The role of interleukin in Alzheimer disease

.
Alzheimer's Donation
Donate Online Now
.

Elevation of the proinflammatory cytokine Interleukin-1 (IL-1) is an integral part of the local tissue reaction to central nervous system (CNS) insult. The discovery of increased IL-1 levels in patients following acute injury and in chronic neurodegenerative disease laid the foundation for two decades of research that has provided important details regarding IL-1's biology and function in the CNS. IL-1 elevation is now recognized as a critical component of the brain's patterned response to insults, termed neuroinflammation, and of leukocyte recruitment to the CNS. These processes are believed to underlie IL-1's function in the setting of acute brain injury, where it has been ascribed potential roles in repair as well as in exacerbation of damage. Explorations of IL-1's role in chronic neurodegenerative disease have mainly focused on Alzheimer disease (AD), where indirect evidence has implicated it in disease pathogenesis. However, recent observations in animal models challenge earlier assumptions that IL-1 elevation and resulting neuroinflammatory processes play a purely detrimental role in AD, and prompt a need for new characterizations of IL-1 function. Potentially adaptive functions of IL-1 elevation in AD warrant further mechanistic studies, and provide evidence that enhancement of these effects may help to alleviate the pathologic burden of disease. J Neuroinflammation. 2008 Feb 26;5(1):7

Study raises concerns over vitamin E and lung health
Long-term and high dose supplementation with vitamin E may result in a "small increased risk" of lung cancer, most notable amongst smokers, says new research. http://www.nutraingredients.com

Posted YVN

50 Years Ago in Biochemistry

.
Alzheimer's Donation
Donate Online Now
.

In the 1950s the field of oxidative phosphorylation was so nebulous and confused that all possible concepts, facilities, and tools were needed to advance knowledge of the subject. When Hotchkiss found that gramicidin blocked phosphate uptake by Staphylococci, we had postulated that this antibiotic uncoupled phosphorylation from oxidation -- a concept we had first proposed for the metabolic effect of 2,4,-dinitrophenol (DNP).[1,2] From then on, we collected antibiotics from many sources hoping that some would be useful inhibitors of cellular respiration and phosphorylation. The first of these found to be effective was usnic acid [3] which, in micromolar concentrations, uncoupled phosphorylation in washed liver particles. We also discovered that antimycin A blocked the respiratory system of bakers yeast and enhanced aerobic fermentation to the anaerobic rate. This information was passed on to Ahmad and Strong in the next laboratory, who were working intensively on antimycin.

By 1958 we had tested more than 60 antibiotics and had found about one of 10 to have interesting effects on mitochondrial metabolism and function. When we later confined our screening to antifungals that were non-toxic to anaerobic bacterial growth, one of every three or four new antibiotics was a "keeper."

The 1958 paper reported the inhibition of mitochondrial respiration by oligomycin and its reversal by DNP. It inhibited ATP hydrolysis induced by DNP, Ca2 + , deoxycholate, and triiodothyroacetic acid. We concluded that oligomycin acts on an enzyme involved in phosphate fixation or in phosphate transfer rather than on enzymes in electron transport. Regardless of which theory of oxidative phosphorylation an investigator espoused, he was soon finding oligomycin useful in his work. We kept no record of the number of requests we received for this antibiotic but I know we disposed of a gross of small vials before we began folding samples into glazed paper and sending them by letter mail.

Valacidin (identical with Pfizer's streptonigrin) was found to reverse respiratory inhibition by oligomycin or antimycin "indicating that it acts as an electron carrier from DPNH to cytochromes."

The paper also reported for the first time the effects of nigericin and dianemycin on mitochondrial respiration, phosphorylation, and ATP hydrolysis.

Dianemycin was named for Diane Johnson, the second author of the paper. She is a "classic" in her own right. After 10 years as my technician Johnson decided to take a doctorate in history of science. Although her undergraduate academic record was brilliant, as a Ph.D. candidate she suffered the disgrace of her only B grade -- in a one-credit seminar. (The professor who awarded it has since left this University and I have wondered whether he was encouraged to do so by the assistant dean of his college -- Diane Johnson.) She is also chairman of the Drug Quality Council for the State of Wisconsin -- their task, to determine whether generic drug products are equivalent to brand name products. Believe it or not, she has just been appointed assistant director of athletics at the University of Wisconsin!

Bill McMurray was a postdoctorate fellow from the University of Western Ontario, where he is now professor of biochemistry and where he later discovered the effects of valinomycin on mitochondria.

I have always considered this one of the trivial papers from our laboratory but am pleased that others have found it useful enough to cite it. - Henry A. Lardy, Institute for Enzyme Research, University of Wisconsin, April 12, 1978

Reference:
H.A. Lardy, D. Johnson, W.C. McMurray, Antibiotics as tools for metabolic studies.I. A survey of toxic antibiotics in respiratory, phosphorylative and glycolytic systems. Arch. Biochem. Biophys. 78:587-97, 1958

References in essay:
1. Lardy H A and Elvehjem C A. Biological oxidations and reductions. Ann. Rev. Biochem. 14:1- 30, 1945.
2. Lardy H A and Phillips P H. The effect of thyroxine and dinitrophenol on sperm metabolism. J. Biol. Chem. 149:177-82, 1943.
3. Johnson R B, Feldott G & Lardy H A. The mode of action of the antibiotic, usnic acid. Arch. Biochem. 28:317-23, 1950. http://www.the-scientist.com

Educational Impact on Detection of Alzheimer’s
People who spend fewer years in school may be slower to realize that they are suffering from the early symptoms of Alzheimer’s disease than those who are more highly educated, a new report found. The lag may explain why, overall, less educated people tend to be diagnosed with Alzheimer’s at a slightly later age than those who are highly educated. At the same time, problems with memory and thinking may have advanced further by the time those with little schooling are diagnosed with the disease.

The findings, published in the Archives of Neurology, come from scientists at the Alzheimer's Disease Research Center at Washington University School of Medicine in St. Louis. The researchers reviewed data on nearly 1,500 Alzheimer's patients from their center. They also reviewed files on more than 21,000 patients from the National Alzheimer's Coordinating Center, a collaboration of approximately 30 Alzheimer's disease research centers nationwide.

"We may have a group of people who are at risk for slightly delayed detection of Alzheimer's disease," said lead author Catherine Roe, Ph.D., a neurology research instructor at Washington University. "Early detection of Alzheimer's disease is important as we progress toward treatments and cures because those treatments will need to be applied as early as possible to have the maximum possible benefit."

The new study revealed that patients with 12 years or more of schooling were on average slightly younger when diagnosed with Alzheimer's disease than patients with less than eight years of schooling. Age of diagnosis for a group with eight to 11 years of schooling fell in-between the other two groups. The researchers also analyzed the severity of patients' dementia when they went to the Alzheimer's disease center for the first time. They found that patients with fewer years of education were likely to be more severely impaired on their first visit.

Fewer years of formal schooling have been linked to an increased risk for Alzheimer’s in earlier studies. Higher levels of education, on the other hand, may be protective. One theory is that education helps build a strong network of interconnections between nerve cells in the brain. This network may act as a so-called “brain reserve,” allowing the brain to function normally as cells die from Alzheimer’s. Why would someone with more schooling, then, be diagnosed with Alzheimer’s sooner? The researchers propose that those with lower education levels may be slower to notice the early signs of disease, only going to see a specialist after their symptoms become impossible to ignore. Those with more education, on the other hand, may become aware of their symptoms while they are still relatively subtle and seek a specialists' help early on in the disease process.

"People with higher education levels may be more likely to have a job or a hobby that makes early cognitive impairment more obvious, as well as better access to medical care," Dr. Roe said. "These could be factors that we need to incorporate into our procedures for screening patients for early signs of cognitive impairment." http://www.medicalnewstoday.com

Enzymes designed to improve berry juice use
A new range of enzymes are designed to improve the juice volume and vitamin yield of blackcurrants for beverage use, in order to maximise the benefits of the superfruits, their manufacturer says. http://www.nutraingredients.com

Posted YVN

Antibiotics and Advanced Dementia

.
Alzheimer's Donation
Donate Online Now
.

A new study by researchers in the US found that people with advanced dementia are frequently given antibiotics toward the end of life, and has thrown into question whether this practice should be curtailed in view of the increased risk of developing drug resistant superbugs. Advanced dementia patients in nursing homes are at high risk of infections and antimicrobial exposure near the end of life, wrote the researchers.

The study is the work of Drs Erika D'Agata and Susan L Mitchell of the Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. D'Agata and Mitchell studied a group of 214 residents, of average age 85.2, with advanced dementia being cared for in 21 nursing homes in and around Boston.

The residents were assessed between 2003 and 2006 and then every three months for up to 18 months. At each assessment, the number and type of antibiotics prescribed, with reasons (indication), were noted from records kept at the nursing home. With regard to the implications of this practice they suggested it should be evaluated with respect to two things: "the individual treatment burden near the end of life and its contribution to the emergence of antimicrobial resistance in the nursing home setting."

They are not suggesting a flat refusal to give antibiotics to severely demented elderly people, or even that policies restricting their use should be introduced. They suggest antibiotics should be considered alongside every other carefully weighed decision such as resuscitation and major surgery. As well as weighing up the the interests of the patient and the risk to others, they concluded that: "All such decisions must ultimately be made individually, based on the medical situation and the expressed wishes of the patient and family, as well as on the physician's judgment of the benefits and risks entailed in treating vs. not treating."

The controversy about the public health implications arises because previous research has shown that nursing homes can harbour drug resistant bacteria, and these can spread into hospitals when nursing home residents are admitted. An Associated Press report notes the comments of various experts, discussing the implications of this study. A geriatrician and ethicist at the University of Chicago Medical Center, Dr Daniel Brauner, said being more careful with antibiotics means doctors would have to keep a much closer watch on nursing home residents. But, he said "I'm sure a lot of these antibiotics were prescribed over the telephone".

Another problem of course, even with close monitoring, is that the doctor sometimes can't tell if the patient is approaching death. Dr Eric Tangalos, a geriatrician at the Mayo Clinic told the Associated Press that: "Until that decision is made that death is imminent, there's always hope. People do recover from those infections."

On the other hand, is the problem of what constitutes quality of life in those last few weeks, as Bruce Jennings, a bioethicist with a research institute on medical ethics, the Hastings Center, put it: "You might rescue the patient from life-threatening pneumonia and they live a few days, weeks or even months longer. But the extra time you have bought them by that rescue is not beneficial." Mitchell said doctors should discuss these things with the patient's family, in the same way as they disucss whether a feeding tube should be used. She also commented that none of the residents in the study had made living wills stating their wishes on antibiotic treatment. http://www.medicalnewstoday.com

Blueberry extracts may cut food intake, reduce obesity
Rats fed extracts from blueberries gained up to 10 per cent less body weight than their furry counterparts not consuming the extracts, says new joint research from New Zealand and the US. http://www.nutraingredients.com

Posted YVN

Intravenous immunoglobulin for treatment of Alzheimer’s

.
Alzheimer's Donation
Donate Online Now
.

Intravenous immunoglobulin (IVIg) has been proposed as a potential agent for Alzheimer's disease (AD) immunotherapy because it contains antibodies against beta-amyloid (Abeta). We carried out an open label dose-ranging study in 8 mild AD patients in which IVIg was added to approved AD therapies for 6 months, discontinued, and then resumed for another 9 months. Infusions were generally well-tolerated. Anti-Abeta antibodies in the serum from AD patients increased in proportion to IVIg dose and had a shorter half-life than anti-hepatitis antibodies and total IgG. Plasma Abeta levels increased transiently after each infusion. Cerebrospinal fluid Abeta decreased significantly at 6 months, returned to baseline after washout and decreased again after IVIg was re-administered for an additional 9 months. Mini-mental state scores increased an average of 2.5 points after 6 months, returned to baseline during washout and remained stable during subsequent IVIg treatment. Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 75, 1472-1474] from a 6-month trial of IVIg in 5 AD patients and justify further studies of IVIg for treatment of AD. http://www.ncbi.nlm.nih.gov

Vegetables, but not fruit, may slash diabetes risk

A higher intake of vegetables, rich sources of fibre, antioxidants, and magnesium, may reduce the risk of developing type-2 diabetes by almost 30 per cent, suggests a new study. http://www.nutraingredients.com

Posted YVN

Diagnose Alzheimer's disease faster

.
Alzheimer's Donation
Donate Online Now
.

Computers are able to diagnose Alzheimer's disease faster and more accurately than experts, according to research published in the journal Brain. The findings may help ensure that patients are diagnosed earlier, increasing treatment options. According to the Alzheimer's Research Trust, there are over 700,000 people currently living in the UK with dementia, of which Alzheimer's disease, a neurodegenerative disease, is the most common form. Alzheimer's is caused by the build up in the brain of plaques and neurofibrillary tangles (tangles of brain tissue filaments), leading the brain to atrophy. Definitive diagnosis is usually only possible after death, but Alzheimer's is usually diagnosed using a combination of brain scans, blood tests and interviews carried out by a trained clinician. The tests are time consuming, and distinguishing the disease from other forms of dementia can be difficult. The accuracy of diagnosis is only about 85%

Now, a team of researchers led by scientists at the Wellcome Trust Centre for Neuroimaging at University College London, has shown that scans of patients with Alzheimer's can be distinguished from those of healthy individuals and patients with other forms of dementia. Computers can identify the characteristic damage of Alzheimer's disease with an accuracy as high as 96%. "The advantage of using computers is that they prove cheaper, faster and more accurate than the current method of diagnosis," explains Professor Richard Frackowiak from the Wellcome Trust Centre for Neuroimaging. "The new method makes an objective diagnosis without the need for human intervention. This will be particularly attractive for areas of the world where there is a shortage of trained clinicians and when a standardised reliable diagnosis is needed, for example in drug trials."

The new method, developed by Professor Frackowiak's team, works by teaching a standard computer the differences between brain scans from patients with proven Alzheimer's disease and people with no signs of the disease at all. The two conditions can be distinguished with a high degree of accuracy on a single clinical MRI scan. This could be especially useful for centres where facilities for extensive diagnostic workup are unavailable. One use might be to reassure the worried elderly well with mild memory problems that they are not suffering from early Alzheimer's.

The research tested scans from the US and the UK, from community and from academic hospitals. The method was shown to be valid by testing it on scans from people who had their status proven by pathological examination - the gold standard. The results were uniformly encouraging. The computer could be taught the distinction between normal and Alzheimer's with one set of scans and then used to correctly "diagnose" scans from another set. In all cases the results were better than the 86% correct diagnostic rate of best clinical practice. The researchers also found they could distinguish Alzheimer's better than clinicians from a similar disease called fronto-temporal dementia.

Professor Frackowiak emphasised that as symptoms from these diseases come on after a considerable amount of damage has already occurred in the brain, so it is important to make an accurate diagnosis early to improve the chances of effectively preventing deterioration. "The next step is to see whether we can use the technique to reliably track progression of the disease in a patient," says Professor Frackowiak. "This could prove a powerful and non-invasive tool for screening the efficacy of new drug treatments speedily, without a need for large costly clinical trials." http://www.medicalnewstoday.com

Science will help support green tea market, report finds
The market for green tea extracts is expected to grow by more than 13 per cent for the next seven years and emerging markets in eastern Europe will open new opportunities. http://www.nutraingredients.com

Posted YVN

Diet plays a major role in causing Alzheimer's

.
Alzheimer's Donation
Donate Online Now
.

Evidence that diet plays a major role in causing Alzheimer's disease was released yesterday after scientists found that African Americans were more than twice as likely to suffer from the condition as people of similar age in Nigeria.

US and Nigerian scientists have spent more than eight years studying thousands of elderly people in two communities - Indianapolis, in Indiana, and Ibadan, in Nigeria. In a paper published in the Journal of the American Medical Association, researchers said that the incidence of Alzheimer's in the 65-plus age group among African Americans was 2.5%. Among the Yoruba people of Ibadan of that age, it was 1.15%. When the scientists looked at all types of dementia, they found an even sharper difference - 3.24% in the US and 1.35% in Nigeria.

One possible conclusion is that the mainly vegetarian diet of the Yoruba, compared with the fatty diet of many Americans, offers protection against Alzheimer's as well as against cardiovascular disease, the biggest killer in the rich world. Hugh Henrie, who led the research at Indiana University, said: "To our knowledge, this is the first report of incidence rate differences for Alzheimer's and dementia between populations in developed and developing countries in studies that used identical methods and groups of investigators."

One possible explanation, they said, was the major difference in risk factors for cardiovascular disease between African Americans and Yoruba. The Nigerians, on average, are leaner, have lower cholesterol levels, and suffer less from high blood pressure and diabetes. "Vascular disease may contribute both to dementia and to the development, progression, and clinical severity of Alzheimer's," the report said. Other studies have already hinted at a link between cardiovascular illness and Alzheimer's. However, there has never been enough evidence before to bracket Alzheimer's disease together with heart disease in public warnings about unhealthy eating. http://www.guardian.co.uk

Dairy body claims natural trans fats not harmful
The European dairy industry says it is confident that there... http://www.nutraingredients.com

Posted YVN

A range of conditions from memory loss to dementia and Alzheimer's

.
Alzheimer's Donation
Donate Online Now
.

A new US study suggests that brain health is improving among older Americans as demonstrated by a decline in thinking and memory problems in this group. The researchers said improved cardiovascular care, better education, and being financially better off could be the main reasons. The nationally representative study found there was a downward trend among people aged 70 and over in the rate of what the authors called "cognitive impairment" a term used by scientists to describe a range of conditions from memory loss to dementia and Alzheimer's disease.

Using data from the National Institute on Aging funded Health and Retirement Study (HRS), the researchers found that between 1993 and 2002, the prevalence of cognitive impairment among Americans aged 70 and over went down 3.5 per cent (from 12.2 to 8.7 per cent over the decade). This translates to a reduction of impairment in hundreds of thousands of US seniors.

The reasons for this decline are not clear, said the researchers, but they suggest older Americans today are more likely to be in receipt of improved care for neurological risk factors such as high blood pressure, smoking and high cholesterol; and more likely to have had more years of formal education and reached a higher economic status compared to their counterparts of a decade earlier. The results showed that among the 11,000 people in the study, those who had been in education longer and had greater personal wealth were also the ones who were less likely to be experiencing cognitive problems.

A key interesting finding was that the more-educated seniors with cognitive problems were also more likely to die within two years of symptoms showing.

The researchers also found that:
About 40 per cent of the decrease in cognitive impairment over the decade ending in 2002 was likely due to increases in education and personal wealth. They found this by comparing two groups of seniors, one at the start of the decade and one at the end.

School attendance requirements, graduation rates in high school, enrollment rates in college or technical school, all went up in the period when the adults in the study were children and young adults.

72 per cent of people aged over 65 living in 2003 had a high school diploma compared with 53 per cent in 1990.

The proportion of college-educated elderly also went up during that time, from 11 to 17 per cent.

Treatments to control cholesterol, blood pressure, and prevent other cardiovascular problems rose significantly in the US in the 1990s. The researchers suggested these may have helped to preserve brain health in older Americans by reducing the incidence of strokes and clogged arteries that impair blood flow to and in the brain.

However, the gains made in the 1990s and early 2000s could be offset by the potential damage of a rising type 2 diabetes epidemic among the elderly, and the unhealthy life style and eating habits of young and middle aged Americans.

Also, although the proportion of older Americans with cognitive impairment might go down, we can't take our eye off the ball, because the actual number could go up, because the population is aging. Co-author of the study and assistant professor of internal medicine at the University of Michigan, Dr Allison Rosen, said: "This demographic reality will continue to make combating Alzheimer's disease and other types of dementia a top public health priority."

The researchers said older Americans should continue to pursue activities that keep their brain sharp and their cardiovascular risk low. These include doing crossword puzzles, volunteering, and making sure they take their blood pressure medication, as well keeping fit through physical exercises like walking. As Langa explained, more and more evidence appears to show that: "Staying mentally engaged with the world in any fashion -- reading, talking with friends, going to church, going to movies -- is also likely to help reduce your risk down the road." http://www.medicalnewstoday.com

Black tea may slash Parkinson's disease risk
Drinking at least 23 cups of black tea a month, or about three-quarters of a cup a day, may slash the risk of developing Parkinson's disease by a whopping 71 per cent, suggests new research from Singapore. http://www.nutraingredients.com

Posted YVN