Outbreak of lead poisoning from a civilian indoor firing range in the UK.

INTRODUCTION: Lead exposure from discharged lead dust is a recognised risk at firing ranges. We report a lead poisoning outbreak among staff and their close contacts at a UK civilian indoor 24 m firing range. METHODS: A retrospective review was undertaken of data collected on all patients at risk of lead poisoning identified either by direct referral to the Clinical Toxicology clinicians at the West Midlands Poisons Unit, or via the Trace Elements Supra-Regional Assay Service Laboratory at Sandwell hospital. RESULTS: Eighty-seven patients were identified as having possible lead exposure, either at the firing range or via close contacts. Of these, 63 patients aged between 6 months and 78 years attended for blood lead concentration (BLC) testing. The highest BLC at presentation was 11.7 µmol/L (242 µg/dL). Only nine patients reported any symptoms at presentation. Fifteen patients received lead chelation therapy with oral dimercaptosuccinic acid (or succimer) 30 mg/kg/day or intravenous sodium calcium edetate (EDTA) 75 mg/kg/day, dependent on stock availability. DISCUSSION: This report highlights the need for vigilance of lead poisoning as an occupational hazard in the UK, including at recreational facilities such as indoor firing ranges. It emphasises the importance of regulation of lead exposure in the workplace, particularly given the vague symptoms of lead poisoning, and proposes re-appraisal of UK legislation. This report also highlights potential issues surrounding stock availability of rarely used antidotes for uncommon presentations in the event of an outbreak of poisoning.

Combined dimercaptosuccinic acid and zinc treatment in neurological Wilson's disease patients with penicillamine-induced allergy or early neurological deterioration.

The clinical data of safety and efficacy of a combined treatment with dimercaptosuccinic acid (DMSA) and Zinc with 2 years' follow-up in 60 neurological Wilson's disease (WD) patients was retrospectively analyzed. All the patients included in the present study were newly diagnosed and initialized with D-penicillamine (DPA) treatment but were found to have either neurological deterioration or allergy, and their treatment was switched to a combined treatment of DMSA and Zinc. Fifty-one patients (85%) had the neurological symptoms improved 1 and 2 years after treatment, 7 (11.67%) experienced a stable neurological condition, and 2 (3.33%) suffered deterioration of neurological symptoms. No early neurological deterioration was observed in all patients. Twenty-five percent patients experienced mild adverse reactions which did not require a discontinuation of the DMSA and Zinc treatment. Our study confirmed the safety and efficacy of the combined DMSA and Zinc therapy as an initial and probably long-term treatment in neurological WD patients.

Chelation for autism spectrum disorder (ASD).

BACKGROUND: It has been suggested that the severity of autism spectrum disorder (ASD) symptoms is positively correlated with the level of circulating or stored toxic metals, and that excretion of these heavy metals, brought about by the use of pharmaceutical chelating agents, results in improved symptoms. OBJECTIVES: To assess the potential benefits and adverse effects of pharmaceutical chelating agents (referred to as chelation therapy throughout this review) for autism spectrum disorder (ASD) symptoms. SEARCH METHODS: We searched the following databases on 6 November 2014: CENTRAL, Ovid MEDLINE, Ovid MEDLINE In-Process, Embase,PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and 15 other databases, including three trials registers. In addition we checked references lists and contacted experts. SELECTION CRITERIA: All randomised controlled trials of pharmaceutical chelating agents compared with placebo in individuals with ASD. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed them for risk of bias and extracted relevant data. We did not conduct a meta-analysis, as only one study was included. MAIN RESULTS: We excluded nine studies because they were non-randomised trials or were withdrawn before enrolment.We included one study, which was conducted in two phases. During the first phase of the study, 77 children with ASD were randomly assigned to receive seven days of glutathione lotion or placebo lotion, followed by three days of oral dimercaptosuccinic acid (DMSA). Forty-nine children who were found to be high excreters of heavy metals during phase one continued on to phase two to receive three days of oral DMSA or placebo followed by 11 days off, with the cycle repeated up to six times. The second phase thus assessed the effectiveness of multiple doses of oral DMSA compared with placebo in children who were high excreters of heavy metals and who received a three-day course of oral DMSA. Overall, no evidence suggests that multiple rounds of oral DMSA had an effect on ASD symptoms. AUTHORS' CONCLUSIONS: This review included data from only one study, which had methodological limitations. As such, no clinical trial evidence was found to suggest that pharmaceutical chelation is an effective intervention for ASD. Given prior reports of serious adverse events, such as hypocalcaemia, renal impairment and reported death, the risks of using chelation for ASD currently outweigh proven benefits. Before further trials are conducted, evidence that supports a causal link between heavy metals and autism and methods that ensure the safety of participants are needed.

Chelation in metal intoxication--Principles and paradigms.

The present review provides an update of the general principles for the investigation and use of chelating agents in the treatment of intoxications by metals. The clinical use of the old chelators EDTA (ethylenediamine tetraacetate) and BAL (2,3-dimercaptopropanol) is now limited due to the inconvenience of parenteral administration, their own toxicity and tendency to increase the neurotoxicity of several metals. The hydrophilic dithiol chelators DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercapto-propanesulphonate) are less toxic and more efficient than BAL in the clinical treatment of heavy metal poisoning, and available as capsules for oral use. In copper overload, DMSA appears to be a potent antidote, although d-penicillamine is still widely used. In the chelation of iron, the thiols are inefficient, since iron has higher affinity for ligands with nitrogen and oxygen, but the new oral iron antidotes deferiprone and desferasirox have entered into the clinical arena. Comparisons of these agents and deferoxamine infusions are in progress. General principles for research and development of new chelators are briefly outlined in this review.

Chelation therapy in intoxications with mercury, lead and copper.

In the present review we provide an update of the appropriate use of chelating agents in the treatment of intoxications with compounds of mercury, lead and copper. The relatively new chelators meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-propanesulphonate (DMPS) can effectively mobilize deposits of mercury as well as of lead into the urine. These drugs can be administered orally and have relatively low toxicity compared to the classical antidote dimercaptopropanol (BAL). d-Penicillamine has been widely used in copper overload, although 2,3-dimercaptosuccinic acid or tetrathiomolybdate may be more suitable alternatives today. In copper-toxicity, a free radical scavenger might be recommended as adjuvant to the chelator therapy.

The scientific basis for chelation: animal studies and lead chelation.

This presentation summarizes several of the rodent and non-human studies that we have conducted to help inform the efficacy and clinical utility of succimer (meso-2,3-dimercaptosuccincinic acid) chelation treatment. We address the following questions: (1) What is the extent of body lead, and in particular brain lead reduction with chelation, and do reductions in blood lead accurately reflect reductions in brain lead? (2) Can succimer treatment alleviate the neurobehavioral impacts of lead poisoning? And (3) does succimer treatment, in the absence of lead poisoning, produce neurobehavioral deficits? Results from our studies in juvenile primates show that succimer treatment is effective at accelerating the elimination of lead from the body, but chelation was only marginally better than the complete cessation of lead exposure alone. Studies in lead-exposed adult primates treated with a single 19-day course of succimer showed that chelation did not measurably reduce brain lead levels compared to vehicle-treated controls. A follow-up study in rodents that underwent one or two 21-day courses of succimer treatment showed that chelation significantly reduced brain lead levels, and that two courses of succimer were significantly more efficacious at reducing brain lead levels than one. In both the primate and rodent studies, reductions in blood lead levels were a relatively poor predictor of reductions in brain lead levels. Our studies in rodents demonstrated that it is possible for succimer chelation therapy to alleviate certain types of lead-induced behavioral/cognitive dysfunction, suggesting that if a succimer treatment protocol that produced a substantial reduction of brain lead levels could be identified for humans, a functional benefit might be derived. Finally, we also found that succimer treatment produced lasting adverse neurobehavioral effects when administered to non-lead-exposed rodents, highlighting the potential risks of administering succimer or other metal-chelating agents to children who do not have elevated tissue lead levels. It is of significant concern that this type of therapy has been advocated for treating autism.

Topical efficacy of dimercapto-chelating agents against lewisite-induced skin lesions in SKH-1 hairless mice.

Lewisite is a potent chemical warfare arsenical vesicant that can cause severe skin lesions. Today, lewisite exposure remains possible during demilitarization of old ammunitions and as a result of deliberate use. Although its cutaneous toxicity is not fully elucidated, a specific antidote exists, the British anti-lewisite (BAL, dimercaprol) but it is not without untoward effects. Analogs of BAL, less toxic, have been developed such as meso-2,3-dimercaptosuccinic acid (DMSA) and have been employed for the treatment of heavy metal poisoning. However, efficacy of DMSA against lewisite-induced skin lesions remains to be determined in comparison with BAL. We have thus evaluated in this study the therapeutic efficacy of BAL and DMSA in two administration modes against skin lesions induced by lewisite vapor on SKH-1 hairless mice. Our data demonstrate a strong protective efficacy of topical application of dimercapto-chelating agents in contrast to a subcutaneous administration 1h after lewisite exposure, with attenuation of wound size, necrosis and impairment of skin barrier function. The histological evaluation also confirms the efficacy of topical application by showing that treatments were effective in reversing lewisite-induced neutrophil infiltration. This protective effect was associated with an epidermal hyperplasia. However, for all the parameters studied, BAL was more effective than DMSA in reducing lewisite-induced skin injury. Together, these findings support the use of a topical form of dimercaprol-chelating agent against lewisite-induced skin lesion within the first hour after exposure to increase the therapeutic management and that BAL, despite its side-effects, should not be abandoned.

Lactobacillus plantarum CCFM8661 alleviates lead toxicity in mice.

Lead causes a broad range of adverse effects in humans and animals. The objective was to evaluate the potency of lactobacilli to bind lead in vitro and the protective effects of a selected Lactobacillus plantarum CCFM8661 against lead-induced toxicity in mice. Nine strains of bacteria were used to investigate their binding abilities of lead in vitro, and L. plantarum CCFM8661 was selected for animal experiments because of its excellent lead binding capacity. Both living and dead L. plantarum CCFM8661 were used to treat 90 male Kunming mice during or after the exposure to 1 g/L lead acetate in drinking water. The results showed oral administration of both living and dead L. plantarum CCFM8661 offered a significant protective effect against lead toxicity by recovering blood δ-aminolevulinic acid dehydratase activity, decreasing the lead levels in blood and tissues, and preventing alterations in the levels of glutathione, glutathione peroxidase, malondialdehyde, superoxide dismutase, and reactive oxygen species caused by lead exposure. Moreover, L. plantarum CCFM8661 was more effective when administered consistently during the entire lead exposure, not after the exposure. Our results suggest that L. plantarum CCFM8661 has the potency to provide a dietary strategy against lead toxicity.

Biodistribution and biocompatibility of DMSA-stabilized maghemite magnetic nanoparticles in nonhuman primates (Cebus spp.).

AIM: This work represents the first reported investigation on the effects of magnetic nanoparticles (MNPs) in nonhuman primates. Biodistribution, biocompatibility and nanotoxicity of maghemite nanoparticles stabilized with dimercaptosuccinic acid (DMSA) were accessed. MATERIALS & METHODS: A control animal was used and three other animals were intravenously injected with DMSA-MNPs and euthanized 12 h, 30 and 90 days following administration. Extracted organs were processed by histological techniques. An additional animal was used to collect blood samples to complementarily assess biocompatibility 12 h, 7, 15, 30, 60 and 90 days after DMSA-MNP injection. RESULTS: DMSA-MNPs were preferentially addressed to the lungs, liver and kidneys. Hematological and serum biochemical results corroborated histological findings, supporting DMSA-MNP biocompatibility while preserving both hepatic and renal normal activity. CONCLUSION: DMSA-MNPs were preferentially distributed to the lung, liver and kidneys. Furthermore, DMSA-MNPs were considered biocompatible, supporting their application as a promising nanomaterial platform for future biomedical use.

Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A--medical results.

BACKGROUND: This study investigated the effect of oral dimercapto succinic acid (DMSA) therapy for children with autism spectrum disorders ages 3-8 years. METHODS: Phase 1 involved 65 children who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo. RESULTS: DMSA greatly increased the excretion of lead, substantially increased excretion of tin and bismuth, and somewhat increased the excretion of thallium, mercury, antimony, and tungsten. There was some increase in urinary excretion of essential minerals, especially potassium and chromium. The Phase 1 single round of DMSA led to a dramatic normalization of RBC glutathione in almost all cases, and greatly improved abnormal platelet counts, suggesting a significant decrease in inflammation. CONCLUSION: Overall, DMSA therapy seems to be reasonably safe, effective in removing several toxic metals (especially lead), dramatically effective in normalizing RBC glutathione, and effective in normalizing platelet counts. Only 1 round (3 days) was sufficient to improve glutathione and platelets. Additional rounds increased excretion of toxic metals.

Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: part B - behavioral results.

BACKGROUND: This study investigated the effects of oral dimercapto succinic acid (DMSA) therapy on the behavioural symptoms of children with autism spectrum disorders (ASD) ages 3-8 years. METHODS: Phase 1 involved 65 children with ASD who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo. RESULTS: The groups receiving one round and seven rounds of DMSA had significant improvements on all the assessment measures. For the seven round group, the degree of improvement on the assessment measures could be partially explained by a regression analysis based on excretion of toxic metals and changes in glutathione (adjusted R2 of 0.28-0.75, p < 0.02 in all cases). One round of DMSA had nearly the same benefit as seven rounds. The assessment measures correlated reasonably with one another at the beginning of the study (r = 0.60-0.87) and even better at the end of the study (r = 0.63-0.94). CONCLUSION: Overall, both one and seven rounds of DMSA therapy seems to be reasonably safe in children with ASD who have high urinary excretion of toxic metals, and possibly helpful in reducing some of the symptoms of autism in those children.

A comparison of sodium calcium edetate (edetate calcium disodium) and succimer (DMSA) in the treatment of inorganic lead poisoning.

INTRODUCTION: This article reviews the experimental and clinical studies that have compared the efficacy (impact on urine lead excretion, blood and tissue lead concentrations, resolution of features and survival) of sodium calcium edetate (edetate calcium disodium) and succimer (DMSA) in the treatment of inorganic lead poisoning. It also summarizes the pharmacokinetic and pharmacodynamic aspects and the adverse effects of treatment. METHODS: Medline, Toxline, and Embase were searched for all available years to June 2009. PHARMACOKINETICS AND PHARMACODYNAMICS: The absorption of oral DMSA is more complete than sodium calcium edetate; the latter has to be administered parenterally. Both antidotes are distributed predominantly extracellularly. Sodium calcium edetate is not metabolized, whereas DMSA is extensively metabolized to mixed disulfides of cysteine. The two antidotes have elimination half-lives of less than 60 min. There is no evidence that either antidote crosses the blood-brain barrier to any major extent. Sodium calcium edetate chelates lead by displacement of the central Ca2+ ion with Pb2+. The nature of the DMSA-lead chelate is less clearly defined. There is evidence that the mixed disulfides of cysteine are the active chelating moiety in humans. If this is the case, this suggests that chelation occurs principally, if not exclusively, in the kidney. The primary source of lead mobilized by sodium calcium edetate is bone with an additional contribution from kidney and liver. EFFICACY: Comparison of the experimental studies is complicated by substantial variations in study design, particularly the antidote dose, the route and duration of treatment, the amount and duration of lead dosing, and lack of direct comparison between antidotes (comparison was usually made with control). In experimental studies that used equimolar and clinically relevant antidote doses and assessed the impact of DMSA and sodium calcium edetate on urine lead excretion and/or blood lead concentrations, similar results were found, though no direct comparison between antidotes was undertaken. DMSA was more effective than sodium calcium edetate in reducing the kidney lead concentration, sodium calcium edetate was more effective than DMSA in reducing bone lead concentrations, and there was no consistently observed effect of chelation therapy on brain lead concentrations in these experimental studies. Only two clinical studies have compared equimolar or similar antidote doses in enhancing urine lead excretion; there was no statistical difference between the antidotes, though both studies had limitations. DMSA and sodium calcium edetate had a comparable impact on lowering blood lead concentrations in a clinical study using similar molar antidote doses. ADVERSE EFFECTS: Sodium calcium edetate causes dose-related nephrotoxicity. Both agents deplete zinc and copper, the effect on zinc being significantly greater with sodium calcium edetate. A transient increase in hepatic transaminase activity has been reported with both antidotes but appears to be more common with DMSA and neither has been associated with clinically significant hepatic toxicity. Skin lesions during treatment with sodium calcium edetate are unusual and have been attributed to zinc deficiency. DMSA has occasionally been associated with a severe mucocutaneous reaction necessitating discontinuation of therapy. CONCLUSIONS: Oral DMSA and parenteral sodium calcium edetate are both effective chelators of lead. There are currently insufficient data, however, to conclude that either antidote is superior in enhancing lead excretion. Both antidotes resolve the symptoms of moderate and severe lead toxicity rapidly. Although there is greater clinical experience with sodium calcium edetate, particularly in the treatment of lead encephalopathy, oral DMSA may now be considered as an alternative in circumstances where oral therapy is preferable.

Dimercaptosuccinic acid (succimer; DMSA) in inorganic lead poisoning.

INTRODUCTION: This article reviews data on the efficacy of succimer (dimercaptosuccinic acid, DMSA) in the treatment of human inorganic lead poisoning, the adverse effects associated with its use, and summarizes current understanding of the pharmacokinetic and pharmacodynamic aspects. METHODS: Medline, Toxline, and Embase were searched and 912 papers were identified and considered. PHARMACOKINETICS AND PHARMACODYNAMICS: DMSA is absorbed rapidly but incompletely after oral administration, probably through an active transporter. There is evidence that enterohepatic circulation occurs. Most DMSA in plasma is protein (mainly albumin)-bound through a disulfide bond with cysteine; only a very small amount is present as free drug, which is filtered at the glomerulus then extensively reabsorbed into proximal tubule cells. Nonfiltered protein-bound DMSA in peritubular capillaries is also available for uptake into proximal tubule cells by active anion transport at the basolateral membrane. DMSA therefore accumulates in the kidney where it is extensively metabolized in humans to mixed disulfides of cysteine. Some 10-25% of an orally administered dose of DMSA is excreted in urine, the majority within 24 h and most (>90%) as DMSA-cysteine disulfide conjugates. It is not known whether protein-bound DMSA can chelate lead; there is evidence that the mixed disulfides of cysteine are the active chelating moiety in humans. If this is the case, this suggests that chelation occurs principally, if not exclusively, in the kidney. DOSE: DMSA 30 mg/kg/day is more effective than either 10 or 20 mg/kg/day in enhancing urine lead excretion. DURATION OF THERAPY: Initial clinical studies with DMSA involved the administration of a 5-day course of treatment. Subsequently, a 19- to 26-day regimen was introduced with the intent of preventing or at least blunting a rebound in the blood lead concentration. Studies suggest, however, that repeated courses of DMSA 30 mg/kg/day for at least 5 days are equally efficacious if a treatment-free period of at least 1 week between courses is included to allow redistribution of lead from bone to soft tissues and blood. There is also evidence that in more severely poisoned patients DMSA 30 mg/kg/day can be given for more than 5 days with benefit. EFFICACY: DMSA 30 mg/kg/day significantly increases urine lead elimination and significantly reduces blood lead concentrations in lead-poisoned patients, though there is substantial individual variation in response. Over a 5-day course, mean daily urine lead excretion exceeds baseline by between 5- and 20-fold and blood lead concentrations fall to 50% or less of the pretreatment concentration, with wide variation. Maximum enhancement of urine lead elimination typically occurs with the first dose. Most symptomatic patients report improvement after 2 days of treatment. However, DMSA did not improve cognition in children < 3 years old with mild lead poisoning, presumably because lead-induced neurological damage occurred during development in utero and/or early infancy. DMSA IN PREGNANCY AND IN THE NEONATE: DMSA is not teratogenic but did produce maternal toxicity (decreased weight gain) and fetotoxicity when given in high dose (100-1,000 mg/kg/day) in experimental studies. For this reason sodium calcium edetate is generally preferred in pregnancy. ADVERSE EFFECTS: A transient modest rise in transaminase activity during chelation occurs in up to 60% of patients but has not resulted in clinically significant sequelae. Skin reactions occur in approximately 6% of treated patients and are occasionally severe. DMSA also increases urine copper and zinc excretion but not to a clinically important extent. CONCLUSIONS: DMSA is an effective lead chelator that primarily chelates renal lead. It is generally well tolerated but may occasionally cause clinically important adverse effects. DMSA may now be considered as an alternative to sodium calcium edetate, particularly when an oral antidote is preferable.

Use of oral dimercaptosuccinic acid (succimer) in adult patients with inorganic lead poisoning.

BACKGROUND: Chelation therapy has been used as a means of reducing the body burden of lead for five decades. Intravenous sodium calcium edetate has been the preferred agent, but there is increasing evidence that dimercaptosuccinic acid (DMSA) is also a potent chelator of lead. METHODS: Oral DMSA 30 mg/kg/day was administered to adults with blood lead concentrations > or = 50 microg/dl. The impact of DMSA on urine lead excretion, on blood lead concentrations and on symptoms was observed. The incidence and severity of adverse effects was also recorded. RESULTS: Thirty-five courses were given to 17 patients. DMSA significantly (P < 0.0001) increased urine lead excretion and significantly (P < 0.0001) reduced blood lead concentrations. Mean daily urine lead excretion exceeded the pre-treatment value by a median of 12-fold with wide variation in response (IQR 8.9-14.8, 95% CI 10.1-14.6). Pre-treatment blood lead concentrations correlated well with 5-day urine lead excretion. Headache, lethargy and constipation improved or resolved in over half the patients within the first 2 days of chelation. DMSA was generally well tolerated, but one course was discontinued due to a severe mucocutaneous reaction. There was a transient increase in alanine aminotransferase (ALT) activity during 14% of chelations. DMSA caused a significant increase in urine copper (P < 0.0001) and zinc (P < 0.05) excretion. CONCLUSION: Oral DMSA 30 mg/kg/day is an effective antidote for lead poisoning, though there is a wide inter- and intra-individual variation in response.

Amphotericin B in poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) nanoparticles against paracoccidioidomycosis.

OBJECTIVES: The present study reports on the preparation and testing of a desoxycholate amphotericin B (D-AMB) sustained delivery system based on poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) polymeric blends (Nano-D-AMB) aimed at reducing the number of AMB administrations required to treat mycosis. METHODS: BALB/c mice were infected with the yeast Paracoccidioides brasiliensis intravenously to mimic the chronic form of paracoccidioidomycosis. At 30 days post-infection, the animals were treated with Nano-D-AMB [6 mg/kg of encapsulated D-AMB, intraperitoneally (ip), interval of 72 h] or D-AMB (2 mg/kg, ip, interval of 24 h). Drug efficacy was investigated by the fungal burden recovery from tissues. Toxicity was assessed by renal and hepatic biochemical parameters, physical appearance of the animals and haematological investigation. The control groups used were non-infected and the infected mice mock treated with PBS. RESULTS: Nano-D-AMB presented results comparable to free D-AMB, with a marked antifungal efficacy. The Nano-D-AMB-treated group presented lower loss of body weight and absence of stress sign (piloerection and hypotrichosis) observed after D-AMB treatment. No renal [blood urea nitrogen (BUN), creatinine] or hepatic (pyruvic and oxalacetic glutamic transaminases) biochemical abnormalities were found. The micronucleus assay showed no significant differences in both the micronucleus frequency and percentage of polychromatic erythrocytes for Nano-D-AMB, indicating the absence of genotoxicity and cytotoxic effects. CONCLUSIONS: The D-AMB-coated PLGA-DMSA nanoparticle showed antifungal efficacy, fewer undesirable effects and a favourable extended dosing interval. Nano-D-AMB comprises an AMB formulation able to lessen the number of drug administrations. Further studies would elucidate whether Nano-D-AMB would be useful to treat systemic fungal infections such as paracoccidioidomycosis, candidiasis, aspergillosis and cryptococcosis.

Effect of succimer on growth of preschool children with moderate blood lead levels.

Growth deficits associated with lead exposure might be ameliorated by chelation. We examined the effect of succimer on growth in 780 children 12-33 months old who had blood lead levels of 20-44 microg/dL and were randomized to receive up to three 26-day courses of succimer or placebo in a multicenter, double-blind trial. The difference in changes in weight and height between succimer and placebo groups at 1-34 months was calculated by fitting cubic splines. The difference in height change in children on succimer compared with placebo was -0.27 cm [95% confidence interval (95% CI), -0.42 to -0.11] from baseline to 9 months, when 99% of children had completed treatment, and -0.43 cm (95% CI, -0.77 to -0.09) during 34 months of follow-up. Similar differences in weight gain were not statistically significant. Although succimer lowers blood lead in moderately lead-poisoned children, it does not have a beneficial effect on growth and may have an adverse effect.

Effect of meso-2,3-dimercaptosuccinic acid on urinary lead excretion in exposed men.

The efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) was evaluated in workers occupationally exposed to lead (Pb; blood level >50 microg/dL). Ten men were given 600 mg of DMSA per orem daily, for five days. Pb concentrations of whole blood and urine were determined throughout therapy. Hematology analyses, blood chemistry, and urinalysis were obtained at the start of the study, at the end of the DMSA treatment, and at 72 hours after the administration of the final dose. DMSA therapy had no influence on hepatic, hematologic, or renal functions and was effective in decreasing the concentration of blood Pb in all the subjects without adverse drug reactions.