This is the last post, attempting to find interesting chemistry for Siromi Samarasinghe’s birthday. Although this one isn’t about smell or being stinky, it is about civet feces.
You’ve probably heard about the really expensive coffee that’s made from an animal’s dung. It’s called Kopi Luwak. Kopi for the Indonesian word for coffee and Luwak for the Asian palm civet, Paradoxurus hermaphroditus. The luwak eats the coffee berries and digests them, imparting a unique flavor to the coffee beans. The beans are retrieved and cleaned from the luwak feces.
Jumhawan et al used gas chromatography with mass spectroscopy (GC-MS) to identify metabolites that can be used to identify genuine Kopi Luwak. From the news blurb: Kopi Luwak sports higher concentrations of malic acid and citric acid, as well as a higher ratio of inositol to pyroglutamic acid.
Selection of Discriminant Markers for Authentication of Asian Palm Civet Coffee (Kopi Luwak): A Metabolomics Approach
GC uses a long coiled tube rather than the large columns, packed with a solid phase, used in liquid chromatography. The mobile phase is gas, hence the name, and the stationary phase is a thin layer of liquid or an insert sold support.
In searching for an alternate picture for this post I found that the palm civet is being exploited due to the high price for Kopi Luwak. Many civets are being caged and feed only coffee berries.
World’s most expensive coffee tainted by ‘horrific’ civet abuse
Maclura pomifera is a tree that grows throughout the US and part of southeastern Canada. It’s related to the mulberry tree although the fruit would make you think it’s citrus. The Osage Indians used it’s wood to make bows and clubs due to it’s resistance to decay and durability. It’s no surprise that modern use of the wood is for fence posts and tool handles. The tree was planted in rows in the Great Plains states to help break the wind, hence the nickname “hedge apple”. The fruit used to be placed under the bed to repel some insects.
Fruits grow to their full size (ca. 500 g) every fall, and each fruit can bear up to 300 seeds per fruit. Osage orange has traditionally been used as an insect repellent and as a home remedy for pest control. Fruit extracts and extracts of the bark, seeds, leaves, and roots, as well as the two major isoflavone constituents of the fruit, osajin and pomiferin, were reported to possess a number of biological activities. Some of the reported activities include insect repellant, antimicrobial, anti-inflammatory/antinociceptive, antitumor, cardioprotective, and cholinesterase inhibitory activities. Osage orange isoflavones, especially pomiferin, also have marked antioxidant activity and have been shown to inhibit lipid peroxidation and to reduce free radicals, reactive oxygen species, and other unstable molecules. At present, there are no osage orange-based dietary supplements available on the market, but its potential has been suggested. Biological evaluation of semisynthetic osajin and pomiferin analogues, iso-osajin and iso-pomiferin, has also been attempted by Orhan et al. Being edible by squirrels, horses, and other animals suggests that osage orange is safe. Nevertheless, the toxicities of the different extracts have not been fully established. References removed for readability
HPLC Determination of Isoflavone Levels in Osage Orange from the Midwest and Southern United States
Ketur Darji, Cristina Miglis, Ashley Wardlow, and Ehab A. Abourashed
You often hear about herbal or Ayurvedic remedies for a whole host of ailments. I won’t talk about homeopathy because that’s too easy to dismiss. Pharmacognosy is the study of medicinal compounds derived from plants. You might hear about ethnobotany and phytochemistry in descriptions of pharmacognosy. Ethnobotany is the study of plants as they relate to culture, predominantly indigenous cultures. Phytochemistry is the study of the chemistry of plants (cue elderberry joke). It’s pharmacognosy that’s used to determine if a “traditional” remedy has any scientific basis. Typically ethnobotany is used to find some candidate plants. I have a friend in this field and if I recall correctly, there was a time when western scientists would go to the jungle (for example) and take plants without working with the local government. Relationships soured and some areas are off limits. I believe most of the studies now have agreements with the local governments and indigenous people so that it’s not the new version of pillaging their gold, i.e., if a derived compound leads to a blockbuster drug, they’ll get a slice of the pie.
After a candidate plant is chosen, Maclura pomifera in this case, compounds are isolated from the bark, fruit, flower, leaves, and roots. Since this is a tree, I’m guessing the roots were not tested. Typically the compounds will be separated based on water solubility. You might know that a lot of old remedies are made with ethanol, i.e., a tincture. Then each compound is analyzed for it’s chemically properties, e.g., structure and then against a host of in vitro assays to scan for potential medicinal uses, possibly beyond what was learned from ethnobotany.
The paper referenced above (which is behind a paywall) used high pressure liquid chromatography (HPLC). Chromatography comes from the Greek chroma “color” and graphein “to write”. There are different types of chromatography but each results in a chromatograph. Its name derives from its early use in separating pigments in plants. Probably using thin layer chromatography (TLC), where a plate or piece of paper is used in a solvent. The sample is placed on one end of the plate/paper and the individual compounds separate as it travels through the solvent. This can be due to size, charge, or polarity. In HPLC, there is a mobile phase and stationary phase. Typically the stationary phase is made of special porous micron-size silica beads and is packed into a steel column. The mobile phase is typically a solvents like toluene or acetonitrile. When the mobile phase is less polar than the stationary phase it’s called normal phase liquid chromatography. When that’s reversed, i.e., the mobile phase is more polar than the stationary phase, it’s called reverse phase liquid chromatography. The reference above used reverse phase.
For a long time the effluent from HPLCs were connected to a UV-Vis (ultraviolet and visible range) spectrophotometer. Each compound has a preference for each phase (mobile or stationary). They travel through the column at different rates and they have different spectra. That’s how you get the chromatograph. In the old days, the spectrometer was tuned to a single wavelength, typically where your compound of interest has a peak. Later, with photodiode array technology, the whole spectrum for each compound was acquired, resulting in a 3D chromatograph. However, now, HPLC detectors are predominantly mass spectrometers (MS). So you get the mass of each compound as it elutes from the column.
Going back to pharmacognosy and Maclura pomifera. Two of the main compounds isolated are pomiferin and osajin . In another study pomiferin was isolated and had an inhibitory effect on the growth of 5 tumor cell types.
Pomiferin, histone deacetylase inhibitor isolated from the fruits of Maclura pomifera.
Son IH, Chung IM, Lee SI, Yang HD, Moon HI.
Bioorg Med Chem Lett. 2007 Sep 1;17(17):4753-5. Epub 2007 Jun 26.
When ScienceSunday first started, Robby Bowles and Allison Sekuler had an idea that photographers could share interesting pictures with real scientist (Robby and Allison) and the Science Sunday team could either answer a science question or add some science goodness. Sunday was chosen because we do this in our “spare” time and Sunday seemed like the best day for spare time. So the hashtag #ScienceSunday was born, followed by the page. As the popularity of the hashtag grew, more curators were added: Rajini Rao, me and then Buddhini Samarasinghe. The hashtag and page continued to grow. So we often have guest curators to help out. Unfortunately a lot of people see a trending hashtag and use it because they think that people won’t want to see their post/photo otherwise. The curators have to sift through a lot of junk to find the good stuff. So welcome Aubrey Francisco our new co-curator with some good stuff. The pictures below were from my trip to the Fox River, Silver Springs State park, yesterday. Enjoy the rest of your #ScienceSunday and don’t forget to tag one of the curators when you have a science question or some science to share.
There was a story on NPR describing a study about asymmetrical tail wagging of dogs. In 2007 Dr. Vallortigara found that a dogs tend to wag their tail to the right when they see something friendly and wag to the left when something is threatening. In 2011 Artellea et al, used a robotic dog to see how dogs would respond to a tail wagging left or right, i.e., does the tail wagging communicate fun or danger? When dogs saw the robot tail wag left, they approached without stopping. When they saw it wag to the right, they were more cautious and stopped frequently as they approached. Dr. Vallortigara followed up his previous study, this time using a video of a dog, either wagging left or right. A group of dogs watching the video had vests, which recorded their heart rate. As expected, the heart rate was normal when the tail was wagging to the right in the video and the heart rate increased (a sign of agitation) when the tail in the video was wagging to the left. The next question is how can we use this information. It should be noted how each study builds on the previous study. That’s how science works.
The image below, from Quaranta et al, 2007, shows the angle/method for determining a left or right bias tail wag. In A the tail is wagging right and in B the tail is wagging left, i.e. left and right determinations were with respect to the dog, not the observer.
EDIT for clarity.
The Tail’s The Tell: Dog Wags Can Mean Friend Or Foe
I was working on my post for #ScienceSunday about medical image visualization and I ended up down a rabbit hole. I hope to finish writing this evening. In the meantime, tell me what science you see in this image. I changed it to my profile pic because it’s me but what else do you see?
Check out this great post by our resident chemistry professor, Siromi Samarasinghe
It reminds me, there was an interesting study using fMRI on volunteers tripping on mushrooms. It is surprising that activity in the brain was lower while on mushrooms. However, I disagree with the article, that just because the results are counter to what was expected, it doesn’t automatically make the results correct. It does make the results un-biased; I agree with that part. The next step should use more quantitative imaging, like PET.
The Good the Bad and the Ugly – the chemical diversity of mushrooms
The world of mushrooms is as complex as the human world. They too have their Good, the Bad and the Ugly. What makes them so? The chemical composition of the mushrooms play a big role in determining their nature.
Gourmet’s delight and Therapeutic mushrooms
✿ Shitake mushrooms (Lentinus edodes, Lentinela edodes) are widely used in East Asian cuisine. These meaty morsels are savoured by the gourmet. Many mouth watering recipes bring forth their culinary flavour.
Sun drying is reported to bring out the umami or savoury flavour of this mushroom. http://goo.gl/8W8bsn
✿ Shitake mushrooms are known to contain the compound Eritadinine which has been isolated from them and characterised. Eritadinine is reported to lower high blood cholesterol levels. http://goo.gl/Cxsg4C
✿ A novel protein designated as lentin, with potent antifungal activity was also isolated from Shitake mushrooms. Lentin is reported to have inhibitory effects on the activity of HIV-1 reverse transcriptase and proliferation of leukemia cells.
✿ An accumulating body of evidence suggests that consumption of dietary mushrooms can protect against breast cancer. In a study carried out in 2010, scientists tested and compared the ability of five commonly consumed mushrooms to modulate cell number balance in the cancer process using MCF-7 human breast cancer cells. The tested mushrooms were: maitake ( Grifola frondosa), crimini (Agaricus bisporus), portabella (Agaricus bisporus), oyster (Pleurotus ostreatus) and white button (Agaricus bisporus). The study suggests that both common and specialty mushrooms may be chemoprotective against breast cancer. http://goo.gl/uhX3Jz
Magic mushrooms (Psychoactive mushrooms)
Intentional or accidental ingestion of these mushrooms which contain hallucinogenic components could be a tragedy to the consumer.
✿ Psilocybin and psilocin are the principal components in ‘magic mushrooms’ which belong to the genus Psilocybe.
Psilocybin is chemically related to the amino acid tryptophan and is structurally similar to the neurotransmitter serotonin.
Psilocybin is a member of the general class of tryptophan-based compounds that originally functioned as antioxidants in earlier life forms before assuming more complex functions in multicellular organisms, including humans.
Biosynthetically, the biochemical transformation from tryptophan to psilocybin involves several enzyme reactions.
✿ In addition to psilocybin and psilocin, studies have clarified psychoactive mushrooms to produce psychoactive agents such as ibotenic acid, and muscimol. However, the status of psychoactive mushrooms in most countries, as illegal hallucinogens, has prevented full investigation of their biochemical properties. Recent studies have shown that many psychoactive agents pass through the blood-brain barrier and act on neurotransmitter receptors.
It has also been shown that psilocybin and psilocin have high therapeutic efficiency for obsessive-compulsive disorder which is a difficult-to-treat nervous disease.
The toxic mushrooms – Lethal beauties, Death caps and Destroying Angels
✿The poisonous substances in mushrooms are generally known as
mycotoxins since mushrooms are fungi.
✿Some of the known toxic compounds in mushrooms are :
Alpha amanitin (deadly: causes liver damage) – principal toxin in genus Amanita. (E.g. Death cap (Amanita phalloides), Destroying angel). The measure of lethality of amanitin (oral LD50 value) is approximately 0.1 mg/kg
Phallotoxin (causes gastrointestinal upset) – also found in poisonous Amanitas
Orellanine (deadly: causes kidney failure) – principal toxin in genus Cortinarius.
Muscarine (sometimes deadly: can cause respiratory failure) – found in genus Omphalotus.
Gyromitrin (deadly: causes neurotoxicity, gastrointestinal upset, and destruction of blood cells) – principal toxin in genus Gyromitra.
Coprine (causes illness when consumed with alcohol) – principal toxin in genus Coprinus.
Ibotenic acid (causes neurotoxicity) and muscimol (hallucinogenic) – principal toxins in A. muscaria, A. pantherina, and A. gemmata.
The Good, the Bad and the Ugly of the Mushroom world continue to be a challenge to scientists, with their diverse chemical compositions, at the same time offering culinary flavours, hallucinogens and medicines to humans.
Thanks Zuleyka Zevallos for this fantastic post about Popular Science disabling comments on their website. I can’t agree more that scientists need to reach out more to the general public. There is so much misinformation out there.
Here’s the LiveScience summary of the article you referenced.
Trolls’ Online Comments Skew Perception of Science
One way to deal with the “nasty effect” is to delete comments and block people. Some people will say, that doing so is censorship. I have to thank A.V. Flox for writing an outstanding post about why that is not the case.
Of course that only works on your posts. For other posts, you’re at the mercy of the owner of that post. I know there is a ton of misinformation about vaccines and pharmaceutical companies, and that has the potential to actually harm people. I go out of my way to explain to people how herd immunity is compromised when one person believes in the anti-vaccine nonsense. This is too important to let a few trolls get in the way.
On the plus side, I can say how nice it is when my science posts cause someone to reach out to me to ask about science, especially young students. Here’s a post about one example.
How Informed Science Can Counter the “Nasty Effect”
Popular Science recently announced they were closing down their comments section. This has lead to many debates, including discussions on our community. I will discuss the role of public science moderation in context of one scientific study that Popular Science used to support its decision to close their comments section. The research shows that people who think they know about science are easily swayed by negative internet discussions, but these people more likely to be poorly informed about science in the first place. For this reason, popular science publications and scientists need to step up their public engagement, not shy away from it due to the so-called “nasty effect” of negative comments made through social media.
Problems with Measuring the “Nasty Effect”
In support of their decision to close down comments on its blog, Popular Science cited a study published in July by the Journal of Computer-Mediated Communication. The study set out to measure online incivility, or as the researchers call it, the “nasty effect” that online comments can have on people’s understanding of emerging technologies.
The researchers surveyed around 2,300 people measuring their “familiarity” with science (in their study, nanotechnology). The researchers did not measure levels of general education nor scientific knowledge specifically. They measured socioeconomic status by aggregating education and income. This variable was not tested against knowledge. This matters because education shapes not simply our ability to think critically. It also gives us the mental tools to process new information, as well as giving us the research skills to seek out alternative and reputable sources of information. Scientific training teaches us how to read articles and data from an objective perspective, using objective theories, concepts and methods. More importantly, it teaches us to argue from a place of knowledge, not from emotion or personal opinion.
The researchers did not measure where people got their information, lumping different newspapers into one category, TV in another, and then the internet. The problem here is that if people are generally getting most of their information from poor sources, their thinking is already coloured by misinformation.
The researchers find that irrespective of their subjective ideas about how much they think they know about science, negative comments influenced people’s opinion. Religious people and those who already held low levels of support for nanotechnology were more likely to perceive a risk of this technology after reading negative discussion. The researchers do not engage with these findings.
Understanding, support and risks associated with science might be understood as the socialisation of science. These biases don’t just exist in individual minds; they are shaped by prior education and exposure to poor scientific debate either through their family culture, religious schooling, or media use.
What this tells us is that people who think they know about science are swayed by others’ negativity. The distinction between “surface” science and “deeper” science might help put this into perspective.
Surface versus Deep Science Communication
Many people think they know science because they find science news and certain factoids and images interesting. This might be seen as “surface level” science. Pop science is lots of fun, but there is wide scope for science to be misleading when it is reported incorrectly. This is the tip of the ice berg as far as science communication is concerned.
Nurturing deeper level scientific engagement is achieved by reading the science directly. This is difficult if you don’t have a science degree because science is written in technical language. Plus articles are hidden behind paywalls that require institutional access. Unless you have a personal fortune to invest in these collections, it’s hard to get access.
The other way to achieve deeper scientific knowledge is by engaging with scientists directly. This is where blogs and social media can help make science debates more accessible. In a community setting, the conversation is shaped through moderation. This was not measured in the study, and this is something that Pop Science has essentially given up on.
How might opinions be swayed when real scientists jump in to lead, moderate and comment on popular science discussions?
Science is about informed debate, not personal opinions. There’s no point putting out science into the public if we give up on informed discussion.
A Call for Scientists to Support Public Debate
It’s interesting that Popular Science is keeping their other social media channels open for discussion, suggesting perhaps that they are happy to support debate so long as it’s not in their direct domain (their website). This suggests, perhaps, that they are washing their hands of moderation, and letting people comment on Facebook, Twitter and so on, without feeling the same pressure to respond to comments. This will only feed the same “familiarity” with science, without the informed discussion. In this way, it only contributes to poor public engagement with science, rather than supporting spaces where the public might learn to think more critically about science.
I sympathise with the difficult task of moderation from personal experience here and in the other communities that I help moderate. It is much easier to publish in journals read by our peers and to present at conferences where everyone already has the same training. But if scientists and popular science news publications give up on public debate, what’s the point of putting out science into the world? The public will continue to write and debate science, picking up little snippets – which are often incorrect. The only outcome is that science continues without informed discussion.
If you’re a qualified scientist and you’re a part of our community, consider contributing to the discussion. We’d like to see more posts written by experts who can make science more accessible. Even if you tell us about your latest research project, or if you do a critical summary of your latest publication, this would improve science outreach. Don’t just throw out a link to your blog post or copy and paste your abstract, tell us about the science!
I was intrigued that so many scientists wrote about their research on this thread about our future community hangouts (http://goo.gl/iLzZCI). I wonder why more of these people are not writing to the rest of the community about their work. Could there be a fear of the “nasty effect”? Is it simply too daunting to write for a larger audience, or is there a fear that it might be too time consuming? Write about what you know. Write about the science you’re currently reading. Write about your lab work. Remember that basic concepts, theories and methods that seem old hat to you would be interesting to others. Link to original sources to give people an opportunity to read the science directly if they have access.
It’d be great to see more of you sharing your research with our community.
In biomedical research statistics are a funny thing. The post below touches on some of them. One thing that I’ve found that is bad but not necessarily fraud, is that many researchers learn a statistical method from a mentor or journal and use only that method, e.g., Student t-test. A t-test is perfectly fine when comparing two groups. If you have more than two groups, you have to switch to an analysis of variance, ANOVA or something else. In some fields and journals, the problem is bad enough that even reviewers don’t catch the statistical flaw. However, all is not doom and gloom. Many if not all universities have a group of statisticians on hand to help you design your study, i.e., statistical method, before you do the research. Many large grants want evidence of this, e.g. in a power calculation.
Here are some examples of publications that don’t quite understand what significance means. http://goo.gl/AgWTRl
#ScienceEveryday
Originally shared by Joerg Fliege
A peculiar prevalence of p-values
Now whats a p-value? In laymans terms, it is a number saying that a particular hypothesis (“All sheeps are black”, “All math teachers are jerks”, “Aspirin helps against cancer”, etc) is not completely bats… crazy. It roughly goes like this. You make up a hypothesis (see above) that you really do not like, and you gather some data (e.g. some sheep, or some math teachers). The p-value corresponding to this hypothesis and this data set then tells you how probable it is to randomly stumble upon that particular data set under the assumption that the hypothesis is true. Small p-values tell you that the hypothesis is probably wrong, which is what you wanted to show anyway.
There is big money in small p-values. Its what you need to ‘show’ that a particular treatment for a particular ailment works in order to bring your pills to the market. [Insert cheap joke about big pharma and certain dysfunctions here.]
Now whats a small p-value?
Well, Ronald Aylmer Fisher wrote the following in The Journal of the Ministry of Agriculture, in the year of the Lord 1926:
If one in twenty does not seem high enough odds, we may, if we prefer it, draw the line at one in fifty (the 2 per cent. point), or one in a hundred (the 1 per cent. point). Personally, the writer prefers to set a low standard of significance at the 5 per cent point, and ignore entirely all results which fail to reach this level. A scientific fact should be regarded as experimentally established only if a properly designed experiment rarely fails to give this level of significance.
In other words, Fisher pulled the number 1/20 = 0.05 out of his ass thin air and was honest about it. Since then, people have followed Fisher’s words as reported in the reputable Journal of the Ministry of Agriculture. Not with pulling numbers out of various orifices, but with sticking to p=0.05 as the special value that shows ‘significance’, like a religious sermon.
Now lets have a look at p-values reported in various recent papers. Say, 3627 of them. This is where the histogram comes from [1]. (The original paper [2] is behind a pay wall. Thank you, Taylor & Francis.)
Look, too many p-values less than 0.05! And too few above 0.05! How peculiar, and utterly surprising!
Some possible explanations [1]:
Publication bias. Report a p-value just above 0.05? Referees will shoot you down.
Give up. Found a p-value just above 0.05? Don’t bother writing up. Because see above.
Tweaking. Fiddle around with your analysis until you make it below 0.05.
Dynamic sample size. Fiddle with the sample size until you make it below 0.05.
Slice and dice. Only report p-values for ‘appropriate’ subsets of data.
Outliers. Only report outliers.
One item is missing from this list: Fraud.
Caveat: the 3627 reported p-values all come from psychology journals. Be careful before you start laughing and point fingers at that particular discipline. Are you sure this stuff doesn’t happen in your neck of the woods?
I came across an article in Psychology Today discussing the Cambridge Declaration on Consciousness. You can read more about the declaration in the links below. Basically a group of scientists met in Cambridge and proclaimed their support for the idea that some animals have a consciousness. Don’t get carried away and confuse that with intelligence. Also the declaration doesn’t say anything about the treatment of animals. I was a bit annoyed that the Psychology Today article kept mentioning abuse, as if to stoke the ire of the animal rights activists. It’s interesting that the article mentions the Animal Welfare Act. It is true that there are some animal studies that the general population might find unsettlingly. However, there are so many regulations on what you can and cannot do when it comes to animal research, that I find the term “abuse” to be disingenuous. Contrast that with the article from io9.
I’m in total agreement that some animals have consciousness and that they should be treated humanely. Here’s an excerpt from the declaration.
The absence of a neocortex does not appear to preclude an organism from experiencing affective states. Convergent evidence indicates that non-human animals have the neuroanatomical, neurochemical, and neurophysiological substrates of conscious states along with the capacity to exhibit intentional behaviors. Consequently, the weight of evidence indicates that humans are not unique in possessing the neurological substrates that generate consciousness. Nonhuman animals, including all mammals and birds, and many other creatures, including octopuses, also possess these neurological substrates.
I’ve talked about birds already (see the PET link below). The rest of this post will focus on something I shared back in December 2011. I shared it privately as I was new to G+. So I’m redoing it here. The image below is a screen capture of a study by a group at the The University of Chicago The video is in the link below, Helping your fellow rat.. Bartal et al showed that rats can demonstrate empathy by having a free rat rescue his or her cagemate, which is placed in a plastic restrainer. Once the rats learned to open the restrainer, they only opened it if there was a cagemate in it, i.e., if it was empty or had an object inside they left it locked. Also, when presented with a locked cagemate and a locked piece of chocolate, the free rat would unlock both and share the chocolate. That’s better than many politicians. Rats were initially startled by the door opening. In later repeated tests, the rats were no longer surprised by the door opening, i.e., it was an expected outcome.
The data suggests that females are more empathetic. All of the females became door openers while only 70% of the males opened the door. Also, the females learned to open the door sooner than the male rats.
Combined with the bird studies, there is mounting evidence that animals have more going on in their brains than some people think.
Here’s another example of some interesting science that doesn’t need any hype. The news blurb is titled Injectable Oxygen Keeps People Alive Without Breathing and was shared here: http://goo.gl/xjmeE4 I promised Rahul Roy that I would follow up after reading the full journal article. Notice the title on the journal article is less sensational, Oxygen Gas–Filled Microparticles Provide Intravenous Oxygen Delivery JN Kheir et al. Sci Transl Med 27 June 2012 http://goo.gl/9tN6yx Techandfacts.com actually did a decent job reporting the science. The title is a little hyped but not bad. I’ve certainly seen worse, e.g., Bench to Bedsidehttp://goo.gl/xudsu
So what is this article about, what’s the science?
❤ Lipidic oxygen-containing microparticles (LOM)
Dr. Kheir et al created microbubbles or LOMs to deliver oxygen when patients have difficulty breathing. This is an important part; it is not a blood substitute. It is not intended for trauma involving blood loss. We’ll get back to that later. What is LOM? When you make a vinaigrette you notice that oil and water don’t mix. You can shake/whisk the mixture or use an emulsifier (like mustard) to make an emulsion (a mixture of two liquids that normally don’t mix). Micelles are formed when a molecule has a hydrophobic part (doesn’t like water) and a hydrophilic part (likes water) and it’s placed in a liquid. If the liquid is water, the hydrophobic parts try to escape the water and end up on the inside of a sphere with the hydrophilic part on the outside. So the lipidic part of LOM is used to make micelles with oxygen inside. They use sound waves (via a sonicator) to disrupt the micelles enough to trap the oxygen inside of them. A red blood cell is 7-8 µm in diameter and the LOMs are 2-4 µm so they have no problem getting through the capillaries.
❤ O2 delivery vs. O2 carrier
So why is this good for short term use when there may be an issue with breathing but not in a trauma, blood loss situation? The LOMs are injected into the bloodstream where they can quickly oxygenate the blood. See the beaker of blood before and after adding LOMs (via the journal article). As the oxygen leaves the LOMs and saturates the hemoglobin in blood, they shrink. Think of a balloon releasing oxygen. The “deflated” LOMs cannot be “re-inflated” in the bloodstream (remember the sonicator was needed to get the oxygen in). You can see a deflated LOM in the lower left of the cartoon. Also carbon dioxide is not removed. In the short term this isn’t an issue. If this were needed for longer use, the CO2 would build up and make the blood acidic.
So what’s the difference between O2 delivery and an O2 carrier? LOMs are an O2 delivery system. Oxygen (or carbon dioxide for that matter) does not go back to the LOMs as they circulate. There two types of artificial oxygen carriers: hemoglobin based and perfluorocarbon (PFC). The LOMs are closer to PFC formulations.
❤ Perfluorocarbon (PFC)
A perfluorocarbon is an organic compound made up of carbon and fluorine. Emulsions of PFCs can be made that carry oxygen. Early on the emulsifiers used in PFC emulsions caused allergic reactions in people. The biggest problem with PFCs in the context of artificial blood is that the oxygen carrying characteristics require high oxygen content in the blood in order to release the oxygen. If you look at the figure below (http://goo.gl/csOsnk) you can see that you need a higher partial pressure (pO2, oxygen concentration) for the PFC relative to blood to release oxygen. Here’s a video that shows a mouse breathing liquid PFC. You might see other videos incorrectly state that it is a mouse breathing water.
So what makes blood or hemoglobin so much better than PFC for oxygen carrying? A little compound called 2,3 diphosphoglycerate (2,3 DPG) is the key. It’s an allosteric effector. Allos from Greek means other and stereos means space. So an allosteric effector changes the shape or folding of a protein when bound or unbound. When 2,3 DPG is bound it shifts hemoglobin to the low affinity state for oxygen, i.e., releasing it more readily. It’s increased levels help in conditions of low oxygen/blood, e.g. traumatic blood loss.
One other tidbit, these microbubbles aren’t new. They have been used as contrast agents for ultrasound imaging, which I’ll talk about in another post. I can also talk more about hemoglobin based oxygen carriers in a future post if there is interest.
Check out this great article by Buddhini Samarasinghe on nature.com‘s soapbox series (http://goo.gl/O6csd6). Buddhini explain two barriers to science: the paywall for scientific publications and the jargon-wall. She also describes her efforts in science outreach. If you aren’t following her already, you need to circle her now.
I’ve been thinking of writing a post about OpenAccess journals because I assume that the journals are like the jargon that’s in them. The lay public doesn’t know which journals are reputable and which one’s are so-called predatory journals. Predatory journals send unsolicited emails to scientist, students, etc. saying how great and open their journals are. What they don’t advertise is that it cost quite a bit to publish in some of those journals. My colleague had a situation where he was reviewing a poorly written manuscript and the editor was trying very hard to get my colleague to be more lenient. The fact that, that journal charges $1,000 per manuscript might have been a factor.
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