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Biomedical subjects

T W Clarkson

Publications and source records attributed to T W Clarkson.

At least 91 records · Page 5Linked to original sources
PubMed1984

Treatment of acute methylmercury ingestion by hemodialysis with N-acetylcysteine (Mucomyst) infusion and 2,3-dimercaptopropane sulfonate.

A case of acute methylmercury ingestion was treated sequentially with oral D-penicillamine, hemodialysis during N-acetylcysteine (NAC) infusion, and 2,3-dimercaptopropane sulfonate (DMPS) an experimental oral agent. Urinary organic mercury elimination rate increased almost 40-fold during and 84-fold after hemodialysis with NAC infusion, compared with elimination during initial D-penicillamine therapy. Mean clearance during hemodialysis was only 13 ml/min with an extraction rate of 3.7 mcg/min. Although whole blood mercury concentrations decreased from 568 to 265 ng/ml during dialysis, a rebound to 525 ng/ml occurred. A total of 1.6 mg mercury was renally eliminated during hemodialysis and in the following 24 hours. A total of 3.3 mg of predominantly organic mercury was renally eliminated during 18 days of combined therapies. Since renal elimination of inorganic mercury is seen with chronic methylmercury poisoning, the high ratio of organic to inorganic mercury in urine supports the acute nature of this exposure. DMPS was begun on day 4 and during the two weeks of administration whole blood concentrations fell by 15% to 355 ng/ml. An expected decrease in elimination half-life to 10 days was not observed during DMPS therapy, possibly due to concurrent administration of vitamins containing zinc and copper. The amount of methylmercury ingested was estimated as 45 mg, based on a post-distribution blood concentration of approximately 450 ng/ml. The patient developed no symptoms of methylmercury poisoning during the one year after the episode. We conclude that NAC may be useful to enhance renal elimination of methylmercury and merits further investigation as a potential binding agent to reduce the body burden of methylmercury.

Acetylcysteine↗
PubMed1984

Differences in the effects of selenite and biological selenium on the chemical form and distribution of mercury after the simultaneous administration of HgCl2 and selenium to rats.

The interaction was compared between inorganic (HgCl2) mercury and selenite (Na2SeO3) vs. the interaction between inorganic mercury and biological selenium (a freeze-dried preparation of liver from rats treated with selenite). Organ concentrations of selenium were always significantly lower after biological selenium than after selenite. Biological selenium affected the organ distribution of inorganic mercury differently than selenite. Furthermore, the speciation of mercury was affected by this form of selenium. A mercury-selenide compound (presumably HgSe) accounted for a greater proportion of total mercury in tissues after selenite than after a dose of biological selenium. Administration of selenomethionine had a similar effect on the speciation of mercury to that seen after biological selenium. As the forms of selenium in selenomethionine or selenium deposited in the liver are most likely nearer than selenite to selenium present in food, our results suggest that, as far as the reaction of mercury with selenide is concerned, experiments with selenite overestimate the protective effect of dietary selenium against inorganic mercury and possibly against methylmercury.

Animals↗
PubMed1983

Mercury.

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Environmental Exposure↗
PubMed1983

Biliary transport of glutathione and methylmercury.

The hepatobiliary transport of glutathione (GSH) and methylmercury (MM) was investigated in male and female rats anesthetized with pentobarbital sodium. When bile flow was altered with either sodium dehydrocholate (DHC), hypertonic sucrose infusion, or by hypothermia, the absolute rates of GSH and MM secretion into bile were not affected, resulting in parallel concentration changes in the bile fluid for both GSH and MM. Indocyanine green and sulfobromophthalein (BSP), but not BSP-glutathione complex, inhibited the biliary secretion of free GSH. This inhibition was accompanied by a parallel inhibition of MM secretion into bile and occurred without any changes in liver GSH or MM levels. On the other hand, the intravenous administration of cysteine, GSH, and penicillamine was associated with an increase in the secretion rate of reduced sulfhydryl groups into bile and an increase in the biliary secretion rate of MM. The increased biliary secretion rate of MM after phenobarbital pretreatment was also associated with an increased rate of secretion of GSH into bile. In addition, sex differences and individual variability in the biliary secretion of MM were correlated with differing abilities to secrete GSH into bile. The results suggest the presence of a biliary transport system for GSH that determines the biliary secretion of MM.

Animals↗
PubMed1983

Public health consequences of heavy metals in dump sites.

Metals differ from most synthetic organic chemicals in that their clinical manifestations are well known and methods for their measurement in the body are generally well established. Since metals are ubiquitous, special care should be taken to identify the source, whether dump site or not. Isotopic ratios may be used for lead. Time of exposure may be highly variable so estimates will be necessary of integrated "dose-commitment." Transmission to man will follow many pathways. The contamination of children's hands and clothing by dust may be an important route. Because effects are so different, the chemical species (e.g., organic versus inorganic forms) of each metal must be identified. Exposure assessment requires identification of suitable indicator media, usually blood in the case of lead, urine with cadmium and inorganic mercury, and blood or hair with regard to methylmercury. Human head hair may have considerable potential, as it may provide a recapitulation of past exposures. The first health complaints associated with most metals are usually nonspecific. The complex social, political, and legal issues strongly indicate the need for objective tests for health effects. Most important is the identification and measurement of the critical effect, i.e., an effect that alerts the public health authorities that further exposure should cease. For example, in the case of lead, the critical effect is hematologic; with cadmium it is the presence in urine of abnormally high concentration of small molecular weight protein; and with mercury no early objective test has yet been devised.

Adult↗
PubMed1982

Developmental changes in the biliary excretion of methylmercury and glutathione.

The long half-time for methylmercury in the neonatal rats is explained by the neonatal liver's inability to secrete the toxin into bile, which in adults is the main route of elimination. The ability to secrete mercury into bile develops between 2 and 4 weeks of age and is correlated with the increasing ability of the developing liver to secrete glutathione into bile.

Age Factors↗
PubMed1981

Ethanol reveals novel mercury detoxification step in tissues.

Volatile mercury was produced de novo by mouse tissue homogenates that contained mercuric ions. Ethanol stimulated the release of tissue mercury into the vapor phase, and the mechanism appears to be an inhibition of reoxidation of volatile mercury. Components responsible for mercury volatilization are heat-labile. The highest volatilizing activity in the liver is associated with the soluble fraction obtained after centrifugation at 105,000g.

Animals↗
PubMed1981

Selective determination of elemental mercury in blood and urine exposed to mercury vapor in vitro.

A method is described to ensure quantitative measurement of dissolved mercury vapor (Hg0) in blood and urine. Room air passed through samples of blood and urine carries with it all the dissolved Hg0 but leaves behind all the ionic mercury (Hg++). Oxidation of Hg0 to Hg++ in blood samples is completely inhibited by addition of ethanol (0.5% v/v). To minimize error due to evaporation of Hg0, it is suggested that samples should be stored at 0 degree C and Hg0 should be determined within 60 min of collection of blood samples and within 10 min of urine samples.

Ethanol↗
PubMed1981

Methylmercury poisoning in the Iraqi suckling infant: a longitudinal study over five years.

In a five-year longitudinal study of mothers and infants exposed to methylmercury during the Iraq epidemic of 1972, the frequencies of signs and symptoms exhibited by the mothers were typical of methylmercury poisoning. When blood concentrations of mercury are corrected to 1 March 1972, mothers with the most severe signs and symptoms had an average blood mercury concentration significantly higher (p less than 0.01) than either the milder or asymptomatic groups. Analytical data indicate that the predominant route of exposure for the infant was through breast milk in which approximately 60% of total mercury was determined, by cold vapor atomic absorption, to be organic mercury. Abnormal neurological signs in these infants became more obvious with time: hyperreflexia was observed in 8 of 22 infants at first examination, and in 17 of 22 at second examination. Delayed motor development became evident at the second and third examinations. The frequency of pathological reflexes and delayed motor developmental milestones was so high as to be considered significant even in the absence of a controlled study. There was no increase in mortality as compared to a control group.

Female↗
PubMed1981

Comparative study of the sensitivity of male and female rats to methylmercury.

Male and female rats were dosed daily by gastric gavage four or five times with 8.0 mg/kg Hg as methylmercury. Treatment lowered the body weight in relation to the body weight of untreated rats to the same extent in male and female rats but when body weight was related to the initial body weight, the effect of methylmercury was more pronounced in females than in males. The important of differences in growth or loss of body weight is that in spite of the similar whole body clearance mercury concentrations were higher in females than in males. After identical doses the brains of females always contained more mercury than those of males and in both sexes the brain concentration of mercury showed a disproportionate elevation when the number of doses was increased from four to five. However, weight change alone does not explain the sex related difference in the brain concentration of mercury as this was evident even 72 h after a single dose. In agreement with the brain concentration of mercury, female rats developed more intensive co-ordination disorders and after five doses they had more extensive damage in the granular layer of the cerebellum than males.

Animals↗
PubMed1981

Dose-response relationship for human fetal exposure to methylmercury.

Eighty-four Iraqi mothers and their infants had been exposed to methylmercury during pregnancy. The methylmercury had been ingested as a fungicide. Peak maternal hair mercury concentrations were related to the frequency of maternal symptoms during pregnancy and to neurological effects in the infants. These include various degrees of psychomotor retardation. Severe neurological deficits were observed in five children whose maternal peak hair mercury concentrations were 165 to 320 ppm. Minimal symptoms were reported for mothers and children when peak maternal hair levels were below 68 ppm. Minimal clinical neurological signs occurred in children when peak maternal hair mercury concentrations were at an undetermined point between 68 and 180 ppm. Greater fetal risk appears to be associated with exposure during the second trimester. This exposure to methylmercury was acute and the results may not be extrapolated to a constant level of exposure throughout pregnancy. The effects of fetal exposure to methylmercury in marine fish may differ.

Dose-Response Relationship, Drug↗
PubMed1981

Tests of efficacy of antidotes for removal of methylmercury in human poisoning during the Iraq outbreak.

Three complexing agents and a thiolated resin were tested for their ability to reduce the T 1/2 of methylmercury in blood during an outbreak of human poisoning. The slope of the line relating the natural logarithm of the blood concentration to time during treatment was calculated by a parametric (linear regression) and a nonparametric (two-point) method. The mean slope for each treatment group was calculated and the T 1/2 was calculated from the mean slope. Both the linear regression and two-point methods yield similar mean values. The "two-point" T 1/2 will be quoted here. The mean T 1/2 in six patients receiving no specific treatment was 65 days and in 10 patients receiving placebo was 61 days, and these values did not differ from those reported in the literature. All four treatments significantly reduced the mean T 1/2 values below the mean for the combined placebo and no treatment groups. Sodium 2,3-dimercaptopropane-1-sulfonate was the most effective agent, reducing the mean T 1/2 in 10 patients to 10 days. The thiolated resin given to eight patients produced a mean T 1/2 of 20 days. The penicillamines also produced a significant reduction in T 1/2 values; the mean T 1/2 for D-penicillamine in 12 patients was 26 days and N-acetyl-DL-penicillamine in 17 patients yielded a mean T 1/2 of 24 days. This is the first report of the effects of sodium 2,3-dimercaptopropane-1-sulfonate and resin in human subjects exposed to methylmercury. No adverse effects were observed in any of the treatment groups. A clinical trial was not possible but it is concluded that agents that reduce blood levels and accelerate excretion are probably clinically useful if given before irreversible damage has occurred.

Adolescent↗
PubMed1981

Interaction of ethanol and inorganic mercury: generation of mercury vapor in vivo.

Mercury exhalation increased after parenteral administration of ethanol to mice injected with a single dose of mercuric chloride (0.5 mg of Hg/Kg). Increased output of the metal was ethanol dose-dependent (blood EC50 = 215 mg/dl) and maximal rates (0.2% of the body burden per 30 min) were about 10-fold higher than controls. The chemical form of exhaled mercury was determined to be the elemental vapor (Hg degrees) indicating an ethanol-sensitive reduction pathway for ionic mercury (Hg++) in the body. Ethanol appeared to selectively affect mercury exhalation inasmuch as no large differences in whole-body mercury retention times or in the distribution of the metal in organs could be detected even after repeated daily doses of ethanol. The results show that at least a portion of the ionic mercury in the body can be mobilized via reduction and Hg++ in tissues is more labile than generally recognized.

Animals↗
PubMed1980

Fetal methylmercury poisoning: clinical and toxicological data on 29 cases.

This report describes psychomotor retardation in infants caused by prenatal exposure to methylmercury. A study of 29 mother-infant pairs established a relationship between maximum maternal hair mercury concentration during pregnancy and the frequency of neurological effects in the infants. The latter included delayed achievement of developmental milestones with or without neurological signs. The infants were 4 1/2 to 5 years of age on last examination. Ten infants of mothers who had maximum hair concentrations in the range of 99 to 384 pars per million (ppm) had a significantly higher frequency of abnormal findings than those in two groups having lower maternal hair mercury concentrations (12 to 85 and 0 to 11 ppm). The group sizes were too small to allow identification of a specific "threshold" maternal hair concentration above which such effects can be expected. Transient paresthesias during pregnancy occurred in 80% of the mothers in the higher concentration group (99 to 384 ppm) as compared with 30% and 22% in the lower groups. Neurological abnormalities were found in some children whose mothers had been asymptomatic during pregnancy.

Abnormalities, Drug-Induced↗
PubMed1980

Comparative study of the sensitivity of virgin and pregnant rats to methylmercury.

Pregnant and virgin female rats were dosed by gastric lavage 10 times or 5 times with 5 mg/kg mercury as methylmercury. Treatment of pregnant animals started on day 3 of gestation and ended on day 14 of gestation with two days break between the 5th and the 6th doses. In Group B, treatment lasted from day 10 to day 14 of gestation. Pregnant and virgin rats responded identically to methylmercury in terms of body weight changes, coordination disorders, and cerebellar histological changes. Furthermore, the brain, liver and kidney concentrations and the rates of methylmercury elimination in the post-treatment period were identical. Thus the results indicate no difference in sensitivity of pregnant versus non-pregnant animals.

Animals↗
PubMed1980

The effect of lactation on methylmercury intoxication.

Four days after parturition 17 weeks old rats of Porton Wistar strain were given 8 mg/kg mercury as methylmercury chloride for 5 days. Virgin females or mothers separated from their offspring immediately after delivery received the same treatment and served as controls. Compared with these controls, lactation delayed the onset of weight loss, shortened the time between the end of treatment and the onset of weight gain, accelerated the elimination of mercury from the whole body and prevented the development of severe co-ordination disorders. However, lactation had no detectable effect on the elimination of mercury from the brain. Moreover control and lactating females had the same degree of histological abnormalities both in the granular layer of the cerebellum and in the dorsal root ganglion cells.

Animals↗