Archive for June, 2007

Cars Constriction

Posted by David Bradley on June 29th, 2007

PaclitaxelCoherent anti-Stokes Raman scattering microscopy has been used to evaluate a new approach to the controlled released of the drug paclitaxel used in preventing a re-narrowing of blood vessels following insertion of a coated-stent to treat the initial condition.

Paclitaxel (aka Taxol) is added to PLGA, poly(lactic-co-glycolic acid, and used to coat blood vessel stents. This reduces the risk of restenosis and cuts target-vessel revascularization. PEG is now added as a plasticizer, but little is known about the release mechanism from these polymer blends.

Now, Kinam Park and colleagues at Purdue University have used CARS microscopy and molecular imaging to reveal details of just how paclitaxel is released from from the polymer blends and why different compositions are better than others. Their results could help refine the formulation of the stent coating and ultimately improve success rates.

You can read more about their work in the Raman channel on SpectroscopyNOW.com

InChI=1/C47H51NO14/c1-25-31(60-43(56)36(52)35(28-16-10-7-11-17-28)48-41(54)29-18-12-8-13-19-29)23-47(57)40(61-42(55)30-20-14-9-15-21-30)38-45(6,32(51)22-33-46(38,24-58-33)62-27(3)50)39(53)37(59-26(2)4 9)34(25)44(47,4)5/h7-21,31-33,35-38,40,51-52,57H,22-24H2,1-6H3,(H,48,54)/t31-,32-,33+,35-,36+,37-,38-,40-,45+,46-,47+/m0/s1/f/h48H

Estrogen Therapy Good, Bad, Good

Posted by David Bradley on June 25th, 2007

Estradiol structureAdvice from various quarters, the medical profession, governments, and pressure groups swings wildly both ways when it comes to whether or not estrogen therapy (hormone replacement therapy) is good or bad for women. Some studies have suggested that it not only reduces the effects of the menopause but reduces osteoporosis risk and even protects women against heart disease. But, then there are studies that say it increases the risk of breast cancer, cardiovascular disease and strokes. Then there are yet others that swing some of those risks one way and the remainder the other, so that the therapy is good for some things, bad for others, and indifferent for the most part.

Of course, all of these studies are based on statistical analyses and epidemiology and deal in minute risks and marginal benefits in mosts cases. There is certainly a case for estrogen therapy to help protect reduce the “symptoms of the menopause, including hot flashes, loss of libido, vaginal changes, as well as in protecting against osteoporosis. However, estrogen therapy does not work for all women, and only those already at increased risk of osteoporosis from genetics, poor diet, lack of exercise or obesity, will really benefit in that instance.

Scaremongering sections of the media would have us believe that the risks of heart attack, stroke, or breast cancer are massively raised by estrogen therapy. They talk of a doubling or trebling of the risk, whereas the real shift in risk is often from one case in several thousand women to 2-3 cases in the same several thousand. A shift of fractions of a percentage point in other words.

Research has now turned again, according to a recent report in the New England Journal of Medicine (NEJM), in which JoAnn Manson of Brigham and Women’s Hospital in Boston have found that estrogen use for seven years or more after menopause can reduce calcification of the arteries, a key indicator of atherosclerosis, by 60%. That means a handful of the few less of the handful in every few thousand who would have suffered.

This is a positive result, nevertheless, but earlier research found that the use of estrogen by women in their 50s could reduce the number of heart attacks per 10,000 women from 27 to 17 and the number of strokes from 17 to 15. That’s a change in risk of heart attack from 0.27% to 0.17%, a difference of a tenth of a percent. And, of course for the women saved from heart attack it means everything. However, such tiny changes in risk cannot be used to underpin medical policy just as their equivalent negative results should not be used to scare women into halting their medication.

InChI=1/C18H24O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-17,19-20H,2,4,6-9H2,1H3

Did Strychnine Kill the Dinosaurs?

Posted by David Bradley on June 20th, 2007

Strychnine structureStrychnine seems to be a commonly searched entry in the ChemSpider database. I am not sure whether that means there are poisoners among the users or whether it is people hoping to find out more about the recent case of a man accused of poisoning his neighbors’ dogs with a gopher bait pesticide containing strychnine. Alternatively, it could be people hoping to learn more about recent research into the unusual poses struck by dinosaur fossils.

Dinosaur fossils always seem to show the creatures “voguing”, as if there were some Jurassic equivalent of the 90s dance craze kicking off some time BC. But, the odd postures of these long-dead animals would actually suggest that they had an agonized death - the wide-open mouth, head thrown back and recurved tail - all point to poisoning, disease, or asphyxiation, according to two Berkeley paleontologists.

The usual explanation for the postures is that the dinosaurs simply died in water and currents dragged their bones into these odd positions and they were frozen in time as sediments settled and fossilization began.

Berkeley veterinarian-turned-paleontologist Cynthia Marshall Faux has seen a lot of animals that have been poisoned, hit by vehicles, or died of painful disease. They often arrive displaying the same postures as these fossils. She believes that the posturing dinosaurs may have met unnatural deaths, choking on volcanic ash, diseased, or poisoned.

The very same posture is seen in several disease states as well as in strychnine poisoning. Srtychnine is a highly bitter alkaloid found in several plant species, but it is its LD50 of approx. 10 mg per kilogram of body weight that points to its highly toxic nature. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion. Virtually all articulated fossils of Archaeopteryx have been found with the characteristic posture of the strychnine poisoned. We may never know exactly how these creatures died, but could it be that there was a dinosaur poisoner in the wild during the time of the dinosaurs?
InChI=1/C21H22N2O2/c24-18-10-16-19-13-9-17-21(6-7-22(17)11-12(13)5-8-25-16)14-3-1-2-4-15(14)23(18)20(19)21/h1-5,13,16-17,19-20H,6-11H2