28.10.07

Drotrecogin alfa (Xigris) - For when things get really bad

  • recombinant form of human activated protein C (APC)
    • APC is a serine protease (a type of protein-cleaving enzyme) that is capable of suppressing inflammation (by inhibiting a number of pro-inflammatory substances and events), blocking coagulation (by cleaving apart Factors Va and VIIIa to block thrombin formation), and restoring normal fibrinolysis (the physiological busting of clots)
    • recombinant protein drugs like drotrecogin alfa are produced by inserting the gene that encodes them into a bunch of fast-growing cells, growing the cells in a culture, and then harvesting all of the protein that the cells have produced
  • used to reduce the number of people that bite the dust after developing severe sepsis, which is essentially sepsis (a whole-body inflammatory response to a severe infection) with acute organ dysfunction due to widespread coagulation (dysfunction of the circulatory system)
  • since it inhibits blood coagulation, it is important to watch for bleeding problems
  • like most recombinant protein drugs, it is very, very, very expensive
- http://en.wikipedia.org/wiki/Drotrecogin_alpha
- http://www.emedicine.com/EMERG/topic533.htm
- http://www.kcom.edu/faculty/chamberlain/website/lectures/lecture/sepsis.htm

21.10.07

Aspirin: The keep 'em in the kitchen drug

An analysis of data from clinical trials evaluating the effect of aspirin on preventing heart attacks suggests that the drug has sexist tendencies. Science be rocking the discrimination lately, eh?

Apparently aspirin is less effective at preventing non-fatal heart attacks in women relative to men. It has been suggested that this gender difference reflects a greater prevalence of aspirin resistance in women. Aspirin resistance refers to the reduced ability of aspirin to thin the blood (i.e. prevent the aggregation of platelets, which can lead to blood clot formation) in some unlucky people.

The less effective in the ladies thing might also have something to do with the fact that women who develop heart disease are typically older and have progressed further along with the disease at the time of diagnosis. The coronary vessels (the blood vessels that supply the heart muscle) are typically smaller in women compared to men, which might also have something to do with it.

The Internet is a great place to find cheap prescription drugs such as Viagra, which has more uses than you might think. Cheap phentermine and other appetite suppressants can help keep you looking and feeling great.

18.10.07

Beta-methylamino-L-alanine (BMAA) - The Guam toxin

  • neurotoxic amino acid that resembles alanine but is not found in proteins
  • thought to be produced by the vast majority of cyanobacteria, an entire phylum of bacteria which are among the most common and abundant organisms on the planet, being present on land, in freshwater, and in the sea
    • cyanobacteria are also known as blue-green algae, although this is a misnomer because they are indeed bacteria, albeit ones capable of carrying out photosynthesis and growing in filaments like algae can
    • cyanobacteria can be found growing in association with fungi (as lichens) and plants, including ferns, cycads and liverworts, with which they have established a mutual symbiotic relationship whereby they fix nitrogen from the air into a form that the fungi or plant can use in return for a carbohydrate source and/or a place to live
  • BMAA has been implicated as the cause of an amyotrophic lateral sclerosis/parkinsonismdementia complex (ALS/PDC, sounds like a whole heap of fun) that has a fantastically high incidence rate (50-100x that of developed countries in the early 1950s) among the indigenous Chamorro people of Guam (my favourite almost-state)
    • BMAA has been found in the brains of Chamorros who died of ALS/PDC and is biomagnified within the ecosystem of Guam
  • cyanobacteria of the genus Nostoc grow on the roots of Cycas micronesica, a cycad tree that produces seeds containing BMAA that are consumed by flying foxes, which are in turn eaten by the Chamorro (who also use cycad seed flour to make food)
    • we're talking an estimated 10,00-fold increase in BMAA concentration from cyanobacteria to flying foxes
  • it is thought that BMAA, resembling alanine closely in structure, can be incorporated into proteins, resulting in messed up proteins that cause neurodegeneration
  • detox drugs are available that can be used to treat opiate addiction
Cox PA et al. Diverse taxa of cyanobacteria produce beta-N-methylamino-L-alanine, a neurotoxic amino acid. Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5074-8. Epub 2005 Apr 4. Erratum in: Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9734.

16.10.07

Tuesday Threefer: Phthalates, statins, and maraviroc

A couple of notes on three news articles that recently came to my attention:

California has passed a law that limits the levels of phthalates, a group of chemicals that are added to plastics to make 'em all bendy and soft-like, in products intended for kids under 3. The maximum concentration has been set at 0.1 percent. Governor Ah-nold, who in the humble opinion of this blogger was totally robbed of a Best Actor for the beautiful film that is Twins, said something about how important it was to prevent kids from being exposed to these chemicals. In that wonderful Austrian accent of his. In contrast to the views of the Californian legislature, my peeps at Health Canada claim that the levels of phthalates currently found in children's products do not represent a significant health risk. As is usually the case for sketchy chemicals like aspartame and saccharin, the scientific literature on phthalates is mixed. They have been shown to mess with reproduction and development in lab animals, and are suspected to be endocrine disruptors in humans. I'm betting that Schwarzenegger and some lawmakers just wanted to pat themselves on the back. And it's not really a ban, as everyone is saying, if they are just setting a limit. It's still in there!

A study by researchers at the Harvard School of Public Health (Public Health represent!) found that statins, a class of drugs given to lower the levels of bad cholesterol in your blood in order to slow the progression of cardiovascular disease, also slow the decline in lung function that occurs in the elderly and in smokers. Can't wait to see how the tobacco companies spin this one. Seriously, watch for it. Those bastards will take what they can get. Anyway, it all has something to do with the supposed ability of statins to reduce lung-based inflammation and smoking-induced injury while providing protection against oxidative damage. I love how they always hide the important science bits at the end of an article. The groups in the study were not randomized and a control group was not used, two important things that researchers usually try to do in order to strengthen their findings. Plus, let's remember here, it's just one paper. It's entirely possible that response papers contesting the findings are being written as I type (typed as I type?).

Finally, Health Canada has approved a new HIV drug. It's called maraviroc (Celsentri) and it's the first of a newfangled class of HIV-fighting drugs called CCR5 antagonists. CCR5 is a receptor found on T cells and a couple of other types of white blood cells that HIV uses as an entry point into the cells. By blocking the receptor, maraviroc prevents HIV from getting into T cells (No Stairway - Denied!), which means less cells getting infected. It's always great to get a new type of HIV drug on the market, since it represents another figurative gun in the arsenal of drugs used to fight HIV. Maraviroc is particularly crucial for people who have a variety of HIV that has become resistant to existing medications. Hooray for new drugs!

Appetite suppressants such as amphetamine and phentermine are drugs that act on your brain to prevent you from feeling hungry. A new appetite suppressant, a hormone called obestatin, was recently discovered and is currently in development. You have to be careful with amphetamine, because like a number of other drugs it can be addictive, and you don't want to end up in drug rehab. Make sure that you get educated on the risks associated with drug use.

- Heudorf U, Mersch-Sundermann V, Angerer J. Phthalates: Toxicology and exposure. Int J Hyg Environ Health. 2007 Oct;210(5):623-34.
- http://en.wikipedia.org/wiki/CCR5

12.10.07

Lipstick - A delightful combination of fryer oil and lead

Lead has allegedly been found in a number of popular brands (Cover Girl, L'Oréal and Christian Dior, to name a few) of red lipstick. An advocacy group went on a lipstick shopping spree (good times) and then shipped their purchases off to an independent lab for testing.

Now, if the analysis by the lab was done correctly, this is bad news. Lead is a toxic heavy metal that likes to hang around in people's bones and cause damage to all sorts of body systems: nervous (neurotoxicity and developmental delays in kids), cardiovascular (hypertension and anemia), gastrointestinal (abdominal pain, NVD, anorexia and weight loss), urinary (kidney damage), and reproductive (male infertility). To quote a friend: "Now we know why hot chicks are so dumb and skinny". Lead poisoning!

But let's take a closer look at this all. The Reuters article puts it like this:

The Campaign for Safe Cosmetics said tests on 33 brand-name red lipsticks by the Bodycote Testing Group in Santa Fe Spring, Calif., found 61 per cent had detectable lead levels of 0.03 to 0.65 parts per million (ppm).
Okay, first of all, 61 per cent works out to 20 of the 33 lipsticks having detectable levels of lead. Of these, only 11 had levels above the FDA's limit for lead in candy. That's right, in candy. The FDA hasn't set a specific limit for lipstick, and the assumption is made that a considerable portion of the wearer's lipstick (and thus the lead) is eventually ingested. I have no idea how reasonable an assumption this is. Lipstick wearers?

But there's more. The FDA's limit for lead in candy is specific to candy likely to be consumed frequently by small children. Lead poses a greater health risk to kids (relative to adults) because they absorb it more readily and are more susceptible to it's toxic effects. Lipstick use is generally (and hopefully) limited to teenagers and adults, who can tolerate greater levels of lead. It's really not as bad as it all sounds.

Incidentally, the FDA thinks the whole thing is a load of crap. They've said that they'll look into it, but brought up the fact that claims of lead in cosmetics pop up every once in a while but are never confirmed.

In case you were wondering, here are the worst ones they tested:
  • L'Oreal Colour Riche "True Red" - 0.65 ppm
  • L'Oreal Colour Riche "Classic Wine" - 0.58 ppm
  • Cover Girl Incredifull Lipcolor "Maximum Red" - 0.56 ppm
  • Dior Addict "Positive Red" - 0.21 ppm

5.10.07

Another COX-2 inhibitor bites the dust

Health Canada has banned the sale of lumiracoxib (Prexige), an anti-inflammatory drug used to treat osteoarthritis, after determining that it poses a significant risk to the livers of those taking it. It was banned in Australia in August (2007) after being linked to serious liver damage, including full out liver failure. As the FDA has not yet granted its approval, this drug is not for sale in the US (and now probably won't ever be), and I've just lost the interest of most of my readers. Stick with me, folks, it's almost over.

Now, lumiracoxib is a selective inhibitor of COX-2. Rofecoxib (Vioxx), another COX-2 selective inhibitor, was withdrawn from the market in 2004 after being linked to an entirely different problem, an increased risk of adverse cardiovascular events (i.e. heart attack and stroke). Lumiracoxib is structurally dissimilar to your standard COX-2 inhibitors, including rofecoxib, which might explain why it causes a different problem. It is known to be metabolized by the liver, so it's possible that certain liver enzymes are capable of transforming it into an extremely reactive metabolite that, unless detoxified by other enzymes, goes on a cell killing spree. Instant hepatitis. It could be that most people possess either too little of the activating enzyme(s) or just enough of the detoxifying enzyme(s) that they are not appreciably harmed by the drug. Please note that the above was pure, slightly educated speculation. In any event, it's off the market, so Canadians are good to go.

If your opiate addiction is ruining your life, treatment options such as methadone detox and suboxone detox can help. Suboxone treatment can get you on the road to recovery from dependence on painkillers.

- Rordorf CM, Choi L, Marshall P, Mangold JB. Clinical pharmacology of lumiracoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet. 2005;44(12):1247-66. Review.
- http://en.wikipedia.org/wiki/Lumiracoxib

3.10.07

Lanthanum (La) - The hidden binder of phosphate

  • rare earth element (atomic number 57) named after the Greek word lanthano, meaning to lie hidden, in reference to the fact that the dude who discovered it found it 'hiding' in a sample of another rare earth element, cerium
    • lanthanum carbonate (Fosrenol) is a phosphate binder, which is a drug used to curtail the gastrointestinal absorption of phosphate from ingested food
    • phosphate binders are an important pharmacological means of alleviating hyperphosphatemia (excessively high blood phosphate levels) in people with chronic renal failure, who are unable to remove phosphate from their body because their kidneys aren't working properly
    • hyperphosphatemia can promote the breakdown of bone, potentially leading to bone deformation, pain, and increased susceptibility to fractures
  • lanthanum carbonate is also used, in an industrial setting, to produce lanthanum strontium manganite, used to make solid oxide fuel cells
  • since it is so good at binding up phosphate, lanthanum is commonly found in pool products intended to remove phosphates, a source of nourishment for algae, from pool water
  • a number of rare earth chlorides, including lanthanum chloride, are capable of inhibiting the clotting of blood
  • has been reported to modulate neurotransmitter systems, including the potentiation of receptors for inhibitory GABA and glycine receptors (which suggests that lanthanum may depress brain function)
- Albaaj F, Hutchison AJ. Lanthanum carbonate (Fosrenol): a novel agent for the treatment of hyperphosphataemia in renal failure and dialysis patients. Int J Clin Pract. 2005 Sep;59(9):1091-6. Review.
- Chang CW, Qu B, Hong Z, Gao GD. Potentiation of inhibitory amino acid receptors-mediated responses by lanthanum in rat sacral dorsal commissural neurons. Neurotoxicol Teratol. 2006 Nov-Dec;28(6):657-63. Epub 2006 Aug 30.
- http://en.wikipedia.org/wiki/Lanthanum