A prolonged ED stay for older admitted patients is associated with an increased risk of an in-hospital AE. The longer hospital LOS associated with AEs further reduces the availability of acute care beds, thus exacerbating ED crowding.
Estrogen and its metabolites are believed to play important roles in breast cancer. The influence of genetic polymorphisms in the enzymes responsible for formation and disposition of estrogen on breast cancer risk may shed light on the importance of estrogen metabolites in this disease. However, for such studies to be valid, it is important to correctly identify the enzymes involved in estrogen bioactivation. Therefore, we assessed the human cytochrome P450 -dependent oxidation of estrone using substrate concentrations that more closely approximate the maximum expected concentrations in breast tissue. The in vitro metabolism of estrone by recombinant human cytochrome P450 enzymes and human liver microsomes was studied. The formation of estrone metabolites (2-hydroxyestrone, 4-hydroxyestrone, and 16A-hydroxyestrone) was monitored by high-performance liquid chromatography. 2-Hydroxyestrone formation was catalyzed predominantly by CYP1A2, CYP1A1, and CYP1B1 enzymes; 4-hydroxyestrone formation was catalyzed predominantly by CYP1B1, CYP1A2, and CYP1A1 enzymes; and 16A-hydroxyestrone formation was catalyzed predominantly by CYP2C19, CYP1A1, and CYP3A5. This study confirms the important role of members of the CYP1 family in the 2-hydroxylation and 4-hydroxylation of estrone, but the enzymes identified as responsible for the 16A-hydroxylation of estrone are different from those previously identified. The relative importance of these enzymes in vivo would depend on the specific tissue expression of the enzymes. These enzymes are all known to be genetically variant in the human population, and additional studies to assess the role CYP1A2, CYP2C19, and CYP3A5 in breast cancer risk are indicated. (Cancer Epidemiol Biomarkers Prev 2006;15(3):551 -8)
CAISP is a new agricultural injury surveillance program in Canada. Data from this system are actively used to inform prevention initiatives, and to indicate priorities for etiological and experimental research in the Canadian agricultural setting.
Ambient and non-ambient particles have different risk management approaches, composition, and likely toxicity. Therefore, a better understanding of their contribution to the indoor environment is important to manage the health risks associated with fine particles (FPs) effectively. As well, a better understanding of the factors Finf can help improve exposure assessment and contribute to reduced exposure misclassification in epidemiologic studies.
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