NHS Choices

Syndicate content
Constantly updated health news across a range of subjects.
Updated: 1 day 9 hours ago

Stem cells could provide a treatment for a 'broken heart'

Tue, 2015-05-19 07:00

"Scientists believe they may have discovered how to mend broken hearts," reports the Daily Mirror.

While it may sound like the subject of a decidedly odd country and western song, the headline actually refers to damage to the heart muscle.

heart attack occurs when the muscle of the heart becomes starved of oxygen causing it to be damaged. If there is significant damage the heart can become weakened and unable to effectively pump blood around the body. This is known as heart failure and can cause symptoms such as shortness of breath and fatigue.

The heart contains "dormant" stem cells, and researchers want to learn more about them to work out ways to get them to help repair damaged heart tissue.

In this new laboratory and animal study, researchers identified a characteristic genetic "signature" of adult mouse heart stem cells. This led to them being more easily identified than they have been previously, making them easier to "harvest" for study.

Injections of these cells into damaged mouse hearts was shown to improve heart function, even though very few of the donor cells remained in the heart.

These findings will help researchers to study these cells better, for example investigating whether they could be chemically triggered to repair the heart without removing them first. While the hope is that this research could lead to treatments for human heart damage, as yet the results are just in mice.

The researchers also note that they need to find out whether human hearts have the equivalent cells.

Where did the story come from?

The study was carried out by researchers from Imperial College London and other UK and US universities. It was funded by the British Heart Foundation, European Commission, European Research Council and the Medical Research Council, with some of the researchers additionally supported by the US National Heart and Lung Institute Foundation and Banyu Life Science Foundation International.

The study was published in the peer-reviewed scientific journal Nature Communications. It is open access, meaning it can be read for free online.

The Mirror’s main report covers the story reasonably, but one of its subheadings – that scientists have identified a protein that if injected can stimulate heart cell regeneration – is not quite right. The researchers have not yet been able to utilise a protein to stimulate heart regeneration. They have just used a specific protein on the surface of the stem cells to identify the cells. So it was the cells, and not the protein, that were used in regeneration.

The Daily Telegraph’s coverage of the study is good and includes some useful quotes from the lead researcher Professor Michael Schneider. The article also makes it clear that this study only involved mice.

What kind of research was this?

This was laboratory and animal research studying the adult stem cells in mice that can develop into heart cells.

A number of diseases cause (or are caused by) damage to the heart. For example, heart attacks occur when some heart muscle cells do not get enough oxygen and die – usually due to a blockage in the coronary arteries that supply the heart muscle with oxygen-rich blood. There are "dormant" stem cells in the adult heart that can generate new heart muscle cells, but are not active enough to completely repair damage.

Researchers are starting to test ways to encourage the stem cells to repair heart damage fully. In this study, the researchers were studying these cells very closely, to understand whether all heart stem cells are the same, or whether there are different types and what they do. This information could help them to identify the right type of cells and conditions they need to fix heart damage.

This type of research is a common early step in understanding how the biology of different organs works, with the aim of eventually being able to develop new treatments for human diseases. Much of human and animal biology is very similar, but there can be differences. Once researchers have developed a good idea of how the biology works in animals, they will then carry out experiments to check to what extent this applies to humans.

What did the research involve?

The researchers obtained stem cells from adult mouse hearts and studied their gene activity patterns. They then went on to study which of these cell types could develop into heart muscle cells in the lab, and which could successfully produce heart muscle cells that could integrate into the heart muscle of living mice.

The researchers started by identifying a population of adult mouse heart cells that is known to contain stem cells. They separated out these into different groups, some of which are known to contain stem cells, and further separated each group into single cells, and studied exactly which genes were active in each cell. They looked at whether the cells showed very similar gene activity patterns (suggesting that they were all the same type of cells, doing the same things), or whether there were groups of cells with different gene activity patterns. They also compared these activity patterns to young heart muscle cells from newborn mice.

Once they identified a group of cells that looked like the cells that could develop into heart muscle cells, they tested whether they would be able to grow and maintain these in the lab. They also injected the cells into the damaged hearts of mice to see if they formed new heart muscle cells. They also carried out various other experiments to further characterise the cells that form new heart muscle cells.

What were the basic results?

The researchers found distinct groups of cells with different gene activity patterns. One particular group of these cells was identified as the cells that have started to develop into heart muscle cells. These cells were referred to as Sca1+ SP cells, and one of the genes they expressed produces a protein called PDGFRα, which is found on the surface of these cells. These cells grew and divided well in the lab, and the offspring cells maintained the characteristics of the original Sca1+ SP cells.

When the researchers injected samples of the offspring cells into damaged mouse hearts, they found that between 1% and 8% of the cells remained in the heart muscle tissue the day after the injection. Over time, most of these cells were lost from the heart muscle, but some remained (about 0.1% to 0.5% at two weeks).

By two weeks, some (10%) of the remaining cells were showing signs of developing into immature muscle cells. At 12 weeks, more of the remaining cells (50%) were showing signs of being muscle cells. These cells were also showing signs of being more developed and forming muscle tissue. However, there were only a few of these donor cells in each heart (5 to 10 cells). Some of the donor cells also appeared to have developed into the two sorts of cells found in blood vessels.

Mice whose hearts had been injected with the donor cells showed better heart function at 12 weeks than those who had a "dummy" injection with no cells. The size of the damaged area was smaller in those with donor cell injections, and the heart was able to pump more blood.

Further experiments showed the researchers that they could identify and separate out the cells that specifically develop into heart muscle cells by looking for the PDGFRα protein on their surface. The cells identified in this way grew well in the lab, and when injected into the heart they could integrate into the heart muscle and showed signs of developing into muscle cells after two weeks.

How did the researchers interpret the results?

The researchers concluded that they had developed a way to identify and separate out a specific subset of adult mouse heart stem cells and can generate new heart muscle cells. They say that at the very least this will help them to study these cells in mice more easily. If a human equivalent of these cells exists, they may also be able to utilise this knowledge to obtain stem cells from adult heart tissue.

Conclusion

This laboratory and animal study has identified a characteristic genetic "signature" of adult mouse heart stem cells. This has allowed them to be more easily identified than they have been previously. Injections of these cells have also been shown to be able to improve heart function after heart muscle damage in mice.

These findings will help researchers to study these cells more closely in the lab and investigate how they can prompt them to repair damaged heart muscle, possibly without removing them from the heart first. While the hope is that this research could lead to treatments for human heart damage, for example after a heart attack, as yet the results are just in mice. The researchers themselves note that they now need to find out whether human hearts have the equivalent cells.

Many researchers are working on the potential uses of stem cells to repair and damage human tissue, and studies such as this are important parts in this process.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Stem cells could be used to repair previously irreversible damage from heart attacks, say scientists. Daily Mirror, May 18 2015

'Heartbreak' stem cells could repair damage of heart attack. The Daily Telegraph, May 19 2015

Links To Science

Noseda M, Harada M, McSweeney S, et al. PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium. Nature Communications. Published online May 18 2015

Categories: News

Bioengineering advances raise fears of 'home-brew heroin'

Tue, 2015-05-19 05:00

The Daily Mirror carries the alarming headline that, "Heroin made in home-brew beer kits could create epidemic of hard drug abuse". It says scientists are "calling for urgent action to prevent criminal gangs gaining access to [this] new technology" following the results of a study involving genetically modified yeast.

This study did not actually produce heroin, but an important intermediate chemical in a pathway that produces benzylisoquinoline alkaloids (BIAs). BIAs are a group of plant-derived chemicals that include opioids, such as morphine.

BIAs have previously been made from similar intermediate chemicals in genetically engineered yeast. Researchers hope that by joining these two parts of the pathway, they will get yeast that can produce BIAs from scratch. This could be cheaper and easier than current production methods, which often still involve extraction from plants.

But because morphine can be refined into heroin using standard chemical techniques and yeast can be grown at home, this has led to concerns about the potential misuse of this discovery.

So, will this lead to a rash of "Breaking Bad"-style heroin labs in criminals' garages and spare rooms? We doubt it – at least in the near future. A strain that can produce morphine has not yet been made and would need to be specially genetically engineered to do this, not just using unmodified home-brewing yeast available off the shelf.

Still, it may be worth raising awareness about the potential need for regulation of opioid-producing strains. 

Where did the story come from?

The study was carried out by researchers from the University of California and Concordia University in Canada.

It was funded by the US Department of Energy, the US National Science Foundation, the US Department of Defense, Genome Canada, Genome Quebec, and a Canada Research Chair.

The study was published in the peer-reviewed journal, Nature Chemical Biology. It is open access, meaning it can be read online for free.

The Daily Mirror's reporting takes a sensationalist angle – the picture caption, for example, reads: "Home-brewed heroin is on the rise, scientists warn". No heroin was made in this study, and complete opioid-producing strains of yeast have not been made yet – home-brewing heroin from yeast is not yet possible, much less on the rise.

The possibility of home-brewing comes from a commentary on the article in Nature, which discusses the findings of this and related studies. This commentary also discusses the potential legal implications, and the ways that risks could be reduced. For example, scientists could only produce yeast strains that make weaker opioids. But they acknowledge that the risk of criminals making opiate-producing yeast strains themselves is low.

The Guardian and BBC News take a slightly more restrained approach, suggesting that home-brew heroin may be a problem in the future but it certainly is not an issue now. The BBC also points out that producing medicines in microbes is not a new thing. 

What kind of research was this?

This laboratory research studied whether a group of chemicals called benzylisoquinoline alkaloids (BIAs) could be produced in yeast. BIAs include a range of chemicals used as drug treatments in humans. This includes opioids used for pain relief, as well as antibiotics and muscle relaxants.

Opioids are among the oldest drugs first identified as being produced naturally by opium poppies. Morphine is an opioid derived from poppies, and it and other derivatives or man-made versions of opioids are used to treat pain.

Opioids also produce euphoria and can be addictive. The illegal drug heroin is an opiate that can be produced by refining morphine to make it more powerful.

The researchers say many of these compounds are still made from plants such as the opium poppy, as they are chemically very complex and therefore difficult and expensive to make from scratch in the lab.

However, now we know much more about how the chemicals are made in plants, it may be possible to genetically engineer microbes in the lab to produce these chemicals in industrial quantities.

The researchers say the yeast S. cerevisiae – sometimes known as baker's or brewer's yeast – has been used to produce BIAs in the lab from intermediate chemicals in the BIA production pathway. The earlier steps in the pathway have not yet been managed in yeast, although they have in bacteria.

In this study, the researchers wanted to see if they could produce the intermediate chemical (S)-reticuline in yeast. This has been tried before, but was not successful. 

What did the research involve?

The researchers knew they needed one particular type of protein called a tyrosine hydroxylase, which would work in yeast to perform the first step in the process of making (S)-reticuline.

They developed a system to allow them to quickly screen a large group of known tyrosine hydroxylases to identify one that would work in yeast. The tyrosine hydroxylase is needed to produce the intermediate chemical dopamine.

The researchers then needed other proteins that convert dopamine and another chemical already present in yeast into another intermediate chemical, and then carry out the other chemical steps needed to form (S)-reticuline. They identified proteins they needed for these stages from the opium poppy and the Californian poppy.

Finally, they genetically engineered yeast cells to produce tyrosine hydroxylase and all of the other proteins needed, and tested whether the yeasts were able to produce (S)-reticuline.  

What were the basic results?

The researchers were able to identify tyrosine hydroxylase from the sugar beet that worked in yeast, allowing them to produce the intermediate chemical dopamine. They used genetic engineering to make a version of this protein in yeast that worked even better than the original one.

They were also able to produce the other proteins they needed in yeast. A yeast strain producing all of these proteins was able to produce (S)-reticuline, the chemical intermediate needed in the production of opioids. 

How did the researchers interpret the results?

The researchers concluded that coupling their work with the work already done, and improving on the yield of the process, "will enable low-cost production of many high-value BIAs".

They say that, "Because of the potential for illicit use of these products, including morphine and its derivatives [such as heroin], it is critical that appropriate policies for controlling such strains be established so that we garner the considerable benefits while minimising the potential for abuse." 

Conclusion

This laboratory study has successfully managed to produce an important intermediate chemical in the pathway that produces benzylisoquinoline alkaloids (BIAs), a group of plant-derived chemicals that include opioids.

BIAs such as morphine have previously been made from similar intermediate chemicals in genetically engineered yeast, but this is the first time the earlier stages have been completed successfully in yeast. The researchers hope that by joining these two parts of the pathways, they will get yeast that can produce BIAs from scratch.

This study has not completed this final step, however. Researchers will need to test this before they know that it will be successful. They acknowledge that further optimisation of their method to produce more of the intermediate chemical is needed before it could be used to produce BIAs.

This study has generated media coverage speculating about the possibility of "home-brew heroin" creating an "epidemic of hard drug use". But the researchers did not produce heroin or any other opioid, only an intermediate chemical. These yeasts have been specially genetically engineered, and the experiments are not the sort of thing most people are going to be able to easily replicate in their garage.

While the likelihood of such strains being successfully made for criminal use seems very small, at least in the short to medium term, criminals can be resourceful. Considering the potential implications of this research and whether policies are needed, both nationally and internationally, may be prudent.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Home-brewed heroin? Scientists create yeast that can make sugar into opiates. The Guardian, May 18 2015

'Home-brewed morphine' made possible. BBC News, May 19 2015

Heroin made in home-brew beer kits could create epidemic of hard drug abuse. Daily Mirror, May 18 2015

Links To Science

DeLoache WC, Russ ZN, Narcross L, et al. An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose. Nature Chemical Biology. Published online May 18 2015

Categories: News

No proof orange juice boosts brain power

Mon, 2015-05-18 06:00

"Drinking orange juice every day could improve brain power in the elderly, research shows," the Mail Online reports. Despite the encouraging words from the media, the small study this headline is based on does not provide strong evidence that an older person would see any noticeable difference in their brain power if they drink orange juice for two months.

The study involved 37 healthy older adults, who were given orange juice or orange squash daily for eight weeks before switching to the other drink for the same amount of time. The 100% orange juice contains more flavonoids, a type of plant compound that has been suggested to have various health benefits.

The researchers gave participants a whole battery of cognitive tests before and after each eight-week period. Both drinks caused very little change on any of the test results and were not significantly different from each other on any of the tests individually.

The researchers also carried out analyses where they combined the test results and looked at the statistical relationships between the drink given and when the test was given. On this occasion, they did find a significant result – overall cognitive function (the pooled result of all the tests combined) was better after the juice than after the squash.

But the overall pattern of the results doesn't seem very convincing. This study does not provide conclusive evidence that drinking orange juice has an effect on brain function.  

Where did the story come from?

The study was carried out by researchers from the University of Reading, and was funded by Biotechnology and Biological Sciences Research Council grants and the Florida Department of Citrus, also known as Florida Citrus.

Florida Citrus is a government-funded body "charged with the marketing, research and regulation of the Florida citrus industry", a major industry in the state. Florida Citrus was reported to have helped design the study.

The study was published in the peer-reviewed American Journal of Clinical Nutrition.

The Mail Online took the study at face value without subjecting it to any critical analysis. Looking into the research reveals rather unconvincing evidence that drinking orange juice would have any effect on a person's brain function.  

What kind of research was this?

This was a randomised crossover trial that aimed to compare the effects of 100% orange juice, which has high flavanone content, and orange-flavoured cordial, which has low flavanone content, on cognitive function in healthy older adults.

Flavonoids are pigments found in various plant foods. It has been suggested they have various health benefits – for example, some studies have suggested that high consumption of flavonoids can have beneficial effects on cognitive function. Flavanones are the specific type of flavonoids found in citrus fruits. This trial investigated the effect of flavanones in orange juice.

This was a crossover trial, meaning the participants acted as their own control, taking both the high and low flavanone content in random order a few weeks apart. The crossover design effectively increases the sample size tested, and is appropriate if the interventions are not expected to have a lasting impact on whatever outcome is being tested. 

What did the research involve?

The study recruited 37 older adults (average age 67) who were given daily orange juice or orange squash for eight weeks in a random order, with a four-week "washout" period in between. They were tested to see whether the drinks differed in their effect on cognitive function.

All participants were healthy, without significant medical problems, did not have dementia and had no cognitive problems. In random order, they were given:

  • 500ml 100% orange juice containing 305mg natural flavanones daily for eight weeks
  • 500ml orange squash containing 37mg natural flavanones daily for eight weeks

The drinks contained roughly the same calories. The participants were not told which drink they were drinking, and the researchers assessing the participants also did not know.

Before and after each of the eight-week periods, participants visited the test centre and had data collected on height, weight, blood pressure, health status and medication. They also completed a large battery of cognitive tests assessing executive function (thinking, planning and problem solving) and memory.

The researchers analysed change in cognitive performance from baseline to eight weeks for each drink, and compared the effects of the two drinks. 

What were the basic results?

On the whole, the two drinks caused very minimal change from baseline on any of the individual tests. There was no statistically significant difference between the two drinks when comparing score change from baseline on any of the tests individually.

There was only a single significant observation when looking at the individual tests at the end of treatment (rather than change from baseline). A test of immediate episodic memory was higher eight weeks after drinking 100% orange juice compared with squash (score 9.6 versus 9.1). However, when this was compared to the change from baseline, it didn't translate into any significant difference between the groups.

The researchers also carried out a statistical analysis looking at the interactions between the drink given and the testing occasion. In this analysis, they did find an interaction between the drink and testing for global cognitive function (when all test results were combined). This showed that, overall, this was significantly better at the eight-week visit after the orange juice intake. 

How did the researchers interpret the results?

The researchers concluded that, "Chronic daily consumption of flavanone-rich 100% orange juice over eight weeks is beneficial for cognitive function in healthy older adults."

They further say that, "The potential for flavanone-rich foods and drinks to attenuate cognitive decline in ageing and the mechanisms that underlie these effects should be investigated." 

Conclusion

Overall, this small crossover study does not provide conclusive evidence that drinking orange juice has an effect on brain function.

A wide variety of cognitive tests were performed in this study before and after the two drinks (orange juice and squash). The individual test results do not indicate any large effects. Notably, both drinks caused very little change from baseline on any of the test results, and were not significantly different.

The only significant results were found for overall cognitive function when combining test results and looking at statistical interactions. The fact a consistent effect wasn't seen across individual measures and the different analyses means the results are not very convincing.

The trial is also quite small, including only 37 people. These participants were also a specific sample of healthy older adults who volunteered to take part in this trial, and none of them had any cognitive impairment, so the results may not be applicable to other groups.

While the participants were not told what they were drinking and the drinks were given in unlabelled containers, they did have to dilute them differently. This and the taste of the drinks may have meant the participants could tell the drinks apart. The researchers did ask participants what they thought they were drinking, and although about half said they did not know, most of those who gave an opinion (16 out of 20) got it right.

There is also only comparison of high- and low-flavanone orange juice. There is no comparison with a flavanone-free drink, or foods or drinks that contain other types of flavonoid.

The possible health benefits of flavonoids or flavanones specifically will continue to be studied and speculated. However, this study can't conclusively tell us that they have an effect on brain power.

A good rule of thumb is what's good for the heart is also good for the brain – taking regular exercise, eating a healthy diet, avoiding smoking, maintaining a healthy weight, and drinking alcohol in moderation.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Two daily glasses of orange juice 'boosts elderly brainpower': Significant improvements can be seen in less than two months, research shows. Mail Online, May 16 2015

Orange juice 'improves brain function'. The Daily Telegraph, May 15 2015

Links To Science

Kean RJ, Lamport DJ, Dodd GF, et al. Chronic consumption of flavanone-rich orange juice is associated with cognitive benefits: an 8-wk, randomized, double-blind, placebo-controlled trial in healthy older adults. The American Journal of Clinical Nutrition. Published online January 14 2015

Categories: News