World First In Organ Transplantation

Recently in September, it has been revealed that a woman in Sweden gave birth to a baby boy, only possible with a womb transplantation. This pivotal event in medical science has given hope to thousands of women around the globe who are unable to conceive. Some cancer treatments and birth defects are a couple pf the reasons why women have this problem. The donor of the uterus was a friend of the 36-year old, who was in her 60's at the time of transplantation. The birth was successful, however premature at 36 weeks, the baby weighing in at 1.8kg (3.9lb). Prior to the birth, the unidentified couple underwent IVF treatment in order to produce 11 embryos. These were frozen until the point of transplantation at the University of Gothenburg. As with the vast majority of organ transplants of today, the woman was given immunosuppressant drugs before the transplant, in order to reduce the risk of rejection by her own immune system.

After the transplant, doctors were then able to select an embryo from the ones frozen to implant into the new uterus. However this was only after a period of a year. In the short period before the birth, the baby was said to have developed an abnormal heart beat, hence the premature birth, however now the baby's condition is said to be 'normal'. However complications with this sort of transplant don't just stop there. If the couple were to have a second child, they would need to consider the fact that the immunosuppressant drugs can be 'damaging in the long term'. It would be considered that if they decide not to have a second child, then removing the transplanted womb would be a necessary precaution.

There have been several fails attempts at womb transplants, whether it be due to the organ becoming diseased, or birth resulting in miscarriages. Now, Professor Mats Brannstrom, who led the surgical team expressed relief and happiness in response to the success. In fact it has emerged that two more women will be receiving womb tranplants by the end of this year; suregons in the UK will be choosing 5 patients out of 60 who will undergo this potenially life changing opeation, according to the Sunday Times.

"Our success is based on more than 10 years of intensive animal research and surgical training". Despite the success however there are still concerns about the 'safety and effectiveness of the invasive procure', according to the BBC. This breakthrough is somewhat comparable to the leap in medical science that IVF allowed over 30 years ago. The Chairman of the British Fertility Society, Dr Allan Pacey said the operation "feels like a step change", however he is aware that it will need to be proved repeatable, reliable, and safe in the future for many more patients.


Credit to Oliver Moody, for his article 'More womb transplant babies on the way' which can be found here.
Additional credit to James Gallagher, Health Correspondent for the BBC, for his article 'First womb transplant baby born', which can be accessed here

Obesity And Its Expensive Relationship WIth The NHS...

Recently, the NHS chief executive Simon Stevens issued a statement to the public at the Public Health England conference in Coventry, which is held each year. In the light of an on-going obesity epidemic, he believes that "Obesity is the new smoking". Describing the disease as a "slow-motion car crash", he, along with thousands across the country, recognise that the costs involved in treating obesity has risen year on year to a point where it'll become unsustainable without raises taxes.

Basic statistics reveal how vast the problem is: 25% of adults and over 20% of children are considered obese. I encourage you to see my other article, 'Fat!', for more interesting statistics.

By many, obesity is considered a disease of all age groups, which makes the numbers affected much larger. Tackling the issue therefore proves an expensive task, as currently the government spends around £9bn every year on treatments.

Stevens added that Britain would be 'piling on the pounds in terms of future taxes'.

Percentage of men and women obese from 1993 - 2009 (BBC article)

However its important to appreciate that obesity isn't just an isolated disease. In the majority of cases, obesity will inevitably lead onto other complications including cancer, diabetes and heart disease. Treating people for these additional problems will only increase the overall cost of treatment. At present, the most common direct treatment for obesity (especially those morbidly or severely obese) is bariatric surgery. There are two main types - gastric band and gastric bypass. A gastric band uses a restriction of stomach size, so than when food is ingested, less is required to make you feel 'full'. The alternative method is a gastric bypass, 'where your digestive system is re-routed past most of your stomach'. This gives the effect of digesting less food, having a similar psychological effect to a gastric band. Despite the obvious benefits, patients are always made aware of the potential complications to their health post-surgery. Internal bleeding or deep vein thrombosis (DVT) are just a named couple. Generally however, patients are enrolled onto a 'rigourous and lifelong plan', including regular exercise and a monitored diet, according to NHS Choices.

However this measure may only be considered suitable for those whose life is at risk and require emergency intervention. Those who register as 'overweight' on the BMI scale, are currently not legible for bariatric surgery.

But how can the nationwide problem be tackled? According to the BBC, one of the future proposals would be to increase spending on 'lifestyle intervention programmes' rather than bariatric and similar surgery. This will be a step forward in combating obesity in the long term. Surgery could be considered a relatively short-term solution. 

Credit to Nick Triggle, BBC Health correspondent, for his article published which can be read here. Also the full speech by CEO Simon Stevens can be read here.

The Small Guys That Help Regulate Protein Synthesis

If you have an interest in cellular biology, the chances are you've come across the different types of nucleic acids that are used to code for proteins and control certain activities of the cell. However, what might be new to you is the existence of MicroRNA or miRNA, in its common notation. Essentially these are regular strands of RNA but very small - in fact a regular sized RNA molecule may be around 100 times longer than the average length miRNA. As miRNA are single stranded, the molecules tend to quite flexible, in contrast to the well known rigid DNA double helix molecule. Originally, scientists tended to believe that in eukaryotic cells at least, there were only two types of RNA: ribosomal RNA and messenger RNA. At first, miRNA were seen to be RNA that were too insignificant to have any real function, they were considered free clumps of nucleotides in short.

Now the importance of miRNA molecules has been realised, thanks to cutting edge research on a particular type of nematode worm - specifically Caenorhabditis elegans. In 1993, the first miRNA identified was named lin-4. What scientists found is that somehow, these minute molecules prevent the development of the larvae. 

After these baby steps into this field of research, the year 2000 saw the discovery of the miRNA molecule let-7. This was found to 'regulate development in C.elegans'. What was more significant however, was that this molecule could be found in all animal and plant cells. But what do we mean by 'regulate development'? This particular miRNA molecule is found to be responsible for controlling aspects of the cell cycle and cell differentiation. But healthy functioning cells doesn't rely on a single miRNA molecule - many different molecules working together ensure cellular processes go on as intended.

But how do miRNA's work?

In an average human cell, over 1000 different miRNA molecules can be found. Each of these specific strands seek to target a particular RNA molecule. With over 60% of RNA molecules being targeted by miRNAs, it could be said that controlling protein synthesis is a very organised and vast operation. What is important to note, is that miRNA molecules are encoded by genes, a lot like proteins in fact. It follows that these genes are present in the cell's DNA.

To synthesise miRNA, firstly one long strand of specially structured RNA is manufactured from miRNA genes. These could be considered the precursors of miRNA (Pri-miRNA) and are subsequently lysed by enzymes and transported from the nucleus, into the cytoplasm. Any two different  miRNAs can align through regular RNA-RNA hydrogen bonded base-pairing. However in some parts, there may be some non-complementary base pairing which would lead to bulges from the molecule. Using specific enzymes, the hydrogen bonds can be broken to leave two separate miRNA molecules which can go on to target their designated RNA molecule.

Due to inconsistencies in base pairing with an mRNA molecule, miRNAs have been found to inhibit protein synthesis by preventing the ribosome translating the RNA molecule. But another way miRNA's function is that they can achieve complete complementary base pairing with an mRNA molecule. Specific degrading enzymes can then recognise this situation and destroy the miRNA-mRNA complex, preventing the protein ever being synthesised.

(Two examples of pri-miRNA - sequences in red represent 'mature' miRNA. Notice there are bulges where there is no complementary base pairing - WIkipedia - microRNA)

Extended research has shown that 'malfunction of miRNAs is implicated in some liver diseases, diseases of the nervous system, cardiovascular disease, cancer and obesity'. One example given in the September issue of the Biological Sciences Review is miRNAs affecting normal nervous function. Individuals with mental retardation sometimes have whats called "fragile X syndrome", where as implied, the X chromosome tends to break easily. In association with this, it has been found that in the nerve cells of these individuals, miRNA molecules have prevented the synthesis of an essential protein by binding with mRNA.

Even miRNA has been believed to be the culprit in some cancers. It isn't always bad that an miRNA molecule binds to RNA - some miRNAs suppress tumour growth whilst others promote it.

At present, it may be difficult to see how miRNAs can be used to treat disease, but I believe there is no doubt that it could one day be widely use to diagnose them. Cancers are a good example. It has been observed that particular concentrations of a miRNA can correlate with different rates of growth of malignant tumours. From miRNA analysis, it may be possible for doctors to predict the best treatment options for patients.

However this does't mean treatment isn't possible! According to Professor Sheila Graham of the University of Glasgow, new research has revealed the potential of "miRNA sponges" in cells. These are non-functioning RNA molecules that "mop up" specific miRNA molecules so that they can't interrupt the synthesis of essential proteins.



Credit to Professor Sheila Graham for her article 'MicroRNAs - small players in big diseases' published in the Biological Sciences Review (Volume 27, Number 1).

Documentary on Tissue Donation

Recently I watched a documentary on the BBC about tissue and organ donation - it focuses on the various people that work in tissue transplantation and those who obtain skin and bone from the deceased. It was really fascinating to see how healthcare workers manage the deceased and what happens to tissue when it is obtained and used to treat patients who long for a donor. It has also made me appreciate that the field of medicine is more than 'dealing with the living'. The documentary was called "The Human Tissue Squad" and I encourage anyone to watch this, although those who are squeamish about blood I advise not to!

Here is the video embedded below:



What is especially striking is that this whole sector of healthcare is solely dependant on people opting for their loved ones' tissues to be donated, and people themselves registering onto the organ donation register. The documentary follows staff at the National Tissue Bank in Liverpool during a time of struggle to obtain tissue surgery on patients who have very particular conditions. One member of staff in the film stressed that "it's younger donors that [they] really need". In the last year this documentary was filmed, only 51 donors were under 35.

The National Tissue Bank stores an incomprehensibly diverse range of tissues, from eyes, to femoral arteries, to Achilles tendons. Tissues generally need to be collected as early as 24 hours after death. However sometimes there is a rising pressure from the bank to supply tissues needed by surgeons in many different hospitals around the country. I was also amazed at the work the nurses do at the bank to support the loved ones of those that have very recently passed away. They talk with families over the phone to decide whether tissues will be donated from the deceased. I can empathise that this could be a distressing task, one nurse mentions she takes up to 24 calls a day. Despite recognises these sad losses, it is of importance that they have enough tissues in stock in supply to the many nationwide hospitals. In one week, the bank may go without one single donation, the next, it may be a 'mad rush' to distribute the tissues with as many as four teams a day on the shift.

One outstanding factor that renders the National Tissue Bank being effective is the teamwork between colleagues within small groups. Also, there is a defining commitment to the job as one pair have to venture out for dissection as early as 5:00AM.

The importance of tissue donation means lives can be saved, however there is always a need for tissue supplies. This relies on the difficult decisions of thousands of families all over the country. An interesting question to consider is whether by law, everyone should be enrolled onto the organ doner register - then it is up to the individual to un-enroll.


Credit to the BBC for their televised documentary "The Human Tissue Squad" (available on iPlayer until 15th September 2014)

Fat!

One of the major health issues facing our world, the western world especially, is obesity. In fact, it is estimated that there are over 1.4 billion people overweight with over 500 million obese. These figures are expect to rise. In 1971, it was estimated that in North America, 14.5% of the population were obese. Now, the figure is over double at 30.9%. These figures were taken from the Biological Sciences Review article 'Lifestyle and Cardiovascular Disease', Volume 26, Number 2. Britain, despite it's small land mass, is considered the second 'fattest' country in the world - in reference to it's people that is. It is not only to do with the fact our country is now becoming overcrowded, our very habits, morals, behaviour and eating patterns have contributed to a dramatic increase in cases of obesity in the last couple of decades. To many people, carbohydrates contribute to the base of a diet. However in many cases an imbalance of this food group inevitably leads to weight gain and the formation of excess fat (adipose) tissue. How does this mechanism work? Well, central to this question is respiration, adipocytes (fat cells) and of course the different types of fat. Here, I want to explain how a weight gain is achieved, even right down to the molecular level.

Firstly, we need to understand that the molecule glucose makes up the vast majority of carbohydrate-based foods. Glucose is essential to our well being, in particular being vital to the function of our nervous system and our muscular system. It's uptake by our many billions of cells initiate the start of the production of the 'energy' molecule ATP, or Adenosine Triphosphate. It is a continuous process, however once our cells are content with the amount of glucose needed to produce ATP, glucose is transported and stored in various tissues of the body.

Adipocytes

Usually, glucose can be converted into glycogen via glycogenesis for "short-term" storage in muscles and the liver. Glycogen can be easily hydrolysed back into glucose for ease of access to body cells and tissues. However alternatively, glucose can be stored as part of fat molecules called triglycerides. These molecules comprise of a glycerol backbone with three attached hydrocarbon chains. These chains were originally carboxylic acids, better known as fatty acids - they take part in a condensation reaction to release three water molecules in forming a triglyceride. The main site in the body in which we would find triglycerides is in adipocytes. However triglycerides can also be utilised by muscle cells in the release of energy if needed. Fats are generally considered a second source of energy after carbohydrates. As well as the storage of glucose, triglycerides can also be formed from the digestion of fatty foods into the base components glycerol and fatty acids before subsequent absorption.

So how exactly is fat managed?

Well, to start with there are two different kinds of adipocytes, white and brown. It is important to distinguish between these two cell types as they have very contrasting roles. When fat is said to be 'stored', it is held within the white adipocytes of the body. When these cells are content with the amount of glucose needed to carry out respiration to yield the maximum number of ATP's, excess glucose is converted into fat here. The receptor that recognises this and promotes the storage of fat is called PPARγ. Conversely, brown adipocytes are considered extremely 'energy ineffecient', "burning" up triglycerides and storing very little, if any, of them. The result is that much heat is produced, a consequence of the many mitochondria this cell has. In fact, it has the most of any cell in the human body. This was once considered a survival mechanism for newborn infants as they had brown adipocytes in large numbers - the heat generated helps to protect the child from comparatively cold conditions to the womb. New research has found that adults posses these exact same cell types, 'roughly 60g in the neck region'. These cells adjust their calorie-burni ctivity in accordance with food intake and external temperature just to name a couple.

Now here is the intriguing part. Recent experiments in mice have shown that an increase in brown adipocytes 'help protect against diet-induced obesity and type 2 diabetes by preventing the build-up of triglycerides in other cell types, such as those in the liver and muscle'.

So what are the potentials of brown adipocytes?

In my view, adipocytes quite fasdcinate me now I've read a lot more into the subject. In cellular respiration, glucose is commonly processed through a series of step-by-step exothermic reactions. However in brown adipocytes, the stage that normally produces the largest number of ATP's is halted. It is known as oxidative phosphorylation. This means rather than using the energy released form the exothermic reactions to produce ATP, it is dissipated as heat energy - usually regardedas very inefficient!

Scientists have spent years of research trying to suggest new methods to combat the ever-pressing problem of obesity. Novel resserach into a particluar protein found in adipocytes called sirtuin has sparked a glimmer of hope. Sirtuin has been found to be associated with 'calorfic restriction' where life expectancy has increased with decreasing the number of calories in the diet gradually over a prolonged period of time. As sirtuin is commonly found in metabolising brown fat cells, there may be potential for sirtuin to be stimulated in white fat cells in combating weight gain. The experiments that scientists carried out confimred that with an increased presence of sirtuin, white fat cells started to show some of the characteristsc of brown fat cells, i.e. genes were becoming switched on that were analogous to brown fat cells. Parallel to this, other genes in the white fat cells were becoming switched off, again the same ones that are switched off in normal brown fat cells.

This phenomenal "growing" effect of white fat cells has significant potential. It is down to the protein sirtuin, how this works requires a little more understanding. Sirtuin is found to bind to the PPARγ receptor and modifies it. This receptor is found on the nucleus of white adipocytes. Therefore this receptor doesn't resume in normal function - instead it 'activates a transcription factor called Prdm16 that stwiches on a set of genes necessary for using up chemical energy to produce heat'.

Another plus side of the 'browning' of white adipocytes is that, in diabetic mice, their responsiveness  to insulin increased.

Is it all too good to be true? Well, not exactly. You see, sirtuin is found in many different types of cell throughout the body, not just adipocytes. This would imply that adjusting concentrations of sirtuin will have additional, even unwanted effects to the body. These problems will need to be investigated further by researchers in the future.


Credit to Joseph Robertson, who writes for the Biological Sciences Review (Volume 26, Number 2), for his article "Fighting the Flab" which was published.