Monitoring of industrial exposure for chloracne

This study (1) established comedogenicity dose response curves for the pure compounds of 3,3$\sp\prime$,4,4$\sp\prime$-tetrachloroazobenzene (TCAB) and 3,3$\sp\prime$,4,4$\sp\prime$-tetrachloroazoxybenzene (TCAOB) individually and as a couple-compound using a rabbit ear model; (2) used a rabbit ear model to establish comedogenicity potential for TCAB and TCAOB as they existed in a given industrial herbicide manufacture process; (3) evaluated actual environmental contamination in a herbicide industrial setting by air monitoring and wipe sampling; (4) biologically monitored potentially exposed workers for alterations in follicular orifice size as an index of actual exposure to chloracnegenic compounds; and (5) biologically monitored potentially exposed workers for changes in weight, cholesterol, triglycerides and blood sugar.^ A silastic monomer mold (an objective measure) was used to measure change in follicular orifice size over time. This required taking impressions of (1) skin of the forehead and right and left malar crescents of workers and (2) the skin of the external ear of the rabbit. Molds were stained using a solution of hematoxylin and digitized using a Nikon UFX microscope (magnification 300 X), a drawing tube and a digitizing tablet attached to an IBM Personal Computer. Comedogenicity assays were used to establish dose-response curves for TCAB, TCAOB and the couple-compound TCAB + TCAOB.^ No evidence of chloracne or toxicity was observed in any of the workers. Nor, was there a statistically significant increase in size of follicular orifice means measured over time. This was attributed to extensive personal and environmental hygiene programs along with teaching the workers about chloracne, its cause and its prevention. These programs may have been the greatest factor in preventing the development of chloracne in this group of workers. Monitoring of the plant environment showed relatively high concentrations of the couple-compound (TCAB + TCAOB). Comedogenicity assays showed a linear dose-response relationship over time for TCAB, TCAOB and the couple-compound. An antagonistic action was found for the TCAB/TCAOB of the couple-compound; such action may provide some protection to workers in this type of setting. It is speculated that the observed antagonistic action may be due to the difference in binding affinities of TCAB/TCAOB for receptor sites. ^

Genetic underpinnings of variation in brain ventricular volume: A genome-wide association study

The ventricular system is a critical component of the central nervous system (CNS) that is formed early in the developmental stages and remains functional through the lifetime. Changes in the ventricular system can be easily discerned via neuroimaging procedures and most of the time it reflects changes in the physiology of the CNS. In this study we attempted to identify specific genes associated with variation in ventricular volume in humans. Methods. We conducted a genome wide association (GWA) analysis of the volume of the lateral ventricles among 1605 individuals of European ancestry from two community based cohorts, the Genetics of Microangiopathic Brain Injury (GMBI; N=814) and Atherosclerosis Risk in Communities (ARIC; N=791). Significant findings from the analysis were tested for replication in both the cohorts and then meta-analyzed to get an estimate of overall significance. Results. In our GWA analyses, no single nucleotide polymorphism (SNP) reached a genome-wide significance of p<10−8. There were 25 SNPs in GMBI and 9 SNPs in ARIC that reached a threshold of p<10 −5. However, none of the top SNPs from each cohort were replicated in the other. In the meta-analysis, no SNP reached the genome-wide threshold of 5×10−8, but we identified five novel SNPs associated with variation in ventricular volume at the p<10 −5 level. Strongest association was for rs2112536 in an intergenic region on chromosome 5q33 (Pmeta= 8.46×10−7 ). The remaining four SNPs were located on chromosome 3q23 encompassing the gene for Calsyntenin-2 (CLSTN2). The SNPs with strongest association in this region were rs17338555 (Pmeta= 5.28×10 −6), rs9812091 (Pmeta= 5.89×10−6 ), rs9812283 (Pmeta= 5.97×10−6) and rs9833213 (Pmeta= 6.96×10−6). Conclusions. This GWA study of ventricular volumes in the community-based cohorts of European descent identifies potential locus on chromosomes 3 and 5. Further characterization of these loci may provide insights into pathophysiology of ventricular involvement in various neurological diseases.^