Posts Tagged ‘medicine’

UK scientists believe they may have found a way to combat the common cold.

Rather than attacking the virus itself, which comes in hundreds of versions, the treatment targets the human host.

It blocks a key protein in the body’s cells that cold viruses normally hijack to self-replicate and spread.

This should stop any cold virus in its tracks if given early enough, lab studies suggest. Safety trials in people could start within two years.

The Imperial College London researchers are working on making a form of the drug that can be inhaled, to reduce the chance of side-effects.

In the lab, it worked within minutes of being applied to human lung cells, targeting a human protein called NMT, Nature Chemistry journal reports.

All strains of cold virus need this human protein to make new copies of themselves.

Researcher Prof Ed Tate said: “The idea is that we could give it to someone when they first become infected and it would stop the virus being able to replicate and spread.

“Even if the cold has taken hold, it still might help lessen the symptoms.

“This could be really helpful for people with health conditions like asthma, who can get quite ill when they catch a cold.”

He said targeting the host rather than the infection was “a bit radical” but made sense because the viral target was such a tricky one.

Cold viruses are not only plentiful and diverse, they also evolve rapidly, meaning they can quickly develop resistance to drugs.

The test drug completely blocked several strains of cold virus without appearing to harm the human cells in the lab. Further studies are needed to make sure it is not toxic in the body though.

Dr Peter Barlow of the British Society for Immunology said: “While this study was conducted entirely in vitro – using cells to model Rhinovirus infection in the laboratory – it shows great promise in terms of eventually developing a drug treatment to combat the effects of this virus in patients.”

Fighting a cold
Colds spread very easily from person to person. And the viruses that cause the infections can live on hands and surfaces for 24 hours.

Painkillers and cold remedies might help ease the symptoms. But currently there is nothing that will halt the infection.

You can catch a cold by:

– inhaling tiny droplets of fluid that contain the cold virus – these are launched into the air when an infected person coughs or sneezes
– touching an object or surface contaminated by infected droplets and then touching your mouth, nose or eyes
– touching the skin of someone who has the infected droplets on their skin and then touching your mouth, nose or eyes

Symptoms – a runny or blocked nose, sneezing and sore throat – usually come on quickly and peak after a couple of days. Most people will feel better after a week or so. But a mild cough can persist for a few weeks.

http://www.bbc.com/news/health-44107481

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Immunofluorescence of β-catenin protein (red) and cell nuclei (blue) in the human hair follicle bulb, the command center for maintaining hair growth.

A new drug could ease the distress of men and women who suffer from baldness, according to researchers from The University of Manchester’s Centre for Dermatology Research.

The study from the laboratory of Prof Ralf Paus, is published last week in the open access journal PLOS Biology

It shows that a drug originally designed as a treatment for osteoporosis has a dramatic stimulatory effect on human hair follicles donated by patients undergoing hair transplantation surgery.

Currently only two drugs – minoxidil and finasteride – are available for treatment of male-pattern balding (androgenetic alopecia).

However, both agents have moderate side effects and often produce disappointing hair regrowth results. The only other option available to patients is hair transplantation surgery.

The PhD project, led by Dr Nathan Hawkshaw and colleagues, sought to develop new ways to promote human hair growth with the hope of finding novel, well-tolerated agents for treating androgenetic alopecia.

The approach was to first identify the molecular mechanisms of an old immunosuppressive drug, Cyclosporine A (CsA).

Cyclosporine A has been commonly used since the 1980s as a crucial drug that suppresses transplant rejection and autoimmune diseases.

However, it often has severe side-effects, the least serious – but most interesting – of which is that it enhances cosmetically unwanted hair growth.

The team carried out a full gene expression analysis of isolated human scalp hair follicles treated with CsA. This revealed that CsA reduces the expression of SFRP1, a protein that inhibits the development and growth of many tissues, including hair follicles.

This identifies a completely novel mechanism of action of this old and widely used immunosuppressant.

The research also explanains why CsA so often induces undesired hair growth in patients as it removes an inbuilt and potent molecular brake on human hair growth.

The inhibitory mechanism is completely unrelated to CsA’s immunosuppressive activities, making SFRP1 a new and highly promising therapeutic target for anti-hair loss strategies.

After some detective work, Dr Hawkshaw found that a compound originally developed to treat osteoporosis, called WAY-316606, targets the same mechanism as CsA by specifically antagonising SFRP1.

When he then treated hair follicles with WAY-316606, the unrelated agent also effectively enhanced human hair growth like CsA.

The external application of WAY-316606 or similar compounds to balding human scalp, he argued, may promote hair growth to the same magnitude as CsA or even better, but without its side effects.

“The fact this new agent, which had never even been considered in a hair loss context, promotes human hair growth is exciting because of its translational potential: it could one day make a real difference to people who suffer from hair loss
Dr Nathan Hawkshaw

Dr Hawkshaw said: “Thanks to our collaboration with a local hair transplant surgeon, Dr Asim Shahmalak, we were able to conduct our experiments with scalp hair follicles that had generously been donated by over 40 patients and were then tested in organ cultures.

“This makes our research clinically very relevant, as many hair research studies only use cell culture.”

He added: “When the hair growth-promoting effects of CsA were previously studied in mice, a very different molecular mechanism of action was suggested; had we relied on these mouse research concepts, we would have been barking up the wrong tree.

“The fact this new agent, which had never even been considered in a hair loss context, promotes human hair growth is exciting because of its translational potential: it could one day make a real difference to people who suffer from hair loss.

“Clearly though, a clinical trial is required next to tell us whether this drug or similar compounds are both effective and safe in hair loss patients.”

http://www.manchester.ac.uk/discover/news/fringe-benefits-drug-side-effects-could-treat-human-hair-loss/


The Dr. Peter Stys lab within the Hotchkiss Brain Institute at the Cumming School of Medicine, University of Calgary, is equipped with highly specialized microscopes used for researching multiple sclerosis, Alzheimer’s and other neurodegenerative disease. In this customized lab, the researchers can’t wear white lab coats, they have to wear dark clothing. Photons could reflect off light clothing and interfere with the experiments. From left: Megan Morgan, research assistant, and Craig Brideau, engineering scientist. Photo by Pauline Zulueta, Cumming School of Medicine

By Kelly Johnston, Cumming School of Medicine

Ridiculous. That’s how Andrew Caprariello says his colleagues described his theory about multiple sclerosis (MS) back when he was doing his PhD in Ohio.

Caprariello’s passion to explore controversial new theories about MS propelled him to seek out a postdoctoral fellowship with a like-minded thinker, whom he found in University of Calgary’s Dr. Peter Stys, a member of the Hotchkiss Brain Institute at the Cumming School of Medicine (CSM).

The collaboration paid off. Caprariello, Stys and their colleagues have scientific proof published in the Proceedings of the National Academy of Sciences (PNAS) that their somewhat radical theory has merit. “I’ve always wondered ‘what if’ MS starts in the brain and the immune attacks are a consequence of the brain damage,” says Caprariello, PhD, and lead author on the study.

Currently, MS is considered to be a progressive autoimmune disease. Brain inflammation happens when the body’s immune system attacks a protective material around nerve fibers in the brain called myelin. Conventional thinking is that rogue immune cells initially enter the brain and cause myelin damage that starts MS.

“In the field, the controversy about what starts MS has been brewing for more than a decade. In medical school, I was taught years ago that the immune attack initiates the disease. End of story,” says Stys, a neurologist and professor in the Department of Clinical Neurosciences at the CSM. “However, our findings show there may be something happening deeper and earlier that damages the myelin and then later triggers the immune attacks.”

To test the theory, the research team designed a mouse model of MS that begins with a mild myelin injury. In this way, researchers could mirror what they believe to be the earliest stages of the disease.

“Our experiments show, at least in this animal model, that a subtle early biochemical injury to myelin secondarily triggers an immune response that leads to additional damage due to inflammation. It looks very much like an MS plaque on MRI and tissue examination,” says Stys. “This does not prove that human MS advances in the same way, but provides compelling evidence that MS could also begin this way.”

With that result, the researchers started to investigate treatments to stop the degeneration of the myelin to see if that could reduce, or stop, the secondary autoimmune response.

“We collaborated with researchers at the University of Toronto and found that by targeting a treatment that would protect the myelin to stop the deterioration, the immune attack stopped and the inflammation in the brain never occurred,” says Stys. “This research opens a whole new line of thinking about this disease. Most of the science and treatment for MS has been targeted at the immune system, and while anti-inflammatory medications can be very effective, they have very limited benefit in the later progressive stages of the disease when most disability happens.”

It can be very hard to find funding to investigate an unconventional theory. The research team was funded by the Brain and Mental Health Strategic Research Fund, established by the Office of the Vice-President (Research) at UCalgary to support innovative, interdisciplinary studies within the Brain and Mental Health research strategy.

“We chose high-risk, novel projects for these funds to support discoveries by teams who did not have the chance to work together through conventional funding sources,” said Ed McCauley, PhD, vice-president (research). “The MS study shows the potential of brain and mental health scholars to expand capacity by tapping into new approaches for conducting research. Their work also exemplifies the type of interdisciplinary research that is propelling the University of Calgary as an international leader in brain and mental health research.”

http://www.ucalgary.ca/utoday/issue/2018-05-04/ucalgary-scientists-discover-new-way-battle-multiple-sclerosis

In a new study researchers from the Institute for Experimental Pediatric Endocrinology of the Charité – Universitätsmedizin Berlin have successfully treat patients whose obesity is caused by a genetic defect. Aside from its beneficial effects on the patients, the researchers also provided insights into the fundamental signaling pathways regulating satiety of the new drug. The results of this research have been published in Nature Medicine*.

A mutation in the gene encoding the leptin receptor (LEPR) can cause extreme hunger starting with the first months of life. As a result, affected individuals develop extreme obesity during childhood. Increased exercise and reduced caloric intake are usually insufficient to stabilize body-weight. In many cases, obesity surgery fails to deliver any benefits, meaning that a drug-based treatment approach becomes increasingly important.

Two years ago, Dr. Peter Kühnen and the working group successfully demonstrated that treatment with a peptide, which activates the melanocortin 4 receptor (MC4R) could play a central role in the body’s energy metabolism and body weight regulation. Leptin, which is also known as the satiety (or starvation) hormone, normally binds to the LEPR, triggering a series of steps that leads to the production of melanocyte-stimulating hormone (MSH). The act of MSH by binding to its receptor, the melanocortin 4 receptor (MC4R) which transduce the satiety signal to the body. However, if the LEPR is defective, the signaling cascade is interrupted. The patient’s hunger remains unabated, placing them at greater risk of becoming obese. As part of this current study, researchers used a peptide that binds to the MC4R in the brain, and this activation trigger the normal satiety signal. Working in cooperation with the Clinical Research Unit at the Berlin Institute of Health (BIH), the researchers were able to record significant weight loss in patients with genetic defects affecting the LEPR.

“We also wanted to determine why the used peptide was so effective and why, in contrast to other preparations with a similar mode of action, it did not produce any severe side effects,” explains Dr. Kühnen. “We were able to demonstrate that this treatment leads to the activation of a specific and important signaling pathway, whose significance had previously been underestimated.” Dr. Kühnen’s team is planning to conduct further research to determine whether other patients might benefit from this drug: “It is possible that other groups of patients with dysfunctions affecting the same signaling pathway might be suitable candidates for this treatment.”

*Clément K, et al., MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency, Nature Medicine (2018), doi:10.1038/s41591-018-0015-9.

https://www.charite.de/en/service/press_reports/artikel/detail/den_unstillbaren_hunger_abschalten/

It’s well known that exposure to extremely loud noises — whether it’s an explosion, a firecracker or even a concert — can lead to permanent hearing loss.
But knowing how to treat noise-induced hearing loss, which affects about 15 percent of Americans, has largely remained a mystery. That may eventually change, thanks to new research from the Keck School of Medicine of USC, which sheds light on how noise-induced hearing loss happens and shows how a simple injection of a salt- or sugar-based solution into the middle ear may preserve hearing. The results of the study were published today in PNAS.

Deafening sound
To develop a treatment for noise-induced hearing loss, the researchers first had to understand its mechanisms. They built a tool using novel miniature optics to image inside the cochlea, the hearing portion of the inner ear, and exposed mice to a loud noise similar to that of a roadside bomb.

They discovered that two things happen after exposure to a loud noise: sensory hair cells, which are the cells that detect sound and convert it to neural signals, die, and the inner ear fills with excess fluid, leading to the death of neurons.

“That buildup of fluid pressure in the inner ear is something you might notice if you go to a loud concert,” says the study’s corresponding author John Oghalai, MD, chair and professor of the USC Tina and Rick Caruso Department of Otolaryngology – Head and Neck Surgery and holder of the Leon J. Tiber and David S. Alpert Chair in Medicine. “When you leave the concert, your ears might feel full and you might have ringing in your ears. We were able to see that this buildup of fluid correlates with neuron loss.”

Both neurons and sensory hair cells play critical roles in hearing.

“The death of sensory hair cells leads to hearing loss. But even if some sensory hair cells remain and still work, if they’re not connected to a neuron, then the brain won’t hear the sound,” Oghalai says.

The researchers found that sensory hair cell death occurred immediately after exposure to loud noise and was irreversible. Neuron damage, however, had a delayed onset, opening a window of opportunity for treatment.

A simple solution

The buildup of fluid in the inner ear occurred over a period of a few hours after loud noise exposure and contained high concentrations of potassium. To reverse the effects of the potassium and reduce the fluid buildup, salt- and sugar-based solutions were injected into the middle ear, just through the eardrum, three hours after noise exposure. The researchers found that treatment with these solutions prevented 45–64 percent of neuron loss, suggesting that the treatment may offer a way to preserve hearing function.

The treatment could have several potential applications, Oghalai explains.

“I can envision soldiers carrying a small bottle of this solution with them and using it to prevent hearing damage after exposure to blast pressure from a roadside bomb,” he says. “It might also have potential as a treatment for other diseases of the inner ear that are associated with fluid buildup, such as Meniere’s disease.”

Oghalai and his team plan to conduct further research on the exact sequence of steps between fluid buildup in the inner ear and neuron death, followed by clinical trials of their potential treatment for noise-induced hearing loss.

https://www.keckmedicine.org/a-simple-treatment-may-minimize-hearing-loss-triggered-by-loud-noises/

High school football player in for the touchdown.; Shutterstock ID 408266332; Purchase Order: –

Researchers reported on Monday in the journal JAMA Neurology that dementia was a possible complication following concussion even if the patient did not lose consciousness.

Scientists from the University of California, San Francisco (UCSF) tracked more than one-third of a million American veterans, and found that the likelihood of dementia more than doubled following concussion.

After adjusting for age, sex, race, education and other health conditions, they found that concussion without loss of consciousness led to 2.36 times the risk for dementia.

According to the study, these risks were slightly elevated for those in the loss-of-consciousness bracket (2.51 times) and were nearly four times higher (3.77 times) for those with the more serious moderate-to-severe traumatic brain injury.

In the total of 357,558 participants, whose average age was 49, half had been diagnosed with traumatic brain injury, of which 54 percent had concussion. The study followed participants for an average of 4.2 years, and 91 percent were male and 72 percent were white.

“There are several mechanisms that may explain the association between traumatic brain injury and dementia,” said the study’s senior author Kristine Yaffe, professor with the UCSF departments of neurology, psychiatry, and epidemiology and biostatistics.

“There’s something about trauma that may hasten the development of neurodegenerative conditions. One theory is that brain injury induces or accelerates the accumulation of abnormal proteins that lead to neuronal death associated with conditions like Alzheimer’s disease,” said Yaffe.

“It’s also possible that trauma leaves the brain more vulnerable to other injuries or aging processes,” said Yaffe, “but we need more work in this area.”

http://www.xinhuanet.com/english/2018-05/08/c_137162226.htm

A study by scientists of the German Center for Neurodegenerative Diseases (DZNE) points to a novel potential approach against Alzheimer’s disease. In studies in mice, the researchers were able to show that blocking a particular receptor located on astrocytes normalized brain function and improved memory performance. Astrocytes are star-shaped, non-neuronal cells involved in the regulation of brain activity and blood flow. The findings are published in the Journal of Experimental Medicine (JEM).

Alzheimer’s disease is a common and currently incurable brain disorder leading to dementia, whose mechanisms remain incompletely understood. The disease appears to be sustained by a combination of factors that include pathological changes in blood flow, neuroinflammation and detrimental changes in brain cell activity.

“The brain contains different types of cells including neurons and astrocytes”, explains Dr. Nicole Reichenbach, a postdoc researcher at the DZNE and first author of the paper published in JEM. “Astrocytes support brain function and shape the communication between neurons, called synaptic transmission, by releasing a variety of messenger proteins. They also provide metabolic and structural support and contribute to the regulation of blood flow in the brain.”

Glitches in network activity

Similar to neurons, astrocytes are organized into functional networks that may involve thousands of cells. “For normal brain function, it is crucial that networks of brain cells coordinate their firing rates. It’s like in a symphony orchestra where the instruments have to be correctly tuned and the musicians have to stay in synchrony in order to play the right melody”, says Professor Gabor Petzold, a research group leader at the DZNE and supervisor of the current study. “Interestingly, one of the main jobs of astrocytes is very similar to this: to keep neurons healthy and to help maintain neuronal network function. However, in Alzheimer’s disease, there is aberrant activity of these networks. Many cells are hyperactive, including neurons and astrocytes. Hence, understanding the role of astrocytes, and targeting such network dysfunctions, holds a strong potential for treating Alzheimer’s.”

Astrocyte-targeted treatment alleviated memory impairment

Petzold and colleagues tested this approach in an experimental study involving mice. Due to a genetic disposition, these rodents exhibited certain symptoms of Alzheimer’s similar to those that manifest in humans with the disease. In the brain, this included pathological deposits of proteins known as “Amyloid-beta plaques” and aberrant network activity. In addition, the mice showed impaired learning ability and memory.

In their study, the DZNE scientists targeted a cell membrane receptor called P2Y1R, which is predominately expressed by astrocytes. Previous experiments by Petzold and colleagues had revealed that activation of this receptor triggers cellular hyperactivity in mouse models of Alzheimer’s. Therefore, the researchers treated groups of mice with different P2Y1R antagonists. These chemical compounds can bind to the receptor, thus switching it off. The treatment lasted for several weeks.

“We found that long-term treatment with these drugs normalized the brain’s network activity. Furthermore, the mice’s learning ability and memory greatly improved”, Petzold says. On the other hand, in a control group of wild type mice this treatment had no significant effect on astrocyte activity. “This indicates that P2Y1R inhibition acts quite specifically. It does not dampen network activity when pathological hyperactivity is absent.”

New approaches for research and therapies?

Petzold summarizes: “This is an experimental study that is currently not directly applicable to human patients. However, our results suggest that astrocytes, as important safeguards of neuronal health and normal network function, may hold the potential for novel treatment options in Alzheimer’s disease.” In future studies, the scientists intend to identify additional novel pathways in astrocytes and other cells as potential drug targets.

Reference:
Reichenbach, N., Delekate, A., Breithausen, B., Keppler, K., Poll, S., Schulte, T., . . . Petzold, G. C. (2018). P2Y1 receptor blockade normalizes network dysfunction and cognition in an Alzheimer’s disease model. The Journal of Experimental Medicine. doi:10.1084/jem.20171487

https://www.dzne.de/en/news/public-relations/press-releases/press/detail/the-brains-rising-stars-new-options-against-alzheimers/