Magical Sunburn Medicines courtesy of TRPV4

28th August 2013

There was a lot of recent coverage of a paper claiming that a particular protein called "TRPV4" causes the pain of sunburn. It has been floated that this could allow us to magic up some really great sunburn relief creams and hugely increasing Q.O.L ... Quality Of Life!!

What I was hoping to do in the blog is discuss (1) why this is not such a good thing! .... (2) why I say they "claim" rather than "show", (3) what the TRPV4 protein is, and finally da da da da daaaaaaa (4) Exerimental treatments.

Why is this new discovery a bad thing?

OK chronic pain... I.e., pain which goes on for weeks, months and years is a terrible thing, and we think of this as a disease in itself. Acute pain is rather different; in some cases it is awful, but frequently it is a really effective warning that something is awry and needs to be sorted. People who lack pain sensing ability have a dreadful time, they injure themselves left right and centre and just don't know until serious harm has been done. There are animals which lack pain sensing for particular types of pain when it suits their lifestyles, but for the rest of us it's a protective mechanism to stop us injuring ourselves. So in this case, not only does the sun age your skin, but it really does, unambiguously give you cancer. The more you can tolerate being burnt, presumably the more you will allow yourself to be burnt and the more likely you are to get cancer.

DOCTOR DOCTOR, I KEEP TRYING TO GIVE MYSELF SKIN CANCER, BUT SUNBURN KEEPS DRIVING ME IN DOORS... WHAT CAN I DO ABOUT IT?

As for pain relief; in theory morphine like drugs and local anaesthetics would already stop the pain if that was all you wished to do. Morphine is considered too dangerous, and local anaesthetics, basically inappropriate. Obviously you should speak to your pharmacist of GP about treatment, but generally they'll say moisturising creams will feel nice and some ibuprofen-like drugs or paracetamol (acetaminophen) may help... a bit.

Why did I say "claim", rather than "show"?

I really hate "scientists have shown" on the news. What they should say is Dr Fred blogs and colleagues have shown... Or possibly "a new research a paper shows". Frequently, these days the truth would be "a University Public Relations press release says"..... Anyway in this case it was a research paper that the information was published. The Journal is called the Proceedings if the National Academy of Sciences (PNAS).

Well it is no suprise that TRPV4 would be involved, it is found all over the body and important for all sorts of things, but there is always scope for skepticism with this type of report. It was published in the journal PNAS, which has an excellent reputation although it has an unusual procedure for selection and review of scientific papers. Some people have raised objections to this. Secondly, there is a tendency for people to always find the particular protein they work on to be the lynchpin of whatever system they happen to work on ;-)

In fact my own colleagues and I were looking at a different protein that seemed important. They don't have to be mutually exlusive though. There are probably many proteins which are involved in sunburn pain.

TRPV4 is likely to be involved however, because it is a protein which is important to sensing much of the normal mechanical (touch) stimulation of the skin. In sunburn we have an oversensitivity to touch, therefore, it stands to reason that if you loose the ability to sense touch, you will also loose the sunburn induced oversensitivity!

What is the TRPV4 protein?

This is top dead centre my area of research. I'd like to step back and remind people that we are, as animals, mostly chemicals and electricity. Now I am sure many people know this, but if you don't its going to sound like sci-fi, but it really is known quite well. All nerves that either transmit senses like touch, pain or pleasure are effectively electric wires. Electric current flows through them like wires running between a switch and a light. The voltage is about a thousandth that of a domestic light, or a hundredth of a modern torch. TRPV4 is a type of protein called an "ion channel" which acts to generate this voltage... An ion channel has two parts conceptually, a battery and a switch. In th case of TRPV4, the sunburn throws the switch thus stimulating the nerve cells which conduct the pain to the brain. In fact this "ion channel" can be activated by all sorts of other things too... Including pressure and some drugs/chemicals. The problem with it, a drug target though, is it really is found so widely throughout the body... Side effects could be a real problem.

Some experimente to see if its true?

I think not! There are a number of chemicals known which inhibit the action of TPRV4 already. Therefore they should prevent the pain of sunburn. It would be irresponsible of me to list them here, but they are no doubt, findable with some Googling. Presumably they would reduce the pain of sunburn. Most of these compounds are expensive and pretty deadly. TRPV4 is found all over the body, so you'd not just loose the sunburn, your kidney would not work properly, your joints would be affected, you'd feel numbness and loose control of your blood pressure. So direct application to the skin? Unfortunately, they tend either to not penetrate the skin, or they do absorb nicely, but they give you cancer :-(

Personally, waiting it out or using paracetamol seems a better idea to me.

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Blame your mum!

There are a lot of things we know you can do in an attempt to fight off the ravages of time:

Don't smoke

Keep fit

Don't be obese

Eat healthily

Don't fight alligators

Don't let yourself get sunburned

...but that said, a new paper published this week in Nature shows that at least some of your ageing is not your fault, but your mum's! Feel better?

Now the science bit... Everyone knows that we inherit loads of features about ourselves from our DNA. This is of course kept safely inside our cells' control centres (nucleus).... However, each of the cells in our body also contains mitochondria. These are the tiny structures which produce the energy necessary to keep cells working. However, it's increasingly become known that they also have their own supply of DNA. It was quite surprising when that was discovered, but we are now quite certain this is the case. Amazingly, you don't inherit your mitochondria from both parents.... you inherit them only from your mum.

It turns out that this mitochondrial DNA confers some of the differences between ageing rate in people.

Ergo.... Some of your propensity to ageing is inherited directly from your mum!

 

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Is Running Good For Your Health?

Here is the update on this blog:  
For a proper academic review of this subject see  Hunter and Eckstein 2009.

Exercise and osteoarthritis, two recent reports have been published with apparently conflicting conclusions:The medically orientated Nature Reviews in Rheumatology suggests there is (as I suggested in the previous blog optimal joint usage for healthy cartilage), and a sports medicine journal article from Dr Williams suggests that long distance running decreases risk of osteoarthritis.  

Naturally, from the Twittersphere, those people who love running feel their pursuit has been justified.  those people who commercial promote exercise will use it as propaganda.  I find it sad that on this issue, just like so many, people pick the evidence that suits their believes rather than balancing evidence.

Now lets start with a reminder.  Osteoarthritis is a condition of painful joints, which involves the whole joint, but one of its hall marks is the loss of cartilage.  Cartilage lines the hip and knee joints.  The cells that make it (chondrocytes) actually sit within the the cartilage of the joint.  They respond to the loads placed upon the joint by producing cartilage... within reason.  If you don't use a knee and hip joint at all, you would expect the muscles to waste away, the bones to become thin and brittle, and the cartilage become thin also.  I think we can probably all agree on this.  However, cartilage is a living tissue.  It is not shoe leather.  Part of the confusion is caused because cartilage has no blood vessels so it does not bleed, and it has no nerve fibers running out of it so you don't feel pain from the cartilage itself.  But it still needs to be loved!  We know for absolute certainty that excessive weight (high BMI) promotes you getting osteoarthritis, even the Dr William's paper shows this.

There is clearly debate as to how much usage is ideal.  The sporty paper could be used to support the argument that "it's the more the merrier", but there are huge confounding variables.  The author did what he could, but it is difficult!!! The analysis was not able to exclude two possibilities (1) That slimmer people (with lower BMI) may run more and (2) That people could start to run less when they get painful joints. If you believe that either (1) or (2) could be true they presumably you will come to the conclusion that this new paper does not really answer the key question of how much usage is ideal.

So the other paper, the Nature review?  Well it is just a few line summary of a very thorough paper in the "Osteoarthritis and Cartilage" journal.  But This is what is reported.  The LEAST active elderly people loose cartilage, but so do the MOST active!!!  Activity is assessed with a PASE survey, and yes age and BMI is taken into account.  Also, the study tracks people and so ceasing activity due to joint pain is less of a factor.  Now bare in mind this is activity assessed by PASE not running marathons!  PASE asks a number of activity questions, see Table 1. They then considered the top 15% and bottom 15% activity rates and compared against the middling people.
...BUT and here is the elephant in the room.  The health crises we have at the moment is due to obesity and lack of exercise of people, not over exercise, so whilst I would suggest that the jury is out on how much exercise is good for your joints.... for the rest of you LOTS of exercise is clearly a great thing.  ...and for me too, but I am lazy :-/

 So the conclusion:  Everything in moderation? 

Table 1: PASE Activities, Performances and Weight Scores
PASE stands for: Physical Activity Scale for the Elderly

Activity	Answer	points
Walking and bicycling	Hour/day	20
Light SRA	Hour/day	21
Moderate SRA	Hour/day	23
Heavy SRA	Hour/day	23
Muscle strength/endurance	Hour/day	30
Paid/unpaid work	Yes/no	21
Light housework	Yes/no	25
Heavy housework	Yes/no	25
Home repairs	Yes/no	30
Lawn work	Yes/no	36
Gardening	Yes/no	20
Caring for others	Yes/no	35

 

Dangerous Dogs

Photo from Flickr under Creative Commons License.

Hover over the image for details.

Here's a little blog about the dangerous dog.

Actually it's going to be quite a big blog...

(a) Are dogs dangerous?

(b) The legislation

(c) Breed not Deed! ..oops other way around!! Deed not Breed.

 

I am an absolutely massive dog lover, always have been and I daresay always will be. I like all breeds, big ones small ones.... Silly ones, sensible ones. However, they can be dangerous. Personally I have been bitten loads of times (no, not by my own!!). I don't know why I get bitten so often? May be I just smell good (...to a dog). May be its because i am irritating? Fortunately for me, I mostly get bitten by little dogs, so I have yet to be maimed, but be in no doubt that any dog has the capacity to do a human major harm if it chose to.

Most characteristics of dogs are mirrored in people though. People can be deadly too of course (Dale Cregan)? But we have a value system that says humans are worth much more than people... and that is the essential difference. To me though, a dog is not just an object. So I don't think they should be punished for things they haven't done.

The 1991 breed legislation was, in my opinion abject. To me, the idea that you could take a nice, friendly dog that has never put a paw out of line and kill it because it was of an illegal breed was barbaric. It is the kind of attitude that moves us further away from the kind of beautiful utopia I picture for the distant future. However, the law was introduced in the imitate aftermath of a couple of horrifying killings of children by dogs. ...and they were absolutely horrifying. But when the legislation came out in the 90s I was horrified by that too. I couldn't find another soul, at the time, that agreed with me :-(

"Yes but what's the life of a dog compared with a child?"

It's sort of impossible to argue with that isn't it. And it could be extended by some many things you could also ban. For example, 3000 people are killed on the roads (mostly children) every year and you could stop that at a swoop if you banned cars. ..but people like cars, and they are considerd more valuable to society.

..but by some miracle, the UK population swung away from the idea that all dogs of a particular breed should be killed and started to modify with control orders etc.

Now the idea is that we should second guess which dogs are dangerous and which are not by their behaviour prior to an attack. To me this is better... But not enough. I don't believe your really can tell which dogs are dangerous from their behaviour. The law will criminalise badly behaved dogs in their own homes? Well I have seen so many houses and yards, where dogs are going berserk the other side of a gate or fence... Or behind their own front door.... And most of these dogs are absolutely fine!!

Ultimately, the only way you can tell a dog is a biter for sure is once it has bitten someone. ....but then it's too late? ...but that is life isn't it?

I suspect not. Before a human kills another human I think there are nearly always violent incidences. Mostly when you hear about a murder, after the trial there will be catalog of tails of how they beat up their girlfriend or beat someone up on the street. This is never taken seriously though! How many times does someone have to beat up their girlfriend before it is blatantly obvious they are unfit for society?!! Once I'd of said. So I am saying, I bet if you look into the past of those dogs which killed children, most cases will follow attacks on people which did not result in death or serious injury. So these are the crimes which should lead to the prosecution of dogs/owner, not barking behind their own front door.

Microchipping? People are saying... How does a microchip stop a brutal attack?

Well it will. So there. It will because many thugs with their dog-weapons deny that the dog is their's when caught. Also, if a dog bites someone, there is no way to register that on a national system, so the dog could bite all sorts of people and never be clocked as a serial offender. But the main thing is that if you take your dog around as a weapon... That weapon will always be traceable with microchips and it sort of limits the value if the weapon as a result. Hopefully less people will use dogs as weapons as a result. Yes, you could probably incinerate the dog and chip.. But that is too much effort for most thugs.

Licenses? I am neutral on licenses. I think they are a good idea, but clumsy use of licensing legislation could result in dogs being thrown out upon renewal. I would suggest a license to breed, sell or buy one. Not an annual renewal license.

So all breeds are the same when it comes to danger? I suspect not. This view is extremely controversial in doggy circles, but you can breed traits into dogs (and any animal) in theory. It has been shown by experiment you can selectively breed dogs to be nervous, passive etc. Why not aggressive?

Well there is a general reasons why selective breeding of aggression doesn't really happen in dogs. The argument starts with the fact that most dogs are bred for family homes. These dogs are bred to NOT be aggressive. If they are aggressive, they tend not to be bred from. Some dogs are bred for the police or army, but they don't want wild dangerous dogs. They are experts and there is no problem there.

So this leaves thugs. OK so you want a dangerous dog: You need (a) to cross your rotten dog with another rotten dog (genes) and (b) you need to keep it from the normal socialization which defuses most potentially dangerous dogs (environment).

(a) These are not easy to find, really... Dogs are so nice and bad dogs are difficult to come by. To find a genuinely rotten dog to breed with is nearly impossible. Not only that, but you have no way of knowing outside of a laboratory type breeding experiment whether the dog is genetically bad or bad due to its environment. So this is all a bit of a non-starter!

(b) To adapt a dog to bring out its dangerous side, you basically have to deprive it of a normal environment. Don't allow it to meet people, don't allow it to meet other dogs. ...but the sort of moron who would attempt this will mostly likely bring his friends around to see. They will be active chaotic homes where people come and go all the time. People will bring their own dogs around... The whole-plan backfires and you are likely to end up with a beautiful friendly dog. I know this happens a lot. I have seen many staffy like dogs abandoned... Not, we think, because they are bad... But because they were to soft or in most peoples eyes... Lovely. They were bought as weapons, but they were no good as weapons so these horrid horrid people throw them out :-(((

That said... I set about calculating the rate of fatal dog attacks between breeds. It is not easy and requires a lot of assumptions. Also, I had to use figures from the USA since I couldn't get them all for the UK. I actually did this as part of a lecture on the brain pathways underlying stress and aggression, but ...well that's another story!

Anyway, the data is there to see (table I). Some breeds are far more commonly involved with attacks than others. I think a huge factor is.... The purpose for which people buy their dog. If you want a weapon you don't buy a Westie (that tip comes free).

I am pretty uncomfortable about this data, as I feel that people will mis-interpret it: but I feel that to not upload it would be. Sort of censorship! An interesting fact... I think (can't remember the figure) about 70% of the owners of the dogs that had killed, had themselves been previously convicted of a violent offence.

Table I Here it is below, please note the caveats, it is just a crude estimate. Also note that in the USA, from where I collected these stats, Staffordshire Bull Terriers, English Bull Terriers and Pit Bulls were all lumped together in a way you would probably never see in the UK.

Further notes on this table (I compiled it in 2006): Dog Attack statistics….Best Figures were from the USA.Of people attacked and killed (238) 76 people killed by “pit-bull types”: of these, 66 of the dogs were registered. I have therefore estimated that 20% of dogs are unregistered in the USA. In the USA at the time registration numbers of Bull Terriers were about 5k (i.e., AST 1.5k, SBT 1K, BT 1.8k). Therefore, Those three pit bulls constitute about 5,000+20% (add the 20% to account for the unreg’d): = 6,000/900,000 dogs in USA (registered in 2006).=about 1% of dogs, but accounted for 76/238 attacks.=32% of attacks.Assuming registered and non-registered equally dangerous:5x worse than next worse… Rotweillers.A word in favour of Pit Bulls…Additional notes: Criminal Records (discussed in Houpt) 90% male and 70% of owners criminal record for violence!

 

 

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Exercise and Obesity

Now I have to say I think the BBC "People men made us thin" series has been great, and in many ways music to my ears.  

The dogma are:

(1) Eating too much makes you fat.

(2) Exercise makes you thin.

(3) Genes

Do diets make you thin?

(1) They have gone some way to debunk this in the program.  Of course they have taken an extreme attitude.  If you don't eat, you will loose weight, but the psychology of dieting is more complex.  The study designs are difficult too.  So they studies showing diets don't work will usually say "here's a dieter 2 years later and they have put on 10lbs/5Kg, but here is a non-dieter and this person put on zero weight: ergo, dieting doesn't work".

There is a fundamental flaw in this argument though.  The people who diet typically have weight control issues and were always going to put on more weight than people who have never had a problem and never diet!!

So my bottom line would be that dieting is in no way all that it is cracked up to be, but if you are over-weight it is better to try and reduce your calorie intake than to just give up!!

(2) Does exercise make you thin

Again the program takes an extremist view of this issue.  I it is true that exercise is a really slow and relatively ineffective way of loosing weight  ...but it depends on the exercise, and whether it was the only lifestyle change you made.  Really this is a life-style thing.  To simply drive to the gym 3 times a week and burn off a few hundred calories is not going to make a significant contribution to a serious weight problem.  Those few hundred calories could easily be swallowed up just by one post exercise trip to Starbucks.  If you control calories and do more exercise, the exercise will prolong your life and keep you healthier, but really its the calorie-control bit that will knock off the pounds. Turn down that free chocolate bar at the checkout and you have just saved the equivalent of about a two mile run!  

(3) Genes

Your genes profoundly affect your weight.  This is mostly by changing the appetite control systems in your body.  Potentially there are many drugs which could change this, but it's not a great idea just yet, because these drugs tend to do too much other stuff.  ..i.e., "side effects".

All this lot is just the same for your pets too.  It's really important to give a dog a great walk or two every day... but weighing their dinners are the secret of weight control!!