Joško Osredkar

The impact of long-term past exposure to elemental mercury on antioxidative capacity and lipid peroxidation in mercury miners

Limited information is available on the effects of chronic mercury exposure in relation to the risk of cardiovascular disease (CVD). It is known from in vitro and in vivo studies that Hg can promote lipid peroxidation through promotion of free radical generation, and interaction with antioxidative enzymes and reduction of bioavailable selenium. The objective of the study was to test the hypothesis that long-term past occupational exposure to elemental Hg (Hg0) can modify antioxidative capacity and promote lipid peroxidation in miners. The study population comprised 54 mercury miners and 58 workers as the control group. The miners were examined in the post-exposure period. We evaluated their previous exposure to Hg0, the putative appearance of certain nonspecific symptoms and signs of micromercurialism, as well as the main behavioural and biological risk factors for CVD, and determined: 1) Hg and Se levels in blood and urine, 2) antioxidative enzymes, Cu/Zn superoxide dismutase (CuZn-SOD), catalase (CAT), and selenoenzyme glutathione peroxidase (GSH-Px) activity in erythrocytes as indirect indices of free radical activity, 3) pineal hormone melatonin (MEL) in blood and urine, and 4) lipid hydroperoxides (LOOHs) and malondialdehyde (MDA) as lipid peroxidation products. The mercury miners were intermittently exposed to Hg0 for periods of 7 to 31 years. The total number of exposure periods varied from 13 to 119. The cumulative U-Hg peak level varied from 794-11,365 microg/L. The current blood and urine Hg concentrations were practically on the same level in miners and controls. Miners showed some neurotoxic and nephrotoxic sequels of micromercurialism. No significant differences in behavioural and biological risk factors for CVD were found between miners and controls. A weak correlation (r = 0.36, p < 0.01) between systolic blood pressure and average past exposure U-Hg level was found. The mean P-Se in miners (71.4 microg/L) was significantly lower (p < 0.05) than in the controls (77.3 microg/L), while the mean U-Se tended to be higher (p < 0.05) in miners (16.5 microg/g creatinine) than in the controls (14.0 microg/g creatinine). Among antioxidative enzyme activities, only CAT in erythrocytes was significantly higher (p < 0.01) in miners (3.14 MU/g Hb) than in the controls (2.65 MU/g Hb). The mean concentration of B-MEL in miners (44.3 ng/L) was significantly higher (p < 0.01) than in the controls (14.9 ng/L). The mean value of U-MEL sulphate (31.8 microg/L) in miners was significantly lower (p < 0.01) than in the control group (46.9 microg/L). Among the observed lipid peroxidative products, the mean concentration of U-MDA was statistically higher (p < 0.01) in miners (0.21 micromol/mmol creatinine) than in the controls (0.17 micromol/mmol creatinine). In the group of miners with high mercury accumulation and the presence of some nonspecific symptoms and signs of micromercurialism, the results of our study partly support the assumption that long-term occupational exposure to Hg0 enhances the formation of free radicals even several years after termination of occupational exposure. Therefore, long-term occupational exposure to Hg0 could be one of the risk factors for increased lipid peroxidation and increased mortality due to ischaemic heart disease (ICH) found among the mercury miners of the Idrija Mine.

Blood cadmium, mercury, and lead in children: an international comparison of cities in six European countries, and China, Ecuador, and Morocco.

Childrens blood-lead concentration (B-Pb) is well studied, but little is known about cadmium (B-Cd) and mercury (B-Hg), in particular for central Europe. Such information is necessary for risk assessment and management. Therefore, we here describe and compare B-Pb, B-Cd and B-Hg in children in six European, and three non-European cities, and identify determinants of these exposures. About 50 school children (7-14 years) from each city were recruited (totally 433) in 2007-2008. Interview and questionnaire data were obtained. A blood sample was analyzed: only two laboratories with strict quality control were used. The European cities showed only minor differences for B-Cd (geometric means 0.11-0.17 μg/L) and B-Pb (14-20 μg/L), but larger for B-Hg (0.12-0.94 μg/L). Corresponding means for the non-European countries were 0.21-0.26, 32-71, and 0.3-3.2 μg/L, respectively. For B-Cd in European samples, traffic intensity close to home was a statistically significant determinant, for B-Hg fish consumption and amalgam fillings, and for B-Pb sex (boys higher). This study shows that European city childrens B-Cd and B-Pb vary only little between countries; B-Hg differs considerably, due to varying tooth restoration practices and fish intake. Traffic intensity seemed to be a determinant for B-Cd. The metal concentrations were low from a risk perspective but the chosen non-European cities showed higher concentrations than the cities in Europe.

Personality traits in miners with past occupational elemental mercury exposure.

In this study, we evaluated the impact of long-term occupational exposure to elemental mercury vapor (Hg0) on the personality traits of ex-mercury miners. Study groups included 53 ex-miners previously exposed to Hg0 and 53 age-matched controls. Miners and controls completed the self-reporting Eysenck Personality Questionnaire and the Emotional States Questionnaire. The relationship between the indices of past occupational exposure and the observed personality traits was evaluated using Pearson’s correlation coefficient and on a subgroup level by machine learning methods (regression trees). The ex-mercury miners were intermittently exposed to Hg0 for a period of 7–31 years. The means of exposure-cycle urine mercury (U-Hg) concentrations ranged from 20 to 120 μg/L. The results obtained indicate that ex-miners tend to be more introverted and sincere, more depressive, more rigid in expressing their emotions and are likely to have more negative self-concepts than controls, but no correlations were found with the indices of past occupational exposure. Despite certain limitations, results obtained by the regression tree suggest that higher alcohol consumption per se and long-term intermittent, moderate exposure to Hg0 (exposure cycle mean U-Hg concentrations > 38.7 < 53.5 μg/L) in interaction with alcohol remain a plausible explanation for the depression associated with negative self-concept found in subgroups of ex-mercury miners. This could be one of the reason for the higher risk of suicide among miners of the Idrija Mercury Mine in the last 45 years.

Cadmium, mercury and lead in the blood of urban women in Croatia, the Czech Republic, Poland, Slovakia, Slovenia, Sweden, China, Ecuador and Morocco

ObjectivesThe aim of the study was to make an international comparison of blood levels of cadmium (B-Cd), lead (B-Pb) and mercury (B-Hg) of women in seven European, and three non-European cities, and to identify determinants.Materials and MethodsAbout 50 women (age: 46–62) from each city were recruited (totally 480) in 2006–2009. Interview and questionnaire data were obtained. Blood samples were analysed in one laboratory to avoid interlaboratory variation.ResultsBetween the European cities, the B-Pb and B-Cd results vary little (range of geometric means: 13.5–27.0 μg/l and 0.25–0.65 μg/l, respectively); the variation of B-Hg was larger (0.40–1.38 μg/l). Between the non-European cities the results for B-Pb, B-Cd and B-Hg were 19.2–68.0, 0.39–0.99 and 1.01–2.73 μg/l, respectively. Smoking was a statistically significant determinant for B-Cd, while fish and shellfish intakes contributed to B-Hg and B-Pb, amalgam fillings also contributed to B-Hg.ConclusionsThe present results confirm the previous results from children; the exposure to lead and cadmium varies only little between different European cities suggesting that other factors than the living area are more important. The study also confirms the previous findings of higher cadmium and lead levels in some non-European cities. The geographical variation for mercury is significant.

Prenatal mercury exposure, neurodevelopment and apolipoprotein E genetic polymorphism

Abstract The aim of the present study was to evaluate the association between prenatal exposure to mercury (Hg) and neurodevelopment of the child, taking into account genetic polymorphism of apolipoprotein E (Apoe) and other relevant confounders. Six hundred and one mother‐child pairs were recruited from the central Slovenia region and 243 from Rijeka, on the Croatian coast of the northern Adriatic. The total Hg in cord blood, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley‐III) assessment at 18 months of age and Apoe genotyping was performed on 361 children; 237 of them were from Slovenia and 124 from Croatia. The results showed negative association between low‐to‐moderate Hg exposure in children with normal neurodevelopmental outcome and cognitive and fine motor scores at 18 months of age as assessed by Bayley III. The Hg‐related decrease in cognitive score was observed only in children carrying at least one Apoe &egr;4 allele, while the decrease in fine motor scores was independent of the Apoe genotype. Adjusting for selenium (Se) and lead (Pb) levels, a positive association between Se and the language score and a negative association between Pb and the motor score was observed, but not in the subgroup of children carrying the &egr;4 allele. HighlightsApoe &egr;4 carriers showed negative association between cord blood Hg and cognitive score.Fine motor score was negatively associated with cord blood Hg in all children.Gene‐environment interaction was confirmed for the cognitive score..Se and Pb levels confounded the association between Hg and neurodevelopment.

Exposure to mercury in susceptible population groups living in the former mercury mining town of Idrija, Slovenia.

Abstract 500 years of mercury (Hg) mining in the town of Idrija has caused severe pollution in Idrija and its surroundings. Following the closure of the mine in 1995, the environment remains contaminated with Hg. Sources of elemental‐, inorganic‐ and methyl Hg exposure were identified, potential environmental level of exposure to Hg was evaluated and actual internal exposure to Hg was assessed in selected susceptible population groups comprising school‐age children and pregnant women living in Idrija and in control groups from rural and urban environments. The study of pregnant women (n=31) was conducted between 2003 and 2008, and the study of school‐age children (n=176) in 2008. Potential interaction of Hg with selenium (Se) in plasma was assessed in both study populations, while in pregnant women antioxidative enzyme activity (glutathione peroxidase, superoxide dismutase and catalase) in erythrocytes of maternal and cord blood was also assessed. Actual exposure to Hg as indicated by levels of Hg in childrens blood (geometric mean (GM) 0.92 &mgr;g/L), mothers blood (GM 1.86 &mgr;g/L), childrens urine (GM 1.08 &mgr;g/g crea.), mothers urine (GM 2.51 &mgr;g/L), childrens hair (GM 241 ng/g) and mothers hair (GM 251 ng/g) was higher in the two study groups from Idrija than in the control groups from rural areas, but was still at the level of a “normal” population and reflects mainly exposure to elemental Hg (Hg°) from dental amalgam and, to a certain extent atmospheric Hg°. Furthermore, the internal doses of Hg received during pregnancy did not decrease the bioavailability of Se. Based on observation in children, the increase in Se protein expression is suggested to be a consequence of moderately elevated exposure to Hg°. The observed changes in activity of antioxidative enzymes, as biomarkers of oxidative stress, appear to be mainly associated with pregnancy per se and not with an increased exposure to Hg. In view of the continuing increased potential for Hg exposure and the low number of pregnant women studied, the results warrant a further longitudinal study of a larger group of pregnant women residing in the area of the former mercury mine. HighlightsEstimated environmental Hg exposure in the town of Idrija still poses a potential risk to susceptible groups of inhabitants.Actual internal exposure reflects mainly exposure to Hg° from dental amalgam and, to a certain extent atmospheric Hg°.The internal doses of Hg received in the Idrija children and pregnant women did not decrease the bioavailability of Se.Changes in activity of antioxidative enzymes were not associated with exposure to Hg in the town of Idrija.

Association of Uremic Toxins and Inflammatory Markers with Physical Performance in Dialysis Patients

Association of higher serum levels of uremic toxins and inflammatory markers with poorer physical performance is understudied. We measured the six-minute walk test (6MWT), 10 repetition sit-to-stand test (STS-10), handgrip strength (HGS), and Human Activity Profile (HAP) questionnaire score in 90 prevalent hemodialysis patents, with low comorbidity to reduce the potential confounding of concomitant disease. Midweek pre-dialysis serum levels of asymmetric dimethyl-arginine (ADMA), β2-microglobulin (B2M), high-sensitivity C-reactive protein (hs-CRP), indoxyl sulfate (IS), insulin-like growth factor 1 (IGF-1), interleukin 6 (IL-6), myostatin, and urea were analyzed as predictor parameters of physical performance measures in adjusted models. Serum levels of most measured toxins were not significantly related to performance, except for ADMA, which was significantly related to poorer performance in the STS-10 test (B = 0.11 ± 0.03 s, p < 0.01). Higher hs-CRP was associated with poorer results in the 6MWT (B = −2.6 ± 0.97 m, p < 0.01) and a lower HAP score (B = −0.36 ± 0.14, p = 0.01). There were no other significant associations found. We conclude that inflammation may be a more important pathway to physical impediment than uremic toxemia. This suggests that there is a large physical rehabilitation potential in non-inflamed uremic patients.

Prenatal mercury exposure and child neurodevelopment outcomes at 18 months: Results from the Mediterranean PHIME cohort

INTRODUCTIONnNeurotoxicity due to acute prenatal exposure to high-dose of mercury (Hg) is well documented. However, the effect of prenatal exposure to low Hg levels on child neurodevelopment and the question about safety of fish-eating during pregnancy remain controversial. International comparisons of Hg concentrations in mother-child biological samples and neurodevelopmental scores embedded in birth cohort studies may provide useful evidence to explore this issue.nnnMATERIALS AND METHODSnThe Mediterranean (Italy, Slovenia, Croatia, and Greece) cohort study included 1308 mother-child pairs enrolled in the Public Health Impact of long-term, low-level, Mixed Element exposure in a susceptible population EU Sixth Framework Programme (PHIME). Maternal hair and venous blood, cord blood and breast milk samples were collected, and total Hg (THg) levels were measured. Demographic and socioeconomic information, lifestyles and nutritional habits were collected through questionnaires at different phases of follow-up. Children at 18 months of age underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Multivariate linear and logistic regressions were performed, for each country, to assess the association between THg and BSID-III scores, obtaining adjusted β coefficients and odds ratios (ORs). These values were used to conduct a meta-analysis, to explore possible heterogeneity among countries and to obtain combined estimates of the association between THg exposure and BSID-III scores.nnnRESULTSnMedian THg (ng/g) was: 704 in maternal hair, 2.4 in maternal blood, 3.6 in cord blood, and 0.6 in breast milk. THg concentrations were highest in Greece and lowest in Slovenia. BSID-III neurodevelopmental scores were higher in Croatia and Slovenia. The meta-analysis of multivariate linear models found an overall positive association between language composite score and receptive communication scaled score and increasing THg in maternal hair (nu202f=u202f1086; βu202f=u202f0.55; 95%CI: 0.05-1.05 and nu202f=u202f1075; βu202f=u202f0.12; 95%CI: 0.02-0.22, respectively). The meta-analysis of logistic regression models showed that the overall adjusted OR between THg in cord blood and suboptimal gross motor score was borderline significant (nu202f=u202f882; ORu202f=u202f1.03; 95%CI: 1.00-1.07). Heterogeneity was found across the four sub-cohorts for language composite score in maternal blood, and for fine motor scaled score in cord blood and breast milk. Language composite score and THg concentrations in maternal venous blood were positively related (nu202f=u202f58; βu202f=u202f4.29; CI95% (-0.02, 8.60)) in Croatia and an increase of 1u202fng/g of THg in maternal venous blood was associated with a reduced risk for children to fall in the lowest quintile of language score by 31% (nu202f=u202f58; ORu202f=u202f0.69; CI 95%: 0.37, 1.01). The comparison of β coefficients obtained by multiple linear regression model showed an inverse association between fine motor score and THg concentrations in cord blood for Croatia (nu202f=u202f54; βu202f=u202f-0.53; CI 95%: -1.10, 0.04) and Slovenia (nu202f=u202f225; βu202f=u202f-0.25; CI 95%: -0.49, -0.01). In Slovenia THg level in breast milk was associated with suboptimal fine motor performance (nu202f=u202f195; ORu202f=u202f5.25; CI 95%: 1.36, 21.10).nnnCONCLUSIONSnThis study showed an inverse relation between THg levels and developmental motor scores at 18 months, although the evidence was weak and partially internally and externally inconsistent. No evidence of detrimental effects of THg was found for cognitive and language outcomes at these concentrations and age.

Platinum, palladium, rhodium, molybdenum and strontium in blood of urban women in nine countries

BACKGROUNDnThere is little reliable information on human exposure to the metals platinum (Pt), palladium (Pd) and rhodium (Rh), despite their use in enormous quantities in catalytic converters for automobile exhaust systems.nnnOBJECTIVESnTo evaluate blood concentrations of Pt (B-Pt), Pd (B-Pd) and Rh (B-Rh) in women from six European and three non-European countries, and to identify potentially influential factors. In addition, molybdenum (Mo) and strontium (Sr) were analysed.nnnMETHODSnBlood from 248 women aged 47-61 was analysed by high resolution inductively coupled plasma mass spectrometry under strict quality control.nnnRESULTSnThe medians were: B-Pt 0.8 (range <0.6-5.2), B-Pd <5 (<5-9.3), B-Rh <0.4 (<0.4-3.6)ng/L and B-Mo 2.0 (0.2-16) and B-Sr 16.6 (3.5-49) μg/L. Two women with highly elevated B-Pt (242 and 60ng/L), previously cancer treated with cis-platinum, were not included in the data analysis. All elements varied geographically (2-3 times) (B-Pd P=0.05; all other elements P<0.001); variations within each area were generally 5-10 times. Traffic was not associated with increased concentrations.nnnCONCLUSIONSnGeneral population blood concentrations of Pt, Pd and Rh are within or below the single digit ng/L range, much lower than in most previous reports. This is probably due to improved analytical performance, allowing for more reliable information at ultra-trace levels. In general, Mo and Sr agreed with previously reported concentrations. All elements showed geographical and inter-individual variations, but no convincing relationships with self-reported traffic intensity were found. Pt from the antineoplastic drug cis-platinum is retained in the body for years.

The impact of gene polymorphisms in angiotensin receptor 1 and aldosterone synthase in peritoneal dialysis patients

AIMnLongevity of peritoneal membrane is an important issue in patients treated with peritoneal dialysis (PD). In our study, we studied the impact of angiotensin receptor 1 (AGT R1) and aldosterone synthase (CYP11B2) gene polymorphism on peritoneal concentrations of interleukin-6 (PI-IL-6), vascular endothelial growth factor (PI-VEGF), plasminogen activator inhibitor-1 (PI-PAI-1), transforming growth factor-β (PI-TGF-β), and cancer antigen-125 (PI-CA-125) as known markers of peritoneal fibrosis. The single nucleotide polymorphism rs5186 (A1166C) in AGT R1 gene is located in 3 untranslated region (UTR) of the gene, while polymorphism rs1799998 (T -344 C) in CYP11B2 gene is located in the promoter region of the gene.nnnMETHODSnWe compared marker concentrations in patients with genotype DD vs. Dd and dd for AGT R1 and patients with genotype HH vs. Hh and hh for CYP11B2.nnnRESULTSnThe results show that polymorphism of CYP11B2 gene is associated with serum concentration of aldosterone. Patients with genotype HH had statistically significantly lower serum concentration of aldosterone (pxa0=xa00.04). These patients also showed a trend to a lower rate of production of I-IL-6 (pxa0=xa00.07), which correlated with lower concentrations of PAI-1 (pxa0=xa00.002) and VEGF (pxa0=xa00.005). AGT R1 gene polymorphism did not show any association with studied variables.nnnCONCLUSIONSnOur findings suggest the possibility of genetic predisposition for development of peritoneal fibrosis that could be important for identification of patients with an unfavorable genotype, which could lead to customized prescription of appropriate therapy and personalized patient management.u2029.