Disease Prone

Goodbye FoS, thanks for all the laughs

2011-07-05T16:31:00.000-07:00

Moving house again…

Well almost, moving addresses anyway. It wasn’t that long ago I moved from Disease of the Week to here at Disease Prone to take advantage of an offer from Field of Science. While I have been super happy here, an amazing opportunity has opened up for me to move the blog over to the Scientific American’s new community and so now I can be found at Disease Prone. I know a few others from FoS are moving too and I’ll let them say their own goodbyes but for me, I wanted to say a big thank you to FoS, it’s bloggers, readers and admin for helping me set up and being so supportive when this offer was extended to me.

At some point in the future this page may be removed so if you would like to continue following me you can find me here at SciAm with my new RSS feed or here on Facebook or here on Twitter.

Thanks FoS, I’ll see you ‘round.

No door? No problem. T. cruzi uses the window to cause Chagas Disease

2011-06-24T16:07:00.000-07:00

For invasive pathogens the only way to survive, and consequently make you sick, is to get inside your cells. This is a rough exercise as you have an immune system working everywhere in the body to prevent this and the cell to be invaded is none too happy with the idea either so invasive pathogens must use tricks.

After evading or surviving the immune system, another post for another day, some exploit a mechanism called receptor mediated endocytosis (RME), in which the pathogen binds to a receptor on the cell triggering the cell to alter its shape to internalise the pathogen. RME is used by cells to recycle extracellular components but it a pathogen can make itself fit the receptor instead it can trick the cell into giving it free access to its insides.

Another mechanism, commonly employed by membrane bound viruses, is membrane fusion. Given that membrane bound viruses contain a secondary structure called the nucleocapsid, which houses the genome, they can fuse their own membranes with the host cell which results in the nucleocapsid's release into the cytoplasm.

(a) HIV entry by fusion and (b) receptor mediated endocytosis of light blue dots ((a) modified from credit and (b) modified from credit

Some recent research has uncovered a novel invasion technique used by the protozoan Trypansoma cruzi, the causative agent of Chagas Disease. We’ll get to that in a moment.

Trypanosoma cruzi (credit)

Chagas Disease is named after the super moustachioed Dr. Carlos Chagas, physician, bacteriologist, parasitologist, epidemiologist and infectious disease superstar. Chagas’ story is interesting enough for its own post, but in short his work achieved a great many things and he is best known for being the only person in history to, on his own, describe a pathogen, its vector, the effect on experimental hosts, clinical manifestations in humans and its epidemiology! All this work would, and should, have been enough for a Nobel Prize, which he was twice nominated for in 1913 and 1921, but Chagas was blocked by his arch nemesis the also impeccably moustachioed Dr. Júlio Afrânio Peixoto a prominent eugenicist.

Left is Carlos Chagas (credit) and right is Afranio Peixoto (credit)

Chagas’ discovery showed that triatome bugs like Rhodnius prolixus spread the parasite between people by biting infected individuals and then moving to new food sources. Chagas thought the parasite was spread as a result of the bite but later studies showed that the parasite survived the insect’s digestive tract and entered the new host when they scratched at the bite pushed the insect’s faeces into the wound. From there the parasite invades nearby cells and reverts to its reproductive form, replicates and then releases the invasive form of the parasite back into the blood to repeat the cycle.

Lifecycle of T. cruzi (credit)

The disease itself is spread into 2 distinct stages. The initial acute stage results in flu-like symptoms (which I have decided would be a great name for a blog given that everything has flu-like symptoms) and a raised area at the bite site. Experienced physicians can also spot something called ‘Romaña's sign’ which is a swelling of the eyelids on the side of the face that was bitten. Most people survive the acute stage with no problems but few actually cure themselves of the disease. The second stage of disease depends on how the host responds to the chronic infection.

Indeterminate Chagas disease is the good version. These people respond positively to Chagas tests but are asymptomatic. The bad version, determinate Chagas disease, is experienced by 20% - 40% of people who pick up the parasite.

Those that pick up the symptomatic chronic form of Chagas disease suffer a number of problems centered around parts of the body that get a lot of blood a lot of the time like the heart, brain and gut.

The parasites activity at the gut paralyses it, resulting in permanent dilation of the gut. This becomes an enormous problem as the co-ordinated contraction of the gut (peristalsis) is what keeps food material moving. If it doesn’t move it rots which is never good but can also result in the consolidation of faecal matter and the formation of faecal tumours, which are even less good.

If the brain and central nervous system are involved then dementia and confusion can set in as well as destruction of motor or sensory neurons effectively paralysing or numbing the sufferer.

Most deaths associated with Chagas disease are due to destruction of cardiac tissues leading to enlargement of the heart, loss of rhythm and subsequent decrease in the efficiency of the heart, clinically referred to as dilated cardiomyopathy. This often results in sudden death as the heart fails and stops.

What makes all of this even more saddening is that currently there is no vaccine and treatment options are limited but the recent observation of T. cruzi’s novel invasion mechanism might enable the development of novel drugs to prevent the continuous re-infection.

T. cruzi invades cells by inducing cell membrane damage. The cell’s response to membrane damage is allows calcium to flow into the cell, which triggers a number of cellular activities including the fusion of lysosomes with the cell membrane. Cells are highly compartmentalised and each component has a specific activity. In a way you can think of a cell as a house where each room has its own activity, bedrooms are for sleeping, kitchens for cooking etc. Lysosomes are like the garbage disposals of cells that contain all the degradative enzymes for the breakdown of cellular waste among other jobs (thanks Dr. Simon :D).

The release of the lysosomal contents results in some of these degradative enzymes getting into the damaged sections of membrane and breaking it further allowing its internalisation and destruction by the cell.

So rather than binding a receptor to force internalisation the parasite damages the cell membrane triggering a repair mechanism that drags the parasite into the cell alongside the membrane to be destroyed.

The really important observation here is that the damage caused by the parasite is due to its binding of the membrane intimately and then trying to swim away causing mechanical stress on the membrane resulting in damage. This suggests the possibility of drug development targeted at preventing attachment of T. cruzi, which would limit the internal spread of the parasite and might even allow immune system clearance and cure of the disease!

References

Jermy A (2011). Parasitology: Adding insult to injury. Nature reviews. Microbiology, 9 (7) PMID: 21625249
Andrade LO, & Andrews NW (2005). The Trypanosoma cruzi-host-cell interplay: location, invasion, retention. Nature reviews. Microbiology, 3 (10), 819-23 PMID: 16175174
Fernandes MC, Cortez M, Flannery AR, Tam C, Mortara RA, & Andrews NW (2011). Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion. The Journal of experimental medicine, 208 (5), 909-21 PMID: 21536739

Anti-cancer Fungi

2011-06-17T20:38:00.000-07:00

Mycology, the study of fungi, is an often-overlooked member of the microbiology family. Having said that there are plenty of dedicated mycologists out there doing all sorts of cool stuff and plenty more fungal species doing all sorts of weird and wonderful things.

I have written about fungi before but only in the recent zombie posts and I feel I may have been a bit negative on fungi. Particularly when they seem to be capable of much good.

In recent years researchers have made some potentially amazing discoveries that could result in significant cancer treatments based on the observations of polysaccharopeptides recovered from some species of fungi.

Polysaccharopeptides are commonly recovered from Coriolus versicolor commonly called Turkey tail fungus or Yun-zhi (credit, credit and credit)

What’s a polysaccharopeptide? It’s a contraction of the full description polysaccharide peptide. Essentially it is a long repeating unit sugar chain connected to a small protein sequence. Sounds innocuous but these molecules (or more accurately the fungi harbouring these polysaccharopeptides) have been used in traditional Asian medicine for a long time.

Beginning in the 1980’s these compounds began to attract more attention due to their apparent anti-tumour activity. The interest in polysaccharopeptides started to build when it was identified that the anti-tumour activity was not due to direct killing of tumour cells, but instead was due to an upregulation of the host immune system assisting the host to take care of its own cancer.

It appears now that polysaccharopeptides have 3 major activities; the activation of phagocytes, the activation of natural killer T-cells and the activation of helper (or CD4⁺) T cells. Without getting into the nitty gritty immunology of it all phagocytes ‘eat’ foreign material, tissue debris and misbehaving cells, natural killer T cells respond to misbehaving cells by ordering them to die and CD4⁺ T cells produce lots of chemicals which assist the immune system in many different ways. Essentially these polysaccharopeptides are acting as a turbo boost button for the immune system.

The real power in a compound that stimulates an immune response to handle a tumour, rather than a compound that directly kills cells, is that the body has in-built defences to make sure it doesn’t destroy its own healthy cells. When you give polysaccharopeptides to healthy individuals their immune systems are activated but with nothing to attack they scale back down again without doing any damage compared to current approaches to cancer therapy including chemo and radiotherapy which cannot target a tumour cell directly which can result in nasty wound as well as side effects like hair loss and infertility.

Clinical trials of polysaccharopeptides are starting to become very exciting as synergistic combinations of traditional treatments are used alongside these compounds often to great effect.

A study in 1995 of 227 Japanese breast cancer sufferers saw that when split into two groups, one receiving standard chemotherapy treatment and the other receiving the chemotherapy and a supplement of polysaccharopeptide saw the 10 year survival rates jump from 64% to 81% in the chemo + polysaccharopeptide group. Similar results were observed in a 1994 study on gastric and oesophageal cancer patients where the 5 year survival rate jumped from 60% to 73% when chemotherapy was supplemented with polysaccharopeptide.

Other trials on colorectal, liver and lung cancers as well as disseminated cancers like leukaemia have also indicated favourable results for the supplementation of current therapies with polysaccharopeptides.

More recently we can add prostate cancer to the list of cancers that may benefit from the addition of polysaccharopeptide to therapeutic protocols. While not human trials, a recent study has found polysaccharopeptides can be used to prevent the development of cancers indicating there may be more to discover about these interesting molecules.

When fed a diet including polysaccharopeptides mice that are genetically engineered to develop prostate cancer simply didn’t. When I say didn’t I mean the mice that received only water got prostate cancer and at the end of 20 weeks the not a single water + polysaccharopeptide mice had a single prostate tumour.

As amazing as this result is the researchers went further and looked at why there were no cancers developing and found that the recently identified cancer stem cells of the prostate (a long lived, self renewing, cancer cell progenitor in the prostate) were being heavily inhibited in the polysaccharopeptide supplemented mice.

While only a small study, it suggests there may be a very important future role to be played by polysaccharopeptides in cancer therapy and, importantly, might lift the reputation of fungi in the eyes of people who ruthlessly destroy all the fungi and mould they can find.

ARGH!!! KILL IT!!! (credit)

References

King-Fai Cheng & Ping-Chung Leung (2008). General review of polysaccharopeptides (PSP) from C. versicolor: Pharmacological and clinical studies Cancer Therapy, 6
Luk SU, Lee TK, Liu J, Lee DT, Chiu YT, Ma S, Ng IO, Wong YC, Chan FL & Ling MT (2011). Correction: Chemopreventive Effect of PSP Through Targeting of Prostate Cancer Stem Cell-Like Population. PloS one, 6 (6) PMID: 21674070

To Tattoo or Not To Tattoo

2011-06-10T16:50:00.000-07:00

Is it something you should do or is it taboo? What about a tattoo of a kazoo?

Okay, I'll stop now.

Recently I’ve been considering getting another tattoo or more work done to complement my existing tattoo. Its not terribly scientific like the Carl Zimmer’s Science Tattoo Emporium but it does mean something to me. I think I’ll probably wait until I finish my PhD, which means I’m looking at getting it in about a year.

Ignore my camera in the top left, the tattoo is too close to my shoulder making it very difficult to get it of of shot. Anyway, it's a raven.

One of the things I didn’t realise about getting a tattoo the first time was just how much mess it makes and how much blood there is. It doesn’t make any sense really given that I was completely aware a bunch of needle were going to repeatedly puncture my skin but, honestly, I’d never really thought about the blood. I can assure you if I had known I probably would have wussed out.

So I started looking at what exactly a tattoo is.

The dermis is the pink bit. Credit

For a tattoo to stick indelible ink must be inserted into the dermal layer of the skin. This gets it between the epidermis, which is the part that is constantly shed, and the blood supply. The introduction of a needle and ink into this area understandably activates your immune system and the damaged tissue becomes inflamed. Among the cells recruited to the damaged tissue are phagocytes and fibroblasts and both of these cell types begin the repair process. During repair the majority of the ink is incorporated into fibroblasts and scar tissue and remains a permanent fixture. Over time tattoos are degraded and so will eventually lose detail and also tend to fade if exposed to direct sunlight regularly.

Traditionally, tattoo colours and designs were limited by the skill of the tattooer, the tattooing equipment available and the pigments recoverable from nature. For this reason traditional designs are swirling or repetitive shapes done in only black ink. Black inks were made using ash but now a full range of colours are available through the generation of inorganic materials specifically designed for inks.

As tattoos become more and more popular, especially through shows like Miami Ink and tattooers become celebrities like Kat Von D it becomes easier to overlook the serious complications possible due to receiving a tattoo.

This isn’t to say you shouldn’t get one, only that you should be informed beforehand.

The establishment that did my tattoo smelt like a hospital, always a good sign. There are serious risks if the equipment is not sterilised properly and prison tattooing (where it would be unusual to find an autoclave available to inmates) carries with it an increased risk of HIV, hepatitis, herpes, tetnus and staph infections. It’s for this reason that if you get a tattoo you can’t give blood for the next 6 months in Australia. By that time I guess you would know if you have picked anything up.

Although rare, some people can have an allergic response to the tattoo itself. It’s believed to be rare because of the way the ink is sequestered into fibroblasts and fibrous tissue but if allergic to mercury and or nickel it can result in a tattoo that remains inflamed and continually weeps fluid. Typically, its red colour in tattoo designs that is more likely to give a reaction but at this stage the reporting of the issue is very low so for many it’s not a concern at all.

As well as allergic type reactions the body can straight up reject the tattoo and form a granulomas around the ink molecules. A granuloma is the body’s way of giving up and making a last ditch effort to attack a foreign invader. Lots and lots of immune cells throw themselves at the ink and fuse together to make a single giant cell and then it stays there with the ink trapped inside. Sometimes these can be felt as little lumps within the tattoo. Inflammation of the dermis and epidermis can also cause problems and tattoos, again rarely, have been linked to the development of eczema and other chronic skin conditions.

Its also worth asking where the ink came from as the cheaper inks have been found to contain known carcinogens and in a report from Europe they found that 40% had not been approved for cosmetic use and 20% of inks contained a known carcinogen!

And after all this there is one other possible complication. Again it’s rare but links have been made between burns and tattoos following magnetic resonance imaging or MRI.

Its been observed that thick black tattooed areas can result it burns following MRI due to the concentrated iron oxide used in the black pigments. The electrons in the iron oxide, which is magnetic, move in response to the moving magnetic field of the MRI, which generates an electric current. This current is resisted by your tissues causing them to absorb this energy and heat up. Due to the intensity of the MRI and therefore the generated current the heat can reach boiling point causing the water in the dermal layer of your skin to boil which can result in second degree burns!

Don't worry guys its not creepy at all when you do that. Also, is the Dr. Turk on the left?

I must stress that all these possible complications are rare and I’ve never met a person who has experienced any problems. I’m fully aware there are risks and they still aren’t going to put me off getting another :)

Now what should I add to it…

Any suggestions?

References

Wagle WA, & Smith M (2000). Tattoo-induced skin burn during MR imaging. AJR. American journal of roentgenology, 174 (6) PMID: 10845532
Tope, W., & Shellock, F. (2002). Magnetic resonance imaging and permanent cosmetics (tattoos): Survey of complications and adverse events Journal of Magnetic Resonance Imaging, 15 (2), 180-184 DOI: 10.1002/jmri.10049
Hartwig, V., Giovannetti, G., Vanello, N., Lombardi, M., Landini, L., & Simi, S. (2009). Biological Effects and Safety in Magnetic Resonance Imaging: A Review International Journal of Environmental Research and Public Health, 6 (6), 1778-1798 DOI: 10.3390/ijerph6061778

Treating the Bends

2011-06-03T14:40:00.000-07:00

Last week I wrote about the Bends, a medical problem based in an understanding of physics that results in bubbles of (primarily) nitrogen in your blood if you move from one atmospheric pressure to another to quickly, typically surfacing from depth while diving too fast.

Of course I meant to point out that decompression occurs when the external atmospheric pressure drops quickly. Most commonly this occurs in divers but also happens in astronauts. I’d never really thought about that before.

Anyway I got as far as explaining how it occurs last time. This time we are interested in how you fix it.

The therapy is actually very simple – take the person back to the depth they were diving at to force the bubbles to resolve into the blood. This immediately solves of the symptoms of the condition but is a little impractical to drive the diver back to the beach and drag them underwater. So, instead, we fake it.

In order to fix your pain I need you to please climb into this fortified chamber. What do you mean no? Credit

In order to fake depth we use a hyperbaric pressure chamber. This chamber allows us to increase the pressure of the air mixture such that the bubbles resolve. Then the operator slowly brings the pressure back to atmospheric levels to allow enough time for the patient to breathe out all the solubilised gas.

To aid this and ensure as much nitrogen as possible is extracted from the patients blood the chamber is often pumped with 100% oxygen. This generates the maximum pp (partial pressure) gradient dragging nitrogen out of the body while also providing the body and its cells with maximum oxygen to facilitate repair of any tissue damage.

The treatment is very simple but relies on an understanding of the physics that caused the problem to begin with.

Hyperbaric oxygen therapy (HBOT) is not just used to treat decompression illness though. In fact since the observation that breathing oxygen at pressure results in huge increases in the amount of oxygen found in the plasma providing a saturating level of oxygen to the tissues many conditions began being listed as ‘treatable’ by HBOT.

Of those conditions treated with HBOT a large number are infections by obligate anaerobic organisms. Conditions like gas gangrene, necrotising fasciitis and osteomyelitis show significant improvement when tissues are saturated with oxygen preventing exaggeration of the infections and even the death of the agents causing the disease.


Instead of showing you actual rotting flesh I opted for a plush gangrene toy. Thank me later.	Credit

Similarly it is thought the increased oxygen carriage facilitates improved wound healing by providing the tissues with every opportunity to function normally. To this end HBOT has been employed in the treatment of diabetic wounds, radiation injury, skin graft and burns.

It’s even started to pick up such a reputation for healing that elite athletes are jumping on the bandwagon and subjecting themselves to HBOT to increase the healing of injuries.

Unfortunately it’s not all smooth sailing. HBOT does have some downsides. Apparently there is such thing as too much oxygen and its effects can be debilitating.

Oxygen poisoning can effect the central nervous system, lungs and eyes in particular. An increased oxygen hit causes the CNS to behave very strangely resulting in tunnel vision, tinnitus, nausea, muscle spasms due to increased neural activity, dizziness and personality changes toward irritated states although this might just be because how rubbish you feel with the rest of that going on. Typically these are the problems that arise in divers as they develop after short term hyperoxia.

Long term hyperoxia is more dangerous then I would have ever expected. Prolonged hyperoxia results in a burning sensation during breathing and can lead to dyspnea (shortness of breath) due to the discomfort. It has also been linked to increased blood flow to the nose and increased permeability of vascular tissues resulting in a massive chance of nose bleeds but the real problems occur in the eyes.

Whilst normally only a problem for premature babies in HBOT chambers used to assist with early life extended use may result in conditions such as myopia or even retinal detachment!

So now you know what a detached retina looks like. Obviously this is not on a premmy baby. Credit

HBOT as its uses but the tendency to use it continuously as some elite sportspeople are beginning to do may have adverse effects. Despite this its popularity will probably continue to rise while its benefits are so numerous. In the mean time for those of us that can’t afford approximately $2,000 an hour for HBOT your best option is to go diving and ascend to quickly, then you get the diving experience and your HBOT for nothing*.

Does not constitute actual advice. I’m a moron, not a doctor. Also only applies to countries like Australia where emergency medicine is supplied to those that need it and not just those that can afford it.

Reference

Vann RD, Butler FK, Mitchell SJ, & Moon RE (2011). Decompression illness. Lancet, 377 (9760), 153-64 PMID: 21215883
Acott, CJ (1999). Oxygen toxicity: A brief history of oxygen in diving. South Pacific Underwater Medicine Society Journal
Clark JM (1974). The toxicity of oxygen. The American review of respiratory disease, 110 (6 Pt 2), 40-50 PMID: 4613232
Hart, GB, & Strauss, MB (1990). Gas Gangrene - Clostridial Myonecrosis: A Review. Journal of Hyperbaric Medicine
Necrotising Soft Tissue Infections

Physics + Medicine = The Bends

2011-05-27T16:14:00.000-07:00

About a fortnight ago I was in the unusual position of teaching human biology to medical physicists and physics to medical students. Interestingly, during this overlapping week a disease came up in both tutes, a physics based medical condition.

Arguably many diseases can be based in physics including heart disease, atherosclerosis and pretty much anything else to do with the pipes in your body but a disease known as ‘the bends’ or ‘decompression sickness’ invokes a bunch of physics laws and principles and then also requires a physics based treatment to deal with it.

The bends gets its name, like Jumping Frenchman of Maine Syndrome, because it literally causes the patient to bend over. This is because the condition is so excruciatingly painful that almost everyone who gets it doubles over in pain.

The bends is caused by rapid decompression resulting in painful phase transitions of solubilised gas into bubbles occurring in the blood, muscles, bones and fatally in the brain. But first it’s a question of how decompression can cause these problems.

The other name for the bends is ‘divers disease’ as it is only divers who really have the ability to increase the external pressure of their environment. As they diver deeper they effectively increase the atmospheric pressure which has important consequences for the composition of air in their lungs.

Now for a little physics. The concept of partial pressure is very important when talking about the bends. So, partial pressure (or pp) is defined as the pressure exerted by one gas in a mixture of gases. Another way of thinking about it is that in a mixture of gases the sum of all the pp of all the individual gases will equal the total pressure of the mixed gas. The air we breathe is a perfect example. Air is made up of approximately 80% nitrogen and 20% oxygen and the rounding errors are a bunch of other trace gases. So the pp of nitrogen at sea level is 80% of atmospheric pressure, which is defined as 1 atmosphere (or 1 atm), therefore 0.80 atm and oxygen has a pp at sea level of 0.20 atm.

Divers however are not at sea level, they are lower and therefore experience higher pressures (and for the purpose of the diagram I have made lets say divers are at a pressure 4 times normal or 4 atm).

Still with me? Well here’s a little more physics.

A guy named Boyle has a law and his law states that pressure is inversely proportional to volume, as you increase the pressure on a gas you decrease the volume that gas occupies. Pretty self-explanatory. Essentially you concentrate the molecules of the gas but don’t change the composition of the gas. So the pp of nitrogen will be 80% of 4 atm or 3.2 atm and the pp of oxygen will be 20% of 4 atm or 0.8 atm. So when you are a diver breathing compressed air at depth you inhale more molecules of gas per breath into your lungs.

So here’s the next bit of physics. The concentrated air in your lungs now needs to get into your blood so that the oxygen can be used. Oxygen moves into the blood based on the pp gradient, there is some oxygen in the lungs, less in the blood and so the oxygen moves in. By the same principle nitrogen dissolves into the blood too, but how much? Henry’s law (the only other law we need here) states that at a gas/liquid interface the amount of gas solubilised into that liquid is determined by the pp of the gas, or, the more gas molecules in a space (lungs) the more gas molecules dissolved into the liquid (blood).

So at this point we have described how the diver would have more nitrogen dissolved in the blood but the pathology develops, as I have said above, when and how it comes back out of the blood.

If the diver ascends to the surface too quickly the solubilised nitrogen is no longer under the increased pressure and so the pp of nitrogen in the blood is 3.2 atm and outside in the air the pp of nitrogen is still 0.80 atm. Moving along the pp gradient nitrogen does its best to rejoin the air as quickly as possible, a problem when it is separated from the rest of the air by your body.

The bends is something that divers all know about but is interesting in so much as it is reasonably medicine free for a disease. Normally the medical conditions we discuss with the medical students are complex matters of biology, anatomy and physiology but this pathology can be understood without knowing much about the body as long as the physics foundations are sound.

Next week I will talk about how the bends get straightened out.

See what I did there?

Reference

Vann RD, Butler FK, Mitchell SJ, & Moon RE (2011). Decompression illness. Lancet, 377 (9760), 153-64 PMID: 21215883

Rain becomes a drizzle

2011-05-20T16:00:00.000-07:00

Oh how I'd love to write up a blog post right now.

Instead I can barely see over the pile of 1st year undergraduate reports on Photosynthesis and next to that pile is another pile of worksheets on agarose gel electrophoresis. I also have thesis corrections and a thousand other little things to do. Oh, and from where I'm sitting I can see that I might even need to mow the lawn before it rains. So while I want to blog it just 'aint going to happen today.

Even though today is 'out' I have some really cool posts in the pipeline so we will see what I can organise for next week.

For now its back to my cup of tea to read attempts by first year students to convince me that photosynthesis occurs in the mitochondria and provides the cell with an unending supply of boiled candies...

I'm more disappointed at my inability to blog than this puppy (Credit: honzasterba)

RSPCA Million Paws Walk recap

2011-05-15T20:14:00.000-07:00

Yesterday (15/5) was the Royal Society for Protection against Cruelty to Animals (RSPCA) major annual fundraising drive, a walk in the park called the Million Paws Walk. The idea is that people can register as individuals or as teams and by registering they raise a little money. Each individual registrant and team can also raise money for themselves to complete the walk.

Last year the South Australian walk was attended by over 6000 people and their dogs and raised over $120,000! This year it was easily bigger and while the numbers don’t seem to be out yet money raised online has exceeded $27,000 and this only includes the donations raised by the individuals and teams involved in the actual walk. It seems that money raised this year will eclipse last years mark.

I have had the donation widget on the page (should be over there >>>) for a while and I wanted to thank anyone who donated to my team. In fact the $400+ dollars we raised made us the 8^th highest team fundraiser (we are Frankie, Micky and Friends)! As a thank you here are some pictures of my dogs :).

Micky with Frankie photobombing in the background

Frankie as a puppy when she still looked like a stuffed toy

I issued the command Yin Yang... They nearly got it. Also, Micky (on the right) is about twice as large as Frankie (on the left) now. Weird seeing him so small again :)

Zombies Pt 2 (or how I distracted my students)

2011-05-06T15:57:00.000-07:00

Last week I mentioned how my students sidetracked me in a tute regarding introductions to the origins of life and in particular the acronym HOMR standing for Homeostasis, Organisation, Metabolism and Replication by initiating a discussion of whether or not zombies technically were alive. Well, the following week they had a test that occupied half the allocated tutorial time so instead of letting them out early I extended the discussion to real world zombies.

After a little investigation it became clear that ‘zombism’ is a lot more common in nature than I expected. While not true zombies the examples I have below represent some of natures best approximation of living dead.

The first one I quite liked was The North American Wood Frog (Rana sylvatica), which undergoes an extreme return from the dead each year.

Sup? I'm just defrosting.

The winter hibernation in northern North America is very important because of how long and extreme it can be. To up the challenge the wood frog hibernates in the leaf litter and consequently freezes solid during winter. By solid I mean properly solid. The frogs can survive multiple freeze/thaw events as long as less than 65% of their water remains unfrozen. Freeze/thaw stops my experiments on bacteria from working but apparently these frogs are just fine. To survive the big freeze the frogs accumulate urea in the tissues and build enormous glycogen stores which breaks into glucose upon ice formation in the tissues. The soluble urea and glucose prevent ice formation and save the frogs. This phenomenal life cycle enables easier and early access to the natal ponds where eggs are laid and tadpoles develop and must leave before the thawing dries up the pools. So the question was posed, is a wood frog alive during winter hibernation? Technically it's dead, no heartbeat, no metabolism and yet it survives. Does this make it a reanimated corpse? Very spooky.

There are lots of zombie ant variations that I could go to but my two favourites are zombifying fungi Ophiocordyceps unilaterius, which zombifies Camponotus leonardi ants and Dicrocoelium dendriticum which zombifies Formic fusca (the European common black ant).

All ants are creepy up close (Photo Credit: D. S. Sikes)

O. unilaterius infects the worker ants via its respiratory system and quickly spreads throughout the ant's body. Importantly the fungus spreads into the brain and the result is the ant alters the way it responds the pheromone messengers.

The zombieness of this interaction does not come from the death of the ant but instead the ant’s loss of ant-ness. Infected ants leave the colony (and in some cases are removed by the colony members directly) and climb. The climbing is very important as the fungus can only grow at a particular temperature and humidity. The ant must locate these conditions based on the chemical instructions of the fungal controller. Once a suitable environment has been found the ant performs its final act, it climbs underneath a leaf and grips with its mandibles, never to let go. Why the underneath? Because the fungus is sensitive to UV light. The fungus continues to grow and kills the ant in the process eventually resulting in the emergence of fungal stalks covered in spores that are sprinkled on the ground near the ant colony that provided the last victim. Is the ant, which continues to satisfy HOMR (except for the ‘R’ that it never did that anyway), actually alive when the fungus takes over? Or is it an animated corpse?

Not as creepy as when they look like this though.

Similarly the Formica fusca have to deal with the mind-controlling pathogen Dicrocoelium dendriticum also known as the Lancet Liver Fluke. The adult flukes reside in the livers of cattle and other grazing mammals and its eggs are released in the faeces of that animal. The eggs sit happily in the poo until consumed by snails. Once eaten the flukes drill into digestive tract of the snail where they develop into juvenile flukes. Obviously the snail would prefer that this didn’t happen and so attempts to wall the flukes of in cysts. It is these cysts that are eventually released by the snail.

The cysts are left behind in the snail trails, which are harvested by the F. fusca and as such this is how they get infected. Similarly to the activity in the snail most flukes get caught up in cyst but one fluke navigates to a bundle of nerves in the ants oesophagus and from there it controls the ants activity.

As the night air cools the infected ants leave the colony and ascend the grass blades and clamp down on the tops with their mandibles and waits. If nothing happens during the night the ant decends in the morning as the temperature rises and it rejoins the colony. However, occasionally a grazing animal will eat the ants along with the grass allowing the infective process to start all over again. Again is this ant alive during the day but a reanimated corpse at night?

Loner ant waiting to be consumed.

Like the fungus and fluke before it the pathogenic barnacle Sacculina is a mind controller but this barnacle has an even more sinister side. Sacculina are castrating parasites of crabs and their lifecycle is as fascinating as it is weird. A female Sacculina will find and attach to a crab exoskeleton and then move around on its surface looking for a gap through which it can invade. It then ejects its own hard shell as it invades the crab’s interior. Once beneath the skeleton the Sacculina infiltrate all parts of the crab but specifically have activity at the genitals of the crab. The male crabs are castrated and rearranged to become females and the female’s egg sack is infiltrated and becomes Sacculina’s new home.

In its new home the parasite prevents the crabs natural molting and regrowing of limbs, as this is not nutritionally beneficial to the parasite, which prevents the crab from growing and repairing damage. Over time a male Sacculina finds the lady Sacculina in its crab host and fertilises her eggs inside the crab. The crab is further manipulated to develop nurturing characteristics and behaves exactly like a pregnant lady crab should. Once ready to be released the crab follows its normal birthing behaviour of climbing to a high rock, massaging her egg sack and swirling her claws to improve water flow except this time they are parasites and not crabs. Ultimately the crab dies as the parasite leaches nutrient faster than the crab can aquire it but in the mean time it has acted as a mindless vehicle for the construction or more zombifying parasites.

A double infection? Could this get any worse? Yeah actually, given the crab will eventually die.

The last one I wanted to mention is Toxoplasmosa gondii. A friend of mine wrote this little guy up here at little while ago but a quick summary of the facts wouldn’t go astray here I don’t think. T. gondii is a protozoan of cats spread primarily in their faeces but that doesn’t mean you wont get it. In fact estimates that as many as 16% of 12 year olds have previously been infected by T. gondii suggest that we eat more cat poo then we should. Having said that, eating poorly prepared meat is much more likely to give you the parasite.

In any case the cats are rarely significantly affected by the infection and even in humans the infections are often subclinical. Or are they?

Sustained infection of the human host has been linked to mental illness and, of all things, traffic incidents.

It also seems that we might be able to explain the ‘crazy cat lady’ on The Simpsons or any other TV show with a ‘scary old woman + cats’. Infected women apparently become generally more extroverted, show decreased inhibition and increased promiscuity while also exhibiting increased intelligence. Conversely men get the opposite, generally introverted and anti-social. Thus crazy cat ladies and crazy cat men rarely meet to produce crazy cat children.

Crazy cat lady and her kitteh quilt

Zombies seems more prevelant in nature than I ever expected it would be and while full zombification (rotting flesh and eating of brains) is not seen complete hijacking of organisms internal and external environments is performed routinely by nature’s little zombifiers, the parasites, and their actions are way to zombie-like for me to stay comfortable.

References

Costanzo JP, Lee RE Jr, & Lortz PH (1993). Glucose concentration regulates freeze tolerance in the wood frog Rana sylvatica. The Journal of experimental biology, 181, 245-55 PMID: 8409827
Andersen, S., Gerritsma, S., Yusah, K., Mayntz, D., Hywel‐Jones, N., Billen, J., Boomsma, J., & Hughes, D. (2009). The Life of a Dead Ant: The Expression of an Adaptive Extended Phenotype The American Naturalist, 174 (3), 424-433 DOI: 10.1086/603640
Jones JL, Kruszon-Moran D, & Wilson M (2003). Toxoplasma gondii infection in the United States, 1999-2000. Emerging infectious diseases, 9 (11), 1371-4 PMID: 14718078
PHILLIPS, W., & CANNON, L. (1978). Ecological observations on the commercial sand crab, Portunus pelagicus (L.), and its parasite, Sacculina granifera Boschma, 1973 (Cirripedia: Rhizocephala) Journal of Fish Diseases, 1 (2), 137-149 DOI: 10.1111/j.1365-2761.1978.tb00014.x
Tarry, D. (2009). Dicrocoelium dendriticum: The Life Cycle in Britain Journal of Helminthology, 43 (3-4) DOI: 10.1017/S0022149X00004971

Zombies Pt. 1 (or how my students distracted me)

2011-04-29T15:00:00.000-07:00

As I mentioned a little while ago I have been made an associate lecturer for first year biology at the University I have been doing my PhD at. Most of my job is taking tutorial classes and the other week during one of these classes I got totally distracted by a very interesting discussion.

Part of the tutorial concerned the requirements and characteristics of life. The students had covered the requirements as being HOMR; Homeostasis, Organisation, Metabolism and Replication. These requirements are pretty self explanatory but we also suggest they know evolution (primarily as it still fits into HOMER) and the other major acronym, MRS GREN (Movement, Respiration, Sensitivity, Growth, Replication, Excretion and Nutrition), illustrated here as a video, and think of them as hallmarks or common attributes of life. For the purposes of this course, if it satisfies HOMR then its 'alive'.

In any case after defining HOMR and giving a few grey area examples like viruses (nope, not alive), dormant bacteria (depends) and parasites in a non-replicative host (sometimes) we were about to move on when one of the students piped up, “what about zombies?”. The whole class stopped. It was interesting to see them all pause and try to work out if she was joking. After a few seconds and the first few giggles had subsided I asked the student to clarify what she meant. She replied with “you know, zombies, like in the movies. Would you class zombies as technically 'alive'?”

Arrrgggghhh living?

On its face it’s an odd question but as this particular class is one of my better ones and the rest of the tute was dull so I wanted to run with it.

My first question was what is a zombie? Most people know zombies as the undead after bbbrrrrrraaaaaiiiiinnnnnnnsssssss but many don’t realise that there are many types of zombies.

First we ruled out the Evil Dead canon of zombies which are raised from the dead by voodoo magic. While this was a silly extension of a concept there was no need to leave science behind all together.

What we are left with are the other canon of zombies like those depicted in 28 Days Later or Zombieland. These are zombies that develop as a result of some sort of pathogen infection. There is a great article that came out a little while ago that considers what a zombie pathogen would have to be capable of, but rather than be concerned with the pathogen, we were more concerned with the host.

Pathogen based zombies could be classed as the living-dead, the host never died and its actions are driven by the pathogen, somehow. Alternatively the pathogen kills the host and somehow drives its reanimation, the so called un-dead. While different, it is these kinds of zombie that we considered in my class.

We might need this later

So after defining the zombie we started to consider the requirements of life. Do zombies maintain homeostasis? We came to the conclusion that the living dead do but the un-dead cannot. The decay would be due to an inability to respond to changes and maintain an internal environment and a creature that has died would, according to the canon, be unable to heal or repair. The living dead however are living but mindless hosts hijacked by the pathogen and there is no reason they couldn’t continue to maintain an internal environment. In fact it could even be important for such a pathogens survival to maintain the internal environment of its host.

O is for organisation. A pathogen would have to be organised and complex in order to pull off the living death of its host and for the host to persist it must retain its cells to tissues to organs to organisms organisation. So as a class we took this one as a given.

Metabolism was easy. Um hello? They crave brains and eat them to provide sustenance. That's good enough for me.

It again seemed pretty reasonable to us that the cravings of a zombie could be irrational, especially if it was a mindless host and cells and pathogens need energy otherwise the living dead become the dead dead.

Finally, replication. I had always been taught that replication specifically meant of the genome and it is here that our host ceases to satisfy HOMR. Replication of zombies occurs via a bite but it does not result in replication of the host’s genome. The replication is only of the pathogen causing the zombification.


...and yet there are zombie children. Is there zombie sex I wonder. I wonder but I'm not going to Google it. Photo credit: D Sharon Pruitt

So zombies failed HOMR but what started as a weird question from an interested student turned into a memorable discussion that cemented these ideas into my students. But to make up for the disappointment of the failure their idea I decided to go looking for zombies…

I’ll leave that bit till next time.

Jump straight to Part 2.

Earth Day 2011

2011-04-22T17:42:00.000-07:00

Okay so I missed it in my timezone but like beer o'clock it’s always the right time somewhere. Earth Day is an important opportunity to look at the way we use the environment and consider ways we alter our impact for the better.

Below is an article that I previously published in the Adelaide Advertiser, the main newspaper from where I live about a much overlooked but vitally important cog in the environment, bacteria. It’s about a year old and I have mentioned it before but some of the info is worth another look.

Happy Earth Day, for yesterday.

Earth view from Orbiter (modified from)

BACTERIA are often victimised and not without good reason. They can make us sick and rot our food, but not all bacteria are bad. Without them, our world would simply cease to function as we know it.

Earth is sometimes referred to as the planet of the microbes because the number of microbes on this planet is simply staggering. We can assume there are roughly seven billion people around the world. Our best estimate on bacterial numbers alone is five million trillion trillion.

This means that for every person on Earth, there are about seven million billion bacteria. To write this number, you would have to start with a seven then put 20 zeros after it.

Even with so many bacteria, viruses still outnumber bacteria 10 to 1. These numbers are simply incomprehensible.

It amounts to one simple fact: Wherever we look for microbes, we will find them.

Bacteria do not simply just exist for the sake of it. More often than not, we find them performing some vital role that keeps our planet ticking over.

For a long time, we have known about bacteria that are capable of surviving the crushing pressures, lack of oxygen and soaring temperatures found within deep-sea vents. These bacteria, called thermophiles (or in some cases extremophiles) not only live, but thrive in these conditions that were considered for a long time by many to be too hostile for any organism. These bacteria also play a very significant role. They are able to absorb toxic compounds produced by other organisms, such as hydrogen, metabolic by-products and other unusual biological compounds, and recycle the base elements back into the food chain allowing a constant food supply to ‘‘trickle up’’ to higher organisms.

But it’s not just the bottom of the sea we find bacteria living out on the edge. The craters of active volcanoes are also teeming with microbial life.

Bacteria mats near the Grand Prismatic Spring in Yellowstone National Park

If you are so inclined, you can even find bacteria when looking in clouds.

Recent research indicates that not only are they up there but we might need them to be. Bacteria can bring the rain.

It seems that some bacteria, particularly some environmental strains like Pseudomonas syringae, have adapted their lifecycles to include ‘‘rain transmission’’. The bacteria are swept up into the atmosphere by wind but once in the air can act as ‘‘nucleation points’’ for condensation and ice crystal formation.

These events can trigger chain reactions resulting in the formation of clouds and eventually rain and snow. It’s important to remember that bacteria do this for a reason. In the case of P. syringae, it is primarily a plant pathogen that enters and leaves plants via leaf structures called stomata.

By adapting to and evolving a method of spread through the rain, the bacteria can greatly increase their own spread throughout the environment. As well as trawling the ocean floor and bringing the rain, bacteria have been implicated in everything from rock formation to preserving water quality and, of course, they play a major role in our ability to stay healthy.

The tools bacteria use to fight each other provide us with options for antibiotics and disinfectants and even by just occupying space on your skin, up your nose and in your gut, they help to try to prevent the bad bacteria being able to get a foothold and make you sick.

So the next time you see something disgusting and immediately blame it on the ‘‘germs’’, just remember that without them we wouldn’t be around to be disgusted.

Discoveries need dollars

2011-04-13T17:44:00.000-07:00

In Australia at the moment there is a real fear that our Government (who are supposed to be on the left side of that political line) is going to cut $400 million from medical research budgets. To protest this rallies are being run in most Australian capital cities to advertise the role of scientists in the community and to show all scientists that collectively we have a voice that can be heard, you just have to start shouting.

Arty farty photo of the rally taken by a friend of Thomas Tu, I'm not sure who

A couple of days ago the rally in my city was held and whilst I couldn't make it (due to teaching obligations) my good friend Thomas Tu, with whom I started Disease of the Week (on which he has also written a post about this) a few years ago, has been heavily involved. You can find a radio interview he did on one of Australia's largest radio stations, Triple J, here (about a third of the way in) and below I have put a video of him giving a speech at the rally. he is standing on the steps of our city's Parliament House.

Kudos Thomas!

So what can you do if you can't make a rally or are in another country but want to show your support? Jump on the Discoveries need Dollars website or the Facebook page and 'Like' or follow the Twitter page and at all these places there is more info.

We are trying to make it a big issue here in Australia to protect our livelihoods and encourage more students into science careers and it makes it very difficult when not only is money taken away but when its predicted to affect early career researchers hardest.

If you can help and you care about medical research I implore you to do as much as you can.

I'll get off my high-horse now :)

Blogging 101 Workshop

2011-04-11T03:36:00.000-07:00

Tonight I attended a Blogging 101 workshop run by a friend of mine Mr. Mike Seyfang (@fang for twits) who is a bit of a social media guru. It was really fun to go back to first principles with a room full of people learning about something I enjoy doing in my spare time and involving themselves in this time blackhole :)

So if you find yourself looking for new blogs to follow can I suggest those from the 'class'? They're new so give them time to develop and, of course, be gentle...

Other Side of Science
Heathers Sciencey Stuff
Bilbies Rule
Turk Thrust
Monianneo
Team Placenta
Sans Science
Tropidoderus
Disease of the Week

Enjoy!

Yes We C(r)an(berry)!

2011-04-08T18:51:00.000-07:00

That title is awful I know but I'm tired. Cut me some slack :)

I ran into a something that I have heard about before but assumed was rubbish and never really looked into it properly. A friend of mine insisted it was the case so I looked it up and I have to say, I was a little surprised.

So this is what cranberries look like. I never knew.

Cranberry juice is apparently very good at prevent urinary tract infection, particularly in women. There have been a few studies approaching it from different angles but, disappointingly, the studies all use different types of cranberry product, different doses and dosing techniques but despite all this the message seems to be pretty clear. Cranberries prevent urinary tract infections kicking in.

Before we can consider how this occurs its important to define what we are talking about. Urinary tract infections or UTIs are generally caused by a strain of Escherichia coli called Uropathogenic E. coli (UPEC) and it gets there by moving from the colon…ew. For this reason men rarely have to worry about them while they can be a chronic problem for women around the world, however the insertion of urinary catheters is a major risk factor for both genders. Clinical symptoms include burning sensation during urination and cloudy urine but these are only really evident once the bacteria have ascended the urethra into the bladder causing urethritis and cystitis respectively. If you want to feel real pain however let the little bastards work their way into your kidneys where kidney infection (or pyelonephritis) results in the above symptoms plus back pain and fever and the possibility of systemic spread.

So the first step in the infective process is generally stable colonisation of the colon. This step is often overlooked but without a source of UPEC it’s hard to get a proper infection going. The next step is invasion of the vaginal microbiota. Not an insignificant task since the vaginal niche is normally fully occupied by lactobacilli and other innocuous strains. Only once this has occurred can the UPEC ascend the urethra.

Having ascended the urethra the UPEC are not in the free and clear because the bladder and urethra have a formidable barrier to infection, the waterfall of flushing, cleansing urine that washes away all in its path. To overcome this UPEC have developed powerful adhesins, proteins used adherence of the bacterium to a surface and in this case specifically to the urinary epithelial tissue.

Adhesins are found in most pathogenic bacterial species but the array and strength of the UPEC adhesins is staggering. Among the most important adhesins produced by the UPEC are the pili. Pili are hair-like structures on the bacterial surface that are often capped with sticky (in the molecular sense) ends that facilitate adhesion. Importantly for UPEC possessing three different sticky caps (S, P and Type 1 pili) increases the chances of binding.

The S pili tend to be more important for adhesion outside of the gentio-urinary tract and so may play a part in systemic spread. In the urine however these pili bind the mannose filled protein uromodulin. Because of this S pili are called mannose sensitive pili and its thought that the ability to bind uromodulin, the most abundant protein in urine, possibly results in bacterial clumping and this allows a better opportunity for the P and Type 1 pili to do their thing. These two pili are responsible for the binding in the urethra and bladder.

Initially the Type 1 pili bind mannose sugars on the surface of the bladder cells allowing the bacteria to get some traction on the bladder/urethra walls before the P pili bind to a different sugar group to cement the interaction. The ability of P pili to bind non-mannose sugars has earned them the alternative title mannose resistant pili whereas type 1 pili are grouped with the mannose sensitive S pili.

The pili are the hairy bits on the picture of E. coli. The paper this pic is from is referenced at the bottom.

Once adhered to the host surface the UPEC can invade the epithelial cells but the bladder’s defence against this is to kick those invaded cells into the urine. A good defence strategy but it may contribute to tissue damage in the urinary tract when infections are recurrent. Also it seems some bacteria can prevent this expulsion of the cell they have invaded and in doing so remain as a reservoir of infection out of the way of the immune system and most antibiotic treatments.

Invasion does not always occur and instead some UPEC strains are able to release toxins directly onto the host epithelial surface due to the close interaction between bacterium and host. These toxins, as well as one of my boss’s favourite little molecules lipopolysaccharide (LPS) cause the inflammation that goes with the UTI.

So that’s the UTI side of things but where does Cranberry juice come into this story?

Cranberries (Vaccinium macrocarpon if you don’t mind) together with blueberries and Concord grapes constitute the only native fruit species to the US and Canada. Bet you didn’t know that, or maybe you did but I didn’t. In any case often the best way to work out what the native flora is capable of you have to look back to the indigenous peoples and, surprise surprise, Native Americans have known about and utilised the medicinal properties of cranberries for many years. Commonly used in different preparations to treat blood disorders, stomach issues, liver trouble and fevers.

By the 1880’s people were trying to work out what was doing what with cranberries and some German researchers found benzoic acid in cranberries. Then as now it was known to be a potent antiseptic and was included in a number of medicines and topical anti-bacteria treatments. This observation set researchers down the wrong path from the get go as the real power of cranberries lies in other activities of other compounds.

Continuing research into the antibacterial properties of cranberries found the benzoic acid was converted to hippuric acid, another antibacterial agent that also has a role in acidifying the urine. Everyone thought they were onto a winner. A powerful antibacterial compound excreted in the urine because you ate some cranberries. This is open and closed right? Well…

Could I be any clearer?

Some very smart research burst the bubble. Bodel et al. showed that even the consumption of a litre of cranberry juice mix (side note – straight cranberry juice tastes horrible, most ‘juices’ only contain 20 - 30% juice and the rest is water and sugar) barely acidified the urine at the detected hippuric acid concentrations were too low to be relevant. In fact it was subsequently shown that, as benzoic acid constitutes <0.1% of the weight of a cranberry in excess of 4 L/day every day of a strong cranberry juice mix would have to be consumed to have any antibacterial effect There had to be something else going on.

Sobota et al. suggested an alternative in 1984. In order to prevent a UTI you don’t have to kill all incoming bacteria, simply preventing them from attaching would also prevent UTIs developing. Using clinical E. coli isolates they were able to show cranberry juice impaired adherence in the majority of strains. Once on the right track research moved quickly. It could be shown that it was the mannose sensitive and mannose resistant pili that were being inhibited, preventing adherence and therefore UTIs. Cranberry juice contains at least two compounds capable of inhibiting adhesion. Being high in fructose allows for inhibition of the mannose sensitive type 1 and S pili and another product, apparently unique to Vaccinium sp. berries is proanthocyanidin, which inhibits the mannose resistant adhesins.

Some really interesting work has shown that the consumption of ‘normal’ amounts of cranberry juice has an anti-adherent effect as soon as 2 hours post consumption and will last approx 10 hours!

Unfortunately from this point onwards it gets a little cloudy. A consensus on mode of dose (pills or juice) and size of dose has not been established which makes it very hard to determine what the best course of action is. What is becoming clearer is that consuming as strong a cranberry juice as you can tolerate on a regular basis will help to prevent UTIs. It seems to be particularly useful in helping those that suffer recurrent UTIs and the literature seems to suggest it could be heavily utilised in women 10 – 35 years old as a background passive type defence against UTI.

I don’t know if it still works when made up like this but does anyone else feel like a vodka cranberry?

References
Raz, R., Chazan, B., & Dan, M. (2004). Cranberry Juice and Urinary Tract Infection Clinical Infectious Diseases, 38 (10), 1413-1419 DOI: 10.1086/386328

Gross, L. (2006). Bacterial Fimbriae Designed to Stay with the Flow PLoS Biology, 4 (9) DOI: 10.1371/journal.pbio.0040314

BODEL PT, COTRAN R, & KASS EH (1959). Cranberry juice and the antibacterial action of hippuric acid. The Journal of laboratory and clinical medicine, 54, 881-8 PMID: 13801916

Sobota AE (1984). Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections. The Journal of urology, 131 (5), 1013-6 PMID: 6368872

Exploding Head Syndrome - No pun required

2011-04-02T16:00:00.000-07:00

This is an old post from my previous blog. Recently it has been seeing a lot of activity so I thought I'd play around with it a bit and re-post it here. Enjoy :)

Sometimes when searching for disease to write about a wonderful thing happens. The clouds part, cherubs descend, angels play intricate harp-based musical compositions, and a beam of light illuminates the link to a wonderful disease. This happened to me the other day, and now, without further ado, let me introduce you to Exploding Head Syndrome. Best. Disease. Name. Ever.

Acute Exploding Head Syndrome sufferer (screenshot from the 1981 movie Scanners)

Okay so heads don’t actually explode but sufferers seem to experience a simulated explosion in the form of an incredibly loud noise coming from inside their own head. This sound can take many forms from ringing and screaming to, of course, explosions. One patient even described the preceding whistle of dropping bombs, the explosion of shells, and then complete silence, similar to an experience she endured as a child during the Blitz in London.

Exploding Head Syndrome is related to equally terrifying syndromes called ‘ice-pick headache’ and ‘needle in the eye syndrome’ but each of those have a pain component where Exploding Head Syndrome doesn’t (I can’t help capitalising Exploding Head Syndrome, it just feels like it should carry capitals).

The syndrome itself is described as “harmless but frightening” for sufferers. I guess the sensation that your head is about to explode isn’t pleasant but frightening doesn’t seem to be enough of a word to describe the torment.

Just to up the scare factor of this syndrome it seems to be associated with sleep. In a case study published in the British Medical Journal a woman described her attacks as…:

“Being wakened by a sudden bang in the head, as if my head was bursting with a flash of light over both fields of vision, after which I would be dazed for a split second" [and then would] "Come round, terrified, my heart thumping. There was no pain, just a frightening sense of explosion.”

Wow.

So what’s happening? Nobody has any idea. It isn’t auditory because deaf sufferers have been reported. It’s not linked to random nerve firing (often reflected in a condition called myoclonic jerks). It’s not linked to epilepsy. It’s not linked to migraines.

So we can’t understand what causes it, we have no idea what’s happening, we can’t say what might trigger it, it doesn’t seem to correlate with any associated conditions, apart from sleep – there’s only one thing missing here. Can we cure it? Of course not, what are you, stoopid?

There have been some reports that sedatives help but also, confusingly, apparently so do stimulants. Anti-depressants apparently help but not in all cases. The best bet for treatment seems to be to let it go away on its own. Many recorded cases had an acute onset where every night’s sleep was disrupted at least once and over a month to years the attacks became less frequent until they appeared to stop altogether.

I guess sufferers can take heart that if nothing else, being diagnosed with an Exploding Head makes for pretty interesting dinner party conversation!

Listerine - Insensitive to Exploding Head Syndrome sufferers since 1914

Chakravarty, A. (2008). Exploding head syndrome: report of two new cases Cephalalgia, 28 (4), 399-400 DOI: 10.1111/j.1468-2982.2007.01522.x
Evans RW, & Pearce JM (2001). Exploding head syndrome. Headache, 41 (6), 602-3 PMID: 11437900
Kallweit U, Khatami R, & Bassetti CL (2008). Exploding head syndrome--more than "snapping of the brain"? Sleep medicine, 9 (5) PMID: 17709298
Pearce JM (1989). Clinical features of the exploding head syndrome. Journal of neurology, neurosurgery, and psychiatry, 52 (7), 907-10 PMID: 2769286

Capsular Polysaccharide and Pneumococcal Disease

2011-03-11T14:41:00.000-08:00

This week looking at the capsular polysaccharide of Streptococcus pneumoniae. Want to know how I know? I wrote it :)

Insert stock photo of pneumo. Check.

It seems a little wrong to blog my own paper but in reality more people will read this blog entry than will read the paper itself, and that’s fine. Its relevance is very narrow and the work very preliminary but really it’s the drive behind the work that is important. So lets talk about Streptococcus pneumoniae (aka the pneumococcus or simply pneumo) for a second to set the scene.

Pneumo is a big deal. It is responsible for roughly a million deaths in children under 5 around the world every year and is such a problem in the developing world its one of the bugs that Bill and Melinda Gates have taken a personal dislike to.

This data is taken striaght from the WHO website. The only modification is I have added Streptococcus pneumoniae as a separate bar. Deaths caused by pneumo make up approximately 2/3 of all lower respiratory infections. I colour coded the bars for some reason for another post, I cant remember the key... #badblogger

Despite being such a huge killer it’s actually a very common bacteria. Every single person on Earth probably has it right now, so in that respect it’s not a great killer but at the same time, it doesn’t want to be. If you kill the host you destroy your home and food source so pneumo is happily carried in populations without causing disease, for the most part.

I have spoken about pneumo like there is only one kind of pneumo but that’s as silly as saying there is only one kind of human. An important common characteristic is that the outside of each pneumo, similarly to humans, doesn’t always look the same. In humans, differences in skin colour, texture, etc allows us to tell people apart, for pneumo however it’s the chemical composition of a structure called the capsule which encases the entire bacterium.

This capsule has, roughly, 90 different common variations and the distributions of these variations (referred to as serotypes) change depending on geographical region, age and community.

The important thing about the capsule is its job. The bacterium uses the capsule to hide from the host immune system, which is what generally triggers an immune response, and so allows the bacteria to persist asymptomatically in the naso-pharynx.

But as I hinted before pneumo doesn’t always sit happily in the naso-pharynx…

Generally during some other infection the pneumo will descend into the lungs and cause pneumonia, from which the bacteria derives its name. Approximately 30% of pneumonia patients will develop bacteremia as the bacteria use the lung damage to gain access to the blood. Once in the blood the bacteria can move all around the body and cause all sorts of disease but importantly they can cause meningitis (inflammation of the meningies in the brain) and this occurs in approximately 30% of bacteraemic patients.

Pneumo relies on its capsule to hide from the immune system during pneumonia, bacteraemia and meningitis (collectively called the invasive pneumococcal disease of IPD’s), but what if you take the capsule away? It turns out the immune system can ‘see’ the bacteria very easily without its capsule and so un-encapsulated bacteria can sit in the naso-pharynx but if they try to cause trouble the immune system can knock them out very easily.

This is where my work comes in.

Now it’s true that we can treat pneumo with antibiotics and we have two vaccines against pneumo but its still a massive problem. Something in the order of 60% of all clinical isolates show some level of antibiotic resistance with up to 10% showing resistance to 4 or more common antibiotics. The vaccines we have are also of limited use as one doesn’t work in children, where most of the disease occurs and the other doesn’t have enough ‘serotype coverage’ to be effective throughout the entire world.

To compensate for this my lab looks at alternative vaccines and that protective capsule layer. My work has really been to investigate how the biosynthesis of this layer is regulated and look for potential to break the regulation and in doing so prevent capsule formation and the invasive potential of the pneumococcus.

The regulation of capsule biosynthesis is achieved through a dynamic phosphorylation cycle that essentially acts like a switch.

This model was developed by my supervisor based on extensive mutagenesis work.

This is the current working model of the regulation. On the left we have the capsule being synthesised. The details are a little much for here but ‘C’ is a protein embedded in the membrane, it interacts with ‘D’, a tyrosine kinase. A tyrosine kinase is an enzyme that adds a chemical group called a phosphate to something else. In this system it actually adds that group to itself and when it does it forces itself to change shape. This altered shape in ‘D’ (represented on the right of the diagram) is thought to either change ‘C’s’ shape as well or the change is simply relayed through ‘C’ to the outside of the cell and production of capsule stops. Instead when ‘D’ is phosphorylated any complete capsule is stuck to the cell wall. As this process is not a one way switch we need to return to the left of the diagram and this is achieved due to the activity of ‘B’ which is able to remove phosphate groups from ‘D’.

For what was published in the paper we (or rather I) performed some mutagenesis on ‘C’ that resulted in it not being able to relay the change in shape of ‘D’. This resulted in switches jammed on to the left or the right but incapable of changing.

Importantly other mutants that have been constructed with an inability to switch capsule biosynthesis properly are unable to cause disease. Our hope however is to reach a point where we know enough about this system that instead of relying on a mutation in ‘C’ to give us a switching defect we might be able to design a drug or inhibitor that blocks ‘C’ activity in vivo. But that’s 5 – 10 years away.

I think I’ll just write this and my other experiments up into my thesis, then worry about the rest of the work that needs doing…

References

Byrne JP, Morona JK, Paton JC, & Morona R (2011). Identification of Streptococcus pneumoniae Cps2C Residues that Affect Capsular Polysaccharide Polymerisation, Cell Wall Ligation and Cps2D phosphorylation. Journal of bacteriology PMID: 21378192
Morona JK, Miller DC, Morona R, & Paton JC (2004). The effect that mutations in the conserved capsular polysaccharide biosynthesis genes cpsA, cpsB, and cpsD have on virulence of Streptococcus pneumoniae. The Journal of infectious diseases, 189 (10), 1905-13 PMID: 15122528

Welcome Canterbury Students!!!

2011-03-04T16:58:00.000-08:00

I put up a post a few weeks ago about the double disaster to hit Queensland. First a devastating flood and then a tropical cyclone of all things! Well things haven’t let up for the southern hemisphere. On the 22 of February a massive and devastating earthquake rocked Christchurch, New Zealand the largest city on the south island with a population of 376,000, breaking the city in half.

This disaster has left Australians and New Zealanders alike shocked at the enormity of the destruction. I include Australians generally because, for better or worse, Australians look at New Zealanders the same way Americans look at Canadians or the English look at the Scots and the Welsh I guess. Its not a paternalistic thing but it feels like a younger sibling perhaps.

Anyway, I’m not trying to sound patronising, I’m trying to explain a deeply felt connection.

The reason I bring this all up is because the University of Canterbury, located in Christchurch, was partially destroyed in the earthquake. This has all happened just outside the start of the new university year putting all of its students in disarray.

This week Professor James McWha, Vice-Chancellor at my university, the University of Adelaide extended an amazing offer to Canterbury. He has offered the uni to first and second year students looking at studying Arts, Science, Commerce and Marketing.

The offer was extended to take on “at least 500 students” and its expected a sizeable proportion will be science students.

With my new position as an Assistant Lecturer for first year biology courses and the associated teaching load there is a good chance I will see at least some of these students.

I would like to say here a big welcome to the exchange students from Canterbury and offer any assistance I can. If I can help out at all with your studies, please just let me know.

This is a great opportunity for Christchurch and Adelaide, University of Canterbury and University of Adelaide, to strengthen ties and develop a real community between the two institutions.

If you know an exchanging student or are one yourself and are studying first year biology please feel free to contact me at james dot byrne at adelaide dot edu dot au for any academic assistance you may require during this transitional period.

Money for Kittehs and Puppehs!

2011-03-01T02:37:00.000-08:00

I've never asked for money on the blog and I never will, for me anyway. I've always blogged for the fun of it and to improve my writing skills etc. etc.

But this post is a little different, because of this guy.

Micky

This is Micky. This September he will turn 2 years old but he is lucky to be with us. He was born at the pound and had been there a little while when we got him. He is the nicest and most polite little dog I have ever owned. A perfect complement to his older sister Frankie (named after Rosalind Franklin no less).

Frankie

Whilst my wife and I consider ourselves very lucky to have both of our dogs many dogs sit in shelters and pounds all around Australia, and of course all around the world.

As a big supporter of the Royal Society for the Prevention of Cruelty to Animals (RSPCA) I will be taking part in their major fund-raising drive 'The Million Paws Walk'. It's a great event where everyone can bring their dogs along and go for one big walk together to raise awareness, and a little cash, for a cause that's very important to me.

I realise that you cant all make it to my home town to go on the walk yourselves given that most of you are actually in the States or the UK but, if you want to, you can be a virtual member of my team and sign up to donate using the widget on the right (you might have to scroll up a it too)*. A couple of bucks makes all the difference so if you have any to share please consider donating. If you can't donate then that's cool too, instead you could volunteer at your local shelter.

Well that's it, I'm not going to push it but if you can help I'd really appreciate it. Plus who could say no to these guys?

*If you do plan on joining my team you will need to fill out a short form and put in the team password which is "paws2011"

What a week!!!

2011-02-25T15:28:00.000-08:00

I have grown accustomed to the largely monotonous and repetitive life of a PhD student recently. Wake up, go to Uni, set up experiment, experiment fail, go home, sleep, rinse and repeat ad infinitum. But this week has been different.

There is significantly less Kung Fu in science than I was led to believe. Turns out its mostly repetitive bench work.

On Monday I woke up and checked my email and found that I had received notification that the Journal of Bacteriology had accepted my first (and probably last as I plan on leaving research after my PhD) scientific paper. Now I just have to find a way to keep it from the prying and critical eyes of the blogosphere. Jimmy don't like criticism, even of his very preliminary data :).

Later on Monday I was contacted by the Faculty of Science at my University (The University of Adelaide) because they wanted to offer me a job! My PhD scholarship was due to run out in June, I think, so I had been looking around for something else to earn money with and applied for an Assistant Lecturer position. I can now officially call myself an Assistant Lecturer and since the position is part time it should allow enough time for my thesis to keep ticking over.

Pretty good week so far and Tuesday and Wednesday were spent preparing and organising myself for my new position.

Then, on Thursday, COSMOS magazine ("Australia's #1 science media brand") posted online a feature I had put together about a month ago. You can find it here and please 'like' and 'share' it as much as possible. This is my first foray into adult, serious, science writing and is a little more formal compared to what makes the blog. My only problem is that is no ability to add references so if you want them just let me know.

Seriously everything. It's an awesome magazine and the online content is awesome.

Friday was my last day in the lab (kind of, I still have one itty bitty experiment to do and I will still have my 'office' in the lab) so we all went to the pub. Any day that includes a pub visit is a good day :)

Finally, this morning I awoke to an email from Chris at The Naked Scientists alerting me to the fact they had published online another of the features I have written. This one can be found here and, as above, all the 'likes' and 'shares' are much appreciated. I really enjoyed writing that piece so I'm glad it got used somewhere.

The Naked Scientists. Good logo or best logo?

If you don't know about The Naked Scientists you should. They produce a wildly popular podcast which is awesome and should be listened too. I've also met Chris (the founder and one of the presenters) twice now and he's a really nice guy.

As I said its been a good week and technically its not quite over so maybe I will win the lottery tomorrow, although I'm sure you have to buy a ticket to be in the draw. Fingers crossed anyway.

Third hand smoking - Can we ban this poison already?

2011-02-18T18:06:00.000-08:00

I’m not going to write a post on why smoking is bad, it’s too obvious and if you don’t understand why then your probably never going to find this post anyway. I’m not even going to talk about second hand smoking, ie. blowing your death cloud at me on the street. Again it’s obvious why it’s bad and may even be worse than smoking the cigarette itself as second hand smokers don’t get the benefit of a filter. No, this post is about third hand smoking, a fun new way smokers can harm those around them long after they have butted out.

Yeah. That looks healthy.

I want to say here I don’t hate smokers, just smoking. That position will change however if you smoke near my food or drink or blow smoke directly at me. If you do that I’m going to nerd rage and you will take both barrels from someone who has spent the last decade in biomedical science. Just a warning…

The terms first, second and third hand smoke describe where the smoke came from. First hand smoke goes directly from the cigarette into the smokers lungs, second hand smoke comes from the exhaled smoke or smouldering end of a lit cigarette into a non-smoking persons lungs and third hand smoke is the contamination and subsequent consumption of items in an environment after the cigarette has been extinguished.

As the smoke dissipates and becomes invisible we tend to forget about it but cigarette smoke is full of fine particulate matter that then settles on everything in the local environment. Subsequent cigarettes layer particulate on top of previous layers and so a build up occurs. The smaller the area you smoke in the quicker the build up, for example the worse place seems to be the car.

Sleiman et al. (2010) looked at the formation of carcinogens on surfaces by looking at the interaction of nicotine and nitrous acid (found in the air) and found that if they left a cellulose pad in a smokers car to absorb third hand smoke and react with the air they could collect known carcinogens. In total they found 11 different carcinogens including, wait for it, polonium-210!!!

Even the cigarettes are sad.

Of course smokers also carry around third hand smoke on their skin and clothes so they too are also a walking, talking source of contamination.

The harm in third hand smoke is exaggerated in children, which of course is excellent. Children have higher respiration rates and so take in second hand smoke faster but also crawl around on the ground and put things in their mouths which are covered in third hand smoke residues. That’s not anecdotal either, children consume up to 20 times the amount of dust that adults do and when third hand smoke residue is present children get the brunt of the exposure.

At this stage no specific diseases have been linked to third hand smoke exposure but it is only a matter of time. In 2006 the US Surgeon General stated that there is no-risk free level of tobacco exposure and with more than 250 identified dangerous chemicals in each cigarette that’s a bit of an understatement. Prolonged second hand smoking is now associated with all sorts of respiratory conditions and cancers. Given that third hand smoking was only first described in 2010 it wont be long till we identify associated problems with cigarette residue exposure. Given the exposure to children is exaggerated many are tipping currently unexplained developmental impairment as a serious consequence of third hand smoking.

So how do we deal with third hand smoke? Easy actually. Beg, plead, cajole and support everyone you know to quit. Clean all your surfaces regularly, particularly around children and quit! Seriously, please quit.

This blog is a no smoking area.

References

Avol EL, Gauderman WJ, Tan SM, London SJ, & Peters JM (2001). Respiratory effects of relocating to areas of differing air pollution levels. American journal of respiratory and critical care medicine, 164 (11), 2067-72 PMID: 11739136
Sleiman M, Gundel LA, Pankow JF, Jacob P 3rd, Singer BC, & Destaillats H (2010). Formation of carcinogens indoors by surface-mediated reactions of nicotine with nitrous acid, leading to potential thirdhand smoke hazards. Proceedings of the National Academy of Sciences of the United States of America, 107 (15), 6576-81 PMID: 20142504

Flooding and disease

2011-02-04T14:16:00.000-08:00

I’m not sure what the coverage has been like overseas but most of the east coast of Australia has been hit pretty hard. First there were biggest floods Australia has seen for a VERY long time that started in Queensland and continue to affect the east cost of Australia. Then, instead of letting Queensland off the hook for a few weeks nature hit the coast with a cyclone THE SIZE OF THE U.S.A. that might move so far inland that it could dump rain into my state, which is a desert, halfway across our island continent.

A map showing Tropical Cyclone Yasi superimposed over the USA / news.com.au

While all of this was occurring I was thinking about what kind of diseases we can expect in flood damaged towns. Luckily, nothing has surfaced and this has been attributed to the integrity of the water supply being maintained (against all odds it should be added) but it could have been so much worse.

Floods can potentially increase the transmission of water and vector transmissible diseases. A vector transmissible disease is the fancy way of saying an infection that spreads between humans but requires an intermediate host, a vector. Malaria is a vector transmissible disease due to the requirement of mosquitoes for example.

Rates of diarrhoea (including cholera and dysentery), respiratory infections, hepatitis A and E, typhoid fever, leptospirosis, and diseases borne by insects are often seen to increase in flood affected areas. However it has also been observed that the increased rates are often small unless water supplies are contaminated or significant portions of the population are displaced causing crowding in the remaining safe areas.

Of particular importance during floods is leptospirosis. This disease (known by lots of names with my personal fav being Rat Catcher’s Yellows) is caused by a spirochaete (kind of bacteria) called leptospira that is commonly found in rodent urine. In floods rodent populations explode and of course rodent urine gets mixed into the water. The leptospira can then catch a free ride to your insides though open wounds (plenty in a crisis) or directly onto your airways or gastrointestinal system. Once there the disease goes through two phases, the first of which is annoyingly general flu-like symptoms but the second phase, separated by a brief period without symptoms, sees the development of meningitis, jaundice and renal failure.

Vector transmissible diseases are generally only a problem if flood waters become still. The initial flow of water will generally wash away any established breeding sites for insects like mosquitoes but after the flow water tends to pool and with lots of water comes lots of mosquitoes. Malaria is always the concern with flooding but previous major floods have resulted in outbreaks of dengue and West Nile Fever so it very difficult to predict what will happen. Luckily, it seems that despite all the extra water its actually the change in human behaviour (sleeping outside, temporary break in disease control and overcrowding of disaster centres) that is the major issues. This is lucky because changes in human behaviour can always be modified with experience of disaster situations.

The final concern many have about disease spread during disasters and particularly flooding is the danger posed by corpses. The Queensland floods took many lives and there were concerns that these individual tragedies could result in the spread of disease. Corpses actually pose very little threat as most agents in a body will die very soon after the host itself with the notable exception of HIV which can persist for up to a week. The major problem is if death occurred due to cholera or haemorrhagic fever both of which were not reported in the Queensland floods.

Flood-waters even got into the CBD

The Queensland floods and the continued devastation of Australia’s east coast (there have been reports of a monsoon in Victoria now as well) have been traumatic but it could have been much worse. The water supply staying safe for the majority of the crisis has undoubtedly saved thousands of lives and so while our hearts must go out to all those effected our thanks should go to the volunteers who helped in any way they could, including those charged with protecting the precious water supply and the medical staff who protected a state during a phenomenal crisis.

References
WHO: Flooding and communicable diseases fact sheet
Ohl, C. (2000). Flooding and human health BMJ, 321 (7270), 1167-1168 DOI: 10.1136/bmj.321.7270.1167
Howard MJ, Brillman JC, & Burkle FM Jr (1996). Infectious disease emergencies in disasters. Emergency medicine clinics of North America, 14 (2), 413-28 PMID: 8635416

Shoutout

2011-02-01T15:45:00.000-08:00

I strongly suggest you go read two very good posts I came across today.

The first by my friend Thomas at Disease of the Week is about leprosy in all its glory and celebrating World Leprosy Day! He's a funny guy and leprosy is always fun to read about.

The second is by FoS blogger Emily Willingham. A great piece on woo and oversimplification of science in the media specifically referring to the 'link' between having your children's tonsils out and your children becoming overweight. Apparently this common surgery is extending the childhood obesity epidemic. Well not really.

I have nothing more today, just liked these posts and thought I would share them :).

The Australia Antigen

2011-01-25T14:21:00.000-08:00

I feel a little left out some times on the internet as many (but certainly not all) of my bloggy friends are English or American. So, just to fill you in, the 26^th of January is Australia Day and it commemorates the landing of our first fleet in 1788 and the planting of the British flag in what was then known as New Holland and is now known as Sydney Cove, New South Wales, Australia. Most people celebrate the day with a public holiday, a beer or two, a barbi and the TripleJ Hottest 100.

We will get back to the Australiana theme in a moment but I want to take it down a notch first by talking about Hepatitis B virus.

Hepatitis diseases are not limited to those induce by viruses. In fact hepatitis just means inflammation of the liver from hepat(o)- for liver and –it is meaning inflammation of. This has led to the common misconception that the Hepatitis viruses (A, B, C, D, E) are related to each other, they’re not, but they do all cause liver inflammation. In fact according to the Balitmore Classification of viruses they fall in completely different families. Furthermore the run of letters, which also suggest relatedness, simply describe the order in which the viruses were identified.

The Baltimore Classification describes the lifecycle of all viruses based on their genome structure. Protein is produced based on the mRNA sequence so that’s why all lines flow back to mRNA.

While all are problematic in their own way for this post we are interested only in Hepatitis B virus (HBV), arguably the biggest problem in the (not) family of hepatitis inducing viruses.

How big a problem is HBV? Well, approximately 2 billion people worldwide are infected, greater than 350 million people are in the chronic phase of infection and its estimated that a quarter of these people will die of liver cancer or other complications directly caused by HBV.

Like many viruses encased in a membrane (a so called enveloped virus), HBV requires body liquid exchanges to transmit from person to person but is not necessarily picky as to which liquid and transmission has been observed by blood exchange, sexual contact and even maternal-foetal exchange across the placenta.

HBV disease is very well characterised and follows a fairly generalised route. Following transmission the viruses work their way into the blood stream and eventually find their way into the liver where they can attach and enter liver cells. Once inside the cells the virus and its components are very stable and viral replication kicks in resulting in huge numbers of virus being produced and seeking out new liver cells. This infection stage can last up to 6 months with almost no symptoms beyond generalised flu-like symptoms or a touch of jaundice.

Following initial viral replication there are three outcomes are possible. Best case scenario, you mount an early, strong and effective immune response that removes all the virus from your system. Worst case scenario #1 (short term), you develop a form of acute hepatitis called fulminant hepatitis which is caused by your immune system reacting too strongly and liquifiying your liver in an attempt to remove the virus resulting in a quick death. Worst case scenario #2 (long term), your immune response is slow or weak and the virus persists resulting in a chronic infection. An interesting little side note here is that if you are a child your chances of developing chronic hepatitis B skyrocket to 95% compared to the 5% chance to adults and at this stage we really don’t understand why.

So your either fine, dead or a time bomb and chronic sufferers can look forward to a life of medications attempting to prevent death. Having said that some chronic HBV patients go on and live lives free of complication or further symptoms but most end up with either a passive or active form of liver destruction depending on whether you show any symptoms or not respectively.

The destruction of the liver is immune mediated which mean the virus doesn’t actually kill liver cells but its presence activates the immune system inducing it to kill any cell with virus. As the liver can regrow your left with constant cell death and constant cell renewal but it all comes at a cost, scars. Scars in tissues are called scar tissue (duh) or more accurately fibroma. Fibromas are a problem as they impair organ function and when you develop too many the organ starts to die as blood cannot flow to all parts of the liver or promotes the liver to overcompensate and regenerate faster leading to cancer – hepatocellular carcinoma.

Pic courtesy of my good friend Thomas Tu from the wonderful blog Disease of the Week. In unvaccinated hosts this is the pathway through HBV infection.

So what can we do about HBV? Currently your best option is vaccination. Its pretty cheap (for me it was any way), very safe and really effective. As well as being the best option, its kind of the only option as all the anti-viral drugs currently available do not ‘cure’ the virus, they can only act to freeze or pause it. When you stop the drugs the virus un-pauses. As I will most definitely talk about at a later date vaccines are awesome, but at least for HBV they might not be the golden bullet they can be for other disease. Vertical transmission, mother to child, in the womb is impossible at this stage to prevent as you just cant vaccinate an embryo but effective vaccination of everyone else will prevent horizontal transmission between all other people.

So I started this with an Australian flavour and that is because I came across some terminology I have never heard before. It turns out the antigen that I've always called HBsAg (Hepatitis B surface antigen) was originally isolated from an Australian aborigine and so was commonly referred to as the Australia antigen. Whilst we do not call it that anymore this antigen is very important as it is used in current vaccines designed to prevent virus entry into cells.

So after a very long and round-about trip from Australia Day to HBV and (kind of back again) I wish you a very happy Aussie Day and encourage you to fulfil all the best Aussie stereotypes. Wear a cork hat (only found in souvenir shops), a blue singlet and very short shorts (only seen on 'Australian in movies'), drink a big Fosters (nobody drinks that rubbish here) and ride around on a kangaroo (one of natures truly most terrifying animals if you ask me). G’Day mates!

See those muscles, remember, he hops on his back legs…

EDIT - 27/1/11 - The very clever Thomas Tu who gave me on of the pics in this article, writes at the stupendous Disease of the Week! and is a HepB researcher has informed me that he thought my wording was a little sloppy. HepB doesn't really get transmitted vertically from mother to child as it is not passed across the placenta. Technically its still horizontal as the virus is passed in the fluids during birth. My point about vaccination in utero still stands but Thomas is right. Lets call is diagonal transmission and be done with it :)

References

Blumberg, B. (1984). Landmark article Feb 15, 1965: A "new" antigen in leukemia sera. By Baruch S. Blumberg, Harvey J. Alter, and Sam Visnich JAMA: The Journal of the American Medical Association, 252 (2), 252-257 DOI: 10.1001/jama.252.2.252
Lee WM (1997). Hepatitis B virus infection. The New England journal of medicine, 337 (24), 1733-45 PMID: 9392700

Halitosis - Your mouth smells like arse

2011-01-21T14:26:00.000-08:00

Sometimes I'm going to write about rare cancers or blood diseases and sometimes I’m going to write about bad breath. That’s just the way I roll.

Halitosis literally means “condition of the breath” and has many causes and just as many home remedies. Original therapies (and by original I mean 1550 BC) like heavily herb infused wines didn’t remove the bad breath but like mints and other modern treatments they just attempted to cover the bad smell with something more pleasant.

Halitosis isn't limited to humans. Ever smelt a dogs mouth?

Halitosis can be divided into two distinct problems, transient halitosis (morning breath) and chronic halitosis. While the difference between these conditions is the time frame of affliction both have the same root cause. Sulphur.

A study by Suarez et al. looked at what caused the odour in people with morning breath and found that the unique smells produced by people were due to three sulphurous gases combining into a malodourous mixture. The gases, hydrogen sulphide (smell of rotting eggs), methanethiol (smell of rotting cabbage) and dimethylsulphide (which has a slight sweet smell), were present in varying quantities between participants giving them all bad morning breath.

The sulphurous gases are produced by bacterial build up in the mouth and in particular on the tongue. During the night your production of saliva drops significantly and with less saliva bacterial numbers increase dramatically. Saliva has a number of jobs in the mouth related to bacterial load but its three main roles are to acts as a tidal wave to wash bacteria out of the mouth, to inhibit bacterial growth using various chemical components and participate in the killing of bacteria by carrying parts of the immune system into the mouth. But less saliva equals more bacteria and consequently, bad breath.

Given this it wasn’t surprising that the treatments that Suarez et al. found good immediate treatments of halitosis (I say immediate because as saliva production increased the bad breath went away naturally) where mechanical scraping of the tongue. Specifically brushing of the teeth with toothpaste did nothing but brushing of the tongue with water was much more effective. Eating a dry bread roll was also very effective as it scraped across the tongue, removing bacteria.

The best treatment was a mouthwash of 5mL of 3% hydrogen peroxide – guess why. This treatment killed huge umbers of bacteria and immediately dropped the concentration of the sulphurous gases, which stayed low for hours afterwards.

While rare there are a few conditions that produce halitosis that has a non–oral origin but they are extraordinarily rare and halitosis is but one of a bevy of symptoms that the patient would possess.

Foetor hepaticus, or the ‘breath of the dead’, is seen in people with late stage liver failure. It is caused by the passage of thiols from the blood into the lung. These compounds are normally removed in the liver but as the liver shuts down thiols remain in the blood and can escape into the lungs. Apparently distinct from typical halitosis foetor hepaticus smells of sweet faeces.

Another condition, known as trimethylaminuria is also known as fish odour syndrome. People suffering from trimethylaminuria lack the metabolic enzyme Flavin containing monooxygenase 3 which breaks down trimethylamine to trimethylamine oxide. The result is that trimethylamine builds up in the blood and is removed in the urine, sweat and breath. Despite its name an odour of fish is rare and most sufferers just have an unusually strong and sometimes unpleasant odour.

So if you have halitosis, but don’t have late stage liver failure or metabolic disease, you can treat your bum breath with breakfast and mouthwash if you pedantic. So no excuse for blowing it in my face on the train from now on!

Reference

Suarez FL, Furne JK, Springfield J, & Levitt MD (2000). Morning breath odor: influence of treatments on sulfur gases. Journal of dental research, 79 (10), 1773-7 PMID: 11077993

Jumping Frenchmen of Maine Syndrome

2011-01-07T14:30:00.000-08:00

Well I’m back! I’m not going to pretend like you missed me but I hope your glad to see another post out of me. I did a bit of writing during my time off to build up a bit of a backlog so hopefully I can keep posting regularly for a while. Anyway, without any further ado…

Jumping Frenchmen of Maine Syndrome

Best. Disease. Name. Ever.

This disease was first observed in 1878 by the neurologist Dr. George Miller Beard, a guy I will definitely talk about again, in French-Canadians, lumberjacks and presumably some French-Canadian lumberjacks living in northern Maine. So that explains the “Frenchman” and “Maine” parts but lets look at what makes this a “Jumping Syndrome”.

This is the famous jumping Frenchman Patrick de Gayardon. He has nothing to do with this story. Left Right.

This syndrome is due to an exaggerated startle reflex resulting in uncontrolled jumps commonly but can also manifest as spasms throughout the body. The startle reflex is very important and forms part of the ‘fight or flight response’ normally.

Essentially a startle (which by definition has an auditory component) has three major neurological routes in the brain that have a number of effects. First, the auditory nerve fibres stimulate the cochlear root neurons (CRN) that form the first part of the central nervous systems auditory processing. Following this stimulation the CRN’s stimulate the nucleus reticularis pontis caudalis cells (PnC) located in the Pons (part of the brainstem). Finally the input into the Pons results in stimulation of motor neurons, particularly to the head and neck and the spinal cord. This results in the jerking response aimed at orientating you to the source of the startle while also priming your body for a response.

Left shows brain side on with exposed brain stem and pons are highlighted while right shows the dorsal view of the brain stem (dorsal means back, think about the location of the dorsal fin on a dolphin) with the CRN highlighted.

One thing that I think is important to point out is how fast this all is. The time taken from the detection of the stimulus to the first muscles to react (in your jaw) is roughly 14 milliseconds! The last muscles to react (unsurprisingly in your feet and legs) receive stimulation after only 400 milliseconds!

Jumping seemed to not be the only unusual response in the Jumping Frenchman. Some exhibited echolalia (one of my favourite words and albums) or echopraxia. Others yelled, spasmed or hit out and another observation was made that confused matters further. Some jumpers would inexplicably follow commands given alongside their stimulus including one man who was startled whilst being given an order to throw causing him to launch the knife in his hand across the room. This was observed to be repeatable and the sufferer was ordered to throw a bunch of objects including a pipe he had just finished packing.

Researchers have looked for something in this community to explain this unusual stimulus response. This isolated community exhibits all the hallmarks of a population that might result in mutations that could develop and persist. Lending credence to this possibility were Beard’s original observations that the jumpers were confined to family groups but so far no genetic analysis has show a causal link to the condition.

These studies have suggested a different cause. In particular the work of the Saint-Hilaire’s which involved videotape evidence of a number of sufferers seems to suggest the response is psychological, not neurological, and may have been brought on by positive re-enforcement of this unusual behaviour in the small community.

Whatever the cause the disease still has a funny name. Almost feels like it should have been a Monty Python sketch if you ask me.

References
Saint-Hilaire MH, Saint-Hilaire JM, & Granger L (1986). Jumping Frenchmen of Maine. Neurology, 36 (9), 1269-71 PMID: 3528919
Saint-Hilaire, M., & Saint-Hilaire, J. (2001). Jumping Frenchmen of Maine Movement Disorders, 16 (3), 530-530 DOI: 10.1002/mds.1080
Howard R, & Ford R (1992). From the jumping Frenchmen of Maine to post-traumatic stress disorder: the startle response in neuropsychiatry. Psychological medicine, 22 (3), 695-707 PMID: 1410093