-
Biomolecules Nov 2022The chelating thiol dimercaptosuccinate (DMSA) and the traditional agent D-penicillamine (PSH) are effective in enhancing the urinary excretion of copper (Cu) and lead... (Review)
Review
The chelating thiol dimercaptosuccinate (DMSA) and the traditional agent D-penicillamine (PSH) are effective in enhancing the urinary excretion of copper (Cu) and lead (Pb) in poisoned individuals. However, DMSA, PSH, EDTA (ethylenediamine tetraacetate), and deferoxamine (DFOA) are water-soluble agents with limited access to the central nervous system (CNS). Strategies for mobilization of metals such as manganese (Mn), iron (Fe), and Cu from brain deposits may require the combined use of two agents: one water-soluble agent to remove circulating metal into urine, in addition to an adjuvant shuttler to facilitate the brain-to-blood mobilization. The present review discusses the chemical basis of metal chelation and the ligand exchange of metal ions. To obtain increased excretion of Mn, Cu, and Fe, early experiences showed promising results for CaEDTA, PSH, and DFOA, respectively. Recent experiments have indicated that p-amino salicylate (PAS) plus CaEDTA may be a useful combination to remove Mn from binding sites in CNS, while the deferasirox-DFOA and the tetrathiomolybdate-DMSA combinations may be preferable to promote mobilization of Fe and Cu, respectively, from the CNS. Further research is requested to explore benefits of chelator combinations.
Topics: Humans; Manganese; Copper; Iron; Chelating Agents; Ions; Metals; Neurotoxicity Syndromes; Succimer; Water
PubMed: 36421727
DOI: 10.3390/biom12111713 -
Journal of Medical Toxicology :... Dec 2013Chelation for heavy metal intoxication began more than 70 years ago with the development of British anti-lewisite (BAL; dimercaprol) in wartime Britain as a potential... (Review)
Review
Chelation for heavy metal intoxication began more than 70 years ago with the development of British anti-lewisite (BAL; dimercaprol) in wartime Britain as a potential antidote the arsenical warfare agent lewisite (dichloro[2-chlorovinyl]arsine). DMPS (unithiol) and DMSA (succimer), dithiol water-soluble analogs of BAL, were developed in the Soviet Union and China in the late 1950s. These three agents have remained the mainstay of chelation treatment of arsenic and mercury intoxication for more than half a century. Animal experiments and in some instances human data indicate that the dithiol chelators enhance arsenic and mercury excretion. Controlled animal experiments support a therapeutic role for these chelators in the prompt treatment of acute poisoning by arsenic and inorganic mercury salts. Treatment should be initiated as rapidly as possible (within minutes to a few hours), as efficacy declines or disappears as the time interval between metal exposure and onset of chelation increases. DMPS and DMSA, which have a higher therapeutic index than BAL and do not redistribute arsenic or mercury to the brain, offer advantages in clinical practice. Although chelation following chronic exposure to inorganic arsenic and inorganic mercury may accelerate metal excretion and diminish metal burden in some organs, potential therapeutic efficacy in terms of decreased morbidity and mortality is largely unestablished in cases of chronic metal intoxication.
Topics: Animals; Arsenic Poisoning; Arsenicals; Chelating Agents; Chelation Therapy; Humans; Mercury Poisoning; Succimer; Treatment Outcome; Unithiol
PubMed: 24178900
DOI: 10.1007/s13181-013-0344-5 -
The Journal of Pediatrics Mar 2011To examine whether succimer, a mercaptan compound known to reduce blood lead concentration in children, reduces blood mercury concentration. (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Chelating Agents; Child, Preschool; Double-Blind Method; Female; Humans; Infant; Intention to Treat Analysis; Limit of Detection; Linear Models; Male; Mercury; Mercury Poisoning; Succimer; United States
PubMed: 20889164
DOI: 10.1016/j.jpeds.2010.08.036 -
Journal of Applied Clinical Medical... Jun 2023Given the potential risk of motion artifacts, acquisition time reduction is desirable in pediatric Tc-dimercaptosuccinic acid (DMSA) scintigraphy. The aim of this study...
PURPOSE
Given the potential risk of motion artifacts, acquisition time reduction is desirable in pediatric Tc-dimercaptosuccinic acid (DMSA) scintigraphy. The aim of this study was to evaluate the performance of predicted full-acquisition-time images from short-acquisition-time pediatric Tc-DMSA planar images with only 1/5th acquisition time using deep learning in terms of image quality and quantitative renal uptake measurement accuracy.
METHODS
One hundred and fifty-five cases that underwent pediatric Tc-DMSA planar imaging as dynamic data for 10 min were retrospectively collected for the development of three deep learning models (DnCNN, Win5RB, and ResUnet), and the generation of full-time images from short-time images. We used the normalized mean squared error (NMSE), peak signal-to-noise ratio (PSNR), and structural similarity index metrics (SSIM) to evaluate the accuracy of the predicted full-time images. In addition, the renal uptake of Tc-DMSA was calculated, and the difference in renal uptake from the reference full-time images was assessed using scatter plots with Pearson correlation and Bland-Altman plots.
RESULTS
The predicted full-time images from the deep learning models showed a significant improvement in image quality compared to the short-time images with respect to the reference full-time images. In particular, the predicted full-time images obtained by ResUnet showed the lowest NMSE (0.4 [0.4-0.5] %) and the highest PSNR (55.4 [54.7-56.1] dB) and SSIM (0.997 [0.995-0.997]). For renal uptake, an extremely high correlation was achieved in all short-time and three predicted full-time images (R > 0.999 for all). The Bland-Altman plots showed the lowest bias (-0.10) of renal uptake in ResUnet, while short-time images showed the lowest variance (95% confidence interval: -0.14, 0.45) of renal uptake.
CONCLUSIONS
Our proposed method is capable of producing images that are comparable to the original full-acquisition-time images, allowing for a reduction of acquisition time/injected dose in pediatric Tc-DMSA planar imaging.
Topics: Child; Humans; Technetium Tc 99m Dimercaptosuccinic Acid; Retrospective Studies; Deep Learning; Radionuclide Imaging; Kidney; Radiopharmaceuticals
PubMed: 37021382
DOI: 10.1002/acm2.13978 -
Journal of Nuclear Medicine : Official... Nov 2017
Topics: Radionuclide Imaging; Technetium Tc 99m Dimercaptosuccinic Acid
PubMed: 29093113
DOI: No ID Found -
Pediatrics and Neonatology Jul 2022For risk stratification and individualized treatment for children with urinary tract infection (UTI), they must be assessed for the presence of acute pyelonephritis...
BACKGROUND
For risk stratification and individualized treatment for children with urinary tract infection (UTI), they must be assessed for the presence of acute pyelonephritis (APN). Our study aimed to combine variables that can predict APN and establish a nomogram for clinical use.
METHODS
In total, 111 children <5 years old hospitalized at Kaohsiung Veterans General Hospital for UTI were classified into APN and simple UTI groups based on a technetium-99 m dimercaptosuccinic acid scan. Their demographic, laboratory test, and renal and urinary bladder sonography (RUBS) data were compared.
RESULTS
Fever peak of >39 °C, serum procalcitonin (PCT) ≥ 0.52 pg/mL, C-reactive protein (CRP) ≥ 2.86 mg/dL, and abnormal RUBS findings were independent variables for predicting APN in children. The nomogram established using the aforementioned variables had an area under the receiver operating characteristic curve (AUC) of 0.89, which was higher than those of PCT and CRP alone (0.776 and 0.774, respectively).
CONCLUSION
The combination of four variables had the highest power in predicting APN in children with UTI. The established nomogram is practical for clinical use.
Topics: Acute Disease; Biomarkers; C-Reactive Protein; Child, Preschool; Humans; Infant; Infant, Newborn; Nomograms; Procalcitonin; Pyelonephritis; Radionuclide Imaging; Radiopharmaceuticals; Risk Assessment; Technetium Tc 99m Dimercaptosuccinic Acid; Urinary Tract Infections
PubMed: 35568634
DOI: 10.1016/j.pedneo.2022.03.006 -
Experimental Biology and Medicine... Jul 2008Mercury is a major toxic metal ranked top in the Toxic Substances List. Cinnabar, which contains mercury sulfide, has been used in Chinese traditional medicines for... (Comparative Study)
Comparative Study Review
Mercury is a major toxic metal ranked top in the Toxic Substances List. Cinnabar, which contains mercury sulfide, has been used in Chinese traditional medicines for thousands of years as an ingredient in various remedies, and 40 cinnabar-containing traditional medicines are still used today. Little is known about toxicology profiles or toxicokinetics of cinnabar and cinnabar-containing traditional medicines, and the high mercury content in these Chinese medicines raises justifiably escalations of public concern. This minireview, by searching the available database of cinnabar and by comparing cinnabar with common mercurials, discusses differences in their bioavailability, disposition, and toxicity. The analysis showed that cinnabar is insoluble and poorly absorbed from the gastrointestinal tract. Absorbed mercury from cinnabar is mainly accumulated in the kidneys, resembling the disposition pattern of inorganic mercury. Heating cinnabar results in release of mercury vapor, which in turn can produce toxicity similar to inhalation of these vapors. The doses of cinnabar required to produce neurotoxicity are 1000 times higher than methyl mercury. Following long-term use of cinnabar, renal dysfunction may occur. Dimercaprol and succimer are effective chelation therapies for general mercury intoxication including cinnabar. Pharmacological studies of cinnabar suggest sedative and hypnotic effects, but the therapeutic basis of cinnabar is still not clear. In summary, cinnabar is chemically inert with a relatively low toxic potential when taken orally. In risk assessment, cinnabar is less toxic than many other forms of mercury, but the rationale for its inclusion in traditional Chinese medicines remains to be fully justified.
Topics: Dose-Response Relationship, Drug; Humans; Medicine, Chinese Traditional; Mercuric Chloride; Mercury; Mercury Compounds; Methylmercury Compounds
PubMed: 18445765
DOI: 10.3181/0712-MR-336 -
International Journal of Environmental... Jul 2010Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form... (Review)
Review
Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents) or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications.
Topics: Antioxidants; Chelating Agents; Drug Therapy, Combination; Heavy Metal Poisoning; Humans; Oxidative Stress; Poisoning
PubMed: 20717537
DOI: 10.3390/ijerph7072745 -
Journal of Nuclear Medicine Technology Jun 2020The phenomenon of adsorption of several Tc-radiopharmaceuticals onto disposable syringes is common knowledge and can reach a level of up to 50%, with the result being...
The phenomenon of adsorption of several Tc-radiopharmaceuticals onto disposable syringes is common knowledge and can reach a level of up to 50%, with the result being inadequate dosing. The resulting underdosing has a substantial influence on the quality of imaging, especially in pediatric patients. Therefore, we aimed to establish a standardized in vitro assessment to investigate the adsorption of several Tc-radiopharmaceuticals on various brands of syringes. The Tc-radiopharmaceuticals were prepared according to manufacturer instructions. For the assessment, the disposable syringes ( = 3) were filled to one third of capacity with the Tc preparation and incubated for 30 min at room temperature. The syringes were emptied into evacuated vials, and the radioactivity of the syringes was measured before and after they were emptied. Furthermore, the dilution effect of Tc preparations was studied. We used 2 different brands of syringes and systematically examined Tc-pertechnetate, Tc-butedronate, Tc-oxidronate, Tc-medronate, Tc-tetrofosmin, Tc-sestamibi, Tc(V)-dimercaptosuccinic acid, and Tc-succimer. Additionally, Tc-succimer was retested with 5 brands of syringes. Tc-pertechnetate, Tc-phosphonates, and Tc(V)-dimercaptosuccinic acid showed no significant adsorption. The measured radioactive retention of 2%-5% was equivalent to the determined dead volume. Using Tc-tetrofosmin, we found a slight but significant adsorption of 4%-7%. The Tc-sestamibi preparation showed a nonsignificant retention of 3%-5%. However, when the Tc-sestamibi was diluted 1:10 with saline, the adsorption rate increased to 9%-13%. Tc-succimer displayed different adsorption levels depending on the brand of syringe and the preparation technique. The adsorption of Tc-succimer, prepared from kits according to the instructions, did not exceed 15%. The 1:10 saline dilution of a Tc-succimer kit preparation, as well as an in-house preparation, demonstrated a radioactive syringe adsorption rate of more than 30%. The results revealed the significance of syringe adsorption of radiopharmaceuticals in the prevention of underdosing. Therefore, a quality assurance assessment is recommended before the introduction of new brands of plastic syringes or routine application of diluted or in-house radiopharmaceuticals.
Topics: Adsorption; Artifacts; Plastics; Radiation Dosage; Radiopharmaceuticals; Syringes; Technetium
PubMed: 31811065
DOI: 10.2967/jnmt.119.235432 -
Nanomedicine (London, England) May 2021Superparamagnetic cubic iron oxide nanoparticles (IONPs) were synthesized and functionalized with meso-2,3-dimercaptosuccinic acid (DMSA) as a potential agent for...
Superparamagnetic cubic iron oxide nanoparticles (IONPs) were synthesized and functionalized with meso-2,3-dimercaptosuccinic acid (DMSA) as a potential agent for cancer treatment. Monodisperse cubic IONPs with a high value of saturation magnetization were synthesized by thermal decomposition method and functionalized with DMSA via ligand exchange reaction, and their cytotoxic effects on HeLa cells were investigated. DMSA functionalized cubic IONPs with an edge length of 24.5 ± 1.9 nm had a specific absorption rate value of 197.4 W/g (15.95 kA/m and 488 kHz) and showed slight cytotoxicity on HeLa cells when incubated with 3.3 × 10, 6.6 × 10 and 9.9 × 10 NP/mL for 24, 48 and 72 h. To the best of our knowledge, this is the first study to investigate both the cytotoxic effects of DMSA-coated cubic IONPs on HeLa cells and hyperthermia performance of these nanoparticles.
Topics: Ferric Compounds; HeLa Cells; Humans; Ligands; Magnetic Iron Oxide Nanoparticles; Magnetite Nanoparticles; Nanoparticles; Succimer
PubMed: 34015971
DOI: 10.2217/nnm-2020-0467