Miroslav Cikrt

EEG Photic Driving in Workers Exposed to Mercury Vapors

OBJECTIVE To assess the potential of EEG photic driving (PD) as an indicator of an early neurotoxic effect of long-term, low-level exposure to mercury vapors. SUBJECTS AND METHODS Twenty-four chloralkali workers exposed to mercury vapors; twenty-four age- and gender-matched control subjects. Level of exposure was determined by urinary mercury excreted both spontaneously and after administration of a chelating agent, sodium 2,3-dimercapto-1-propane sulfonate. A computerized method for quantitative evaluation of PD was developed. Five parameters describing PD were compared. RESULTS The number of stimulation frequencies eliciting PD was higher in the exposed group, with a median of 17 frequencies, as compared to 10 frequencies in the control group (P < 0.001). The maximum value of PD was higher in the exposed group, with a median of 24.6 z-units as compared to 9.4 in the control group (P < 0.001). The median of the stimulation frequency with maximum PD was shifted from 15 Hz in the control group to 20 Hz in the exposed group (P < 0.01). The median of the sum of PD and the median of the index of PD were significantly higher in the exposed than in the control group (P < 0.001). The increased PD was particularly prominent at high stimulation frequencies in the beta range. There was no significant association between the measures of PD and the measures of exposure. CONCLUSIONS In comparison with a control group, significantly increased photic driving was observed in a group of workers exposed to mercury vapors. The issue of whether or nor the intergroup differences in PD are mercury related, could not be determined on the basis of our results. Should the enhanced PD be caused by mercury, then this electrophysiological phenomenon might be regarded as a marker of the CNS hyperexcitability due to an early neurotoxic effect of mercury, the clinical expression of which is erethism.

In vivo and in vitro efficacy of a new carbodithioate for the mobilization of cadmium.

Female Wistar rats with chronic cadmium intoxication (oral exposure to low dosages of CdCl2 in drinking water over a period of 90 d) were used to examine the in vivo ability of a newly developed chelator, sodium N-(4-methylbenzyl)-4-O-(beta-D-galactopyranosyl)-D-glucamine-N- carbodithioate (MeBLDTC), singly and in combination with sodium 4-carboxy-amidopiperidine-N-carbodithioate (INADTC) as agents to induce the biliary and urinary excretion of cadmium. The combined administration of the two dithiocarbamates, which differ greatly in molecular weight and structural features, led to a synergistic increase in the biliary excretion of cadmium and an enhanced reduction of renal cadmium levels. The use of such a coadministration produced an increase in the biliary excretion of cadmium that was more than double that expected if the compounds acted in an additive fashion. Such mixed-chelation therapy has potential utility in the treatment of human chronic cadmium intoxication. The hepatocytes isolated from chronically Cd-intoxicated rats were used as an in vitro screening model system for the new chelator. The plasma membrane integrity study with MeBLDTC at 0.48 mmol/20 ml of hepatocyte incubate using the trypan blue exclusion test and lactate dehydrogenase (LDH) leakage test revealed no differences in the cell viability with or without chelator. The cellular metabolic competence measured as the rate of urea synthesis also did not show any marked deviation from that of controls when incubated with MeBLDTC at three different concentrations. In the hepatocyte cultures, MeBLDTC induced a significant removal of cadmium from the hepatocytes at concentrations as low as 0.04 mmol/20 ml.

Distribution and excretion of cadmium and nickel after simultaneous exposure and the effect of N‐benzyl‐d‐glucamine dithiocarbamate on their biliary and urinary excretion

A rat model for combined exposure to cadmium and nickel is presented that involves the administration of drinking water containing these elements over a period of 90 d. Coadministration of these two ions in drinking water leads to brain levels of both elements that are significantly higher than results from the administration of equal doses of the metals individually. The enhanced biliary excretion of cadmium in rats given sodium N-benzyl-D-glucamine dithiocarbamate (BGDTC) is almost twice as great in those animals given cadmium and nickel as in those animals given cadmium only. The excretion of nickel is reduced by the administration of this chelating agent. Although equal amounts of nickel and cadmium were administered to these animals, liver and kidney cadmium levels were approximately 100 times greater than the corresponding nickel levels. The results suggest that combined exposure to these elements may lead to enhanced levels of nickel and cadmium in the brain and a level of nervous system damage not predictable from information obtained under conditions of exposure to only one of these elements.

Synergistic enhancement of the biliary excretion of cadmium by the simultaneous administration of two dithiocarbamates

The simultaneous i.p. administration of the two chelating agents bis(2-hydroxyethyl)dithiocarbamate (DEDTC) and 4-carboxamidopiperidinedithiocarbamate (INADTC) to rats given cadmium in their drinking water at a level of 50 mg cadmium/liter for 39 days led to a large synergistic effect on the biliary excretion of cadmium. A much smaller synergistic effect on the urinary excretion of cadmium was also noted. When treated with a similar mixture of chelating agents after a similar cadmium-drinking water exposure of 180 days, rats showed significant decreases in both renal and brain cadmium levels.

Effect of chronic administration of carbon tetrachloride on copper, zinc, and mercury binding in bile in rats.

Abstract Carbon tetrachloride (1 ml/kg) was given sc to rats twice a week during 3 months. After 3 months the bile ducts were cannulated in rats of one group, whereas the animals in another group were sacrificed and their livers removed. Solutions of 64 CuCl 2 , 65 ZnCl 2 , or 203 HgCl 2 were administered iv to the rats with cannulated bile ducts. It was found that CCl 4 treatment provoked changes in copper and zinc concentrations in the bile and in the liver proteins. Treatment with copper or zinc salts resulted in changes in bile components of high molecular weight. The quantity of copper bound in different bile components was not changed after CCl 4 treatment whereas that of zinc did change. The findings indicate that mercury is bound in bile in a different way than copper or zinc. The changes in the binding of copper and zinc with bile components in rats given CCl 4 are reflected in changes of cumulative excretion of copper and zinc via bile during the 24 hr following their administration.

Influence of spironolactone on the mercury biliary excretion mechanism in rats

Abstract Spironolactone (SPL), administered intragastrically to rats 24 and 2 h prior to i.v. application of 203HgCl2, was found to change the pattern of 203Hg distribution among the individual bile fractions. In spironolactone-pretreated rats there was a more rapid biliary excretion of 203Hg which was ascribed to the presence of mercury in the low-molecular bile fraction (fraction 2). This accelerated mercury excretion persisted for as long as the spironolactonemercury complex was present in the animal organism.

Policy and practice in occupational health services in the Czech Republic

Structure of Czech occupational health services and their distribution and coverage In the Czech Republic (and in its predecessor, the former Czechoslovakia), there is a long history of governmental commitment to occupational health (OH) issues. The first Department for Occupational Medicine in Czechoslovakia was established at the Charles University in Prague in 1932. The system of Czech OH services before 1989 arguably served as a model worth following in several respects, including in its approaches to resources and staffing. Research in OH was at a very high level, and work environment standards were relatively strict in comparison with many European countries. In practice, however, the system did not always work as expected. For example, during the Communist era (1948–1989), there were frequent bans on the disclosure of information about workplace hazards and risk management. The gap between political proclamations and reality was widening. Nevertheless, there were some progressive practices in place during that time which, unfortunately, have been abandoned and almost completely lost since the Velvet Revolution in 1989.

Sodium bis(hydroxyethyl)dithiocarbamate reduces acute lung tissue damage induced by cadmium in rats

The protective effect of three dithiocarbamates against lung tissue damage induced by a single intratracheal instillation of cadmium chloride was examined in rats. The relative efficacy of these compounds was tested by comparing characteristic features of lung tissue damage: the increase of lung weight, and the changes in the synthesis and content of structural proteins. Of three compounds administered intraperitoneally at a dose of 2.46 mmol/kg body weight, the most effective in suppressing lung damage was sodium bis(hydroxyethyl)dithiocarbamate (DEDTC). Its efficacy was dependent on the time interval between administration of cadmium chloride and the DEDTC. The parameters of lung tissue damage which were examined approached control values when DEDTC and cadmium chloride were administered simultaneously.

Biliary excretion of lead in rats drinking lead-containing water

In three groups of rats, drinking lead-containing water (at 100, 250 and 2500 mg lead (Pb)/l) for 80 days, biliary excretion of Pb was studied. In comparison with a control group (0.05 +/- 0.04 micrograms Pb/ml) biliary excretion of Pb in the exposed groups reached 0.08 +/- 0.01, 0.20 +/- 0.04 and 1.46 +/- 0.09 micrograms/ml, respectively. In rats receiving 2500 mg Pb/l, i.v. administration of CaEDTA (0.2 mumol/kg body weight) significantly decreased biliary Pb excretion and increased the concentration of Pb in the kidneys.

Distribution and excretion of 203Hg2+ in rats after unitiol, spironolactone and polythiol resin treatment

Rats were given 203HgCl2 i.v. at a dose level of 120 microgram of Hg2+ per rat. The effect of unitiol (UNI; sodium 2, 3-dimercaptopropanosulphonate) and a combined UNI, spironolactone (SPL) and polythiol resin treatment on wholebody retention, organ distribution and excretion were studied for 48 h. In both treated groups significant increases in excretion and decreases in whole-body retention of 203Hg were observed. In the combination-treated group significantly lower values of 203Hg in plasma, kidney and brain were found.