Additionally, nuclear factor kB and its subunits p50 and p65 showed
enrichment. Immunohistochemical analyses of 10 TFs from the upregulated set showed 9 to be present in AAA tissue. Based on gene ontology analysis of biological process categories of the upregulated target genes of enriched TFs, 10 TFs had enrichment in immune system process among their target genes.
Conclusions-Our genome-wide analysis provides further evidence of ETS and nuclear factor kB involvement in AAA. Additionally, our results provide novel insight for future studies aiming to dissect the pathogenesis of AAA and have uncovered potential therapeutic targets for AAA prevention. (Circ Cardiovasc Genet. 2009;2:565-572.)”
“Comparative HPLC-UV and LC-MS/MS studies of impurity profiles of a reference sample (Xenical (R), F. Hoffmann La Roche Ltd., Switzerland) vs. generic (Lipiblock (R), EMS Sigma Pharma, a generic drug) were carried out small molecule library screening with ethanol extracts of commercial samples. The generic formulation contained higher levels of common impurities as well as a considerable number of impurities not found in the reference product. The detected impurity profile of Lipiblock (R) revealed that it most likely is based on fermentation. Since the effect of the impurities is unknown, at this point fully synthetic Xenical (R)
appears to offer a better safety margin than Lipiblock (R) which, however, compares quite well to other generic formulations.”
“Background-Disruption AZD0530 solubility dmso of the elastic lamina, find more as an early indicator of aneurysm formation, and vascular calcification frequently occur together in atherosclerotic lesions of humans.
Methods and Results-We now report evidence of shared genetic basis for disruption of the elastic lamina (medial disruption) and medial calcification in an F(2) mouse intercross between C57BL/6J and C3H/HeJ on a hyperlipidemic apolipoprotein E (ApoE(-/-)) null background.
We identified 3 quantitative trait loci (QTLs) on chromosomes 6, 13, and 18, which are common to both traits, and 2 additional QTLs for medial calcification on chromosomes 3 and 7. Medial disruption, including severe disruptions leading to aneurysm formation, and medial calcification were highly correlated and occurred concomitantly in the cross. The chromosome 18 locus showed a striking male sex-specificity for both traits. To identify candidate genes, we integrated data from microarray analysis, genetic segregation, and clinical traits. The chromosome 7 locus contains the Abcc6 gene, known to mediate myocardial calcification. Using transgenic complementation, we show that Abcc6 also contributes to aortic medial calcification.
Conclusions-Our data indicate that calcification, though possibly contributory, does not always lead to medial disruption and that in addition to aneurysm formation, medial disruption may be the precursor to calcification. (Circ Cardiovasc Genet. 2009;2:573-582.