succimer and Mercury-Poisoning

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.

Topics: Administration, Oral; Animals; Chelating Agents; Chelation Therapy; Copper; Drug Therapy, Combination; Evidence-Based Medicine; Free Radical Scavengers; Humans; Infusions, Parenteral; Lead Poisoning; Mercury Poisoning; Penicillamine; Succimer; Trientine; Unithiol

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

Within the body of this review, we provide updates on the mechanisms involved in the renal handling mercury (Hg) and the vicinal dithiol complexing/chelating agents, 2,3-bis(sulfanyl)propane-1-sulfonate (known formerly as 2,3-dimercaptopropane-1-sulfonate, DMPS) and meso-2,3-bis(sulfanyl)succinate (known formerly as meso-2,3-dimercaptosuccinate, DMSA), with a focus on the therapeutic effects of these dithiols following exposure to different chemical forms of Hg. We begin by reviewing briefly some of the chemical properties of Hg, with an emphasis on the high bonding affinity between mercuric ions and reduced sulfur atoms, principally those contained in protein and nonprotein thiols. A discussion is provided on the current body of knowledge pertaining to the handling of various mercuric species within the kidneys, focusing on the primary cellular targets that take up and are affected adversely by these species of Hg, namely, proximal tubular epithelial cells. Subsequently, we provide a brief update on the current knowledge on the handling of DMPS and DMSA in the kidneys. In particular, parallels are drawn between the mechanisms participating in the uptake of various thiol S-conjugates of Hg in proximal tubular cells and mechanisms by which DMPS and DMSA gain entry into these target epithelial cells. Finally, we discuss factors that permit DMPS and DMSA to bind intracellular mercuric ions and mechanisms transporting DMPS and DMSA S-conjugates of Hg out of proximal tubular epithelial cells into the luminal compartment of the nephron, and promoting urinary excretion.

Topics: Animals; Chelating Agents; Dicarboxylic Acid Transporters; gamma-Glutamyltransferase; Humans; Kidney; Mercury; Mercury Poisoning; Organic Anion Transporters; Succimer; Sulfhydryl Compounds; Unithiol

Mercury exposure is the second-most common cause of toxic metal poisoning. Public health concern over mercury exposure, due to contamination of fish with methylmercury and the elemental mercury content of dental amalgams, has long been a topic of political and medical debate. Although the toxicology of mercury is complex, there is evidence for antioxidant protection in the prevention of neurological and renal damage caused by mercury toxicity. Alpha-lipoic acid, a coenzyme of pyruvate and alpha-ketoglutarate dehydrogenase, has been used in Germany as an antioxidant and approved treatment for diabetic polyneuropathy for 40 years. Research has attempted to identify the role of antioxidants, glutathione and alpha-lipoic acid specifically, in both mitigation of heavy metal toxicity and direct chelation of heavy metals. This review of the literature will assess the role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity.

Topics: Animals; Antioxidants; Blood-Brain Barrier; Chelating Agents; Food Contamination; Glutathione; Humans; Kidney; Mercury; Mercury Poisoning; Succimer; Thioctic Acid; Tissue Distribution; Unithiol

Topics: Acute Disease; Chelating Agents; Chelation Therapy; Child; Diagnosis, Differential; Dimercaprol; Environmental Exposure; Humans; Mercury; Mercury Poisoning; Penicillamine; Succimer; United States

Heavy metals are, unfortunately, present in the air, water, and food supply. Cases of severe acute lead, mercury, arsenic, and cadmium poisoning are rare; however, when they do occur an effective, non-toxic treatment is essential. In addition, chronic, low-level exposure to lead in the soil and in residues of lead-based paint, to mercury in the atmosphere, in dental amalgams and in seafood, and to cadmium and arsenic in the environment and in cigarette smoke is much more common than acute exposure. Meso-2,3-dimercaptosuccinic acid (DMSA) is a sulfhydryl-containing, water-soluble, non-toxic, orally-administered metal chelator which has been in use as an antidote to heavy metal toxicity since the 1950s. More recent clinical use and research substantiates this compound s efficacy and safety, and establishes it as the premier metal chelation compound, based on oral dosing, urinary excretion, and its safety characteristics compared to other chelating substances.

Topics: Arsenic Poisoning; Cadmium Poisoning; Chelating Agents; Heavy Metal Poisoning; Humans; Lead Poisoning; Mercury Poisoning; Poisoning; Succimer

Topics: Dental Amalgam; Humans; Lead Poisoning; Mercury Poisoning; Succimer; Unithiol; Volatilization

Topics: Animals; Arsenic Poisoning; Chelating Agents; Chelation Therapy; Dimercaprol; Edetic Acid; Humans; Lead Poisoning; Mercury Poisoning; Poisoning; Succimer

Topics: Animals; Antidotes; Arsenic Poisoning; Biotransformation; Cadmium Poisoning; Dimercaprol; Forecasting; Humans; Kinetics; Lead Poisoning; Mercury Poisoning; Metals; Solubility; Succimer; Sulfhydryl Compounds; Unithiol

To examine whether succimer, a mercaptan compound known to reduce blood lead concentration in children, reduces blood mercury concentration.. 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.. 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.. 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

The present investigation was performed to determine the effect of 14-day oral administration of meso-2.3-dimercaptosuccinic acid (DMSA) on the urinary mercury excretion and the potential reduction of blood and plasma mercury concentrations, and also to relate these effects to possible decrease of symptoms, allegedly associated with amalgam fillings. Twenty subjects, relating their symptoms to mercury from amalgam fillings, received 20 mg/kg DMSA or placebo for 14 days. Their symptoms and mood states were recorded during the study and at a check-up 3 months later. Interpretation was based on intra-individual differences. DMSA-treatment resulted in an average increase in urinary mercury excretion by 65% and a decrease in blood mercury levels of 0.04 microgram/L/day. At the check-up after 3 months, urinary mercury excretion had returned to the pre-treatment level. No treatment effect of DMSA was apparent on subjective symptoms and mood state. One statistically significant treatment effect was noted-a decrease in fatigue-inertia in the DMSA-group-but there was no demonstrable correlation with increased urinary excretion or decreased blood concentration of mercury. Three subjects showed hypersensitive reactions, probably DMSA-specific, at the end of the treatment period. This placebo-controlled study provides no scientific support for diagnostic or therapeutic administration of DMSA for symptoms allegedly associated with chronic mercury exposition from dental amalgam fillings.

Topics: Administration, Oral; Adult; Affect; Dental Amalgam; Dose-Response Relationship, Drug; Double-Blind Method; Fatigue; Female; Humans; Male; Mercury; Mercury Poisoning; Middle Aged; Personality Inventory; Regression Analysis; Succimer

Mercury is a naturally occurring heavy metal that finds wide application in industrial and household settings. It exists in three chemical forms which include elemental (Hg0 ), inorganic mercurous (Hg+) or mercuric (Hg++) salts, and organic compounds. All forms are highly toxic, particularly to the nervous, gastrointestinal, and renal systems. Common circumstances of exposure include recreational substance use, suicide or homicide attempts, occupational hazards, traditional medicines, and endemic food ingestions as witnessed in the public health disasters in Minamata Bay, Japan and in Iraq. Poisoning can result in death or long-term disabilities. Clinical manifestations vary with chemical form, dose, rate, and route of exposure.. To summarize the incidence of mercury poisoning encountered at an Indian Poison Center and use three cases to highlight the marked variations observed in clinical manifestations and long-term outcomes among poisoned patients based on differences in chemical forms and routes of exposure to mercury.. A structured retrospective review of the enquiry-database of the Poison Information Center and medical records of patients admitted between August 2019 and August 2021 in a tertiary care referral center was performed. All patients with reported exposure to mercury were identified. We analyzed clinical data and laboratory investigations which included heavy metal (arsenic, mercury, and lead) estimation in whole blood and urine samples. Additionally, selected patients were screened for serum voltage-gated potassium ion channels (VGKC)- contactin-associated protein-like 2 (CASPR2) antibodies. Three cases with a classical presentation were selected for detailed case description.. Twenty-two cases were identified between August 2019 and August 2021. Twenty (91%) were acute exposures while two (9%) were chronic. Of these, three representative cases have been discussed in detail. Case 1 is a 3.5-year-old girl who was ought to the emergency department with suspected elemental-mercury ingestion after biting a thermometer. Clinical examination was unremarkable. Chest and abdominal radiography revealed radiodense material in the stomach. Subsequent serial radiographs documented distal intestinal transit of the radiodense material. The child remained asymptomatic. This case exemplifies the largely nontoxic nature of elemental mercury ingestion as it is usually not absorbed from the gastrointestinal tract. Case 2 is a 27-year-old lady who presented with multiple linear nodules over both upper limbs after receiving a red intravenous injection for anemia. Imaging revealed metallic-density deposits in viscera and bones. Nodular biopsy was suggestive of mercury granulomas. A 24-hour urine mercury levels were elevated. She was advised chelation therapy with oral dimercaptosuccinic acid (DMSA). Case 3 is a 22-year-old lady who presented with acrodynia, neuromyotonia, tremulousness, postural giddiness, tachycardia, and hypertension for 2 months, associated with intractable, diffuse burning pain over the buttocks and both lower limbs, 1 month after completing a 3-week course of traditional medications for polycystic ovarian syndrome. A 24-hour urine normetanephrine levels and mercury levels were markedly elevated. Serum anti-VGKC antibodies were present. She was treated with glucocorticoids and oral DMSA with a favorable clinical response.. The clinical manifestations of mercury toxicity are highly variable depending on the source, form, and route of mercury exposure and are related to its toxicokinetics.

Topics: Adult; Child; Child, Preschool; Female; Humans; Mercury; Mercury Poisoning; Poison Control Centers; Poisons; Succimer; Young Adult

Mercury exposure is common and can be toxic, especially in children. Children are often drawn to elemental mercury because of its density, color, and proclivity to form beads.. We present data on 49 children with mercury intoxication (MI) and 60 children with mercury exposure from Turkey.. The most common source of mercury was broken thermometer in schools. Inhaling mercury vapor was the most common route of exposure. The median exposure time was 6 (6-16) hours in the MI group, and the time to 1st symptoms was 10 (0-24) hours. In the MI group, the median blood mercury level was 21 μg/L (13-32.3), the median spot urine mercury level was 40 μg/L (7.66-78), and the median 24-hour urine mercury level was 25.8 μg/L (11-64). The most common symptoms in patients with MI were malaise, muscle pain, muscle cramps, abdominal pain, nausea, headache, and decreased appetite. The patients were treated with n-acetyl cysteine, 2,3-dimercaptopropane sulfonic acid, D-penicillamine, and meso 2,3-dimercaptosuccinic acid. A positive correlation was found between exposure time and urinary mercury level in the MI group (r = 0.793, P < 0.001). A positive moderate correlation was found between exposure time and blood level in the mercury exposure group (r = 0.535, P < 0.00). The neurological and systemic examinations of patients were all normal at the 1st follow-up visit 1 month after discharge.. Diagnosis, removal of the exposure source, and use of chelation therapy can result in complete resolution of the signs and symptoms of MI.

Topics: Acetylcysteine; Child; Humans; Mercury; Mercury Poisoning; Penicillamine; Prognosis; Retrospective Studies; Succimer; Sulfonic Acids

Topics: Adult; Air Pollution, Indoor; Antidotes; Female; Gastric Lavage; Health Personnel; Humans; Mercury; Mercury Poisoning; Occupational Exposure; Succimer

Topics: Adolescent; Autoimmune Diseases; Chelating Agents; Diagnosis, Differential; Environmental Exposure; Female; Humans; Immunologic Factors; Mercury Poisoning; Rituximab; Succimer

Mercury poisoning is an uncommon diagnosis in the United States, but it is a differential diagnosis that physicians should consider because it can lead to potentially fatal complications if untreated. Due to the nonspecific presentation of mercury poisoning, which includes symptoms such as fever, nausea, vomiting, and abdominal pain, misdiagnosis may occur unless a proper history is taken.. In the present case, a white female patient was misdiagnosed repeatedly with a viral illness and sent home from the local hospital. The patient presented with a diffuse full-body rash, fever, myalgias, headache, peripheral neuropathy, oral paresthesias, and tender cervical posterior lymphadenopathy. After obtaining a thorough history, it was discovered that the patient and her family were exposed to mercury through a spill of elemental mercury in their home. Blood mercury levels in the patient were 170 ng/mL. The patient was treated with a course of dimercaprol. Her symptoms improved and she was discharged on hospital day 5. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Ultimately, mercury poisoning is a treatable condition, but if exposure continues and the patient is not treated, it may lead to complications such as severe pneumonitis, renal tubular necrosis, and neurological dysfunction. In some instances, neurological symptoms may persist even if the source of exposure is removed. For these reasons, recognition and prompt treatment after a suspected exposure is important.

Topics: Adult; Chelating Agents; Chelation Therapy; Emergency Service, Hospital; Environmental Exposure; Exanthema; Female; Fever; Humans; Mercury; Mercury Poisoning; Myalgia; Succimer

A 17-month-old child presented with hypertension, fussiness, constipation, and arthralgia due to mercury toxicity from a skin-lightening cosmetic used by her mother and grandmother. Blood mercury level was 26 mcg/L and urine level was 243 mcg/g creatinine. She was chelated with succimer. The home was contaminated and needed remediation.

Topics: Chelating Agents; Environmental Restoration and Remediation; Female; Humans; Infant; Mercury; Mercury Poisoning; Skin Lightening Preparations; Succimer

Young children are highly vulnerable to elemental mercury toxicity, and elementary mercury exposure in young children in China unfortunately occurs regularly because of the wide use of fluorescent lamps, glass thermometers, and other mercury-contained items. This study aimed to summarize such recent cases in a referral clinic and to make recommendations for postexposure treatment and prevention of future exposure.. Patients were evaluated between January 2007 and December 2009 in environmental health facilities throughout China and were referred to our clinic. A total of 6 children younger than 4 years with significant elemental mercury exposure were included in this case series analysis. The total mercury content in blood and hair (fetal hair if necessary) and average 24-hour urine mercury concentrations were analyzed. Meso-2,3-dimercaptosuccinic acid or surgery was prescribed for the patient if necessary.. Young children were found to be exposed in 3 ways as follows: prenatal exposure through maternal occupational contact in compact fluorescent-lamp factories (2 cases), broken thermometers (3 cases), and other causes of accidental inhalation of mercury vapor during the embryonic and lactation periods (1 case). For 3 cases caused by broken thermometers, x-ray images helped to identify the position of mercury residues. Local excision was used to remove mercury from the floor of the mouth in 1 case. One child was prescribed oral meso-2,3-dimercaptosuccinic acid, and a good response was received.. Substitution of mercury-in-glass thermometers and vigilance to prevent women of childbearing age from occupational mercury exposure were suggested. Treatment selection should vary according to patient situations.

Topics: Antidotes; Child, Preschool; China; Female; Humans; Infant; Male; Maternal Exposure; Mercury Poisoning; Occupational Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Succimer; Thermometers

We present a patient aged 54 years with early onset of dementia, epilepsy and peripheral polyneuropathy. A mercury intoxication was diagnosed in 2010, chelation therapy with 2,3-dimercaptopropane-1-sulfonate had failed. A source of exposure could not be identified. MRI showed unspecific hyperintense brain lesions in 2015. She was referred for diagnosis and treatment. Neuropsychological testing indicated severe memory loss and nerve conduction speed measurements showed chronic neurogenically changed potentials. Mercury levels in blood and urine and neuron-specific enolase (NSE) were elevated. A detailed patient history revealed a daily application of mercury-containing skin lightening creams for 6 years. Treatment with 2,3-dimercaptosuccinic acid (DMSA) was started, blood mercury levels were falling during treatment. She was discharged with DMSA prescriptions. A renewed MRI revealed unchanged brain lesions. Blood and urine mercury levels and NSE were falling. Memory function had improved qualitatively and quantitatively.

Topics: Chelating Agents; Dementia; Epilepsy; Female; Humans; Mercury; Mercury Poisoning; Middle Aged; Polyneuropathies; Skin Cream; Succimer

Topics: Adolescent; Chelating Agents; Diagnosis, Differential; Exanthema; Female; Humans; Hypertension; Mercury; Mercury Poisoning; Skin Lightening Preparations; Succimer; Tachycardia

Topics: Animals; Bird Diseases; Chelating Agents; Eagles; Edetic Acid; Fatal Outcome; Female; Fractures, Comminuted; Mercury Poisoning; Radiography; Sarcocystis; Sarcocystosis; Seizures; Succimer; Thoracic Vertebrae

Constraints arise naturally in many scientific experiments/studies such as in, epidemiology, biology, toxicology, etc. and often researchers ignore such information when analyzing their data and use standard methods such as the analysis of variance (ANOVA). Such methods may not only result in a loss of power and efficiency in costs of experimentation but also may result poor interpretation of the data. In this paper we discuss constrained statistical inference in the context of linear mixed effects models that arise naturally in many applications, such as in repeated measurements designs, familial studies and others. We introduce a novel methodology that is broadly applicable for a variety of constraints on the parameters. Since in many applications sample sizes are small and/or the data are not necessarily normally distributed and furthermore error variances need not be homoscedastic (i.e. heterogeneity in the data) we use an empirical best linear unbiased predictor (EBLUP) type residual based bootstrap methodology for deriving critical values of the proposed test. Our simulation studies suggest that the proposed procedure maintains the desired nominal Type I error while competing well with other tests in terms of power. We illustrate the proposed methodology by re-analyzing a clinical trial data on blood mercury level. The methodology introduced in this paper can be easily extended to other settings such as nonlinear and generalized regression models.

Topics: Analysis of Variance; Antidotes; Chelating Agents; Computer Simulation; Humans; Linear Models; Mercury; Mercury Poisoning; Research Design; Succimer

On September 16, 2013, the North Carolina Division of Public Health was notified of an elemental (metallic and liquid) mercury spill on a school bus. An elementary student boarded the bus with approximately 1 pound (454 g) of elemental mercury contained in a film canister, which the student had taken from an adult relative who had found it in a neighbor's shed. The canister was handled by several students before the contents spilled on the bus floor. Ten passengers aboard the bus were exposed, including eight students and two staff members. Although elemental mercury is not readily absorbed from skin contact or ingestion, it does vaporize at room temperatures and inhalation of the vapor can be harmful. The bus driver promptly notified school officials. Firefighters and a local hazardous materials team directed decontamination procedures (i.e., changing clothes and washing hands and shoes) for the 10 exposed passengers. The bus was immediately taken out of service and sent for disposal because of its age and the cost of decontamination.

Topics: Adult; Chelation Therapy; Child; Decontamination; Environmental Exposure; Humans; Mercury; Mercury Poisoning; Motor Vehicles; North Carolina; Residence Characteristics; Schools; Succimer; United States; United States Environmental Protection Agency

Mercury is an extremely toxic heavy metal that can devastate central nervous system. We present the case of a 15 year old adolescent with mercury intoxication following 4 days of exposure to elemental mercury at home who was consulted by department of pediatrics with complaints of demonstrated emotional lability, memory impairment, disinhibition, and impulsivity. Olanzapin 2,5 mg/day was initiated. Her neuropsychological performance was evaluated by a neuropsychological test battery at initial examination. Deterioration in neuropsychological functions like interference effect and attention (Stroop Test TBAG form), verbal fluency and switching to other category (Verbal Fluency Test, /(VFT), verbal short term and long term memory and recognition (Auditory Verbal Learning Test, /(AVLT) was detected. In 9 months follow up period her complaints resolved. Initial neuropsychological deficits were also fully recovered at follow up. There was an increase in intelligence scores with increased ability to pay and sustain attention. She had better performance at Stroop Test TBAG form, VFT and AVLT which was similar to her normal peers. In this case report, the clinical aspects of central nervous system involvement in mercury intoxication and protection from potential toxic effects of laboratory materials like mercury at schools were discussed. School administrators should be aware of and parents and students should be given necessary protective information.

Topics: Adolescent; Antidotes; Chelating Agents; Female; Humans; Mercury; Mercury Poisoning; Neuropsychological Tests; Succimer

Topics: Chelating Agents; Child; Female; Humans; Mercury Poisoning; Succimer; Unithiol

Topics: Chelating Agents; Dimercaprol; Edetic Acid; Humans; Male; Mercury Poisoning; Succimer; Suicide; Unithiol

Public awareness of methylmercury in fish has caused patients to seek testing for mercury poisoning. In some patients, the diagnosis of mercury poisoning has been made based on urine mercury excretions following oral dosing of meso-dimercaptosuccinic acid (DMSA), a metal chelator. However, studies comparing urine mercury excretion following DMSA in healthy non-fish eaters with healthy fish eaters could not be located.. To describe urinary mercury excretion before and after DMSA in healthy fish eaters and non-fish eaters, and to determine whether urine mercury excretion after DMSA would rise above baseline levels to a greater extent in fish eaters.. A total of 24 healthy physicians were assigned to 1 of 3 groups based on fish consumption: non-fish eaters; 1 to 2 fish servings per week; and 3 or more servings per week. Blood mercury concentrations and 12-hour urine mercury and creatinine excretions were measured before and after oral ingestion of 30 mg of DMSA per kilogram of body weight.. A total of 24 subjects completed the study, and 2 subsequently were excluded. No difference in baseline urinary mercury excretion was detected between groups. All groups demonstrated an increase in urinary mercury excretion following DMSA, which was higher in fish eaters (P = .04). Multiple linear regression found that the best predictor of a rise in urine mercury excretion following DMSA challenge was the prechelation blood mercury concentration.. In this study of healthy physicians, oral DMSA produced a rise in urine mercury excretion both in non-fish eaters and fish eaters. The increase in chelated mercury excretion was higher in fish eaters. A simple rise in chelated mercury excretion over baseline excretion is not a reliable diagnostic indicator of mercury poisoning.

Topics: Administration, Oral; Adult; Animals; Body Burden; Chelating Agents; Diet; Environmental Exposure; Feeding Behavior; Female; Fishes; Humans; Male; Mercury; Mercury Poisoning; Middle Aged; Seafood; Succimer

Thoughts and moods are the result of biological processes; disordered thoughts and moods may be the result of disordered biological processes. As brain dysfunction can manifest with emotional symptoms or behavioral signs, the etiology of some mental health afflictions and some abnormal conduct is pathophysiological rather than pathopsychological. Various studies confirm that some chemical toxicants which modify brain physiology have the potential to affect mood, cognitive function, and to provoke socially undesirable outcomes. With pervasive concern about myriad chemical agents in the environment and resultant toxicant bioaccumulation, human exposure assessment has become a clinically relevant area of medical investigation. Adverse exposure and toxicant body burden should routinely be explored as an etiological determinant in assorted health afflictions including disordered thinking, moods, and behavior. The impact of toxicant bioaccumulation in a patient with neuropsychiatric symptoms is presented for consideration as an example of the potential benefit of recognizing and implementing exposure assessment.

Topics: Adult; Animals; Chelating Agents; Fatigue; Feeding Behavior; Forensic Psychiatry; Humans; Male; Mental Disorders; Mercury Poisoning; Sleep Initiation and Maintenance Disorders; Succimer; Tuna

A 19-year-old male with an unremarkable medical history presented with his father, who requested an evaluation of a pathology specimen from a reported "lump" under the skin in the middle of the son's lower abdomen. The lump had been excised by a surgeon approximately 3 months prior, per parental request. Upon gross inspection, the specimen appeared to contain small metallic droplets. The patient denied self-injection of any metals, including mercury, despite the results of a 24-hour urine heavy-metal screen (without chelation) that revealed an elevated concentration of mercury (87.6 microg/g creatinine; reference range for nonexposed adults: <4 microg/g creatinine). Confirmatory analysis of the tissue sample included gross and microscopic examination, electron microscopy using secondary and backscattered electron imaging modes, and energy dispersive x-ray spectrum analysis of isolated tissue particles. Grossly, the tissue had small silver spherules suggestive of elemental mercury; these droplets were identified histologically with associated foreign body reaction. Numerous smooth, round-to-oval particles scattered randomly throughout the tissue were identified ultrastructurally, which produced an x-ray energy spectrum corresponding to mercury.. Elemental mercury is liquid at room temperature and may be injected into the body for recreational, psychiatric, and other purposes. Isolated cases of mercury injection following accidents with broken thermometers have been reported, as well as cases of elevated metallothionein concentration following human gingival amalgam tattoos.. In cases of surreptitious injection, histology and ultrastructural evidence may be used to confirm the presence of mercury.

Topics: Abdominal Wall; Adult; Chelating Agents; Connective Tissue; Foreign-Body Reaction; Humans; Male; Mercury; Mercury Poisoning; Succimer; Treatment Outcome

Intravenous injection of mercury has seldom been reported, especially in cases of attempted suicide, and is associated with variable clinical outcomes.. A young woman came to our attention after self-injecting and ingesting mercury drawn from 37 thermometers. The patient suffered lung embolization complicated by adult respiratory distress syndrome (ARDS), toxic dermatitis, anemia, mild hepato-renal impairment, and died after 30 days. Mercury was monitored in biological fluids (blood, plasma, urine, and bronchoalveolar fluid) to study its toxicokinetics and to evaluate dose-effect relationships. Its urinary clearance significantly increased after a chelation challenge test with meso-2,3-dimercaptosuccinic acid (DMSA) (median values of 2.48 and 8.85 before and after the test, respectively, p < 0.05).. Mercury poisoning by intravenous injection is a clinical emergency, potentially leading to death. When injected, the element has a very slow clearance, mainly renal. Our data do not allow any conclusion about the effectiveness of chelation therapy.

Topics: Adult; Chelating Agents; Dose-Response Relationship, Drug; Female; Humans; Injections, Intravenous; Mercury; Mercury Poisoning; Pulmonary Embolism; Respiratory Distress Syndrome; Succimer; Suicide; Thermometers

A 2-year-old girl presented with hypertension, anorexia and vomiting, restlessness, insomnia and acrodynia. Her blood pressure upon arrival was 145/98 mmHg. Ultrasound of the abdomen, CT scan of chest, abdomen and pelvis, and echocardiogram, were normal. Urinary levels of catecholamines were elevated, urine level of mercury was found to be high (33.2 microg/g creatinine), although blood level was normal (>0.5 microg/dl, reference value 0-4 microg/dl). Following a 1-month course of oral treatment with dimercaptosuccinic acid (DMSA) the child's symptoms and signs resolved, and urinary mercury and catecholamines levels normalized. Mercury intoxication should be suspected in a patient with severe hypertension, personality changes and acrodynia. Normal blood levels of mercury do not exclude this diagnosis, and catecholamine levels may serve as a surrogate marker for confirmation of the diagnosis and to evaluate response to treatment.

Topics: Acrodynia; Antidotes; Biomarkers; Catecholamines; Chelating Agents; Child, Preschool; Female; Humans; Hypertension; Mercury; Mercury Poisoning; Succimer; Treatment Outcome

Pure inorganic heavy metal ingestions for suicidal intent are a rare occurrence. Most case reports on this subject focus on the serious neurological, hepatic, or renal side effects. We describe two cases of significant heavy metal poisonings (arsenic trioxide and mercuric chloride) that were successfully managed with aggressive decontamination and combined chelation therapy. Both chemicals were obtained in pure powder form through the Internet.

Topics: Adult; Arsenic Poisoning; Arsenic Trioxide; Arsenicals; Chelation Therapy; Decontamination; Dimercaprol; Drug Therapy, Combination; Humans; Male; Mercuric Chloride; Mercury Poisoning; Oxides; Polyethylene Glycols; Solvents; Succimer; Suicide, Attempted; Therapeutic Irrigation

We report the case of an 81-year-old woman in whom clinical signs and features of electromyographic activity patterns were consistent with amyotrophic lateral sclerosis (ALS). Increased blood level and massive urinary excretion of mercury proved mercury intoxication. Despite a chelation treatment with Meso 2-3 dimercaptosuccininc acid (DMSA), she died after 17 months. The pathophysiology of sporadic ALS remains unclear. However, the role of environmental factors has been suggested. Among some environmental factors, exposure to heavy metals has been considered and ALS cases consecutive to occupational intoxication and accidental injection of mercury have been reported. Although no autopsy was performed, we discuss the role of mercury intoxication in the occurrence of ALS in our case, considering the results of experimental studies on the toxicity of mercury for motor neuron.

Topics: Activities of Daily Living; Aged, 80 and over; Chelating Agents; Chronic Disease; Disease Progression; Fatal Outcome; Female; Humans; Mercury; Mercury Poisoning; Motor Neuron Disease; Motor Neurons; Neurologic Examination; Succimer

There is a broad array of mercury species to which humans may be exposed. While exposure to methylmercury through fish consumption is widely recognized, the public is less aware of the sources and potential toxicity of inorganic forms of mercury. Some oral and laboratory thermometers, barometers, small batteries, thermostats, gas pressure regulators, light switches, dental amalgam fillings, cosmetic products, medications, cultural/religious practices, and gold mining all represent potential sources of exposure to inorganic forms of mercury. The route of exposure, the extent of absorption, the pharmacokinetics, and the effects all vary with the specific form of mercury and the magnitude and duration of exposure. If exposure is suspected, a number of tissue analyses can be conducted to confirm exposure or to determine whether an exposure might reasonably be expected to be biologically significant. By contrast with determination of exposure to methylmercury, for which hair and blood are credible indicators, urine is the preferred biological medium for the determination of exposure to inorganic mercury, including elemental mercury, with blood normally being of value only if exposure is ongoing. Although treatments are available to help rid the body of mercury in cases of extreme exposure, prevention of exposure will make such treatments unnecessary. Knowing the sources of mercury and avoiding unnecessary exposure are the prudent ways of preventing mercury intoxication. When exposure occurs, it should be kept in mind that not all unwanted exposures will result in adverse health consequences. In all cases, elimination of the source of exposure should be the first priority of public health officials.

Topics: Antidotes; Biomarkers; Environmental Exposure; Environmental Pollutants; Humans; Mercury; Mercury Poisoning; Risk Factors; Succimer; Suicide

A 43-year-old man presented to hospital with pneumonia but only after discharge from hospital did he admit to deliberate prior inhalation of mercury. His pulmonary involvement appeared to resolve almost completely with antibiotics and supportive care. Nevertheless, persisting elevated urinary excretion of mercury required two courses of chelation therapy. No serious systemic sequelae were observed.

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Cefuroxime; Chelating Agents; Chelation Therapy; Clarithromycin; Humans; Male; Mercury Poisoning; Pneumonia; Radiography; Self-Injurious Behavior; Succimer; Volatilization

Intravenous injection of elemental mercury (Hg) is rare and considered relatively harmless. Treatment recommendations vary and the effectiveness of chelation therapy is controversial.. A 27-year-old man intravenously injected 1.5 mL of elemental Hg. Within 12 hours he became febrile, tachycardic and dyspneic. Physical examination was unremarkable. X-rays showed scattered radiodense deposits in the lung, heart, intestinal wall, liver and kidney. The serum Hg level on admission was 172 microg/L and peaked on day 6 at 274 microg/L. Cumulative renal elimination during a five day oral treatment period with 2,3-dimercaptopropane-1-sulfonate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) was 8 mg and 3 mg, respectively.. Although urinary excretion could be enhanced during chelation therapy, Hg deposits in organs resulted in negligible elimination of mercury compared to the exposed dose.

Topics: Adult; Chelating Agents; Colon; Heart Ventricles; Humans; Injections, Intravenous; Kidney; Liver; Lung; Male; Mercury; Mercury Poisoning; Radiography; Succimer; Suicide, Attempted; Unithiol

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.

Topics: Antidotes; Female; Half-Life; Humans; Infant; Mercury; Mercury Poisoning; Succimer

Oral chelation tests have been used to try to define mercury toxicity in individuals with dental amalgams, who are suffering from a variety of non-specific symptoms.. Self-reported healthy individuals volunteered to undergo an oral chelation test using dimercaptosuccinic acid (DMSA) at a dose of 30 mg/kg body weight. Urinary mercury : creatinine ratios were measured pre-dose and 3 h post-dose.. Urinary mercury : creatinine ratios were similar to levels previously reported in individuals with symptoms that could have been attributed to mercury toxicity. One volunteer suffered a serious reaction to DMSA.. The oral chelation test using DMSA may lead to misleading diagnostic advice regarding potential mercury toxicity and can be associated with serious side effects.

Topics: Administration, Oral; Adult; Body Weight; Case-Control Studies; Chelating Agents; Creatinine; Dental Amalgam; Healthy People Programs; Humans; Mercury; Mercury Poisoning; Middle Aged; Succimer

Clinical chelation therapy of mercury poisoning generally uses one or both of two drugs--meso-dimercaptosuccinic acid (DMSA) and dimercaptopropanesulfonic acid (DMPS), commercially sold as Chemet and Dimaval, respectively. We have used a combination of mercury L(III)-edge X-ray absorption spectroscopy and density functional theory calculations to investigate the chemistry of interaction of mercuric ions with each of these chelation therapy drugs. We show that neither DMSA nor DMPS forms a true chelate complex with mercuric ions and that these drugs should be considered suboptimal for their clinical task of binding mercuric ions. We discuss the design criteria for a mercuric specific chelator molecule or "custom chelator", which might form the basis for an improved clinical treatment.

Topics: Chelating Agents; Chelation Therapy; Mercury; Mercury Poisoning; Spectrum Analysis; Succimer; Unithiol

Peritoneal exposure to mercury has been rarely reported and long-term consequences of this type of exposure have not been documented. We report the clinical course of a patient who has survived almost eight years with a massive intraperitoneal load of mercury. She has suffered formication, pruritus, fatigue, irritiability, insomnia, alopecia, dizziness, a gait disturbance, loss of balance and multiple falls, abdominal pain, choking, and headaches. Two courses of chelation with dimercaptosuccinic acid using the standard protocol were undertaken, resulting in increased daily excretion, but without demonstrable objective or subjective benefit or lasting effect. She had multiple medical problems before the mercury intoxication, which complicates the attribution of all her problems to mercury intoxication. It is of particular interest that the patient survived and did not suffer any marked cognitive deterioration. She died in 2002 shortly after being diagnosed with lung cancer and declaring that she would fight it. Phasing out of mercury-weighted tubes is recommended.

Topics: Chelating Agents; Creatine; Crohn Disease; Electroencephalography; Fatal Outcome; Female; Humans; Intestinal Obstruction; Intubation, Gastrointestinal; Irritable Mood; Mercury; Mercury Poisoning; Middle Aged; Neurotoxicity Syndromes; Peritoneum; Postoperative Complications; Radiography; Succimer

Deliberate self-injection of metallic mercury into subcutaneous tissue is uncommon. A 41-year-old lady with a history of schizophrenia was admitted to our hospital after deliberate injection of metallic mercury into her right wrist and antecubital fossa. Physical examination was unremarkable except for the injection marks over right antecubital fossa and wrist. The presence of subcutaneous mercury deposits in her right elbow and wrist was confirmed by X-rays and ultrasound scan. Three days later, erythema, swelling, induration and tenderness were seen over the injection sites. At the operation on day 9, mercury streaks were seen within the brachialis muscle belly, surrounded by friable necrotic tissues along the tract. A similar picture was noted in her right wrist. The necrotic tissues and mercury streaks were removed. The patient had been unco-operative and she only received incomplete treatment with dimercaprol and 2,3-dimercaptosuccinic acid. Her total blood mercury level (normal < 50 nmol/L) decreased from 101-151 nmol/L in the first two weeks to 42 nmol/L 3 months later. Her 24-hour urinary mercury excretion (normal < 10 nmol) changed from 55.7-209.5 nmol in the first 7 weeks to 125.4 nmol 3 months later. This case illustrates that soft tissue metallic mercury can produce local necrosis and may allow continuous absorption with persistent elevations in blood and urinary mercury levels. Therefore, early surgical removal of subcutaneous mercury deposits is required to prevent local complications and minimize the risk of systemic absorption and toxicity.

Topics: Adult; Arm; Chelating Agents; Dimercaprol; Female; Humans; Injections, Subcutaneous; Mercury; Mercury Poisoning; Necrosis; Radiography; Self Administration; Subcutaneous Tissue; Succimer; Wrist

Some medical practitioners prescribe GSH and vitamin C alone or in combination with DMPS or DMSA for patients with mercury exposure that is primarily due to the mercury vapor emitted by dental amalgams.. This study tested the hypothesis that GSH, vitamin C, or lipoic acid alone or in combination with DMPS or DMSA would decrease brain mercury.. Young rats were exposed to elemental mercury by individual nose cone, at the rate of 4.0 mg mercury per m3 air for 2 h per day for 7 consecutive days. After a 7-day equilibrium period, DMPS, DMSA, GSH, vitamin C, lipoic acid alone, or in combination was administered for 7 days and the brain and kidneys of the animals removed and analyzed for mercury by cold vapor atomic absorption.. None of these regimens reduced the mercury content of the brain. Although DMPS or DMSA was effective in reducing kidney mercury concentrations, GSH, vitamin C, lipoic acid alone, or in combination were not.. One must conclude that the palliative effect, if any, of GSH, vitamin C, or lipoic acid for treatment of mercury toxicity due to mercury vapor exposure does not involve mercury mobilization from the brain and kidney.

Topics: Administration, Inhalation; Animals; Antioxidants; Ascorbic Acid; Brain; Chelating Agents; Drug Therapy, Combination; Glutathione; Kidney; Male; Mercury Poisoning; Rats; Rats, Sprague-Dawley; Succimer; Thioctic Acid; Unithiol; Volatilization

Most reported cases of inorganic mercury poisoning are from mercuric chloride. We report a case of mercuric oxide (HgO) powder ingestion. A 31-year-old man presented to an emergency department after ingestion of approximately 40 g of HgO. Soon after ingestion, he developed nausea, vomiting, and abdominal cramping. Abdominal radiograph revealed densely radiopaque material in the stomach. Gastrointestinal decontamination was accomplished with activated charcoal and whole-bowel irrigation with polyethylene glycol solution (Golytely) for 24 hours until repeat abdominal radiographs no longer demonstrated the substance in the gastrointestinal tract. He was also chelated with British anti-Lewisite for 5 days, followed by succimer for 10 days. He had markedly elevated urine and blood mercury levels after ingestion, but except for a mildly depressed serum bicarbonate (19 mEq/L), his chemistry results remained normal including blood urea nitrogen and creatinine. He had an uncomplicated hospital course and remained asymptomatic at 6 months postingestion. Despite elevated urine and blood mercury levels after ingestion of HgO, our patient did not develop the end-organ toxicity typical of inorganic mercury poisoning.

Topics: Adult; Charcoal; Chelating Agents; Dimercaprol; Electrolytes; Humans; Intestines; Male; Mercury Poisoning; Polyethylene Glycols; Succimer; Suicide, Attempted; Therapeutic Irrigation

Topics: Adolescent; Adult; Chelating Agents; Chelation Therapy; Child; Child, Preschool; Female; Humans; Male; Mercury; Mercury Poisoning; Middle Aged; Schools; Succimer

Mercury is a complex toxin with clinical manifestations determined by the chemical form, route, dose, and acuity of the exposure. Parenteral injection of elemental mercury remains uncommon.. A 40-year-old male injected 3 mL of elemental mercury intravenously and ingested 3 mL as a suicide attempt. Within 24 hours, he became dyspneic, febrile, tachycardic, and voiced mild gastrointestinal complaints. Chest X-ray revealed scattered pulmonary infiltrates and embolized mercury bilaterally. A ventilation/perfusion scan demonstrated ventilation/ perfusion deficits. Additionally, his renal function declined, as manifest by minor elevations in blood urea nitrogen and creatinine and decreased urine output. Pulmonary therapy, intravenous hydration, and chelation using 2,3-dimercaptoscuccinic acid (DMSA/Succimer) were started. Over the next 36 hours, the patient's pulmonary and renal functions improved. Temperature and heart rate subsequently normalized, and symptoms at discharge were mild exertional dyspnea.. Liquid mercury injected intravenously embolizes to the pulmonary vasculature and perhaps vessels in other organs such as heart and kidney. In-situ oxidation to inorganic mercury, which is directly toxic to a variety of tissues, may help explain the multisystem involvement.. Significant pulmonary dysfunction accompanied by radiographically demonstrated mercury emboli and temporary abnormalities in several organs improved shortly after initiation of chelation. The impact of chelation on long-term outcome of parenteral mercury exposure remains uncharacterized.

Topics: Administration, Oral; Adult; Chelation Therapy; Fluid Therapy; Humans; Injections, Intravenous; Kidney; Lung; Male; Mercury; Mercury Poisoning; Pulmonary Embolism; Pulmonary Ventilation; Radiography, Thoracic; Respiration; Succimer; Suicide, Attempted

Topics: Arsenic Poisoning; Cadmium Poisoning; Chelating Agents; Humans; Lead Poisoning; Mercury Poisoning; Poisoning; Succimer

Sixty consecutive patients who had undergone replacement of dental amalgam fillings and a protocol of nutritional support and heavy metal detoxification using dimercapto-propanyl-sulfate and neural therapy were surveyed. A questionnaire was mailed to the patients and 42 responded, resulting in a response rate of 70%. The reasons for undergoing treatment were many, ranging from a patient's desire to avoid potential health problems in the future to treatment of serious current disease. Although medical diagnoses were made when possible before treatment, this survey studied only the patients' estimations of their most distressing symptoms and their evaluations of response to treatment. The most common complaints were problems with memory and/or concentration; muscle and/or joint pain; anxiety and insomnia; stomach, bowel, and bladder complaints; depression; food or chemical sensitivities; numbness or tingling; and eye symptoms, in descending order of frequency. The most distressing symptoms were headache and backache, fatigue, and memory and concentration problems. Headache and backache responded best to treatment, but all symptoms showed considerable improvement on average. Of the respondents, 78% reported that they were either satisfied or very satisfied with the results of treatment, and 9.5% reported that they were disappointed.

Topics: Chelating Agents; Dental Amalgam; Herbicides; Humans; Inactivation, Metabolic; Mercury Poisoning; Propanil; Succimer; Sulfates

Topics: Cerebellar Diseases; Cerebral Cortex; Chelation Therapy; Chemical Phenomena; Chemistry; Fatal Outcome; Female; Humans; Mercury; Mercury Poisoning; Methylmercury Compounds; Middle Aged; Mutagens; Occupational Exposure; Succimer

Topics: Adrenal Gland Neoplasms; Chelating Agents; Child, Preschool; Diagnosis, Differential; Humans; Hypertension; Male; Mercury Poisoning; Pheochromocytoma; Succimer; Sweating

Topics: Chelating Agents; Environmental Monitoring; Humans; Male; Mercury; Mercury Poisoning; Neuropsychological Tests; Occupational Exposure; Predictive Value of Tests; Succimer

Mercury poisoning is a rare cause of hypertension in children. Urinary excretion sometimes remains low despite severe clinical intoxication.. A 32 month-old girl was admitted with hypertension, tachycardia, apathy, irritability and excessive sweating. Erythromelalgia and neurologic symptoms permitted the diagnosis of acrodynia. Urine mercury remained normal until chelation. Captopril significantly increased urine mercury concentration but failed to improve clinical manifestations. Clinical improvement required infusions of BAL for 5 days then oral dimercaptosuccinic acid for 3 months. Metal vapors originated from the mercury which spilled from a broken thermometer onto the carpet.. Low basal urine mercury could be associated with real mercury poisoning. Small amounts of metal mercury held in a thermometer could produce a high level of mercury vapor leading to intoxication in young children. The binding capacity of metal ions by captopril could be used to increase urine mercury output. Nevertheless, captopril therapy fails to improve acrodynia. Total elimination of mercury requires long-term therapy with BAL or dimercaptosuccinic acid.. An unexpected mode of intoxication and low basal urine mercury are not decisive arguments against mercury poisoning, which is the only cause of acrodynia.

Topics: Administration, Oral; Captopril; Child, Preschool; Dimercaprol; Female; Humans; Hypertension; Injections, Intramuscular; Mercury Poisoning; Succimer

Topics: Animals; Antidotes; Body Burden; Chelating Agents; Dose-Response Relationship, Drug; Female; Injections, Intraperitoneal; Mercury Poisoning; Mercury Radioisotopes; Rats; Succimer; Tissue Distribution

1. We report two cases of acute mercury vapour intoxication in humans. The mercury vapour was released from smelting alloys (gold-mercury amalgam). The alloy was apparently contaminated with an unknown amount of mercury. 2. Within half an hour of the incident, the victims began having moderate headache, nausea, lumbar pain and shortness of breath at rest. The patients were treated with BAL (2,3 dimercaptopropanol), followed by DMSA (2,3 dimercaptosuccinic acid). 3. Serial measurements of mercury metal in plasma and in urine were made for ten days. 4. The results suggest that in spite of the treatment, relatively high concentrations of mercury remain in the plasma for a very long time, and this could be explained by the progressive release of mercury from red blood cells and tissues after oxidation. However, BAL and DMSA did not seem to be the most efficient antidotes. They reduce the plasma inorganic mercury uptake at concentrations of < 50 micrograms I-1.

Topics: Administration, Oral; Adult; Alloys; Dimercaprol; Drug Therapy, Combination; Electrocardiography; Electroencephalography; Erythrocytes; Humans; Male; Mercury; Mercury Poisoning; Metallurgy; Middle Aged; Occupational Diseases; Occupational Exposure; Oxidation-Reduction; Succimer

Sodium dimercaptosuccinate (Na-DMS) ip 1 g.kg-1, dimercaptosuccinic acid (DMSA) ig 1 g.kg-1, DMSA ig 1 g.kg-1 with NaHCO3 or Na-citrate ig 3 g.kg-1 was given to mice, separately. It enhanced the excretion of 210Pb in urine about 3.4, 3.8, 3.6, and 2.3 times vs control, respectively within 24 h. It enhanced the excretion of 203Hg in urine about 2.4, 2.3, 3.3, and 2.7 times, respectively within 24 h. Fecal excretion was not significantly elevated vs control. Tissue radioactivities showed a remarkable decrease in the levels of 210Pb and 203Hg in most organs, but DMSA increase the 210Pb content in kidney. The therapeutic effect of ig DMSA was similar to that of ip sodium dimercaptosuccinate.

Topics: Animals; Lead; Lead Poisoning; Male; Mercury; Mercury Poisoning; Mice; Succimer; Tissue Distribution

Topics: Acetaminophen; Chemical and Drug Induced Liver Injury; Child; Drug Synergism; Female; Humans; Mercury; Mercury Poisoning; Succimer

Monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS) was found to be superior to meso-2,3-dimercaptosuccinic acid (DMSA) in decreasing the body burden of 203Hg in rats under conditions of early treatment. In this experiment Mi-ADMS was used as late treatment for mercury removal. Albino rats aged 6 weeks and 7-day-old sucklings received a single intraperitoneal injection of 203Hg (as nitrate). Two weeks later they were treated with DMSA or Mi-ADMS (0.25 mmole/kg bw) on two consecutive days. The radioactivity in the carcass (whole body after removal of the gastrointestinal tract), liver, kidneys and brain was determined by solid crystal gamma scintillation counting six days after chelation therapy administration (3 weeks after 203Hg application). Both chelators reduced the body burden of mercury compared to controls. The effect of Mi-ADMS was superior to DMSA treatment in older rats for decreasing carcass and kidney retention, and in suckling rats for decreasing carcass, liver, and kidney retention. They were equally effective in decreasing brain retention in older rats and had no effect on brain retention in sucklings. The efficiency of Mi-ADMS in reducing the body burden of mercury was generally higher than the efficiency of the DMSA treatment. Therefore, Mi-ADMS deserves further attention as a late treatment for mercury removal.

Topics: Aging; Animals; Animals, Suckling; Chelation Therapy; Mercury Poisoning; Rats; Rats, Wistar; Succimer; Time Factors

Mercury is an extremely toxic heavy metal that can devastate the central nervous system. The neuropsychological consequences of mercury vapor intoxication have been studied primarily in adults. We present two adolescent half-siblings, ages 13 and 15, who were unintentionally exposed to concentrated mercury vapor for 3 months. Both children participated in neuropsychological evaluations shortly after being diagnosed with mercury toxicity, and again 1 year later. Results from the initial assessments documented functional deficits consistent with diffuse encephalopathy. Upon follow-up, neuropsychological functioning had improved, but deficits remained in visuoperceptual and constructional skills, nonverbal memory, and conceptual abstraction. The deficits persisted despite removal from exposure, return of urinary and blood mercury to acceptable levels, and resolution of neuropsychiatric symptoms. The deficits were similar to, but more severe than, those found in adults suffering from mercury vapor intoxication. The results suggest that the developing brain may be especially vulnerable to mercury vapor toxicity.

Topics: Adolescent; Air Pollution, Indoor; Attention; Brain Damage, Chronic; Female; Follow-Up Studies; Humans; Male; Mercury; Mercury Poisoning; Neuropsychological Tests; Pattern Recognition, Visual; Psychomotor Performance; Substance-Related Disorders; Succimer; Volatilization

Methyl mercury has been reported to be embryotoxic and teratogenic in numerous systems such as fish, birds, and mammals. meso-2,3-Dimercaptosuccinic acid (DMSA) has been useful for prevention and treatment of mercury poisoning. In this study, the protective activity of DMSA on methyl mercury-induced embryo/fetotoxicity was evaluated in mice. A series of four DMSA injections was administered subcutaneously to pregnant Swiss mice immediately after oral administration of 25 mg/kg methyl mercury chloride (MMC) given on Day 10 of gestation, and at 24, 48, and 72 hr thereafter. DMSA effectiveness was tested at 0, 80, 160, and 320 mg/kg/day. Oral administration of MMC resulted in a high rate of resorptions and dead fetuses as well as a reduced fetal body weight. Moreover, cleft palate (46.9%) and various developmental variations were found in the positive control group. Treatment with DMSA at 160 and 320 mg/kg/day significantly decreased the embryolethality of MMC, whereas at 320 mg DMSA/kg/day the incidence of skeletal anomalies and cleft palate (2.8%) was also significantly reduced. According to these results, DMSA offers encouragement with regard to its therapeutic potential for pregnant women exposed to methyl mercury.

Topics: Animals; Bone and Bones; Disease Models, Animal; Drug Evaluation, Preclinical; Embryonic and Fetal Development; Female; Fetal Death; Mercury Poisoning; Mice; Pregnancy; Succimer

The efficiency of meso-2,3-dimercaptosuccinic acid (DMSA) and the monoisoamyl ester of meso-2,3-dimercaptosuccinic acid (Mi-ADMS) in decreasing 203Hg retention was evaluated in rats in relation to age and time of treatment. The experiments were performed on six-week- and seven-day-old Wistar rats, which received 203Hg by intraperitoneal administration. The chelators DMSA or Mi-ADMS were also administered intraperitoneally, twice, on two consecutive days, in doses of 0.25 mmol/kg body weight as early (0.5 and 24 h) or delayed treatment (24 and 48 h, or 48 and 72 h) after 203Hg administration. The retention of 203Hg was determined in the carcass, liver, kidneys and brain six days after administration using gamma scintillation counters (double crystal, well type). In all experimental conditions, regardless of the animals' age and time of chelation therapy, Mi-ADMS was found to be superior to DMSA in reducing the body burden of 203Hg in whole body and organs. Mi-ADMS therefore seems to be a very promising chelator in the treatment of mercury poisoning.

Topics: Animals; Body Burden; Chelation Therapy; Mercury; Mercury Poisoning; Rats; Rats, Wistar; Succimer

Topics: Adult; Arsenic Poisoning; Humans; India; London; Male; Medicine, Traditional; Mercury Poisoning; Poisoning; Succimer; Unithiol

Seven monoesters of meso-2,3-dimercaptosuccinic acid (DMSA) were evaluated for relative activities in mobilizing and promoting excretion of mercury in mercury-laden mice. Compounds assessed were the ethyl (M-EDMS), n-propyl (Mn-PDMS), isopropyl (Mi-PDMS), n-butyl (Mn-BDMS), isobutyl (Mi-BDMS), n-amyl (Mn-ADMS), and isoamyl (Mi-ADMS) esters. 2,3-Dimercaptopropane-1-sulfonate (DMPS) and DMSA were used as positive controls. After the first oral dose of each compound at 0.5 mmol/kg, DMSA and DMPS reduced the corporal mercury burden 16% and 24%, respectively, compared to controls, while the monoesters effected reductions of 35% (M-EDMS) to 49% (Mi-ADMS). After the second treatment at the same dose, the respective reductions produced by DMSA and DMPS were 24% and 38%, and those conferred by the monoesters ranged from 52% (M-EDMS) to 61% (Mn-BDMS). Determination of the comparative dose-response relationships of DMSA and Mi-ADMS on corporal and renal mercury concentrations revealed the monoester to be more active than DMSA on both parameters at each dose used. The cumulative amount of mercury excreted in urine by control mice over a 3-day period was 7.08 micrograms; this was increased 22%, 85%, and 94% by daily i.p. injections of DMSA, DMPS, and Mi-ADMS, respectively, at a daily dose of 0.1 mmol/kg. The respective cumulative 3-day totals recovered in feces from control mice and from mice treated with DMSA, DMPS, and Mi-ADMS were 9.76, 8.21, 10.44, and 11.73 micrograms. Parallel daily measurements of retained whole body radioactivity from 203Hg in mice were in good agreement with the values calculated from the excretion data.

Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Esters; Male; Mercury; Mercury Poisoning; Mice; Succimer; Unithiol

A family of four developed toxic blood levels of mercury after the mother vacuumed a spilled jar of liquid mercury from a closet in their apartment. The youngest son developed severe thrombocytopenia which was initially diagnosed as idiopathic thrombocytopenic purpura secondary to viral illness. A possible association between acute mercury toxicity and idiopathic thrombocytopenic purpura has not been previously reported. Chelation therapy with penicillamine for the older child was administered soon after toxic blood mercury levels were known by the physician. Because thrombocytopenia has been reported to occur in up to 5% of patients receiving penicillamine therapy, the younger child was treated with dimercaptosuccinic acid. The mother was also treated with dimercaptosuccinic acid. The father received dimercaprol therapy. The toxic effects and rationale for now outdated therapeutic uses of mercury are discussed.

Topics: Adult; Child, Preschool; Family; Female; Humans; Male; Mercury Poisoning; Penicillamine; Purpura, Thrombocytopenic, Idiopathic; Succimer

Topics: Dental Amalgam; Electrogalvanism, Intraoral; Humans; Mercury Poisoning; Succimer

Meso-2,3-dimercaptosuccinic acid (DMSA) is bound to plasma albumin in humans and appears to be excreted in the urine as the DMSA-cysteine mixed disulfide. The pharmacokinetics of DMSA have been determined after its administration to humans po. For the blood, the tmax and t1/2 were 3.0 h + 0.45 SE and 3.2 h + 0.56 SE, respectively. The Cmax was 26.2 microM + 4.7 SE. To determine whether dental amalgams influence the human body burden of mercury, we gave volunteers the sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS). The diameters of dental amalgams of the subjects were determined to obtain the amalgam score. Administration of 300 mg DMPS by mouth increased the mean urinary mercury excretion of subjects over a 9 h period. There was a positive correlation between the amount of mercury excreted and the amalgam score. DMPS might be useful for increasing the urinary excretion of mercury and thus increasing the significance and reliability of this measure of mercury exposure. DMSA analogs have been designed and synthesized in attempts to increase the uptake by cell membranes of the DMSA prototype chelating agents. The i.v. administration of the monomethyl ester of DMSA, the dimethyl ester of DMSA or the zinc chelate of dimethyl DMSA increases the biliary excretion of platinum and cadmium in rats.

Topics: Adult; Aniline Compounds; Animals; Dental Amalgam; Dimercaprol; Humans; Male; Mercury; Mercury Poisoning; Molecular Structure; Protein Binding; Rats; Succimer; Unithiol

Exposure to elemental mercury vapour is known to influence renal function; however, severe renal disease has not been consistently identified. Eleven men were evaluated for renal disease after acute, massive mercury poisoning. Significant hyperchloraemia was identified in this group of patient and a reversible renal tubular defect was suggested by low normal serum bicarbonate, a normal serum anion gap and a positive urinary anion gap. The only other evidence of renal dysfunction was transient, mild proteinuria in one of the 11 patients. During this same time period, neuropsychological impairment was identified on a test of cognitive and visual-motor function, 'Trailmaking B', in seven of the 11 patients. Additionally, dysuria and ejaculatory pain occurred without evidence of urological disease. These complaints were more frequent in those patients with impairment on 'Trailmaking B' suggesting a neurological basis for these symptoms. The findings of this study support earlier observations that the brain rather than the kidney is the critical target organ after elemental mercury vapour exposure.

Topics: Adult; Chelation Therapy; Chlorides; Construction Materials; Humans; Male; Mercury Poisoning; Middle Aged; Neuropsychological Tests; Occupational Diseases; Penicillamine; Prognosis; Proteinuria; Succimer; Urogenital System

Mercury poisoning occurred after the acute, prolonged exposure of 53 construction workers to elemental mercury. Of those exposed, 26 were evaluated by clinical examination and tests of neuropsychological function. Patients received treatment with chelation therapy in the first weeks after exposure. Eleven of the patients with the highest mercury levels were followed in detail over an extended period. Observations included the evaluation of subjective symptoms of distress, using the 'Symptom Check List 90-Revised' (SCL-90R) and tests of visual-motor function such as 'Trailmaking Parts A and B', 'Finger Tapping', 'Stroop Colour Word Test' and 'Grooved Pegboard.' On day 85 +/- 11 (mean +/- s.d.) after exposure, these 11 men again received either 2,3-dimercaptosuccinic acid (DMSA) or N-acetyl-D, L-penicillamine (NAP) in a short-term study designed to compare the potential to mobilize mercury and the incidence of drug-induced toxicity of these two chelating agents. Rapidly resolving metal fume fever was the earliest manifestation of symptoms. CNS symptoms and abnormal performance on neuropsychological tests persisted over the prolonged period of follow-up. There were significant correlations between neuropsychological tests and indices of mercury exposure. Serial mercury in the blood and urine verified the long half-life and large volume of distribution of mercury. Chelation therapy with both drugs resulted in the mobilization of a small fraction of the total estimated body mercury. However, DMSA was able to increase the excretion of mercury to a greater extent than NAP. These observations demonstrate that acute exposure to elemental mercury and its vapour induces acute, inorganic mercury toxicity and causes long-term, probably irreversible, neurological sequelae.

Topics: Adult; Chelation Therapy; Construction Materials; Humans; Male; Mercury; Mercury Poisoning; Middle Aged; Neuropsychological Tests; Occupational Diseases; Penicillamine; Prognosis; Succimer

Three siblings with inhaled elemental mercury toxicity are described, and the signs and symptoms of mercury toxicity, interpretation of mercury concentrations, and management of elemental mercury exposure are reviewed. A 4-year-old girl was admitted to the hospital with a history of fever and increasing irritability, fatigue, malaise, insomnia, headache, anorexia, and ataxia. She was discharged two days later with a diagnosis of acute cerebellar ataxia. During the following 18 days, the child's condition worsened, and she was rehospitalized. Meanwhile her 11-year-old sister was hospitalized for evaluation of fatigue, weakness, lower back pain, and ataxia. The older girl's blood mercury concentration, at 5.5 micrograms/dL, was in the toxic range. Twenty-four-hour urine mercury screening confirmed mercury intoxication in both children. Questioning revealed that the girls' brother had recently spilled 0.5-1 oz of elemental mercury in the house. All family members underwent blood and urine mercury testing. The brother underwent a dimercaprol challenge to determine his tissue mercury burden, which was found to be greater than 2.4 micrograms/dL. The sisters underwent two courses of chelation therapy with dimercaprol. Symptoms persisted in all three children, and they underwent five 10-day cycles of N-acetyl-D,L-penicillamine (NAP) therapy; the youngest underwent a third dimercaprol regimen. All siblings continued NAP chelation therapy because of extensive tissue mercury burden until the results of repeated urine mercury concentration determinations were normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Administration, Oral; Child; Child, Preschool; Dimercaprol; Female; Humans; Mercury; Mercury Poisoning; Penicillamine; Succimer

A 70-year-old white female presented approximately 24 h after ingesting three 475 mg tablets (1.425 g) of mercuric chloride in a suicide attempt. Acute renal failure necessitated the initiation of haemodialysis approximately 4 d after the ingestion. Treatment with BAL (2,3-dimercaptopropanol) resulted in only small increases in mercury output into dialysate. A new procedure involving the extracorporeal infusion of the chelating agent dimercaptosuccinic acid (DMSA) into the arterial blood line during haemodialysis was initiated. This procedure of Extracorporeal Regional Complexing Haemodialysis (ERCH) had been effective in increasing methylmercury removal in patients poisoned by contaminated grain. The first DMSA-ERCH procedure was performed 6 d after poisoning. There was a dramatic increase in mercury output into the dialysate. During three treatment sessions of 80 min each, 1189 micrograms of mercury were removed from the patient. The dialysed mercury represented the only mercury output since the patient was anuric and not producing faeces. DMSA-ERCH appears to be much more effective than BAL and haemodialysis in the treatment of acute inorganic mercury poisoning. The long interval between poisoning and initiation of treatment probably contributed to the patients ultimate demise, 28 d after poisoning. Efficacy of the DMSA-ERCH procedure for inorganic mercury poisoning is likely to be improved as the interval between exposure and treatment is reduced.

Topics: Aged; Arteries; Female; Humans; Mercury; Mercury Poisoning; Renal Dialysis; Succimer; Sulfhydryl Compounds; Time Factors; Veins

The inhibitory effect of mercuric chloride on mouse kidney enzymes and the treatment of this inhibition with some thiol-containing compounds, e.g., dithiothreitol (DTT), dimercaptosuccinic acid (DMS) and D-penicillamine (Pen) was examined. To produce a significant inhibition of renal enzymes in vivo, it was necessary to administer 5 mg Hg/kg/day, s.c., once daily for 3 doses, and to sacrifice the animals 1 day after the last injection. With this Hg dose, microsomal Mg2+-Na+-K+-ATPase, mitochondrial Mg2+-HCO-3-ATPase and supernatant carbonic anhydrase activities decreased to about 30%, 70% and 60% of normal values, respectively. Combined administration of DTT (5-20 mg/kg, i.p.) and DMS (5-20 mg/kg, i.p.) with HgCl2 restored the enzyme activities to near normal or normal levels in parallel to the administered doses. The effect of Pen was slightly less than that of the above 2 compounds. This may be due to the number of thiol radicals, as Pen is a monothiol and the other 2 compounds are dithiol compounds. Since the toxicity of DMS is very low compared with DTT, DMS may be more suitable for the treatment of mercury poisoning.

Topics: Adenosine Triphosphatases; Animals; Antidotes; Carbonic Anhydrase Inhibitors; Dithiothreitol; Kidney; Male; Mercuric Chloride; Mercury; Mercury Poisoning; Mice; Microsomes; Mitochondria; Penicillamine; Succimer; Sulfhydryl Compounds

The distribution and excretion of mercury were studied in mice given a single injection of HgCl2 with or without chelation treatment. DMS (2,3-dimercaptosuccinic acid) given intravenously (0.5 mmol SH/kg) to mice 24 h after the mercury injection reduced the kidney Hg level significantly, while NAPA (N-acetyl-DL-penicillamine) and BAL (2,3-dimercaptopropanol) did not. The effectivity of DMS to remove Hg from kidneys was comparable to that of BAL-sulph (2,3-dimercaptopropane-1-sulfonate), irrespective of whether these chelating agents were given orally or intravenously. Immediate chelation treatment with DMS or mercaptodextran reduced the renal Hg level to about 50% of control levels, as measured 3 d after the treatment. Combination of DMS with immediate intraperitoneal treatment with spironolactone was even more effective in reducing the renal levels, and acted both by increasing the fecal and urinary excretion. The DMS treatment, as well as DMS + spironolactone in combination, could protect against kidney damage following injection of 30 mumol HgCl2/kg. Such treatment was essentially nontoxic.

Topics: Animals; Brain; Chelating Agents; Dextrans; Dimercaprol; Diuretics; Female; In Vitro Techniques; Injections, Intraperitoneal; Injections, Intravenous; Kidney; Mercuric Chloride; Mercury; Mercury Poisoning; Mice; Penicillamine; Succimer; Sulfhydryl Compounds; Tissue Distribution

Topics: Animals; Drug Evaluation, Preclinical; Kinetics; Male; Mercury; Mercury Poisoning; Models, Biological; Rats; Succimer; Sulfhydryl Compounds; Time Factors

Topics: Animals; Brain; Citric Acid Cycle; Male; Mercury Poisoning; Oxidoreductases; Rats; Succimer; Sulfhydryl Compounds

We have studied the brain regional distribution of methyl mercury following intravenous administration of CH3 203HgCl in rat. Early peak levels were obtained in cerebellum, medulla oblongata and midbrain. The efficacy of removal of 203Hg by different chelators is also region dependent. The most efficient chelator for brain mercury proved to be mesodimercaptosuccinic acid.

Topics: Animals; Brain; Chelating Agents; Male; Mercury Poisoning; Methylmercury Compounds; Penicillamine; Rats; Succimer; Tissue Distribution

Topics: Humans; Mercury; Mercury Poisoning; Poisoning; Succimer; Succinates