Friday, July 31, 2009
The compound used in the Spinal Injury study was Coomassie Brilliant Blue G, which is commonly used as a protein stain for gel electrophoresis and in the Bradford protein assay. As you can see, they are not quite the same - Coomassie has a couple of extra methyl groups, and the substituent on the "top" benzene in this image is different.
The interesting thing to me is how it "works." According to the research article published in PNAS, the initial injury to the spinal cord is followed by a secondary injury. Over time, the area of damaged tissue expands from the original site of injury and the researchers reasoned that this expansion should be preventable.
The P2X7 receptor is a membrane channel that opens in response to increased ATP. In the injuries studied, the traumatized tissue releases a lot of ATP which in turn activates the P2X7 channels causing them to open. This has been linked to the spread of the injury, so anything that prevented the opening of the P2X7 channel could be expected to reduce or eliminate the secondary injury.
The Coomassie Blue acts as an antagonist for the P2X7 receptor. It binds to the receptor but does not activate the receptor - so the channel remains closed. Presumably Coomassie Blue and ATP both bind to the same site on P2X7 and only one can occupy the binding site at a time. Because the receptor is bound to the Coomassie Blue, ATP is unable to bind and activate the receptor. Since the opening of the channel is what leads to the expansion of the injury, keeping it closed will limit this expansion.
This is an exciting discovery, but it is likely to be only the first step. In the study, they treated the spinal cord injuries after 15 minutes. People who suffer spinal cord injuries might be helped by treatment with Coomassie Blue, but it is unlikely that they would receive treatment within 15 minutes.
Peng, W., Cotrina, M., Han, X., Yu, H., Bekar, L., Blum, L., Takano, T., Tian, G., Goldman, S., & Nedergaard, M. (2009). From the Cover: Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury Proceedings of the National Academy of Sciences, 106 (30), 12489-12493 DOI: 10.1073/pnas.0902531106
Thursday, July 30, 2009
Wednesday, July 22, 2009
|The Daily Show With Jon Stewart||Mon - Thurs 11p / 10c|
Monday, July 20, 2009
Why information is its own reward - same neurons signal thirst for water, knowledge:
To me, and I suspect many readers, the quest for information can be an intensely rewarding experience. Discovering a previously elusive fact or soaking up a finely crafted argument can be as pleasurable as eating a fine meal when hungry or dousing a thirst with drink. This isn't just a fanciful analogy - a new study suggests that the same neurons that process the primitive physical rewards of food and water also signal the more abstract mental rewards of information.
As commenter oscarzoalaster puts it:
So there is actual objective evidence that curiosity can be as important a desire as food and water! I feel more normal now!!! Thank you!
If only teaching were so easy.
via Learning makes your brain happy - Boing Boing
Friday, July 17, 2009
Thirteen years after it was first discovered, Element 112 has been officially added to the Periodic Table and its discoverers have suggested the name Copernicium (Cp) in honor of Polish astronomer Nicolaus Copernicus who proposed the heliocentric model of the solar system.
Of course, IUPAC is cautious and the name isn't official yet.
Image: Wikimedia Commons
BBC NEWS | Science & Environment | New element named 'copernicium'
Monday, July 13, 2009
Surfactants are molecules that lower the surface tension in water. They behave this way because of their dual nature: a long, hydrophobic carbon tail attached to an ionic end, typically an acid or ammonium group. Surfactants are used in a variety of industrial applications including detergents and wetting agents. A number of widely used surfactants are problematic in that they are non-biodegradable and toxic. PFOA and PFOS are perfluorinated compounds (all hydrogens replaced with fluorines) – the fluorines make the compounds very good surfactants, but also very unreactive (and not biodegradable). They are also known carcinogens. SDS and SLES are not so bad, but still they are irritants and contain sulfonate groups that make them not as easily biodegradable as other compounds.
This article describes the synthesis of an alternative surfactant that is both more biologically friendly (non-toxic and biodegradable) and uses “green” chemistry methods that improve the efficiency of the synthesis and reduce hazardous waste products. N-Acyl palmitoyl ethanolamine is derived from two common constituents of biological lipids: the fatty acid palmitic acid and ethanolamine. Like soap, this surfactant is cheap, non-toxic and biodegradable. Like many industrial surfactants, and unlike soap, it is not prone to forming soap scum with hard water.They used the enzyme Lipase to catalyze the reaction between ethanolamine and a fatty acid (or its ethyl ester). There are two possible products depending on which end of the ethanolamine reacts: either a hydroxy amide or an amino ester. Perhaps not too surprisingly, the hydroxy amide is formed exclusively. Amides are generally more stable than esters, amines are stronger nucleophiles than alcohols, and as the authors point out themselves amino esters with only two carbons between the N and O will rearrange on their own to the more stable amide form. Lipase was chosen because it is a flexible catalyst and the reaction takes place under mild conditions (no strong acids or bases to neutralize at the end).
- reactants in solution, conventional heat source
- reactants in solution, microwave heating
- reactants in solid state, microwave heating
The enzyme itself was attached to porous resin beads. For the solution-phase experiments, the enzyme and reactants were added to dioxane. For the solid-phase experiment, the reactants were dissolved in a small amount of solvent which was added to the enzyme and then evaporated to leave the reactants as a film on the enzyme-containing beads. Both microwave-heated reactions went considerably faster than conventional heating, and the solid-phase reaction was faster that the solution.
What exactly makes this "green?" While dioxane is not the most desirable solvent, it can be recovered afterwards and re-used. Otherwise, there is little waste. If fatty acids are used as the starting material instead of the corresponding ester there are no waste byproducts (such as ethanol) to separate and dispose of safely, and no strong acids or bases to neutralize. Even the enzyme is re-usable. And the product hydroxy amide is of low toxicity and should be biodegradable as well. If the solid-phase reaction with microwave heating turns out to be practical, it would greatly improve the efficiency of the process by speeding-up the reaction and improving the yield and purity of the products.
Kidwai, M., Poddar, R., & Mothsra, P. (2009). N-acylation of ethanolamine using lipase: a chemoselective catalyst. Beilstein Journal of Organic Chemistry, 5 DOI: 10.3762/bjoc.5.10
Sunday, July 12, 2009
Saturday, July 11, 2009
The original source is the Medico-Pharmaceutical Critic and Guide (1907), edited by William J. Robinson, which goes on to say:
This, as Dr. J. A. Paris says, was economy in right earnest, for a single pill would serve a whole family during their lives and might be transmitted as an heirloom to their posterity. We have heard of a lady, says the Doctor, who, having swallowed one of these pills became seriously alarmed at its not passing. "Madam," said her physician, "fear not. It has already passed thru a hundred patients without any difficulty."And then finishes with this keen observation:
We do not think that the everlasting pill would be popular at the present time.I wonder why antimony was chosen? Antimony and its compounds have been used in treating parasites, but I don't know it that would have anything to do with the supposed "cathartic" properties of the "Everlasting Pill." Of course, antimony is toxic. According to wikipedia, antimony poisoning is similar to arsenic poisoning, which only makes sense since antimony is right below arsenic in the periodic table. I don't know how much metallic antimony you would absorb through the gut, but I doubt it would be a good idea to use this device.
You can read the original, and many other interesting articles in the Medico-Pharmaceutical Critic and Guide which is available by way of Google Books. This book is out of copyright, so you can read the whole thing for free on line, or download a PDF copy for yourself. As a bonus, you can also search and copy selections on line - which is how I got the quote above. Since the PDF version is just a scanned image it can't be searched or copied so easily.
Image: Wikimedia commons
Scribal Terror: The everlasting pill by way of Neatorama,
Monday, July 6, 2009
First a little background. Both compounds affect cancerous cells the way they do because they bind to Protein Kinase C (PKC). PKC is an enzyme that contributes to a number of signaling pathways within the cell, particularly having to do with cell differentiation, proliferation and apoptosis. PKC's involvement in cellular growth cycles also results in its involvement in carcinogenesis, and it has been a target for developing anti-cancer drugs for this reason.
The curious thing about PKC is that some molecules that bind to PKC activate the enzyme, while others de-activate it. Even stranger, some activators promote tumor formation and other activators do not.
PKC activators have shown some promise for treating diseases such as Alzheimers or AIDS, but their tumor-promoting behavior is a big drawback. Ideally you would want to find a PKC activator that was also non-tumor promoting. Bryostatins fit this description, but the compounds are too complex to be easily made in the laboratory. In nature, bryostatins are made by a coral-like organism but in extremely small amounts. According to Wikipedia, you would need a ton (2000 lb) of bryozoans to obtain just one gram of bryostatin.
Aplysiatoxin binds to PCK as a tumor promoting activator. Compound 1 was designed as a simpler version of aplysiatoxin that might be a PKC activator without also being a tumor promoter. As it turns out, compound 1 shows minimal tumor-promoting activity, and it counteracts the effects of the tumor-promoter 12-O-tetradecanoylphorbol-13 acetate. It's anti-cancer activity as well as it's mode of binding to PKC seems to be comparable to the bryostatins. The authors report that they can make Compound 1 in only 22 steps, which makes it a promising alternative to bryostatins as a potential therapeutic agent.
Nakagawa, Y., Yanagita, R., Hamada, N., Murakami, A., Takahashi, H., Saito, N., Nagai, H., & Irie, K. (2009). A Simple Analogue of Tumor-Promoting Aplysiatoxin Is an Antineoplastic Agent Rather Than a Tumor Promoter: Development of a Synthetically Accessible Protein Kinase C Activator with Bryostatin-like Activity Journal of the American Chemical Society, 131 (22), 7573-7579 DOI: 10.1021/ja808447r
Sunday, July 5, 2009
The first episode is a good place to start. As a science geek, I particularly liked Schrödinger’s Familiar. If you aren't familiar with the gazillion monsters character might run into, a Lich is a sort of undead sorcerer.