Sun. Jul 21st, 2019

263 APCNO REPORT FOR TESTING

263APCNO14APR2019

 

In this issue:

  1. Face off — Cyclists not human enough for drivers: study
  2. On the keto diet? Ditch the cheat day, says UBC study
  3. Vitamin C can shorten the length of stay in the ICU
  4. CU Anschutz study reveals exercise is more critical than diet to maintain weight loss
  5. Dietary supplement boosts cognitive function in vegetarians
  6. Antioxidants protect cells from harmful water contaminant
  7. Could eating garlic reduce aging-related memory problems?
  8. Common food additive may weaken defenses against influenza
  9. Spicy compound from chili peppers slows lung cancer progression
  10. Australian research uncovers link between dietary fiber and lung disease
  11. Vitamin B12 is identified as the inhibitor of a key enzyme in hereditary Parkinson’s disease
  12. High-dose vitamin D shows benefit in patients with advanced colorectal cancer
  13. Over-the-counter antioxidant mix improved vascular health in some heart failure patients
  14. Melatonin’s heart protective effects not related to its antioxidant properties
  15. Experts provide new guidelines to athletes on protein intake
  16. Zinc oxide reduces body odor caused by bacteria and aids wound healing
  17. Study highlights anti-tumor activity of curcumin on stomach cancer
  18. Mauritian medical herbs possess antitumor properties
  19. Ginkgo seed extracts show antibacterial activity on skin pathogens
  20. Omega-3 expert supports new research that shows omega-6 is good for you
  21. CBD reduces impairment caused by cannabis
  22. Eating elderberries can help minimize influenza symptoms
  23. A spoonful of peppermint helps the meal go down
  24. Cranberry oligosaccharides might help prevent UTIs
  25. Can the effects of the ketogenic diet help prevent epilepsy after traumatic brain injury?
  26. Clinical trial looks at absorption levels of sunscreen active ingredients into bloodstream
  27. Training for first-time marathon ‘reverses’ aging of blood vessels

 

PUBLIC RELEASE: 26-MAR-2019

Face off — Cyclists not human enough for drivers: study

Monash University, QUT and Melbourne University

A new Australian study has found that more than half of car drivers think cyclists are not completely human, with a link between the dehumanisation of bike riders and acts of deliberate aggression towards them on the road.

The study by researchers at Monash University, QUT’s Centre for Accident Research & Road Safety – Queensland (CARRS-Q) and the University of Melbourne’s School of Psychological Sciences, is the first study to look at a road-user group with the problem of dehumanisation, which is typically studied in relation to attitudes towards racial or ethnic groups.

But if drivers can put a human face to cyclists, researchers say this could reduce aggression directed at cyclists and road trauma involving riders.

The research, Dehumanization of cyclists predicts self-reported aggressive behaviour toward them published in Transportation Research Part F: Traffic Psychology and Behaviour, notes that cyclists have been conceptualised as a minority group and a target of negative attitudes and behaviour.

The study, involving 442 respondents in Victoria, New South Wales and Queensland, identified people’s attitude to cyclists and whether they were cyclists or non-cyclists themselves.

Participants in the study were given either the iconic evolution of ape to man image, or an adaption of that image showing the stages of evolution from cockroach to human.

Lead author Dr Alexa Delbosc, Senior Lecturer in the Institute of Transport Studies (Faculty of Civil Engineering) at Monash University, said the insect-human scale (below) was designed for the study because of the many informal slurs against cyclists comparing them to “cockroaches” or “mosquitoes”.

On both ape-human and insect-human scales, 55 per cent of non-cyclists and 30 per cent of cyclists rated cyclists as not completely human.

Acts of aggression towards cyclists were not uncommon, with 17 per cent saying they had used their car to deliberately block a cyclist, 11 per cent had deliberately driven their car close to a cyclist and 9 per cent had used their car to cut off a cyclist.

“When you don’t think someone is ‘fully’ human, it’s easier to justify hatred or aggression towards them. This can set up an escalating cycle of resentment,” Dr Delbosc said.

“If cyclists feel dehumanised by other road users, they may be more likely to act out against motorists, feeding into a self-fulfilling prophecy that further fuels dehumanisation against them.

“Ultimately we want to understand this process so we can do a better job at putting a human face to people who ride bikes, so that hopefully we can help put a stop to the abuse.”

Co-author of the paper CARRS-Q Centre Director Narelle Haworth said the study revealed that the problem of dehumanisation on the roads was not just a case of car driver versus cyclist.

“The bigger issue is that significant numbers of both groups rank cyclists as not 100 per cent human,” Professor Haworth said.

“Amongst people who ride, amongst people who don’t ride, there is still people who think that cyclists aren’t fully human.

“The dehumanisation scale is associated with the self-reporting of direct aggression.

“Using your car to deliberately block a cyclist, using your car to deliberately cut off a cyclist, throwing an object at a cyclist – these acts of direct aggression are dangerous.”

Professor Haworth said there was a growing push to avoid the word cyclist, which many viewed with negative connotations.

“Let’s talk about people who ride bikes rather than cyclists because that’s the first step towards getting rid of this dehumanisation,” she said.

PUBLIC RELEASE: 27-MAR-2019

On the keto diet? Ditch the cheat day, says UBC study

Just one dose of carbohydrates can damage blood vessels

UNIVERSITY OF BRITISH COLUMBIA OKANAGAN CAMPUS

The often embraced ‘cheat day’ is a common theme in many diets and the popular ketogenic diet is no exception. But new research from UBC’s Okanagan campus says that just one 75-gram dose of glucose–the equivalent a large bottle of soda or a plate of fries–while on a high fat, low carbohydrate diet can lead to damaged blood vessels.

“The ketogenic–or keto–diet has become very common for weight loss or to manage diseases like type 2 diabetes,” says Jonathan Little, associate professor in the School of Health and Exercise Sciences at UBCO and study senior author. “It consists of eating foods rich in fats, moderate in protein, but very low in carbohydrates and it causes the body to go into a state called ketosis.”

Little says the diet can be very effective because once the body is in ketosis and starved for its preferred fuel glucose, the body’s chemistry changes and it begins to aggressively burn its fat stores. This leads to weight loss and can reverse the symptoms of diseases like Type 2 diabetes.

“We were interested in finding out what happens to the body’s physiology once a dose of glucose is reintroduced,” says Cody Durrer, UBC Okanagan doctoral student and study first author. “Since impaired glucose tolerance and spikes in blood sugar levels are known to be associated with an increased risk in cardiovascular disease, it made sense to look at what was happening in the blood vessels after a sugar hit.”

For their test, the researchers recruited nine healthy young males and had them consume a 75-gram glucose drink before and after a seven-day high fat, low carbohydrate diet. The diet consisted of 70 per cent fat, 10 per cent carbohydrates and 20 per cent protein, similar to that of a modern ketogenic diet.

“We were originally looking for things like an inflammatory response or reduced tolerance to blood glucose,” says Durrer. “What we found instead were biomarkers in the blood suggesting that vessel walls were being damaged by the sudden spike in glucose.”

Little says the most likely culprit for the damage is the body’s own metabolic response to excess blood sugar, which causes blood vessel cells to shed and possibly die.

“Even though these were otherwise healthy young males, when we looked at their blood vessel health after consuming the glucose drink, the results looked like they might have come from someone with poor cardiovascular health,” adds Little. “It was somewhat alarming.”

The researchers point out that with only nine individuals included in the study, more work is needed to verify their findings, but that the results should give those on a keto diet pause when considering a cheat day.

“My concern is that many of the people going on a keto diet–whether it’s to lose weight, to treat Type 2 diabetes, or some other health reason–may be undoing some of the positive impacts on their blood vessels if they suddenly blast them with glucose,” he says. “Especially if these people are at a higher risk for cardiovascular disease in the first place.”

“Our data suggests a ketogenic diet is not something you do for six days a week and take Saturday off.”

PUBLIC RELEASE: 27-MAR-2019

Vitamin C can shorten the length of stay in the ICU

UNIVERSITY OF HELSINKI

The biochemistry of vitamin C is complex. For example, it is involved in the synthesis of norepinephrine and vasopressin, both of which influence the cardiovascular system, and carnitine, which is involved in energy metabolism. Through its epigenetic effects, vitamin C may influence hundreds of genes. In controlled trials, vitamin C has lowered blood pressure, decreased the incidence of atrial fibrillation, decreased bronchoconstriction, decreased pain, decreased glucose levels in patients with type 2 diabetes, and it has shortened the duration of colds.

Very low vitamin C plasma levels are not uncommon in hospitals. Furthermore, vitamin C metabolism is changed in many conditions that involve physiological stress, such as infections, surgery, traumas, and burns, in which case vitamin C levels can decline dramatically. Although 0.1 grams per day of vitamin C can maintain a normal plasma level in healthy persons, much higher doses, up to 4 grams per day, are needed for critically ill patients to increase their plasma vitamin C levels to the range of normal healthy people. Therefore, high vitamin C doses may be needed to compensate for the increased metabolism in critically ill patients.

Given that vitamin C has shown diverse effects on medical conditions, and the accumulated evidence for low vitamin C levels and increased metabolism of vitamin C in critically ill patients, vitamin C might influence practical outcomes such as the length of ICU stay, without any restrictions on the specific medical conditions that cause the stay in the ICU.

Dr. Harri Hemilä from the University of Helsinki, Finland, and Dr. Elizabeth Chalker from the University of Sydney, Australia, carried out a systematic review of vitamin C for ICU patients. They identified 18 relevant controlled trials, and 12 of them were included in the meta-analysis on the length of stay. On average, vitamin C administration shortened ICU stay by 7.8%. In six trials, orally administered vitamin C with an average dose of 2 grams per day reduced the length of ICU stay on average by 8.6%.

According to Hemilä and Chalker, “Vitamin C is a safe, low-cost essential nutrient. Given the consistent evidence from the trials published so far, vitamin C might be administered to ICU patients, although further studies are needed to find out optimal protocols for its administration. A few common cold studies have indicated that there may be a linear dose response for vitamin C on common cold duration for up to 6 and 8 grams per day. Evidently the dose response for doses higher than 2 grams per day should also be investigated for ICU patients.”

PUBLIC RELEASE: 29-MAR-2019

CU Anschutz study reveals exercise is more critical than diet to maintain weight loss

Physical activity helps to prevent weight regain when previously overweight

UNIVERSITY OF COLORADO ANSCHUTZ MEDICAL CAMPUS

A new study from the University of Colorado Anschutz Health and Wellness Center (AHWC) at the CU Anschutz Medical Campus revealed physical activity does more to maintain substantial weight loss than diet.

The study, published in the March issue of Obesity, was selected as the Editor’s Choice article.

“This study addresses the difficult question of why so many people struggle to keep weight off over a long period. By providing evidence that a group of successful weight-loss maintainers engages in high levels of physical activity to prevent weight regain – rather than chronically restricting their energy intake – is a step forward to clarifying the relationship between exercise and weight-loss maintenance,” said Danielle Ostendorf, PhD, a postdoctoral fellow at the CU Anschutz Health and Wellness Center.

The findings reveal that successful weight-loss maintainers rely on physical activity to remain in energy balance (rather than chronic restriction of dietary intake) to avoid weight regain. In the study, successful weight-loss maintainers are individuals who maintain a reduced body weight of 30 pounds or more for over a year.

Key findings include:

  • The total calories burned (and consumed) each day by weight-loss maintainers was significantly higher (300 kcal/day) compared with that in individuals with normal body weight controls but was not significantly different from that in the individuals with overweight/obesity.
  • Notably, of the total calories burned, the amount burned in physical activity by weight-loss maintainers was significantly higher (180 kcal/day) compared with that in both individuals of normal body weight and individuals with overweight/obesity. Despite the higher energy cost of moving a larger body mass incurred by individuals with overweight/obesity, weight-loss maintainers were burning more energy in physical activity, suggesting they were moving more.
  • This is supported by the fact that the weight-loss maintainer group also demonstrated significantly higher levels of steps per day (12,000 steps per day) compared to participants at a normal body weight (9,000 steps per day) and participants with overweight/obesity (6,500 steps per day).

“Our findings suggest that this group of successful weight-loss maintainers are consuming a similar number of calories per day as individuals with overweight and obesity but appear to avoid weight regain by compensating for this with high levels of physical activity,” said Victoria A. Catenacci, MD, a weight management physician and researcher at CU Anschutz Medical Campus.

The study looked at successful weight-loss maintainers compared to two other groups: controls with normal body weight (Body Mass Index (BMI) similar to the current BMI of the weight-loss maintainers); and controls with overweight/obesity (whose current BMI was similar to the pre-weight-loss BMI of the maintainers). The weight-loss maintainers had a body weight of around 150 pounds, which was similar to the normal weight controls, while the controls with overweight and obesity had a body weight of around 213 pounds.

This study is one of the few to measure total daily energy expenditure in weight-reduced individuals using the gold standard doubly labeled water method. This method allows researchers to precisely determine an individual’s energy expenditure through collecting urine samples over one to two weeks after people are given a dose of doubly labeled water. Doubly labeled water is water in which both the hydrogen and the oxygen atoms have been replaced (i.e. labeled) with an uncommon isotope of these elements for tracing purposes.

The measure of total daily energy expenditure from doubly labeled water also provides an estimate of energy intake when people are weight stable, as they were in this study. Prior studies used questionnaires or diet diaries to measure energy intake, which have significant limitations.

The researchers also measured each individual’s resting metabolic rate in order to understand how much of the total daily energy expenditure is from energy expended at rest versus energy expended during physical activity. Prior studies used self-reported measures or activity monitors to measure physical activity, which are techniques that cannot provide the same accuracy.

The findings are consistent with results from the longitudinal study of “The Biggest Loser” contestants, where physical activity energy expenditure was strongly correlated with weight loss and weight gain after six years.

PUBLIC RELEASE: 8-APR-2019

Dietary supplement boosts cognitive function in vegetarians

Vegetarians showed greater visual memory gains than meat eaters after taking creatine

AMERICAN PHYSIOLOGICAL SOCIETY

Orlando, Fla. (April 8, 2019)–Vegetarians who take the dietary supplement creatine may enjoy improved brain function, according to a new study. The research will be presented today at the American Physiological Society’s (APS) annual meeting at Experimental Biology 2019 in Orlando, Fla.

Creatine is a chemical stored in the muscles and brain that helps build lean muscle. In addition to being produced by the human body, creatine is also naturally occurring in red meats and seafood–and in smaller amounts, dairy products. People who do not eat animal products generally have lower creatine levels in the brain than those who consume meat.

Researchers from Stetson University in Florida studied vegetarian volunteers as well as those who ate either up to 10 or 10 or more servings of beef, chicken, pork or fish each week. The volunteers were split into two groups selected randomly. One group took a daily creatine supplement for four weeks, and the other group did not. Before and after the trial, all participants took the ImPACT test, a widely used standardized measure of neurocognitive function. The vegetarian supplement group scored higher on the ImPACT test than the group that ate 10 or more servings of meat, poultry or seafood per week. “Meat eaters did not show any significant improvement of cognition following supplementation because [their] creatine levels were already elevated [from their diet],” explained Kaitlyn Smith, first author of the study.

“This is a pilot study for future research in the field of cognition, and specifically in vegetarians, as [there is] a shift to meat- and dairy-free alternatives in society,” Smith added.

Kaitlyn Smith, an undergraduate student at Stetson University, will present the poster “Effect of creatine-monohydrate on cognitive function in subjects who differ in dietary meat consumption” on Monday, April 8, in the Exhibit Hall-West of the Orlando County Convention Center.

PUBLIC RELEASE: 8-APR-2019

Antioxidants protect cells from harmful water contaminant

Findings could lead to treatment that reduces health risks from exposure to hexavalent chromium

EXPERIMENTAL BIOLOGY

Orlando, Fla. (April 8, 2019) – Antioxidants such as vitamin C could help reduce harmful effects from hexavalent chromium, according to a new study performed with human cells. The contaminant, which is often produced by industrial processes, was featured in the biographical movie Erin Brockovich.

Federal data from nationwide drinking water tests show that the compound contaminates water supplies for more than 200 million Americans in all 50 states. The concentration of hexavalent chromium that is safe for drinking water is now under review by the U.S. Environmental Protection Agency.

“This is the first study to use human cells to test the effects of hexavalent chromium and protection by antioxidants,” said Tim Mayotte, an undergraduate student at Olivet Nazarene University who performed the study. “If the new findings are further validated and go on to clinical trials, it might be possible to treat at-risk water sources with antioxidants like vitamin C to lower the risk for cancer caused by hexavalent chromium.”

Mayotte will present this research at the American Society for Biochemistry and Molecular Biology annual meeting during the 2019 Experimental Biology meeting to be held April 6-9 in Orlando, Fla.

In a study designed to find out whether antioxidants might prevent cell toxicity, the researchers exposed two types of human cells to various concentrations of hexavalent chromium. They observed toxic effects for both cell types at 200 parts per billion (ppb) or higher concentrations of hexavalent chromium. However, this toxicity could be blocked by vitamin C at 10 parts per million (ppm) or the antioxidant epigallocatechin gallate at 15 (ppm). Epigallocatechin gallate is the primary antioxidant found in green tea.

In other experiments, the researchers saw DNA mutations in bacteria exposed to 20 ppb or more of hexavalent chromium. However, these mutations didn’t occur when the bacteria were also treated with 20 ppm of vitamin C.

The new findings reveal that an oxidative mechanism is likely responsible for the contaminant’s toxicity, which could be prevented by treating the water with antioxidants. These results could help inform water quality monitoring and regulation.

Tim Mayotte will present the findings from 11:45 a.m. -1:00 p.m. Monday, April 8, in Exhibit Hall-West Hall B, Orange County Convention Center (poster E238 634.9) (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

PUBLIC RELEASE: 8-APR-2019

Could eating garlic reduce aging-related memory problems?

New study finds that garlic protects memory by improving gut health

EXPERIMENTAL BIOLOGY

Orlando, Fla. (April 8, 2019) – Consuming garlic helps counteract age-related changes in gut bacteria associated with memory problems, according to a new study conducted with mice. The benefit comes from allyl sulfide, a compound in garlic known for its health benefits.

“Our findings suggest that dietary administration of garlic containing allyl sulfide could help maintain healthy gut microorganisms and improve cognitive health in the elderly,” said Jyotirmaya Behera, PhD, who lead the research team with Neetu Tyagi, PhD, both from University of Louisville.

Behera will present the research at the American Physiological Society’s annual meeting during the 2019 Experimental Biology meeting to be held April 6-9 in Orlando, Fla.

The gut contains trillions of microorganisms collectively referred to as the gut microbiota. Although many studies have shown the importance of these microorganisms in maintaining human health, less is known about health effects linked to gut microbiota changes that come with age.

“The diversity of the gut microbiota is diminished in elderly people, a life stage when neurodegenerative diseases such as Alzheimer’s and Parkinson’s develop and memory and cognitive abilities can decline,” said Tyagi. “We want to better understand how changes in the gut microbiota relate to aging-associated cognitive decline.”

For the study, the researchers gave oral allyl sulfide to mice that were 24 months old, which correlates to people between 56 and 69 years of age. They compared these mice with 4- and 24-month-old mice not receiving the dietary allyl sulfide supplement.

The researchers observed that the older mice receiving the garlic compound showed better long- and short-term memory and healthier gut bacteria than the older mice that didn’t receive the treatment. Spatial memory was also impaired in the 24-month-old mice not receiving allyl sulfide.

Additional experiments revealed that reduced gene expression of neuronal-derived natriuretic factor (NDNF) in the brain was likely responsible for the cognitive decline. This gene was recently discovered by the University of Louisville researchers and is required for long-term and short-term memory consolidation.

The researchers found that mice receiving the garlic compound exhibited higher levels of NDNF gene expression. In addition, recombinant-NDNF protein therapy in the brain restored the cognitive abilities of the older mice that did not receive the garlic compound. The researchers also found that oral allyl sulfide administration produces hydrogen sulfide gas — a messenger molecule that prevents intestinal inflammation — in the gut lumen.

Overall, the new findings suggest that dietary allyl sulfide promotes memory consolidation by restoring gut bacteria. The researchers are continuing to conduct experiments aimed at better understanding the relationship between the gut microbiota and cognitive decline and are examining how garlic might be used as a treatment in the aging human population.

PUBLIC RELEASE: 7-APR-2019

Common food additive may weaken defenses against influenza

Study finds tert-butylhydroquinone (tBHQ) impairs immune system, may make flu shot less effective

EXPERIMENTAL BIOLOGY

Orlando, Fla. (April 7, 2019) – Research conducted in mice suggests the food additive tert-butylhydroquinone (tBHQ)–found in many common products from frozen meat to crackers and fried foods–suppresses the immune response the body mounts when fighting the flu. In addition to increasing the severity of flu symptoms, the study found evidence that tBHQ exposure could reduce the effectiveness of the flu vaccine through its effects on T cells, a vital component of the immune system.

Researchers say the connection may help explain why seasonal influenza continues to pose a major health threat worldwide. An estimated 290,000-650,000 people globally die from flu-related respiratory problems each year.

“Our studies showed that mice on a tBHQ diet had a weakened immune response to influenza (flu) infection,” said Robert Freeborn, a fourth-year PhD candidate at Michigan State University. “In our mouse model, tBHQ suppressed the function of two types of T cells, helper and killer T cells. Ultimately, this led to more severe symptoms during a subsequent influenza infection.”

Freeborn will present the research at the American Society for Pharmacology and Experimental Therapeutics annual meeting during the 2019 Experimental Biology meeting, held April 6-9 in Orlando, Fla.

When a person is infected with influenza virus, helper T cells direct other parts of the immune system and help coordinate an appropriate response, while killer T cells hunt down infected cells and clear them from the body. In their experiments, the researchers found mice eating a tBHQ-spiked diet were slower to activate both helper T cells and killer T cells, resulting in slower clearance of the virus.

“Right now, my leading hypothesis is that tBHQ causes these effects by upregulating some proteins which are known to suppress the immune system,” said Freeborn. “Expression of these proteins, CTLA-4 and IL-10, was upregulated in two different models we use in the lab. However, more work is necessary to determine if upregulation of these suppressive proteins is indeed causative for the effects of tBHQ during influenza infection.”

What’s more, when the mice were later re-infected with a different but related strain of influenza, those on the tBHQ diet had a longer illness and lost more weight. This suggests that tBHQ impaired the “memory response” that typically primes the immune system to fight a second infection, Freeborn said. Since the memory response is central to how vaccines work, impairment of this function could potentially reduce the efficacy of the flu vaccine.

T cells are involved in the immune response to a variety of diseases, so tBHQ could also play a role in other types of infectious diseases, Freeborn added.

tBHQ is an additive used to prevent spoilage, with a maximum allowed concentration of 200 parts per million in food products. It is unclear how much tBHQ people are exposed to, though estimates based on model diets have suggested some U.S. consumers eat almost double the maximum allowable amount of tBHQ suggested by the Joint FAO/WHO Expert Committee on Food Additives and that people in other parts of the world may consume up to 11 times the maximum allowable amount. The level of tBHQ exposure in Freeborn’s studies falls within estimates of human exposure.

“It can be hard to know if you are consuming tBHQ, as it is not always listed on ingredient labels,” said Freeborn, adding that this is often the case when tBHQ is used in food preparation, such as in the oil used to fry a chip. “The best way to limit tBHQ exposure is to be cognizant about food choices. Since tBHQ is largely used to stabilize fats, a low-fat diet and cutting down on processed snacks will help reduce tBHQ consumption.”

Freeborn emphasized that getting a yearly flu shot remains the best way to prevent influenza infection. Though it is possible to contract the flu after getting the vaccine, being vaccinated has been shown to significantly reduce the length and severity of the illness.

Building on their studies conducted in mice, the researchers plan to use human blood samples to further investigate how tBHQ affects T cell activity.

Robert Freeborn will present this research on Sunday, April 7, from 9 a.m.-4 p.m. in Exhibit Hall-West Hall B, Orange County Convention Center (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

PUBLIC RELEASE: 6-APR-2019

Spicy compound from chili peppers slows lung cancer progression

Cell, animal studies show potential of capsaicin as lung cancer treatment

EXPERIMENTAL BIOLOGY

Orlando, Fla. (April 6, 2019) – Findings from a new study show that the compound responsible for chili peppers’ heat could help slow the spread of lung cancer, the leading cause of cancer death for both men and women. Most cancer-related deaths occur when cancer spreads to distant sites, a process called metastasis.

“Lung cancer and other cancers commonly metastasize to secondary locations like the brain, liver or bone, making them difficult to treat,” said Jamie Friedman, a doctoral candidate who performed the research in the laboratory of Piyali Dasgupta, PhD, at Marshall University Joan C. Edwards School of Medicine. “Our study suggests that the natural compound capsaicin from chili peppers could represent a novel therapy to combat metastasis in lung cancer patients.”

Friedman will present the research at the American Society for Investigative Pathology annual meeting during the 2019 Experimental Biology meeting to be held April 6-9 in Orlando, Fla.

In experiments involving three lines of cultured human non-small cell lung cancer cells, the researchers observed that capsaicin inhibited invasion, the first step of the metastatic process. They also found that mice with metastatic cancer that consumed capsaicin showed smaller areas of metastatic cancer cells in the lung compared to mice not receiving the treatment.

Additional experiments revealed that capsaicin suppresses lung cancer metastasis by inhibiting activation of the protein Src. This protein plays a role in the signaling that controls cellular processes such as proliferation, differentiation, motility and adhesion.

“We hope that one day capsaicin can be used in combination with other chemotherapeutics to treat a variety of lung cancers,” said Friedman. “However, using capsaicin clinically will require overcoming its unpleasant side effects, which include gastrointestinal irritation, stomach cramps and a burning sensation.”

The researchers are working to identify capsaicin analogs that will be non-pungent while retaining the anti-tumor activity of capsaicin. They are also trying to identify natural non-pungent capsaicin-like compounds with anti-cancer activity.

PUBLIC RELEASE: 4-APR-2019

Australian research uncovers link between dietary fiber and lung disease

Dietary fiber found to protect against COPD

UNIVERSITY OF TECHNOLOGY SYDNEY

 

Dietary fibre may be a new tool in the prevention of progressive lung disease, thanks to the production of anti-inflammatory short chain fatty acids (SCFA), according to a new study by Australia’s Priority Research Centre for Healthy Lungs at University of Newcastle, and the Centre for Inflammation, a partnership between The University of Technology Sydney and Centenary Institute.

The research was presented to lung health experts at the Australia and New Zealand Annual Scientific Meeting for Leaders in Lung Health & Respiratory Science (TSANZRS 2019 ).

“For several years now the Priority Research Centre for Healthy Lungs has been leading world research into the link between dietary fibre and healthy lungs. Our previous research has established how fibre supplements can be used to treat asthma. Now, our findings suggest fibre could be used to not just treat but also help prevent chronic obstructive pulmonary disease (COPD),” said lead researcher Professor Phil Hansbro, Director of the Centre for Inflammation.

COPD is an umbrella term for progressive lung conditions such as emphysema, chronic bronchitis and chronic asthma, affecting 1 in 7 Australians over the age of 40. COPD is characterised by difficulty breathing and causes include smoking, long-term exposure to air pollutants and a rare genetic disorder.

Whilst many people live with a mild form of COPD without even knowing it, for those with severe disease, it can severely impair quality of life. COPD is a leading cause of death in Australia and is the second leading cause of avoidable hospital admissions. It is the world’s third biggest killer disease. Existing treatments are only partially effective and some don’t work at all.

The NSW study exposed mice to cigarette smoke – one of the known causes of COPD – to trigger onset of the disease. At the same time, the diet of some mice was supplemented with fermentable fibre.

If found that cigarette smoke reduced the production of anti-inflammatory short chain fatty acids but that the resulting inflammation could be offset by a high fibre diet.

“We found that dietary fibre is able to reduce lung inflammation and damage, resulting in improved lung function,” explains Professor Hansbro. “For the first time, we have also connected these changes to the gastrointestinal microbiome and its production of protective metabolites.”

The findings, say researchers, could have important implications for people with or at risk of COPD and their health providers.

“Diet can be an important addition to current treatments to help sustain the quality of life in patients and potentially influence the development of COPD in those at risk. Public health bodies should consider targeting diet and fibre as an additional safe and inexpensive treatment for lung disease,” said Professor Hansbro.

The researchers point out that the consumption of dietary fibre by mice didn’t protect against every symptom of COPD and so should be used as a supplement to, not a replacement of, currently approved interventions.

The findings also pave the way for the development of new therapeutic treatments.

“The greater our understanding of the biochemistry involved in the breakdown of dietary fibre and its impact on lung health, the closer we get to developing new, effective treatments. By understanding the critical role short chain fatty acids pay in preventing lung damage, we can better develop treatments and dietary modifications that can induce them as potential new preventions and treatments for COPD,” said Professor Allan Glanville, President of the Thoracic Society of Australia and New Zealand (TSANZ).

In the meantime, the message is clear: if you want healthy lungs, eat your fibre.

PUBLIC RELEASE: 4-APR-2019

Vitamin B12 is identified as the inhibitor of a key enzyme in hereditary Parkinson’s disease

It could be used as a basis to develop new therapies to combat hereditary Parkinson’s

UNIVERSITY OF THE BASQUE COUNTRY

 

Parkinson’s is the most common, chronic neurodegenerative movement disorder affecting 1% of the global population over seventy years of age. Right now, there is no cure for this disease and the available treatments focus on addressing its symptoms but not its progression.

Although most cases of Parkinson’s are sporadic, the inheritable variants of the disease are mainly associated with mutations of the gene that encodes the LRRK2 enzyme. In 2004 an international research team, in which researchers from the Basque Country participated, established the link between one of the mutations in this enzyme and patients diagnosed with the disease.

So the LRRK2 enzyme, which is also known internationally by the name “dardarina”, the Basque word that means tremor, has become one of the most attractive therapeutic targets for developing new drugs to combat inheritable Parkinson’s. Neurotoxicity, or the pathogenic effects as a whole associated with LRRK2, is mainly due to the fact that pathogenic mutations increase the kinase activity of this enzyme, which has prompted an international race to develop inhibitors. Right now, specific, powerful inhibitors of the kinase activity of LRRK2 do in fact exist. Yet many of them cause undesirable side effects or produce very unclear clinical results.

This research conducted by Iban Ubarretxena, the Ikerbasque researcher and director of the Biofisika Institute (mixed centre of the CSIC-Spanish National Research Council and the UPV/EHU-University of the Basque Country) at the UPV/EHU’s Science Park (Leioa-Erandio Area), together with an international research team, has revealed that AdoCbl, one of the active forms of vitamin B12, acts as an inhibitor of the kinase activity of LRRK2 in cultured cells and brain tissue. It also significantly prevents the neurotoxicity of the LRRK2 variants associated with Parkinson’s in cultured cells of primary rodents, as well as in various genetically modified models used to study this disease. The results of the research have been published in the prestigious journal Cell Research.

So according to the study, vitamin B12 has turned out to be a new class of modulator of the kinase activity of LRRK2, which, as Iban Ubarretxena pointed out, “constitutes a huge step forward because it is a neuroprotective vitamin in animal models and has a mechanism unlike that of currently existing inhibitors. So it could be used as a basis to develop new therapies to combat hereditary Parkinson’s associated with pathogenic variants of the LRRK2 enzyme”.

PUBLIC RELEASE: 9-APR-2019

High-dose vitamin D shows benefit in patients with advanced colorectal cancer

DANA-FARBER CANCER INSTITUTE

BOSTON – Results of a small clinical trial suggest that supplementing chemotherapy with high doses of vitamin D may benefit patients with metastatic colorectal cancer by delaying progression of the disease, say scientists from Dana-Farber Cancer Institute.

Prompted by the “very encouraging” results of the SUNSHINE clinical trial, the potential benefits of vitamin D supplementation in metastatic colorectal cancer will be evaluated in a larger clinical trial planned to open at several hundred sites across the United States later this year, said Kimmie Ng, MD, MPH, director of Clinical Research in Dana-Farber’s Gastrointestinal Cancer Center, and corresponding author of the SUNSHINE study. “To our knowledge, this study is the first completed randomized clinical trial of vitamin D supplementation for treatment of advanced or metastatic colorectal cancer,” Ng said.

In the high-dose group, patients had a median delay of 13 months before their disease worsened; in the low-dose group, the median delay was 11 months. In addition, patients in the high-dose vitamin D group were 36 percent less likely to have disease progression or death during the follow-up period of 22.9 months. The trial included too few patients to determine whether those who took high-dose vitamin D experienced improved overall survival.

“The results of our trial suggest an improved outcome for patients who received vitamin D supplementation, and we look forward to launching a larger trial to confirm these exciting and provocative findings,” said Charles Fuchs, MD, MPH, formerly of Dana-Farber as senior author of the study and now Director of Yale Cancer Center.

The initial findings were reported at the 2017 meeting of the American Society of Clinical Oncology. Those results, along with additional data, are now being published in JAMA.

The SUNSHINE trial randomized 139 patients with previously untreated metastatic colorectal cancer. One group took pills containing 4,000 international units (IU) of vitamin D per day along with standard chemotherapy, while the other group took 400 units (about the dose found in a multivitamin) along with chemotherapy.

Vitamin D, which is necessary for bone health, is made in the body through a chemical reaction dependent on sun exposure and is contained in some foods. In laboratory studies, vitamin D has demonstrated anti-cancer properties such as triggering programmed cell death, inhibiting cancer cell growth and reducing metastatic potential. Prospective observational studies have linked higher blood levels of vitamin D with a lower risk of colorectal cancer and improved survival of patients with the disease, but those studies could not prove that vitamin D was the cause.

Against this backdrop, the randomized, prospective phase 2 SUNSHINE trial recruited patients at 11 academic and community centers across the United States to test whether vitamin D supplementation can improve outcomes in patients with metastatic colorectal cancer. All patients received standard chemotherapy with a regimen called mFOLFOX6 plus bevacizumab. Patients in the high-dose vitamin D group initially took 8,000 IU a day for 14 days, then 4,000 IU a day thereafter. The low or standard-dose vitamin D group took 400 IU daily during all cycles. All patients were asked not to take any other vitamin D or calcium supplements during the trial period.

The trial’s primary outcome measure was progression-free survival – the time until the disease began to worsen, or death – which was longer in the high-dose group. Another measure that was calculated – the hazard ratio for disease progression or death – revealed 36 percent lower odds in the high-dose group.

The researchers also sampled patients’ blood to measure changes in the levels of 25-hydroxyvitamin D [25(OH)D], which is a standard test to determine a person’s vitamin D status. This test showed that only 9 percent of the patients in the clinical trial had sufficient vitamin D at the beginning of treatment. Over the course of the study, patients receiving low-dose had no substantial change in their vitamin D levels, while those in the high-dose group soon reached the vitamin D-sufficient range and maintained it.

Analysis of the results showed that the benefit of high-dose vitamin D appeared to be less in patients who were obese, and those whose tumors contained a mutated KRAS gene, suggesting “that certain subsets of patients may need even higher doses of vitamin D for anti-tumor activity,” the researchers said. They cautioned, however, that high doses of vitamin D shouldn’t be taken except within the context of a clinical trial.

The study and its findings are “extremely important,” Ng said, because “it identifies a cost-effective, safe, and easily accessible agent as a potential new treatment for metastatic colorectal cancer. This could therefore potentially have a large and wide-reaching impact globally, regardless of a patient’s socioeconomic status or a country’s resources.”

The research was supported by National Cancer Institute grants P50CA127003, R01CA205406, and R01CA118553; a Gloria Spivak Faculty Advancement Award; a Friends of Dana-Farber Cancer Institute Award; the Project P Fund; Consano, Pharmavite LLC, and Genetech.

Dr. Ng reports grants from National Cancer Institute, grants and non-financial support from Pharmavite, grants from Genentech, and grants from Consano during the conduct of the study; grants and non-financial support from Pharmavite, personal fees from Genentech, personal fees from Lilly, grants from Gilead Sciences, grants and personal fees from Tarrex Biopharma, personal fees from Bayer, personal fees from Seattle Genetics, grants from Celgene, and grants from Trovagene outside the submitted work.

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PUBLIC RELEASE: 9-APR-2019

Over-the-counter antioxidant mix improved vascular health in some heart failure patients

Patients given a mix of vitamins C, E and alpha lipoic acid showed improvement in markers of vascular health

AMERICAN PHYSIOLOGICAL SOCIETY

Orlando, Fla. (April 7, 2019)–A combination of over-the-counter antioxidants shows promise for mitigating some damaging effects of heart failure with preserved ejection fraction (HFpEF), a new study reports. The research, which will be presented today at the American Physiological Society’s (APS) annual meeting at Experimental Biology 2019 in Orlando, Fla., is the first to evaluate the efficacy of antioxidants to improve vascular function in patients with HFpEF.

HFpEF, previously known as diastolic heart failure, is a chronic condition in which the heart does not fill properly. It is the most common form of heart failure among the elderly, particularly women. To date, very few treatments have proven successful in improving clinical status in patients with HFpEF. Because of this, there is a focus on treating the many comorbidities that accompany the disease, such as inflammation, which can impair vascular function.

In a double-blind study, 16 patients with HFpEF were given a placebo or an antioxidant cocktail consisting of alpha lipoic acid (600mg), vitamin C (1,000mg) and vitamin E (600IU). This was a balanced, cross-over study, which means that all participants receive both treatments sequentially, thus serving as their own controls. The research team measured various markers of vascular function, inflammation and oxidative stress. Though the measures of small blood vessel function and oxidative stress did not show changes, the measure of function in large blood vessels and of inflammation improved with treatment. Similarly, the presence of biologically available nitric oxide, a compound that helps blood vessels dilate, also increased.

The findings provide “new insight into the mechanisms that govern peripheral vascular dysfunction” in HFpEF patients, the researchers explained, and suggest that antioxidant administration may represent a simple and readily available option to improve vascular health in this patient group.

Stephen Ratchford, PhD, a postdoctoral fellow at the University of Utah Department of Internal Medicine and the Salt Lake City VA Geriatric Research, Education, and Clinical Center (GRECC), will present “Impact of acute antioxidant administration on inflammation and vascular function in heart failure with preserved ejection fraction” Sunday, April 7, as part of the oral session “Aging, exercise and heart failure: common connections and new targets” in the Orange County Convention Center W312A. He will also present the poster on Tuesday, April 9, during the APS Cardiovascular Section Young Investigators poster session in West Hall B of the exhibit hall of the Orange County Convention Center.

PUBLIC RELEASE: 9-APR-2019

Melatonin’s heart protective effects not related to its antioxidant properties

Antiarrhythmic benefit from melatonin is distinct from its antioxidant effect

AMERICAN PHYSIOLOGICAL SOCIETY

Orlando, Fla. (April 9, 2019)–Although melatonin does improve the outcomes of induced heart attacks in rats, those improvements are not the result of its antioxidant effect, new research finds. The study comparing antioxidant activity and heart protection will be presented today at the American Physiological Society (APS) annual meeting at Experimental Biology 2019 in Orlando, Fla..

Antiarrhythmic agents are substances that treat irregular electrical activity in the heart. Melatonin has previously been shown to have antiarrhythmic effects, with the assumption that this was due to its known antioxidant properties. In this current study, an international team of researchers examined precisely how melatonin affected the heart in a rat model of heart attacks.

One group of rats was given 10 mg of melatonin daily for seven days, while another received a placebo. Researchers then measured the electrical activity in the rats’ hearts before, during and after a cardiac event. They later examined the hearts for measures of oxidative stress and antioxidant activity.

Ventricular tachycardia (VT) and ventricular fibrillation (VF) are two kinds of dangerous irregular electrical activity in the heart that can result from a heart attack. Incidence of both VT and VF was reduced in melatonin-treated rats. A marker of antioxidant activity was also higher in the treated rats. However, there was no association between the presence of oxidative stress and incidence of irregular electrical activity.

In previous work, the research team observed that blocking melatonin-specific receptors removed the antiarrhythmic benefit of melatonin. When taken together with this current study, these results suggest that melatonin’s protective effects for the heart “are related to its antiarrhythmic action, and this effect is related not to antioxidative properties but to melatonin receptor stimulation,” said lead author Jan Azarov, PhD, of the Komi Science Center, Komi Republic, Russian Federation.

Jan Azarov, PhD, of the Institute of Physiology of the Komi Science Center, Syktyvkar, Komi Republic, Russian Federation, will present the poster “Antiarrhythmic effects of chronic melatonin treatment are not associated with its antioxidative action in rat myocardial ischemia/reperfusion model” on Tuesday, April 9, in West Hall B of the exhibit hall of the Orange County Convention Center.

PUBLIC RELEASE: 12-APR-2019

Experts provide new guidelines to athletes on protein intake

UNIVERSITY OF STIRLING

A review led by a sports scientist at the University of Stirling has set out new international guidelines for protein intake in track and field athletes.

The findings of the paper form part of the updated International Association of Athletics Federations’ (IAAF) consensus statement on Sports Nutrition for Track and Field Athletes.

Dr Oliver Witard, from Stirling’s Faculty of Health Sciences and Sport, led the protein theme of the statement alongside experts at the Norwegian Olympic and Paralympic Committee and Confederation of Sport, and McMaster University in Hamilton, Canada.

Explaining the findings, Dr Witard, of the Physiology, Exercise and Nutrition Research Group at Stirling, said: “Track and field athletes engage in vigorous training that place stress on physiological systems requiring nutritional support for optimal recovery. In this paper, we highlight the benefits of dietary protein intake for training adaptation, manipulating body composition and optimising performance in track and field athletes.

“We recommend that, to facilitate the remodelling of our muscle proteins – which are turning over rapidly due to their high training volumes – track and field athletes should aim for protein intakes of around 1.6 grams per kilogram of body mass each day if their goal is to increase muscle mass.”

The paper also offers guidance to those track and field athletes aiming to optimise their ratio of strength, power or endurance to body weight for a performance advantage.

“Track and field athletes who are restricting energy intake – and have the goal of minimising the loss of lean body mass – should target protein intakes of between 1.6 and 2.4 grams per kilogram of body mass a day,” Dr Witard continued.

The previous IAAF consensus statement was published in 2007 and, in the time since, evidence underpinning nutrition strategies for adaptation and physique manipulation in athletes has evolved considerably. The updated statement was led by Professor Louise M Burke, of the Australian Institute of Sport and Australian Catholic University.

Dr Witard added: “High-performance athletes now have access to an up-to-date consensus statement that informs best practice protein nutrition for optimising body composition.”

NEWS RELEASE 12-APR-2019

Zinc oxide reduces body odor caused by bacteria and aids wound healing

EUROPEAN SOCIETY OF CLINICAL MICROBIOLOGY AND INFECTIOUS DISEASES

 

New research presented at this week’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam, Netherlands (13-16 April) shows that a formulation containing zinc oxide is effective at reducing armpit odour through killing the responsible bacteria, and assists in wound healing. The study was carried out by Professor Magnus S. Ågren, Copenhagen Wound Healing Center, Bispebjerg Hospital, Copenhagen, Denmark (where the study took place) and Khaled Saoud Ali Ghathian, Department of Clinical Microbiology, Hvidovre Hospital, Hvidovre, Denmark and colleagues.

Bothersome odour from the axilla (under the armpit) is in most cases caused by Corynebacterium spp. and Staphylococcus spp. The antimicrobial effects of zinc oxide (ZnO) have been extensively documented. In experimental studies, ZnO prevented bacterial generation of short-chain fatty acids with a bad smell. Furthermore, topical ZnO reduced the occurrence of corynebacteria and bad odour from open surgical wounds, which gave the idea to the researchers to test the compound on body odour directly.

The axilla is warm, moist and nutrient rich, all of which are conditions that increase pH. Because the solubility of ZnO is pH-dependent, the efficacy may vary due to the skin surface pH. Moreover, there is no consensus on the effect of gender on axillary pH level.

The primary aim of this double-blind, placebo-controlled trial (ZINC-ON) was to study if repeated application of ZnO formulated in an oil-in-water emulsion reduced underarm odour in healthy volunteers. The association with the overall bacterial growth and specifically of Corynebacterium spp. and S. hominis was also studied. Skin surface pH was monitored in parallel. Secondly, the anti-inflammatory and wound-healing effects of topical ZnO were studied by assessing the extent of skin erythema and keratin evolution in two standardised wound models: one inflicted by a contact-activated lancet producing small bleeding wounds and the other was induced by ablative CO2 laser producing dry erosions in the skin.

The trial included 30 healthy volunteers (15 female/15 male) of mean age of 25.6 years. Participants’ left and right axilla were randomised to ZnO application or placebo and treated for 13 consecutive days with 5 visits to the hospital. The participants were enrolled, swabbed and started treatment on day minus 8; on day 0 bacterial swabs were obtained again and wounds were inflicted, and then the participants were seen on days 3, 4 and 5. At the last visit day 5, the participants were asked (1) whether they had observed a difference in the odour from the left and right axillae and, if so, (2) to state which axilla they judged superior with respect to odour.

Treatment with ZnO reduced self-perceived bad odour compared with placebo. The overall bacterial growth and specifically the odour-generating Corynebacterium spp. and S. hominis were reduced with ZnO treatment despite increasing skin surface pH (all results were statistically significant). Topical ZnO reduced peri-wound erythema (redness) around the lancet-induced wounds and promoted the formation of keratin.

The authors conclude: “Daily application of ZnO reduced malodour from the axilla and causative bacteria, increased skin surface pH and attenuated wound inflammation.”

Professor Ågren says: “The most frequent response we had from participants was: ‘where can I buy this fantastic product?’. Even though it contained no fragrance like conventional deodorants, the participants could identify that it had neutralised any bad odour under the arm where it was applied. The product has since been progressed to commercialisation by Colgate-Palmolive, who produced the product and sponsored this trial.”

NEWS RELEASE 22-APR-2019

Study highlights anti-tumor activity of curcumin on stomach cancer

A review article authored by Brazilian researchers evaluated several compounds with therapeutic potential against gastric tumors

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO

Curcumin is widely used to impart color and flavor to food, but scientists have discovered that this yellow powder derived from the roots of the turmeric plant (Curcuma longa) can also help prevent or combat stomach cancer.

The study by researchers at the Federal University of São Paulo (UNIFESP) and the Federal University of Pará (UFPA) in Brazil identified possible therapeutic effects of this pigment and of other bioactive compounds found in food on stomach cancer, the third and fifth most frequent type of cancer among Brazilian men and women, respectively.

The study was part of a Thematic Project supported by São Paulo Research Foundation – FAPESP. Its findings have been published in the journal Epigenomics.

“We undertook a vast review of the scientific literature on all nutrients and bioactive compounds with the potential to prevent or treat stomach cancer and found that curcumin is one of them,” Danielle Queiroz Calcagno, a professor at UFPA and first author of the study, told.

According to Calcagno, who conducted postdoctoral research at UNIFESP with a scholarship from FAPESP, compounds such as cholecalciferol (a form of vitamin D), resveratrol (a polyphenol) and quercetin can prevent or combat stomach cancer because they are natural regulators of histone activity.

Histones are proteins in cell nuclei that organize the DNA double helix into structural units called nucleosomes. Each nucleosome is made of DNA coiled like a spool around eight histone proteins (a histone octamer) to compact the DNA so that it fits in the cell, where it is packaged into chromatin.

Posttranslational chemical modification of the amino acid chain in these proteins, such as acetylation (introduction of an acetyl group) or methylation (addition of a methyl group), can affect chromatin compaction and hence gene expression.

“If the histones are acetylated, for example, the chromatin will be less condensed, and a gene in a region of the DNA segment inside it will be available to be expressed. In contrast, if the histones aren’t acetylated, the chromatin will be more condensed, and the gene won’t be expressed,” Calgano explained.

Research conducted in recent years has suggested that posttranslational histone modification causes alterations in gene expression without affecting the DNA sequence. These epigenetic variations influence the development of different types of cancer.

To determine whether this hypothesis also applied to stomach cancer, several groups of researchers coordinated by Marília de Arruda Cardoso Smith, a professor at UNIFESP, studied histone acetylation patterns in stomach cell samples from healthy individuals and patients diagnosed with stomach cancer.

The researchers found that the cells from stomach cancer patients displayed alterations in the pattern of expression of histone acetyltransferases (HATs) and histone deacetylases (HDACs). These alterations are epigenetic and affect the structure and integrity of the genome in many tumors, including stomach cancer.

Because recent research has also shown that nutrients and bioactive compounds can regulate the activity of HATs and HDACs, the scientists at UNIFESP and UFPA set out to identify any that might influence histone acetylation and hence help prevent stomach cancer or even treat the disease.

In addition to curcumin, other compounds found to play a key role in modulating histone activity were cholecalciferol, resveratrol (present mainly in grape seeds and red wine), quercetin (abundant in apples, broccoli and onions), garcinol (isolated from the bark of the kokum tree, Garcinia indica), and sodium butyrate (produced by gut bacteria via fermentation of dietary fiber).

“These compounds can favor the activation or repression of genes involved in the development of stomach cancer by promoting or inhibiting histone acetylation,” Calcagno said.

Curcumin, for example, influences histone modifications primarily by inhibiting HATs and HDACs to suppress cancer cell proliferation and induce apoptosis (programmed cell death). Garcinol, whose chemical structure resembles that of curcumin, inhibits HATs and helps prevent stomach cancer by neutralizing free radicals.

“We now plan to clarify the anticancer and epigenetic effects of bioactive compounds derived from plants in the Amazon, such as açaí [Euterpe oleracea] and nanche or hogberry [Byrsonima crassifolia], with a view to their future use in the prevention and treatment of stomach cancer,” Calcagno said.

NEWS RELEASE 22-APR-2019

Mauritian medical herbs possess antitumor properties

They contain biologically active substances of these species have shown to contain effective inhibitors of esophageal cancer cells

FAR EASTERN FEDERAL UNIVERSITY

Far Eastern Federal University (FEFU) scientists teamed up with colleagues from the UK and Mauritius and experimentally demonstrated that extracts of the endemic (i.e. growing only on this island) medicinal herb leaves Acalypha integrifoliaEugenia tinifolia, and Labourdonnaisia glauca stop the proliferation of oesophageal squamous carcinoma cells, ones of the most deadly cancer type worldwide. A related article is published in the Acta Naturae journal.

Researchers found out that the extracts contain natural chemical compounds to inhibit the propagation of cancer cells. Namely, they restrain the G2/M stages transition in malignant tumor cells by activating AMPK signaling pathway. Currently, the search for AMPK activators is an urgent problem in molecular oncology. Having studied the medical herbs of Mauritius, scientists may have accomplished an important step, if not a breakthrough in this direction.

“Mauritius Island is a treasure island of the global biodiversity, and the story of continuing tragedy of human greed, barbarian appetite (remember the Dodo bird from the Alice story, RIP) and neglection of true wonders of the planet designed to save human lives. About one-third of the local plants are used in traditional medicine, but there is still a lack of scientific evidence of their therapeutic potential, while genocide of nature is most evident on such small pieces of lost paradise. To date, only 15 percent of the island’s plant species have been examined for their medicinal properties, which is still better than in many countries. Ethnobotany combined with modern organic chemistry and cell biology is an extremely fruitful interdisciplinary field for scientific research. We hope to proceed working in this direction, thanks to the growing globally Bio2bio* movement supported by the Global Young Academy**. In particular, further study of the active compounds from the leaves extracts of A. integrifolia, E. tinifolia and L. Glauca promises to reveal prototypes of the future drugs to treat oesophageal cancer, and other deadly diseases” – said Alexander Kagansky, the Head of the Center for Genomic and Regenerative Medicine of the School of Biomedicine FEFU, an expert in the field of cancer epigenetics and chromosome biology.

The lead scientist noted that oesophageal cancer is a growing global concern due to the diets and other detrimental side effects of modern lifestyles, technologies, and culture. At the present time, there is not enough effective means of its treatment, while the existing radiotherapy, chemotherapy resection may prolong lives by few months, usually spent in tremendous suffering. The aggressive disease prevents eating, digestion, and come along with a very negative prognosis. Oesophageal squamous carcinoma together with adenocarcinoma represent the sixth main death cause in the global oncological practice. Less than 15 percent of patients survive for five years from the time of diagnosis. On average, people with such diagnoses live less than a year. These types of cancer are treated with broad-spectrum chemo. The drugs are extremely toxic and evoke a number of side effects worsening the patients’ quality of life. At the same time, the efficacy of current chemotherapy for this disease is not very assuring, to say the least.

More than half of all anti-cancer drugs employing today were developed from natural sources. At the same time, most of the world’s population treats cancer by means of thousands of herb species that have been known to traditional medicine for centuries, each of those coming with many different naturally chemistries, evolved for use in nature for millions of years. Taking into the account centuries-old human understanding of nature, modern biomedicine needs to develop new anti-cancer compounds from a wide range of natural sources, such as plants, fungi, bacteria, insects, and marine organisms.

During the study, FEFU scientists in cooperation with foreign colleagues studied in the laboratory carefully isolated and fractionated extracts of five species of Mauritian endemic medicinal plants: Acalypha integrifolia Willd (Euphorbiaceae), Labourdonnaisia glauca Bojer(family Sapotaceae), Dombeya acutangula Cav. subsp. rosea Friedmann (Malvaceae), Gaertnera psychotrioides (DC.) Baker (Rubiaceae), Eugenia tinifolia Lam (Murtaceae). They were tested on the cell lines from two different types of patients’ malignant tumors. Three of the five biologically active substances of these species have shown to contain effective inhibitors of oesophageal cancer cells, stopping their growth and contributing to their death.

Alexander Kagansky emphasized that the future of global medicine depends on the saving of the planet’s biodiversity. He reminded that currently the total number of living species is steadily declining. Bringing on the example of medicinal plants of Mauritius, which he and colleagues took an effort to study, the scientist pointed out that they are devastated at an incredible rate at which species are being erased from existence as a result of human ‘progressive’ activities, such as lumber, energy, and food generation. At the meanwhile, so far these unique species do not grow anywhere else on the planet, a few additional 5-star hotels, bank building, or a golf-course could end up their existence once and for all. Given this, Kagansky became a co-organizer of the Bio2Bio* international consortium thanks to the support of the Global Young Academy and the Interacademy Partnership***. The task of Bio2bio is to protect biodiversity and nature which are sources of valuable biological compounds, as well as to create a database of natural molecules that will provide a basis for drug components elucidation, and for linking traditional medicine systems with each other and modern medicine via integration of other areas such as pharmacognosy, ethnobotany, synthetic and analytic chemistry, immunology, pharmacology, molecular and cell biology, metabolomics, etc.

“Our research should serve the benefit of humanity and show by evidence that on the mechanistic level people depend on natural chemistries, which will reward us by reducing deaths and suffering of ourselves, our parents, and children”, the scientist said.

NEWS RELEASE 18-APR-2019

Ginkgo seed extracts show antibacterial activity on skin pathogens

Experiments were guided by a prescription in a 16th-century text

EMORY HEALTH SCIENCES

Extracts from the seeds of the Ginkgo biloba tree show antibacterial activity on pathogens that can cause skin infections such as acne, psoriasis, dermatitis and eczema, a study at Emory University finds. Frontiers in Microbiology is publishing the results of laboratory experiments showing that the extracts inhibit the growth of Cutibacterium acnes, Staphylococcus aureus and Streptococcus pyogenes.

A nearly 200-year-old copy of a 16th-century text on traditional Chinese medicine, the Ben Cao Gang Mu, guided the researchers in their experiments. “It was like blowing the dust off knowledge from the past and rediscovering something that had been there all along,” says Xinyi (Xena) Huang, co-first author of the paper.

Huang, a native of China, began the project for her senior thesis as a biology major at Emory. She has since graduated from Emory and is now a student at the University of Maryland School of Pharmacy.

“To the best of our knowledge, this is the first study to demonstrate the antibacterial activity of ginkgo seeds on skin pathogens,” says Cassandra Quave, senior author of the paper and assistant professor at Emory’s Center for the Study of Human Health and the School of Medicine’s Department of Dermatology. “This paper is just one more example of how much we still have to learn about the pharmacological potential of the complex chemistry of plants.”

Quave is an ethnobotanist, studying how indigenous people use plants in their healing practices, to uncover promising candidates for new drugs.

“Our results give validity to the use of ginkgo seeds as a topical antimicrobial as prescribed in this 16th-century text,” says Francois Chassagne, co-first author of the paper and a pharmacist in the Quave lab.

Many hurdles remain, he adds, before ginkgo seed extracts could be considered for use in a modern-day medical context. In its concentrated form, the main compound that a statistical analysis identified as likely responsible for the antibacterial activity, ginkgolic acid C15:1, has been demonstrated to have skin toxicity.

“One possible strategy in the search for new antibiotics would be to investigate ways to modify the structure of the particular ginkgolic acid tied to the antibacterial activity, to try to improve its efficacy and also to reduce its toxicity to human skin cells,” Chassagne says.

James Lyles, a chemist in the Quave lab, is an additional co-author of the study.

The ginkgo tree, a native of China, is one of the oldest tree species, going back at least 270 million years. The tree is known for its distinctive fan-shaped leaves and its long history in traditional Chinese medicine. Modern-day researchers have studied ginkgo extensively in search of medical benefits for everything from memory enhancement to macular degeneration, but there is still “no conclusive evidence that ginkgo is helpful for any health condition,” according to the web page of the National Institutes of Health’s National Center for Complementary and Integrative Health.

Most previous studies have focused on the ginkgo leaves.

When walking across campus, pondering what to focus on for her senior thesis, a ginkgo tree caught Huang’s eye. She knew that the tree was used in traditional Chinese medicine, although she did not know any details, so she decided to research it.

Huang’s interest grew when she learned that Emory has an 1826 version of the Ben Cao Gang Mu, or Compendium of Materia Medica. Considered the most comprehensive book on traditional Chinese medicine, it was compiled and written in the 16th century by Li Shi-zhen during the heyday of the Ming Dynasty. The original compendium is vast, encompassing dozens of volumes, but Huang had only seen greatly condensed versions that are sold in Chinese bookstores.

Emory’s copy resides in the Candler School of Theology’s Pitts Theology Library. The 1826 version passed at one stage through a London book dealer. The unnumbered pages are block-printed in Chinese characters, but at some point were rebound into 10 volumes with covers labeled in English.

Huang never imagined she would be touching such an old copy of the Ben Cao Gang Mu. “You can feel the history in it,” she says. “The paper is so yellow, thin and fragile that I was afraid I would break the pages as I was turning them.”

A volume labeled “Grains, Vegetables, Fruits” described 17 traditional uses for the ginkgo seed, including eight for skin disorders such as chapped hands and feet, rosacea, crab louse-induced itchiness, dog-bite wound abscesses and pustules. Li Shi-Zhen recommended preparing a paste of ground up seeds mixed with rice wine or other alcohol, or by immersing the crushed seeds in rape seed oil. The paste could then be applied to the affected area.

A previous study found that ginkgo seed coats demonstrated antibacterial activity against some intestinal bacterial pathogens. And ginkgo leaves have shown antibacterial activity on both some intestinal bacteria and on the skin pathogen S. aureus.

Huang, however, wanted to test the information she had gleaned from the ancient text for the use of ginkgo seeds as a topical treatment for skin disorders. Skin pathogens are of particular interest to the Quave lab, which focuses on finding new approaches to treat antibiotic-resistant bacteria.

Huang gathered ginkgo samples for testing. Extractions from the seeds were processed as closely as possible to the recommendations of the Ben Cao Gang Mu, using either water, ethanol or rape seed oil. Huang and Chassagne conducted microbial experiments — including the evaluation of ginkgo extracts from the seed nut, immature seeds and the seed coat — on 12 different bacterial strains.

The results showed that the ginkgo seed coats and the immature seeds exhibited antibacterial activity on three of the strains tested: C. acnesS. aureus and S. pyogenes. Statistical analysis also found a positive correlation between the antimicrobial activity of the ginkgo samples and the concentration of ginkgolic acid C15:1, suggesting it was involved in the activity.

“Our finding is still in a basic, benchtop phase — these extracts have not yet been tested in animal or human studies — but it is still a thrill for me to learn that this ancient story in the Ben Cao Gang Mu appears to be real,” Huang says. “As a student pharmacist, this gives me more appreciation for the value of using ancient plant remedies to guide modern-day research.”

NEWS RELEASE 17-APR-2019

Omega-3 expert supports new research that shows omega-6 is good for you

New Circulation study shows those who consume the most omega-6 are less likely to develop CVD

WRIGHT ON MARKETING & COMMUNICATIONS

 

There has been a fierce debate over the last decade or so about the health benefits of omega-6 fatty acids. One side believes they are too ubiquitous in the diet and fuel the inflammation underpinning many of today’s chronic diseases. Another side believes that the most consumed omega-6 — linoleic acid (LA) — could be just as important as omega-3s in reducing disease risk.

To address this, two studies using the same methodology — i.e., comparing the risk for developing a disease over time as a function of blood LA levels — looked specifically at cardiovascular disease (CVD) as well as diabetes.

The latest study, published in Circulation, pooled data from 30 prospective observational studies from 13 countries involving about 69,000 people. The data included both baseline blood LA levels and subsequent risk for developing and/or dying from CVD.

People in the top 10% of LA levels were 7% less likely to develop any CVD and 22% less likely to die of CVD. They were also 12% less likely to have an ischemic stroke (i.e., blocked brain artery) compared with those in the bottom 10% of LA levels.

A similarly conducted study, published in 2017 in The Lancet, analyzed data from 20 studies involving almost 40,000 people from 10 countries, in whom 4,347 new cases of diabetes occurred over time. These studies included adults with a wide range of ages and without any diagnosis of type 2 diabetes at the onset of the studies, when they were laboratory tested for levels of two key omega-6 markers — LA and arachidonic acid (AA). In this study, people with the highest LA levels were 35% less likely to develop diabetes than those in the lowest 10% of LA levels.

“The health benefits or harms that may come from the consumption of omega-6 fatty acids [especially LA, which constitutes 99% of the omega-6 fatty acids in the diet] are controversial,” said Bill Harris, PhD, one of the authors on the latest Circulation paper. “These two studies indicate that consuming more LA will likely lower risk for diabetes and CVD. This means that LA is good for us, not bad.”

According to Dr. Harris, because LA can be converted into AA, which is the precursor to many pro-inflammatory molecules, some researchers believe LA should be considered pro-inflammatory itself.

But Dr. Harris and other experts believe this view is too simplistic because 1) extremely little LA is converted to AA, 2) AA also makes anti-inflammatory molecules, and 3) LA itself can be converted to anti-inflammatory molecules.

“Regardless of the biochemistry (what molecules LA gets turned into and what they may do in the body), the larger question of ‘Do people who eat more LA (or better yet, have higher blood levels of LA) get sicker than people who have lower levels?’ is just now beginning to get answered,” Dr. Harris commented.

These new findings confirm the prediction made 10 years ago in an AHA Scientific Advisory on Omega-6 Fatty Acids and Cardiovascular Disease, the lead author of which was Dr. Harris: “To reduce omega-6 PUFA intakes from their current levels would be more likely to increase than to decrease risk.”

NEWS RELEASE 23-APR-2019

CBD reduces impairment caused by cannabis

UNIVERSITY COLLEGE LONDON

The more cannabidiol (CBD) in a strain of cannabis, the lower the impairment to brain function, finds a new UCL-led brain imaging study.

The research, published in the Journal of Psychopharmacology, is the first study using fMRI (functional magnetic resonance imaging) to gauge how different strains of cannabis impact brain function.

“Over the last two decades, rates of addiction and psychosis linked to cannabis have been on the rise, while at the same time stronger strains of cannabis with more THC and less CBD have become increasingly common,” said the study’s lead author, Dr Matt Wall (UCL Clinical Psychopharmacology Unit and Invicro).

“We have now found that CBD appears to buffer the user against some of the acute effects of THC on the brain.”

There is growing evidence that THC is implicated in addiction and cannabis-induced psychosis. CBD, on the other hand, is being researched for a range of therapeutic functions, but the interplay between THC and CBD is not yet well-known.

In the present study, the researchers monitored brain activity at rest in 17 people after taking different strains of cannabis.

The two strains have equal levels of tetrahydrocannabinol (THC), but one of them also has high levels of CBD while the other strain, a high-strength cannabis commonly known as skunk, contained negligible levels of CBD. Both strains are comparable to the different strains of cannabis in common usage.

The researchers found that the low-CBD strain impaired functional connectivity in the brain’s default mode (particularly in the posterior cingulate area) and salience networks, while the high-CBD strain caused only a minimal disruption to the these regions, suggesting that the CBD counteracts some of THC’s harmful effects.

The salience network supports other brain networks and determines what sensory or emotional inputs we pay attention to, and disruptions of the network have previously been implicated in addiction and psychosis.

The researchers also found that the THC-induced disruption of functional connectivity in the posterior cingulate was strongly correlated with participants’ reports of subjective experiences, such as feeling more ‘stoned’ or ‘high’, suggesting that the brain area may be central to driving cannabis’ subjective effects. This relationship between the posterior cingulate and subjective effects was also blocked by CBD.

The researchers say their findings add to evidence that cannabis strains with greater CBD content may be less harmful, suggesting that CBD content of cannabis should perhaps be regulated in jurisdictions where it’s legal.

“As cannabis is becoming legal in more parts of the world, people buying cannabis should be able to make an informed decision about their choice of cannabis strain and be aware of the relative risks,” said Dr Wall.

The findings also provide insight into why CBD holds potential for medicinal uses.

“If CBD can restore disruption to the salience network, this could be a neuroprotective mechanism to explain its potential to treat disorders of salience such as psychosis and addiction,” added senior author Professor Val Curran (UCL Clinical Psychopharmacology Unit).

NEWS RELEASE 23-APR-2019

Eating elderberries can help minimize influenza symptoms

UNIVERSITY OF SYDNEY

Folk medicines and herbal products have been used for millennia to combat a whole range of ailments, at times to the chagrin of modern scientists who have struggled to explain their medicinal benefits.

However a recent study by researchers at the University of Sydney has determined exactly how a popular ancient remedy, the elderberry fruit, can help the fight against influenza.

Conducted by Professor Fariba Deghani, Dr Golnoosh Torabian and Dr Peter Valtchev as part of the ARC Training Centre for the Australian Food Processing Industry that was established within the university’s Faculty of Engineering and IT, the study showed that compounds from elderberries can directly inhibit the virus’s entry and replication in human cells, and can help strengthen a person’s immune response to the virus.

Although elderberry’s flu-fighting properties have long been observed, the group performed a comprehensive examination of the mechanism by which phytochemicals, compounds that positively effect health, from elderberries combat influenza infections.

“What our study has shown is that the common elderberry has a potent direct antiviral effect against the flu virus. It inhibits the early stages of an infection by blocking key viral proteins responsible for both the viral attachment and entry into the host cells,” said Dr Golnoosh Torabian.

The researchers used commercially farmed elderberries which were turned into a juice serum and were applied to cells before, during and after they had been infected with the influenza virus.

The phytochemicals from the elderberry juice were shown to be effective at stopping the virus infecting the cells, however to the surprise of the researchers they were even more effective at inhibiting viral propagation at later stages of the influenza cycle when the cells had already been infected with the virus.

“This observation was quite surprising and rather significant because blocking the viral cycle at several stages has a higher chance of inhibiting the viral infection,” explained Dr Peter Valtchev.

“In addition to that, we identified that the elderberry solution also stimulated the cells to release certain cytokines, which are chemical messengers that the immune system uses for communication between different cell types to coordinate a more efficient response against the invading pathogen,” said Centre Director, Professor Fariba Deghani.

The team also found that the elderberry’s antiviral activity can be attributed to its anthocyanidin compounds — phytonutrients responsible for giving the fruit its vivid purple colouring.

Otherwise known as Sambucus nigra, the elderberry is a small, antioxidant rich fruit common to Europe and North America that is still commonly consumed as a jam or wine.

The influenza virus is one of the leading causes of mortality worldwide, affecting nearly 10 per-cent of the world population and contributing to one million deaths annually.

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NEWS RELEASE 26-APR-2019

A spoonful of peppermint helps the meal go down

A pilot study at the Medical University of South has found that peppermint oil improved symptoms, including difficulty swallowing and non-cardiac chest pain, in patients with certain disorders of the esophagus.

MEDICAL UNIVERSITY OF SOUTH CAROLINA

Imagine that while eating a delicious meal at your favorite restaurant, your joy is cut short because of difficulty swallowing your food, followed by chest pain.

If you go see a doctor about these symptoms, and there is no evidence of a cardiac cause of the chest pain, you could be diagnosed as having some sort of disorder of the esophagus.

Peppermint can help with the difficulty swallowing and non-cardiac chest pain experienced by some patients with disorders of the esophagus, report investigators at the Medical University of South Carolina (MUSC) in Digestive Diseases & Sciences. Of the 38 patients enrolled in the MUSC pilot study, 63 percent overall reported improvement of symptoms. Patients were recruited from the Esophageal Disorders Clinic at the MUSC Health Digestive Disease Center.

“Peppermint oil is an established agent in the treatment of irritable bowel syndrome. We tried to examine its effect on patients with swallowing and chest pain issues with no apparent cause,” says Mohamed Khalaf, M.D., an esophageal disorders research fellow at the MUSC Health Digestive Disease Center and first author on the article.

“Our findings suggest that peppermint may help prevent these symptoms by relaxing the smooth muscle in the lower esophagus,” says Donald O. Castell, M.D., a professor emeritus in the MUSC College of Medicine, a nationally recognized gastroenterologist, and senior author on the article.

Peppermint oil has been known to have therapeutic effects in multiple disorders due to its muscle-relaxing properties. However, only two previous studies have investigated its role in the upper digestive tract.

The MUSC study found that patients who took peppermint oil tablets before eating felt better after meals than those who did not. Those with both non-cardiac chest pain and unobstructed difficulty swallowing saw the most benefits: 73 percent of them reported feeling better. Of patients with just one of the symptoms, those with non-cardiac chest pain had a more positive response from the peppermint oil (63 percent) than those with difficulty swallowing (53 percent).

The results were even better among patients with spastic disorders of the esophagus: 83 percent reported feeling better or slightly better. Although less well-known than esophageal disorders such as acid reflux, spastic disorders of the esophagus can also disrupt a patient’s life. In these disorders, the esophagus undergoes painful spasms that can interfere with eating. Because the spasms occur only from time to time, these disorders are difficult to diagnose and treat.

Current standard of care calls for these disorders involves trying multiple drugs, including tricyclic antidepressants and calcium channel blockers, and hoping that one works.

Peppermint offers an attractive first line of defense for these patients, who experience intermittent symptoms, because they can take it freely as symptoms occur.

“In this study, patients who had experienced difficulty swallowing took two pieces of a commercially available peppermint right before meals. Those with chest pain took the peppermint tablets as needed,” says Khalaf.

This study highlights the effects of the so-called Charleston Approach, which advocates a “start low and go slow” treatment strategy. The Charleston Approach differs from current standard of care in that it uses peppermint oil as a first attempt to relieve symptoms.

Castell and Khalaf caution that patients must first be examined by a doctor to rule out heart disease and undergo a procedure known as an endoscopy to rule out obstruction before they are offered peppermint as a first-line treatment. Endoscopy involves inserting a flexible tube fitted with a light and camera into the esophagus.

One of the drawbacks of the study was that researchers did not know the precise dosage of peppermint being given since it was a commercial candy (only one type of which was effective) with a proprietary recipe. Another was the study relied on self-reporting by patients to determine whether symptoms improved.

Although the preliminary findings of this study are promising, they need to be confirmed in a trial that compares outcomes in patients who receive a specific dose of peppermint oil and those who receive only a placebo.

In the meantime, however, patients who have been diagnosed as having spastic disorders of the esophagus and who have no heart disease or obstruction can try using peppermint to see if it relieves their symptoms.

“Given the safety profile, low cost, and widespread availability, there are no risks from empirical use of peppermint oil,” says Khalaf.

NEWS RELEASE 1-MAY-2019

Cranberry oligosaccharides might help prevent UTIs

AMERICAN CHEMICAL SOCIETY

Many people have heard that drinking cranberry juice can help prevent urinary tract infections (UTIs). Although clinical trials of this popular folk remedy have produced mixed results, some studies have shown that drinking cranberry juice can keep bacteria that cause UTIs from sticking to cells lining the urinary tract. Now, researchers reporting in ACS’ Journal of Natural Products have identified cranberry oligosaccharides in the urine of cranberry-fed pigs that could be responsible for this activity.

According to the U.S. Department of Health and Human Services, about half of all U.S. women will have a UTI sometime during their lives. Doctors usually prescribe antibiotics to treat the painful condition, but this could contribute to the rise of antibiotic-resistant bacteria. To enable better UTI prevention strategies, Christina Coleman, Daneel Ferreira and colleagues from several institutions wanted to identify active compounds from cranberries that end up in urine and potentially keep bacteria from adhering to human cells.

The researchers fed female pigs dried cranberry powder, collected their urine and used chromatography to separate it into fractions of differently sized molecules. Then, they screened the samples for anti-adhesion activity against the E. coli bacteria that cause UTIs. To the researchers’ surprise, proanthocyanidins, the compounds previously proposed to be responsible for cranberry’s apparent UTI prevention properties, were absent from the active urine fractions. Instead, the researchers detected oligosaccharides called arabinoxyloglucans in those samples. These complex carbohydrates, related to cellulose, are difficult to detect and isolate, which could explain why they hadn’t previously been identified as anti-adhesive components of cranberry, the researchers say.

 

NEWS RELEASE 30-APR-2019

Can the effects of the ketogenic diet help prevent epilepsy after traumatic brain injury?

A drug-mimic of the ketogenic diet improves brain function in mice after TBI

TUFTS UNIVERSITY, HEALTH SCIENCES CAMPUS

BOSTON (April 30, 2019, noon ET)–Neuroscientists led by Chris Dulla at Tufts University School of Medicine prevented the development of epileptic activity in mice after traumatic brain injury by using a drug that mimics the metabolic effects of the ketogenic diet. An advance copy of the study is published today in JCI Insight.

The ketogenic diet was originally developed in the 1920s to treat drug-resistant epilepsy in children. By limiting carbohydrates in the diet, the body is forced to burn fat rather than glucose, the usual source of energy in the body. Although researchers do not know exactly how the therapeutic effects of the diet works, evidence to date suggests the change in metabolism is key.

“While we know the ketogenic diet can control seizures in people with epilepsy, we wanted to learn if it would be able to prevent the development of post-traumatic epilepsy,” says Jenny Koenig, an M.D. and Ph.D. student at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts who works in Dulla’s lab.

Post-traumatic epilepsy develops within three years of a traumatic brain injury (TBI) in about 1 out of 10 people. TBIs lead to the dysfunction of the brain’s inhibitory network, including the cells that normally quiet down brain activity. Without inhibition, brain activity increases, causing the behavioral and cognitive challenges seen after injury.

Along with increased activity comes an increased demand for energy production through a process called glycolysis, a system that provides energy to the brain by burning glucose, or sugar. Rather than focus directly on reducing neuronal activity, the research team inhibited glycolysis with a drug called 2-deoxyglucose (2-DG) to mimic the metabolic effects of the ketogenic diet.

By recording brain activity from cells in the injured area with a common electrophysiological technique called whole-cell recording, the researchers determined that excitatory cells were more active in injured tissue, compared to control brain tissue from mice.

Comparatively, the cells which usually inhibit others were dying after injury, leaving the brain without a brake on activity. Application of 2-DG directly on the brain tissue was able to reduce cell excitation and epileptic activity from TBI.

In a follow-up experiment, the research team gave mice 2-DG or saline, as a control, in injection form for one week after injury to assess its effect. They found that 2-DG treatment reduced cell excitation, lessened cell loss, and prevented the development of epileptic brain activity.

“We found that treatment with a small molecule-mimic of the ketogenic diet improves neuronal survival and brain function after TBI. We also established that different types of neurons use energy in different ways, allowing cell type-specific manipulation of neuronal metabolism,” said Dulla, whose lab at Tufts University School of Medicine explores the function of neuronal networks, particularly as they relate to epilepsy and other neurological diseases.

“While preliminary, our study suggests that manipulating brain metabolism – through a specific diet or a mimic of that – could be an effective way to prevent the very development of epilepsy or epileptogenesis after TBI and restore normal synaptic communication in the brain,” he continued. “Importantly, 2-DG is already being investigated to help treat cancer and other diseases, suggesting this approach might be used clinically if properly tested in brain injury.”

The authors caution that long-term exposure to 2-DG has been associated with cardiac toxicity.

Additionally, the research group did not investigate the specific cells impacted by 2-DG but note that the results point to a new therapeutic path for post-traumatic epilepsy prevention.

 

NEWS RELEASE 6-MAY-2019

Clinical trial looks at absorption levels of sunscreen active ingredients into bloodstream

JAMA

Bottom Line: The U.S. Food and Drug Administration recommends that active ingredients in sunscreen absorbed into the bloodstream above a certain level undergo toxicology testing. Researchers from the FDA conducted this small randomized clinical trial of 24 healthy volunteers to determine bloodstream concentrations of four active ingredients (avobenzone, oxybenzone, octocrylene and ecamsule) in four sunscreens applied four times per day for four days with blood samples collected from study participants over seven days. Researchers report that all four active ingredients were found in blood samples at levels exceeding the threshold recommended for toxicology testing. The effect of these concentrations is unknown and further studies are needed to determine the clinical significance of these findings. Some limitations of this clinical trial include that it was conducted under indoor conditions without exposure to heat, sunlight or humidity, which may affect the rate of sunscreen absorption, and the study wasn’t designed to look at differences in absorption by the type of sunscreen formulation, skin type or age of the user. Researchers emphasize that their results don’t suggest people refrain from using sunscreen, which prevents skin damage.

Authors: David G. Strauss, M.D., Ph.D., U.S. Food and Drug Administration, Silver Spring, Maryland, and coauthors

(doi:10.1001/jama.2019.5586)

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

NEWS RELEASE 3-MAY-2019

Training for first-time marathon ‘reverses’ aging of blood vessels

Older and slower runners benefit the most

EUROPEAN SOCIETY OF CARDIOLOGY

Venice, Italy – 3 May 2019: Training for and completing a first-time marathon “reverses” ageing of major blood vessels, according to research presented today at EuroCMR 2019, a scientific congress of the European Society of Cardiology (ESC).1 The study found that older and slower runners benefit the most.

Study author Dr Anish Bhuva, a British Heart Foundation Fellow at University College London, UK, said: “Novice runners who trained for six months and completed their first marathon had a four-year reduction in arterial age and a 4 mmHg drop in systolic blood pressure. This is comparable to the effect of medication, and if maintained translates to approximately 10% lower risk of stroke over a lifetime.”

A hallmark of normal ageing is stiffening of the blood vessels, which increases the risk of stroke and heart disease even in healthy people. Compared to their peers, lifelong athletes have biologically younger blood vessels. This study investigated whether training for a marathon could modify aortic stiffness even in novice runners.

The study included 139 healthy first-time marathon runners aged 21-69 years who were advised to follow a first-time finisher training programme and ran an estimated 6-13 miles (10-20 km) a week for six months ahead of completing the 2016 or 2017 London Marathon.2,3

Before they started training and two weeks after completing the marathon, participants had magnetic resonance imaging (MRI) and ultrasound scans of the heart and blood vessels, a fitness test, and measurements of blood pressure and heart rate. Biological age of the aorta was calculated at both time points.

After completing the marathon, aortic stiffness had reduced and the aorta was four years younger than before training. Older participants and those with longer marathon finish times had greater reductions in aortic stiffness after training. Reductions in aortic stiffness were independent of changes in blood pressure.

Dr Bhuva said: “You don’t have to be an elite athlete to gain the benefits from marathon running, in fact the benefits appeared greatest in those who were older and slower. By completing training, and getting to the finish line, it is possible to rejuvenate the cardiovascular system of first-time marathon runners.”

Fitness improved and heart rate dropped after training – both to a modest extent. “The minimal impact on these conventional markers of health suggests that study participants trained within their personal limits,” said Dr Bhuva. “Aortic stiffness and blood pressure changed more than fitness and heart rate.”

Dr Bhuva noted that participants had been running for less than two hours a week before marathon training and their finish times were slower than average, which was expected as it was their first race. “The study shows that the health gains of lifelong exercise start to appear after a relatively brief training programme,” he said. “Training for a marathon can be a good motivator to keep active. Many people enjoy it and continue running, which should increase the likelihood of sustaining the benefits.”

Professor Sanjay Sharma, medical director of the London Marathon and an author of the study, said: “The benefits of exercise on the heart and circulation are well established, and are associated with lower cardiovascular disease and mortality. Recent studies have shown that exercise may retard ageing of the cardiovascular system. Our study shows that a first-time marathon makes the cardiovascular system ‘younger’ therefore participants will reap these benefits whilst running for a good cause.”

 

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