A number of arguments counted against the COX-3 hypothesis: COX-2-selective inhibitors react weakly with the COX-3 enzymatic site, because the site is identical to that in COX-1, but they are as good at reducing fever as older NSAIDs. The fever response has also been clearly associated with a rapid induction of COX-2 expression and an associated increase in prostaglandin E2 production, with no role for COX-1 or a COX-1 gene product (., COX-3). Finally, the sites of COX-3 expression do not appear to fit in well with those sites associated with fever, and the protein should be present within the hypothalamus rather than the cerebral cortex . All these considerations appeared to argue against COX-3 being the site of the antipyretic actions of NSAIDs and COX-2-selective agents. However, the results could be read as showing that paracetamol acts at a different site than the other NSAIDs and that more than one COX isoform contribute to the fever response.
"Tamoxifen therapy has also been linked to the development of fatty liver and steatohepatitis . In some prospective studies, up to one third of women have developed fatty liver during long term tamoxifen therapy, as shown by routine imaging using computerized tomography. Fatty liver usually becomes demonstrable within 1 to 2 years of starting tamoxifen but is usually not accompanied by symptoms, although serum aminotransferase levels may be elevated modestly in up to half of patients. Liver biopsy may demonstrate steatohepatitis and a proportion of women develop hepatic fibrosis. Several instances of cirrhosis have been described after therapy with tamoxifen for 3 to 5 years. Serum aminotransferase elevations and fatty liver generally improve once tamoxifen is stopped, but the improvement may be slow and in rare instances, signs and symptoms of portal hypertension persist."