Health impact of air pollution to children

Health impact of air pollution to children was studied over the last twenty years in heavily polluted parts of the Czech Republic during. The research program (Teplice Program) analyzed these effects in the polluted district Teplice (North Bohemia) and control district Prachatice (Southern Bohemia).     

Four novel point mutations in the PMP22 gene with phenotypes of HNPP and Dejerine-Sottas neuropathy

We report four novel point mutations in the PMP22 gene with two different phenotypes: mutation p.Ser79Thr arose de novo in a patient with the Dejerine-Sottas neuropathy (DSN) phenotype; and mutations c.78+5 G>A, c.320-1 G>C, and p.Trp140Stop segregated with HNPP in 5 families.Our findings show that point mutations in PMP22 may be more likely in HNPP patients than in CMT1 patients after exclusion of CMT1A/HNPP.     

Biomarkers of exposure and effect��interpretation in human risk assessment

The effect of exposure to carcinogenic polycyclic aromatic hydrocarbons adsorbed onto respirable air particles (PM2.5, diameter 相似文献   

Role of GSTT1 deletion in DNA oxidative damage by exposure to polycyclic aromatic hydrocarbons in humans

A useful approach for studies on the mechanisms of genetic variation in cancer susceptibility is to use intermediary biochemical endpoints with mechanistic relevance to the genes under study. We examined the effects of individual genotype at seven metabolic gene loci on a marker of oxidative DNA damage, 8-oxo-7,8-dihydro-2-deoxyguanosine, in people exposed to polycyclic aromatic hydrocarbons (PAH) from three Central European cities. The GSTT1 homozygous deletion variant was associated with a significant protective effect for exposure to total PAHs and to eight specific PAHs, although the magnitude and significance of the effect varied among these compounds. Categorical sensitivity analysis was used to determine that the frequency of the GSTT1 deletion was significantly higher in people who proved to be more resistant to the DNA damaging effects of PAH exposure than in people who were the most sensitive. There is a growing literature on the protective effect of GSTT1 deletion in both disease and intermediary endpoints related to environmental carcinogenesis. The mechanism for this effect might be related to specific PAH substrate specificities, or could be related to other functions of GSTT1 gene in oxidative stress induced damage pathways.     

Environmental exposure to carcinogenic polycyclic aromatic hydrocarbons--the interpretation of cytogenetic analysis by FISH

The capital city of Prague is one of the most polluted localities of the Czech Republic. The effect of exposure to carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) adsorbed onto respirable air particles (<2.5 microm) on chromosomal aberrations was studied in a group of city policemen (street patrol, aged 34+/-8 years) working in the downtown area of Prague and spending daily >8h outdoors (N=61) in months of January and March 2004. Ambient air particles (PM10, PM2.5) and c-PAHs were monitored using Versatile Air Pollution Sampler (VAPS), and personal exposure was evaluated using personal samplers during working shift. Chromosomal aberrations were analyzed by fluorescent in situ hybridization (FISH) and conventional cytogenetic analysis. Urinary cotinine, plasma levels of vitamins A, E and C, folate, total cholesterol, HDL, LDL cholesterols and triglycerides were also analyzed as possible effect modifiers. During the sampling period the particulate air pollution monitored by VAPS was in January versus March as follows: PM10 55.6 microg/m3 versus 36.4 microg/m3, PM2.5 44.4 microg/m3 versus 24.8 microg/m3, c-PAHs 19.7 ng/m3 versus 3.6 ng/m3, and B[a]P 4.3 ng/m3 versus 0.8 ng/m3. Significant differences were observed for all FISH endpoints studied for the sampling in January and March (%AB.C.=0.27+/-0.18 versus 0.16+/-0.17, p<0.001, F(G)/100=1.32+/-1.07 versus 0.85+/-0.95, p<0.01, AB/1000 (aberrations/1000 cells)=4.27+/-3.09 versus 2.59+/-2.79, p<0.001) while conventional cytogenetic analysis did not reveal any differences in the frequency of chromosomal aberrations. Factors associated with an increased level of translocations by FISH indicated the effect of age, cholesterol, LDL-cholesterol and vitamin C. We may conclude that FISH indicates that the city policemen in Prague represent a group of increased genotoxic risk. This is the first study reporting that translocations induced by c-PAHs in peripheral lymphocytes last only several weeks.     

The DNA repair gene XPD/ERCC2 polymorphisms Arg156Arg (exon 6) and Lys751Gln (exon 23) are closely associated

In the context of a molecular epidemiology study dealing with the effects of individual genetic susceptibility on childhood respiratory morbidity, DNA repair genotypes for the XPD/ERCC2 gene in exon 6 (Arg156Arg) and exon 23 (Lys751Gln) have been analyzed by PCR/RFLP assays in DNA samples isolated from the fetal parts of placentas. The study was performed using a cohort of 729 children born in 1994-1998 in two districts of the Czech Republic. On the basis of these data, we tested the association between the two genotypes. The principal finding of this study is that the exon 6 and exon 23 polymorphisms in the XPD/ERCC2 gene are tightly associated, with persons who are homozygous CC in exon 23 being mostly (81%) homozygous CC in exon 6, and persons homozygous AA in exon 6 mostly (88%) homozygous AA in exon 23. This strong association may have serious consequences for the interpretation of cancer susceptibility and other molecular epidemiology studies dealing with the XPD6 and XPD23 genotypes, since the observed effects of the silent XPD6 polymorphism might be, in fact, the result of XPD23 polymorphism, which is connected with an amino acid substitution in the resulting XPD protein.     

Long‐term health outcome and mortality evaluation after invasive coronary treatment using drug eluting stents with or without the IVUS guidance. Randomized control trial. HOME DES IVUS

Objective : To assess the role of the intravascular ultrasound (IVUS) during implantation of Drug‐eluting stents (DES) on long‐term outcome in patients with complex coronary artery disease and high clinical risk profile with special attention to the development of late stent thrombosis (LST). Methods : Two hunderd and ten patients were randomly assigned to receive DES either with (N = 105) or without (N = 105) the IVUS guidance. Dual antiplatelet treatment was administered for 6 months in all patients. At 18‐month follow‐up, the rates of Major adverse cardiac events (MACEs) (death, myocardial infarction, and reintervention) were assessed in both groups with special attention to possible LST. Stent thrombosis was classified according to Academic Research Consortium (ARC). Results : At the 18‐month follow‐up, there was no significant difference between both groups regarding MACE (11% vs. 12%; P = NS). Stent thrombosis has occurred in four patients (3.8%) in the group with and in 6 patients (5.7%; P = NS) in the group without the IVUS guidance. Conclusions : In our randomized trial we failed to demonstrate the superiority of the IVUS guidance during DES implantation over standard high‐pressure postdilatation. However we confirmed worrisome results concerning DES thrombosis after discontinuation of dual antiplatelet‐treatment with documented stent thrombosis related events in almost 5% of patients with 50% of mortality in this high‐risk clinical scenario. © 2009 Wiley‐Liss, Inc.     

Linking the sub-Saharan and West Eurasian gene pools: maternal and paternal heritage of the Tuareg nomads from the African Sahel

The Tuareg presently live in the Sahara and the Sahel. Their ancestors are commonly believed to be the Garamantes of the Libyan Fezzan, ever since it was suggested by authors of antiquity. Biological evidence, based on classical genetic markers, however, indicates kinship with the Beja of Eastern Sudan. Our study of mitochondrial DNA (mtDNA) sequences and Y chromosome SNPs of three different southern Tuareg groups from Mali, Burkina Faso and the Republic of Niger reveals a West Eurasian-North African composition of their gene pool. The data show that certain genetic lineages could not have been introduced into this population earlier than ∼9000 years ago whereas local expansions establish a minimal date at around 3000 years ago. Some of the mtDNA haplogroups observed in the Tuareg population were involved in the post-Last Glacial Maximum human expansion from Iberian refugia towards both Europe and North Africa. Interestingly, no Near Eastern mtDNA lineages connected with the Neolithic expansion have been observed in our population sample. On the other hand, the Y chromosome SNPs data show that the paternal lineages can very probably be traced to the Near Eastern Neolithic demic expansion towards North Africa, a period that is otherwise concordant with the above-mentioned mtDNA expansion. The time frame for the migration of the Tuareg towards the African Sahel belt overlaps that of early Holocene climatic changes across the Sahara (from the optimal greening ∼10 000 YBP to the extant aridity beginning at ∼6000 YBP) and the migrations of other African nomadic peoples in the area.     

Factor VIII gene deletions in haemophilia A patients in Czechoslovakia

Genomic DNA from 90 Czechoslovak haemophilia A patients from 81 pedigrees was analysed by Southern blotting and hybridization with factor VIII cDNA probes. Three partial deletions of the factor VIII gene were identified and characterized: a 4.8 kilobase (kb) deletion eliminating exon 10 in one patient with severe haemophilia A without inhibitor, a 6.1 kb deletion eliminating the 3' part of intron 13 and the 5' part of exon 14 in two related severe haemophiliacs, but only one of them produced inhibitor, and a 4.6 kb deletion eliminating the 3' part of intron 13 and the 5' part of exon 14 in a severe haemophiliac with high-titre inhibitor. Besides these three deletions, three different restriction site variants without apparent loss of DNA sequence were found.