245 CNO Report 07 JUL 2017

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CNO Report # 245

Release Date  07 JUL 2017

Draft Report Compiled by

Ralph Turchiano

http://www.clinicalnews.org

 

 

 

 

In this issue:

1.       Plant compound more powerful than AZT against HIV

2.       Could broccoli be a secret weapon against diabetes?

3.       Replacing saturated fat with healthier fat may lower cholesterol as well as drugs

4.       Gut bacteria might one day help slow down aging process

5.       Grape-based compounds kill colon cancer stem cells in mice

6.       We are much more unique than assumed

7.       African plant extract offers new hope for Alzheimer’s

8.       High fat diet reduces gut bacteria, Crohn’s disease symptoms

9.       With health care cuts looming, low-cost magnesium a welcome option for treating depression

10.   Sunscreen creams break down into dangerous chemical compounds under the sunlight

11.   Patients with multiple sclerosis may benefit from over-the-counter therapy

12.   Researchers find link between food allergies and childhood anxiety

13.   Vegetable colouring agent may suppress inflammation

14.   Sugar intake during pregnancy is associated with allergy and allergic asthma in children

15.   Smelling your food makes you fat

16.   Vitamin D may improve sunburn, according to new clinical trial

 

Public Release: 14-Jun-2017

Plant compound more powerful than AZT against HIV

University of Illinois at Chicago

A plant found throughout Southeast Asia traditionally used to treat arthritis and rheumatism contains a potent anti-HIV compound more powerful than the drug AZT, according to a new paper published in the Journal of Natural Compounds.

The chemical, patentiflorin A, is derived from the willow-leaved Justicia, and was identified in a screening of more than 4,500 plant extracts for their effect against the HIV virus.

The discovery is one of the results of a multi-year research partnership made up of scientists from the University of Illinois at Chicago, Hong Kong Baptist University, and the Vietnam Academy of Science and Technology working together as an International Cooperative Biodiversity Group. These groups, funded by the National Institutes of Health, National Science Foundation and the U.S. Department of Agriculture, look for natural products that may have applications in health and medicine, and also work to support sustainable use of these resources in low-income countries.

Lijun Rong, professor of microbiology and immunology in the UIC College of Medicine; Harry Fong, associate director of the World Health Organization Program for Traditional Medicine; and Doel Soejarto, professor emeritus of medicinal chemistry and pharmacognosy in the UIC College of Pharmacy, led the UIC team. Rong is an expert at identifying antiviral agents, Soejarto is a renowned plant scientist, and Fong is a well-known pharmacologist.

The willow-leaved Justicia extract had been taken from the leaves, stems and roots of plants that had been collected in Cuc Phuong National Park in Hanoi, Vietnam more than 10 years ago by Soejarto. The UIC/Hong Kong/Vietnam ICBG analyzed the extract along with thousands of others as part of their efforts to identify new drugs against HIV, tuberculosis, malaria and cancer.

Rong and his colleagues zeroed in on patentiflorin A because of its ability to inhibit an enzyme needed for HIV to incorporate its genetic code into a cell’s DNA. AZT, the first anti-HIV drug developed and marketed in 1987, and which remains the cornerstone of HIV drug cocktails today, inhibits this enzyme, called reverse transcriptase. In studies of human cells infected with the HIV virus, patentiflorin A had a much more significant inhibition effect on the enzyme.

“Patentiflorin A was able to inhibit the action of reverse transcriptase much more effectively than AZT, and was able to do this both in the earliest stages of HIV infection when the virus enters macrophage cells, and alter infection when it is present in T cells of the immune system,” said Rong. It also was effective against known drug-resistant strains of the HIV virus, making it a very promising candidate for further development into a new HIV drug.

“Patentiflorin A represents a novel anti-HIV agent that can be added to the current anti-HIV drug cocktail regimens to increase suppression of the virus and prevention of AIDS,” Rong said.

The researchers were also able to synthesize patentiflorin A. “If we can make the drug in the lab, we don’t need to establish farms to grow and harvest the plant, which requires significant financial investment, not to mention it has an environmental impact,” Rong said.

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Along with Soejarto and Fong, additional co-authors on the paper include Emily Rumschlag-Booms, UIC College of Medicine; Hong-Jie Zhang, Yi-Fu Guan, Dong-Ying Wang, Kang-Lun Liu, and Wan-Fei Li, Hong Kong Baptist University; and Van Nguyen and Nguyen Cuong, Vietnam Academy of Science and Technology. This project was supported by the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKBU 262912); the Health and Medical Research Fund (12132161) of the Food and Health Bureau, Hong Kong SAR; the Hong Kong Baptist University Interdisciplinary Research Matching Scheme (RC-IRMS/15-16/02), Hong Kong Baptist University (FRG2/11-12/134 and FRG2/14-15/047); NIH Grants 3U01TW001015-10S1 and 2U01TW001015-11A1, administered by the Fogarty International Center, as part of an International Cooperative Biodiversity Groups program; and a grant from the Mr. Kwok Yat Wai and Madam Kwok Chung Bo Fun Graduate School Development Fund.

Public Release: 14-Jun-2017

Could broccoli be a secret weapon against diabetes?

American Association for the Advancement of Science

Concentrated broccoli sprout extract may help type 2 diabetes patients manage their blood sugar, according to a new study. The findings could offer a much needed alternative to address the condition, which has become a worldwide epidemic. Type 2 diabetes afflicts more than 300 million people globally, and as many as 15% of those patients cannot take the first-line therapy metformin because of kidney damage risks. Seeking a more viable path forward, Annika Axelsson and colleagues used a computational approach to identify compounds that might counter the disease-associated gene expression changes associated with type 2 diabetes. The researchers constructed a signature for type 2 diabetes based on 50 genes, then used publically available expression datasets to screen 3,852 compounds for drugs that potentially reverse disease. The most promising chemical — sulforaphane, a naturally occurring compound found in cruciferous vegetables — tamped down glucose production by liver cells growing in culture, and shifted liver gene expression away from a diseased state in diabetic rats. When the researchers gave concentrated broccoli sprout extracts to 97 human type 2 diabetes patients in a 12-week randomized placebo-controlled trial, obese participants who entered the study with dysregulated disease demonstrated significantly decreased fasting blood glucose levels compared to controls. The authors say developing gene signatures to investigate large public repositories of gene expression data could be a valuable strategy to rapidly identify clinically relevant compounds.

Public Release: 15-Jun-2017

Replacing saturated fat with healthier fat may lower cholesterol as well as drugs

American Heart Association Presidential Advisory

American Heart Association

DALLAS, June 17, 2017 – The American Heart Association continues to recommend replacing saturated fats with poly- and mono-unsaturated vegetable oil to help prevent heart disease, according to a new American Heart Association advisory, published in the association’s journal Circulation.

Periodically, the evidence supporting limiting saturated fats has been questioned in scientific literature and the popular press. This advisory was commissioned to review the current evidence and explain the scientific framework behind the American Heart Association’s long-standing recommendation to limit foods high in saturated fats.

“We want to set the record straight on why well-conducted scientific research overwhelmingly supports limiting saturated fat in the diet to prevent diseases of the heart and blood vessels,” said Frank Sacks, M.D., lead author of the advisory and professor of Cardiovascular Disease Prevention at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts. “Saturated fat increases LDL – bad cholesterol – which is a major cause of artery-clogging plaque and cardiovascular disease.”

Saturated fats are found in meat, full-fat dairy products and tropical oils such as coconut, palm and others. Other types of fats include poly-unsaturated fats, found in corn, soybean, peanut and other oils, and mono-unsaturated fats, found in olive, canola, safflower, avocado and other oils. The advisory reports that:

·         Randomized controlled trials that lowered intake of dietary saturated fat and replaced it with polyunsaturated vegetable oil reduced cardiovascular disease by approximately 30 percent -similar to that achieved by cholesterol-lowering drugs, known as statins.

·         Prospective observational studies in many populations showed that lower intake of saturated fat coupled with higher intake of polyunsaturated and monounsaturated fat is associated with lower rates of cardiovascular disease.

·         Several studies found that coconut oil – which is predominantly saturated fat and widely touted as healthy – raised LDL cholesterol in the same way as other saturated fats found in butter, beef fat and palm oil.

·         Replacement of saturated fat with mostly refined carbohydrate and sugars is not associated with lower rates of CVD.

“A healthy diet doesn’t just limit certain unfavorable nutrients, such as saturated fats, that can increase the risk of heart attacks, strokes and other blood vessel diseases. It should also focus on healthy foods rich in nutrients that can help reduce disease risk, like poly- and mono-unsaturated vegetable oils, nuts, fruits, vegetables, whole grains, fish and others,” Sacks said.

Examples of healthy dietary patterns include the Dietary Approaches To Stop Hypertension (DASH) diet and a Mediterranean-style diet, both of which emphasize unsaturated vegetable oils, nuts, fruits, vegetables, low-fat dairy products, whole grains, fish and poultry and limits red meat, as well as foods and drinks high in added sugars and salt.

Public Release: 15-Jun-2017

Gut bacteria might one day help slow down aging process

Baylor College of Medicine

Slowing down the aging process might be possible one day with supplements derived from gut bacteria. Scientists at Baylor College of Medicine and the University of Texas Health Science Center at Houston have identified bacterial genes and compounds that extend the life of and also slow down the progression of tumors and the accumulation of amyloid-beta, a compound associated with Alzheimer’s disease, in the laboratory worm C. elegans. The study appears in the journal Cell.

“The scientific community is increasingly aware that our body’s interactions with the millions of microbes in our bodies, the microbiome, can influence many of our functions, such as cognitive and metabolic activities and aging,” said corresponding author Dr. Meng Wang, associate professor of molecular and human genetics at Baylor and the Huffington Center On Aging. “In this work we investigated whether the genetic composition of the microbiome might also be important for longevity.”

This question is difficult to explore in mammals due to technical challenges, so the researchers turned to the laboratory worm C. elegans, a transparent, simple organism that is as long as a pinhead and shares essential characteristics with human biology. During its 2 to 3 week long lifespan, the worm feeds on bacteria, develops into an adult, reproduces, and progressively ages, loses strength and health and dies. Many research laboratories around the world, including the Wang lab, work with C. elegans to learn about basic biological processes.

“We think that C. elegans is a wonderful system in which to study the connection between bacterial genes and aging because we can very fine tune the genetics of microbes and test many genes in the worm in a relatively short time,” Wang said.

Testing thousands of genes, one at a time.

To study the effect of individual bacterial genes on the lifespan of C. elegans, Wang joined efforts with Dr. Christophe Herman, associate professor of molecular and human genetics and molecular virology and microbiology at Baylor, and other colleagues who are experts in bacterial genetics. They employed a complete gene-deletion library of bacterium E. coli; a collection of E. coli, each lacking one of close to 4,000 genes. “We fed C. elegans each individual mutant bacteria and then looked at the worms’ life span,” Wang said. “Of the nearly 4,000 bacterial genes we tested, 29, when deleted, increased the worms’ lifespan. Twelve of these bacterial mutants also protected the worms from tumor growth and accumulation of amyloid-beta, a characteristic of Alzheimer’s disease in humans.”

Further experiments showed that some of the bacterial mutants increased longevity by acting on some of the worm’s known processes linked to aging. Other mutants encouraged longevity by over-producing the polysaccharide colanic acid. When the scientists provided purified colanic acid to C. elegans, the worms also lived longer. Colanic acid also showed similar effects in the laboratory fruit fly and in mammalian cells cultured in the lab.

The researchers propose that, based on these results, it might be possible in the future to design preparations of bacteria or their compounds that could help slow down the aging process.

Colanic acid mediates crosstalk between bacteria and mitochondria

Interestingly, the scientists found that colanic acid regulates the fusion-fission dynamics of mitochondria, the structures that provide the energy for the cell’s functions.

“These findings are also interesting and have implications from the biological point of view in the way we understand host-microbe communication,” Wang said. “Mitochondria seem to have evolved from bacteria that millions of years ago entered primitive cells. Our finding suggests that products from bacteria today can still chime in the communication between mitochondria in our cells. We think that this type of communication is very important and here we have provided the first evidence of this. Fully understanding microbe-mitochondria communication can help us understand at a deeper level the interactions between microbes and their hosts.”

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Other contributors to this work include Bing Han, Priya Sivaramakrishnan, Chih-Chun J. Lin, Isaiah A.A. Neve, Jingquan He, Li Wei Rachel Tay, Jessica N. Sowa, Antons Sizovs, Guangwei Du and Jin Wang.

Financial support for this project was provided by the National Institutes of Health grants R01AG045183, R01AT009050, DP1DK113644, R01HL119478, R01GM088653, R01GM115622, R01CA207701 and Howard Hughes Medical Institute Faculty Scholar Award.

Public Release: 19-Jun-2017

Grape-based compounds kill colon cancer stem cells in mice

Penn State

Compounds from grapes may kill colon cancer stem cells both in a petri dish and in mice, according to a team of researchers.

The compounds — resveratrol –which are found in grape skins and seeds, could also eventually lead to treatments to help prevent colon cancer, said Jairam K.P. Vanamala, associate professor of food sciences, Penn State. Colorectal cancer is the second leading cause of cancer-related deaths in the U.S., according to the American Cancer Society.

“The combination of resveratrol and grape seed extract is very effective at killing colon cancer cells,” said Vanamala, who is also a faculty member at the Penn State Hershey Cancer Institute. “And what we’re learning is the combination of these compounds is not toxic to healthy cells.”

The researchers, who reported their findings in a recent issue of BMC Complementary and Alternative Medicine, suggest that the findings could pave the way for clinical testing of the compounds on human colon cancer, which is the second most common cancer in women and the third in men. If successful, the compounds could then be used in a pill to help prevent colon cancer and lessen the recurrence of the disease in colon cancer survivors.

“We are particularly interested in targeting stem cells because, according to cancer stem-cell theory, cancerous tumors are driven by cancer stem cells,” said Vanamala. “Cancer stem cells are capable of self-renewal, cellular differentiation and maintain their stem cell-like characteristics even after invasion and metastasis.”

When taken separately in low doses, resveratrol and grape seed extract are not as effective against cancer stem-cell suppression as when they are combined together, according to the researchers.

The combined effect of grape seed extract and resveratrol may offer clues as to why cultures with a plant-based diet tend to have lower colon cancer rates, said Vanamala. These diets may naturally be providing a shotgun approach to cancer prevention by using a wide variety of beneficial compounds to target multiple pathways that cancer stem cells use to survive.

“This also connects well with a plant-based diet that is structured so that the person is getting a little bit of different types of plants, of different parts of the plant and different colors of the plant,” said Vanamala. “This seems to be beneficial for not only promoting bacterial diversity, but also preventing chronic diseases and eliminating the colon cancer stem cells.”

If successful in human trials, the compounds could be taken in low doses using currently available supplements for grape seed extract and resveratrol, which are also found in wine.

However, he added that there is still more work to do to understand the mechanism behind the anti-cancer properties of the grape extract, as well as other colorful fruits and vegetables. Further research would be aimed at finding specific anti-cancer compounds and better understanding how those compounds work synergistically to create more effective colon-cancer prevention and treatment strategies.

For the animal study, the researchers separated 52 mice with colon cancer tumors into three groups, including a control group and groups that were fed either the grape compounds or sulindac, an anti-inflammatory drug, which was chosen because a previous study showed it significantly reduced the number of tumors in humans.

The incidence of tumors was suppressed in the mice consuming the grape compounds alone by 50 percent, similar to the rate in the group consuming the diet with sulindac.

Public Release: 19-Jun-2017

We are much more unique than assumed

Computational biologists discover surprisingly strong effects from protein variation

Technical University of Munich (TUM)

Every human being has a unique DNA “fingerprint”. In other words, the genetic material of any two individuals can be clearly distinguished. Computational biologists at the Technical University of Munich (TUM) have now determined that the impact of these variations has been greatly underestimated. The new insights could importantly impact advances in personalized medicine.

Proteins are the machinery of life. Without them, no cell can function. About 20,000 different proteins are responsible for metabolism, growth and regeneration in the human body. The building blocks of proteins are the amino acids. These are assembled in the cell according to a defined blueprint contained in DNA.

An extensive study in which blood samples of 60,000 people were examined has shown that surprisingly wide variations exist between the proteins of healthy individuals: In two non-related individuals, on average 20,000 building blocks — i.e. amino acids — have differences known as SAVs (single amino acid variants). The MacArthur Lab in the USA has assembled about 10 million of these SAVs.

“Until now, many experts believed most of these variants to have no substantial impact upon protein function,” says Prof. Burkhard Rost, Chair for Bioinformatics and Computational Biology at TUM. This assumption is difficult to prove: Experimental studies cannot be carried out for such an enormous number of SAVs. In fact, relevant experimental data are available for fewer than 0.01 percent of the SAVs.

The TUM researchers have therefore developed a method that enables predicting the effects of the SAVs through computer simulations. Using data obtained in laboratory experiments, a program predicts the probable effect for the 99.99 percent of the SAVs about which nothing is known. “Along with statistical methods, we use artificial intelligence, and in particular machine learning and neural networks. That enables us to create models,” explains Yannick Mahlich, lead author of the study.

The researchers were surprised by their own results: For millions of SAVs in the proteins of healthy people, strong effects were predicted. Sequence variations seen in more than five percent of the population, are predicted to have a bigger impact on cell functions than rare variations, i.e. those observed in fewer than one percent of the people.

The computational biologists cannot determine the exact nature of the effects, however. The variations might, e.g. affect our ability to detect smells or might result in differences in metabolism; they might lead to disease, or increase the immunity to pathogens. They can also affect an individual’s response to environmental influences or medications. “None of these effects might be detected in everyday life,” says Prof. Rost. “But under certain conditions some of them could become significant, for example when we are given a certain drug or are exposed to a certain influence for the first time.”

In his view, the effects of the protein variations cannot be simply categorized as good or bad. “The comparison of the effects of the variations between individuals as well as between humans and related species suggests that every species tries out many variations.” These may even be detrimental to individuals under today’s conditions. But if the environmental conditions change, it is conceivable that the same variations might help the species to survive.

“Research into the effects of variations on the structure and function of proteins is just getting started,” says Prof. Rost. However, he believes that the new insights will deliver important impetus paving the way to advances in personalized medicine: “The capabilities already exist to use DNA to discover the function of individual proteins. In the future we will also be able to use that information to determine the best foods and drugs for the individual.”

Public Release: 20-Jun-2017

African plant extract offers new hope for Alzheimer’s

University of Nottingham

A plant extract used for centuries in traditional medicine in Nigeria could form the basis of a new drug to treat Alzheimer’s disease, researchers at The University of Nottingham have found.

Their study, published in the journal Pharmaceutical Biology, has shown that the extract taken from the leaves, stem and roots of Carpolobia lutea, could help to protect chemical messengers in the brain which play a vital role in functions including memory and learning.

The tree extract could pave the way for new drugs to tackle patient symptoms but without the unwanted side-effects associated with some current treatments.

The study was led by Dr Wayne Carter in the University’s Division of Medical Sciences and Graduate Entry Medicine, based at Royal Derby Hospital. He said: “As a population we are living longer, and the number of people with dementia is growing at an alarming rate. Our findings suggest that traditional medicines will provide new chemicals able to temper Alzheimer’s disease progression.”

Neurodegenerative diseases represent a huge health burden globally, placing pressure on health services and having a negative impact on the lives of patients and their families.

Researchers and drug companies are racing to discover new treatments for these disorders and have begun looking to plant extracts as a potential source of novel drugs.

In patients with Alzheimer’s disease and other diseases such as Parkinson’s disease and myasthenia gravis, the activity of the neurotransmitter acetylcholine, is reduced, leading to problems with memory and attention.

Current drugs – called acetylcholinesterase inhibitors – reduce the normal breakdown of acetylcholine. Extensive research is underway to find new versions of these drugs but with additional beneficial properties.

Carpolobia lutea, known more commonly as cattle stick, is a small shrub or tree found native to Central and West Africa. Herbalists in Nigerian tribes use the essence of the root as an aphrodisiac and the treatment of genitourinary infections, gingivitis, and waist pains.

It has also been reported to possess other anti-inflammatory, anti-arthritic, antimicrobial, antimalarial, and analgesic properties. This could be particularly important in Alzheimer’s disease as there is more evidence emerging that Alzheimer’s patients have inflammation in the brain.

The Nottingham study found that the plant was highly effective in preventing the breakdown of acetylcholine but had other beneficial antioxidant properties in fighting free radicals – unstable atoms that can cause damage to cells and contribute to ageing and disease – damage that may be exacerbated in Alzheimer’s disease.

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The paper, Anti-Acetylcholinesterase Activity and Antioxidant Properties of Extracts and Fractions of Carpolobia lutea, is published in the journal Pharmaceutical Biology and was carried out in collaboration with the University of Port Harcourt in Nigeria and Mansoura University in Egypt.

Public Release: 22-Jun-2017

High fat diet reduces gut bacteria, Crohn’s disease symptoms

Results could lead to new anti-inflammatory probiotics

Case Western Reserve University

Researchers at Case Western Reserve University School of Medicine have shown a high fat diet may lead to specific changes in gut bacteria that could fight harmful inflammation–a major discovery for patients suffering from Crohn’s disease. Crohn’s disease, a type of inflammatory bowel syndrome, causes debilitating intestinal swelling, cramping, and diarrhea. The disease affects half a million people in the United States, but its cause is yet unclear.

In the new study, a diet of plant-derived “good” fats, including coconut oil or cocoa butter, drastically reduced bacterial diversity in mice with Crohn’s-like disease. Mice fed beneficial fatty diets had up to thirty percent fewer kinds of gut bacteria as those fed a normal diet, collectively resulting in a very different gut microbial composition. Some of the species changes showed up in feces, while others were different in cecum, a portion of the intestine commonly inflamed in Crohn’s disease. Mice fed even low concentrations of coconut oil or cocoa butter also had less severe small intestine inflammation.

“The finding is remarkable because it means that a Crohn’s patient could also have a beneficial effect on their gut bacteria and inflammation by only switching the type of fat in their diet,” said Alexander Rodriguez-Palacios, DVM, DVSc, PhD, first author on the study and Assistant Professor of Medicine at Case Western Reserve University. “Patients would only need to replace a ‘bad’ fat with a ‘good’ fat, and eat normal amounts.”

The study is one of the first to identify specific changes in gut bacteria–our microbiome–associated with Crohn’s disease. It is also the first to show how high fat diets can alter gut bacteria to combat inflammation. Rodriguez-Palacios presented his results at the annual Digestive Disease Week® conference in Chicago, Illinois earlier this month. The study was one of six accepted for presentation at the conference out of the laboratory of Fabio Cominelli, MD, PhD, Professor of Medicine and Pathology at Case Western Reserve University, and Division Chief of Gastroenterology at University Hospitals Cleveland Medical Center.

Results from the study could help doctors identify bacteria to use in probiotics to treat patients suffering from inflammatory bowel syndromes. “Ongoing studies are now helping us to understand which component of the ‘good’ and ‘bad’ fats make the difference in the gut microbes and make mice healthier,” Rodriguez-Palacios said. “Ultimately, we aim to identify the ‘good’ fat-loving microbes for testing as probiotics.”

The researchers anticipate their findings may have varying effects for patients. “Not all ‘good’ fats might be good in all patients,” Rodriguez-Palacios cautioned. “Mice indicate that each person could respond differently. But diet is something we are very hopeful could help at least some patients without the side-effects and risks carried by drugs. The trick now is to really discover what makes a fat ‘good’ or ‘bad’ for Crohn’s disease.”

Public Release: 27-Jun-2017

With health care cuts looming, low-cost magnesium a welcome option for treating depression

Larner College of Medicine at the University of Vermont

Depression presents an enormous disease burden, with a reported 350 million people worldwide suffering from the disease, but traditional SSRI treatments carry a burden of their own – in dollars and side effects. New clinical research published today in PLoS One shows that over-the-counter magnesium appears safe and effective to treat mild to moderate depression.

Critical to such body functions as heart rhythm, blood pressure and bone strength, the mineral magnesium plays a role in combating inflammation in the body and has been proven to have an association with depression. However, few clinical trials have studied the supplement’s effects.

Emily Tarleton, MS, RD, CD, a graduate student in Clinical and Translational Science and the bionutrition research manager in the University of Vermont’s Clinical Research Center, and colleagues conducted a clinical trial of over-the-counter oral magnesium tablets for mild-to-moderate depression. Their results showed that magnesium is safe and effective and comparable to prescription SSRI treatments in effectiveness.

The researchers at the University of Vermont’s Larner College of Medicine conducted an open-label, blocked, randomized cross-over trial involving 126 adults in outpatient primary care clinics. The study participants, who were currently experiencing mild-to-moderate depression, had a mean age of 52, with 38 percent of them male. Participants in the active arm of the study received 248 milligrams of elemental magnesium per day over six weeks, while those in the control arm received no treatment. Depression symptom assessments were conducted on all participants on a bi-weekly basis.

The study team found that in 112 participants with analyzable data, consumption of magnesium chloride for six weeks resulted in a clinically significant improvement in measures of depression and anxiety symptoms. In addition, these positive effects were shown quickly, at two weeks, and the supplements were well tolerated and similarly effective regardless of age, sex, or use of antidepressants, among other factors.

“This is the first randomized clinical trial looking at the effect of magnesium supplementation on symptoms of depression in U.S. adults,” says Tarleton. “The results are very encouraging, given the great need for additional treatment options for depression, and our finding that magnesium supplementation provides a safe, fast and inexpensive approach to controlling depressive symptoms.”

Tarleton and colleagues say the next step is to see if their promising results can be replicated in a larger, more diverse population.

Public Release: 27-Jun-2017

Sunscreen creams break down into dangerous chemical compounds under the sunlight

Scientists of Moscow State University have found out that avobenzone decomposes into harmful chemical compounds

Lomonosov Moscow State University

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IMAGE: Scientists from the Faculty of Chemistry of the Lomonosov Moscow State University have demonstrated in their research the nature of hazardous chemical compounds formed as a result of the breakdown… view more

Credit: Albert Lebedev

Scientists from the Faculty of Chemistry of the Lomonosov Moscow State University have demonstrated in their research the nature of hazardous chemical compounds formed as a result of the breakdown of avobenzone, a component of many sunscreen products, when it interacts with chlorinated water and ultraviolet radiation. The chemists have presented the results in the Chemosphere journal.

The chemists from the Lomonosov Moscow State University have chosen avobenzone as an object of research. Avobenzone is a derivative of a chemical compound, named dibenzoylmethane. This choice has been conditioned by the fact that this is the most popular UV filter in the world. Avobenzone was patented in 1973 and in 1988 approved by FDA (the Food and Drug Administration, a federal agency of the United States Department of Health and Human Services), dealing with control and supervision of food products, pharmaceutical drugs, cosmetics, tobacco products and some other categories of products. The ability of avobenzone to absorb ultraviolet light in a wide range of wave lengths has ended in its widespread use in the following products: lipsticks, creams and other cosmetics.

Sunscreen products, containing avobenzone, are applied by millions of people all over the world. Chemical UV filters like avobenzone absorb ultraviolet light due to the peculiarities of their structures. Absorbing ultraviolet radiation avobenzone translates it into waves with other length, which aren’t harmful for the skin (in other words, it translates energy of light into thermal energy). Thus the substance in itself is safe, however, the Russian scientists have managed to prove that in water solution it’s capable of breaking down into hazardous chemical compounds.

The scientists from the Lomonosov Moscow State University have defined the products forming as a result of the breakdown of avobenzone in chlorinated water and under the sunlight. These experiments simulated the real situation, when a sunscreen, applied on the skin of swimming people, gets into contact with the water in swimming pools. The breakdown of avobenzone may take place right on the wet human skin, on which a sunscreen is spread.

The chemists have revealed that avobenzone breaks down in the water, forming various organic compounds, belonging to the classes of aromatic acids and aldehydes, phenols and acetyl benzenes. Phenols and chlorinated acetyl benzenes have turned out to be the most toxic products. The latter ones and, in particular chloracetophenone, enter into the composition of lachrymatory mixtures, used by police for disrupting meetings.

Albert Lebedev, Doctor of Chemistry, one of the project authors says: “On the basis of the experiments one could make a conclusion that a generally safe compound transforms in the water and forms more dangerous products. In spite of the fact that there are no precise toxicological profiles for the most established products, it’s known that acetyl benzenes and phenols, especially chorinated ones, are quite toxic.”

Chromatomass spectrometry became the basic research method. This reliable and effective method allows conducting qualitative and quantitative analysis of the most complex mixtures of chemical compounds.

Albert Lebedev continues: “Studying the products of transformation of any popular cosmetics is very important as very often they turn out to be much more toxic and dangerous than their predecessors. In principle, basing on such researches, one could obtain results, which could restrict or even put under a ban the usage of one or another product, and preserve health of millions of people.”

At the moment the scientists are studying the transformation of avobenzone under conditions of chlorination and bromination of fresh and sea water. During chlorination or bromination of sea water the number of the breakdown products of avobenzone will be even wider. And if water contains copper salts (which are added into many swimming pools for getting nice light-blue color), then bromoform is formed in large quantities. This substance could provoke dysfunctions of liver and kidneys, along with nervous system disorder.

Public Release: 29-Jun-2017

Patients with multiple sclerosis may benefit from over-the-counter therapy

Results from OHSU-led research will be tested in large-scale clinical trial

Oregon Health & Science University

Treatment options currently are limited for people suffering from secondary progressive multiple sclerosis. However, an OHSU pilot study suggests over-the-counter antioxidant lipoic acid holds promise in improving patients’ lives.

The research was published June 28 in the journal Neuroimmunology & Neuroinflammation.

The randomized double-blind study involved 51 participants who completed the two-year trial. Twenty-seven people were given a 1,200-milogram daily dose of lipoic acid, with the remaining 24 participants given a placebo. Researchers are using the findings from the pilot trial to design the expanded multi-site clinical trial to begin later this year in Portland and other sites that have yet to be finalized.

“These are high doses,” said lead author Rebecca Spain, M.D., M.S.P.H., an assistant professor of neurology in the OHSU School of Medicine. “And while it seems safe, we won’t know whether it actually improves the lives of people with MS until we can replicate the results in the pilot study through a much bigger clinical trial. Fortunately, we’re going to be able to answer that question with the participation of kind volunteers.”

MS is a chronic condition that affects an estimated 2.3 million people worldwide. In MS, the sheath covering nerve fibers in the brain and spinal cord becomes damaged, slowing or blocking electrical signals from the brain reaching the eyes, muscles and other parts of the body.

The major finding of the pilot study involved measuring the degree to which lipoic acid arrested the rate of whole brain atrophy, as measured through magnetic resonance imaging.

The study revealed a 68 percent improvement over the placebo in slowing the rate of whole brain atrophy in patients with secondary progressive MS. For the sake of comparison, a clinical trial involving the recent FDA-approved pharmaceutical Ocrevus showed an 18 percent improvement over a placebo in slowing the rate of whole brain atrophy for patients with primary progressive forms of the disease.

In addition, the pilot study suggested improved walking times and fewer falls among study participants who took a daily dose of lipoic acid compared with those who received the placebo. Researchers are eager to test those outcomes in the larger clinical trial.

A companion study, published concurrently by Neuroimmunology & Neuroinflammation, measured the rate of absorption and clearance of lipoic acid through periodic blood tests of pilot study participants. The results will help to inform the design of additional clinical trials.

Lipoic acid was determined to be safe and well-tolerated by pilot study participants. Stomach upset was the most frequent side effect.

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The study was funded by the Department of Veterans Affairs (B7493, Spain) and the National Institutes of Health (UL1TR000128). Pure Encapsulations of Sudbury, Massachusetts, provided the lipoic acid and placebo.

Public Release: 29-Jun-2017

Researchers find link between food allergies and childhood anxiety

Columbia University’s Mailman School of Public Health

June 29, 2017 — Researchers at Columbia University’s Mailman School of Public Health and Albert Einstein College of Medicine studied the link between food allergy and childhood anxiety and depression among a sample of predominantly low socioeconomic status minority children. The results showed that children with a food allergy had a significantly higher prevalence of childhood anxiety. Food allergies were not associated with symptoms of childhood depression or with symptoms of anxiety or depression among their caregivers. The results are published in the Journal of Pediatrics.

Food allergies are increasingly common among youth in the U.S. with recent estimates as high as 8 percent. Until now little was known about the prevalence of food allergy in low socioeconomic ethnic minority populations.

The researchers studied 80 pediatric patients ages 4-12 years, 8 years old on average, with and without food allergy and their caregivers from urban pediatric outpatient clinics in the Bronx, New York. They controlled for an asthma diagnosis in the children, as anxiety and mood disorders are more prevalent among youth with asthma and especially more common in low socioeconomic minority children.

Among the children with a food allergy, 57 percent reported having symptoms of anxiety compared to 48 percent of children without a food allergy. Approximately 48 percent of the children had symptoms of depression with or without a food allergy.

“Management of food allergy can be expensive both in terms of food shopping, meal preparation, and the cost of epinephrine auto-injectors, which expire annually,” said Renee Goodwin, PhD, in the Department of Epidemiology at the Mailman School of Public Health and lead author. “These demands could result in higher levels of anxiety for those with fewer financial resources and further heighten anxiety symptoms in children and their caregivers.”

The results suggest that food allergy is particularly linked to elevated social anxiety and fear of social rejection and humiliation. “There are a number of possible explanations for the relationship found between food allergy diagnosis and increased social anxiety issues in this sample of pediatric patients,” noted Dr. Goodwin. “Management of a potentially life-threatening condition may be anxiety provoking, and some children may experience increased social anxiety about being “different” from other children depending on their age and how food allergy is managed by adults in a particular setting.”

The researchers also point out a possible explanation for not finding a link between food allergy and depression in children. The sample was young, and the mean age of onset for depression is significantly later than anxiety. “It would be worthwhile to examine these relationships among older adolescents and young adults with food allergy who are at the peak of risk for depression onset, especially because early anxiety is associated with increased risk for subsequent onset of depression,” said Jonathan Feldman, PhD, professor at Ferkauf Graduate School of Psychology, Yeshiva University.

“With the high prevalence of food allergies today, education in schools remains a priority,” said Dr. Goodwin. “Given the strong association between food allergy and social anxiety in children future investigations on the food allergy-mental health relationship are also warranted in clinical, school, and community-based settings which could aid in the development of interventions.”

Public Release: 5-Jul-2017

Vegetable colouring agent may suppress inflammation

Linköping University

Lutein, a nutrient found in several highly coloured vegetables and fruits, can suppress inflammation, according to a new study by researchers at Linkoping University, Sweden. The results, published in Atherosclerosis, suggest that lutein itself has anti-inflammatory effects in patients with coronary artery disease.

Inflammation is a key factor in many types of coronary artery disease, such as myocardial infarction and angina.

“A considerable number of patients who have experienced myocardial infarction still have low-level chronic inflammation in the body, even after receiving effective treatment with revascularisation, drugs and lifestyle changes. We know that chronic inflammation is associated with a poorer prognosis,” says Lena Jonasson, professor in the Department of Medical and Health Sciences and consultant in cardiology, who has led the study.

Previous research has suggested that our diet influences inflammatory processes in the body. One group of substances that may be interesting are the carotenoids, a large family of fat-soluble natural colouring agents found in plants. Beta-carotene and lycopene are among the more well-known substances in the family. Several previous studies have shown that the levels of carotenoids are inversely correlated with inflammation markers. The question has thus arisen whether carotenoids themselves have anti-inflammatory effects.

Most previous studies into the relationship between carotenoids and inflammation have been carried out on animals or healthy human volunteers. However, the cells of the immune system in people with low-level inflammation are more prone to stimulation, and may react differently than the corresponding cells in healthy people. The researchers who carried out the new study, therefore, wanted to investigate whether carotenoid has anti-inflammatory effects in patients with coronary artery disease.

“Our study confirms that one particular carotenoid, lutein, can suppress long-term inflammation in patients with coronary artery disease. We have also shown that lutein is absorbed and stored by the cells of the immune system in the blood,” says Rosanna Chung, postdoc at the Department of Medical and Health Sciences at Linkoping University.

The researchers started by measuring the levels of the six most common carotenoids in blood from 193 patients with coronary artery disease. At the same time, they measured the level of inflammation in the blood using the inflammatory marker interleukin-6, IL-6. Lutein was the only carotenoid whose level was correlated with IL-6. The higher the level of lutein in the blood, the lower the level of IL-6.

“The patients were receiving the best possible treatment for their disease according to clinical guidelines, but even so, many of them had a persistent inflammation. At the same time, the patients had lower levels of lutein,” says Lena Jonasson.

This led the researchers to investigate whether lutein can influence the cells in the blood that are involved in inflammatory processes. They collected cells of the immune system from blood from patients with coronary artery disease. They found that the inflammatory activity of the cells became significantly lower when they were treated with lutein.

The researchers now plan to investigate whether increased intake of food rich in lutein has a positive effect on the immune system in patients with coronary artery disease. Vegetables with dark-green leaves, such as spinach, are particularly rich in lutein.

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Public Release: 5-Jul-2017

Sugar intake during pregnancy is associated with allergy and allergic asthma in children

Queen Mary University of London

High maternal sugar intake during pregnancy may increase the risk of allergy and allergic asthma in the offspring, according to an early study led by Queen Mary University of London (QMUL) involving almost 9,000 mother-child pairs.

While some research has reported an association between a high consumption of sugar-containing beverages and asthma in children, the relation between maternal sugar intake during pregnancy and allergy and asthma in the offspring has been little studied.

The team, which included researchers from University of Bristol, used data from a world-leading birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC), also known as ‘Children of the 90s’. The cohort recruited mothers who were pregnant in the early 1990s and has been following up their offspring ever since.

The current study, which is published in the European Respiratory Journal, analysed associations between maternal intake of free sugars* in pregnancy and allergy (defined by positive skin tests to common allergens, namely dust mite, cat and grass) and asthma at seven years of age.

While there was only weak evidence for a link between free sugar intake in pregnancy and asthma overall, there were strong positive associations with allergy and allergic asthma (where the child was diagnosed with asthma and had positive skin tests to allergens).

When comparing the 20 per cent of mothers with the highest sugar intake versus the 20 per cent of mothers with the lowest sugar intake, there was an increased risk of 38 per cent for allergy in the offspring (73 per cent for allergy to two or more allergens) and 101 per cent for allergic asthma. The team found no association with eczema or hay fever.

Lead researcher Professor Seif Shaheen from QMUL said: “We cannot say on the basis of these observations that a high intake of sugar by mothers in pregnancy is definitely causing allergy and allergic asthma in their offspring. However, given the extremely high consumption of sugar in the West, we will certainly be investigating this hypothesis further with some urgency.

“The first step is to see whether we can replicate these findings in a different cohort of mothers and children. If we can, then we will design a trial to test whether we can prevent childhood allergy and allergic asthma by reducing the consumption of sugar by mothers during pregnancy. In the meantime, we would recommend that pregnant women follow current guidelines and avoid excessive sugar consumption.”

The team speculate that the associations may be explained by a high maternal intake of fructose causing a persistent postnatal allergic immune response leading to allergic inflammation in the developing lung.

The researchers controlled for numerous potential confounders in their analyses, such as background maternal characteristics, social factors and other aspects of maternal diet, including foods and nutrients that have been previously linked to childhood asthma and allergy.

Importantly, the offspring’s free sugar intake in early childhood was found to have no association with the outcomes seen in the analysis.

As the study is observational, it does not prove a causal link between maternal sugar intake and allergies or asthma. A randomised controlled trial would be needed to definitively test causality.

Public Release: 5-Jul-2017

Smelling your food makes you fat

Mice that lost sense of smell stayed slim on high fat diet, while littermates ballooned in weight

University of California – Berkeley

Our sense of smell is key to the enjoyment of food, so it may be no surprise that in experiments at the University of California, Berkeley, obese mice who lost their sense of smell also lost weight.

What’s weird, however, is that these slimmed-down but smell-deficient mice ate the same amount of fatty food as mice that retained their sense of smell and ballooned to twice their normal weight.

In addition, mice with a boosted sense of smell — super-smellers — got even fatter on a high-fat diet than did mice with normal smell.

The findings suggest that the odor of what we eat may play an important role in how the body deals with calories. If you can’t smell your food, you may burn it rather than store it.

These results point to a key connection between the olfactory or smell system and regions of the brain that regulate metabolism, in particular the hypothalamus, though the neural circuits are still unknown.

“This paper is one of the first studies that really shows if we manipulate olfactory inputs we can actually alter how the brain perceives energy balance, and how the brain regulates energy balance,” said Céline Riera, a former UC Berkeley postdoctoral fellow now at Cedars-Sinai Medical Center in Los Angeles.

Humans who lose their sense of smell because of age, injury or diseases such as Parkinson’s often become anorexic, but the cause has been unclear because loss of pleasure in eating also leads to depression, which itself can cause loss of appetite.

The new study, published this week in the journal Cell Metabolism, implies that the loss of smell itself plays a role, and suggests possible interventions for those who have lost their smell as well as those having trouble losing weight.

 

“Sensory systems play a role in metabolism. Weight gain isn’t purely a measure of the calories taken in; it’s also related to how those calories are perceived,” said senior author Andrew Dillin, the Thomas and Stacey Siebel Distinguished Chair in Stem Cell Research, professor of molecular and cell biology and Howard Hughes Medical Institute Investigator. “If we can validate this in humans, perhaps we can actually make a drug that doesn’t interfere with smell but still blocks that metabolic circuitry. That would be amazing.”

Riera noted that mice as well as humans are more sensitive to smells when they are hungry than after they’ve eaten, so perhaps the lack of smell tricks the body into thinking it has already eaten. While searching for food, the body stores calories in case it’s unsuccessful. Once food is secured, the body feels free to burn it.

Zapping olfactory neurons

The researchers used gene therapy to destroy olfactory neurons in the noses of adult mice but spare stem cells, so that the animals lost their sense of smell only temporarily — for about three weeks – before the olfactory neurons regrew.

The smell-deficient mice rapidly burned calories by up-regulating their sympathetic nervous system, which is known to increase fat burning. The mice turned their beige fat cells — the subcutaneous fat storage cells that accumulate around our thighs and midriffs – into brown fat cells, which burn fatty acids to produce heat. Some turned almost all of their beige fat into brown fat, becoming lean, mean burning machines.

In these mice, white fat cells — the storage cells that cluster around our internal organs and are associated with poor health outcomes — also shrank in size.

The obese mice, which had also developed glucose intolerance – a condition that leads to diabetes — not only lost weight on a high-fat diet, but regained normal glucose tolerance.

On the negative side, the loss of smell was accompanied by a large increase in levels of the hormone noradrenaline, which is a stress response tied to the sympathetic nervous system. In humans, such a sustained rise in this hormone could lead to a heart attack.

Though it would be a drastic step to eliminate smell in humans wanting to lose weight, Dillin noted, it might be a viable alternative for the morbidly obese contemplating stomach stapling or bariatric surgery, even with the increased noradrenaline.

“For that small group of people, you could wipe out their smell for maybe six months and then let the olfactory neurons grow back, after they’ve got their metabolic program rewired,” Dillin said.

Dillin and Riera developed two different techniques to temporarily block the sense of smell in adult mice. In one, they genetically engineered mice to express a diphtheria receptor in their olfactory neurons, which reach from the nose’s odor receptors to the olfactory center in the brain. When diphtheria toxin was sprayed into their nose, the neurons died, rendering the mice smell-deficient until the stem cells regenerated them.

Separately, they also engineered a benign virus to carry the receptor into olfactory cells only via inhalation. Diphtheria toxin again knocked out their sense of smell for about three weeks.

In both cases, the smell-deficient mice ate as much of the high-fat food as did the mice that could still smell. But while the smell-deficient mice gained at most 10 percent more weight, going from 25-30 grams to 33 grams, the normal mice gained about 100 percent of their normal weight, ballooning up to 60 grams. For the former, insulin sensitivity and response to glucose – both of which are disrupted in metabolic disorders like obesity – remained normal.

Mice that were already obese lost weight after their smell was knocked out, slimming down to the size of normal mice while still eating a high-fat diet. These mice lost only fat weight, with no effect on muscle, organ or bone mass.

The UC Berkeley researchers then teamed up with colleagues in Germany who have a strain of mice that are supersmellers, with more acute olfactory nerves, and discovered that they gained more weight on a standard diet than did normal mice.

“People with eating disorders sometimes have a hard time controlling how much food they are eating and they have a lot of cravings,” Riera said. “We think olfactory neurons are very important for controlling pleasure of food and if we have a way to modulate this pathway, we might be able to block cravings in these people and help them with managing their food intake.”

Public Release: 6-Jul-2017

Vitamin D may improve sunburn, according to new clinical trial

Results show high doses of vitamin D reduce swelling, inflammation

Case Western Reserve University

High doses of vitamin D taken one hour after sunburn significantly reduce skin redness, swelling, and inflammation, according to double-blinded, placebo-controlled clinical trial out of Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center. The trial results were recently published in the Journal of Investigative Dermatology.

In the study, 20 participants were randomized to receive a placebo pill or 50,000, 100,000, or 200,000 IU of vitamin D one hour after a small UV lamp “sunburn” on their inner arm. Researchers followed up with the participants 24, 48, 72 hours and 1 week after the experiment and collected skin biopsies for further testing. Participants who consumed the highest doses of vitamin D had long-lasting benefits — including less skin inflammation 48 hours after the burn. Participants with the highest blood levels of vitamin D also had less skin redness and a jump in gene activity related to skin barrier repair.

“We found benefits from vitamin D were dose-dependent,” said Kurt Lu, MD, senior author on the study and Assistant Professor of Dermatology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center. “We hypothesize that vitamin D helps promote protective barriers in the skin by rapidly reducing inflammation. What we did not expect was that at a certain dose, vitamin D not only was capable of suppressing inflammation, it was also activating skin repair genes.”

The trial is the first to describe acute anti-inflammatory benefits from taking vitamin D. According to the authors, despite widespread attention given to vitamin D deficiency, “there is a lack of evidence demonstrating that intervention with vitamin D is capable of resolving acute inflammation.” By measuring gene activity in the biopsies, the researchers also uncovered a potential mechanism behind how vitamin D aids skin repair. The results suggest vitamin D increases skin levels of an anti-inflammatory enzyme, arginase-1. The enzyme enhances tissue repair after damage and helps activate other anti-inflammatory proteins.

The study may have people flocking to vitamin supplement aisles, but Lu stresses that the trial tested very high doses of vitamin D that far exceed daily allowances. The Food and Drug Administration’s recommended adult daily allowance for vitamin D is 400 IU. Said Lu, “I would not recommend at this moment that people start taking vitamin D after sunburn based on this study alone. But, the results are promising and worthy of further study.” Lu and colleagues are planning additional studies that could inform treatment plans for burn patients.