The frequency of treatment-related side effects in the two paromomycin groups was similar. Six weeks after the start of treatment, 80.6% of MA subjects were clinically cured compared to 48.3% in the PR-MBCL (X2 = 6.1, P = 0.014) and 40% in the PM-U groups (X2 = 12.6, P = 0.002). By 12 weeks, the proportion of clinically cured subjects in the MA (91.7%) compared to PM-MBCL (79.3%) or PM-U (70%) groups was not significantly different (P > 0.05). MA-treated subjects clinically cured by 12 weeks had a faster mean healing time (29.5 +/- 12.2 days) compared to those in the PM-MBCL (versus 43.1 +/- 14.4 days, t = -3.7, P = 0.001) or PR-U groups (43.5 +/- 17 days; t = -3.2, P = 0.002). During the 48-week post-treatment follow-up period, infection reactivation was observed in 15.2% of the MA subjects compared to 17.4% in the PM-MBCL and 10.5% PM-U of subjects diagnosed as clinically healed by 12 weeks (P > 0.05). The results suggest that although the time required for the clinical healing of ulcerated lesions takes longer, topical paromomycin may be an acceptable therapeutic alternative in endemic areas where meglumine antimoniate is not available, is too costly or medically contraindicated.

Administration, Topical↗

New considerations about the separation and quantification of antimony species by ion chromatography-hydride generation atomic fluorescence spectrometry.

A new method for the speciation of inorganic [Sb(III) and Sb(V)] and organic (Me3SbCl2) antimony species by using a polystyrene-divinylbenzene-based anion-exchange HPLC column (Hamilton PRP-X100) coupled to hydride generation atomic fluorescence spectrometry (HG-AFS) is presented. Several mobile phases were tested for the baseline separation of these three antimony species, investigating in detail experimental parameters such as concentration and pH. The best efficiency and resolution was achieved by using a gradient elution between diammonium tartrate 250 mmol l(-1) pH 5.5 (A) and KOH 20 mmol l(-1) pH 12 (B). The gradient programme used was 100% B for 1.5 min, decreasing to 0% B in 0.1 min and maintained the elution with 100% A for 5.5 min. Analysis time was less than 7 min. Equilibration of the column with the complexing mobile phase was found to be critical in order to avoid Sb(III) double peak formation. Dilution in diammonium tartrate medium was necessary in order to avoid Sb(III) oxidation at microg l(-1) concentration level. Detection limits of 0.06 microg l(-1) for Sb(V), 0.09 microg l(-1) for Me3SbCl2 and 0.04 microg l(-1) for Sb(III) as well as repeatability and reproducibility better than 5% R.S.D. (n = 10) and 9% R.S.D. (n = 30) (for 1 and 5 microg l(-1) of Sb(V) and Sb(III) and 5 and 10 microg l(-1) of Me3SbCl2) were obtained. Accuracy and recovery studies were carried out by analysing one river freshwater sample and two water certified reference materials. The proposed methodology can be considered reliable and straightforward for antimony speciation in fresh water samples.

Antimony↗

Long term improvement in the treatment of canine leishmaniosis using an antimony liposomal formulation.

Pharmacokinetic and clinical effectiveness of liposome-encapsulated N-methylglucamine antimoniate (LMA) was performed in dogs suffering from experimental leishmaniosis. LMA was compared with N-methylglucamine antimoniate (MGA), the same drug in its free form. Sb plasma concentrations for LMA were always higher than those for MGA. Mean residence time (MRT), half-life time (t(1/2)) and clearance (Cl) showed that Sb was eliminated slower after liposome administration. The high volume of distribution (Vd) obtained with LMA suggests that Sb could achieve therapeutic concentrations in parasite-infected tissues. Average plasma concentration at steady state (Css(ave)) shows that Sb body concentrations after LMA treatment (9.8 mg/kg Sb, each 24h) would be effective in Leishmania infantum canine infection. Comparing LMA with MGA in a 1-year follow-up we observed no relapses for LMA and total protein and gammaglobulin concentrations were within normal range, while for MGA both began to rise 3 months after treatment. Use of antimonial liposomal formulations may restore effectiveness to an existing drug and reduce toxicity.

Animals↗

Pharmacokinetics of meglumine antimoniate after administration of a multiple dose in dogs experimentally infected with Leishmania infantum.

Pharmacokinetics of meglumine antimoniate in dogs with experimentally induced leishmaniosis has been investigated. After infection, dogs received a dose of 75 mg kg-1 of meglumine antimoniate twice daily by subcutaneous injection for 10 days. Blood samples were collected throughout the treatment. No statistical differences were found in the kinetic behaviour of the drug administered as a single dose to healthy dogs and that administered as a multiple dose to infected animals. However, peak plasma concentrations (Cmax) of 30.8 +/- 12.8 micrograms ml-1 found after this dosage regimen were higher than those observed after the single dose administration of 100 mg kg-1 24 h-1. Furthermore, sustained antimony concentrations of 1.14 +/- 0.52 micrograms Sb ml-1 were detected throughout the treatment. No signs of toxicity were found in the animals treated indicating that this regimen would be very appropriate to treat canine leishmaniosis.

Analysis of Variance↗

Biological activity of inorganic arsenic and antimony reflects oxidation state in cultured human keratinocytes.

Sodium arsenite is much more potent than sodium arsenate in producing adverse effects in animals and in cultured cells. Although arsenate may exhibit toxicity as a phosphate analogue, its potency in vivo appears to be enhanced by reduction to arsenite. To understand the relative importance of this reduction, which is critical in evaluating the responsiveness of cell culture models to the different oxidation states and thus to elucidating the mechanism of arsenic action, present work has correlated the extent of reduction with biological activity in human keratinocytes. The results show that at biologically relevant concentrations, arsenate reduction to appreciable levels required several days, helping rationalize a previous empirical observation that it was approximately one-third as potent as arsenite. The relatively low conversion rate also emphasizes a limitation of culture; arsenate was nearly as efficacious as arsenite, but the time required for it to reach maximal effect exceeded ordinary medium change intervals. In keratinocytes, an important role for purine nucleoside phosphorylase in the reduction could not be demonstrated, indicating that another pathway is dominant in this cell type. Methylation of inorganic arsenic, uptake of methylated forms, and their reduction were all very slow. These findings suggest that the reduced methylated forms have only a small contribution to skin carcinogenesis unless they are supplied through the circulation. In parallel experiments, trivalent antimony was similar to arsenite in potency and efficacy, whereas pentavalent antimony was virtually without biological effect. Conversion of antimony in the pentavalent to the trivalent oxidation state was not detectable in keratinocytes. These findings emphasize the importance of intracellular reduction of the metalloids for biological effects.

Animals↗

Physico-chemical characterization of meglumine antimoniate.

The leishmanicidal drug, meglumine antimoniate (MA), has been synthesized by the reaction of antimony oxyhydrated and N-methyl glucamine. Infrared and solid state NMR 13C analysis of MA and the ligand strongly suggests that antimony binds to N-methyl glucamine through the oxygen of C-3 carbon. Potentiometric titration indicated that, between pH 4.5 and 7.5, MA exists in the zwitterionic form.

Antiprotozoal Agents↗

Dual mode antimony electrode for simultaneous measurements of PO2 and pH.

BACKGROUND: In biomedical research and clinical medicine there is a demand for potent sensors to measure the components that make up blood gas analyses. Today, as when the electrochemical PO2, PCO2 and pH electrodes were first introduced, these measurements are usually made with the same type of sensor technology. The aims of the present study were, firstly, to find out whether the platinum cathode in the Clark electrode can be replaced by antimony for oxygen measurements (amperometry (A)); secondly, whether, during oxygen measurements, the inherent corrosion potential of the antimony metal can be used for measurement of pH in the same measurement area (potentiometry (P)). METHODS: An electrode of purified, crystallographically orientated monocrystalline antimony (COMA) connected to a reference electrode (silver-silver chloride) was used for the P measurements. Measurements of A (at -900 mV) and P were made in an aqueous environment regulated for oxygen, pH, and temperature. RESULTS: Reproducible oxygen sensitivities of 0.925 nA/% oxygen (2% CV (coefficient of variation)) (A), 10.7 mV/% (P), and 0.7 mV/% (P) were found in the oxygen range: 0-21%, <5%, and above 5%, respectively. The pH sensitivity was 57 mV/pH unit (P). Oxygen and pH measurements were less accurate at oxygen concentrations close to 0%. CONCLUSIONS: Both the oxygen and pH part of the composite electrode signal can be identified by this dual mode technique (A and P). The sensor seems to be promising as it provides measurements of two separate variables (oxygen and pH) and also has the desirable characteristics of a solid state sensor.

Antimony↗

Antimony: a traffic-related element in the atmosphere of Buenos Aires, Argentina.

Vehicular traffic is one of the main sources of antimony in highly populated urban areas like Buenos Aires where an overall traffic density of 1 500 000 vehicles per day (corresponding to 7500 vehicles km(-2)) is estimated. In this context, a study was undertaken to ascertain the levels of Sb and other traffic-related elements (TRE) in the atmosphere of this city. To this end, sixty-seven samples of PM-10 particulate matter were collected during eight days in nine representative sampling sites located downtown Buenos Aires and spread over an area of about 30 km2. The collection of particulate matter was performed on ash-free glass-fibre filters using high volume samplers with PM-10 sampling heads. A combination of aqua regia and perchloric acid was used for leaching metals from filters. The resulting solutions were evaporated and then diluted with 0.1 mol l(-1) HCl. Antimony was determined by inductively coupled plasma-quadrupole mass spectrometry (ICP-QMS) at ng g(-1) levels. Concentrations of Sb varied from 12.9 +/- 0.9 to 375 +/- 23 microg g(-1)(equivalent to 0.87 +/- 0.06 to 15.3 +/- 0.8 ng m(-3)). Statistical analysis was performed on the data set including the measured PM-10 mass and Sb concentrations for the monitored period. Correlations of Sb with other TRE namely, Cu and Mo were also assessed. The highest concentrations of Sb were detected at two sites (Hospital Alemán and Casa Rapallini) located in streets with traffic consisting mostly of passenger cars and showing a "stop-and-go" pattern in peak hours. Antimony levels in the Buenos Aires PM-10 are by far below the level of 0.5 mg m(-3)(for an 8 hour workday, 40 hour work week) set by the US Occupational Safety and Health Administration (OSHA) for occupational exposure. However, monitoring of Sb and other TRE should be carried out in a systematic fashion to detect the possibility of increases in from the present levels.

Air Pollutants↗

Immunochemotherapy for cutaneous leishmaniasis: a controlled trial using killed Leishmania (Leishmania) amazonensis vaccine plus antimonial.

BACKGROUND: Leishmaniasis is endemic in 88 countries in the world, and 350 million individuals are at risk of acquiring the disease. Treatment for American cutaneous leishmaniasis (ACL) is long, expensive, and associated with important side-effects. METHODS: In this double-blind, placebo-controlled study, we treated 102 patients with ACL using either a combination of a single-strain Leishmania amazonensis killed promastigote vaccine plus a half dose of meglumine antimoniate, or placebo plus the same half dose regimen of meglumine antimoniate, in 10-day series followed by 10-day intervals. RESULTS: Of the 47 patients in the experimental arm, 47 (100%) were cured after four series of treatment, compared to four of 49 (8.2%) in the control group (P < 0.0001). Six patients were lost to follow-up. CONCLUSIONS: The combination of a single-strain Leishmania (Leishmania) amazonensis killed promastigote vaccine with a half dose regimen of antimonial is highly effective for the treatment of ACL.

Adolescent↗

Treatment of cutaneous leishmaniasis with antimony: intramuscular versus intralesional administration.

The various methods used to treat cutaneous leishmaniasis (CL) have not given consistent results. The aim of the present study was to compare the efficacy of a solution of meglumine antimoniate (MA; 85 mg Sb/ml) given intralesionally (i.l.) with that of the same solution given intramuscularly (i.m.). Eighty CL patients, with a total of 147 lesions, were randomly allocated into the two treatment groups. Forty were injected i.m. with MA (15 mg Sb/kg.day) on 6 days/week until 12 injections had been given to each. The lesions of the other 40 patients were infiltrated with MA (0.2-0.8 ml/lesion) every other day for 30 days. After 15 days' therapy, none of the lesions on those treated i.m. had fully healed (although five lesions showed some improvement) whereas two lesions on those treated i.l. had fully healed and 10 showed good improvement. After 30 days, 46 (68%) of the 68 lesions on those treated i.m. had healed completely, 11 (16%) had improved, and five (8%) worsened. The corresponding values for the 66 lesions on those treated i.l. were 48 (73%), 10 (15%) and three (5%). There was no statistically significant difference between the two treatment groups, either in terms of satisfactory response (lesions fully healed or improved) or unsatisfactory response (lesions unchanged or advanced), when assessed on day 30 (P > 0.5). Intralesional antimony is a rapidly effective, safe and economical method of treating simple CL, particularly in patients with cardiac, liver or renal disease, for whom antimonials are contra-indicated.

Adolescent↗