Resident Evil Best Seller for Capcom, Street Fighter in 3rd

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Resident Evil, despite being the “newest” of the three franchises this post will talk about, is Capcom’s top seller of all time. The franchise has sold an unheard of 40 million units combined, which puts our estimate at 400 gaztrillion zombies killed. Roughly.

Following that up is the Mega Man franchise, which has entered gamers homes 28 million times, despite 28,000 variants. The only multi-player title in the top of the chart is Street Fighter, coming in behind Mega Man by only a million units which Street Fighter IV could eventually break.

Street Fighter has the last laugh however, as the original Street Fighter II on the Super NES is the single biggest hit, clocking in at 6.8 million copies. Today’s gaming kids probably don’t have a clue how huge that was, ending up on every magazine cover, sometimes multiple times in a row. Then again, to some of those kids, the concept of a gaming magazine may seem foreign… *sigh*

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Drug that eases tamoxifen side effect may also hinder its effectiveness.

Cancer Weekly December 23, 2003 2003 DEC 23 – (NewsRx.com & NewsRx.net) — An antidepressant used to ease a common side effect of the drug tamoxifen for breast cancer may conceivably reduce the effectiveness of tamoxifen by interfering with the breakdown of the drug into its active metabolites. site nexium side effects

Researchers reported the finding in the December 3, 2003, issue of the Journal of the National Cancer Institute (Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst, 2003;95:1758-64).

Hot flashes are the most common side effect of tamoxifen. New antidepressant drugs, such as the selective serotonin reuptake inhibitors (SSRIs) paroxetine and fluoxetine, are effective in treating tamoxifen-associated hot flashes. These drugs, however, have also been shown to inhibit the enzyme that converts tamoxifen to its known most potent metabolite, 4-hydroxy-tamoxifen, and other active metabolites. The implication is that co-prescription of SSRIs with tamoxifen may reduce the effectiveness of tamoxifen.

Vered Stearns, MD, now at Johns Hopkins University in Baltimore, Maryland; David A. Flockhart, MD, PhD, of the Indiana University School of Medicine, Indianapolis; and their colleagues examined the effect of paroxetine on levels of tamoxifen and its metabolites in blood samples from 12 women with breast cancer who were being treated with adjuvant tamoxifen. Paroxetine inhibits CYP2D6, an enzyme that is primarily responsible for the metabolism of tamoxifen into its active metabolites. The women received paroxetine for 4 weeks during their standard course of tamoxifen. They were also tested to determine their CYP2D6 genotype.

The researchers identified that a previously unrecognized active metabolite, which they named endoxifen, was present in substantially higher concentrations than 4-hydroxy-tamoxifen. They observed that: website nexium side effects

1) after paroxetine treatment, endoxifen levels decreased, whereas levels of 4-hydroxy-tamoxifen did not.

2) Treatment with paroxetine reduced the concentration of endoxifen from 12.4 ng/mL before paroxetine administration to 5.5 ng/mL after paroxetine administration.

3) Endoxifen concentrations decreased by 64% in women with a normal CYP2D6 genotype but by only 24% in women with a variant CYP2D6 genotype.

Stearns and colleagues say these findings “raise the possibility that pharmacogenetic variation in CYP2D6 activity may influence therapeutic outcomes from tamoxifen treatment.” However, they write, “larger trials are required to evaluate the clinical implications of low circulating endoxifen concentrations and, until further data become available, the results of this small study should not alter treatment recommendations.” In an accompanying editorial, Matthew P. Goetz, MD, and Charles L. Loprinzi, MD, of the Mayo Clinic in Rochester, Minnesota, caution that the clinical implications of reduced levels of endoxifen remain unclear. Furthermore, they say, “because the newer antidepressants studied for the treatment of hot flashes (venlafaxine, fluoxetine, and paroxetine) have differing levels of CYP2D6 inhibition, the pharmacokinetic interaction between tamoxifen and these antidepressants needs to be studied.” This article was prepared by Cancer Weekly editors from staff and other reports.