Slovakia is characterised by an unusually high number of patients affected by genetic Creutzfeldt-Jakob disease (CJD) with E200K mutation at the PRNP gene. Penetrance of the mutation is incomplete (59%). Therefore, for the onset of the clinical manifestation, an influence of other endo- or exogenous factors could not be excluded. Experimental data suggest that copper and manganese levels may play an important role in the pathogenesis of prion diseases. The highest number of Slovak genetic CJD patients originates from Orava – the northern region of central Slovakia. Manganese is a dominant pollutant in Orava. The objective of this study was to clarify a possible exogenous influence of environmental Mn/Cu imbalance on the CJD clustering. Mn and Cu levels were analysed in the brain tissue of genetic CJD cases (from Orava and from control regions of Slovakia), as well as of sporadic CJD patients and controls. Analyses demonstrate i) significantly higher Mn level in focally accumulated, "clustering" genetic CJD cases in comparison to all other groups, ii) Cu status differences between compared groups were without statistical significance; decreased concentrations were found in genetic cases from extrafocal genetic CJD areas, iii) Mn/Cu ratios were increased in all CJD groups in comparison to controls. Metal ratios in clustering gCJD cases were significantly higher in comparison to sporadic cases and also to controls, but not to the extrafocal genetic CJD subgroup. These results indicate that more important than increasing Mn level in pathogenesis of CJD appears to be the role of the Mn/Cu imbalance in the CNS. The imbalance observed in the cluster of genetic CJD cases is probably a result of both: the excessive environmental Mn level and the disturbance of Mn/Cu ratios in the Orava region. Presented findings indicate an environmental Mn/Cu imbalance as a possible exogenous CJD risk co-factor which may, in coincidence with endogenous (genetic) CJD risk, contribute to the focal accumulation (cluster) of genetic CJD in Slovakia.
- MeSH
- Creutzfeldtova-Jakobova nemoc epidemiologie etiologie genetika MeSH
- lidé MeSH
- mangan analýza škodlivé účinky MeSH
- měď analýza škodlivé účinky MeSH
- mozek - chemie MeSH
- polymerázová řetězová reakce MeSH
- polymorfismus genetický MeSH
- priony genetika MeSH
- rizikové faktory MeSH
- shluková analýza MeSH
- studie případů a kontrol MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- zeměpis MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Geografické názvy
- Slovenská republika MeSH
A method of Se determination in human milk by AAS using electrothermal atomization and a Zeeman background correction is described. The matrix modifier (Pd(NO3)2) concentration, sample dilution, ashing and atomization temperatures were optimised. For calculation of the results, the calibration curve method was used. Se concentrations in human milk were measured in eight Slovak localities. The mean Se level (14.27 ?g kg?1) was considerably lower compared with neighbouring countries
A simple method for methylmercury (MeHg+) determination in human venous blood is described using GCICP- MS. The blood sample preparation consists in the extraction with a mixture of 6M HCl and NaCl, pH adjustment, derivatization of mercury species using NaBPh4 with simultaneous extraction of products into hexane. The detection limits for MeHg+ were 86 ppt (as Hg) in the optimized method. The sample volume for repeated measurements was 150 l. The total Hg level in blood was determined by AAS using the amalgamation technique.
