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Christopher S Brazel - One of the best experts on this subject based on the ideXlab platform.
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t1 and t2 relaxivities of Succimer coated mfe23 o4 m mn2 fe2 and co2 inverse spinel ferrites for potential use as phase contrast agents in medical mri
Journal of Magnetism and Magnetic Materials, 2009Co-Authors: Donghyun Kim, Huadong Zeng, Christopher S BrazelAbstract:Abstract Superparamagnetic MFe 2 3+ O 4 (M=Mn 2+ , Fe 2+ and Co 2+ ) inverse spinel ferrite (ISF) nanoparticles with narrow size distribution having average diameters of 6–8 nm were synthesized by a diol reduction of organic metals and the surface was modified to be hydrophilic by coating with Succimer. Magnetic resonance imaging (MRI) contrast enhancement by dipolar coupling defined interactions between the synthesized ISFs and protons in the bulk water was investigated with initial susceptibility, magnetization and anisotropy of the Succimer-coated ISFs. The relaxivity ratios, r 2 / r 1 , for MnFe 2 O 4 , Fe 3 O 4 and CoFe 2 O 4 were measured to be 12.2, 23.1 and 62.3, respectively, which demonstrate the potential usefulness of these magnetic nanoparticles as T 2 contrast agents for MRI.
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T1 and T2 relaxivities of Succimer-coated MFe23+O4 (M=Mn2+, Fe2+ and Co2+) inverse spinel ferrites for potential use as phase-contrast agents in medical MRI
Journal of Magnetism and Magnetic Materials, 2009Co-Authors: Donghyun Kim, Huadong Zeng, Christopher S BrazelAbstract:Abstract Superparamagnetic MFe 2 3+ O 4 (M=Mn 2+ , Fe 2+ and Co 2+ ) inverse spinel ferrite (ISF) nanoparticles with narrow size distribution having average diameters of 6–8 nm were synthesized by a diol reduction of organic metals and the surface was modified to be hydrophilic by coating with Succimer. Magnetic resonance imaging (MRI) contrast enhancement by dipolar coupling defined interactions between the synthesized ISFs and protons in the bulk water was investigated with initial susceptibility, magnetization and anisotropy of the Succimer-coated ISFs. The relaxivity ratios, r 2 / r 1 , for MnFe 2 O 4 , Fe 3 O 4 and CoFe 2 O 4 were measured to be 12.2, 23.1 and 62.3, respectively, which demonstrate the potential usefulness of these magnetic nanoparticles as T 2 contrast agents for MRI.
Walter J. Rogan - One of the best experts on this subject based on the ideXlab platform.
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The impact of Succimer chelation on blood cadmium in children with background exposures: a randomized trial.
The Journal of pediatrics, 2013Co-Authors: Yang Cao, Aimin Chen, Matteo Bottai, Kathleen L. Caldwell, Walter J. RoganAbstract:Succimer lowers blood lead concentrations in children, and the structure of Succimer chelates of lead and cadmium are similar. Using blood samples from a randomized trial of Succimer for lead poisoning, however, we found that Succimer did not lower blood cadmium in children with background exposure.
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Research | Children’s Health The Effect of Chelation on Blood Pressure in Lead-Exposed Children: A Randomized Study
2013Co-Authors: Aimin Chen, Mikhail Salganik, George G. Rhoads, Bo Cai, Walter J. RoganAbstract:Studies in children suggest a weak association between blood lead concentration and blood pressure. To understand this better, we tested the strength of the association in children with elevated blood lead concentrations and whether Succimer chelation changed blood pressure as it did blood lead. In a randomized clinical trial of 780 children with blood lead concentrations of 20–44 µg/dL at 12–33 months of age, we compared the systolic and diastolic blood pressure in the Succimer-treated group and placebo group for up to 5 years of follow-up. We also analyzed the relation of blood lead to blood pressure. Children in the Succimer group had lower blood lead concentrations for 9–10 months during and after treatment, but their blood pressure did not differ from those in the placebo group during this period. During 1–5 years of follow-up, children in the Succimer group had systolic blood pressure 1.09 (95 % confidence interval, 0.27–1.90) mmHg higher than did untreated children in a model with repeated measurements, but the difference in diastolic blood pressure was not statistically significant. No association between blood lead and blood pressure was found. Overall, there is no association between blood lead and blood pressure in these children with moderately high lead exposure, nor does chelation with Succimer change blood pressure. Key words: blood pressure, chelation, child, lead, Succimer. Environ Health Perspect 114:579–583 (2006). doi:10.1289/ehp.8634 available vi
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Efficacy of Succimer chelation of mercury at background exposures in toddlers: a randomized trial.
The Journal of pediatrics, 2011Co-Authors: Yang Cao, Aimin Chen, Kathleen L. Caldwell, Robert L. Jones, Jerilynn Radcliffe, Kim N. Dietrich, Shyamal D. Peddada, Walter J. RoganAbstract:Objective To examine whether Succimer, a mercaptan compound known to reduce blood lead concentration in children, reduces blood mercury concentration. Study design We used samples from a randomized clinical trial of Succimer chelation for lead-exposed children. We measured mercury levels in pre-treatment samples from 767 children. We also measured mercury levels in blood samples drawn 1 week after treatment began (n = 768) and in a 20% random sample of the children who received the maximum 3 courses of treatment (n = 67). A bootstrap-based isotonic regression method was used to compare the trend with time in the difference between the adjusted mean mercury concentrations in the Succimer group and that in the placebo group. Results The adjusted mean organic mercury concentration in the Succimer group relative to the placebo group fell from 99% at baseline to 82% after 3 courses of treatment ( P for trend=.048), but this resulted from the prevention of the age-related increase in the Succimer group. Conclusion Succimer chelation for low level organic mercury exposure in children has limited efficacy.
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Does background postnatal methyl mercury exposure in toddlers affect cognition and behavior
Neurotoxicology, 2009Co-Authors: Yang Cao, Aimin Chen, Kathleen L. Caldwell, Robert L. Jones, Jerilynn Radcliffe, Kim N. Dietrich, Walter J. RoganAbstract:Because the toxicological effects of mercury (Hg) are more serious in the developing central nervous system of children than adults, there are growing concerns about prenatal and early childhood Hg exposure. This study examined postnatal methylmercury (MeHg) exposure and cognition and behavior in 780 children enrolled in the Treatment of Lead (Pb)-exposed Children clinical trial (TLC) with 396 children allocated to the Succimer and 384 to the placebo groups. Mercury exposure was determined from analyses of blood drawn 1 week before randomization and 1 week after treatment began when Succimer had its maximal effect on blood Pb (PbB). The baseline MeHg concentrations were 0.54 microg/L and 0.52 microg/L and post-treatment concentrations were 0.51 microg/L and 0.48 microg/L for placebo and Succimer groups, respectively. Because the baseline characteristics in the two groups were balanced and because Succimer had little effect on MeHg concentration and no effect on the cognitive or behavioral test scores, the groups were combined in the analysis of MeHg and neurodevelopment. The children's IQ and neurobehavioral performance were tested at age 2, 5 and 7 years. We saw weak, non-significant but consistently positive associations between blood MeHg and IQ test scores in stratified, spline regression and generalized linear model data analyses. The behavioral problem scores were constant or decreased slightly with increasing MeHg concentration. Additional adjustment for PbB levels in multivariable models did not alter the conclusion for MeHg and IQ scores, but did confirm that concurrent PbB was strongly associated with IQ and behavior in TLC children. The effects of MeHg on neurodevelopmental indices did not substantially differ by PbB strata. We conclude that at the present background postnatal MeHg exposure levels of US children, adverse effects on children's IQ and behavior are not detectable.
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The effect of chelation on blood pressure in lead-exposed children: a randomized study.
Environmental health perspectives, 2006Co-Authors: Aimin Chen, George G. Rhoads, Bo Cai, M.p. Salganik, Walter J. RoganAbstract:Studies in children suggest a weak association between blood lead concentration and blood pressure. To understand this better, we tested the strength of the association in children with elevated blood lead concentrations and whether Succimer chelation changed blood pressure as it did blood lead. In a randomized clinical trial of 780 children with blood lead concentrations of 20–44 μg/dL at 12–33 months of age, we compared the systolic and diastolic blood pressure in the Succimer-treated group and placebo group for up to 5 years of follow-up. We also analyzed the relation of blood lead to blood pressure. Children in the Succimer group had lower blood lead concentrations for 9–10 months during and after treatment, but their blood pressure did not differ from those in the placebo group during this period. During 1–5 years of follow-up, children in the Succimer group had systolic blood pressure 1.09 (95% confidence interval, 0.27–1.90) mmHg higher than did untreated children in a model with repeated measurements, but the difference in diastolic blood pressure was not statistically significant. No association between blood lead and blood pressure was found. Overall, there is no association between blood lead and blood pressure in these children with moderately high lead exposure, nor does chelation with Succimer change blood pressure.
Donald R. Smith - One of the best experts on this subject based on the ideXlab platform.
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The scientific basis for chelation: animal studies and lead chelation.
Journal of medical toxicology : official journal of the American College of Medical Toxicology, 2013Co-Authors: Donald R. Smith, Barbara J. StruppAbstract: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.
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Articles Oral Succimer Decreases the Gastrointestinal Absorption of Lead in Juvenile Monkeys
2013Co-Authors: John D. Cremin, Nellie K. Laughlin, Melissa L. Luck, Donald R. SmithAbstract:Although Succimer (Chemet, meso-2,3-dimercaptosuccinic acid, DMSA) is considered to be a safe and effective chelating agent for the treatment of lead poisoning in humans, there is concern that it may increase the gastrointestinal (GI) absorption and retention of Pb from exposures suffered concurrent with treatment. This concern is justified because the availability of Pb-safe housing during outpatient treatment with oral Succimer is limited. We used a juvenile nonhuman primate model of moderate childhood Pb intoxication and a sensitive double stable Pb isotope tracer methodology to determine whether oral Succimer chelation affects the GI absorption and wholebody retention of Pb. Infant rhesus monkeys (n = 17) were exposed to Pb daily for 1 year postpartum to reach and maintain a target blood lead (BPb) level of 35–40 µg/dL. Animals were administered Succimer (n = 9) or vehicle (n = 8) over two successive 19 day Succimer treatment regimens beginning at 53 and 65 weeks of age. The present study was conducted over the second chelation regimen only. Animals received a single intravenous (iv) dose of stable 204 Pb tracer (5 µg, 24.5 nmol) followed by a single oral dose of stable 206 Pb tracer (72.6 µg, 352 nmol) immediately before chelation, in order to specifically evaluate GI Pb absorption and whole-body Pb retention with treatment. We collected complete urine and fecal samples over the first 5 days an
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Succimer chelation normalizes reactivity to reward omission and errors in lead-exposed rats
Neurotoxicology and teratology, 2006Co-Authors: Stéphane A. Beaudin, Donald R. Smith, Diane E. Stangle, David A. Levitsky, Barbara J. StruppAbstract:Abstract This study evaluated the efficacy of a 3-week course of Succimer treatment to alleviate behavioral deficits in rats exposed to lead (Pb) for the first 4 weeks of life. A 3 × 2 factorial design was used: three levels of lead exposure (No Pb, Moderate, and High Pb) and two levels of chelation (Succimer or vehicle). Behavioral testing was conducted following chelation therapy, from 2 to 9 months of age; this report presents the results of two of the administered tasks: (1) a conditional olfactory discrimination task (baseline task), and (2) a conditional olfactory discrimination task with periodic reward omission on some correct trials (RO task). In the RO task, the performance disruption produced by committing an error on the previous trial was significantly greater for both unchelated lead-exposed groups than for controls. The High Pb rats were also more sensitive to reward omission than controls, providing converging evidence for impaired regulation of arousal or emotion. Importantly, Succimer treatment was effective in normalizing the heightened reactivity of the lead-exposed animals to both errors and reward omission. In addition, non-lead-exposed rats that were treated with Succimer tended to be more affected by a prior error than controls in their latency to respond on post-error trials. In sum, these findings provide new evidence that Succimer chelation can significantly lessen the lasting neurobehavioral dysfunction produced by early lead exposure, but also suggest that there may be risks of administering the drug to individuals without elevated blood lead levels.
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Succimer chelation improves learning, attention, and arousal regulation in lead-exposed rats but produces lasting cognitive impairment in the absence of lead exposure.
Environmental health perspectives, 2006Co-Authors: Diane E. Stangle, Donald R. Smith, Stéphane A. Beaudin, David A. Levitsky, Myla Strawderman, Barbara J. StruppAbstract:Chelating agents have been used to treat lead-exposed children since the 1950s, but the metric for gauging therapeutic efficacy has changed over time. When these drugs were first implemented for clinical use, it was common for poor, inner-city children to be brought to emergency rooms with signs of Pb-induced encephalopathy. The chelating agents used at that time, CaNa2EDTA (calcium disodium versenate) and BAL (dimer-caprol), are credited with dramatically reducing the mortality rate in such children, estimated to be 66% before the advent of chelating agents (Foreman 1961) relative to 1–2% thereafter (Chisholm 1968). Fortunately, blood Pb levels of U.S. children have declined dramatically over the past 20 years [Centers for Disease Control and Prevention (CDC) 2005], and Pb-induced encephalopathy is rare. However, as evidence mounts that even slightly elevated Pb levels are associated with impaired cognitive functioning in children (e.g., Canfield et al. 2003), there appears to be growing pressure for clinicians to prescribe chelation therapy at very low exposure levels. The CDC (2005) and the American Academy of Pediatrics (2005) recommend chelation for blood Pb levels > 45 μg/dL, but surveillance data from 10 states indicate chelation therapy occurring at blood Pb levels well below this recommended level (CDC, unpublished data). There are surprisingly little data upon which to gauge the benefits and possible risks of chelation therapy in children with subclinical Pb poisoning. With respect to Succimer (dimercaptosuccinic acid), the most widely administered chelating agent, only one clinical trial conducted to date has included cognitive measures. This study did not detect a benefit of chelation, relative to placebo, in children with blood Pb levels between 20 and 44 μg/dL (Dietrich et al. 2004; Rogan et al. 2001). However, several studies using animal models reported that Succimer normalized various behaviors altered by Pb exposure, including forced-swim immobility (Stewart et al. 1996), activity level, and habituation rate (Gong and Evans 1997). Using a rodent model of early childhood Pb exposure, the present study was designed to a) determine whether treatment with a Succimer regimen shown to produce significant reductions in blood and brain Pb levels (Cremin et al. 1999; Smith et al. 1998, 2000b; Stangle et al. 2004) also lessens the lasting cognitive and affective changes that are produced by a short period of early developmental Pb exposure; and b) determine whether Succimer produces lasting cognitive and/or affective impairment when administered in the absence of Pb exposure. Findings from the latter group are needed to gauge the safety of prolonged regimens when treating Pb-exposed children, as well as the safety of the drug for treating autistic children, as currently advocated on numerous websites by physicians, autism parent groups, and organizations such as the American College for Advancement in Medicine. In this article, we describe a subset of the administered tests—namely, a series of visual attention tests designed to tap several functions reported to be affected in Pb-exposed children, including sustained and selective attention, inhibitory control, learning/associative ability, and regulation of arousal or emotion. Two of these tasks, the sustained attention and selective attention tasks, are similar to ones commonly used to assess attention in human subjects, such as the Continuous Performance Test and Leonard’s 5-choice Serial Reaction Task (reviewed by Robbins 2002).
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Reductions in blood lead overestimate reductions in brain lead following repeated Succimer regimens in a rodent model of childhood lead exposure.
Environmental health perspectives, 2004Co-Authors: Diane E. Stangle, Donald R. Smith, Myla Strawderman, Mareike Kuypers, Barbara J. StruppAbstract:Although many studies have demonstrated the efficacy of Succimer chelation in reducing blood and brain lead levels, the relative efficacy of the drug in the two tissues is less well understood. This issue is important because blood lead levels after chelation are used clinically to estimate reductions in the brain, the most critical organ in considering lead-induced neurotoxicity. The present study was designed to further investigate this issue, using multiple chelation regimens. Long-Evans rats were exposed to one of three lead exposure regimens from birth until postnatal day 40, followed by treatment with Succimer (one or two 3-week regimens) or vehicle. The results indicated that one Succimer regimen was significantly superior to vehicle treatment in lowering lead levels in both blood and brain across the entire 8-week follow-up period. Similarly, a second Succimer regimen offered significant additional benefit relative to one regimen for both blood and brain across the 4-week follow-up period. However, several findings revealed that Succimer-induced reductions in brain lead lagged behind reductions in blood lead and were generally smaller in magnitude. Furthermore, a rebound was detected in blood, but not brain, lead levels after both Succimer regimens. Given the results of this study, we urge caution in using blood lead as a surrogate for brain lead levels, particularly during and immediately after chelation treatment when reductions in blood lead levels overestimate reductions in brain lead levels. The present results suggest that, in clinical use, Succimer treatment may need to extend beyond the point at which blood lead levels have dropped to an "acceptable" target value in order to effectively reduce brain lead levels and minimize neurotoxicity.
Gideon Koren - One of the best experts on this subject based on the ideXlab platform.
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Toxicokinetics of Mercury Elimination by Succimer in Twin Toddlers
Pediatric Drugs, 2005Co-Authors: Ibrahim Fayez, Michelle Paiva, Margaret Thompson, Zulfukarali Verjee, Gideon KorenAbstract:We describe the toxicokinetics of mercury in two twin toddlers poisoned by an East Indian remedy for teething. Succimer (dimercaprosuccinic acid, DMSA) decreased the plasma elimination half-life of mercury by 3-fold in the patient with high exposure; a more modest effect was observed in the other twin. Succimer is a chelation agent used in the treatment of heavy metal intoxication. A water-soluble agent, it increases the urinary excretion of lead and mercury. The drug is rapidly but variably absorbed through the gastrointestinal tract, with peak levels occurring at 1–2 hours. After its absorption, peak mercury excretion through the urine occurs within 2–4 hours. In the poisoned twin sisters, Succimer administration led to a mercury plasma elimination half-life of 6 weeks. Although Succimer has been used in mercury poisoning in adults and children, the toxicokinetics of mercury have not previously been characterized in either age group. We believe this is the first such description. More studies on the toxicokinetics and dynamics of mercury chelation with Succimer in young children are needed to ensure the optimal use of the drug in this population.
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Toxicokinetics of Mercury Elimination by Succimer in Twin Toddlers
Paediatric drugs, 2005Co-Authors: Ibrahim Fayez, Michelle Paiva, Margaret Thompson, Zulfukarali Verjee, Gideon KorenAbstract:We describe the toxicokinetics of mercury in two twin toddlers poisoned by an East Indian remedy for teething. Succimer (dimercaprosuccinic acid, DMSA) decreased the plasma elimination half-life of mercury by 3-fold in the patient with high exposure; a more modest effect was observed in the other twin.
Donghyun Kim - One of the best experts on this subject based on the ideXlab platform.
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t1 and t2 relaxivities of Succimer coated mfe23 o4 m mn2 fe2 and co2 inverse spinel ferrites for potential use as phase contrast agents in medical mri
Journal of Magnetism and Magnetic Materials, 2009Co-Authors: Donghyun Kim, Huadong Zeng, Christopher S BrazelAbstract:Abstract Superparamagnetic MFe 2 3+ O 4 (M=Mn 2+ , Fe 2+ and Co 2+ ) inverse spinel ferrite (ISF) nanoparticles with narrow size distribution having average diameters of 6–8 nm were synthesized by a diol reduction of organic metals and the surface was modified to be hydrophilic by coating with Succimer. Magnetic resonance imaging (MRI) contrast enhancement by dipolar coupling defined interactions between the synthesized ISFs and protons in the bulk water was investigated with initial susceptibility, magnetization and anisotropy of the Succimer-coated ISFs. The relaxivity ratios, r 2 / r 1 , for MnFe 2 O 4 , Fe 3 O 4 and CoFe 2 O 4 were measured to be 12.2, 23.1 and 62.3, respectively, which demonstrate the potential usefulness of these magnetic nanoparticles as T 2 contrast agents for MRI.
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T1 and T2 relaxivities of Succimer-coated MFe23+O4 (M=Mn2+, Fe2+ and Co2+) inverse spinel ferrites for potential use as phase-contrast agents in medical MRI
Journal of Magnetism and Magnetic Materials, 2009Co-Authors: Donghyun Kim, Huadong Zeng, Christopher S BrazelAbstract:Abstract Superparamagnetic MFe 2 3+ O 4 (M=Mn 2+ , Fe 2+ and Co 2+ ) inverse spinel ferrite (ISF) nanoparticles with narrow size distribution having average diameters of 6–8 nm were synthesized by a diol reduction of organic metals and the surface was modified to be hydrophilic by coating with Succimer. Magnetic resonance imaging (MRI) contrast enhancement by dipolar coupling defined interactions between the synthesized ISFs and protons in the bulk water was investigated with initial susceptibility, magnetization and anisotropy of the Succimer-coated ISFs. The relaxivity ratios, r 2 / r 1 , for MnFe 2 O 4 , Fe 3 O 4 and CoFe 2 O 4 were measured to be 12.2, 23.1 and 62.3, respectively, which demonstrate the potential usefulness of these magnetic nanoparticles as T 2 contrast agents for MRI.
