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Biomolecules Feb 2020High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of... (Review)
Review
High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered.
Topics: Animals; Antidotes; Arsenic; Arsenic Poisoning; Arsenicals; Chelating Agents; Dimercaprol; Drinking Water; Humans; Models, Molecular; Occupational Exposure; Oxidative Stress; Succimer; Unithiol; Water Pollutants, Chemical
PubMed: 32033229
DOI: 10.3390/biom10020235 -
Pediatric Nephrology (Berlin, Germany) Sep 2022Urinary tract infection (UTI) is one of the most common bacterial infections in childhood and is associated with long-term complications. We aimed to assess the effect... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Urinary tract infection (UTI) is one of the most common bacterial infections in childhood and is associated with long-term complications. We aimed to assess the effect of adjuvant dexamethasone treatment on reducing kidney scarring after acute pyelonephritis (APN) in children.
METHODS
Multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial (RCT) where children from 1 month to 14 years of age with proven APN were randomly assigned to receive a 3-day course of either an intravenous corticosteroid (dexamethasone 0.30 mg per kg/day) twice daily or placebo. The late technetium 99 m-dimercaptosuric acid scintigraphy (> 6 months after acute episode) was performed to assess kidney scar persistence. Kidney scarring risk factors (vesicoureteral reflux, kidney congenital anomalies, or urinary tract dilatation) were also assessed.
RESULTS
Ninety-one participants completed the follow-up and were finally included (dexamethasone n = 49 and placebo n = 42). Both groups had similar baseline characteristics. Twenty participants showed persistent kidney scarring after > 6 months of follow-up without differences in incidence between groups (22% and 21% in the dexamethasone and placebo groups, p = 0.907). Renal damage severity in the early DMSA (β = 0.648, p = 0.023) and procalcitonin values (β = 0.065 p = 0.027) significantly modulated scar development. Vesicoureteral reflux grade showed a trend towards significance (β = 0.545, p = 0.054), but dexamethasone treatment showed no effect.
CONCLUSION
Dexamethasone showed no effect on reducing the risk of scar formation in children with APN. Hence, there is no evidence for an adjuvant corticosteroid treatment recommendation in children with APN. However, the study was limited by not achieving the predicted sample size and the expected scar formation.
TRIAL REGISTRATION
Clinicaltrials.gov, NCT02034851. Registered in January 14, 2014. "A higher resolution version of the Graphical abstract is available as Supplementary information."
Topics: Acute Disease; Child; Cicatrix; Dexamethasone; Glomerulonephritis; Humans; Infant; Kidney; Pyelonephritis; Technetium Tc 99m Dimercaptosuccinic Acid; Urinary Tract Infections; Vesico-Ureteral Reflux
PubMed: 35041042
DOI: 10.1007/s00467-021-05398-w -
Journal of Medical Toxicology :... Dec 2013This presentation summarizes several of the rodent and non-human studies that we have conducted to help inform the efficacy and clinical utility of succimer... (Review)
Review
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.
Topics: Animals; Behavior, Animal; Body Burden; Brain; Chelating Agents; Chelation Therapy; Disease Models, Animal; Humans; Lead; Lead Poisoning; Risk Assessment; Risk Factors; Succimer; Time Factors; Treatment Outcome
PubMed: 24113857
DOI: 10.1007/s13181-013-0339-2 -
Anales Del Sistema Sanitario de Navarra 2003Metals are amongst the oldest toxic substances known to man. In today's industrialized world the sources of exposure to metals are ubiquitous both in the field of work... (Review)
Review
Metals are amongst the oldest toxic substances known to man. In today's industrialized world the sources of exposure to metals are ubiquitous both in the field of work and from polluted water, foodstuffs and the environment. Their toxicity is characterized by the metallic element in question, but this is modified by the type of compound, whether organic or inorganic, and its characteristics of hydrosolubility and liposolubility, which determines its toxicokinetics and thus the possibilities of it reaching its targets. The biomolecules most affected by metals are the proteins with enzymatic activity, which is why their pathology is multisystemic. The principal systems affected are the gastrointestinal, central and peripheral neurological, haematic and renal. Some metallic compounds are carcinogenic. Metals's treatment is conditioned by their chemical reactivity. They can be deactivated and eliminated by the administering of chelating agents that produce complex molecules, which are non-toxic and can be excreted. The principal chelating agents are: BAL (British Anti-Lewisite or dimercaprol) DMPS (2,3-Dimercapto-1-propanesulfonic Acid) and DMSA (meso-2,3-Dimercaptosuccinic or Succimer), EDTA, Penicilamine (b,b-dimethylcysteine) and Deferoxamine. Toxicokinetic characteristics, mechanism of action, clinical picture and treatment of some of the most relevant metals and metalloids: lead, mercury and arsenic, are considered.
Topics: Acute Disease; Arsenic Poisoning; Humans; Lead Poisoning; Mercury Poisoning; Metals
PubMed: 12813482
DOI: No ID Found -
Journal of Nuclear Medicine Technology Mar 2015It has been widely reported that (99m)Tc-succimer adsorbs to plastic syringes significantly (up to 50%), often resulting in a lower administered dose than intended or...
UNLABELLED
It has been widely reported that (99m)Tc-succimer adsorbs to plastic syringes significantly (up to 50%), often resulting in a lower administered dose than intended or inaccurate dosing. This adsorption rate is especially problematic in the pediatric population. To improve (99m)Tc-succimer dosing, we compared the adsorption of (99m)Tc-succimer with 2 types of syringes: silicone-coated syringes with nonlatex rubber on the plunger and inert nonreactive syringes with no silicone coating and no rubber on the plunger.
METHODS
(99m)Tc-succimer kits were compounded according to the manufacturer's instructions. (99m)Tc-succimer doses (37-185 MBq) were drawn into 3-mL (silicone-coated or inert nonreactive) syringes in a 1-mL volume. Thirty min, 1 h, 2 h, and 4 h later, the syringes were assayed in a dose calibrator and assayed again after being emptied and rinsed with saline. In addition, we examined the data collected from 129 (99m)Tc-succimer doses administered in a pediatric department, in which 52 were dispensed in silicone-coated syringes and 77 were dispensed in inert nonreactive syringes. The doses were assayed immediately before and after injection. The syringes were flushed with normal saline.
RESULTS
The labeling efficiency of the (99m)Tc-succimer kits was more than 95%. Residual activity left in the inert nonreactive syringes was 0.73% (SD, ±0.18%), which was significantly lower than the activity left in the silicone-coated syringes, 20.9% (SD, ±5.6%; P < 0.0001). The extent of adsorption did not change significantly between 30 min and 4 h of incubation. The clinical data showed that the residual activity was 30.6% (SD, ±12.5%) from doses dispensed in silicone-coated syringes and 6.38% (SD, ±2.95%) from doses dispensed in inert nonreactive syringes (P < 0.001).
CONCLUSION
The inert nonreactive syringes had significantly less residual of (99m)Tc-succimer than silicone-based syringes, making it possible to accurately administer calculated doses of (99m)Tc-succimer to pediatric patients.
Topics: Adsorption; Child; Humans; Radiochemistry; Rubber; Silicones; Syringes; Technetium Tc 99m Dimercaptosuccinic Acid; Time Factors
PubMed: 25537761
DOI: 10.2967/jnmt.114.147983 -
Daru : Journal of Faculty of Pharmacy,... Dec 2021Lead Poisoning is a major health problem in Iran. We aimed to compare efficacy of a standard regimen (Succimer) with that of a low-priced combination of D-penicillamine... (Comparative Study)
Comparative Study
PURPOSE
Lead Poisoning is a major health problem in Iran. We aimed to compare efficacy of a standard regimen (Succimer) with that of a low-priced combination of D-penicillamine and Garlic in outpatients with lead poisoning.
METHODS
In this retrospective cross-sectional study, year-long clinical files of outpatients with lead poisoning in two referral toxicology clinics in Mashhad, Iran were reviewed. A total of 79 patients (all men), received either Succimer or a combination of D-penicillamen plus garlic (DPN + Gar), for 19 and 30 days, respectively. Clinical and laboratory data, including blood lead level (BLL), were analyzed and treatment expanses were compared between the two regimens.
RESULTS
Of 79 male patients, 42 were treated by DPN + Gar and 37 received Succimer. Mean BLL of DPN + Gar group before treatment (965.73 ± 62.54 µg/L) was higher than that of the Succimer group (827.59 ± 24.41) (p < 0.001). After treatment, BLL in both groups significantly reduced to 365.52 ± 27.61 µg/L and 337.44 ± 26.34 µg/L, respectively (p < 0.001). The price of a 19-day treatment with Succimer was approximately 28.6 times higher than a one-month course of treatment with garlic plus DPN. None of the treatments caused serious side effects in the patients.
CONCLUSION
Combination therapy with DPN + Gar is as effective as Succimer in Pb poisoning, while treatment with Succimer is significantly more expensive.
Topics: Adult; Antidotes; Cost-Benefit Analysis; Cross-Sectional Studies; Drug Therapy, Combination; Garlic; Humans; Iran; Lead; Lead Poisoning; Male; Penicillamine; Phytochemicals; Retrospective Studies; Succimer; Treatment Outcome
PubMed: 34313939
DOI: 10.1007/s40199-021-00407-7 -
Journal of Medical Toxicology :... Oct 2021
Topics: Chelating Agents; Humans; Lead Poisoning; Succimer
PubMed: 34031804
DOI: 10.1007/s13181-021-00848-1 -
Journal of Medical Toxicology :... Dec 2013These proceedings will review the role of chelation in five metals-aluminum, cadmium, chromium, cobalt, and uranium-in order to illustrate various chelation concepts.... (Review)
Review
These proceedings will review the role of chelation in five metals-aluminum, cadmium, chromium, cobalt, and uranium-in order to illustrate various chelation concepts. The process of "chelation" can often be oversimplified, leading to incorrect assumptions and risking patient harm. For chelation to be effective, two critical assumptions must be fulfilled: the presumed "metal toxicity" must correlate with a given body or a particular compartment burden, and reducing this compartmental or the body burden (through chelation) attenuates toxicity. Fulfilling these assumptions requires an established dose-response relationship, a validated, reproducible means of toxicity assessment (clinical, biochemical, or radiographical), and an appropriate assessment mechanisms of body or compartment burden. While a metal might "technically" be capable of chelation (and readily demonstrable in urine or feces), this is an insufficient endpoint. Clinical relevance must be affirmed. Deferoxamine is an accepted chelator for appropriately documented aluminum toxicity. There is a very minimal treatment window in order to address chelation in cadmium toxicity. In acute toxicity, while no definitive chelation benefit is described, succimer (DMSA), diethylenetriaminepentaacetate (DTPA), and potentially ethylenediaminetetraacetic acid (EDTA) have been considered. In chronic toxicity, chelation is unsupported. There is little evidence to suggest that currently available chromium chelators are efficacious. Similarly, scant human evidence exists with which to provide recommendation for cobalt chelation. DTPA has been recommended for cobalt radionuclide chelation, although DMSA, EDTA, and N-acetylcysteine have also been suggested. DTPA is unsupported for uranium chelation. Sodium bicarbonate is currently recommended, although animal evidence is conflicting.
Topics: Aluminum; Animals; Biomarkers; Body Burden; Chelating Agents; Chelation Therapy; Heavy Metal Poisoning; Humans; Metals, Heavy; Poisoning; Predictive Value of Tests; Treatment Outcome
PubMed: 24113858
DOI: 10.1007/s13181-013-0343-6