Biomedical subjects

T W Clarkson

Publications and source records attributed to T W Clarkson.

At least 127 records · Page 7Linked to original sources

PubMed1977

Factors involved in heavy metal poisoning.

The heavy metals include at least 40 elements but cadmium, lead, and mercury have been most extensively studied. The biological properties of heavy metals are discussed in terms of three important characteristics: the ability to form, irreversibly, complexes and chelates with organic ligands; the properties to form organic-metallic bonds; and the potential to undergo oxidation-reduction reactions. The formation of complexes and chelates within the body is shown to influence greatly the dynamics of transport, distribution, and excretion of several important metal cations. The excretion of uranium is influenced by acid-base balance in the body because uranium forms complexes with bicarbonate anions that are filtered by the kidneys. The biliary excretion of methylmercury depends on the formation of small molecular weight complexes with sulfur-containing amiono acids and the peptides in the liver. The degree of enterohepatic recirculation of a variety of heavy metals appears to depend on the chemical nature of the bilary complexes. The oxidation of elemental to divalent ionic mercury is the crurial step in the retention and tissue deposition of inhaled mercury vapor. That the oxidation process is, at least in part, catalyzed by the enzyme, catalase, explains the effects of ethanol, aminotriazole and the state of acatalasemia on the metabolism of inhaled vapor in man and animals. The formation of covalent bonds between metal cations and the carbon atom usually greatly modifies the biological properties of the metal. Methylarsenic and methylmercury compounds both differ from the inorganic forms in accumulation in animals.

Animals↗

PubMed1977

An extracorporeal complexing hemodialysis system for the treatment of methylmercury poisoning. II. In vivo applications in the dog.

An extracorporeal regional complexing hemodialysis procedure is described which has been successfully applied for the enhancement of removal of methylmercury in the dog. The procedure utilizes the extracorporeal addition of cysteine to arterial blood entering a hemodialyzer, forming a large pool of complexed dialyzable methylmercury in plasma. Diffusion of this methylmercury complex across the dialyzer membrane into dialysate accounts for large amounts of methylmercury being removed from the animal. In conjunction with methylmercury removal, the majority of the infused cysteine is also removed resulting in comparatively low systemic doses of cysteine to the animal. At blood flow rates of 45 ml/min, and dialysate flow rates of approximately 550 ml/min, the mean percentage of methylmercury cleared from blood passing through the dialyzer was 39%. Rates of elimination of methylmercury from the dog could be increased by a factor of 100 during the extracorporeal regional complexing hemodialysis procedure. Regional collimated counting of radioactivity along the length of the dog revealed a decline in all areas including the head region. The procedure was void of any noticeable side effects during treatment or as evidence by histological evaluation of liver and kidney after treatment.

Animals↗

PubMed1976

Perinatal methylmercury poisoning in Iraq.

The signs and symptoms of methylmercury poisoning and the concentrations of mercury in samples of blood, hair, and milk are reported and compared in two infant-mother pairs exposed in the recent Iraq outbreak. In one pair, the infant was born prior to the exposure of the mother, and was exposed only from ingestion of methylmercury in mother's milk. In the other pair, the mother was exposed during pregnancy and did not breast feed the infant, who died 30 days after birth. Both mothers had some signs and symptoms of poisoning, but the infants did not. The infants had maximum estimated blood mercury levels between 500 and 1,000 ng/ml, well above the minimum toxic levels for adults. Hair and blood concentrations of mercury correlated closely, the average hair-blood ratio being about 250. Maternal milk averaged 8.6% of the simultaneous blood level, but the relationship was nonlinear at blood mercury levels below 50 ng/ml. Postnatal exposure by suckling led to substantial infant blood mercury concentration (over 600 ng/ml), and prenatal exposure resulted in blood mercury levels in the infant at birth higher than those in the mother, even after corrections for differences in hematocrit level.

Adult↗

PubMed1976

Biochemical changes in rat kidney on exposure to elemental mercury vapor: effect on biosynthesis of metallothionein.

Evidence is presented that exposure of rats to elemental mercury vapor results in increased amounts of a metallothionein-like protein in kidney tissue but not in liver. After three or more daily exposures, each of 2 h duration, to elemental mercury vapor, more than 50% of the mercury in kidney tissue is bound to a protein having a molecular weight (mol. wt.) of about 10 000 as determined by Sephadex G-75 gel filtration chromatography. Cystine is incorporated into a 10 000 mol. wt. protein fraction from kidneys of rats which were injected with [U-14C] cystine after five daily 2-h exposures to mercury vapor. In contrast, no significant incorporation of [U-14C] cystine into this protein fraction was observed in kidneys of control rats or in livers of both control and mercury vapor-exposed rats. The in vivo incorporation of 109Cd into the fraction followed the same pattern as that of [14C] cystine in rats injected with tracer doses of CdCl2 labeled with radioactive 109Cd isotope. This 10 000 mol. wt. protein, newly synthesized in response to repeated exposures to mercury vapor, exhibited identical properties to metallothionein, namely in its subcellular localization, molecular weight, heat stability and isoelectric points. A significant incorporation of [U-14C]-cystine into this protein in rat kidney alone on exposure to mercury vapor confirms its induced biosynthesis in the kidney.

Animals↗

PubMed1976

The effect of oral doses of a polythiol resin on the excretion of methylmercury in mice treated with cysteine, D-penicillamine or phenobarbitone.

Mice dosed with methylmercury chloride (0.5 to 2.0 mg Hg/kg i.p.) labeled with the 203Hg isotope were given polythiol resin in their food (2% w/w). The effect of pretreatment with phenobarbitone, or co-administration of D-penicillamine or L-cysteine, was tested on the efficacy of the resin to accelerate the excretion of methylmercury. The effect of the polythiol resin in enhancing fecal excretion was dependent on the dose of methylmercury, it being significantly greater at doses of 1.0 and 2.0 than at 0.5 mg Hg/kg. In animals given the resin and phenobarbitone (0.1% w/w drinking water), fecal excretion was approx. 36% greater than in animals given resin alone. Penicillamine (2.5 mg/ml drinking water) actually retarted elimination of methylmercury in animals given the resin. Despite the enhanced efficacy of the resin plus phenobarbitone, the brain levels of methylmercury were not reduced beyond those seen in animals given resin alone. The mechanisms and implications of these effects are discussed.

Animals↗

PubMed1976

A radioactive mercury vapor generating and exposing system for small scale animal experiments.

An apparatus is described for exposing small animals to high specific activity elemental mercury vapor. The vapor is generated by reduction of mercury chloride labelled with the 203HG isotope. The vapor is carried by a constant stream of air into the exposure chamber. The method has been used to expose rats or mice to constant air concentrations of mercury vapor in the range from 0.008 to 0.32 mg/m3. The specific activity of the mercuric chloride used in the study was approximately 1.8 mCi/mgHg. This is sufficiently high to allow measurement of tissue deposition of mercury after an exposure period of only 30 minutes.

Animals↗

PubMed1976

Clinical observations on treatment of alkylmercury poisoning in hospital patients.

Twenty-six patients suffering from methylmercury poisoning were treated by different therapeutic regimes. Seven received penicillamine or N-acetyl-d-L-penicillamine, 10 were treated with dimercaprol sulfonate and 9, who could not be treated, were given a placebo and were used as controls. Penicillamine, N-acetyl-d-L-penicillamine, and dimercaprol sulfonate reduced the blood level of mercury and increased its urinary excretion. No appreciable clinical improvement was noticed among the severe or very severe cases, while mild or moderate cases improved clinically irrespective of the treatment given.

Adolescent↗

PubMed1976

Tissue levels of mercury in autopsy specimens of liver and kidney.

Fifty-one autopsy specimens of liver were analysed for total mercury. Thirteen specimens contained less than 10 mg/kg of mercury, with a minimum value of 1.4 mg/kg, indicating that death in suspected cases was not always due to lethal exposure to methylmercury. The methylmercury concentration in 28 livers was 10-30 mg/kg. Limited additional estimations have shown that 71% of the liver mercury was organic and that the level of mercury in the liver of a 7-month-old fetus was only 25% of that in the liver of the mother. In a patient who died in hospital with a blood mercury level of 4.1 mug/ml, the liver contained 16.5 mg/kg of mercury.Differences between these results and those found in the outbreak of methylmercury poisoning in Japan are discussed. Any extrapolation of tissue mercury levels in relation to the toxic effects of methylmercury must take account of the intensity and duration of exposure.

Adolescent↗

PubMed1976

An outbreak of methylmercury poisoning due to consumption of contaminated grain.

An outbreak of methylmercury poisoning took place in the fall and winter of 1971-72 in Iraq. Six thousand five hundred and thirty cases were admitted to hospitals throughout the country and 459 died in hospital. The outbreak was the result of eating homemade bread prepared from wheat treated with a methylmercury fungicide. The wheat was intended for planting purposes only. Signs and symptoms of poisonings in adults indicate that the major site of action of this form of mercury is the central nervous system. Severe brain damage also resulted from prenatal exposure when the mother ingested large amounts of the contaminated bread. The frequency of signs and symptoms in an exposed population was found to be related to the estimated maximum blood levels, i.e., the concentration in blood at the end of exposure. A small percentage of the population exhibited a significant increase in complaints of paresthesia at maximum blood levels in the range of 240 to 480 ng Hg/ml. At higher blood levels a greater proportion of the population complained of paresthesia and other signs and symptoms became apparent.

Central Nervous System Diseases↗

PubMed1975

An extracorporeal complexing hemodialysis system for the treatment of methylmercury poisoning. I. In vitro studies of the effects of four complexing agents on the distribution and dialyzability of methylmercury in human blood.

Almost all of the methylmercury (MM) in human blood is protein bound, primarily to sulfhydryl ligands. Sulfhydryl agents such as penicillamine, N-acetylpenicillamine, cysteine and N-acetyleysteine are capable of reversing the protein binding of MM when they are added to whole human blood. The magnitude of the protein binding reversal was similar for each compound as predicted by the determination of their relative affinities for MM in vitro. Concentration-dependent reversals of protein binding of MM in blood was observed at increasing sulfhydryl concentrations from 10-4 to 10-2 M. At 10-2 M, a 55- to 60-fold increase in non-protein-bound plasma MM was observed, when compared to blood with no added sulfhydryl agent. Both the complexing agent and the MM complex formed in blood were readily dialyzable using a Travenol 145 twin coil hemodialyzer. At cysteine concentrations of 10-2 M in whole blood, up to 44 percent of whole blood MM was dialyzed on a single pass at a dialyzer blood flow rate of 55 ml/min. Under the same conditions, up 50 94 percent of plasma cysteine was dialyzed. A system is presented for use in vivo on experimental animals. The potential advantages of this method over existing therapeutic regimens for MM poisoning are discussed.

Acetates↗

PubMed1974