209CNO29JUN2015
CNO Report 209
Release Date 26 JUN 2015
Draft Report Compiled by
Ralph Turchiano
In This Issue:
1. Vitamin D status related to immune response to HIV-1
2. Researchers correlate rheumatoid arthritis and giant cell arteritis with solar cycles
3. Avocados may hold the answer to beating leukemia
4. UA researchers discover component of cinnamon prevents colorectal cancer in mice
5. New study finds that orange sweet potato reduces diarrhea in children
6. Not-so-guilty pleasure: Viewing cat videos boosts energy and positive emotions
7. Extreme exercise linked to blood poisoning
8. Fructose powers a vicious circle
9. Individuals with social phobia have too much serotonin — not too little
10. Scientists identify amino acid that stops seizures in mice
11. Knowledge about alternative medicine connected to education, income
12. Model could help counteract poisoning from popular painkiller
13. New Zealand blackcurrants good for the brain
14. WSU scientists turn white fat into obesity-fighting beige fat
15. A person’s diet, acidity of urine may affect susceptibility to UTIs
16. Compound in magnolia may combat head and neck cancers
17. New study: Tart cherry juice reduced post-race respiratory tract symptoms after a marathon
Public Release: 15-Jun-2015
Vitamin D status related to immune response to HIV-1
Penn State
Vitamin D plays an important part in the human immune response and deficiency can leave individuals less able to fight infections like HIV-1. Now an international team of researchers has found that high-dose vitamin D supplementation can reverse the deficiency and also improve immune response.
“Vitamin D may be a simple, cost-effective intervention, particularly in resource-poor settings, to reduce HIV-1 risk and disease progression,” the researchers report in today’s (June 15) online issue of Proceedings of the National Academy of Sciences.
The researchers looked at two ethnic groups in Cape Town, South Africa, to see how seasonal differences in exposure to ultraviolet B radiation, dietary vitamin D, genetics, and pigmentation affected vitamin D levels, and whether high-dose supplementation improved deficiencies and the cell’s ability to repel HIV-1.
“Cape Town, South Africa, has a seasonal ultraviolet B regime and one of the world’s highest rates of HIV-1 infection, peaking in young adults, making it an appropriate location for a longitudinal study like this one,” said Nina Jablonski, Evan Pugh Professor of Anthropology, Penn State, who led the research.
One hundred healthy young individuals divided between those of Xhosa ancestry — whose ancestors migrated from closer to the equator into the Cape area — and those self-identified as having Cape Mixed ancestry — a complex admixture of Xhosa, Khoisan, European, South Asian and Indonesian populations — were recruited for this study. The groups were matched for age and smoking. The Xhosa, whose ancestors came from a place with more ultraviolet B radiation, have the darkest skin pigmentation, while the Khoisan — the original inhabitants of the Cape — have adapted to the seasonally changing ultraviolet radiation in the area and are lighter skinned. The Cape Mixed population falls between the Xhosa and Khoisan in skin pigmentation levels.
Cape Town is situated in the southern hemisphere at about the same distance from the equator as the Florida panhandle, slightly more than 30 degrees latitude. Ultraviolet B levels show a winter decline anywhere above 30 degrees latitude, so Cape Town has a definite winter with low levels of the ultraviolet B wavelengths needed to produce precursor vitamin D3. Add to this the fact that people now spend more time indoors during winter and wear more clothing, and exposure to ultraviolet B in winter may be insufficient to prevent vitamin D deficiency.
The researchers note that sunscreen use is not a factor in these populations. However, the darker the skin’s pigment, the more ultraviolet B radiation necessary to trigger the precursor chemicals in the body to produce vitamin D.
“The skin of the indigenous people of the Cape, the Khoisan, is considerably lighter than that of either study group and may represent a long-established adaptation to seasonal UVB,” according to the researchers. “The darker skin of both study populations — Xhosia and Cape mixed — denotes a degree of mismatch between skin pigmentation and environmental UVB resulting from their recent migration into the region.”
The researchers found that both groups exhibited vitamin D deficiency during the winter, with women in both groups being more deficient, on average, than the men. Because of vitamin D’s impact on the immune system, the researchers provided six weeks of supplemental vitamin D3 to 30 of the Xhosa participants, which brought 77 percent of the participants to optimal vitamin D status.
Jablonski and her team determined that diet, genetics and other variables played very small roles in vitamin D status, although some genetic variations did influence the success of supplementation.
To test how vitamin D status affected the immune system and HIV-1 in particular, the researchers exposed blood samples from Xhosa and Cape mixed participants taken during the summer and winter when the subjects were vitamin D sufficient or deficient. They found that after nine days, the winter blood samples had greater infection than those taken in summer. After six weeks of vitamin D supplementation, the Xhosa blood sample levels of HIV-1 infection were the same as those during the summer.
“High-dosage oral vitamin D3 supplementation attenuated HIV-1 replication, increased circulating white blood cells and reversed winter-associated anemia,” the researchers reported. “Vitamin D3 presents a low-cost supplementation to improve HIV-associated immunity.”
Public Release: 15-Jun-2015
Researchers correlate rheumatoid arthritis and giant cell arteritis with solar cycles
DOE/Princeton Plasma Physics Laboratory
What began as a chat between husband and wife has evolved into an intriguing scientific discovery. The results, published in May in BMJ (formerly British Medical Journal) Open, show a “highly significant” correlation between periodic solar storms and incidences of rheumatoid arthritis (RA) and giant cell arteritis (GCA), two potentially debilitating autoimmune diseases. The findings by a rare collaboration of physicists and medical researchers suggest a relationship between the solar outbursts and the incidence of these diseases that could lead to preventive measures if a causal link can be established.
RA and GCA are autoimmune conditions in which the body mistakenly attacks its own organs and tissues. RA inflames and swells joints and can cause crippling damage if left untreated. In GCA, the autoimmune disease results in inflammation of the wall of arteries, leading to headaches, jaw pain, vision problems and even blindness in severe cases.
Inspiring this study were conversations between Simon Wing, a Johns Hopkins University physicist and first author of the paper, and his wife, Lisa Rider, deputy unit chief of the Environmental Autoimmunity Group at the National Institute of Environmental Health Sciences in the National Institutes of Health, and a coauthor. Rider spotted data from the Mayo Clinic in Rochester, Minnesota, showing that cases of RA and GCA followed close to 10-year cycles. “That got me curious,” Wing recalled. “Only a few things in nature have a periodicity of about 10-11 years and the solar cycle is one of them.”
Wing teamed with physicist Jay Johnson of the U.S. Department of Energy’s Princeton Plasma Physics Laboratory, a long-time collaborator, to investigate further. When the physicists tracked the incidence of RA and GCA cases compiled by Mayo Clinic researchers, the results suggested “more than a coincidental connection,” said Eric Matteson, chair of the division of rheumatology at the Mayo Clinic, and a coauthor. This work drew upon previous space physics research supported by the DOE Office of Science.
The findings found increased incidents of RA and GCA to be in periodic concert with the cycle of magnetic activity of the sun. During the solar cycle, dramatic changes that can affect space weather near Earth take place in the sun. At the solar maximum, for example, an increased number of outbursts called coronal mass ejections hurl millions of tons of magnetic and electrically charged plasma gas against the Earth’s magnetosphere, the magnetic field that surrounds the planet. This contact whips up geomagnetic disturbances that can disrupt cell phone service, damage satellites and knock out power grids. More importantly, during the declining phase of the solar maximum high-speed streams develop in the solar wind that is made up of plasma that flows from the sun. These streams continuously buffet Earth’s magnetosphere, producing enhanced geomagnetic activity at high Earth latitudes.
The research, which tracked correlations of the diseases with both geomagnetic activity and extreme ultraviolet (EUV) solar radiation, focused on cases recorded in Olmsted County, Minnesota, the home of the Mayo Clinic, over more than five decades. The physicists compared the data with indices of EUV radiation for the years 1950 through 2007 and indices of geomagnetic activity from 1966 through 2007. Included were all 207 cases of GCA and all 1,179 cases of RA occurring in Olmsted County during the periods and collected in a long-term study led by Sherine Gabriel, then of the Mayo Clinic and now dean of the Rutgers Robert Wood Johnson Medical School.
Correlations proved to be strongest between the diseases and geomagnetic activity. GCA incidence — defined as the number of new cases per capita per year in the county — regularly peaked within one year of the most intense geomagnetic activity, while RA incidence fell to a minimum within one year of the least intense activity. Correlations with the EUV indices were seen to be less robust and showed a significantly longer response time.
The findings were consistent with previous studies of the geographic distribution of RA cases in the United States. Such research found a greater incidence of the disease in sections of the country that are more likely to be affected by geomagnetic activity. For example, the heaviest incidence lay along geographic latitudes on the East Coast that were below those on the West Coast. This asymmetry may reflect the fact that high geomagnetic latitudes — areas most subject to geomagnetic activity — swing lower on the East Coast than on the opposite side of the country. While Washington, D.C., lies just 1 degree farther north than San Francisco geographically, for example, the U.S. capital is 7 degrees farther north in terms of geomagnetic latitude.
Although the authors make no claim to a causal explanation for their findings, they identify five characteristics of the disease occurrence that are not obviously explained by any of the currently leading hypotheses. These include the east-west asymmetries of the RA and GCA outbreaks and the periodicities of the incidences in concert with the solar cycle. Among the possible causal pathways the authors consider are reduced production of the hormone melatonin, an anti-inflammatory mediator with immune-enhancing effects, and increased formation of free radicals in susceptible individuals. A study of 142 electrical power workers found that excretion of melatonin — a proxy used to estimate production of the hormone — was reduced by 21 percent on days with increased geomagnetic activity.
Confirming a causal link between outbreaks of RA and GCA and geomagnetic activity would be an important step towards developing strategies for mitigating the impact of the activity on susceptible individuals. These strategies could include relocating to lower latitudes and developing methods to counteract direct causal agents that may be controlled by geomagnetic activity. For now, say the authors, their findings warrant further investigations covering longer time periods, additional locations and other autoimmune diseases.
Public Release: 15-Jun-2015
Avocados may hold the answer to beating leukemia
University of Waterloo
Rich, creamy, nutritious and now cancer fighting. New research reveals that molecules derived from avocados could be effective in treating a form of cancer.
Professor Paul Spagnuolo from the University of Waterloo has discovered a lipid in avocados that combats acute myeloid leukemia (AML) by targeting the root of the disease – leukemia stem cells. Worldwide, there are few drug treatments available to patients that target leukemia stem cells.
AML is a devastating disease and proves fatal within five years for 90 per cent of seniors over age 65. Spagnuolo’s new avocado-derived drug could one day significantly increase life expectancy and quality of life for AML patients.
“The stem cell is really the cell that drives the disease,” said Professor Spagnuolo, in Waterloo’s School of Pharmacy. “The stem cell is largely responsible for the disease developing and it’s the reason why so many patients with leukemia relapse. We’ve performed many rounds of testing to determine how this new drug works at a molecular level and confirmed that it targets stem cells selectively, leaving healthy cells unharmed.”
Spagnuolo’s research is published today in Cancer Research, a top-ten oncology journal. Through partnership with the Centre for Commercialization of Regenerative Medicine (CCRM) he has also filed a patent application for the use of the compound, named avocatin B, to treat AML.
“It’s an exciting time for our lab. With the help of CCRM we are now pursuing commercial partnership that would take avocatin B into clinical trials,” said Professor Spagnuolo. “Not only does avocatin B eliminate the source of AML, but its targeted, selective effects make it less toxic to the body, too.”
The drug is still years away from becoming approved for use in oncology clinics, but Spagnuolo is already performing experiments to prepare the drug for a Phase I clinical trial. This is the first round of trials where people diagnosed with AML could have access to the drug.
Professor Spagnuolo is among only a handful of researchers worldwide, applying the pharmaceutical industry’s rigorous drug discovery research processes to food-derived compounds, called nutraceuticals.
There are multiple potential applications for Avocatin B beyond oncology, and the drug is just one of several promising compounds that Spagnuolo and his team have isolated from a library of nutraceuticals. Most labs would use food or plant extracts, but Spagnuolo prefers the precision of using nutraceuticals with defined structures.
“Extracts are less refined. The contents of an extract can vary from plant to plant and year to year, depending on lots of factors – on the soil, the location, the amount of sunlight, the rain,” said Spagnuolo. “Evaluating a nutraceutical as a potential clinical drug requires in-depth evaluation at the molecular level. This approach provides a clearer understanding of how the nutraceutical works, and it means we can reproduce the effects more accurately and consistently. This is critical to safely translating our lab work into a reliable drug that could be used in oncology clinics.”
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Public Release: 15-Jun-2015
UA researchers discover component of cinnamon prevents colorectal cancer in mice
University of Arizona College of Pharmacy study shows compound that gives cinnamon its distinctive flavor and smell is a potent inhibitor
University of Arizona, College of Pharmacy
Research conducted at the University of Arizona College of Pharmacy and the UA Cancer Center indicates that a compound derived from cinnamon is a potent inhibitor of colorectal cancer.
Georg Wondrak, Ph.D., associate professor, and Donna Zhang, Ph.D., professor, both of the UA College of Pharmacy Department of Pharmacology and Toxicology, recently completed a study in which they proved that adding cinnamaldehyde, the compound that gives cinnamon its distinctive flavor and smell, to the diet of mice protected the mice against colorectal cancer. In response to cinnamaldehyde, the animals’ cells had acquired the ability to protect themselves against exposure to a carcinogen through detoxification and repair.
‘This is a significant finding,’ says Zhang, who, along with Wondrak, is a member of the UA Cancer Center. ‘Because colorectal cancer is aggressive and associated with poor prognoses, there is an urgent need to develop more effective strategies against this disease.’
‘Given cinnamon’s important status as the third-most-consumed spice in the world,’ Wondrak adds, ‘there’s relatively little research on its potential health benefits. If we can ascertain the positive effects of cinnamon, we would like to leverage this opportunity to potentially improve the health of people around the globe.’
Drs. Wondrak and Zhang’s study, ‘Nrf2-dependent suppression of azoxymethane/dextrane sulfate sodium-induced colon carcinogenesis by the cinnamon-derived dietary factor cinnamaldehyde,’ has been published online and will appear in a print issue of Cancer Prevention Research later this spring.
A story about the cinnamaldehyde study appears on the UA College of Pharmacy’s website.
The next step in the research is to test whether cinnamon, as opposed to cinnamaldehyde, prevents cancer using this same cancer model. Because cinnamon is a common food additive already considered safe — it’s not a synthetic, novel drug — a study in humans may not be too far off.
Wondrak outlines questions to investigate going forward: ‘Can cinnamon do it, now that we know pure cinnamaldehyde can? And can we use cinnamaldehyde or cinnamon as a weapon to go after other major diseases, such as inflammatory dysregulation and diabetes? These are big questions to which we might be able to provide encouraging answers using a very common spice.’
Public Release: 15-Jun-2015
New study finds that orange sweet potato reduces diarrhea in children
HarvestPlus
Washington, June 15 — A new study has found that orange sweet potato (OSP) reduced both the prevalence and duration of diarrhea in young children in Mozambique.
The OSP was conventionally bred to provide more vitamin A in the diet. In Africa, more than 40 percent of children aged under five are estimated to be at risk of vitamin A deficiency. This increases the risk of diseases such as diarrhea, which is one of the leading causes of mortality in children, taking more than 350,000 lives of children under five in Africa every year.
Other studies have shown that vitamin A supplementation reduces diarrhea incidence in children, particularly those who are undernourished or suffering from severe infections. This newly published research is the first to show that an agricultural food-based approach can improve health in young children.
The study found a 42 percent reduction in the likelihood that children under the age of five who ate OSP within the past week would experience diarrhea. For children under three years of age who ate OSP, the likelihood of having diarrhea was reduced by more than half (52 percent). The OSP had an impact not only on reducing the incidence, but also the duration of diarrhea. For children who had diarrhea, eating OSP reduced the duration of the illness by more than 10 percent in children under five, and more than 25 percent in children aged under three. The children had all eaten OSP within the past week.
‘The beta-carotene in OSP is converted into vitamin A the same day the OSP is eaten,’ says Dr. Erick Boy, the head of Nutrition at HarvestPlus, a global program to improve nutrition that funded the field research. ‘This vitamin A is used by the cells lining the gut to help form a barrier to invading germs. These cells are regenerated every few days, so cells that have been weakened due to lack of vitamin A are quickly replaced by healthy cells when there is enough vitamin A. It should be noted that access to clean water and sanitation, targeted immunization, and breastfeeding are also important in helping to prevent diarrhea.’
The study also found that there was greater impact in reducing diarrhea in children with educated mothers, who are likely better able to understand the health benefits of OSP, and also to change children’s diets.
‘Both vitamin A supplements and vitamin A-rich foods like orange sweet potato can provide sufficient vitamin A. From a public health perspective, they are complementary — neither alone is able to reach every child who needs vitamin A,’ says Alan de Brauw, a Senior Research Fellow at the International Food Policy Research Institute. ‘But vitamin A supplements can be expensive, as much as $2.71 per dose. Alleviating this deficiency worldwide through supplements alone would cost almost $3 billion per year. Using OSP to provide vitamin A is a fraction of that cost. Given the popularity of OSP — children especially love its taste– we think it’s a sustainable solution to improving nutrition and child health in many countries, complemented, of course, by supplementation where it is cost-effective.’
Public Release: 16-Jun-2015
Not-so-guilty pleasure: Viewing cat videos boosts energy and positive emotions
Indiana University
BLOOMINGTON, Ind. — If you get a warm, fuzzy feeling after watching cute cat videos online, the effect may be more profound than you think.
The Internet phenomenon of watching cat videos, from Lil Bub to Grumpy Cat, does more than simply entertain; it boosts viewers’ energy and positive emotions and decreases negative feelings, according to a new study by an Indiana University Media School researcher.
The study, by assistant professor Jessica Gall Myrick, surveyed almost 7,000 people about their viewing of cat videos and how it affects their moods. It was published in the latest issue of Computers in Human Behavior. Lil Bub’s owner, Mike Bridavsky, who lives in Bloomington, helped distribute the survey via social media.
“Some people may think watching online cat videos isn’t a serious enough topic for academic research, but the fact is that it’s one of the most popular uses of the Internet today,” Myrick said. “If we want to better understand the effects the Internet may have on us as individuals and on society, then researchers can’t ignore Internet cats anymore.
“We all have watched a cat video online, but there is really little empirical work done on why so many of us do this, or what effects it might have on us,” added Myrick, who owns a pug but no cats. “As a media researcher and online cat video viewer, I felt compelled to gather some data about this pop culture phenomenon.”
Internet data show there were more than 2 million cat videos posted on YouTube in 2014, with almost 26 billion views. Cat videos had more views per video than any other category of YouTube content.
In Myrick’s study, the most popular sites for viewing cat videos were Facebook, YouTube, Buzzfeed and I Can Has Cheezburger.
Among the possible effects Myrick hoped to explore: Does viewing cat videos online have the same kind of positive impact as pet therapy? And do some viewers actually feel worse after watching cat videos because they feel guilty for putting off tasks they need to tackle?
Of the participants in the study, about 36 percent described themselves as a “cat person,” while about 60 percent said they liked both cats and dogs.
Participants in Myrick’s study reported:
· They were more energetic and felt more positive after watching cat-related online media than before.
· They had fewer negative emotions, such as anxiety, annoyance and sadness, after watching cat-related online media than before.
· They often view Internet cats at work or during studying.
· The pleasure they got from watching cat videos outweighed any guilt they felt about procrastinating.
· Cat owners and people with certain personality traits, such as agreeableness and shyness, were more likely to watch cat videos.
· About 25 percent of the cat videos they watched were ones they sought out; the rest were ones they happened upon.
· They were familiar with many so-called “celebrity cats,” such as Nala Cat and Henri, Le Chat Noir.
Overall, the response to watching cat videos was largely positive.
“Even if they are watching cat videos on YouTube to procrastinate or while they should be working, the emotional pay-off may actually help people take on tough tasks afterward,” Myrick said.
The results also suggest that future work could explore how online cat videos might be used as a form of low-cost pet therapy, she said.
For each participant who took the survey, Myrick donated 10 cents to Lil Bub’s foundation, raising almost $700. The foundation, Lil Bub’s Big Fund for the ASPCA, has raised more than $100,000 for needy animals.
Public Release: 16-Jun-2015
Extreme exercise linked to blood poisoning
Monash University
Researchers have discovered that extreme exercise can cause intestinal bacteria to leak into the bloodstream, leading to blood poisoning.
Experts at Monash University monitored people participating in a range of extreme endurance events, including 24-hour ultra-marathons and multi-stage ultra-marathons, run on consecutive days.
“Blood samples taken before and after the events, compared with a control group, proved that exercise over a prolonged period of time causes the gut wall to change, allowing the naturally present bacteria, known as endotoxins, in the gut to leak into the bloodstream. This then triggers a systemic inflammatory response from the body’s immune cells, similar to a serious infection episode.
Significantly the study found that individuals who are fit, healthy and follow a steady training program to build up to extreme endurance events, develop immune mechanisms to counteract this, without any side effects.
However individuals who take part in extreme endurance events, especially in the heat and with little training, put their bodies under enormous strain above the body’s protective capacity. With elevated levels of endotoxins in the blood, the immune system’s response can be far greater than the body’s protective counter-action. In extreme cases, it leads to sepsis induced systemic inflammatory response syndrome, which can be fatal if it is not diagnosed and treated promptly.
The study, led by Dr Ricardo Costa, from the Department of Nutrition and Dietetics, is the first to identify a link between extreme endurance exercise and the stress it may place on gut integrity.
“Nearly all of the participants in our study had blood markers identical to patients admitted to hospital with sepsis. That’s because the bacterial endotoxins that leach into the blood as a result of extreme exercise, triggers the body’s immune cells into action.”
The 24-hour ultra-marathon study, published in the International Journal of Sports Medicine and the multi-stage ultra-marathon study, published in Exercise Immunology Reviews, both by Dr Costa’s team, reinforces current guidelines for people wanting to take part in extreme endurance events. These include getting a health check first and developing a training program that builds fitness and endurance progressively to meet the stresses and strains of the event.
Dr Costa said anything over four hours of exercise and repetitive days of endurance exercise is considered extreme.
“Exercising in this way is no longer unusual – waiting lists for marathons, Ironman triathlon events and ultra-marathons are the norm and they’re growing in popularity,” he said.
“It’s crucial that anyone who signs up to an event, gets a health check first and builds a slow and steady training program, rather than jumping straight into a marathon, for example, with only a month’s training,” he said.
The research team found that people who were fitter and trained over a longer period of time leading into the ultra-marathon event had higher levels of Interleukin 10 – an anti-inflammatory agent, which allowed them to dampen down the negative health impacting immune response.
“The body has the ability to adapt and put a brake on negative immune responses triggered by extreme endurance events. But if you haven’t done the training and you’re unfit – these are the people who can get into trouble,” Dr Costa said.
The next phase will see Dr Costa’s team conduct further research into fully understanding the degree to which exercise, with and without heat, impacts gut integrity and function. They will also investigate and develop strategies for individuals to prevent and manage gut damage and symptoms caused by exercise and heat stress.
Fructose powers a vicious circle
‘Walk through any supermarket and take a look at the labels on food products, and you’ll see that many of them contain fructose, often in the form of sucrose (table sugar)’ — that’s how Wilhelm Krek, professor for cell biology at ETH Zurich’s Institute for Molecular Health Sciences, summarises the problem with today’s nutrition. Prepared foods and soft drinks in particular, but even purportedly healthy fruit juices contain fructose as an artificial additive — often in high quantities. In recent decades fructose spread throughout the food market, due to a reputation as being less harmful than glucose. In contrast to glucose, fructose barely increases blood glucose levels and insulin secretion. This avoids frequently recurring insulin spikes after any glucose consumption, which are judged harmful. In addition, fructose is sweeter to the taste.
But there’s a downside: the liver converts fructose very efficiently into fat. People who consume too much high-fructose food can in time become overweight and develop high blood pressure, dyslipidaemia with fatty liver and insulin resistance — symptoms that doctors group together under the name metabolic syndrome.
Unchecked growth of the heart muscle
A new paper by Krek and his team member Peter Mirtschink describes a further, more troubling side effect of fructose. The researchers have discovered a previously unknown molecular mechanism that points to fructose as a key driver of uncontrolled growth of the heart muscle, a condition that can lead to fatal heart failure. Their study was recently published in Nature.
When a person has high blood pressure, the heart has to grow as it is harder to pump the blood through the circulatory system. These growing heart muscle cells require a considerable amount of oxygen. However, since not enough oxygen is available to adequately supply the increased growth, the cells switch to an alternative energy supply. Instead of drawing energy from fatty acids, they rely more on an anaerobic process called glycolysis — literally, the ‘splitting of sugars’. If the heart muscle cells can access fructose in addition to glucose, this can set off a fatal chain reaction.
Flipping the switch for fructose metabolism
In the study, Krek’s research group demonstrates that a lack of oxygen in the heart cells cues the appearance of the HIF molecule. This is a universal molecular switch that flips whenever a pathological growth process is under way, such as cardiac enlargement or cancer. HIF causes the heart muscle cells to produce ketohexokinase-C (KHK-C), the central enzyme in fructose metabolism. KHK-C has a high affinity for fructose and can therefore process it very efficiently. The production of KHK-C also has a reinforcing effect on glycolysis. Since fructose metabolism doesn’t involve any negative feedback regulation, a vicious cycle starts that can lead to heart failure.
To investigate this mechanism, the researchers used not only mouse models but also biological samples from patients with pathological heart enlargement accompanied by a narrowing of the aortic valve. Samples of heart muscle cells taken by surgeons during heart operations provided the ETH researchers with the means for proving that such cells really do have more HIF and KHK-C molecules. In mice that were suffering from chronic high blood pressure, the researchers turned off the KHK enzyme, which indeed inhibited enlargement of the heart.
One gene, two enzymes
Another fact worthy of note is that the body also contains KHK-A, an enzyme very similar to KHK-C except that it has poor preference for fructose. Both these enzymes have the same genetic code; the difference between them comes from how a molecular cutting tool tailors their construction blueprint — their messenger RNA, which is a transcript of the relevant gene. Depending on requirements, one of two blueprints can be generated from the same gene to produce either of two different enzymes. The expert term for this process is ‘alternative splicing’. Krek explains, ‘About 95 percent of all human genes are alternatively spliced. It’s a major way to create the extraordinary variety of proteins, enzymes and regulators in the human body.’
Normally primarily liver cells produce the fructose-friendly KHK-C enzyme; other organs produce almost exclusively KHK-A. Now for the first time, the ETH researchers are showing that even an organ like the heart is capable of producing KHK-C, the more efficient of the two enzymes, if it is exposed to pathogenic stress factors. In the process, HIF activates the molecular cutting tool, or splicing factor, SF3B1. This molecule is often genetically altered in many types of cancer, which possibly indicates that even the growth of cancer can be affected by fructose.
Normal fruit consumption safe
Large volumes of fructose are added to many foods, but especially to sweet beverages and soft drinks. This practice drove up per capita consumption of high fructose corn syrup in the USA between 1970 and 1997, from 230 grams per year to over 28 kilograms.
But Mirtschink provides reassurance that eating a normal amount of fruit daily is safe and healthy. ‘Besides fructose, fruit contains plenty of important trace elements, vitamins and fibre,’ he says. People should, however, avoid overly sweet soft drinks and fruit juices — these often have sugar added — as well as ready-made meals and other foods to which large amounts of fructose are added as a flavour carrier. ‘Just this surplus of fructose can help trigger the mechanism we have described if one of the stress factors is present, such as cardiac valve disease or high blood pressure,’ Mirtschink emphasises.
Public Release: 17-Jun-2015
Individuals with social phobia have too much serotonin — not too little
Uppsala University
Previous studies have led researchers to believe that individuals with social anxiety disorder/ social phobia have too low levels of the neurotransmitter serotonin. A new study carried out at Uppsala University, however, shows that the situation is exactly the opposite. Individuals with social phobia make too much serotonin. The more serotonin they produce, the more anxious they are in social situations.
Many people feel anxious if they have to speak in front of an audience or socialise with others. If the anxiety becomes a disability, it may mean that the person suffers from social phobia which is a psychiatric disorder.
Social phobia is commonly medicated using SSRI compounds. These change the amount of the neurotransmitter serotonin in the brain. Based on previous studies, it was believed that individuals with social phobia had too little serotonin and that SSRIs increased the amount of available serotonin. In a new study published in the scientific journal JAMA Psychiatry, researchers from the Department of Psychology at Uppsala University show that individuals with social phobia make too much serotonin.
The research team, led by professors Mats Fredrikson and Tomas Furmark, used a so-called PET camera and a special tracer to measure chemical signal transmission by serotonin in the brain. They found that patients with social phobia produced too much serotonin in a part of the brain’s fear centre, the amygdala. The more serotonin produced, the more anxious the patients were in social situations.
A nerve cell, which sends signals using serotonin, first releases serotonin into the space between the nerve cells. The nerve signal arises when serotonin attaches itself to the receptor cell. The serotonin is then released from the receptor and pumped back to the original cell.
‘Not only did individuals with social phobia make more serotonin than people without such a disorder, they also pump back more serotonin. We were able to show this in another group of patients using a different tracer which itself measures the pump mechanism. We believe that this is an attempt to compensate for the excess serotonin active in transmitting signals’, says Andreas Frick, a doctoral student at Uppsala University Department of Psychology.
This discovery is a major leap forward when it comes to identifying changes in the brain’s chemical messengers in people who suffer from anxiety. Earlier research has shown that nerve activity in the amygdala is higher in people with social phobia and thus that the brain’s fear centre is over-sensitive. The new findings indicate that a surplus of serotonin is part of the underlying reason.
‘Serotonin can increase anxiety and not decrease it as was previously often assumed’, says Andreas Frick.
Public Release: 17-Jun-2015
Knowledge about alternative medicine connected to education, income
San Francisco State University
People with lower educational levels and incomes are less likely to know about yoga, acupuncture, natural products and chiropractic medicine, according to a new study from San Francisco State University.
Studies on the use of complementary and alternative medicine (CAM) have typically focused on learning more about who use these types of practices and why. Less is known about trends among those who do not partake, which inspired new research by Professor of Health Education Adam Burke, published in PLOS ONE on June 17.
“It’s very important to know why somebody is not doing a particular behavior,” said Burke, who is also the director of SF State’s Institute for Holistic Health Studies. “If your child isn’t eating broccoli and you want him to, you need to know why. If it’s just a matter of the pieces being too big, you can cut it up. But if you don’t know why, the child will not eat the broccoli.”
The research, based on the 2007 National Health Interview Survey, looked at data from more than 13,000 respondents who said they had never used acupuncture, chiropractic, natural products or yoga, four common CAM practices.
Lack of knowledge as a reason for non-use was strongly associated with lower education levels and income. Those who attended college were 58 percent less likely to indicate lack of knowledge as a reason for non-use, and individuals with higher incomes were 37 percent less likely.
“The implication of this study is that the lack of access to health knowledge is a root of health inequity,” Burke said. “If you are poor, you have less access to health information for a variety of reasons.”
Physical activity levels were also found to correlate with knowledge. People who described themselves as less physically active were significantly more likely to claim a lack of knowledge of all four complementary practices.
One finding of the study that surprised Burke was that the results held true for survey respondents who experienced lower back pain. Since back pain is the medical condition most commonly linked to use of complementary health treatments, Burke and his coauthors hypothesized that back-pain sufferers would have greater knowledge about these treatments even if they opted not to use them, as their pain would compel them to learn about a variety of remedies. But Burke found that the relationship between lower education levels and lack of knowledge remained — in other words, back pain did not seem to be a significant enough motivator to seek out these common alternative treatments.
But it’s especially important for people with back pain to know about CAM methods, Burke said. “Often, the solution for chronic pain is addictive prescription medications, which are problematic in all communities, especially in lower-income communities,” Burke said. “Complementary methods have the potential to mitigate such addiction problems, and may help address the root problem rather than just managing the symptoms, which is a real benefit.”
This study indicates a greater need among doctors to follow best-practice guidelines for sharing information about integrative practices, combining conventional western and CAM approaches, Burke said.
“It’s highly likely that a lack of knowledge prevents some individuals from using these integrative approaches — if they knew more, they would use them more,” Burke said. “These are cost-effective treatments that have limited side effects and may actually help remediate people’s problems. Especially in lower-income communities, it is important for health care providers to recommend them.”
“Limited health knowledge as a reason for non-use of four common complementary health practices” by Adam Burke and co-authors Richard L. Nahin and Barbara J. Stussman of the National Center for Complementary and Integrative Health was published in PLOS ONE on June 17.
Public Release: 18-Jun-2015
WSU scientists turn white fat into obesity-fighting beige fat
A new twist on the health benefits of resveratrol
Washington State University
PULLMAN, Wash. – Washington State University scientists have shown that berries, grapes and other fruits convert excess white fat into calorie-burning “beige” fat, providing new strategies for the prevention and treatment of obesity.
In the study, mice were fed a high fat diet. Those receiving resveratrol in amounts equivalent to 12 ounces of fruit per day for humans gained about 40 percent less weight than control mice. Resveratrol is a polyphenol, a type of antioxidant found in most fruits.
Previous studies have suggested that resveratrol can help prevent obesity but how it did that was unclear. Most of the research, including highly publicized studies on wine, also used very large concentrations of resveratrol, much more than a human could consume in a normal diet.
Professor of animal sciences Min Du and visiting scientist Songbo Wang demonstrated that mice fed a diet containing 0.1 percent resveratrol were able to change their excess white fat into the active, energy-burning beige fat.
“Polyphenols in fruit, including resveratrol, increase gene expression that enhances the oxidation of dietary fats so the body won’t be overloaded,” said Du. “They convert white fat into beige fat which burns lipids off as heat – helping to keep the body in balance and prevent obesity and metabolic dysfunction.”
The researchers also showed that an enzyme called AMPK, which regulates the body’s energy metabolism, stimulates this transition of white fat into beige fat.
The study was recently published in the International Journal of Obesity. It was funded by the National Institutes of Health, the National Natural Science Foundation of China and an Emerging Research Issues Internal Competitive Grant from the WSU College of Agriculture, Human, and Natural Resource Sciences. None of the funders had a role in the interpretation of the results.
The whole package
Resveratrol has been billed as a natural way to slow aging and fight cancer, heart disease, Alzheimer’s disease, obesity and diabetes but many of the claims are still under debate.
Du said resveratrol is only one of the polyphenolic compounds found in fruit that provides beneficial health effects.
“We are using resveratrol as a representative for all of the polyphenols,” he said.
“We are still using it as a pure compound to be consistent with the study that came out 20 years ago in the medical journal, The Lancet, showing that resveratrol in wine has beneficial effects.”
“In reality, it’s the total polyphenolic content that is more important,” Du said. “We think you can increase your total intake of polyphenol compounds by directly increasing fruit consumption.”
Du said those compounds are high in all fruits but especially rich in blueberries, strawberries, raspberries, grapes and apples. Twelve ounces is about two or three servings per day.
Wines like merlot or cabernet sauvignon, in contrast, contain only a fraction of resveratrol and other phenolic compounds found in grapes, he said.
“Many of the beneficial polyphenols are insoluble and get filtered out during the wine production process,” he said.
For consumers who want to add fiber and these bioactive compounds to their diet, it’s much better to eat the whole fruit, Du said.
Three types of fat
Researchers had always assumed there were only two types of fat, said Du – the white fat where lipids are stored as energy and brown fat that burns lipids to produce heat.
Several years ago, scientists discovered a new type of fat – beige fat – which is in between white and brown fat. Du said beige fat is generated from white fat in a process called “browning.”
“Resveratrol can enhance this conversion of white fat to beige fat and when you have high rates of browning, it can partially prevent obesity,” he said.
In the study, adult female mice were fed a high-fat diet. Those supplemented with resveratrol were 40 percent less likely to develop diet-induced obesity compared to control mice who gained weight.
Du said white fat is protective when it’s healthy. But too much leads to imbalance and disease.
“The current theory is that when we eat excessively, the extra lipids are stored in white fat. With obesity, the fat cells enlarge to a point where they’re saturated and can’t uptake more lipids,” he said. “As the fat cells become overloaded and die, they release toxins and cause inflammation leading to health problems like insulin resistance and diabetes.
“Polyphenols like resveratrol are good as they enhance the oxidation of fat so it won’t be overloaded. The excess is burned off as heat,” he said.
Public Release: 18-Jun-2015
Increased anxiety associated with sitting down
Low-energy activities that involve sitting down are associated with an increased risk of anxiety, according to research published in the open-access journal BMC Public Health
BioMed Central
Low energy activities that involve sitting down are associated with an increased risk of anxiety, according to research published in the open access journal BMC Public Health. These activities, which include watching TV, working at a computer or playing electronic games, are called sedentary behavior. Further understanding of these behaviors and how they may be linked to anxiety could help in developing strategies to deal with this mental health problem.
Many studies have shown that sedentary behavior is associated with physical health problems like obesity, heart disease, type 2 diabetes and osteoporosis. However, there has been little research into the link between sedentary behavior and mental health. This is the first systematic review to examine the relationship between anxiety and sedentary behavior.
Anxiety is a mental health illness that affects more than 27 million people worldwide. It is a debilitating illness that can result in people worrying excessively and can prevent people carrying out their daily life. It can also result in physical symptoms, which amongst others includes pounding heartbeat, difficulty breathing, tense muscles, and headaches.
Megan Teychenne, lead researcher and lecturer at Deakin University’s Centre for Physical Activity and Nutrition Research (C-PAN) in Australia, said: “Anecdotally – we are seeing an increase in anxiety symptoms in our modern society, which seems to parallel the increase in sedentary behavior. Thus, we were interested to see whether these two factors were in fact linked. Also, since research has shown positive associations between sedentary behavior and depressive symptoms, this was another foundation for further investigating the link between sedentary behavior and anxiety symptoms.”
C-PAN researchers analyzed the results of nine studies that specifically examined the association between sedentary behavior and anxiety. The studies varied in what they classified as sedentary behavior from television viewing/computer use to total sitting time, which included sitting while watching television, sitting while on transport and work-related sitting. Two of the studies included children/adolescents while the remaining seven included adults.
It was found in five of the nine studies that an increase in sedentary behavior was associated with an increased risk of anxiety. In four of the studies it was found that total sitting time was associated with increased risk of anxiety. The evidence about screen time (TV and computer use) was less strong but one study did find that 36% of high school students that had more than 2 hours of screen time were more like to experience anxiety compared to those who had less than 2 hours.
The C-PAN team suggests the link between sedentary behavior and anxiety could be due to disturbances in sleep patterns, social withdrawal theory and poor metabolic health. Social withdrawal theory proposes that prolonged sedentary behavior, such as television viewing, can lead to withdrawal from social relationships, which has been linked to increased anxiety. As most of the studies included in this systematic-review were cross-sectional the researchers say more follow-up work studies are required to confirm whether or not anxiety is caused by sedentary behavior.
Megan Teychenne said: “It is important that we understand the behavioral factors that may be linked to anxiety – in order to be able to develop evidence-based strategies in preventing/managing this illness. Our research showed that evidence is available to suggest a positive association between sitting time and anxiety symptoms – however, the direction of this relationship still needs to be determined through longitudinal and interventional studies.”
Public Release: 19-Jun-2015
Scientists identify amino acid that stops seizures in mice
Finding suggests novel mechanism for treating epilepsy
Johns Hopkins Medicine
An amino acid whose role in the body has been all but a mystery appears to act as a potent seizure inhibitor in mice, according to a study by researchers at Johns Hopkins.
In a series of experiments, the amino acid D-leucine, found in many foods and certain bacteria, interrupted prolonged seizures, a serious condition known as status epilepticus, and it did so just as effectively as the epilepsy drug diazepam — the choice of treatment for patients in the throes of convulsions — but without any of the drug’s sedative side effects.
Results of the federally funded research, reported online June 4 in the journal Neurobiology of Disease, also suggest that D-leucine works differently from all current anti-seizure therapies — a finding that may pave the way for much-needed treatments for the nearly one-third of people with epilepsy with drug-resistant forms of the condition, marked by recalcitrant seizures.
“Epilepsy treatments over the last 50 years have not improved much, so there’s an acute need for better therapeutic approaches, especially for the millions of people with drug-resistant epilepsy,” says lead investigator Adam Hartman, M.D., a pediatric neurologist at the Johns Hopkins Children’s Center and an associate professor of neurology at the Johns Hopkins University School of Medicine. “If confirmed in larger animals and humans, our results carry a real promise for those suffering from unremitting seizures.”
Amino acids, the building blocks of proteins, are sources of energy and are critical for many biochemical reactions in the body, but many specific roles of the various amino acids remain elusive.
In the current study, investigators started out with the premise that certain amino acids may play a role in seizure prevention because they produce some of the same metabolic by-products as high-fat ketogenic diets, an alternative therapy for patients whose seizures are not well controlled on medication. A form of the diet was used as standard epilepsy treatment in the 1920s and 1930s during the pre-medication era but fell out of favor when the first epilepsy drugs emerged. An improved version of the diet, brought back into vogue by the late Johns Hopkins neurologist John Freeman, offered relief to countless children with drug-resistant seizures. However, the food regimen requires complex calculations, can be challenging to follow and doesn’t always provide complete seizure control.
In an initial set of experiments, researchers pre-treated mice with the amino acid L-leucine and another one, called D-leucine, which has a nearly identical structure to L-leucine and is essentially its biochemical mirror image.
When researchers induced seizures with shock therapy, animals pre-treated with either amino acid fared better, developing seizures at notably higher electric currents than mice that received placebo, a sign of greater seizure resistance.
To see whether D-leucine and L-leucine could also interrupt ongoing seizures, researchers induced seizures in a group of animals and, once convulsions began, they administered low and high doses of both amino acids. L-leucine failed to abort ongoing seizures, while D-leucine effectively interrupted convulsions. Strikingly, the researchers say, D-leucine terminated seizures even at low doses. Next, researchers compared the ability of D-leucine to terminate prolonged, unrelenting seizures against the sedative diazepam, commonly used stop such seizures in humans. Both treatments terminated seizures, but D-leucine did so about 15 minutes earlier. In addition, mice treated with D-leucine resumed normal behavior faster and experienced none of the drowsiness and sluggishness observed in animals treated with the drug, also common side effects seen in human patients.
A final set of experiments measured D-leucine interaction with several nerve receptors known to be involved in cell-to-cell signaling and seizure activity. Surprisingly, D-leucine interacted with none of the signaling pathways known to spark or avert seizures.
“Our results suggest that D-leucine affects neurons differently from other known therapies to control seizures,” says senior investigator J. Marie Hardwick, Ph.D., the David Bodian Professor in microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health. “This finding gives us hope of new approaches to epilepsy on the horizon.”
Model could help counteract poisoning from popular painkiller
Reversing the deadly side effects of Tylenol overdose
Duke University
DURHAM, N.C. — New research could help reverse deadly side effects caused by excessive doses of the drug acetaminophen, the major ingredient in Tylenol and many other over-the-counter and prescription medicines.
Researchers at Duke University have developed a mathematical model of acetaminophen metabolism based on data from lab rats. The findings suggest that giving patients glutamine — a common amino acid in the body — alongside the standard antidote for acetaminophen overdose could prevent liver damage and boost the body’s ability to recover.
The results appear online and are scheduled to be published in the July 2015 issue of the Journal of Theoretical Biology.
Known for relieving minor aches and pains without upsetting the stomach like some other pain medicines, acetaminophen is a major ingredient in Tylenol and more than 600 other store brand pain relievers, fever reducers, cold remedies and allergy medicines, as well as prescription painkillers like Percocet and Vicodin.
One in four people in the U.S. take at least one acetaminophen-containing product a week. More than 27 billion doses of acetaminophen-containing products were sold in the U.S. in 2009 alone, making it the most widely-used over-the-counter or prescription drug in the country.
Available without a prescription for more than 50 years, the drug is safe when used as directed. But taking more than the maximum recommended dose of four grams per day can damage the liver. In extreme cases patients die unless they get a liver transplant.
More than 44,000 people end up in the emergency room and four hundred people die in the U.S. each year as a result of acetaminophen overdose. Many cases involve children or infants whose parents accidentally measure the wrong dose in the middle of the night, or combine different medicines without realizing that they all contain the same ingredient — for example, Tylenol for a fever and then a second medicine for a cough.
To find out if tweaking current overdose protocols could prevent fatal liver damage, Duke mathematicians Lydia Bilinsky and Mike Reed and Duke biologist Fred Nijhout developed a mathematical model of acetaminophen metabolism, based on previous studies of lab rats given high doses of the drug.
Acetaminophen is broken down in the body into several byproducts, one of which can be toxic to the liver.
At normal doses, the liver is able to clean this toxin from the body with the help of a naturally-occurring protective molecule called glutathione. Trouble starts when the recommended dose of acetaminophen is exceeded, and the body’s natural detox process requires more glutathione than the liver can make.
The standard antidote for acetaminophen overdose is a drug called N-acetylcysteine, or NAC, which helps restore glutathione levels to normal by adding the glutathione precursor that is usually in shortest supply.
But by modeling the dozens of biochemical reactions involved in synthesizing, transporting and breaking down glutathione in the body, the researchers found that the rarest ingredient changes over time.
Most of what the body needs to make glutathione comes from three amino acid precursors — glycine, glutamate and cysteine. Usually the glutathione precursor in shortest supply is cysteine, which is also found in NAC.
But the researchers discovered that after an overdose, liver cells turn on a gene that shuttles desperately-needed cysteine into the cell but pumps glutamate out, until eventually glutamate levels start to run low, too.
To test the model, the researchers plan to treat overdosed mice with different relative concentrations of NAC and glutamine — which the liver converts to glutamate — to see which dosing combinations maximize their survival.
“NAC has been the standard antidote for acetaminophen overdose for decades, and we are excited at the chance of improving it,” the authors said.
Public Release: 24-Jun-2015
New Zealand blackcurrants good for the brain
New Zealand Institute for Plant and Food Research
Research has shown that New Zealand blackcurrants are good for keeping us mentally young and agile, a finding that could have potential in managing the mental decline associated with aging populations, or helping people with brain disorders such as Parkinson’s disease or depression.
The research, conducted by scientists at Plant & Food Research (New Zealand) in collaboration with Northumbria University (UK), showed that compounds found in New Zealand blackcurrants increased mental performance indicators, such as accuracy, attention and mood. The study also showed that juice from a specific New Zealand blackcurrant cultivar, ‘Blackadder’, also reduced the activity of a family of enzymes called monoamine oxidases, which regulate serotonin and dopamine concentrations in the brain. These chemicals are known to affect mood and cognition, and are the focus for treatments of both neurodegenerative symptoms associated with Parkinson’s disease and mood disorders, including stress and anxiety.
Results of the research have been published online in the Journal of Functional Foods, a leading journal in the field.
“This study is the first to look at the effects of berry consumption on the cognitive performance of healthy young adults,” says Dr. Arjan Scheepens, the Plant & Food Research scientist who led the study. “Our previous research has suggested that compounds found in certain berryfruit may act like monoamine oxidase inhibitors, similar to a class of pharmaceuticals commonly used in the treatment of both mood disorders and neurodegenerative diseases like Parkinson’s disease. This research has shown that New Zealand-grown blackcurrants not only increase mental performance, but also reduce the activity of monoamine oxidases.”
“One of the key trends in the food industry is the development of ingredients and foods that have beneficial effects on human health,” says professor Roger Hurst, Science Group Leader Food & Wellness at Plant & Food Research. “Understanding what, and how, foods affect mental performance could lead to the development of new foods designed for populations or situations where mental performance or mental decline is a factor, such as older people or those suffering from stress, anxiety or other mood disorders. This research shows how New Zealand blackcurrants can potentially add value, both for the food industry and for people looking for foods that naturally support their own health aspirations.”
Participants in the study — 36 healthy adults aged between 18 and 35 years — consumed a 250ml drink prior to conducting a set of demanding mental performance assessments. The participants consumed either a sugar and taste-matched placebo (no blackcurrant), an anthocyanin-enriched New Zealand blackcurrant extract (Delcyan™ from Just the Berries) or a cold-pressed juice from the New Zealand blackcurrant cultivar ‘Blackadder’, bred by Plant & Food Research. The assessments showed that after consuming the Delcyan™ and ‘Blackadder’ drinks, attention and mood were improved while mental fatigue was reduced. In addition, blood tests showed that the activity of the monoamine oxidase enzymes (MAO) was strongly decreased after consuming the ‘Blackadder’ juice, indicating the potential for compounds found in ‘Blackadder’ blackcurrants as a functional food ingredient to support brain health or managing the symptoms of disorders like Parkinson’s disease.
Public Release: 25-Jun-2015
A person’s diet, acidity of urine may affect susceptibility to UTIs
Washington University School of Medicine
The acidity of urine — as well as the presence of small molecules related to diet — may influence how well bacteria can grow in the urinary tract, a new study shows. The research, at Washington University School of Medicine in St. Louis, may have implications for treating urinary tract infections, which are among the most common bacterial infections worldwide.
The study appears in the June 26 issue of the Journal of Biological Chemistry.
Urinary tract infections (UTIs) often are caused by a strain of bacteria called Escherichia coli (E. coli), and doctors long have relied on antibiotics to kill the microbes. But increasing bacterial resistance to these drugs is leading researchers to look for alternative treatment strategies.
“Many physicians can tell you that they see patients who are particularly susceptible to urinary tract infections,” said senior author Jeffrey P. Henderson, M.D., Ph.D., assistant professor of medicine. “We often don’t know why certain people seem to be prone to recurrent UTIs. For a long time, we had inexpensive antibiotics that worked really well for this. But over the last 10-15 years, we have seen a huge jump in bacterial infections that are resistant to many of these drugs.”
With this in mind, Henderson and his team, including first author Robin R. Shields-Cutler, a graduate student in Henderson’s lab, were interested in studying how the body naturally fights bacterial infections. They cultured E. coli in urine samples from healthy volunteers and noted major differences in how well individual urine samples could harness a key immune protein to limit bacterial growth.
“We could divide these urine samples into two groups based on whether they permitted or restricted bacterial growth,” Henderson said. “Then we asked, what is special about the urine samples that restricted growth?”
The urine samples that prevented bacterial growth supported more activity of this key protein, which the body makes naturally in response to infection, than the samples that permitted bacteria to grow easily. The protein is called siderocalin, and past research has suggested that it helps the body fight infection by depriving bacteria of iron, a mineral necessary for bacterial growth. Their data led the researchers to ask if any characteristics of their healthy volunteers were associated with the effectiveness of siderocalin.
“Age and sex did not turn out to be major players,” Shields-Cutler said. “Of all the factors we measured, the only one that was really different between the two groups was pH — how acidic or basic the urine was.”
Henderson said that conventional wisdom in medicine favors the idea that acidic urine is better for restricting bacterial growth. But their results were surprising because samples that were less acidic, closer to the neutral pH of pure water, showed higher activity of the protein siderocalin and were better at restricting bacterial growth than the more acidic samples.
Importantly, the researchers also showed that they could encourage or discourage bacterial growth in urine simply by adjusting the pH, a finding that could have implications for how patients with UTIs are treated.
“Physicians are very good at manipulating urinary pH,” said Henderson, who treats patients with UTIs. “If you take Tums, for example, it makes the urine less acidic. But pH is not the whole story here. Urine is a destination for much of the body’s waste in the form of small molecules. It’s an incredibly complex medium that is changed by diet, individual genetics and many other factors.”
After analyzing thousands of compounds in the samples, the researchers determined that the presence of small metabolites called aromatics, which vary depending on a person’s diet, also contributed to variations in bacterial growth. Samples that restricted bacterial growth had more aromatic compounds, and urine that permitted bacterial growth had fewer.
Henderson and his colleagues suspect that at least some of these aromatics are good iron binders, helping deprive the bacteria of iron. And perhaps surprisingly, these molecules are not produced by human cells, but by a person’s gut microbes as they process food in the diet.
“Our study suggests that the body’s immune system harnesses dietary plant compounds to prevent bacterial growth,” Henderson said. “We identified a list of compounds of interest, and many of these are associated with specific dietary components and with gut microbes.”
Indeed, their results implicate cranberries among other possible dietary interventions. Shield-Cutler noted that many studies already have investigated extracts or juices from cranberries as UTI treatments but the results of such investigations have not been consistent.
“Its possible that cranberries may be more effective when paired with a treatment to make the urine less acidic,” Henderson said. “And even then, maybe cranberries only work in people who have the right gut microbes.”
The investigators also studied the bacteria’s strategies for resisting the body’s innate immunity. E.coli make a compound called enterobactin that binds strongly to iron, stealing it from the host. The new study showed that enterobactin is particularly good at binding iron in urine. So finding ways to block it may open up new opportunities for developing antimicrobial drugs that work very differently from traditional antibiotics.
The researchers said there are many future directions for this research, including working out more of the details governing whether the body or the bacteria will win the battle over iron, and exploring the specifics of the gut microbiomes of their healthy volunteers.
Public Release: 25-Jun-2015
Compound in magnolia may combat head and neck cancers
Honokiol, from magnolia bark, shuts down cancer cells in lab
Veterans Affairs Research Communications
Magnolias are prized for their large, colorful, fragrant flowers. Does the attractive, showy tree also harbor a potent cancer fighter?
Yes, according to a growing number of studies, including one from VA and the University of Alabama at Birmingham that is now online in the journal Oncotarget.
The study focused on squamous cell head and neck cancers, a scourge among those who use tobacco and alcohol. According to the National Cancer Institute, at least 3 in 4 head and neck cancers are caused by the use of tobacco and alcohol. The cancers have only a 50 percent survival rate, killing some 20,000 Americans each year.
Enter honokiol–chemical formula C18H18O2. As one of the major active compounds in magnolia extract, the phytochemical has been used for centuries in traditional Chinese and Japanese medicine to treat anxiety and other conditions. More recently, scientists have been discovering that the compound, found in magnolia bark, is a wily and versatile adversary of cancer. It seems to exploit many biochemical pathways to shrink tumors of various types, or to keep them from growing in the first place.
The Alabama scientists have now shown how it works against head and neck cancers: It blocks a protein called epidermal growth factor receptor, or EGFR. Prior research has found that almost all head and neck cancer cells display an over-abundance of the protein, and it had been suggested in the literature as a potential target.
The VA-UAB team says, based on its lab studies, that honokiol binds more strongly with EGFR than does the drug gefitinib (sold as Iressa), which is commonly used to treat head and neck cancers.
The researchers tested honokiol on cell lines derived from human cancers of the oral cavity, larynx, tongue, and pharynx. In all cases, the botanical shut down the aberrant cells. The team also tested it against tumors implanted into mice, with similar results.
Senior author Dr. Santosh K. Katiyar and his colleagues wrote, “Conclusively, honokiol appears to be an attractive bioactive small molecule phytochemical for the management of head and neck cancer which can be used either alone or in combination with other available therapeutic drugs.”
Katiyar has published extensively in the past on other natural substances that work against tumors, especially skin cancer. Some of his recent work has focused on compounds in green tea, for example, and grape seed proanthocyanidins.
Public Release: 25-Jun-2015
New study: Tart cherry juice reduced post-race respiratory tract symptoms after a marathon
Weber Shandwick Worldwide
LANSING, Mich. June 25 — While previous research suggests tart cherry juice may help aid muscle recovery after extensive exercise, a new pilot study published in the Journal of the International Society of Sports Nutrition found that Montmorency tart cherry juice reduced upper respiratory tract symptoms associated with marathon running in study participants. Post-race sniffles are a common problem among endurance athletes.
The U.K. research team, led by Glyn Howatson at Northumbria University and Lygeri Dimitriou at Middlesex University, found that marathon runners who consumed the tart cherry juice had lower markers for inflammation than a placebo group at 24 and 48 hours post-marathon, and had no reported incidences of upper respiratory tract symptoms (URTS) up to 48 hours after the race. For the runners who did not drink the tart cherry juice, 50 percent suffered from URTS.
“Many athletes can suffer from colds and sore throats following strenuous bouts of exercise, like marathon running and triathlons. This is the first study to provide encouraging evidence of the potential role of Montmorency tart cherries in reducing symptoms associated with the development of exercise-induced respiratory problems,” said Howatson, who has conducted previous studies on tart cherry juice and exercise recovery. “We should be looking at all the potential ways we can help athletes recover from strenuous exercise, and protection of the respiratory system is another dimension.”
Research Methodology
For this study, 20 recreational Marathon runners consumed two servings of either a placebo drink or a blend of Montmorency tart cherry juice combined with apple juice twice a day (morning and afternoon) for eight consecutive days — five days leading up to a marathon, on the day of the race and two days afterwards. Each 236 ml serving (about 8-ounces) contained the equivalent of 50-60 whole Montmorency tart cherries and at least 40 mg anthocyanins. Montmorency tart cherries are the most common variety of tart cherries grown in the U.S., and are available year-round in dried, frozen and juice forms.
Markers of stress, inflammation, mucosal immunity and upper respiratory tract symptoms were measured on four occasions: the day before the marathon, immediately after, and at 24 hours and 48 hours post-marathon. C-reactive protein, a marker for inflammation was significantly elevated in both groups, but its response at 24 and 48 hours following the marathon was blunted in the cherry juice group compared to the placebo. This is consistent with previous studies that examined the impact of cherry juice on post-exercise inflammation indices in marathon runners and cyclists. 2,3,4 All participants refrained from nutritional supplements, pharmacological interventions and strenuous exercise (other than completing marathon training runs) for the duration of the study.
The authors conclude that the results of this pilot study offer an important new opportunity for research, building on the existing body of evidence providing support for the use of Montmorency tart cherry juice in exercise recovery. They suggest future work should examine the prevalence of URTS beyond 48 hours post-marathon.