The influence of cytochrome P450 2D6 (CYP2D6) genetic variability was examined in psychiatric inpatients by evaluating adverse drug events (ADEs), hospital stays, and total costs over a 1-year period in an extension of a previously published brief report. One hundred consecutive psychiatric patients from Eastern State Hospital in Lexington, Kentucky, were genotyped for CYP2D6 expression. ADEs were evaluated by a neurologic rating scale, modified Udvalg for Kliniske Undersogelser Side Effect Rating Scale, or chart review. Information on total hospitalization days and total costs were gathered for a 1-year period. Forty-five percent of the patients received medications that were primarily dependent on the CYP2D6 enzyme for their elimination. When the analysis was restricted to just those patients in each group receiving medication heavily dependent on the CYP2D6 enzyme, the following were observed: (1) a trend toward greater numbers of ADEs from medications as one moved from the group with ultrarapid CYP2D6 activity (UM) to the group with absent CYP2D6 activity (PM); (2) the cost of treating patients with extremes in CYP2D6 activity (UM and PM) was on average $4,000 to $6,000 per year greater than the cost of treating patients in the efficient metabolizer (EM) and intermediate metabolizer (IM) groups; and (3) total duration of hospital stay was more pronounced for those in CYP2D6 PM group. Variance of hospital stays and costs calculated from these preliminary data suggests that 1,500 to 2,000 patients must be evaluated over at least a 1-year period to determine whether the CYP2D6 genetic variation significantly alters the duration of hospital stay and costs.
Carvacrol is one of the members of monoterpene phenol and is present in the volatile oils of Thymus vulgaris, Carum copticum, origanum and oregano. It is a safe food additive commonly used in our daily life, and few studies have indicated that carvacrol has anti-hepatocarcinogenic activities. The rationale of the study was to examine whether carvacrol affects apoptosis of human hepatoma HepG2 cells. In this study, we showed that carvacrol inhibited HepG2 cell growth by inducing apoptosis as evidenced by Hoechst 33258 stain and Flow cytometric (FCM) analysis. Incubation of HepG2 cells with carvacrol for 24 h induced apoptosis by the activation of caspase-3, cleavage of PARP and decreased Bcl-2 gene expression. These results demonstrated that a significant fraction of carvacrol treated cells died by an apoptotic pathway in HepG2 cells. Moreover, carvacrol selectively altered the phosphorylation state of members of the MAPK superfamily, decreasing phosphorylation of ERK1/2 significantly in a dosedependent manner, and activated phosphorylation of p38 but not affecting JNK MAPK phosphorylation. These results suggest that carvacrol may induce apoptosis by direct activation of the mitochondrial pathway, and the mitogen-activated protein kinase pathway may play an important role in the antitumor effect of carvacrol. These results have identified, for the first time, the biological activity of carvacrol in HepG2 cells and should lead to further development of carvacrol for liver disease therapy.
Background: There have been no published reports comparing the CYP450 GeneChip ® microarray assay with more standard methods of genetic testing. Methods: We collected 20-mL blood samples from 236 volunteers for DNA isolation and testing before each individual ingested 60 mg of dextromethorphan, and collected their urine. CYP2D6 alleles *3 to *7, *9, *17, and *41, and multiple CYP2D6 gene copies were tested by allele-specific PCR (AS-PCR), whereas alleles *2 to *4 and *6 to *11 were tested by the Affymetrix CYP450 GeneChip assay. Five of the CYP2D6 alleles (*3, *4, *6, *7, and *9) were tested by both AS-PCR and the CYP450 GeneChip assay in an independent and blinded fashion in 232 of the 236 healthy volunteers. The combined CYP2D6 genotype from both methods was used to divide the population into four subgroups, poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs), based on their relative function and ability to express the CYP2D6 gene. The urinary elimination of dextromethorphan was assessed in each of these CYP2D6 subgroups.
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