Cold Sore Virus Might Play Role In Alzheimer’s

A gene known to be a major risk factor for Alzheimer’s disease puts out the welcome mat for the virus that causes cold sores, allowing the virus to be more active in the brain compared to other forms of the gene. The new findings, published online in the journal Neurobiology of Aging, add some scientific heft to the idea, long suspected by some scientists, that herpes somehow plays a role in bringing about Alzheimer’s disease.

The work links a form of the ApoE gene known as ApoE-4, which after advanced age is the leading known risk factor for getting Alzheimer’s disease, with the form of herpes – herpes simplex 1 or HSV – that infects more than 80 percent of Americans and causes cold sores around the mouth. The findings from a group at the University of Rochester Medical Center show that the particular form of the gene that puts people at risk also creates a fertile environment for herpes in the brain, allowing the virus to be more active than other forms of the ApoE gene permit.

Scientists have known for more than 15 years that the ApoE-4 gene is a player in Alzheimer’s disease, but the idea that it works in concert with the herpes virus is new.

“This work raises the question whether herpes in concert with ApoE-4 increases the risk of Alzheimer’s disease. The data suggests that ApoE-4 may support the ability of HSV to be a more virulent pathogen,” said Howard Federoff, M.D., Ph.D., the leader of the team and professor of Neurology, Medicine, and Microbiology & Immunology. He worked closely with post-doctoral research associate Renee Miller, Ph.D., on the project.

The findings, which are based on measurements of the activity levels of the herpes virus in the brains of mice with different forms of the human ApoE gene, bring together several lines of research that have pointed toward a possible role for herpes in Alzheimer’s disease.

Ruth Itzhaki of the University of Manchester has led the way with several studies showing a correlation between herpes and Alzheimer’s. She has shown that Alzheimer’s patients who have the ApoE-4 form of the gene have more herpes DNA in the brain regions that are affected by Alzheimer’s, compared to Alzheimer’s patients who also have herpes but who have a different form of the ApoE gene. And she has shown that people with the ApoE-4 version of the gene who are infected with herpes are more likely to get Alzheimer’s disease than people infected with herpes who have a different form of the ApoE gene, or than people who have the ApoE-4 gene but who don’t have herpes.

Other scientists have found that a herpes infection is active more often – causing the tell-tale cold sores around the mouth – in the 25 percent of people who have a copy of the ApoE-4 gene. In other words, people who are frequently troubled by cold sores are more likely to have the gene that makes them more vulnerable to Alzheimer’s disease.

Cold sores that come and go are the outward sign of the two different phases of the virus’s life cycle. Herpes simplex is a chronic infection that lives in a person for a lifetime, periodically flaring up in a “lytic” phase where it causes cell damage, then retreating and seeking safe harbor within the body’s nerves in a “latent” phase. The virus spends most of its time in the latent phase, sequestered in cells, not active and not replicating. But occasionally, when triggered by factors like stress, fatigue, certain foods, or even sunlight, the virus becomes active, traveling from its hiding places in the nervous system to cells around the mouth, damaging cells and causing cold sores.

It was this cycle of activity and latency that Miller and Federoff focused on while looking at the brain cells of mice with different forms of the ApoE gene. They looked at four groups of mice: Some had ApoE-3, which is what the majority of people carry; some had ApoE-4, which in people makes them more likely to get Alzheimer’s; some had ApoE-2, which makes people less likely to get the disease; and some had no ApoE gene at all.

The team found that the virus infiltrates brain cells about the same no matter which gene is involved. But they found that the subsequent activity level of the virus generally mirrored the disease-causing potential of the gene. They found that in animals with the ApoE-4 gene, the virus is less likely to be in the quiet, latent stage of its life cycle, suggesting it has more of an opportunity to replicate. In animals with the ApoE-2 gene, the virus was less active.

The work suggests that ApoE-4 may alter the balance between the HSV life cycle forms. It’s possible that the ApoE gene works as a sort of bodyguard that tries to keep cells safe from herpes, perhaps by facilitating latency. Somehow the ApoE-2 version is extremely effective at keeping the virus at bay, while in this study, the ApoE-4 version wasn’t any more effective than not having an ApoE gene at all.

The ApoE gene is well known to Alzheimer’s researchers. The gene, which normally plays a role in ferrying cholesterol around the body, is associated with both the cellular tangles and amyloid plaques that are found in the brains of patients with the disease. Researchers have found several ways in which the gene might make a person vulnerable to getting a disease like Alzheimer’s. In people with the ApoE-4 gene, brain cells don’t seem to recover as well from injury, and the cells don’t form new connections as well as cells equipped with either ApoE-2 or ApoE-3. Other scientists have shown that the gene plays a role in clearing toxic amyloid beta from the brain.

“Just how ApoE-4 makes people vulnerable to Alzheimer’s disease isn’t resolved at all,” said Federoff, who is director of the University’s Center for Aging and Developmental Biology. “It may be that it works in multiple ways.”

The team is exploring different ways that herpes might affect the development of Alzheimer’s disease. In one study the team looking at the role of Nectin-1, a cell adhesion molecule that herpes uses as one route to infect a cell. Nectin-1 plays a crucial role in forming synapses, the structures between brain cells that move information and signals from one cell to the next. The team is studying whether herpes somehow disturbs the receptor, possibly altering the structure and function of the synapse. Damage to synapses is one of the earliest signs of Alzheimer’s disease.

Another possibility is that the body’s immune response against herpes somehow damages the brain, and that such damage is worse in people with the ApoE-4 copy of the gene. Earlier this year Federoff’s team published a study that showed inflammation is the earliest change that could be detected in a brain affected by Alzheimer’s disease, before any of the hallmark plaques or tangles and certainly long before any behavioral changes are seen. Such inflammation often is a byproduct when the immune system fights an infection.

Contact: Tom Rickey

University of Rochester Medical Center

Chernobyl: 25 Years Later, Mikhail Gorbachev Co-Writes

Twenty-five years after the worst civilian nuclear disaster in history, what have we learned? In the latest issue of Bulletin of the Atomic Scientists, published today by SAGE, highly influential writers debate the legacy of Chernobyl and the lessons learned. The writers, including Mikhail Gorbachev, former President of the Soviet Union, examine the need for prevention of further accidents and the future of nuclear power.

In their article, If the unlikely becomes likely: Medical response to nuclear accidents, Robert Peter Gale and Alexandr Baranov, who were members of the US-Soviet medical team that responded to Chernobyl, look at how public concern is increasing regarding the health consequences of radiation exposure – shaped largely by the potential use of nuclear weapons, improvised nuclear devices, or stolen conventional radiation sources by rogue states and terrorist groups. The authors write about their experience treating the Chernobyl victims – and what lessons can be applied to future government strategies.
The authors write:

“The US has the medical capacity to respond to a nuclear event like Chernobyl, but even an adequate medical response to a catastrophic nuclear event would be impossible. Dealing effectively with a nuclear disaster requires diverse strategies, including policy decisions, public education, and, as a last resort, medical preparedness and interventions.”

The article When safe enough is not good enough: Organizing safety at Chernobyl by Sonja D. Schmid highlights the organizational structure of the nuclear industry in the Soviet Union at the time of the Chernobyl disaster. Schmid reviews initial reports that accused operators of violating instructions, but also looks at evidence that surfaced in the early 1990s, which suggested that the reactor design, combined with a lack of information sharing, were to blame for the explosion.
Schmid says:

“Chernobyl was not a disaster waiting to happen, but occurred despite ongoing efforts to improve technical design, operator training, and inter-organizational communication.”

Schmid reminds us that our best efforts at ensuring nuclear safety may therefore not be good enough.

In his essay titled Chernobyl 25 Years Later: Many Lessons Learned Gorbachev reflects on the Chernobyl disaster and writes how, two and a half decades later, the nuclear accident offers many lessons for preventing, managing, and recovering from such a horrible event – he also writes about key issues that must be addressed for the further development of nuclear power.

The issue also includes an interview with Olli Heinonen, deputy director and senior inspector of the International Atomic Energy Agency (IAEA) who discusses the possibility that a nuclear weapon will be used in the next 10 years.

The March/April issue of the Bulletin of the Atomic Scientists is published today (March 1, 2011). Selected content will be freely available for a limited period from:
“Bulletin of the Atomic Scientists”

Source: Sage Publications

Some Kids Suffering Vocal Cord Dysfunction Are Misdiagnosed With Asthma

Vocal cord dysfunction (VCD) is the sudden, abnormal narrowing of the vocal cords during inhalation causing obstruction of the airflow, and is characterized by a noise that can mimic the sound of wheezing. A VCD attack can easily be mistaken for an asthma attack though it does not respond to asthma medications.

Treatment of VCD relies on correct identification of the disorder using breathing and relaxation techniques to help the vocal cords relax. During an acute VCD attack, spirometry (a device that measures airflows) can show patterns that are highly suggestive of VCD.

Doctors at Columbus Children’s Hospital performed a clinical research study using spirometry in Children’s Emergency Department to try to identify adolescents who had findings suggestive of VCD compared to an acute asthma attack. The year-long study (February 2005-February 2006) included patients 12-21-years-old who suffered from acute episodes of respiratory distress. The manuscript was published in the July issue of Pediatric Pulmonology.

“Both asthma and VCD are very common, and emergency departments across the country are seeing more and more kids with these kinds of symptoms,” said Karen McCoy, MD, chief of Pulmonology at Columbus Children’s Hospital and a faculty member at The Ohio State University College of Medicine. “While they may appear similar to parents, the conditions act differently and must be treated differently. It is important that parents, coaches and family doctors are aware of the differences.”

According to the study, 12 of the 17 adolescents who presented to the Emergency Department with difficulty breathing, but with high normal oxygen levels, were found to have evidence of VCD on spirometry. This led to a change in the therapy for these patients. Spirometry used in the acute setting of difficulty breathing can help differentiate VCD from asthma attacks.

“Our study suggests that if more emergency departments made use of the spirometry test, it could cut down on the number of kids who are misdiagnosed and potentially hospitalized,” said Muffy Chrysler BS, RRT, NPS, AE, a co-author on the study and an asthma coordinator in Respiratory Care at Columbus Children’s Hospital.

Paul Nolan, MD, FAAP, the study’s lead author, was a fellow at Columbus Children’s Hospital while working on this manuscript. Nolan, a pediatric pulmonologist, is now with Texas Tech University Health Sciences Center and is a faculty member in the Department of Pediatrics at Texas Tech.

Source: Marti Leitch

Columbus Children’s Hospital

Researchers Explore Novel Protein As Potential Target In Alzheimer’s Treatment

A South Dakota State University researcher and his colleagues elsewhere have discovered a previously unreported mitochondrial protein that interacts with a protein known to play a role in Alzheimer’s disease.

The discovery adds to what is known about the memory-inhibiting disease as researchers continue to search for ways to treat it.

The research is reported in June 2010 in the European Journal of Neuroscience, Vol. 31. Assistant professor Hemachand Tummala in SDSU’s Department of Pharmaceutical Sciences is the lead author of the journal article, which builds on work he carried out while at the University of Memphis. His co-authors are Xiaofan Li of the Mayo School of Graduate Medical Education and the University of Tennessee Health Science Center; and Ramin Homayouni of the University of Memphis and the University of Tennessee Health Science Center.

Alzheimer’s disease affected 5.5 million Americans in 2009 alone. With a rapidly aging baby boomer population, this number is predicted to reach 16 million by 2050. Besides patient distress, Alzheimer’s disease also inflicts health care costs to society of $172 billion annually. Currently, Alzheimer’s disease has no cure.

“In Alzheimer’s disease, there is a protein involved called APP, Amyloid precursor protein. If this protein is mutated, it causes early onset Alzheimer’s disease. We don’t know exactly what this protein does,” Tummala said. “One thing is very well documented in Alzheimer’s disease, mitochondria in a cell are damaged. They lose their function. This happens long before the appearance of symptoms. So there is a theory that mitochondria play a big role in the disease progression.”

Mitochondria are membrane-enclosed structures in cells that generate the cell’s supply of energy and are involved in processes such as signaling, cell death, cell growth, and possibly aging.

Neurons are special cells in the brain that help the body to carry out functions associated with hearing, seeing, moving, remembering information and learning new things. In Alzheimer’s disease neurons that function in learning and memory die. That’s why Alzheimer’s disease symptoms include memory loss and the other behavioral cognitive problems.

Tummala said he and his colleagues’ important finding shows that APP binds to the mitochondrial protein, NIPSNAP1. NIPSNAP1 is specifically seen in neurons, and it may have a role in neuronal death in Alzheimer’s disease. “Taken together, our data suggest that APP directly interacts with the neuron-speci?¬?c mitochondrial protein NIPSNAP1 and may thereby regulate mitochondrial function in neurons,” the scientists note in their journal article.

Tummala said his next step, working with his University of Memphis colleague, Dr. Ramin Homayouni, will be a closer examination of NIPSNAP1 using mouse models. Tummala already has won a grant of $96,926 through South Dakota’s 2010 Competitive Research Grant Program, accompanied by an SDSU match of $98,978. The grant will help fund his work learning more about the protein as a potential drug target for treating Alzheimer’s disease.

“This is still at the preliminary stages. If everything goes well, if we establish the link, this may in the future become a new therapeutic target,” Tummala said. “Our hypothesis is that mitochondria are damaged long before the appearance of symptoms. If you could stop that mitochondrial damage, it may slow down neuronal death and halt the disease progression. But that would be far in the future, not now.”


South Dakota State University

Red Cross Opens Safe And Well Website For California Earthquake

Residents in California affected by today’s earthquake are urged to register themselves and their loved ones on the Safe and Well website, to let family and friends around the country know of their status. Safe and Well is an easy way to assist people seeking to locate those who’ve registered their status during this emergency. Letting your family know that you are safe during an emergency can bring great peace of mind.

“At the American Red Cross we want to make difficult situations like this a little bit easier by giving families and friends a resource to get this important information,” said Joe Becker, Senior Vice President, Disaster Services. “Knowing that those we care about are safe is a relief that allows people to focus on what to do next.”

The Safe and Well website is easy to use:

- Visit redcross, and click on the Safe and Well link

- If you are currently affected by the earthquakes, click: “List Myself as Safe and Well”, enter your pre-disaster address and phone number, and select any of the standard message options

- If you are concerned about a loved one, click “Search” and enter the person’s name and pre-disaster phone number OR address. If they have registered, you will be able to view the messages that they posted.

- If you don’t have internet access, you can call 1-800-RED-CROSS (1-800-733-2767) to register yourself and your family. Follow the prompts for disaster information.

Please note that the Safe and Well site safeguards the privacy of the disaster victim. Although these messages will be viewable by friends or family members who conduct a successful search, the site does not reveal a specific location or contact information. Personal information entered into the Safe and Well Web site will not be sold or shared with other organizations. The Red Cross is a charitable organization – not a government agency – and depends on volunteers and the generosity of the American public to perform its humanitarian mission.

- More information on what to do after an earthquake is available on redcross.

All American Red Cross disaster assistance is free, made possible by voluntary donations of time and money from the American people. You can help the victims of thousands of disasters across the country each year, disasters like earthquakes, by making a financial gift to the American Red Cross Disaster Relief Fund, which enables the Red Cross to provide shelter, food, counseling and other assistance to victims of disaster. The American Red Cross honors donor intent. If you wish to designate your donation to a specific disaster please do so at the time of your donation. Call 1-800-REDCROSS or 1-800-257-7575 (Spanish). Contributions to the Disaster Relief Fund may be sent to your local American Red Cross chapter or to the American Red Cross, P. O. Box 37243, Washington, DC20013. Internet users can make a secure online contribution by visiting redcross.

American Red Cross

Swine Flu Update Issued On Monday 29 June 2009, Wales

– 17 confirmed cases in Wales, with 0 new cases.

– There are 5 clinically presumed cases in Wales including 1 new case:

- An 18-year-old male from Bridgend County Borough directly linked to a confirmed case in Exeter. Close contacts have been identified. He has been offered antiviral medicine and is recovering well.

Up until now, the NPHS has been testing everyone who has potentially come into contact with swine flu and who has symptoms. We are moving to the position where swine flu is circulating so freely in the community that we will test very few people as patient’s doctors will assume that anyone with flu-like symptoms has contracted swine flu. As part of the transition towards this phase, we are now reporting clinically presumed cases. They are household contacts of confirmed cases of swine flu, who have symptoms of swine flu and are presumed to have swine flu but will not be laboratory tested. In such cases, there is enough evidence that the patient has contracted swine flu for their doctor to treat them and testing is unnecessary to reach a diagnosis.

– 193 people have been under investigation in Wales. Of these, swine flu has been confirmed in 17 cases, clinically presumed in 5 cases (see above) and ruled out in 145 cases, leaving 26 still under investigation. All of these are displaying, or have displayed, mild symptoms.

– Of the 26 people under investigation, 7 were well when first identified, but reported recent flu-like symptoms following travel to affected areas. Blood tests are being undertaken on these individuals to see if they had the flu and to help the NPHS understand the pattern of the disease from the past. Their symptoms may or may not have been due to swine flu. Testing will be conducted in a number of weeks to check whether these people did have swine flu – scientifically it won’t work before that. Investigations have shown that people they had close contact with did not catch flu from them when they were ill.

– One person with swine flu has been hospitalised in Wales and has been discharged.

– No further details will be confirmed or denied about cases in order to protect their right to confidentiality.

– There are now 4,328 laboratory confirmed cases in the UK – 17 cases in Wales, 922 cases in Scotland, 3,364 cases in England and 25 in Northern Ireland.

– A second death from swine flu in the UK has been reported. The patient was from Scotland and had serious underlying health conditions. The earlier death was also in Scotland, in a patient with underlying health conditions.

– Swine flu cases have been confirmed in 112 countries. For the latest international figures for the spread of swine flu, visit the website of the World Health Organization at

Comment from Welsh Assembly Government and National Public Health Service for Wales

– Chief Medical Officer for Wales, Dr Tony Jewell, said:

“We have made it clear that there would be cases in Wales and that the number of cases would rise. Therefore everyone must continue to be vigilant and try to reduce the spread of the virus.
“Our advice to the public remains the same, people should follow good respiratory and hand hygiene to help prevent the spread of influenza – always using a tissue to catch sneezes, throwing away used tissues where germs can linger and killing germs by regularly washing your hands, or cleaning them with a sanitising gel. In short, catch it, bin it, kill it.

“So far the virus is generally mild in most people, but proving more severe in a small number of cases, and two people have died in Scotland.

“We have warned that we need to expect that, with large numbers of people contracting swine flu, there will be deaths, particularly in patients with underlying health conditions. Even with the seasonal flu, we do see deaths occurring.

“Although it is natural for people to feel apprehensive, I would like to reassure the public that we have been working to prepare for the arrival of the virus for many years and have robust procedures in place.”

– Dr Roland Salmon, Director of the Communicable Disease Surveillance Centre, National Public Health Service for Wales, said:

“Because this particular type of swine flu is new, people have little or no immunity to it. For this reason, we know it will spread across the country eventually.

“The pandemic will reach different countries at different times. While the outbreak is dying away in Mexico it is still growing here.

“Whereas we are currently investigating and responding to individual cases and prescribing antivirals to all close contacts to prevent the quick spread of the disease, there will come a time when it is sensible to change this approach so that our focus moves to treating people who are ill and preventing illness in people who are most at risk. There will be a greater emphasis on local risk assessments by public health professionals.

“The World Health Organization considers the overall severity of the pandemic to be moderate. This means that most people recover from infection without the need for hospitalisation or medical care. Levels of clinically severe or fatal cases appear similar to levels seen with seasonal influenza.

“Nevertheless, the death of a second patient in Scotland shows we must not be complacent about the effects of the virus in those with pre-existing health conditions.

“Seasonal flu can be severe, particularly for elderly and vulnerable people, so there is still good reason for us all to take action to reduce its effects. Flu is often confused with a bad cold but is in fact far more serious and leads to many deaths each year in Wales.

“We continue to advise that anyone who has flu-like symptoms and has returned from an area where swine flu is circulating, or who has been in close contact with a confirmed case, should stay at home and phone their GP or NHS Direct Wales on 0845 46 47.

“People should not go to Accident and Emergency Departments or to their GP surgery without ringing first, as this may risk spreading the infection. It also places undue pressure on the emergency services.

“The National Public Health Service for Wales will continue to assess any person with flu-like symptoms.”

Public health advice and messages

– If you have flu-like symptoms and have returned from an area where swine flu is circulating or have been in close contact with a confirmed case, stay at home, phone your GP or NHS Direct Wales and you will be assessed and receive treatment if necessary. Do not go into your GP surgery or Accident and Emergency department unless you are advised to do so or are seriously ill, as you may spread the illness to others.

– It is always good practice to follow respiratory and hand hygiene such as:

- Covering your nose and mouth when coughing or sneezing, using a tissue when possible.
- Disposing of dirty tissues promptly and carefully.
- Maintaining good basic hygiene, for example washing hands frequently with soap and water to reduce the spread of the virus from your hands to face or to other people.
- Cleaning hard surfaces (e.g. door handles) frequently using a normal cleaning product.
- Helping your children follow this advice.


– Although we are aware that facemasks were being given out to the public in Mexico, the available scientific evidence does not support the general wearing of facemasks by those who are not ill whilst going about their normal activities. We are, however, reviewing NHS supplies and stockpiles of facemasks for healthcare workers who are likely to come into regular contact with people who may have symptoms. The UK will receive an additional 227 million surgical facemasks and 34 million respirators. Wales will receive its proportionate share.

Control measures

– Agreements have been signed between the UK Government and vaccine manufacturers to secure supplies of up to 90 million doses of H1N1 vaccine by the autumn. This will not affect the usual seasonal flu vaccination and will be made available to frontline healthcare workers and vulnerable people. Advance purchase arrangements are also in place to buy enough vaccine for the whole population.

– The Welsh Assembly Government’s Health Emergency Preparedness Unit has issued guidance to Local Health Boards on anti-viral distribution. The unit is co-ordinating work on identifying appropriate collection points and the necessary arrangements to support this process.

– People who have flu-like symptoms and have returned from an area where swine flu is circulating or who have been in close contact with a confirmed case have been advised to stay at home and call NHS Direct Wales on 0845 4647 or phone their GP for health advice.

– The National Public Health Service for Wales has provided advice to port health authorities on arrangements for returning travellers.

Features of the outbreak

– Based on assessment of all available information and following several expert consultations, the World Health Organization (WHO) declared the level of influenza pandemic alert at phase six on 11 June 2009.

– Phase six indicates there is human-to-human spread of the virus in at least two countries in one World Health Organization region, with community level outbreaks in at least one other country in a different WHO region.

– A change to phase six means that vaccine manufacturers will need to meet the contractual obligations of advance purchase agreements for vaccines that countries, including the UK, have already agreed in the event of phase six being declared.

– A crucial step towards large scale production of a vaccine against swine flu has been completed in the UK by the National Institute for Biological Standards and Control, part of the Health Protection Agency.

– A strain of virus suitable for vaccine manufacture has now been produced and is being made available to the pharmaceutical industry and other flu laboratories.

– Testing has shown that the human swine influenza H1N1 can be treated with the antiviral oseltamavir (Tamiflu®) and zanamivir (Relenza®).

– Further information on swine flu and Pandemic Flu is available bilingually from

– Further information from the Welsh Assembly Government response is available bilingually at wales

Welsh Assembly Government

View drug information on Relenza; Tamiflu capsule.

APA Offers Resources On Managing Traumatic Stress In Wake Of Haiti Earthquake

For those who may be struggling to cope from a distance or are having trouble dealing with the images of the Haiti earthquake aftermath, the American Psychological Association (APA) offers free resources on managing distress from afar and tips for recovering from disasters on its Psychology Help Center.

“The sheer number of lost lives, the wounded and the destruction of homes and communities as a result of the earthquake is tragic,” said APA President Carol Goodheart, Ed.D. “This is also a difficult time for those who are witnessing from a distance the loss of friends and family and the destruction of land in their native country.”

People living in the United States who have lost family and friends or are waiting for news of their loved ones are most likely to feel distress about this disaster. APA offers the following tips to help people mange any distress:

. Take a news break. Watching endless replays of footage from the disaster can make your stress even greater. Although you will want to keep informed – especially if you have loved ones in Haiti – taking a break from watching the news or social media updates can lessen your distress.

. Control what you can. There are routines in your life that you can continue, such as going to work or school and making meals. It helps to maintain these routines to give yourself a break from constantly thinking about the earthquake.

. Find a productive way to help if you can. Many organizations are providing various forms of aid to survivors. Contributing or volunteering is a positive action that can help you to make a difference.

. Keep things in perspective. While an earthquake can bring tremendous hardship and loss, remember to focus on the things that are good in your life. Persevere and trust in your ability to get through the challenging days ahead.

For additional information on managing traumatic stress in the aftermath of disasters, visit APA’s Help Center. And follow the APA Help Center on Twitter and read APA’s Mind/Body Health campaign blog, Your Mind Your Body.

The American Psychological Association

Chronic arthritis pain and the disappointment of u-opioid therapy

Experimental study indicates ineffectiveness of activating natural painkillers in joint tissue for managing long-term arthritis pain –

Nearly one third of the world’s adult population suffers with the pain of arthritis. While NSAIDs and COX-2 inhibitors offer the promise of relief, these drugs also bring the risk of adverse effects, from stomach ulcers to heart attack. Recent studies have suggested the potential of tapping into the body’s supply of painkilling peptides as a safe, natural approach to arthritis pain management. Extraneous substances such as morphine can be disadvantageous in arthritis pain therapy due to a large number of adverse side-effects associated with these compounds. In addition, the lack of selectivity of morphine means that precise targeting of u-opioid receptors to control chronic pain has proven to be problematic. What’s more, several clinical and experimental studies of m-opioid therapy have shown ambiguous results. The recent discovery of a natural morphine-like compound in joints called endomorphin 1 could circumvent these therapeutic drawbacks due to its greater selectivity for the u-opioid receptor. Endomorphin 1 has the potential, therefore, to be a major painkilling agent in the body with less chance of risk.

Researchers at the University of Calgary set out to determine the effectiveness of endomorphin 1, with a painkilling capacity equal to or greater than morphine – on knee joint pain. Their subjects were male rats with induced arthritis, both acute and chronic. Their findings, featured in the October 2005 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis), shed light on why u-opioid therapy may not work to control long-term arthritis pain.

Previous research into u-opioid therapy for arthritis has primarily focused on changes occurring in the hours immediately following tissue inflammation. This study is the first to examine the impact on chronic inflammation. The rat models were randomly assigned to the different treatment groups: acute (48-hour) inflammation, chronic (1-week and 3-week) inflammation, and normal controls.

Under anesthesia, endomorphin 1 was injected into the arthritic knee joints of all affected rats. Therapeutic effectiveness was assessed by measures of joint edema formation and sensory nerve activity associated with pain.

In rats with acute arthritis, endomorphin 1 worked to significantly reduce the hypersensitivity of joint nerves by as much as 75 percent. In the rats with chronic arthritis, however, endomorphin 1 had no observable effect on the telltale triggers of pain. On the strength of these findings, researchers concluded that chronic inflammation negates the pain-relieving benefits of the body’s u-opioid receptors.

“These observations highlight a possible inadequacy of the endogenous opioid system to alleviate chronic arthritis pain,” notes study author Dr. Jason McDougall. By offering clear insights into the disappointment of u-opioid therapy, this study suggests the need for rethinking the best use of endomorphin 1 and redirecting pain management research toward more promising alternatives for long-term arthritis sufferers.

Article: “Chronic Arthritis Down-Regulates Peripheral u-Opioid Receptor Expression With Concomitant Loss of Endomorphin 1 Antinociception,” Zongming Li, David Proud, Chunfen Zhang, Shahina Wiehler, and Jason J. McDougall, Arthritis & Rheumatism, October 2005; 52:10; pp. 3210-3219. What are Opioids?
For more information on what opioids are, and opioid-induced constipation (OIC), please see:
All About Opioids and Opioid-Induced Constipation (OIC)

John Wiley & Sons, Inc.

Drug For Alzheimer Disease Does Not Appear To Slow Cognitive Decline

Although there were promising results in a phase 2 trial, patients with mild Alzheimer disease who received the drug tarenflurbil as part of a phase 3 trial did not have better outcomes on measures of cognitive decline or loss of activities of daily living compared to patients who received placebo, according to a study in the December 16 issue of JAMA.

A leading theory on the pathophysiology of Alzheimer disease (AD) is the overproduction of amyloid-?? (A??; a peptide of certain amino acids that appear to be the main constituent of amyloid plaques in the brains of patients with AD), particularly 42 amino acid peptide A??42. “Tarenflurbil, a selective A??42-lowering agent, demonstrated encouraging results on cognitive and functional outcomes among mildly affected patients in an earlier phase 2 trial,” the authors write.

Robert C. Green, M.D., M.P.H., of the Boston University Schools of Medicine and Public Health, and colleagues conducted a large phase 3, randomized trial of tarenflurbil for patients with mild AD to determine its efficacy, safety and tolerability. The study, conducted at 133 trial sites in the United States, included 1,684 participants who were randomized, of whom 1,649 were included in the analysis, and 1,046 completed the 18-month trial. Patients were randomized to tarenflurbil, 800 mg, or placebo, administered twice a day.

The researchers found that tarenflurbil had no beneficial effect on the primary outcomes of cognition and activities of daily living after 18 months. There were also no significant differences on secondary outcomes, which included other AD assessment measures such as quality of life and caregiver burden.

Regarding adverse events, more participants taking tarenflurbil than those taking placebo experienced dizziness, upper respiratory tract infections and anemia.

“Our results are ??¦ a reminder that interventions affecting amyloid have not yet been shown to alter the course of AD,” the authors conclude.

(JAMA. 2009;302[23]:2557-2564)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Late-Life Dementias – Does This Unyielding Global Challenge Require a Broader View?

In an accompanying editorial, Thomas J. Montine, M.D., Ph.D., of the University of Washington, and Eric B. Larson, M.D., M.P.H., of the Group Health Research Institute, Seattle, comment on the findings of the two studies in this week’s JAMA regarding dementia and Alzheimer disease.

“The null outcome for the leading ??-secretase modulator [tarenflurbil] in a phase 3 trial and the surprisingly strong association between plasma leptin and incident Alzheimer disease underscore the need to broaden the current view of potential therapeutic approaches to cognitive impairment and dementia in older individuals. Research must seek a fuller understanding of the complex convergence of Alzheimer disease with vascular disease and Lewy body disease [a type of dementia], the application of biomarkers and other surrogates to clinical trials to quantify specific pharmacologic effects, and a multimodal approach to prevention and treatment. Doing so could have profound effects on the increasing numbers of older persons and on the societies confronting the global challenge of late-life dementias in decades to come.”

(JAMA. 2009;302[23]:2593-2594)

American Medical Association (AMA)

25 Years On – HIV Akin To A Tsunami Every Month, Says Virus Discoverer

Twenty five years after the first case was reported, HIV/AIDS is killing over 250,000 people each month – akin to a tsunami every month, says Professor Robert Gallo, co-discoverer of the virus and developer of the HIV/AIDS blood test.

His article is part of a special HIV/AIDS theme issue of Student BMJ, in which he calls for sustained research to ensure new ways of preventing and treating this global pandemic.

Gallo provides a fascinating personal insight into the 25 years that the disease has been with us, including his work on human retroviruses and the discovery of the HIV in the early 1980s.

“Those early years of 1982-85 may be regarded as representing the fastest pace ever achieved in medical science from the time of the birth of a new disease to advances in its understanding, diagnosis, prevention, and therapy,” he writes.

But he also talks of his concern as he watched the epidemic take hold, and his initial pessimism about the prospects of effectively treating HIV.

It’s nearly 23 years since we knew the cause of AIDS, he says. Where are we today? Can we expect things to improve significantly?

He believes this is impossible to predict, but is clear that we must never forget the essential role still to be played by medical science. “We have effective therapy only because of the basic research in HIV and new forms of therapy will only come from more research,” he writes.

The ultimate answer, of course, is a successful preventive vaccine. Although this is a formidable challenge, Gallo is optimistic for the future. “Perhaps this will be the last time that 25-year reflection is needed,” he suggests.

If we are to achieve the dream of not “celebrating” the 50th anniversary, we need to act fast, adds Balaji Ravichandran, Editor of Student BMJ. Equal attention must be paid to both prevention and treatment, while scientific enquiry into all aspects of the disease should never be ignored.

“For it is science that discovered the virus behind the pandemic, science that attempts to prevent and treat it, and only science that will, one day, put a complete end to it,” he writes.

Professor Robert Gallo,
Institute of Human Virology, Departments of Microbiology and Immunology and Medicine,
University of Maryland, Baltimore, USA

Balaji Ravichandran, Editor,
Student BMJ, British Medical Journal, London, UK

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Also in this issue: the challenges facing doctors who are HIV positive and one doctor’s experience of fighting AIDS in a conflict zone.

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Source: Student BMJ