Cholesterol treatment used in treatment of hepatitis C?

By Kathryn Higgins

A molecule that is known to take up cholesterol into a cell has recently been identified to allow entry of the hepatitis C virus (HCV) into liver cells. This may lead the way for new therapies to be developed.

Hepatitis C is a disease that primarily affects the liver. It is caused by HCV, which is spread by blood-to-blood contact. Once infected, HCV can persist in the liver causing scarring and ultimately leading to liver failure or cancer. The World Health Organisation (WHO) estimates that three per cent of the world’s population (about 170 million) have hepatitis C, and although treatment is available, more effective therapies are needed. Liver transplantation is one such treatment, but infected patients find the virus attacks the new liver.

Previous studies have shown the involvement of cholesterol in HCV infection, thus it was hypothesised by researchers at the University of Illinois at Chicago that a cell surface molecule (a receptor) called Niemann-Pick C1-like 1 (NPC1L1), which is known to facilitate the uptake of cholesterol into the cell, may also be involved in trafficking the virus into the cell.

The research team headed by Susan Uprichard, assistant professor of Medicine, Microbiology and Immunology, conducted experiments to determine the role of NPC1L1 on viral uptake. Experiments involved blocking the receptor and reducing expression by using knock-out models. The results demonstrated that blockade or knock-out of NPC1L1 impaired liver cell infection with HCV.

To confirm these studies further, an inhibitor of NPC1L1 called ezetimibe, which is clinically used to lower cholesterol levels, was also tested. Results validate previous findings showing blockade of HCV uptake into the cells and preventing infection.

Current drugs used to treat hepatitis C are known to be toxic, and cannot be used by transplant patients, therefore ezetimibe may provide a solution as a new anti-hepatitis agent. Therapy with ezetimibe alone or in combination with current drugs may improve patient treatment by targeting the receptor NPC1L1 and preventing HCV entry into liver cells.

Reference:
Sainz et al, (2012) Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor. Nature Medicine. Ahead of print.

The paper can be found at: http://www.nature.com/nm/journal/vaop/ncurrent/pdf/nm.2581.pdf

Transparent tissues offer a window into the brain

By Kathryn Higgins

 

A revolutionary reagent has been developed that can literally turn biological tissues transparent. Researchers from the RIKEN Brain Science Institute in Japan have developed a reagent which allows 3D imaging of the neuronal network deep inside a mouse brain.

Imaging and labelling of cell populations deep within tissue has been a challenge for scientists for many years. Although advances have been made in cell imaging there are still many obstacles to overcome. Tissues often have to be sliced 1mm thick for viewing under a microscope to dissect networks since imaging within deep tissues leads to many problems due to the lack of transparency of the tissue. Several clearing solutions have been developed but these have disadvantages such as expense and quenching of fluorescently labelled proteins that are often used in cell research to visualise the structures.

A research team led by Atsushi Miyawaki, however, have recently developed a reagent, after a chance observation, which may revolutionise deep tissue imaging by obtaining 3D images that are valuable for improving our understanding of biological organisms and how they function.

The reagent, called ScaleA2, is a highly effective clearing reagent, greatly improving the transparency of tissues, and stabilising fluorescently labelled proteins. This allows imaging to be done at a much greater depth than currently possible, providing detailed 3D visualisation of neuronal networks within the brain than has ever been managed before.

Current research using ScaleA2 was done using dead embryo tissue for imaging neurones and blood vessels deep inside the mouse brain. Miyawaki and his research team, however, believe that the scope for using ScaleA2 in other tissues and organisms is not limited, and are currently trying to optimise the reagent for use in live tissue. This would open the door to experiments that have never before been possible.

 

Image shows two murine embryos. The left embryo was placed in PBS, whilst the embryo on the right was incubated for 2 weeks in ScaleA2 solution.

 

 

Reference:

Hama et al, (2011) Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain. Nature Neuroscience. Ahead of print.

The paper can be found at:

http://www.nature.com/neuro/journal/vaop/ncurrent/pdf/nn.2928.pdf

A Sweet Way to Heal Wounds

 

By Kathryn Higgins

 

We’ve all heard the term rubbing salt into the wounds, but using sugar instead may be a new treatment for wound healing and reducing pain.

Moses Murandu, a Senior Lecturer in Adult Nursing at the School of Health and Well Being at the University of Wolverhampton, Birmingham, has just been awarded a £25,000 grant to continue a study in the effect of sugar on wounds and cuts.

Originally raised in Zimbabwe, Moses grew up following traditional African remedies, one of which involved treating wounds with cane sugar. Trained as a senior nurse, Moses was surprised to find that this was not common practise when he came to the UK stating “when I was a child, my father used sugar or salt and I grew up without realising that something that works is not widely used”.

Leading a study at Selly Oak Hospital in Birmingham, involving 21 patients whose wounds had not responded to conventional treatment, Moses poured granulated sugar onto bed sores, leg ulcers or amputations before the wound was dressed. However, he did point out that the sugar used was not taken straight off the supermarket shelves, but was certified, sterile sugar direct from the manufacturer.

The study found that a solution of 25% sugar was effective in not only reducing pain associated with wounds, but also improved healing. The sugar solution works by drawing water out of the wound into the dressing. Bacteria need water to survive so when sugar is added bacteria are killed leading to healing of the wound and reducing pain.

An abstract of this work was submitted by Mr Murandu to the Fondation Le Lous, and was awarded the Fondation Le Lous Research Innovation Award and £25,000 to continue his research for a further two years.

This innovative practise would save the NHS millions of pounds a year, with treatment costing about £1.49 each time compared to hundreds of pounds to hire equipment to drain wounds.

 

For further details of the study see:

http://www.wlv.ac.uk/default.aspx?page=24330

http://wlv.ac.uk/default.aspx?page=21067

 

Blood Groups Could Become a Thing of the Past

 

Written by Matt Farley

 

New research from McGill University in Canada could do away with the need to classify blood by ‘type’, following a new technique to prevent mismatched blood from being rejected after a transfusion.

Along with the well-known A, B and O blood groups, there are a further 26 different blood types which have to be matched carefully when carrying out a blood transfusion – a mismatch can lead to the donated blood being rejected by the body which can be fatal. The ideal situation is for a ‘universal’ blood type which would be compatible with any recipient blood type.

Rejection occurs when the antigens on the surface of the donor red blood cells are of a different type to those on the recipient’s cells – previous attempts at avoiding this have focused on either removing the surface antigens from the donated blood using enzymes, or producing the blood outside the body from stem cells. These techniques have shown some success, but are hindered by their expense and complexity. The latest method, presented by Dr. Maryam Tabrizian and colleagues, instead aims to cover up the antigens and hide them from the host immune system – known as ‘immunocamouflage’.

Red blood cells from a selection of volunteers were coated in a layer of polyelectrolytes – small repeating units which self-assemble on the cell surface. Previous attempts at coating cells in this way using yeast and E.coli had shown promise, but it remained to be seen whether the delicate red blood cells would be able to withstand the process.

After coating, the cells were exposed to their opposite antibody and observed for any agglutination, or clumping of cells, that occurred. The coated cells were shown to remain free after addition of the antibody, suggesting that the antibodies had failed to recognise and bind the cell surface antigens. This was in contrast to the uncoated cells, which clumped together in the manner normally seen when mismatched blood samples are mixed.

Perhaps most importantly, the red blood cells showed no significant reduction in their ability to take up oxygen, implying that they would still be able to carry out their function within the body. The cells were also seen to produce ATP, an energy carrier – a good sign that metabolism was also functioning as normal.

It remains to be seen whether the technique will be as effective when tested in a living organism, but the results obtained so far appear promising. If effective, future blood transfusions could become a lot easier, and a lot less dangerous.

The paper accompanying this article is available online:

http://pubs.acs.org/stoken/presspac/presspac/full/10.1021/bm101200c

Red blood cells

What? A molecule that enables hearing

 

By Kathryn Vaughan

Researchers at the University of Sheffield have identified a molecule that underlies mechanisms of hearing loss and deafness.

In the inner ear ‘cochlear hair cells’ are responsible for receiving sound as sensory information before it can be converted into electrical nerve signals to be sent to the brain, and these hair cells mature during embryonic development. To examine the mechanisms that regulate cochlear hair cell maturation, researchers led by Walter Marcotti from the University of Sheffield have investigated the role of a molecule named miR-96. The molecule miR-96 is a microRNA, a short genetic sequence that regulates the expression of a range of genes, and is itself highly expressed in developing cochlear hair cells.

Mice that do not express miR-96, referred to as ‘knockouts’, were compared with control mice that do express miR-96. To examine differences in structure, hair cells from the two groups of mice were observed under a microscope and measurements were taken of both cell length and sensitivity to a neurotransmitter. By placing a speaker 20cm directly in front of each mouse and recording a ‘Preyer reflex’, whereby a mouse flicks its ear in the direction of sound, the researchers also measured auditory brainstem responses, which reflect the activity of the hair cell.

The researchers found that the cochlear hair cells of the mice that do not express miR-96 were thinner, shorter in length and more immature when compared to hair cells of control mice, identifying a role for miR-96 in the maturation of cochlear hair cells. To investigate the activity of the hair cells by measuring the auditory brainstem responses, the knockout mice could not be used since they have no auditory response at all. Instead, mice with limited miR-96 expression were compared with control mice and were found to be less responsive, indicating a defect in their hearing due to the limited miR-96 expression.

Measurements were also recorded to examine the sensitivity of hair cells to a neurotransmitter called acetylcholine. Acetylcholine is a molecule released from nerve endings and can act upon cochlear hair cells to initiate the conversion of an auditory response into an electrical nerve signal. Sensitivity to acetylcholine was reduced in knockout mice whilst control mice responded as usual, implicating miR-96 in hair cell activity.

These results indicate that in the maturation of cochlear hair cells, which is vital for the fundamentals of hearing, miR-96 plays an essential role. By understanding these mechanisms the researchers propose that the research “could provide us with clues to help develop therapies to ameliorate the effects associated with nonsyndromic progressive hearing loss”.

Cochlear hair cells in a Guinea Pig

 References:

Kuhn et al (2011) miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells. Proc Natl Acad Sci USA, 108 (6), 2355-2360.

The paper can be found at:

http://www.pnas.org/content/108/6/2355.full.pdf+html

Vitamin D to treat respiratory diseases?

 

Kathryn Vaughan

Research from a team in Australia has made a new link between Vitamin D and lung disease.

A deficiency in vitamin D is associated with many diseases, including rickets, but it has also been implicated in the pathogenesis of chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), whereby it has been suggested that vitamin D deficiency reduces lung function.

Vitamin D is mainly involved in calcium homeostasis (the concentration of calcium in the bloodstream). This is why deficiencies in vitamin D are commonly associated with bone disorders.

It has been suggested that a vitamin D deficiency can reduce lung function, thus associating the vitamin deficiency with respiratory diseases. Dr Graeme Zosky, a senior lecturer in Child Health Research, headed a research group from Western Australia, to determine what effect, if any, a deficiency of vitamin D has on the lung.

A vitamin D deficient mouse model, developed by modification of their diet, was used and compared with mice that were not deficient in vitamin D, i.e. wild-type control mice. Measurements in lung volume, lung structure and lung function were assessed to determine if there were any differences relating to vitamin D deficiency.

Differences were found in both the lung size and lung volume of the mice. Vitamin D deficient mice had substantially reduced lung size compared to controls, suggesting altered lung growth, and this correlated with reductions in the thoracic gas volume measurement. In relation to the reduction in lung volume the mechanics of the lung were also affected in vitamin D deficient mice.

The researchers conclude from this investigation that “vitamin D deficiency causes deficits in lung function which are primarily explained by differences in lung volume” and “may explain the association between obstructive lung disease and vitamin D status”.  The results therefore may have important implications for the prevention/treatment of respiratory diseases in those with vitamin D deficiencies.

 

Zosky et al (2011) Vitamin D deficiency causes deficits in lung function and alters lung structure. American Journal of Respiratory and Critical Care Medicine, ahead of print.

The paper can be found at:

http://ajrccm.atsjournals.org/cgi/reprint/201010-1596OCv1?maxtoshow=&hits=10&RESULTFORMAT=&author1=zosky&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

Spaghetti provides inspiration for a new treatment for spinal cord injury

Matt Farley

Researchers at the University of Milan-Biccoca in Italy have developed a new method to repair damaged spinal cords, after being inspired by spaghetti. Named the ‘bucatini project’ after the hollow pasta of the same name, the results suggest that the technique may be used in the future to treat people with paraplegia.

One of the major hindrances in the healing of damaged spinal cords is the formation of fluid-filled cysts, which impair the development of new nerve and blood cells at the site of the injury. Fabrizio Gelain is just one of many researchers around the world investigating ways to ‘bridge’ over these cysts.

Gelain’s team developed small hollow tubes made from biodegradable plastics which were around 3 millimetres long and could be implanted into areas of damage. The tubes were coated in small peptides, which anchored new cells around the tubes – effectively making them more ‘sticky’ and able to grab onto any new cells. “These tubes provide the reference points for the cells, and tissue starts to build up” says Gelain’s colleague, Angelo Vescovi.

Bundles of these tubes were implanted directly into the cysts of rats which had damaged spinal cords, paralysing their hind legs. A gel containing natural growth factors to stimulate nerve cell growth was also added.

After six months, new nerve cells and blood vessels were seen to have grown all the way across the treated areas, along with other types of ‘supporting cells’ which are vital for maintenance of the nerve fibres. The rats also regained some mobility in their hind legs, which was not seen in the untreated control rats.

What is unsure is whether the new nerve cells are successfully growing into the spinal column at the other end of the cyst, which is required for significant regeneration of the spinal column. Gelain intends to carry out further experiments to determine whether the new cells are making all the necessary connections.

The paper that accompanied this research is available online:

Gelain, F et al. 2011. Transplantation of Nanostructured Composite Scaffolds Results in the Regeneration of Chronically Injured Spinal Cords. ACS Nano 5, pp227-236

Fluorescent probes make nerves glow during surgery

 

Claire Tree-Booker

Scientists at the San Diego School of Medicine, University of California have developed fluorescent protein fragments, also known as peptides, which specifically label nerves. It is hoped this new technology will help surgeons avoid damaging nerves during surgery.

Accidental damage to nerves during surgery can cause many problems including pain, numbness and even paralysis.

The scientists report, in the 6 February 2011 edition of Nature Biotechnology, that when the fluorescent peptides were injected into mice, nerves were labelled within two hours; this created a ten-fold contrast compared to other body tissues, allowing the nerves to be easily seen.

The fluorescent labelling was found to have no effect on the activity of the nerves or the animals’ behaviour.

Whilst surgeons can identify nerves by their appearance or by electrical stimulation, they can sometimes be missed if they are buried or have a different appearance.  Dr Quyen T. Nguyen, carrying out the study, said “if surgery is required in the setting of trauma or infection, the affected nerves might not look as they normally would, or their location may be distorted”.

 “We have yet to test the peptide in patients, but we have shown that the fluorescent probe also labels nerves in human tissue samples”, says Nguyen.

Damaged nerves were also fluorescently labelled, suggesting that this technique could be useful in nerve repair surgery in the future.

The paper can be found at http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.1764.html

Social media: students go cold turkey

Michaela Livingstone

200 students from the University of Maryland have kicked off a global study looking at young adult’s use of media, finding that the students actually experience symptoms akin to drug withdrawal.

The study, called Unplugged, which has also taken place at Bournemouth University, asked its students to go 24 hours without using any form of media: newspapers, televisions, iPods, phones, laptops, Facebook, Twitter or radio, and then blog about it afterwards.

As reported on the Unplugged website, many students reported feelings of loneliness, isolation and even physical symptoms like feeling fidgety.

“I noticed physically, that I began to fidget”, said one student, another reporting that instant messaging and texting their friends was comforting.

Students in the British contingent noted that making any plans was almost impossible without phones and Facebook, as things change within minutes, so making plans the day before was pointless.

The conclusion of the American study states that today’s youths’ use of media has not just changed the way they find and use information, but has also, “…caused them to make different and distinctive social, and arguably moral, decisions”. The study’s conclusions also draw light to the fact that the youth of today are “fickle” and do not care where their information comes from, rather it is the information itself that is coveted the most.

Although only a small and qualitative study that maybe cannot be considered to be truly representative of the teenage and young adult population of the US or the UK, it may well be seen as a worrying sign that our youth are just too dependent on media, and the potential harm this may be having.

The study did however find that the young were capable of developing coping skills during their media abstinence. So maybe it’s not all bad news.

Coffee and cake can be good for you!

 

Maria Panagiotidi

Coffee and cake might be bad for your waistline but not for your brain! At least that is what a recent study published in the journal “Human Psychopharmacology: Clinical and Experimental” suggests.

Caffeine and glucose are part of our everyday life and are known to have stimulant effects. Previous studies have suggested that caffeine can have positive effects on cognitive function when consumed in moderation.  Other studies focused on the effects of glucose have found similar effects. However, only a few researchers so far had looked at the synergistic effect of those two substances on behaviour and cognitive function.

A group from the University of Barcelona have now done a novel study to investigate whether the consumption of caffeine and glucose, alone and combined, has any effect on cognitive performance. They tested their hypothesis by asking seventy-two healthy subjects to perform a variety of tasks after being administered either doses of water, water with caffeine, water with glucose, or water with both caffeine and glucose. The tests examined a number of functions like attention, memory, fine motor skills, and reaction time.

The most robust effects were observed in the group that consumed caffeine and glucose. More specifically, these participants performed better on tasks requiring attention, learning and verbal memory. The consumption of caffeine alone also lead to improvements in simple reaction time tasks. Similarly, glucose was associated with improved performance on reaction time and fine motor skills task.

 

Adan, A. and Serra-Grabulosa, J. M. (2010). Effects of caffeine and glucose, alone and combined, on cognitive performance. Hum. Psychopharmacol. Clin. Exp., 25(4):310-317. http://onlinelibrary.wiley.com/doi/10.1002/hup.1115/abstract