Physiologically based pharmacokinetic modeling of perfluoroalkyl substances in the human body

Currently, there are limited data on the levels of perfluoroalkyl substances other than perfluorooctane sulfonic acid and perfluorooctanoic acid in the human body. Most of this information has been extracted from biological monitoring of plasma while the occurrence of perfluoroalkyl substances in other human tissues is rarely studied. The objective of the present study was to develop a physiologically based pharmacokinetic model to assess the concentration of perfluoroalkyl substances in human tissues, based on an existing model previously validated for perfluorooctane sulfonic acid and perfluorooctanoic acid. Experimental data on concentrations of perfluoroalkyl substances in human tissues from individuals in Tarragona County (Catalonia, Spain) were used to estimate the values of some distribution and elimination parameters needed for the simulation. No significant correlations were found between these parameters and the chain lengths. The model was finally validated for five perfluoroalkyl substances.     

Relationship between Coefficient of Inbreeding and Parasite Burden in Endangered Gazelles

Abstract: We studied the effects of inbreeding depression on parasite infection in three species of endangered gazelles: Gazella cuvieri , G. dama, and G. dorcas . Coefficients of inbreeding were calculated for all individuals because complete genealogies were available. The levels of inbreeding differ both intra- and interspecifically. We collected samples of feces and determined nematode infection by counting nematode eggs in the samples. At the interspecific level, the species with the highest mean levels of inbreeding (  G. cuvieri ) had the highest levels of gastrointestinal parasites. Analyses done at the intraspecific level revealed a positive relationship between individual coefficient of inbreeding and parasite infection in G. cuvieri , but not in the species with the intermediate and lowest levels of inbreeding. Our findings suggest that high levels of inbreeding may make individuals more susceptible to parasitism, even under favorable environmental conditions, so this factor should be taken into account by those managing endangered species.     

Atmospherically deposited major and trace elements in the winter snowpack along a gradient of altitude in the Central Pyrenees: The seasonal record of long-range fluxes over SW Europe

The chemistry of high mountain snowpacks is a result of the long-range atmospheric transport and deposition of elements. Pyrenean snowpacks contain information about the fluxes of elements over SW Europe in winter. Here we analysed Al, Ti, Mn, Fe, Ni, Cu, Zn, As, Se, Cd and Pb in the 2004–05 winter snowpack in the Central Pyrenees, at an altitude range of 1820–3200 m a.s.l. Ni, As, Se and Cd were not detected in most cases. The concentrations of the remaining elements were comparable to those found in other high mountain areas in Europe and North America considered representative of regional background of atmospheric deposition in populated areas. In contrast, our measurements were higher than those of polar areas, which represent the global background. Single measurements of concentrations and snow accumulation were subject to considerable spatial variability, which may be attributable to strong wind drift and other post-depositional processes. The major ions chemistry of the snow indicated three possible origins for the solutes: terrigenous dust, sea salt spray and polluting S and N aerosols. We found no association between Cu, Zn and Pb and any of these possible sources. This observation therefore indicates that these elements were not preferentially bound to any particular kind of aerosol. Snow collected at altitudes of up to 2050 m a.s.l. presented higher concentrations of several elements than snow above this altitude, thereby indicating a local influence. Snow collected above 2300 m a.s.l. was therefore more representative of broad regional inputs. At these higher altitudes, snow was not enriched in Al, Ti, Mn, Fe or As compared with the composition of the upper continental crust and the local lithology, and these elements (except Mn) appeared almost exclusively in the particulate fraction. This observation indicates that Al, Ti, Mn, Fe and As were present mainly as part of dust particles of terrigenous origin. In contrast, Cu, Zn, and Pb presented medium to high enrichment factors and showed a higher proportion of soluble forms, thereby indicating their polluting character.     

Prenatal diagnosis and fetal pathology of partial trisomy 20p–monosomy 4p resulting from paternal translocation

Amniocentesis was performed in view of a paternal balanced chromosomal rearrangement t(4;20)(p16;p12), inv(18)(p11q11). The pregnancy was complicated by severe oligohydramnios. The fetal karyotype was unbalanced: 46XX, der(4), t(4;20)(p16;p12), inv(18) (p11q11)pat., thus resulting in partial trisomy 2Op and monosomy 4p. In addition, the amniotic fluid alpha-fetoprotein (AFP) became increasingly elevated with gestational age. The pregnancy was terminated at 25 weeks. The fetus presented with typical facial dysmorphic features, unilateral cleft lip and palate, severe renal hypoplasia, consistent with the 4p- (Wolf-Hirschhorn) syndrome.     

Pilot study for the neonatal screening of fragile X syndrome

An Erratum has been published for this article in Prenatal Diagnosis 23 (9), 2003, 771. Fragile X syndrome (SFX) is the commonest form of inherited mental retardation. Due to the highly variable phenotype clinical diagnosis is complicated. In nearly all cases, the disorder is caused by expansion of a CGG-repeat in the 5′-untranslated region of the FMR1 (fragile X mental retardation-1) gene. We have evaluated the feasibility, efficiency and costs of two methodologies in order to develop a simple test to screen large populations: PCR and fragile X mental retardation-1 protein (FMRP) immunodetection. We studied 100 newborn males using PCR and immunodetection (26.91 Euro). All but one amplified the CGG repeat of the FMR1 gene within the normal size range. The sample that failed to amplify showed only 28% of FMRP expression by immunodetection study; both results indicated an affected male. A further 100 males were studied only by polymerase chain reaction (PCR) (7.8 Euro); all of them amplified within the normal size range. Both methodologies, PCR and immunodetection, are feasible for screening large populations, PCR being the most suitable, economical and less time-consuming. However, it is advisable to keep slides for immunodetection when PCR fails or the external control shows no amplification. Early detection of SFX-affected individuals would represent a great benefit for their maximum social integration, due to appropriate treatment and early stimulation and would permit a cascade screening in their pedigree. Copyright © 2002 John Wiley & Sons, Ltd.     

An approach to preimplantation diagnosis of β-thalassaemia

Using the polymerase chain reaction (PCR), it was possible to amplify a single copy fragment of the β-globin gene from 2–32 human embryonic cells obtained from arrested preimplantation embryos. For the detection of β-thalassaemia mutations, allele specific priming of the PCR using nested primers was employed using approximately 10 pg of DN A from individuals known to carry these mutations. This approach was successful in detecting the presence or absence of five Asian Indian β-thalassaemia mutations that were selected for this study. In spite of meticulous precautions against contamination, false-positive amplification was observed, a problem that will have to be overcome before this approach can be used in clinical practice.     

Prenatal diagnosis of 5p deletion syndrome following abnormally low maternal serum human chorionic gonadotrophin

Prenatal diagnosis of 5p deletion syndrome, or cri du chat, following an abnormally low measurement of a screening of serum human chorionic gonadotrophin (hCG), is reported. Karyotyping following amniocentesis revealed a terminal deletion in the short arm of one chromosome 5. The pregnancy was electively terminated. 5p deletion syndrome has been described with abnormally high hCG levels and normal hCG levels. This is the first report of its association with abnormally low levels. The association between chromosomal abnormalities and hCG is discussed. Copyright © 2003 John Wiley & Sons, Ltd.