C. Barrot

Excretion of hexachlorobenzene and metabolites in feces in a highly exposed human population.

A set of 53 individuals from a population highly exposed to airborne hexachlorobenzene (HCB) were selected to study the elimination kinetics of this chemical in humans. The volunteers provided blood, 24-hr urine, and feces samples for analysis of HCB and metabolites. The serum HCB concentrations ranged from 2.4 to 1,485 ng/mL (mean +/- SD, 124 +/- 278), confirming that this human population has the highest HCB blood levels ever reported. All analyzed feces samples contained unchanged HCB (range, 11-3,025 ng/g dry weight; mean +/- SD, 395 +/- 629). The HCB concentration in feces strongly correlated with HCB in serum (r = 0.85; p < 0.001), suggesting an equilibrium in feces/serum that is compatible with a main pulmonary entrance of the chemical and low intestinal excretion of nonabsorbed foodborne HCB. The equilibrium is also compatible with a nonbiliary passive transfer of the chemical to the intestinal lumen. Two HCB main metabolites, pentachlorophenol (PCP) and pentachlorobenzenethiol (PCBT), were detected in 51% and 54% of feces samples, respectively. All urine samples contained PCP and PCBT, confirming the conclusions of a previous study [Environ Health Perspect 105:78-83 (1997)]. The comparison between feces and urine showed that whereas daily urinary elimination of metabolites may account for 3% of total HCB in blood, intestinal excretion of unchanged HCB may account for about 6%, thus showing the importance of metabolism in the overall elimination of HCB. The elimination of HCB and metabolites by both routes, however, appears to be very small (< 0.05%/day) as compared to the estimated HCB adipose depots. Features of HCB kinetics that we present in this study, i.e., nonsaturated intestinal elimination of HCB and excretion in feces and urine of inert glutathione derivatives, may explain, in part, the absence of porphyria cutanea in this human population heavily exposed to HCB. ImagesFigure 1Figure 2

Characterisation of three Amerindian populations from Hidalgo State (Mexico) by 15 STR-PCR polymorphisms

The purpose of this study is to report allele frequency data of three ethnic Amerindian population samples: the Otomi (Hña-hñu) from eastern Sierra Madre and Ixmiquilpan valley and the Huasteco from La Huasteca. These groups were characterised by 15 STR-PCR polymorphisms (HumTH01, HumvWA, D18S51, HumTPOX, D19S433, D16S539, D13S317, D8S1179, D7S820, D5S818, HumFGA, CSF1PO, D2S1338, D3S1358 and D21S11). No significant deviations in observed allelic frequencies from Hardy-Weinberg equilibrium were found for all the studied systems. From the forensic point of view, the heterozygosity value, power of discrimination and the a priori chance of exclusion were calculated.

Genetic Diversity of 15 STRs in Choles From Northeast of Chiapas (Mexico)

Allele frequencies for 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D19S433, HUMVWA31A, HUMTPOX, D18S51, D3S1358, HUMTHO1, D13S317, D16S539, D2S1338, D5S818, and HUMFGA) were analyzed in a Mexican population: Choles from Chiapas State. The aim of the study was to obtain accurate allele frequencies data and other genetic parameters of forensic interest on the Amerindian ethnic groups from Mexico, using an automatic method and commercial amplification kit. The agreement with HWE (Hardy-Weinberg equilibrium) was confirmed for all loci (based on the X2-test).

The Fang population of Equatorial Guinea characterised by 15 STR-PCR polymorphisms

Allele frequencies for 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D19S433, HUMVWA31A, HUMTPOX, D18S51, D3S1358, HUMTHO1, D13S317, D16S539, D2S1338, D5S818 and HUMFGA) were analysed in the Fang population of Bioko Island, Equatorial Guinea. No deviation from Hardy-Weinberg equilibrium was found for all loci. Statistical parameters demonstrated the forensic utility of the analysed systems.

Dopamine DRD2/ANKK1 Taq1A and DAT1 VNTR polymorphisms are associated with a cognitive flexibility profile in pathological gamblers

Like drug addiction, pathological gambling (PG) has been associated with impairments in executive functions and alterations in dopaminergic functioning; however, the role of dopamine (DA) in the executive profile of PG remains unclear. The aim of this study was to identify whether the DRD2/ANKK1 Taq1A-rs1800497 and the DAT1-40 bp VNTR polymorphisms are associated with cognitive flexibility (measured by Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT)) and inhibition response (measured by Stroop Color and Word Test (SCWT)), in a clinical sample of 69 PG patients. Our results showed an association between DA functioning and cognitive flexibility performance. The Taq1A A1+ (A1A2/A1A1) genotype was associated with poorer TMT performance (p < 0.05), while DAT1 9-repeat homozygotes displayed better WCST performance (p < 0.05) than either 10-repeat homozygotes or heterozygotes. We did not find any association between the DRD2 or DAT1 polymorphisms and the inhibition response. These results suggested that pathological gamblers with genetic predispositions toward lower availability of DA and D2 receptor density are at a higher risk of cognitive flexibility difficulties. Future studies should aim to shed more light on the genetic mechanisms underlying the executive profile in PG.

Analyzing the genetic structure of the Tepehua in relation to other neighbouring Mesoamerican populations. A study based on allele frequencies of STR markers.

We report data on the genetic variation of the Tepehua population based on 15 autosomal microsatellites. The Tepehua, whose language belongs to the Totonac family, are settled throughout the Sierra Madre Oriental in Mexico and constitute a group in demographic decline. The results suggest that the Tepehua population remained isolated throughout a large part of its history. Phylogenetic analyses performed with other indigenous and admixed populations of Mesoamerica allow us to address their biological history. The results suggest a genetic affinity between the Tepehua and the Huastecos due to their previous shared history, and a certain degree of differentiation from the Otomões groups and the Choles (who are of Mayan origin). A clear genetic differentiation is also apparent between native and admixed populations within the greater region of Mesoamerica. It is currently accepted that the genetic composition of the American populations fits a trihybrid model of admixture. The genetic structure based on comparison of 34 populations throughout the continent (9 indigenous and 23 admixed) using hierarchical cluster analysis with an explained variance of 61.17% suggests the existence of four large groups distinguished according to the degree of admixture between Amerindians, Europeans, and Africans. Am. J. Hum. Biol., 2008.

A Truncated‐Flt1 Isoform of Breast Cancer Cells Is Upregulated by Notch and Downregulated by Retinoic Acid

We have previously reported that the major isoform of Flt1/VEGFR‐1 expressed in MDA‐MB‐231 breast cancer cells was a truncated intracellular isoform transcribed from intron 21 (i21Flt1). This isoform upregulated the active form of Src and increased breast cancer cell invasiveness. Since expression of the transmembrane and soluble Flt1 isoforms of HUVEC is activated by Notch signaling, we wondered whether the expression of the intracellular isoform i21Flt1 was also dependent on Notch activation. We report here that the expression of i21Flt1 in HUVEC and MDA‐MB‐231 cells is downregulated by the γ‐secretase inhibitor DAPT. In addition, treatment of MDA‐MB‐231 cells with siRNA specific for Notch‐1 and Notch‐3 downregulates the expression of i21Flt1. In agreement with these findings, HUVEC and MDA‐MB‐231 breast cancer cells, cultured on dishes coated with recombinant human Dll4 extracellular domain, express higher levels of i21Flt1. In cancer cells, Flt1 is a target of the micro RNA family miR‐200. In MDA‐MB‐231 breast cancer cells, the truncated intracellular isoform i21Flt1 is also negatively regulated by miR‐200c. Retinoic acid interferes i21Flt1 expression by downregulating Notch‐3 and upregulating miR‐200 expression. Treatment of MDA‐MB‐231 breast cancer cells with both a γ‐secretase inhibitor and retinoic acid suppresses the expression of i21Flt1, providing a new mechanism to explain the effectiveness of this therapeutic approach. J. Cell. Biochem. 115: 52–61, 2014.

Polimorfismos genéticos como indicadores de la vulnerabilidad individual a la adicción al tabaco

BACKGROUND AND OBJECTIVES In line with genetic and pharmacological studies suggesting that neurotransmitter pathways play a role in nicotine dependence, research was conducted in connection with 4 genetic polymorphisms: OPRM1, TPH1, ADRA2A and HTR1B. This study compares the genotype and allele frequencies in 3 groups (non-smokers, former smokers and smokers) of unrelated individuals (n=490) from Catalonia (north east Spain) in order to find any relationship. MATERIAL AND METHODS All polymorphisms were genotyped in each population group and statistical analysis was performed. RESULTS Data obtained show that there is a relationship between sex, age and the TPH1 locus, indicating a trend towards a lower frequency of the AA genotype in former smokers for the TPH1 locus. CONCLUSIONS The results indicate that a role is played by the TPH1 polymorphism as an indicator of therapeutic failure in smoking cessation.

Huastecos Amerindian population (Mexico) characterised by 12 STR-PCR polymorphisms

The purpose of this study is to report allele frequency data of a Huastecos ethnic group population sample (n=89) from La Huasteca (Hidalgo, Mexico) for 12 STR-PCR polymorphisms (HumTH01, HumvWA, D18S51, HumTPOX, D19S433, D16S539, D13S317, D8S1179, D7S820, D5S818, HumFGA and D21S11). No significant deviations from Hardy-Weinberg expectation were found for all short-tandem repeats (STR). From forensic point of view, the heterozygosity value, power of discrimination and the a priori chance exclusion value were calculated. D 2003 Elsevier B.V. All rights reserved.