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PubMedDate not supplied

Somatomedin activity before and after chelation therapy in lead-intoxicated children.

Somatomedin activity was measured in 21 lead-intoxicated children to determine whether plumbism interferes with the processes of statural (bone) growth. Somatomedin activity was measured both by the rabbit coastal cartilage bioassay and by radioimmunoassay of somatomedin-C. Compared to values in normal children, both the bioassay and radioimmunoassay somatomedin activity was increased. The degree of body lead burden was so extensive that the 21 study children required chelation therapy. Following EDTA or BAL + EDTA chelation therapy, the overall somatomedin activity of these children with plumbism further increased significantly. In contrast, measures of body lead burden--including blood lead levels--decreased after treatment in all lead-intoxicated youngsters. We conclude that plumbism is associated with increased somatomedin activity. Hence the increased somatomedin activity may explain why clinical experience fails to find any long-term deleterious effect of saturnism on statural (bone) growth. Possible mechanisms underlying the increased somatomedin activity in the lead-intoxicated children remain to be defined.

Calcium↗
PubMed1981

Lead encephalopathy in infants in Kuwait. A study of 20 infants with particular reference to clinical presentation and source of lead poisoning.

Twenty patients aged between one and eighteen months (mean six months) were found to have lead encephalopathy. They were seen in one 30-bed ward during a four year period from 1977 to 1980. Blood lead was determined in 19 children and ranged between 2.9 and 12.4 mumol/l (60 and 257 micrograms/dl) mean 5.42 mumol/l (113 micrograms/dl). Two patients died before starting treatment. Of the 18 patients treated with B.A.L. (2.3 dimercaptopropanol) and EDTA (ethylenediaminetetra-acetic acid), three died. Eleven patients made an apparently complete recovery and four had neurological sequelae. The source of lead was traced in 18 patients: in 11 it was due to the liberal use of Kohl (also known as surma) commonly used as an eye cosmetic in the Arabian peninsula. Other local sources of lead poisoning are discussed.

Brain Diseases↗
PubMed1993

Relative effectiveness of dithiol and dithiocarbamate chelating agents in reducing retention of polonium-210 in rats.

Nine different sulphur-based chelators, including dithiols and dithiocarbamates, were examined for their ability to remove Po-210 from the rat. In general, treatments merely caused a redistribution of Po-210 in the body. Greatest reduction of Po-210 in blood was achieved by 2,3-dimercaptopropanol (BAL), sodium diethyldithiocarbamate (DDTC), and N-(2,3-dimercaptopropyl) phthalamidic acid (DMPA). Nearly all the compounds tested decreased Po-210 in the spleen and muscle. On the other hand, BAL and DDTC substantially increased the accumulation of Po-210 in the brain while DMPA, DMPS (sodium 2,3-dimercaptopropane-1-sulphonate) and DMSA (meso-2,3-dimercaptosuccinic acid) increased by several times the Po-210 in kidneys. A less pronounced increase of Po-210 was sometimes observed in liver (due to DDTC and DMPA) and in muscle (due to BAL and DDTC). Three of the dithiocarbamates (BGDTC, MeOBGDTC and BLDTC) did not increase accumulation of Po-210 in the brain and muscle but they reduced Po-210 in blood to a lesser degree than DDTC. A derivative of DMSA (Mi-ADMS) reduced Po-210 in blood, bone and muscle more than DMSA, but at the same time increased Po-210 in the kidney. When BAL or DDTC were combined with other agents there was a greater reduction in the whole-body burden of Po-210. Removal of Po-210 from the bone, spleen and kidneys by BAL was increased by repeated treatment. However, under similar experimental conditions the effect of a single injection of BAL on Po-210 in blood was less pronounced when the period of observation was prolonged. Total-body retention of Po-210 could not be reduced to less than 85% of the untreated controls by any of the chelators tested. In spite of this some of them (BAL, DMPS, DMSA, DMPA) could still have a useful role in reducing the toxicity of Po-210.

Animals↗
PubMed1979

Note on the metabolism of the mercury chelating agent sodium 2,3-dimercaptopropane-1-sulfonate.

Chromatographic analysis of the radioactive urine obtained after injection into rats of [1,3-(14)C] dimercaptopropane sodium sulfonate (DMPS, Dimaval) showed that part of the administered chelating agent is excreted unchanged. This was confirmed by the results of studies of sulfur excretion in the different fractions of the urine as well as by titration of the excreted thiol groups. The results show that, at least in rats, DMPS is not involved in important metabolic reactions.

Animals↗
PubMed1980

Biliary mobilization of cadmium by 2,3-dimercaptopropanol and some related compounds.

No effective therapeutic agent for mobilizing tissue Cd has been reported to date, but the results presented here demonstrate that 2,3-dimercaptopropanol (BAL) , at doses approaching and surpassing the maximum tolerated, can produce a rapid transient enhancement of Cd excretion in the rat. When BAL (75 mg/kg) was administered by a single injection 24 h after a tracer dose of 109Cd, as much as 32% of the administered Cd appeared in the bile. A correlation between the appearance of radiocadmium and the biliary sulfhydryl concentration was found. There was indirect evidence for a 1:3 Cd-BAL complex in the bile, which may explain the efficacy of higher doses of BAL. A comparative study with some selected dithiol compounds suggests that vicinal sulfhydryl groups on an aliphatic chain are the more effective Cd mobilizing compounds, but BAL was the most effective agent. Although suspending vehicles alone showed no Cd mobilizing ability, the combination of BAL and oil was far superior to any other BAL-vehicle combination used. A spectrophotometric method for the determination of sulfhydryl groups in bile and urine is also presented.

Animals↗
PubMed1980

Biliary excretion of cadmium in rat. VI. Mobilization of cadmium from metallothionein by 2,3-dimercaptopropanol.

Cadmium was preferentially bound to metallothionein in tissues 24 h after CdCl2 injection. Of a number of chelating agents examined, only 2,3-dimercapto-1-propanol (BAL) was effective in mobilizing Cd from metallothionein into bile. Structurally similar dithiols such as 1,3-dimercaptopropanol and 2,3-dimercapto-1-propanesulfonic acid were not effective. Diethylenetriamine pentaacetic acid increased only the urinary excretion of Cd. Biliary excretion of Cd increased with increasing dose of BAL, and there was a concurrent decrease in hepatic Cd levels without any increase in renal concentration. BAL was effective even 14 d after Cd injection. The form of Cd excreted in the bile after BAL injection in chronic exposure has not yet been characterized. Initial studies suggested that it was not metallothionein but was a low-molecular-weight Cd complex, probably with BAL.

Animals↗
PubMed1982

Biliary excretion of cadmium in rat. V. Effects of structurally related mercaptans on chelation of cadmium from metallothionein.

The effects of several mono-, di-, and trithiols (400 mumol/kg) in mobilizing Cd from metallothionein were studied in rats 24 h after a single injection of 109CdCl2 (1 mg kg/Cd). BAL (2,3-dimercaptopropanol) and propanetrithiol (1,2,3-trimercaptopropane) were the most effective mercaptans in increasing the biliary excretion of Cd (3.1 and 5.5% of administered dose, respectively, compared to 0.04% in control injected with propylene glycol) in in situ experiments with a significant decrease in hepatic Cd. Propane-1-thiol was inactive and propanetrithiol was the most toxic of the compounds studied. A number of propane dithiols having sulfhydryl groups at different carbon positions with and without substituents (OH or SO-3) and dimercaptoethane were also tested for effectiveness in removing Cd. All the lipophilic compounds with two adjacent sulhydryl groups were effective in increasing the biliary excretion of Cd, but were less effective than BAL and propanetrithiol. The major form of Cd in liver cytosols of rats pretreated with CdCl2 and injected with mercaptans was metallothionein. A small amount of Cd in liver cytosol and a major portion of biliary Cd in propanetrithiol-injected rats were bound to high-molecular-weight proteins when fractionated on Sephadex G-75 columns. On the other hand, after injection of BAL, most of the Cd in the bile was associated with a fraction of molecular weight 10,000. Even though Cd was present mainly as metallothionein in livers of Cd-pretreated rats, the biliary forms of Cd after injection of BAL and propanetrithiol were different. Similar results were obtained when Cd was added in vitro to bile samples collected from control rats that were injected with these chelating agents alone. However, the Sephadex G-75 elution profile of Cd-BAL and Cd-propanetrithiol after direct addition to control rat bile showed Cd complexes of identical molecular weight (less than 6000). These results suggested that the Cd-binding ligands present in bile after injection of BAL and propanetrithiol were different from and had a higher molecular weight than the complexes in vitro with Cd and the respective chelating agents.

Animals↗
PubMedDate not supplied

In vivo screening of potential antidotes for chronic cadmium intoxication.

Nineteen chelating agents have been screened under identical conditions of metal loading in an attempt to establish their relative ability to mobilize cadmium from the liver and kidney in mice with chronic cadmium intoxication. The compounds investigated were divided into five groups: polyaminocarboxylic acids, monothiols, dithiols, macrocycles, and a miscellaneous category. Only 2,3-dimercaptopropanol (BAL) and sodium diethyldithiocarbamate (NaDDTC) were able to produce a statistically significant (at the 95% level) reduction in the cadmium content of the kidney. The closely related dithiols sodium 2,3-dimercaptopropane-1-sulfonate and 2,3-dimercaptosuccinic acid produced statistically significant increases in the liver cadmium contents, as did N-(2-mercaptopropionyl)-glycine. The reduction in kidney cadmium levels produced by both BAL and NaDDTC was just under 40%.

Animals↗
PubMed1986

Effects of the mobilization of aged tissue cadmium by chelating agents.

An examination of the kidney and liver subsequent to the mobilization of aged cadmium deposits from them by the use of both dithiocarbamates and 1,2-dimercapto-1-propranolol (BAL) was carried out. No striking permanent effects due to cadmium mobilization were noted in the kidneys or livers for most of the chelating agents used. After the mobilization of part of the cadmium burden, the remaining cadmium gives evidence of undergoing a redistribution, leading to a renewed increase in both the kidney and liver levels of this element.

Animals↗
PubMed1989

[Case of acute poisoning by mercuric oxycyanide].

We report the case of a 25-year-old woman who voluntary swallowed mercuric oxycyanide and presented an anuric acute renal failure. The treatment was classically based upon the use of chelating agents and haemodialysis. Recovery of renal function was excellent. We discuss then more widely the clinical, physiopathologic and therapeutic aspects of acute intoxication with inorganic mercury salts.

Acute Kidney Injury↗
PubMed1988

Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus.

We have examined the function of class I MHC-restricted cytotoxic T cells in experimental respiratory syncytial virus (RSV) infection of BALB/c mice by transfer of T cell line MJC-A2 and CTL clone E8a into RSV-infected mice. The T cell line cleared pulmonary RSV infection within 5 d in persistently infected gamma-irradiated mice, but caused acute respiratory disease. This was only seen in infected mice and was often lethal after transfer of greater than 3 x 10(6) CTL. Lower numbers of CTL produced less severe disease but still cleared lung RSV, albeit over a longer time course (up to 10 d). Clearance of lung RSV in immunocompetent mice by the T cell line and CTL clone was again accompanied by acute and sometimes lethal respiratory disease. Bronchoalveolar lavage showed severe lung hemorrhage and frequent neutrophil efflux in mice with CTL-augmented disease.

Animals↗
PubMed1990

2,3 Dimercapto-1-propanol inhibits HIV-1 tat activity, viral production, and infectivity in vitro.

We have examined the effect of 2,3 dimercapto-1-propanol (DMP), which is known as an anti-heavy metal-poisoning drug, against human immunodeficiency virus type 1 (HIV-1). We demonstrate that DMP inhibited transactivation directed by tat protein, which is a metal containing transcriptional transactivating factor and also interfered with viral production. Furthermore, treatment and pretreatment of cells with DMP strongly reduced their sensitivity for HIV-1 infection through unknown mechanisms. These results indicate that DMP reveals pleuripotent effects on HIV-1 infection and production in vitro and thus may provide an exploitable hypothesis for designing new drugs against AIDS.

Amino Acid Sequence↗