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Perhaps the most obvious is the trend toward outsourcing, particularly to biotechnology companies, as a primary strategy for drug discovery.
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Continued from page 26 against the enzyme that was pretty promising. So I think that those approaches plus the approach that we've taken--which is to do more traditional structure-activity relationships in other words, make analogues of the molecules we have in a very systematic generalized approach to determine what are the minimum requirements [structurally] for an inhibitor of viral growth that doesn't inhibit cell growth ; --I think all of those approaches complement each other and will generate good results for integrase. And again, the same kind of approaches probably need to be done for other targets as well. transcriptase inhibitor than alone in reducing virus replication. And the less viral replication there is, the less likelihood of resistance there will be. So I think resistance, at least when integrase is used in multiple drug therapies, is likely to be less of a problem. And finally, in work that we haven't published yet but we're working on right now, the drug resistant variant is attenuated for growth. What that suggests is that although you can get resistance, the virus then doesn't grow as well, and the overall benefit then will be a balance between resistance and poor growth phenotype. And it will be hard to know if that is true in any given individual, until such trials are performed. Searchlight: In your early papers, you took pains to show that your integrase inhibitors are not inhibitors of the other enzymes of the virus. Robinson: I think that that's important because biscatechols, the class of compound that these fall under, are notorious for being relatively non-specific agents. And so we wanted to ensure that our drugs only acted, or at least acted very selectively, against integrase to get a better idea of whether that's how they were working inside a cell. It's also obvious that non-specific activity is not a problem with this particular group of bis-catechols [L-chicoric acid and the DCQAs] because we don't see cell toxicity, and we use very stringent criteria for cell toxicity. So there's no evidence that they're at all toxic. Actually in that paper that you referred to [by Sam Chow] we were very careful to look for inhibition of other metalloenzymes and were able to show that they were very specific for integrase. And finally, the reason we tried to raise a drug resistant mutant to L-chicoric acid was that by demonstrating that a single point mutation in integrase conferred resistance to the compound, we demonstrated the drug is acting, at least in part, through inhibition of integrase. Really up until that paper there was no direct evidence that you could even inhibit viral replication through inhibition of integrase with a small molecule. We had lots of indirect evidence but that was the first real direct evidence that a small molecule inhibitor was acting on integrase.

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Are well placed to make early diagnoses of PCOS and to help patients avoid the longterm consequences. Clinical Course Young women of reproductive age most frequently seek attention initially because of irregular menses, hirsutism, or infertility, but PCOS has a long prodrome with detectable abnormalities throughout the life cycle of affected women. The earliest manifestations of PCOS are discernible in the peripubertal years. Ovarian hyperandrogenism and insulin resistance develop with increased frequency in adolescent girls who have premature pubarche.11, 12 In the early reproductive period, chronic anovulation results in reduced rates of conception. When pregnancy is achieved, it frequently terminates in spontaneous, firsttrimester loss or is associated with gestational diabetes.6 Approximately 25 to 30 percent of these women show impaired glucose tolerance by the age of 30, and 8 percent of women with PCOS develop frank type 2 diabetes mellitus annually.7 Markers of premature coronary artery and and progesterone.
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And would you recommend bringing any documentation to to medical examiner stating the amount of control i have over my diabetes letter from my doctor, medical records, etc and seroquel.
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